TY - JOUR AU - Spoormans, E.M. AU - Lemkes, J.S. AU - Janssens, G.N. AU - Hoeven, N.W. Van Der AU - Jewbali, L.S.D. AU - Dubois, E.A. AU - Ven, P.M. van de AU - Meuwissen, M. AU - Rijpstra, T.A. AU - Bosker, H.A. AU - Blans, M.J. AU - Bleeker, G.B. AU - Baak, R. AU - Vlachojannis, G.J. AU - Eikemans, B.J.W. AU - Harst, P.V. der AU - Horst, I.C. van der AU - Voskuil, M. AU - Heijden, J.J. van der AU - Beishuizen, A. AU - Stoel, M. AU - Camaro, C. AU - Hoeven, H. van der AU - Henriques, J.P.S. AU - Vlaar, A.P.J. AU - Vink, Matthijs AU - Bogaard, B. van den AU - Heestermans, T. AU - Ruijter, W. de AU - Delnoij, T.S.R. AU - Crijns, H. AU - Jessurun, G.A. AU - Oemrawsingh, P.V. AU - Gosselink, M.T.M. AU - Plomp, K. AU - Magro, M. AU - Elbers, P.W.G. AU - Appelman, Y. AU - Royen, N. van PY - 2021 UR - https://hdl.handle.net/2066/229274 AB - BACKGROUND: Whether sex is associated with outcomes of out-of-hospital cardiac arrest (OHCA) is unclear. OBJECTIVES: This study examined sex differences in survival in patients with OHCA without ST-segment elevation myocardial infarction (STEMI). METHODS: Using data from the randomized controlled Coronary Angiography after Cardiac Arrest (COACT) trial, the primary point of interest was sex differences in OHCA-related one-year survival. Secondary points of interest included the benefit of immediate coronary angiography compared to delayed angiography until after neurologic recovery, angiographic and clinical outcomes. RESULTS: In total, 522 patients (79.1% men) were included. Overall one-year survival was 59.6% in women and 63.4% in men (HR 1.18; 95% CI: 0.76-1.81;p = 0.47). No cardiovascular risk factors were found that modified survival. Women less often had significant coronary artery disease (CAD) (37.0% vs. 71.3%;p < 0.001), but when present, they had a worse prognosis than women without CAD (HR 3.06; 95% CI 1.31-7.19;p = 0.01). This was not the case for men (HR 1.05; 95% CI 0.67-1.65;p = 0.83). In both sexes, immediate coronary angiography did not improve one-year survival compared to delayed angiography (women, odds ratio (OR) 0.87; 95% CI 0.58-1.30;p = 0.49; vs. men, OR 0.97; 95% CI 0.45-2.09;p = 0.93). CONCLUSION: In OHCA patients without STEMI, we found no sex differences in overall one-year survival. Women less often had significant CAD, but when CAD was present they had worse survival than women without CAD. This was not the case for men. Both sexes did not benefit from a strategy of immediate coronary angiography as compared to delayed strategy with respect to one-year survival. CLINICAL TRIAL REGISTRATION NUMBER: Netherlands trial register (NTR) 4973. TI - Sex differences in patients with out-of-hospital cardiac arrest without ST-segment elevation: A COACT trial substudy EP - 22 SN - 0300-9572 SP - 14 JF - Resuscitation VL - vol. 158 DO - https://doi.org/10.1016/j.resuscitation.2020.10.026 ER - TY - JOUR AU - Roesthuis, L.H. AU - Berg, M.J.W. van den AU - Hoeven, H. van der PY - 2021 UR - https://hdl.handle.net/2066/231094 TI - Non-invasive method to detect high respiratory effort and transpulmonary driving pressures in COVID-19 patients during mechanical ventilation SN - 2110-5820 IS - iss. 1 JF - Annals of Intensive Care VL - vol. 11 DO - https://doi.org/10.1186/s13613-021-00821-9 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/231094/231094.pdf?sequence=1 ER - TY - JOUR AU - Bersselaar, L.R. van den AU - Hoeven, J.G. van der AU - Jong, B. De PY - 2021 UR - https://hdl.handle.net/2066/231596 TI - Feeling Death, Being Alive: 4-Methylethcathinone/Pentedrone Addiction and 3-Methoxyphencyclidine Intoxication EP - 73 SN - 1531-5754 IS - iss. 1 SP - 69 JF - Addictive Disorders & Their Treatment VL - vol. 20 DO - https://doi.org/10.1097/ADT.0000000000000214 ER - TY - JOUR AU - Koomen, Erik AU - Webster, Craig S. AU - Konrad, David AU - Hoeven, J.G. van der AU - Best, Thomas AU - Kesecioglu, Jozef AU - Gommers, Diederik A. M. P. J. AU - Vries, Willem B. de AU - Kappen, Teus H. PY - 2021 UR - https://hdl.handle.net/2066/231622 TI - Reducing medical device alarms by an order of magnitude: A human factors approach EP - 61 SN - 0310-057X IS - iss. 1 SP - 52 JF - Anaesthesia and Intensive Care VL - vol. 49 DO - https://doi.org/10.1177/0310057X20968840 ER - TY - PAT AU - Netea, M.G. AU - Deuren, M. van AU - Meer, H. van der AU - Veerdonk, F.L. van de AU - Mast, Q. de AU - Bruggemann, R.J.M. AU - Hoeven, J.G. van der PY - 2020 UR - https://hdl.handle.net/2066/228267 PB - [S.l. : s.n.] TI - Treatment of ARDS and other parameters related to Covid-19 ER - TY - JOUR AU - Geense, W.W. AU - Zegers, H.W. AU - Dieperink, Peter AU - Vermeulen, H. AU - Hoeven, J.G. van der AU - Boogaard, M. van den PY - 2020 UR - https://hdl.handle.net/2066/214092 TI - Changes in frailty among ICU survivors and associated factors: Results of a one-year prospective cohort study using the Dutch Clinical Frailty Scale EP - 193 SN - 0883-9441 SP - 184 JF - Journal of Critical Care VL - vol. 55 DO - https://doi.org/10.1016/j.jcrc.2019.10.016 ER - TY - JOUR AU - IJland, M.M. AU - Lemson, J. AU - Hoeven, H. van der AU - Heunks, L.M.A. PY - 2020 UR - https://hdl.handle.net/2066/223867 TI - The impact of critical illness on the expiratory muscles and the diaphragm assessed by ultrasound in mechanical ventilated children SN - 2110-5820 IS - iss. 1 JF - Annals of Intensive Care VL - vol. 10 DO - https://doi.org/10.1186/s13613-020-00731-2 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/223867/223867.pdf?sequence=1 ER - TY - JOUR AU - Gommans, D.H.F. AU - Nas, J. AU - Pinto-Sietsma, S.J. AU - Koop, Y. AU - Konst, R.E. AU - Mensink, F.B. AU - Aarts, G.W.A. AU - Konijnenberg, L.S.F. AU - Cortenbach, K.R. AU - Verhaert, D.V.M. AU - Thannhauser, J. AU - Mol, J.H.Q. AU - Rooijakkers, M.J.P. AU - Vos, J.L. AU - Rumund, A. van AU - Vart, P. AU - Hassing, R.J. AU - Cornel, J.H. AU - Jager, C.P.C. de AU - Heuvel, M. van den AU - Hoeven, J.G. van der AU - Royen, N. van AU - Kimmenade, R.R.J. van PY - 2020 UR - https://hdl.handle.net/2066/224636 TI - Rationale and design of the PRAETORIAN-COVID trial: A double-blind, placebo-controlled randomized clinical trial with valsartan for PRevention of Acute rEspiraTORy dIstress syndrome in hospitAlized patieNts with SARS-COV-2 Infection Disease EP - 68 SN - 0002-8703 SP - 60 JF - American Heart Journal VL - vol. 226 DO - https://doi.org/10.1016/j.ahj.2020.05.010 ER - TY - JOUR AU - Oppersma, Eline AU - Doorduin, J. AU - Roesthuis, L.H. AU - Hoeven, J.G. van der AU - Veltink, Peter H. AU - Heunks, L.M.A. PY - 2020 UR - https://hdl.handle.net/2066/222162 TI - Patient-Ventilator Interaction During Noninvasive Ventilation in Subjects With Exacerbation of COPD: Effect of Support Level and Ventilator Mode EP - 1322 SN - 0020-1324 IS - iss. 9 SP - 1315 JF - Respiratory Care VL - vol. 65 DO - https://doi.org/10.4187/respcare.07159 ER - TY - JOUR AU - Geense, W.W. AU - Boogaard, M. van den AU - Peters, Marco A. A. AU - Simons, K.S. AU - Ewalds, Esther AU - Vermeulen, H. AU - Hoeven, J.G. van der AU - Zegers, H.W. PY - 2020 UR - https://hdl.handle.net/2066/222163 TI - Physical, Mental, and Cognitive Health Status of ICU Survivors Before ICU Admission: A Cohort Study EP - 1279 SN - 0090-3493 IS - iss. 9 SP - 1271 JF - Critical Care Medicine VL - vol. 48 DO - https://doi.org/10.1097/CCM.0000000000004443 ER - TY - JOUR AU - Witjes, M. AU - Jansen, N.E. AU - Dongen, J. Van AU - Herold, I.H.F. AU - Otterspoor, L. AU - Haase-Kromwijk, B. AU - Hoeven, J.G. van der AU - Abdo, W.F. PY - 2020 UR - https://hdl.handle.net/2066/225441 AB - BACKGROUND: One of the most important bottlenecks in the organ donation process worldwide is the high family refusal rate. AIMS AND OBJECTIVES: The main aim of this study was to examine whether family guidance by trained donation practitioners increased the family consent rate for organ donation. DESIGN: This was a prospective intervention study. METHODS: Intensive and coronary care unit nurses were trained in communication about donation (ie, trained donation practitioners) in two hospitals. The trained donation practitioners were appointed to guide the families of patients with a poor medical prognosis. When the patient became a potential donor, the trained donation practitioner was there to guide the family in making a well-considered decision about donation. We compared the family consent rate for donation with and without the guidance of a trained donation practitioner. RESULTS: The consent rate for donation with guidance by a trained donation practitioner was 58.8% (20/34), while the consent rate without guidance by a trained donation practitioner was 41.4% (41/99, P = 0.110) in those patients where the family had to decide on organ donation. CONCLUSIONS: Our data suggest that family guidance by a trained donation practitioner could benefit consent rates for organ donation. RELEVANCE TO CLINICAL PRACTICE: Trained nurses play an important role in supporting the families of patients who became potential donors to guide them through the decision-making process after organ donation request. TI - Appointing nurses trained in organ donation to improve family consent rates EP - 304 SN - 1362-1017 IS - iss. 5 SP - 299 JF - Nursing in Critical Care VL - vol. 25 DO - https://doi.org/10.1111/nicc.12462 ER - TY - JOUR AU - Stolk, R.F. AU - Pasch, E. van der AU - Naumann, F.V. AU - Schouwstra, J. AU - Bressers, S. AU - Herwaarden, A.E. van AU - Gerretsen, J.J.F. AU - Schambergen, R. AU - Ruth, M.M. AU - Hoeven, J.G. van der AU - Leeuwen, H. van AU - Pickkers, P. AU - Kox, M. PY - 2020 UR - https://hdl.handle.net/2066/225483 AB - Rationale: Sepsis is characterized by a dysregulated immune response to infection. Norepinephrine, the cornerstone vasopressor used in septic shock, may contribute to immune dysregulation and impact host defense.Objectives: To investigate effects of norepinephrine and the alternative vasopressor vasopressin on the immune response and host defense.Methods: Leukocytes from six to nine donors were stimulated in the presence or absence of norepinephrine and vasopressin. A total of 190 C57BL/6J mice received a continuous infusion of norepinephrine or vasopressin via microosmotic pumps and were challenged with LPS or underwent cecal ligation and puncture. Thirty healthy volunteers were randomized to a 5-hour infusion of norepinephrine, vasopressin, or saline and intravenously challenged with LPS. The relationship between the norepinephrine infusion rate and the use of β-blockers and plasma cytokines was assessed in 195 patients with septic shock.Measurements and Main Results: Norepinephrine attenuated the production of proinflammatory mediators and reactive oxygen species and augmented antiinflammatory IL-10 production both in vitro and in LPS-challenged mice. Norepinephrine infusion during cecal ligation and puncture resulted in increased bacterial dissemination to the spleen, liver, and blood. In LPS-challenged volunteers, norepinephrine enhanced plasma IL-10 concentrations and attenuated the release of the proinflammatory cytokine IFN-γ-induced protein 10. Vasopressin exerted no immunomodulatory effects across these experimental setups. In patients, higher norepinephrine infusion rates were correlated with a more antiinflammatory cytokine balance, whereas β-blocker use was associated with a more proinflammatory cytokine balance.Conclusions: Norepinephrine dysregulates the immune response in mice and humans and compromises host defense. Therefore, it may significantly contribute to sepsis-induced immunoparalysis, whereas vasopressin does not have untoward immunologic effects. TI - Norepinephrine Dysregulates the Immune Response and Compromises Host Defense during Sepsis EP - 842 SN - 1073-449X IS - iss. 6 SP - 830 JF - American Journal of Respiratory and Critical Care Medicine VL - vol. 202 DO - https://doi.org/10.1164/rccm.202002-0339OC ER - TY - JOUR AU - Kok, N. AU - Hoedemaekers, A. AU - Hoeven, H. van der AU - Zegers, M. AU - Gurp, J.L.P. van PY - 2020 UR - https://hdl.handle.net/2066/225342 TI - Recognizing and supporting morally injured ICU professionals during the COVID-19 pandemic EP - 1654 SN - 0342-4642 IS - iss. 8 SP - 1653 JF - Intensive Care Medicine VL - vol. 46 DO - https://doi.org/10.1007/s00134-020-06121-3 ER - TY - JOUR AU - Pickkers, P. AU - Hoeven, H. van der AU - Citerio, G. PY - 2020 UR - https://hdl.handle.net/2066/225389 TI - COVID-19: 10 things I wished I'd known some months ago EP - 1452 SN - 0342-4642 IS - iss. 7 SP - 1449 JF - Intensive Care Medicine VL - vol. 46 DO - https://doi.org/10.1007/s00134-020-06098-z ER - TY - JOUR AU - Kotsopoulos, A.M.M. AU - Vos, P . de AU - Jansen, N.E. AU - Bronkhorst, E.M. AU - Hoeven, J.G. van der AU - Abdo, W.F. PY - 2020 UR - https://hdl.handle.net/2066/220528 AB - BACKGROUND: Controlled donation after circulatory death (cDCD) is a major source of organs for transplantation. A potential cDCD donor poses considerable challenges in terms of identification of those dying within the predefined time frame of warm ischemia after withdrawal of life-sustaining treatment (WLST) to circulatory arrest. Several attempts have been made to develop models predicting the time between treatment withdrawal and circulatory arrest. This time window determines whether organ donation can occur and influences the quality of the donated organs. However, the selected patients used for these models were not always restricted to potential cDCD donors (eg, patients with cancer or severe infections were also included). This severely limits the generalizability of those data. OBJECTIVE: The objectives of this study are the following: (1) to develop a model predicting time to death within 60 minutes in potential cDCD patients; (2) to validate and update previous prediction models on time to death after WLST; (3) to determine timing and patient characteristics that are associated with prognostication and the decision-making process that leads to initiating end-of-life care; (4) to evaluate the impact of timing of family approach on organ donation approval; and (5) to assess the influence of variation in WLST processes on postmortem organ donor potential and actual postmortem organ donors. METHODS: In this multicenter observational prospective cohort study, all patients admitted to the intensive care unit of 3 university hospitals and 3 teaching hospitals who met the criteria of the cDCD protocol as defined by the Dutch Transplant Foundation were included. The target of enrolment was set to 400 patients. Previously developed models will be refitted in our data set. To further update previous prediction models, we will apply least absolute shrinkage and selection operator (LASSO) as a tool for efficient variable selection to develop the multivariable logistic regression model. RESULTS: This protocol was funded in August 2014 by the Dutch Transplant Foundation. We expect to have the results of this study in July 2020. Patient enrolment was completed in July 2018 and data collection was completed in April 2020. CONCLUSIONS: This study will provide a robust multimodal prediction model, based on clinical and physiological parameters, that can predict time to circulatory arrest in cDCD donors. In addition, it will add valuable insight in the process of WLST in cDCD donors and will fill an important knowledge gap in this essential field of health care. TRIAL REGISTRATION: ClinicalTrials.gov NCT04123275; https://clinicaltrials.gov/ct2/show/NCT04123275. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/16733. TI - Prediction Model for Timing of Death in Potential Donors After Circulatory Death (DCD III): Protocol for a Multicenter Prospective Observational Cohort Study SN - 1929-0748 IS - iss. 6 JF - JMIR Research Protocols VL - vol. 9 DO - https://doi.org/10.2196/16733 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/220528/220528.pdf?sequence=1 ER - TY - JOUR AU - Roesthuis, L.H. AU - Hoeven, J.G. van der AU - Hees, H.W.H. van AU - Schellekens, W.M. AU - Doorduin, J. AU - Heunks, L.M. PY - 2020 UR - https://hdl.handle.net/2066/220537 AB - BACKGROUND: Inappropriate ventilator assist plays an important role in the development of diaphragm dysfunction. Ventilator under-assist may lead to muscle injury, while over-assist may result in muscle atrophy. This provides a good rationale to monitor respiratory drive in ventilated patients. Respiratory drive can be monitored by a nasogastric catheter, either with esophageal balloon to determine muscular pressure (gold standard) or with electrodes to measure electrical activity of the diaphragm. A disadvantage is that both techniques are invasive. Therefore, it is interesting to investigate the role of surrogate markers for respiratory dive, such as extradiaphragmatic inspiratory muscle activity. The aim of the current study was to investigate the effect of different inspiratory support levels on the recruitment pattern of extradiaphragmatic inspiratory muscles with respect to the diaphragm and to evaluate agreement between activity of extradiaphragmatic inspiratory muscles and the diaphragm. METHODS: Activity from the alae nasi, genioglossus, scalene, sternocleidomastoid and parasternal intercostals was recorded using surface electrodes. Electrical activity of the diaphragm was measured using a multi-electrode nasogastric catheter. Pressure support (PS) levels were reduced from 15 to 3 cmH(2)O every 5 min with steps of 3 cmH(2)O. The magnitude and timing of respiratory muscle activity were assessed. RESULTS: We included 17 ventilated patients. Diaphragm and extradiaphragmatic inspiratory muscle activity increased in response to lower PS levels (36 ± 6% increase for the diaphragm, 30 ± 6% parasternal intercostals, 41 ± 6% scalene, 40 ± 8% sternocleidomastoid, 43 ± 6% alae nasi and 30 ± 6% genioglossus). Changes in diaphragm activity correlated best with changes in alae nasi activity (r(2) = 0.49; P < 0.001), while there was no correlation between diaphragm and sternocleidomastoid activity. The agreement between diaphragm and extradiaphragmatic inspiratory muscle activity was low due to a high individual variability. Onset of alae nasi activity preceded the onset of all other muscles. CONCLUSIONS: Extradiaphragmatic inspiratory muscle activity increases in response to lower inspiratory support levels. However, there is a poor correlation and agreement with the change in diaphragm activity, limiting the use of surface electromyography (EMG) recordings of extradiaphragmatic inspiratory muscles as a surrogate for electrical activity of the diaphragm. TI - Recruitment pattern of the diaphragm and extradiaphragmatic inspiratory muscles in response to different levels of pressure support SN - 2110-5820 IS - iss. 1 JF - Annals of Intensive Care VL - vol. 10 DO - https://doi.org/10.1186/s13613-020-00684-6 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/220537/220537.pdf?sequence=1 ER - TY - JOUR AU - Loon, Lex M. van AU - Hoeven, H. van der AU - Veltink, Peter H. AU - Lemson, J. PY - 2020 UR - https://hdl.handle.net/2066/227282 TI - The inspiration hold maneuver is a reliable method to assess mean systemic filling pressure but its clinical value remains unclear SN - 2305-5839 IS - iss. 21 JF - Annals of Translational Medicine VL - vol. 8 DO - https://doi.org/10.21037/atm-20-3540 ER - TY - JOUR AU - Bersselaar, L.R. van den AU - Brule, J.M.D. van den AU - Hoeven, J.G. van der PY - 2020 UR - https://hdl.handle.net/2066/224862 AB - Acetaminophen and flucloxacillin both interfere with the γ-glutamyl cycle. Long-lasting concomitant use of flucloxacillin and acetaminophen can lead to 5-oxoproline accumulation and severe high anion gap metabolic acidosis. Females and patients with sepsis, impaired kidney and/or liver function, malnutrition, advanced age, congenital 5-oxoprolinase deficiency and supratherapeutic acetaminophen and flucloxacillin dosage are associated with increased risk. Therefore, a critical attitude towards the prescription of acetaminophen concomitant with flucloxacillin in these patients is needed. We present the case of a 79-year-old woman with severe 5-oxoprolinaemia after long-lasting treatment with flucloxacillin and acetaminophen, explaining the toxicological mechanism and risk factors, and we make recommendations for acetaminophen use in patients with long-lasting flucloxacillin treatment. LEARNING POINTS: Although rare, long-lasting treatment with flucloxacillin concomitant with acetaminophen can lead to severe high anion gap metabolic acidosis.When prescribing long-lasting flucloxacillin therapy in combination with acetaminophen, regular blood gas analysis is needed to evaluate pH and the anion gap.In cases of 5-oxoproline-induced high anion gap metabolic acidosis in patients with long-lasting acetaminophen and flucloxacillin therapy, acetaminophen prescription should be stopped immediately. Replacing flucloxacillin with another antibiotic agent should be considered. TI - Acetaminophen Use Concomitant with Long-Lasting Flucloxacillin Therapy: A Dangerous Combination SN - 2284-2594 IS - iss. 7 JF - European Journal of Case Reports in Internal Medicine VL - vol. 7 DO - https://doi.org/10.12890/2020_001569 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/224862/224862.pdf?sequence=1 ER - TY - JOUR AU - Duprey, Matthew S. AU - Boogaard, M.H.W.A. van den AU - Hoeven, J.G. van der AU - Pickkers, P. AU - Briesacher, Becky A. AU - Saczynski, Jane S. AU - Griffith, John L. AU - Devlin, John W. PY - 2020 UR - https://hdl.handle.net/2066/218801 TI - Association between incident delirium and 28-and 90-day mortality in critically ill adults: a secondary analysis SN - 1466-609X IS - iss. 1 JF - Critical Care VL - vol. 24 DO - https://doi.org/10.1186/s13054-020-02879-6 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/218801/218801.pdf?sequence=1 ER - TY - JOUR AU - Berg, M.J.W. van den AU - Hoeven, H. van der PY - 2020 UR - https://hdl.handle.net/2066/229442 TI - In Patients with ARDS, Optimal PEEP Should Not Be Determined Using the Intersection of Relative Collapse and Relative Overdistention EP - 1189 SN - 1073-449X IS - iss. 8 SP - 1189 JF - American Journal of Respiratory and Critical Care Medicine VL - vol. 202 DO - https://doi.org/10.1164/rccm.202006-2175LE ER - TY - JOUR AU - IJland, M.M. AU - Roesthuis, L.H. AU - Kamphuis, K. AU - Hoeven, J.G. van der AU - Lemson, J. PY - 2020 UR - https://hdl.handle.net/2066/229420 TI - Extreme Expiratory Flow Limitation in a Child due to a Double Aortic Arch EP - 1709 SN - 1073-449X IS - iss. 12 SP - 1707 JF - American Journal of Respiratory and Critical Care Medicine VL - vol. 202 DO - https://doi.org/10.1164/rccm.202006-2468IM ER - TY - JOUR AU - Lassche, G. AU - Frenzel, T. AU - Mignot, M.H. AU - Jonker, M.A. AU - Hoeven, H. van der AU - Herpen, C.M.L. van AU - Scheffer, G.J. PY - 2020 UR - https://hdl.handle.net/2066/218323 AB - BACKGROUND: Extracorporeally induced whole-body hyperthermia (eWBH) might be a beneficial treatment in cancer patients. Objectives of this pig study were to assess thermal distribution, (patho-)physiological effects, and safety of eWBH with a new WBH device. METHODS: Fourteen healthy adult pigs were anesthetized, mechanically ventilated, and cannulated; 12 were included in the analysis. Blood was heated in 11 pigs (one pig served as control) using a WBH device (Vither Hyperthermia B.V.) containing two separate fluidic circuits and a heat exchanger. Temperature was monitored on nine different sites, including the brain. Core temperature (average of 4 deep probes) was elevated to 42 degrees C for 2 hr. RESULTS: Elevation of core body temperature to 42 degrees C took on average (+/- standard deviation) 38 +/- 8 min. Initially observed temperature spikes diminished after lowering maximal blood temperature to 45 degrees C. Hereafter, brain temperature spikes never exceeded 42.5 degrees C, mean brain temperature was at highest 41.9 degrees C during maintenance. WBH resulted in increased heart rates and decreased mean arterial pressures. The vast amounts of fluids required to counter hypotension tended to be smaller after corticosteroid administration. Hemodialysis was started in three animals (potassium increase prevention in two and hyperkalemia treatment in one). Severe rhabdomyolysis was observed in all pigs (including the control). All animals survived the procedure until planned euthanasia 1, 6, or 24 hr post procedure. CONCLUSION: Fast induction of eWBH with homogenous thermal distribution is feasible in pigs using the Vither WBH device. Severe hemodynamic disturbances, rhabdomyolysis, and hyperkalemia were observed. TI - Thermal distribution, physiological effects and toxicities of extracorporeally induced whole-body hyperthermia in a pig model SN - 2051-817X IS - iss. 4 JF - Physiological Reports VL - vol. 8 DO - https://doi.org/10.14814/phy2.14366 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/218323/218323.pdf?sequence=1 ER - TY - JOUR AU - Kotsopoulos, A.M.M. AU - Jansen, N.E. AU - Vos, P . de AU - Witjes, M. AU - Volbeda, M. AU - Epker, J.L. AU - Sonneveld, H.P.C. AU - Simons, K.S. AU - Bronkhorst, E.M. AU - Hoeven, H. van der AU - Abdo, W.F. PY - 2020 UR - https://hdl.handle.net/2066/229141 AB - Controlled donation after circulatory death (cDCD) occurs after a decision to withdraw life-sustaining treatment and subsequent family approach and approval for donation. We currently lack data on factors that impact the decision-making process on withdraw life-sustaining treatment and whether time from admission to family approach, influences family consent rates. Such insights could be important in improving the clinical practice of potential cDCD donors. In a prospective multicenter observational study, we evaluated the impact of timing and of the clinical factors during the end-of-life decision-making process in potential cDCD donors. Characteristics and medication use of 409 potential cDCD donors admitted to the intensive care units (ICUs) were assessed. End-of-life decision-making was made after a mean time of 97 hours after ICU admission and mostly during the day. Intracranial hemorrhage or ischemic stroke and a high APACHE IV score were associated with a short decision-making process. Preserved brainstem reflexes, high Glasgow Coma Scale scores, or cerebral infections were associated with longer time to decision-making. Our data also suggest that the organ donation request could be made shortly after the decision to stop active treatment and consent rates were not influenced by daytime or nighttime or by the duration of the ICU stay. TI - Determining the impact of timing and of clinical factors during end-of-life decision-making in potential controlled donation after circulatory death donors EP - 3581 SN - 1600-6135 IS - iss. 12 SP - 3574 JF - American Journal of Transplantation VL - vol. 20 DO - https://doi.org/10.1111/ajt.16104 ER - TY - JOUR AU - Sonnemans, L.J.P. AU - Bayat, A.R. AU - Bruinen, Aniek R.C. AU - Wely, M.H. van AU - Brouwer, M.A. AU - Bosboom, D.G. AU - Hoeven, J.G. van der AU - Prokop, M. AU - Klein, W.M. PY - 2020 UR - https://hdl.handle.net/2066/219245 TI - Comparing thoracoabdominal injuries of manual versus load-distributing band cardiopulmonary resuscitation EP - 201 SN - 0969-9546 IS - iss. 3 SP - 197 JF - European Journal of Emergency Medicine VL - vol. 27 DO - https://doi.org/10.1097/MEJ.0000000000000642 ER - TY - JOUR AU - Spoormans, E.M. AU - Lemkes, Jorrit S. AU - Janssens, Gladys N. AU - Hoeven, Nina W. van der AU - Jewbali, Lucia S.D. AU - Dubois, Eric A. AU - Blans, Michiel J. AU - Camaro, C. AU - Hoeven, H. van der AU - Appelman, Y. AU - Royen, N. van PY - 2020 UR - https://hdl.handle.net/2066/228692 TI - Data on sex differences in one-year outcomes of out-of-hospital cardiac arrest patients without ST-segment elevation SN - 2352-3409 JF - Data in Brief VL - vol. 33 DO - https://doi.org/10.1016/j.dib.2020.106521 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/228692/228692.pdf?sequence=1 ER - TY - JOUR AU - Vreman, J.T.M. AU - Loon, Lex M. van AU - Biggelaar, Wilma van den AU - Hoeven, J.G. van der AU - Lemson, J. AU - Boogaard, M. van den PY - 2020 UR - https://hdl.handle.net/2066/228518 TI - Contribution of alarm noise to average sound pressure levels in the ICU: An observational cross-sectional study SN - 0964-3397 JF - Intensive and Critical Care Nursing VL - vol. 61 DO - https://doi.org/10.1016/j.iccn.2020.102901 ER - TY - JOUR AU - Loon, L.M. van AU - Stolk, R.F. AU - Hoeven, J.G. van der AU - Veltink, P.H. AU - Pickkers, P. AU - Lemson, J. AU - Kox, M. PY - 2020 UR - https://hdl.handle.net/2066/218558 AB - AIM: Comparing the effects of different vasopressors in septic shock patients is hampered by high heterogeneity and the fact that current guidelines dictate the use of norepinephrine. Herein, we studied the effects of three vasopressor agents, norepinephrine, phenylephrine, and vasopressin, on the macro- and microcirculation during experimental human endotoxemia, a standardized, controlled model of systemic inflammation in humans in vivo. METHODS: We performed a randomized controlled study in which 40 healthy male volunteers were assigned to a 5-h infusion of either 0.05 mug/kg/min norepinephrine (n = 10), 0.5 mug/kg/min phenylephrine (n = 10), 0.04 IU/min vasopressin (n = 10), or saline (n = 10), starting 1 h before intravenous administration of 2 ng/kg lipopolysaccharide (LPS). The macrocirculation was monitored using arterial catheter-derived parameters with additional blood pressure waveform contour analysis (PCA) until 4.5 h following LPS administration. Sublingual microcirculatory density and flow were assessed using a handheld video microscope until 6 h post-LPS. RESULTS: LPS administration affected all macrocirculatory and microcirculatory parameters. The LPS-induced decrease in blood pressure and systemic vascular resistance (SVR) was refractory to low-dose norepinephrine and phenylephrine, and to a lesser extent, to vasopressin. Only vasopressin exerted effects on PCA parameters compared with placebo, by mitigating the LPS-induced decrease in diastolic blood pressure by stabilizing SVR and cardiac output. The endotoxemia-induced decreased indices of microvascular flow and density were not influenced by vasopressor therapy. CONCLUSIONS: In a highly controlled model of systemic inflammation in humans in vivo, a 5-h infusion of various vasopressors revealed distinctive effects on macrohemodynamic variables without affecting the sublingual microcirculation. TI - Effect of Vasopressors on the Macro- and Microcirculation During Systemic Inflammation in Humans In Vivo EP - 174 SN - 1073-2322 IS - iss. 2 SP - 171 JF - Shock VL - vol. 53 DO - https://doi.org/10.1097/SHK.0000000000001357 ER - TY - JOUR AU - Roesthuis, L.H. AU - Berg, M.J.W. van den AU - Hoeven, H. van der PY - 2020 UR - https://hdl.handle.net/2066/220518 TI - Advanced respiratory monitoring in COVID-19 patients: use less PEEP! SN - 1466-609X IS - iss. 1 JF - Critical Care VL - vol. 24 DO - https://doi.org/10.1186/s13054-020-02953-z L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/220518/220518.pdf?sequence=1 ER - TY - JOUR AU - Veerdonk, F.L. van de AU - Netea, M.G. AU - Deuren, M. van AU - Meer, J.W.M. van der AU - Mast, Q. de AU - Bruggemann, R.J.M. AU - Hoeven, H. van der PY - 2020 UR - https://hdl.handle.net/2066/220675 AB - COVID-19 patients can present with pulmonary edema early in disease. We propose that this is due to a local vascular problem because of activation of bradykinin 1 receptor (B1R) and B2R on endothelial cells in the lungs. SARS-CoV-2 enters the cell via ACE2 that next to its role in RAAS is needed to inactivate des-Arg9 bradykinin, the potent ligand of the B1R. Without ACE2 acting as a guardian to inactivate the ligands of B1R, the lung environment is prone for local vascular leakage leading to angioedema. Here, we hypothesize that a kinin-dependent local lung angioedema via B1R and eventually B2R is an important feature of COVID-19. We propose that blocking the B2R and inhibiting plasma kallikrein activity might have an ameliorating effect on early disease caused by COVID-19 and might prevent acute respiratory distress syndrome (ARDS). In addition, this pathway might indirectly be responsive to anti-inflammatory agents. The COVID-19 pandemic represents an unprecedented threat to global health. Millions of cases have been confirmed around the world, and hundreds of thousands of people have lost their lives. Common symptoms include a fever and persistent cough and COVID-19 patients also often experience an excess of fluid in the lungs, which makes it difficult to breathe. In some cases, this develops into a life-threatening condition whereby the lungs cannot provide the body's vital organs with enough oxygen. The SARS-CoV-2 virus, which causes COVID-19, enters the lining of the lungs via an enzyme called the ACE2 receptor, which is present on the outer surface of the lungs' cells. The related coronavirus that was responsible for the SARS outbreak in the early 2000s also needs the ACE2 receptor to enter the cells of the lungs. In SARS, the levels of ACE2 in the lung decline during the infection. Studies with mice have previously revealed that a shortage of ACE2 leads to increased levels of a hormone called angiotensin II, which regulates blood pressure. As a result, much attention has turned to the potential link between this hormone system in relation to COVID-19. However, other mouse studies have shown that ACE2 protects against a build-up of fluid in the lungs caused by a different molecule made by the body. This molecule, which is actually a small fragment of a protein, lowers blood pressure and causes fluid to leak out of blood vessels. It belongs to a family of molecules known as kinins, and ACE2 is known to inactivate certain kinins. This led van de Veerdonk et al. to propose that the excess of fluid in the lungs seen in COVID-19 patients may be because kinins are not being neutralized due to the shortage of the ACE2 receptor. This had not been hypothesized before, even though the mechanism could be the same in SARS which has been researched for the past 17 years. If this hypothesis is correct, it would mean that directly inhibiting the receptor for the kinins (or the proteins that they come from) may be the only way to stop fluid leaking into the lungs of COVID-19 patients in the early stage of disease. This hypothesis is unproven, and more work is needed to see if it is clinically relevant. If that work provides a proof of concept, it means that existing treatments and registered drugs could potentially help patients with COVID-19, by preventing the need for mechanical ventilation and saving many lives. eng TI - Kallikrein-kinin blockade in patients with COVID-19 to prevent acute respiratory distress syndrome SN - 2050-084X JF - Elife VL - vol. 9 DO - https://doi.org/10.7554/eLife.57555 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/220675/220675.pdf?sequence=1 ER - TY - JOUR AU - Veerdonk, F.L. van de AU - Kouijzer, I.J.E. AU - Nooijer, A.H. de AU - Hoeven, H. van der AU - Maas, C. AU - Netea, M.G. AU - Brüggemann, R.J.M. PY - 2020 UR - https://hdl.handle.net/2066/225335 AB - This case-control study examines the association between receipt of the bradykinin 2 (B2) receptor antagonist icatibant and improved oxygenation in patients with coronavirus disease 2019 (COVID-19). TI - Outcomes Associated With Use of a Kinin B2 Receptor Antagonist Among Patients With COVID-19 SN - 2574-3805 IS - iss. 8 JF - JAMA Network Open VL - vol. 3 DO - https://doi.org/10.1001/jamanetworkopen.2020.17708 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/225335/225335.pdf?sequence=1 ER - TY - JOUR AU - Kooistra, E.J. AU - Waalders, N.J.B. AU - Grondman, I. AU - Janssen, N.A.F. AU - Nooijer, A.H. de AU - Netea, M.G. AU - Veerdonk, F.L. van de AU - Hoeven, J.G. van der AU - Joosten, I. AU - Kox, M. AU - Pickkers, P. PY - 2020 UR - https://hdl.handle.net/2066/228401 TI - Anakinra treatment in critically ill COVID-19 patients: a prospective cohort study SN - 1466-609X IS - iss. 1 JF - Critical Care VL - vol. 24 DO - https://doi.org/10.1186/s13054-020-03364-w L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/228401/228401.pdf?sequence=1 ER - TY - JOUR AU - Jonkman, A.H. AU - Roesthuis, L.H. AU - Boer, E.C. de AU - Vries, H.J.C. de AU - Girbes, Armand R.J. AU - Hoeven, J.G. van der AU - Tuinman, P.R. AU - Heunks, L.M.A. PY - 2020 UR - https://hdl.handle.net/2066/220795 TI - Inadequate Assessment of Patient-Ventilator Interaction Due to Suboptimal Diaphragm Electrical Activity Signal Filtering EP - 144 SN - 1073-449X IS - iss. 1 SP - 141 JF - American Journal of Respiratory and Critical Care Medicine VL - vol. 202 DO - https://doi.org/10.1164/rccm.201912-2306LE ER - TY - JOUR AU - Kox, M. AU - Frenzel, T. AU - Schouten, J.A. AU - Veerdonk, F.L. van de AU - Hemelaar, P. AU - Beunders, R. AU - Hoeven, J.G. van der AU - Gerretsen, J.J.F. AU - Netea, M.G. AU - Joosten, L.A.B. AU - Janssen, N.A.F. AU - Grondman, I. AU - Nooijer, A.H. de AU - Mast, Q. de AU - Jaeger, M. AU - Kouijzer, I.J.E. AU - Lemmers, H.L.M. AU - Crevel, R. van AU - Maat, J.S. van de AU - Moorlag, S.J.C.F.M. AU - Taks, E.J.M. AU - Debisarun, A. AU - Wertheim, H.F.L. AU - Hopman, J. AU - Rahamat-Langendoen, J.C. AU - Bleeker-Rovers, C.P. AU - Fasse, E. AU - Rijssen, E. van AU - Cranenbroek, B. van AU - Smeets, R.L. AU - Joosten, I. AU - Koenen, H.J. AU - Pickkers, P. PY - 2020 UR - https://hdl.handle.net/2066/220045 TI - COVID-19 patients exhibit less pronounced immune suppression compared with bacterial septic shock patients SN - 1466-609X IS - iss. 1 JF - Critical Care VL - vol. 24 DO - https://doi.org/10.1186/s13054-020-02896-5 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/220045/220045.pdf?sequence=1 ER - TY - JOUR AU - Made, C.I. van der AU - Simons, A. AU - Schuurs-Hoeijmakers, J.H.M. AU - Heuvel, Guus van den AU - Mantere, T. AU - Kersten, S. AU - Deuren, R.C. van AU - Steehouwer, M. AU - Reijmersdal, S.V. van AU - Jaeger, M. AU - Astuti, G.D. AU - Corominas-Galbany, J. AU - Hoeven, J.G. van der AU - Hagmolen of ten Have, W. AU - Mast, Q. de AU - Bleeker-Rovers, C.P. AU - Joosten, L.A.B. AU - Yntema, H.G. AU - Gilissen, C.F. AU - Nelen, M.R. AU - Meer, J.W.M. van der AU - Brunner, H.G. AU - Netea, M.G. AU - Veerdonk, F.L. van de AU - Hoischen, A. PY - 2020 UR - https://hdl.handle.net/2066/222168 TI - Presence of Genetic Variants Among Young Men With Severe COVID-19 EP - 673 SN - 0098-7484 IS - iss. 7 SP - 663 JF - Jama : Journal of the American Medical Association VL - vol. 324 DO - https://doi.org/10.1001/jama.2020.13719 ER - TY - JOUR AU - Berkel, M. van AU - Kox, M. AU - Frenzel, T. AU - Bruse, N. AU - Kooistra, E.J. AU - Touw, H.R.W. AU - Hemelaar, P. AU - Beunders, R. AU - Hoeven, J.G. van der AU - Gerretsen, J.J.F. AU - Heesakkers, H.G.P. AU - Netea, M.G. AU - Joosten, L.A.B. AU - Janssen, N.A.F. AU - Grondman, I. AU - Nooijer, A.H. de AU - Mast, Q. de AU - Jaeger, M. AU - Kouijzer, I.J.E. AU - Lemmers, H.L.M. AU - Crevel, R. van AU - Maat, J.S. van de AU - Moorlag, S.J.C.F.M. AU - Taks, E.J.M. AU - Debisarun, A. AU - Wertheim, H.F.L. AU - Hopman, J. AU - Rahamat-Langendoen, J.C. AU - Bleeker-Rovers, C.P. AU - Fasse, E. AU - Rijssen, E. van AU - Cranenbroek, B. van AU - Smeets, R.L. AU - Joosten, I. AU - Pickkers, P. AU - Schouten, J.A. PY - 2020 UR - https://hdl.handle.net/2066/229373 TI - Biomarkers for antimicrobial stewardship: a reappraisal in COVID-19 times? SN - 1466-609X IS - iss. 1 JF - Critical Care VL - vol. 24 DO - https://doi.org/10.1186/s13054-020-03291-w L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/229373/229373.pdf?sequence=1 ER - TY - JOUR AU - Kolk, B.M. van der AU - Boogaard, M. van den AU - Hoeven, J.G. van der AU - Noyez, L. AU - Pickkers, P. PY - 2019 UR - https://hdl.handle.net/2066/209694 TI - Sustainability of clinical pathway guided care in cardiac surgery ICU patients; 9-years experience in over 7500 patients EP - 463 SN - 1353-4505 IS - iss. 6 SP - 456 JF - International Journal for Quality in Health Care VL - vol. 31 DO - https://doi.org/10.1093/intqhc/mzy190 ER - TY - JOUR AU - Roesthuis, L.H. AU - Hoeven, H. van der AU - Sinderby, C. AU - Frenzel, T. AU - Ottenheijm, C. AU - Brochard, L. AU - Doorduin, J. AU - Heunks, L. PY - 2019 UR - https://hdl.handle.net/2066/208617 AB - PURPOSE: Respiratory muscle weakness frequently develops in critically ill patients and is associated with adverse outcome, including difficult weaning from mechanical ventilation. Today, no drug is approved to improve respiratory muscle function in these patients. Previously, we have shown that the calcium sensitizer levosimendan improves calcium sensitivity of human diaphragm muscle fibers in vitro and contractile efficiency of the diaphragm in healthy subjects. The main purpose of this study is to investigate the effects of levosimendan on diaphragm contractile efficiency in mechanically ventilated patients. METHODS: In a double-blind randomized placebo-controlled trial, mechanically ventilated patients performed two 30-min continuous positive airway pressure (CPAP) trials with 5-h interval. After the first CPAP trial, study medication (levosimendan 0.2 microg/kg/min continuous infusion or placebo) was administered. During the CPAP trials, electrical activity of the diaphragm (EAdi), transdiaphragmatic pressure (Pdi), and flow were measured. Neuromechanical efficiency (primary outcome parameter) was calculated. RESULTS: Thirty-nine patients were included in the study. Neuromechanical efficiency was not different during the CPAP trial after levosimendan administration compared to the CPAP trial before study medication. Tidal volume and minute ventilation were higher after levosimendan administration (11 and 21%, respectively), whereas EAdi and Pdi were higher in both groups in the CPAP trial after study medication compared to the CPAP trial before study medication. CONCLUSIONS: Levosimendan does not improve diaphragm contractile efficiency. TI - Effects of levosimendan on respiratory muscle function in patients weaning from mechanical ventilation EP - 1381 SN - 0342-4642 IS - iss. 10 SP - 1372 JF - Intensive Care Medicine VL - vol. 45 DO - https://doi.org/10.1007/s00134-019-05767-y L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/208617/208617.pdf?sequence=1 ER - TY - JOUR AU - Bogaerts, J.M.A. AU - Hoeven, J.G. van der AU - Arts, E.E.A. AU - Kolk, B.M. van der AU - Brosens, L.A.A. PY - 2019 UR - https://hdl.handle.net/2066/208636 TI - Fish scale crystals: an under-recognised cause of intestinal necrosis SN - 0021-9746 IS - iss. 8 SP - 567 JF - Journal of Clinical Pathology : the Journal of the Association of Clinical Pathologists VL - vol. 72 DO - https://doi.org/10.1136/jclinpath-2018-205203 ER - TY - JOUR AU - Witjes, M. AU - Kruijff, P.E.V. AU - Haase-Kromwijk, B. AU - Hoeven, J.G. van der AU - Jansen, N.E. AU - Abdo, W.F. PY - 2019 UR - https://hdl.handle.net/2066/208686 AB - BACKGROUND: The aim of this nationwide observational study is to identify modifiable factors in communication about organ donation that influence family consent rates. METHODS: Thirty-two intensivists specialized in organ donation systematically evaluated all consecutive organ donation requests with physicians in the Netherlands between January 2013 and June 2016, using a standardized questionnaire. RESULTS: Out of 2528 consecutive donation requests, 2095 (83%) were evaluated with physicians. The questionnaires of patients registered with consent or objection in the national donor registry were excluded from analysis. Only those questionnaires, in which the family had to make a decision about donation, were analyzed (n = 1322). Independent predictors of consent included: requesting organ donation during the conversation about futility of treatment (OR 1.8; p = 0.004), understanding of the term 'brain death' by the family (OR 2.4; p = 0.002), and consulting a donation expert prior to the donation request (OR 3.4; p < 0.001). CONCLUSIONS: Our study showed that decoupling the organ donation conversation from the conversation about futility of treatment was associated with lower family consent rates. Comprehension of the concept of brain death by the family and consultation with a transplant coordinator before the organ donation request by the physician could positively influence consent rates. TI - Physician Experiences with Communicating Organ Donation with the Relatives: A Dutch Nationwide Evaluation on Factors that Influence Consent Rates EP - 364 SN - 1541-6933 IS - iss. 2 SP - 357 JF - Neurocritical Care VL - vol. 31 DO - https://doi.org/10.1007/s12028-019-00678-8 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/208686/208686.pdf?sequence=1 ER - TY - JOUR AU - Rood, P.J.T. AU - Zegers, M. AU - Slooter, A.J. AU - Beishuizen, Albertus AU - Simons, K.S. AU - Voort, P.H. van der AU - Hoeven, J.G. van der AU - Pickkers, P. AU - Boogaard, M.H.W.A. van den PY - 2019 UR - https://hdl.handle.net/2066/206245 TI - Prophylactic Haloperidol Effects on Long-term Quality of Life in Critically Ill Patients at High Risk for Delirium Results of the REDUCE Study EP - 335 SN - 0003-3022 IS - iss. 2 SP - 328 JF - Anesthesiology VL - vol. 131 DO - https://doi.org/10.1097/ALN.0000000000002812 ER - TY - JOUR AU - Verlaat, C.W.M. AU - Wubben, N. AU - Visser, I.H. AU - Hazelzet, J.A. AU - Waardenburg, D. van AU - Dam, Nicolette A. van AU - Hoeven, J.G. van der AU - Lemson, J. AU - Boogaard, M. van den PY - 2019 UR - https://hdl.handle.net/2066/206255 TI - Retrospective cohort study on factors associated with mortality in high-risk pediatric critical care patients in the Netherlands SN - 1471-2431 IS - iss. 1 JF - BMC Pediatrics VL - vol. 19 DO - https://doi.org/10.1186/s12887-019-1646-9 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/206255/206255.pdf?sequence=1 ER - TY - JOUR AU - Blans, M.J. AU - Bosch, F.H. AU - Hoeven, J.G. van der PY - 2019 UR - https://hdl.handle.net/2066/206870 TI - A practical approach to critical care ultrasound EP - 164 SN - 0883-9441 SP - 156 JF - Journal of Critical Care VL - vol. 51 DO - https://doi.org/10.1016/j.jcrc.2019.01.002 ER - TY - JOUR AU - Loon, L.M. van AU - Hoeven, J.G. van der AU - Lemson, J. PY - 2019 UR - https://hdl.handle.net/2066/206550 AB - The administration of beta-blockers in patients with sepsis is a trending topic in intensive care medicine since the landmark study by Morelli and colleagues, showing a striking decrease in 28-day mortality compared to standard care. While the available evidence suggests that the use of beta-blockers in septic shock is safe, the effects on hemodynamics are controversial. In this paper, we review the effect of beta-blockade in septic shock on hemodynamics from animal models to critically ill patients. TI - Hemodynamic response to beta-blockers in severe sepsis and septic shock: A review of current literature EP - 143 SN - 0883-9441 SP - 138 JF - Journal of Critical Care VL - vol. 50 DO - https://doi.org/10.1016/j.jcrc.2018.12.003 ER - TY - JOUR AU - Witjes, M. AU - Jansen, N.E. AU - Hoeven, J.G. van der AU - Abdo, W.F. PY - 2019 UR - https://hdl.handle.net/2066/206616 AB - BACKGROUND: The last decade, there have been many initiatives worldwide to increase the number of organ donors. However, it is not clear which initiatives are most effective. The aim of this study is to provide an overview of interventions aimed at healthcare professionals in order to increase the number of organ donors. METHODS: We systematically searched PubMed, EMBASE, CINAHL, PsycINFO, and the Cochrane Library for English language studies published until April 24, 2019. We included studies describing interventions in hospitals aimed at healthcare professionals who are involved in the identification, referral, and care of a family of potential organ donors. After the title abstract and full-text selection, two reviewers independently assessed each study's quality and extracted data. RESULTS: From the 18,854 records initially extracted from five databases, we included 22 studies in our review. Of these 22 studies, 14 showed statistically significant effects on identification rate, family consent rate, and/or donation rate. Interventions that positively influenced one or more of these outcomes were training of emergency personnel in organ donation, an electronic support system to identify and/or refer potential donors, a collaborative care pathway, donation request by a trained professional, and additional family support in the ICU by a trained nurse. The methodological quality of the studies was relatively low, mainly because of the study designs. CONCLUSIONS: Although there is paucity of data, collaborative care pathways, training of healthcare professionals and additional support for relatives of potential donors seem to be promising interventions to increase the number of organ donors. TRIAL REGISTRATION: PROSPERO, CRD42018068185. TI - Interventions aimed at healthcare professionals to increase the number of organ donors: a systematic review SN - 1466-609X IS - iss. 1 SP - 227 JF - Critical Care VL - vol. 23 DO - https://doi.org/10.1186/s13054-019-2509-3 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/206616/206616.pdf?sequence=1 ER - TY - JOUR AU - Bersselaar, L.R. van den AU - Hoeven, J.G. van der AU - Jong, B. De PY - 2019 UR - https://hdl.handle.net/2066/206724 AB - Pesticide self-poisoning is rare in developed countries. We report a suicide case after inhalation of a pyrethrins containing insecticide spray. The patient presented at the emergency department with respiratory failure. Despite mechanical ventilation, he developed severe pulmonary inflammation with a systemic inflammatory response syndrome and died 5 days later. Studies reporting on acute pyrethrins or pyrethroids insecticide poisoning in both occupational and non-occupational cases usually describe mild and self-limiting respiratory symptoms as the predominant symptom. Severe or fatal cases of pyrethrins or pyrethroids poisoning are very rare. Patients with asthma or allergies are apparently more at risk for severe symptoms. In these cases, early and aggressive treatment with bronchodilatators, steroids, antihistamines and epinephrine should be considered. TI - Suicide after inhaling a pyrethrins containing insecticide spray SN - 1757-790X IS - iss. 4 JF - BMJ Case Reports VL - vol. 12 DO - https://doi.org/10.1136/bcr-2018-227936 ER - TY - JOUR AU - Witjes, M. AU - Kotsopoulos, A.M.M. AU - Otterspoor, L. AU - Herold, I.H.F. AU - Simons, K.S. AU - Woittiez, K. AU - Eijkenboom, J.J. AU - Hoeven, J.G. van der AU - Jansen, N.E. AU - Abdo, W.F. PY - 2019 UR - https://hdl.handle.net/2066/215536 AB - BACKGROUND: The aim of this study was to evaluate the implementation process of a multidisciplinary approach for potential organ donors in the emergency department (ED) in order to incorporate organ donation into their end-of-life care plans. METHODS: A new multidisciplinary approach was implemented in 6 hospitals in The Netherlands between January 2016 and January 2018. The approach was introduced during staff meetings in the ED, intensive care unit (ICU), and neurology department. When patients with a devastating brain injury had a futile prognosis in the ED, without contraindications for organ donation, an ICU admission was considered. Every ICU admission to incorporate organ donation into end-of-life care was systematically evaluated with the involved physicians using a standardized questionnaire. RESULTS: In total, 55 potential organ donors were admitted to the ICU to incorporate organ donation into end-of-life care. Twenty-seven families consented to donation and 20 successful organ donations were performed. Twenty-nine percent of the total pool of organ donors in these hospitals were admitted to the ICU for organ donation. CONCLUSIONS: Patients with a devastating brain injury and futile medical prognosis in the ED are an important proportion of the total number of donors. The implementation of a multidisciplinary approach is feasible and could lead to better identification of potential donors in the ED. TI - The Implementation of a Multidisciplinary Approach for Potential Organ Donors in the Emergency Department EP - 2365 SN - 0041-1337 IS - iss. 11 SP - 2359 JF - Transplantation VL - vol. 103 DO - https://doi.org/10.1097/TP.0000000000002701 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/215536/215536.pdf?sequence=1 ER - TY - JOUR AU - Blans, M.J. AU - Bosch, F.H. AU - Hoeven, J.G. van der PY - 2019 UR - https://hdl.handle.net/2066/215548 AB - BACKGROUND: In critical care medicine, the use of transthoracic echo (TTE) is expanding. TTE can be used to measure dynamic parameters such as cardiac output (CO). An important asset of TTE is that it is a non-invasive technique. The Probefix is an external ultrasound holder strapped to the patient which makes it possible to measure CO using TTE in a fixed position possibly making the CO measurements more accurate compared to separate TTE CO measurements. The feasibility of the use of the Probefix to measure CO before and after a passive leg raising test (PLR) was studied. Intensive care patients were included after detection of hypovolemia using Flotrac. Endpoints were the possibility to use Probefix. Also CO measurements with and without the use of Probefix, before and after a PLR were compared to the CO measurements using Flotrac. Side effects in terms of skin alterations after the use of Probefix and patient's comments on (dis)comfort were evaluated. RESULTS: Ten patients were included; in eight patients, sufficient recordings with the use of Probefix could be obtained. Using Bland-Altman plots, no difference was found in accuracy of measurements of CO with or without the use of Probefix before and after a PLR compared to Flotrac generated CO. There were only mild and temporary skin effects of the use of Probefix. CONCLUSIONS: In this small feasibility study, the Probefix could be used in eight out of ten intensive care patients. The use of Probefix did not result in more or less accurate CO measurements compared to manually recorded TTE CO measurements. We suggest that larger studies on the use of Probefix in intensive care patients are needed. TI - The use of an external ultrasound fixator (Probefix) on intensive care patients: a feasibility study SN - 2524-8987 IS - iss. 1 SP - 26 JF - The Ultrasound Journal VL - vol. 11 DO - https://doi.org/10.1186/s13089-019-0140-9 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/215548/215548.pdf?sequence=1 ER - TY - JOUR AU - Loon, L.M. van AU - Rongen, G.A.P.J.M. AU - Hoeven, J.G. van der AU - Veltink, P.H. AU - Lemson, J. PY - 2019 UR - https://hdl.handle.net/2066/215563 AB - Clinical data suggests that heart rate (HR) control with selective beta1-blockers may improve cardiac function during septic shock. However, it seems counterintuitive to start beta-blocker infusion in a shock state when organ blood flow is already low or insufficient. Therefore, we studied the effects of HR control with esmolol, an ultrashort- acting beta1-selective adrenoceptor antagonist, on renal blood flow (RBF) and renal autoregulation during early septic shock. In 10 healthy sheep, sepsis was induced by continuous i.v. administration of lipopolysaccharide, while maintained under anesthesia and mechanically ventilated. After successful resuscitation of the septic shock with fluids and vasoactive drugs, esmolol was infused to reduce HR with 30% and was stopped 30-min after reaching this target. Arterial and venous pressures, and RBF were recorded continuously. Renal autoregulation was evaluated by the response in RBF to renal perfusion pressure (RPP) in both the time domain and frequency domain. During septic shock, beta-blockade with esmolol significantly increased the pressure dependency of RBF to RPP. Stopping esmolol showed the reversibility of the impaired renal autoregulation. Showing that clinical diligence and caution are necessary when treating septic shock with esmolol in the acute phase since esmolol reduced RPP to critical values thereby significantly reducing RBF. TI - beta-Blockade attenuates renal blood flow in experimental endotoxic shock by reducing perfusion pressure SN - 2051-817X IS - iss. 23 SP - e14301 JF - Physiological Reports VL - vol. 7 DO - https://doi.org/10.14814/phy2.14301 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/215563/215563.pdf?sequence=1 ER - TY - JOUR AU - Geense, W.W. AU - Boogaard, M. van den AU - Hoeven, J.G. van der AU - Vermeulen, H. AU - Hannink, G.J. AU - Zegers, M. PY - 2019 UR - https://hdl.handle.net/2066/215482 AB - OBJECTIVE: ICU survivors suffer from long-lasting physical, mental, and cognitive health impairments, also called "postintensive care syndrome". However, an overview of the effectiveness of interventions to prevent or mitigate these impairments is lacking. The aim of this study is to assess the effectiveness of nonpharmacologic interventions. DATA SOURCES: PubMed, CINAHL, PsycINFO, Embase, and Cochrane Library were systematically searched from inception until July 19, 2018. STUDY SELECTION: (Non)randomized clinical trials, controlled before-after studies, and interrupted time series were included. Outcomes of interest included patients physical, mental and cognitive outcomes, quality of life, and outcomes such as social functioning and functional status, measured after hospital discharge. DATA EXTRACTION: Two independent reviewers selected studies, extracted data, and assessed the risk of bias. Pooled mean differences and standardized mean differences were calculated using random-effect meta-analyses. DATA SYNTHESIS: After screening 17,008 articles, 36 studies, including 10 pilot studies, were included (n = 5,165 ICU patients). Interventions were subdivided into six categories: 1) exercise and physical rehabilitation programs; 2) follow-up services; 3) psychosocial programs; 4) diaries; 5) information and education; and 6) other interventions. Many outcomes favored the interventions, but significant differences were only found for diaries in reducing depression (two studies, n = 88; standardized mean difference, 0.68; 95% CI, 0.14-1.21) and anxiety (two studies, n = 88; standardized mean difference, 0.44; 95% CI, 0.01-0.87) and exercise programs in improving the Short Form Health Survey-36 Mental Component Score (seven studies, n = 664; mean difference, 2.62; 95% CI, 0.92-4.32). CONCLUSIONS: There is thin evidence that diaries and exercise programs have a positive effective on mental outcomes. Despite outcomes favoring the intervention group, other commonly used nonpharmacologic interventions in daily ICU practice are not supported by conclusive evidence from this meta-analysis. To improve recovery programs for ICU survivors, more evidence is needed from robust intervention studies using standardized outcomes. TI - Nonpharmacologic Interventions to Prevent or Mitigate Adverse Long-Term Outcomes Among ICU Survivors: A Systematic Review and Meta-Analysis EP - 1618 SN - 0090-3493 IS - iss. 11 SP - 1607 JF - Critical Care Medicine VL - vol. 47 DO - https://doi.org/10.1097/CCM.0000000000003974 ER - TY - JOUR AU - Rood, P.J.T. AU - Frenzel, T. AU - Verhage, R. AU - Bonn, M. AU - Hoeven, H. van der AU - Pickkers, P. AU - Boogaard, M. van den PY - 2019 UR - https://hdl.handle.net/2066/204752 TI - Development and daily use of a numeric rating score to assess sleep quality in ICU patients EP - 74 SN - 0883-9441 SP - 68 JF - Journal of Critical Care VL - vol. 52 DO - https://doi.org/10.1016/j.jcrc.2019.04.009 ER - TY - JOUR AU - Lestrade, P.P. AU - Bentvelsen, R.G. AU - Schauwvlieghe, A. AU - Schalekamp, S. AU - Velden, W.J.F.M. van der AU - Kuiper, E.J. AU - Paassen, J. van AU - Hoven, B. van der AU - Lee, H.A.L. van der AU - Melchers, W.J.G. AU - Haan, A.F. de AU - Hoeven, H. van der AU - Rijnders, B.J.A. AU - Beek, M.T. van der AU - Verweij, P.E. PY - 2019 UR - https://hdl.handle.net/2066/204852 AB - BACKGROUND: Triazole resistance is an increasing problem in invasive aspergillosis (IA). Small case series show mortality rates of 50%-100% in patients infected with a triazole-resistant Aspergillus fumigatus, but a direct comparison with triazole-susceptible IA is lacking. METHODS: A 5-year retrospective cohort study (2011-2015) was conducted to compare mortality in patients with voriconazole-susceptible and voriconazole-resistant IA. Aspergillus fumigatus culture-positive patients were investigated to identify patients with proven, probable, and putative IA. Clinical characteristics, day 42 and day 90 mortality, triazole-resistance profiles, and antifungal treatments were investigated. RESULTS: Of 196 patients with IA, 37 (19%) harbored a voriconazole-resistant infection. Hematological malignancy was the underlying disease in 103 (53%) patients, and 154 (79%) patients were started on voriconazole. Compared with voriconazole-susceptible cases, voriconazole resistance was associated with an increase in overall mortality of 21% on day 42 (49% vs 28%; P = .017) and 25% on day 90 (62% vs 37%; P = .0038). In non-intensive care unit patients, a 19% lower survival rate was observed in voriconazole-resistant cases at day 42 (P = .045). The mortality in patients who received appropriate initial voriconazole therapy was 24% compared with 47% in those who received inappropriate therapy (P = .016), despite switching to appropriate antifungal therapy after a median of 10 days. CONCLUSIONS: Voriconazole resistance was associated with an excess overall mortality of 21% at day 42 and 25% at day 90 in patients with IA. A delay in the initiation of appropriate antifungal therapy was associated with increased overall mortality. TI - Voriconazole Resistance and Mortality in Invasive Aspergillosis: A Multicenter Retrospective Cohort Study EP - 1471 SN - 1058-4838 IS - iss. 9 SP - 1463 JF - Clinical Infectious Diseases VL - vol. 68 DO - https://doi.org/10.1093/cid/ciy859 ER - TY - JOUR AU - Beumer, M.C. AU - Koch, R.M. AU - Beuningen, D. van AU - Oude Lashof, A.M.L. AU - Veerdonk, F.L. van de AU - Kolwijck, E. AU - Hoeven, J.G. van der AU - Bergmans, D.C. AU - Hoedemaekers, C.W.E. PY - 2019 UR - https://hdl.handle.net/2066/202056 TI - Influenza virus and factors that are associated with ICU admission, pulmonary co-infections and ICU mortality EP - 65 SN - 0883-9441 SP - 59 JF - Journal of Critical Care VL - vol. 50 DO - https://doi.org/10.1016/j.jcrc.2018.11.013 ER - TY - JOUR AU - Oppersma, Eline AU - Doorduin, J. AU - Gooskens, Petra J. AU - Roesthuis, L.H. AU - Heijden, E. van der AU - Hoeven, J.G. van der AU - Veltink, Peter H. AU - Heunks, L.M.A. PY - 2019 UR - https://hdl.handle.net/2066/203017 TI - Glottic patency during noninvasive ventilation in patients with chronic obstructive pulmonary disease EP - 57 SN - 1569-9048 SP - 53 JF - Respiratory Physiology & Neurobiology VL - vol. 259 DO - https://doi.org/10.1016/j.resp.2018.07.006 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/203017/203017.pdf?sequence=1 ER - TY - JOUR AU - Lemkes, Jorrit S. AU - Janssens, Gladys N. AU - Hoeven, Nina W. van der AU - Jewbali, Lucia S.D. AU - Dubois, Eric A. AU - Meuwissen, Martijn AU - Stoel, M.A. AU - Camaro, C. AU - Hoeven, H. van der AU - Oudemans-van Straaten, Heleen M. AU - Royen, N. van PY - 2019 UR - https://hdl.handle.net/2066/203311 TI - Coronary Angiography after Cardiac Arrest without ST-Segment Elevation EP - 1407 SN - 0028-4793 IS - iss. 15 SP - 1397 JF - The New England Journal of Medicine VL - vol. 380 DO - https://doi.org/10.1056/NEJMoa1816897 ER - TY - JOUR AU - Kiers, D. AU - Eijk, L.T.G.J. van AU - Hoeven, J.G. van der AU - Swinkels, D.W. AU - Pickkers, P. AU - Kox, M. PY - 2019 UR - https://hdl.handle.net/2066/205269 TI - Hypoxia attenuates inflammation-induced hepcidin synthesis during experimental human endotoxemia EP - 232 SN - 0390-6078 IS - iss. 6 SP - 230 JF - Haematologica VL - vol. 104 DO - https://doi.org/10.3324/haematol.2018.202796 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/205269/205269.pdf?sequence=1 ER - TY - JOUR AU - Jonkman, Annemijn H. AU - Jansen, D. AU - Gadgil, Suvarna AU - Keijzer, Christiaan AU - Girbes, Armand R.J. AU - Scheffer, G.J. AU - Hoeven, J.G. van der AU - Sinderby, Christer S. AU - Heunks, L.M.A. PY - 2019 UR - https://hdl.handle.net/2066/206223 TI - Monitoring patient-ventilator breath contribution in the critically ill during neurally adjusted ventilatory assist: reliability and improved algorithms for bedside use EP - 271 SN - 8750-7587 IS - iss. 1 SP - 264 JF - Journal of Applied Physiology VL - vol. 127 DO - https://doi.org/10.1152/japplphysiol.00071.2019 ER - TY - JOUR AU - Koch, R.M. AU - Kox, M. AU - Kieboom, C.H. van den AU - Ferwerda, G. AU - Gerretsen, J. AU - Bruggencate, Sandra ten AU - Hoeven, J.G. van der AU - Jonge, M.I. de AU - Pickkers, P. PY - 2018 UR - https://hdl.handle.net/2066/190080 TI - Short-term repeated HRV-16 exposure results in an attenuated immune response in vivo in humans SN - 1932-6203 IS - iss. 2 JF - PLoS One VL - vol. 13 DO - https://doi.org/10.1371/journal.pone.0191937 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/190080/190080.pdf?sequence=1 ER - TY - JOUR AU - Boogaard, M.H.W.A. van den AU - Slooter, A.J. AU - Bruggemann, R.J.M. AU - Schoonhoven, L. AU - Beishuizen, Albertus AU - Hannink, G.J. AU - Vermeijden, J.Wytze AU - Simons, K.S. AU - Hoeven, J.G. van der AU - Pickkers, P. PY - 2018 UR - https://hdl.handle.net/2066/189820 TI - Effect of Haloperidol on Survival Among Critically Ill Adults With a High Risk of Delirium The REDUCE Randomized Clinical Trial EP - 690 SN - 0098-7484 IS - iss. 7 SP - 680 JF - Jama : Journal of the American Medical Association VL - vol. 319 DO - https://doi.org/10.1001/jama.2018.0160 ER - TY - JOUR AU - Simons, K.S. AU - Boogaard, M.H.W.A. van den AU - Hendriksen, Eva AU - Gerretsen, J. AU - Hoeven, J.G. van der AU - Pickkers, P. AU - Jager, C.P. de PY - 2018 UR - https://hdl.handle.net/2066/191949 TI - Temporal biomarker profiles and their association with ICU acquired delirium: a cohort study SN - 1466-609X JF - Critical Care VL - vol. 22 DO - https://doi.org/10.1186/s13054-018-2054-5 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/191949/191949.pdf?sequence=1 ER - TY - JOUR AU - Haerkens, M.H.T.M. AU - Kox, M. AU - Noe, Pieter M. AU - Hoeven, J.G. van der AU - Pickkers, P. PY - 2018 UR - https://hdl.handle.net/2066/194345 TI - Crew Resource Management in the trauma room: a prospective 3-year cohort study EP - 287 SN - 0969-9546 IS - iss. 4 SP - 281 JF - European Journal of Emergency Medicine VL - vol. 25 DO - https://doi.org/10.1097/MEJ.0000000000000458 ER - TY - JOUR AU - Vinke, E.J. AU - Eyding, J. AU - Korte, C.L. de AU - Slump, C.H. AU - Hoeven, J.G. van der AU - Hoedemaekers, C.W.E. PY - 2018 UR - https://hdl.handle.net/2066/191340 AB - OBJECTIVE: The aim of this study was to investigate the feasibility of simultaneous visualization of the cerebral macrocirculation and microcirculation, using ultrasound perfusion imaging (UPI). In addition, we studied the sensitivity of this technique for detecting changes in cerebral blood flow (CBF). MATERIALS AND METHODS: We performed an observational study in ten healthy volunteers. Ultrasound contrast was used for UPI measurements during normoventilation and hyperventilation. For the data analysis of the UPI measurements, an in-house algorithm was used to visualize the DICOM files, calculate parameter images and select regions of interest (ROIs). Next, time intensity curves (TIC) were extracted and perfusion parameters calculated. RESULTS: Both volume- and velocity-related perfusion parameters were significantly different between the macrocirculation and the parenchymal areas. Hyperventilation-induced decreases in CBF were detectable by UPI in both the macrocirculation and microcirculation, most consistently by the volume-related parameters. The method was safe, with no adverse effects in our population. CONCLUSIONS: Bedside quantification of CBF seems feasible and the technique has a favourable safety profile. Adjustment of current method is required to improve its diagnostic accuracy. Validation studies using a 'gold standard' are needed to determine the added value of UPI in neurocritical care monitoring. TI - Quantification of Macrocirculation and Microcirculation in Brain Using Ultrasound Perfusion Imaging EP - 120 SN - 0065-1419 SP - 115 JF - Acta Neurochirurgica. Supplementum VL - vol. 126 DO - https://doi.org/10.1007/978-3-319-65798-1_25 ER - TY - JOUR AU - Loon, Lex M. van AU - Hoeven, J.G. van der AU - Veltink, Peter H. AU - Lemson, J. PY - 2018 UR - https://hdl.handle.net/2066/197410 TI - The influence of esmolol on right ventricular function in early experimental endotoxic shock SN - 2051-817X IS - iss. 19 JF - Physiological Reports VL - vol. 6 DO - https://doi.org/10.14814/phy2.13882 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/197410/197410.pdf?sequence=1 ER - TY - JOUR AU - Jansen, D. AU - Jonkman, A.H. AU - Roesthuis, L.H. AU - Gadgil, S. AU - Hoeven, J.G. van der AU - Scheffer, G.J. AU - Girbes, A. AU - Doorduin, J. AU - Sinderby, C.S. AU - Heunks, L.M. PY - 2018 UR - https://hdl.handle.net/2066/196104 AB - BACKGROUND: Diaphragm dysfunction develops frequently in ventilated intensive care unit (ICU) patients. Both disuse atrophy (ventilator over-assist) and high respiratory muscle effort (ventilator under-assist) seem to be involved. A strong rationale exists to monitor diaphragm effort and titrate support to maintain respiratory muscle activity within physiological limits. Diaphragm electromyography is used to quantify breathing effort and has been correlated with transdiaphragmatic pressure and esophageal pressure. The neuromuscular efficiency index (NME) can be used to estimate inspiratory effort, however its repeatability has not been investigated yet. Our goal is to evaluate NME repeatability during an end-expiratory occlusion (NMEoccl) and its use to estimate the pressure generated by the inspiratory muscles (Pmus). METHODS: This is a prospective cohort study, performed in a medical-surgical ICU. A total of 31 adult patients were included, all ventilated in neurally adjusted ventilator assist (NAVA) mode with an electrical activity of the diaphragm (EAdi) catheter in situ. At four time points within 72 h five repeated end-expiratory occlusion maneuvers were performed. NMEoccl was calculated by delta airway pressure (DeltaPaw)/DeltaEAdi and was used to estimate Pmus. The repeatability coefficient (RC) was calculated to investigate the NMEoccl variability. RESULTS: A total number of 459 maneuvers were obtained. At time T = 0 mean NMEoccl was 1.22 +/- 0.86 cmH2O/muV with a RC of 82.6%. This implies that when NMEoccl is 1.22 cmH2O/muV, it is expected with a probability of 95% that the subsequent measured NMEoccl will be between 2.22 and 0.22 cmH2O/muV. Additional EAdi waveform analysis to correct for non-physiological appearing waveforms, did not improve NMEoccl variability. Selecting three out of five occlusions with the lowest variability reduced the RC to 29.8%. CONCLUSIONS: Repeated measurements of NMEoccl exhibit high variability, limiting the ability of a single NMEoccl maneuver to estimate neuromuscular efficiency and therefore the pressure generated by the inspiratory muscles based on EAdi. TI - Estimation of the diaphragm neuromuscular efficiency index in mechanically ventilated critically ill patients SN - 1466-609X IS - iss. 1 JF - Critical Care VL - vol. 22 DO - https://doi.org/10.1186/s13054-018-2172-0 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/196104/196104.pdf?sequence=1 ER - TY - JOUR AU - Brule, J.M.D. van den AU - Stolk, R.F. AU - Vinke, Elisabeth Janine AU - Loon, Lex Maxim van AU - Pickkers, P. AU - Hoeven, J.G. van der AU - Kox, M. AU - Hoedemaekers, C.W.E. PY - 2018 UR - https://hdl.handle.net/2066/194771 TI - Vasopressors Do Not Influence Cerebral Critical Closing Pressure During Systemic Inflammation Evoked by Experimental Endotoxemia and Sepsis in Humans EP - 535 SN - 1073-2322 IS - iss. 5 SP - 529 JF - Shock VL - vol. 49 DO - https://doi.org/10.1097/SHK.0000000000001003 ER - TY - JOUR AU - Doorduin, J. AU - Roesthuis, L.H. AU - Jansen, D. AU - Hoeven, J.G. van der AU - Hees, H.W.H. van AU - Heunks, L.M.A. PY - 2018 UR - https://hdl.handle.net/2066/194889 TI - Respiratory Muscle Effort during Expiration in Successful and Failed Weaning from Mechanical Ventilation EP - 501 SN - 0003-3022 IS - iss. 3 SP - 490 JF - Anesthesiology VL - vol. 129 DO - https://doi.org/10.1097/ALN.0000000000002256 ER - TY - JOUR AU - Oerlemans, A.J.M. AU - Jonge, E. de AU - Hoeven, J.G. van der AU - Zegers, M. PY - 2018 UR - https://hdl.handle.net/2066/195155 TI - A systematic approach to develop a core set of parameters for boards of directors to govern quality of care in the ICU EP - 550 SN - 1353-4505 IS - iss. 7 SP - 545 JF - International Journal for Quality in Health Care VL - vol. 30 DO - https://doi.org/10.1093/intqhc/mzy048 ER - TY - JOUR AU - Brule, J.M.D. van den AU - Hoeven, J.G. van der AU - Hoedemaekers, C.W.E. PY - 2018 UR - https://hdl.handle.net/2066/196359 AB - Out of hospital cardiac arrest is the leading cause of death in industrialized countries. Recovery of hemodynamics does not necessarily lead to recovery of cerebral perfusion. The neurological injury induced by a circulatory arrest mainly determines the prognosis of patients after cardiac arrest and rates of survival with a favourable neurological outcome are low. This review focuses on the temporal course of cerebral perfusion and changes in cerebral autoregulation after out of hospital cardiac arrest. In the early phase after cardiac arrest, patients have a low cerebral blood flow that gradually restores towards normal values during the first 72 hours after cardiac arrest. Whether modification of the cerebral blood flow after return of spontaneous circulation impacts patient outcome remains to be determined. TI - Cerebral Perfusion and Cerebral Autoregulation after Cardiac Arrest SN - 2314-6133 JF - Biomed Research International VL - vol. 2018 DO - https://doi.org/10.1155/2018/4143636 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/196359/196359.pdf?sequence=1 ER - TY - JOUR AU - Brule, J.M.D. van den AU - Kaam, C.R. van AU - Hoeven, J.G. van der AU - Claassen, J.A.H.R. AU - Hoedemaekers, C.W.E. PY - 2018 UR - https://hdl.handle.net/2066/196407 AB - Objective: To determine if increasing variability of blood pressure influences determination of cerebral autoregulation. Methods: A prospective observational study was performed at the ICU of a university hospital in the Netherlands. 13 comatose patients after cardiac arrest underwent baseline and intervention (tilting of bed) measurements. Mean flow velocity (MFV) in the middle cerebral artery and mean arterial pressure (MAP) were measured. Coefficient of variation (CV) was used as a standardized measure of dispersion in the time domain. In the frequency domain, coherence, gain, and phase were calculated in the very low and low frequency bands. Results: The CV of MAP was significantly higher during intervention compared to baseline. On individual level, coherence in the VLF band changed in 5 of 21 measurements from unreliable to reliable and in 6 of 21 measurements from reliable to unreliable. In the LF band 1 of 21 measurements changed from unreliable to reliable and 3 of 21 measurements from reliable to unreliable. Gain in the VLF and LF band was lower during intervention compared to baseline. Conclusions: For the ICU setting, more attention should be paid to the exact experimental protocol, since changes in experimental settings strongly influence results of estimation of cerebral autoregulation. TI - Influence of Induced Blood Pressure Variability on the Assessment of Cerebral Autoregulation in Patients after Cardiac Arrest SN - 2314-6133 JF - Biomed Research International VL - vol. 2018 DO - https://doi.org/10.1155/2018/8153241 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/196407/196407.pdf?sequence=1 ER - TY - JOUR AU - Douw, G. AU - Huisman-de Waal, G.J. AU - Zanten, A.R.H. AU - Hoeven, J.G. van der AU - Schoonhoven, L. PY - 2018 UR - https://hdl.handle.net/2066/196447 AB - BACKGROUND: Rapid response systems aim to improve early recognition and treatment of deteriorating general ward patients. Sole reliance on deviating vital signs to escalate care in rapid response systems disregards nurses' judgments about a patient's condition based on worry and other indicators of deterioration. To make worry explicit, the Dutch-Early-Nurse-Worry-Indicator-Score was developed, summarising non-quantifiable signs of deterioration in the nine indicators: breathing, circulation, temperature, mentation, agitation, pain, unexpected trajectory, patient indicates not feeling well and nurses' subjective observations. Nurses' worry can be present even when vital signs are largely unchanged, enabling treatment to commence at an early stage. On the other hand, reliance on nurses' worry might lead to unnecessary calls for medical assistance or an overuse of rapid response teams. OBJECTIVES: Explore the occurrence of nurses' worry in real time, determine whether acting on worry leads to unnecessary action and determine the indicators present at different levels of deterioration. DESIGN: A prospective cohort study. SETTING: Three surgical wards in a tertiary, university affiliated teaching hospital. PARTICIPANTS: All nurses participated and adult, surgical, native speaking patients were included in the study. METHODS: A descriptive analysis is performed on one year of data on surgical ward nurses' experience of worry and its underlying indicators in addition to routinely measured vital signs. RESULTS: Out of a total of 46,571 measurements, vital signs were normal 18,727 times, with worry expressed 605 times (3%), resulting in 62 calls (10.2%) to the attending physician. More than half of these calls resulted in necessary interventions. Calls for assistance and subsequent intervention after worry was expressed increase in parallel with early warning scores. The breathing indicator showed the highest increase in frequency with increasing deviation in vital signs. CONCLUSION: This study suggests that worry has potential as an early indicator of deterioration, alerting nurses and encouraging them to start timely interventions. Overuse of medical assistance could not be determined, The Dutch-Early-Nurse-Worry-Indicator-Score objectifies worry when vital signs do not support its presence and systematic assessment of these indicators is recommended. TI - Surgical ward nurses' responses to worry: An observational descriptive study EP - 95 SN - 0020-7489 SP - 90 JF - International Journal of Nursing Studies VL - vol. 85 DO - https://doi.org/10.1016/j.ijnurstu.2018.05.009 ER - TY - JOUR AU - Oppersma, E. AU - Doorduin, J. AU - Hoeven, J.G. van der AU - Veltink, P.H. AU - Hees, H.W.H. van AU - Heunks, L.M.A. PY - 2018 UR - https://hdl.handle.net/2066/184063 TI - The effect of metabolic alkalosis on the ventilatory response in healthy subjects EP - 53 SN - 1569-9048 SP - 47 JF - Respiratory Physiology & Neurobiology VL - vol. 249 DO - https://doi.org/10.1016/j.resp.2018.01.002 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/184063/184063.pdf?sequence=1 ER - TY - JOUR AU - Felten-Barentsz, K.M. AU - Oorsouw, Roel van AU - Haans, Antonius J.C. AU - Staal, J.B. AU - Hoeven, J.G. van der AU - Nijhuis-van der Sanden, M.W.G. PY - 2018 UR - https://hdl.handle.net/2066/197984 TI - Patient views regarding the impact of hydrotherapy on critically ill ventilated patients: A qualitative exploration study EP - 327 SN - 0883-9441 SP - 321 JF - Journal of Critical Care VL - vol. 48 DO - https://doi.org/10.1016/j.jcrc.2018.09.021 ER - TY - JOUR AU - Vinke, Elisabeth J. AU - Eyding, Jens AU - Korte, C.L. de AU - Slump, Cornelis H. AU - Hoeven, J.G. van der AU - Hoedemaekers, C.W.E. PY - 2017 UR - https://hdl.handle.net/2066/179605 TI - REPEATABILITY OF BOLUS KINETICS ULTRASOUND PERFUSION IMAGING FOR THE QUANTIFICATION OF CEREBRAL BLOOD FLOW EP - 2764 SN - 0301-5629 IS - iss. 12 SP - 2758 JF - Ultrasound in Medicine and Biology VL - vol. 43 DO - https://doi.org/10.1016/j.ultrasmedbio.2017.08.1880 ER - TY - JOUR AU - Hoedemaekers, C.W.E. AU - Ainslie, P.N. AU - Hinssen, S. AU - Aries, M.J. AU - Bisschops, L.L. AU - Hofmeijer, J. AU - Hoeven, J.G. van der PY - 2017 UR - https://hdl.handle.net/2066/182574 AB - AIM OF THE STUDY: Estimation of cerebral anaerobic metabolism in survivors and non-survivors after cardiac arrest. METHODS: We performed an observational study in twenty comatose patients after cardiac arrest and 19 healthy control subjects. We measured mean flow velocity in the middle cerebral artery (MFVMCA) by transcranial Doppler. Arterial and jugular blood samples were used for calculation of the jugular venous-to-arterial CO2/arterial to-jugular venous O2 content difference ratio. RESULTS: After cardiac arrest, MFVMCA increased from 26.0[18.6-40.4]cm/sec on admission to 63.9[48.3-73.1]cm/sec after 72h (p<0.0001), with no significant differences between survivors and non-survivors (p=0.4853). The MFVMCA in controls was 59.1[52.8-69.0]cm/sec. The oxygen extraction fraction (O2EF) was 38.9[24.4-47.7]% on admission and decreased significantly to 17.3[12.1-26.2]% at 72h (p<0.0001). The decrease in O2EF was more pronounced in non-survivors (p=0.0173). O2EF in the control group was 35.4[32.4-38.7]%. The jugular bulb-arterial CO2 to arterial-jugular bulb O2 content difference ratio was >1 at all time points after cardiac arrest and did not change during admission, with no differences between survivors and non-survivors. Values in cardiac arrest patients were similar to those in normal subjects. CONCLUSIONS: In this study, low CBF after cardiac arrest is not associated with anaerobic metabolism. Hypoperfusion appears to be the consequence of a decrease of neuronal functioning and metabolic needs. Alternatively, hypoperfusion may decrease cerebral metabolism. Subsequently, metabolism increases in survivors, consistent with resumption of neuronal activity, whereas in non-survivors lasting low metabolism reflects irreversible neuronal damage. TI - Low cerebral blood flow after cardiac arrest is not associated with anaerobic cerebral metabolism EP - 50 SN - 0300-9572 SP - 45 JF - Resuscitation VL - vol. 120 DO - https://doi.org/10.1016/j.resuscitation.2017.08.218 ER - TY - JOUR AU - Azoulay, E. AU - Vincent, J.L. AU - Angus, D.C. AU - Arabi, Y.M. AU - Brochard, L. AU - Brett, S.J. AU - Citerio, G. AU - Cook, D.J. AU - Curtis, J.R. AU - Santos, C.C. Dos AU - Ely, E.W. AU - Hall, J. AU - Halpern, S.D. AU - Hart, N. t AU - Hopkins, R.O. AU - Iwashyna, T.J. AU - Jaber, S. AU - Latronico, N. AU - Mehta, S. AU - Needham, D.M. AU - Nelson, J. AU - Puntillo, K. AU - Quintel, M. AU - Rowan, K. AU - Rubenfeld, G. AU - Berghe, G. Van den AU - Hoeven, J.G. van der AU - Wunsch, H. AU - Herridge, M. PY - 2017 UR - https://hdl.handle.net/2066/182582 AB - In this review, we seek to highlight how critical illness and critical care affect longer-term outcomes, to underline the contribution of ICU delirium to cognitive dysfunction several months after ICU discharge, to give new insights into ICU acquired weakness, to emphasize the importance of value-based healthcare, and to delineate the elements of family-centered care. This consensus of 29 also provides a perspective and a research agenda about post-ICU recovery. TI - Recovery after critical illness: putting the puzzle together-a consensus of 29 SN - 1466-609X IS - iss. 1 JF - Critical Care VL - vol. 21 DO - https://doi.org/10.1186/s13054-017-1887-7 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/182582/182582.pdf?sequence=1 ER - TY - JOUR AU - Kolk, M. van der AU - Boogaard, M.H.W.A. van den AU - Becking-Verhaar, F. AU - Custers, H. AU - Hoeven, H. van der AU - Pickkers, P. AU - Laarhoven, K. van PY - 2017 UR - https://hdl.handle.net/2066/181924 AB - INTRODUCTION: Medical and nursing protocols in perioperative care for pancreaticoduodenectomy are mainly mono-disciplinary, limiting their integration and transparency in a continuous health care system. The aims of this study were to evaluate adherence to a multidisciplinary clinical pathway for all pancreaticoduodenectomy patients during their entire hospital stay and to determine if the use of this clinical pathway is associated with beneficial effects on clinical end points. MATERIALS AND METHODS: A prospective cohort study was conducted in 95 pancreaticoduodenectomy patients treated according to a clinical pathway, including a variance report, compared to a historical control group (n = 52) with a traditional treatment regime. RESULTS: Process evaluation of the clinical pathway group revealed that protocol adherence throughout all units was above 80%. Major complications according to Clavien-Dindo classification grade >/=3 decreased from 27 to 13%; p = 0.02. Hospital length of stay was significantly shorter in the clinical pathway group, median 10 days [IQR 8-15], compared with the control group, median 13 days [IQR 10-18]; p = 0.02. CONCLUSION: The use of a clinical pathway in pancreaticoduodenectomy patients was associated with high protocol adherence, improved outcome and shorter hospital length of stay. Variance report analysis and protocol adherence with a Prepare-Act-Reflect Cycle are essential in surveillance of outcome. TI - Implementation and Evaluation of a Clinical Pathway for Pancreaticoduodenectomy Procedures: a Prospective Cohort Study EP - 1441 SN - 1091-255X IS - iss. 9 SP - 1428 JF - Journal of Gastrointestinal Surgery VL - vol. 21 DO - https://doi.org/10.1007/s11605-017-3459-1 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/181924/181924.pdf?sequence=1 ER - TY - JOUR AU - Kolk, B.M. van der AU - Boogaard, M.H.W.A. van den AU - Brugge-Speelman, Corine ter AU - Hol, Jeroen AU - Noyez, L. AU - Laarhoven, K. van AU - Hoeven, H. van der AU - Pickkers, P. PY - 2017 UR - https://hdl.handle.net/2066/181522 TI - Development and implementation of a clinical pathway for cardiac surgery in the intensive care unit: Effects on protocol adherence EP - 1298 SN - 1356-1294 IS - iss. 6 SP - 1289 JF - Journal of Evaluation in Clinical Practice VL - vol. 23 DO - https://doi.org/10.1111/jep.12778 ER - TY - JOUR AU - Oppersma, Eline AU - Hatam, Nima AU - Doorduin, J. AU - Hoeven, J.G. van der AU - Marx, Gernot AU - Goetzenich, Andreas AU - Heunks, L.M.A. AU - Bruells, Christian S. PY - 2017 UR - https://hdl.handle.net/2066/180432 TI - Functional assessment of the diaphragm by speckle tracking ultrasound during inspiratory loading EP - 1070 SN - 8750-7587 IS - iss. 5 SP - 1063 JF - Journal of Applied Physiology VL - vol. 123 DO - https://doi.org/10.1152/japplphysiol.00095.2017 ER - TY - JOUR AU - Vinke, E.J. AU - Kortenbout, A.J. AU - Eyding, J. AU - Slump, C.H. AU - Hoeven, J.G. van der AU - Korte, C.L. de AU - Hoedemaekers, C.W.E. PY - 2017 UR - https://hdl.handle.net/2066/181786 AB - Contrast-enhanced ultrasound (CEUS) has been suggested as a new method to measure cerebral perfusion in patients with acute brain injury. In this systematic review, the tolerability, repeatability, reproducibility and accuracy of different CEUS techniques for the quantification of cerebral perfusion were assessed. We selected studies published between January 1994 and March 2017 using CEUS to measure cerebral perfusion. We included 43 studies (bolus kinetics n = 31, refill kinetics n = 6, depletion kinetics n = 6) with a total of 861 patients. Tolerability was reported in 28 studies describing 12 patients with mild and transient side effects. Repeatability was assessed in 3 studies, reproducibility in 2 studies and accuracy in 19 studies. Repeatability was high for experienced sonographers and significantly lower for less experienced sonographers. Reproducibility of CEUS was not clear. The sensitivity and specificity of CEUS for the detection of cerebral ischemia ranged from 75% to 96% and from 60% to 100%. Limited data on repeatability, reproducibility and accuracy may suggest that this technique could be feasible for use in acute brain injury patients. TI - Potential of Contrast-Enhanced Ultrasound as a Bedside Monitoring Technique in Cerebral Perfusion: a Systematic Review EP - 2757 SN - 0301-5629 IS - iss. 12 SP - 2751 JF - Ultrasound in Medicine and Biology VL - vol. 43 DO - https://doi.org/10.1016/j.ultrasmedbio.2017.08.935 ER - TY - JOUR AU - Sluisveld, N. van AU - Oerlemans, A.J.M. AU - Westert, G.P. AU - Hoeven, J.G. van der AU - Wollersheim, H.C. AU - Zegers, M. PY - 2017 UR - https://hdl.handle.net/2066/174300 AB - BACKGROUND: Evidence indicates that suboptimal clinical handover from the intensive care unit (ICU) to general wards leads to unnecessary ICU readmissions and increased mortality. We aimed to gain insight into barriers and facilitators to implement and use ICU discharge practices. METHODS: A mixed methods approach was conducted, using 1) 23 individual and four focus group interviews, with post-ICU patients, ICU managers, and nurses and physicians working in the ICU or general ward of ten Dutch hospitals, and 2) a questionnaire survey, which contained 27 statements derived from the interviews, and was completed by 166 ICU physicians (21.8%) from 64 Dutch hospitals (71.1% of the total of 90 Dutch hospitals). RESULTS: The interviews resulted in 66 barriers and facilitators related to: the intervention (e.g., feasibility); the professional (e.g., attitude towards checklists); social factors (e.g., presence or absence of a culture of feedback); and the organisation (e.g., financial resources). A facilitator considered important by ICU physicians was a checklist to structure discharge communication (92.2%). Barriers deemed important were lack of a culture of feedback (55.4%), an absence of discharge criteria (23.5%), and an overestimation of the capabilities of general wards to care for complex patients by ICU physicians (74.7%). CONCLUSIONS: Based on the barriers and facilitators found in this study, improving handover communication, formulating specific discharge criteria, stimulating a culture of feedback, and preventing overestimation of the general ward are important to effectively improve the ICU discharge process. TI - Barriers and facilitators to improve safety and efficiency of the ICU discharge process: a mixed methods study EP - 251 SN - 1472-6963 IS - iss. 1 SP - 251 JF - BMC Health Services Research VL - vol. 17 DO - https://doi.org/10.1186/s12913-017-2139-x L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/174300/174300.pdf?sequence=1 ER - TY - JOUR AU - Sluisveld, N. van AU - Bakhshi-Raiez, F. AU - Keizer, N. de AU - Holman, R. AU - Westert, G.P. AU - Wollersheim, H.C. AU - Hoeven, J.G. van der AU - Zegers, M. PY - 2017 UR - https://hdl.handle.net/2066/174318 AB - BACKGROUND: Variation in intensive care unit (ICU) readmissions and in-hospital mortality after ICU discharge may indicate potential for improvement and could be explained by ICU discharge practices. Our objective was threefold: (1) describe variation in rates of ICU readmissions within 48 h and post-ICU in-hospital mortality, (2) describe ICU discharge practices in Dutch hospitals, and (3) study the association between rates of ICU readmissions within 48 h and post-ICU in-hospital mortality and ICU discharge practices. METHODS: We analysed data on 42,040 admissions to 82 (91.1%) Dutch ICUs in 2011 from the Dutch National Intensive Care Evaluation (NICE) registry to describe variation in standardized ICU readmission and post-ICU mortality rates using funnel-plots. We send a questionnaire to all Dutch ICUs. 75 ICUs responded and their questionnaire data could be linked to 38,498 admissions in the NICE registry. Generalized estimation equations analyses were used to study the association between ICU readmissions and post-ICU mortality rates and the identified discharge practices, i.e. (1) ICU discharge criteria; (2) bed managers; (3) early discharge planning; (4) step-down facilities; (5) medication reconciliation; (6) verbal and written handover; (7) monitoring of post-ICU patients; and (8) consulting ICU nurses. In all analyses, the outcomes were corrected for patient-related confounding factors. RESULTS: The standardized rate of ICU readmissions varied between 0.14 and 2.67 and 20.8% of the hospitals fell outside the 95% control limits and 3.6% outside the 99.8% control limits. The standardized rate of post-ICU mortality varied between 0.07 and 2.07 and 17.1% of the hospitals fell outside the 95% control limits and 4.9% outside the 99.8% control limits. We could not demonstrate an association between the eight ICU discharge practices and rates of ICU readmissions or post-ICU in-hospital mortality. Implementing a higher number of ICU discharge practices was also not associated with better patient outcomes. CONCLUSIONS: We found both variation in patient outcomes and variation in ICU discharge practices between ICUs. However, we found no association between discharge practices and rates of ICU readmissions or post-ICU mortality. Further research is necessary to find factors, which may influence these patient outcomes, in order to improve quality of care. TI - Variation in rates of ICU readmissions and post-ICU in-hospital mortality and their association with ICU discharge practices SN - 1472-6963 IS - iss. 1 SP - 281 JF - BMC Health Services Research VL - vol. 17 DO - https://doi.org/10.1186/s12913-017-2234-z L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/174318/174318.pdf?sequence=1 ER - TY - JOUR AU - Verlaat, C.W.M. AU - Visser, I.H. AU - Wubben, N. AU - Hazelzet, J.A. AU - Lemson, J. AU - Waardenburg, D. van AU - Heide, D. van der AU - Dam, N.A. van AU - Jansen, N.J. AU - Heerde, M. van AU - Starre, C. van der AU - Asperen, R. van AU - Kneyber, M. AU - Woensel, J.B. van AU - Boogaard, M.H.W.A. van den AU - Hoeven, J.G. van der PY - 2017 UR - https://hdl.handle.net/2066/177587 AB - OBJECTIVE: To determine differences between survivors and nonsurvivors and factors associated with mortality in pediatric intensive care patients with low risk of mortality. DESIGN: Retrospective cohort study. SETTING: Patients were selected from a national database including all admissions to the PICUs in The Netherlands between 2006 and 2012. PATIENTS: Patients less than 18 years old admitted to the PICU with a predicted mortality risk lower than 1% according to either the recalibrated Pediatric Risk of Mortality or the Pediatric Index of Mortality 2 were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In total, 16,874 low-risk admissions were included of which 86 patients (0.5%) died. Nonsurvivors had more unplanned admissions (74.4% vs 38.5%; p < 0.001), had more complex chronic conditions (76.7% vs 58.8%; p = 0.001), were more often mechanically ventilated (88.1% vs 34.9%; p < 0.001), and had a longer length of stay (median, 11 [interquartile range, 5-32] d vs median, 3 [interquartile range, 2-5] d; p < 0.001) when compared with survivors. Factors significantly associated with mortality were complex chronic conditions (odds ratio, 3.29; 95% CI, 1.97-5.50), unplanned admissions (odds ratio, 5.78; 95% CI, 3.40-9.81), and admissions in spring/summer (odds ratio, 1.67; 95% CI, 1.08-2.58). CONCLUSIONS: Nonsurvivors in the PICU with a low predicted mortality risk have recognizable risk factors including complex chronic condition and unplanned admissions. TI - Factors Associated With Mortality in Low-Risk Pediatric Critical Care Patients in The Netherlands EP - e161 SN - 1529-7535 IS - iss. 4 SP - e155 JF - Pediatric Critical Care Medicine VL - vol. 18 DO - https://doi.org/10.1097/PCC.0000000000001086 ER - TY - JOUR AU - Brule, J.M.D. van den AU - Vinke, E.J. AU - Loon, L.M. van AU - Hoeven, J.G. van der AU - Hoedemaekers, C.W.E. PY - 2017 UR - https://hdl.handle.net/2066/177627 AB - OBJECTIVE: To investigate spontaneous variability in the time and frequency domain in mean flow velocity (MFV) and mean arterial pressure (MAP) in comatose patients after cardiac arrest, and determine possible differences between survivors and non-survivors. METHODS: A prospective observational study was performed at the ICU of a tertiary care university hospital in the Netherlands. We studied 11 comatose patients and 10 controls. MFV in the middle cerebral artery was measured with simultaneously recording of MAP. Coefficient of variation (CV) was used as a standardized measure of dispersion in the time domain. In the frequency domain, the average spectral power of MAP and MFV were calculated in the very low, low and high frequency bands. RESULTS: In survivors CV of MFV increased from 4.66 [3.92-6.28] to 7.52 [5.52-15.23] % at T=72h. In non-survivors CV of MFV decreased from 9.02 [1.70-9.36] to 1.97 [1.97-1.97] %. CV of MAP was low immediately after admission (1.46 [1.09-2.25] %) and remained low at 72h (3.05 [1.87-3.63] %) (p=0.13). There were no differences in CV of MAP between survivors and non-survivors (p=0.30). We noticed significant differences between survivors and non-survivors in the VLF band for average spectral power of MAP (p=0.03) and MFV (p=0.003), whereby the power of both MAP and MFV increased in survivors during admission, while remaining low in non-survivors. CONCLUSIONS: Cerebral blood flow is altered after cardiac arrest, with decreased spontaneous fluctuations in non-survivors. Most likely, these changes are the consequence of impaired intrinsic myogenic vascular function and autonomic dysregulation. TI - Low spontaneous variability in cerebral blood flow velocity in non-survivors after cardiac arrest EP - 115 SN - 0300-9572 SP - 110 JF - Resuscitation VL - vol. 111 DO - https://doi.org/10.1016/j.resuscitation.2016.12.005 ER - TY - JOUR AU - Brule, J.M.D. van den AU - Vinke, E. AU - Loon, L.M. van AU - Hoeven, J.G. van der AU - Hoedemaekers, C.W.E. PY - 2017 UR - https://hdl.handle.net/2066/177630 AB - AIM: This study estimated the critical closing pressure (CrCP) of the cerebrovascular circulation during the post-cardiac arrest syndrome and determined if CrCP differs between survivors and non-survivors. We also compared patients after cardiac arrest to normal controls. METHODS: A prospective observational study was performed at the ICU of a tertiary university hospital in Nijmegen, the Netherlands. We studied 11 comatose patients successfully resuscitated from a cardiac arrest and treated with mild therapeutic hypothermia and 10 normal control subjects. Mean flow velocity (MFV) in the middle cerebral artery was measured by transcranial Doppler at several time points after admission to the ICU. CrCP was determined by a cerebrovascular impedance model. RESULTS: MFV was similar in survivors and non-survivors upon admission to the ICU, but increased stronger in non-survivors compared to survivors throughout the observation period (P<0.001). MFV was significantly lower in survivors immediately after cardiac arrest compared to normal controls (P<0.001), with a gradual restoration toward normal values. CrCP decreased significantly from 61.4[51.0-77.1]mmHg to 41.7[39.9-51.0]mmHg in the first 48h, after which it remained stable (P<0.001). CrCP was significantly higher in survivors compared to non-survivors (P=0.002). CrCP immediately after cardiac arrest was significantly higher compared to the control group (P=0.02). CONCLUSIONS: CrCP is high after cardiac arrest with high cerebrovascular resistance and low MFV. This suggests that cerebral perfusion pressure should be maintained at a sufficient high level to avoid secondary brain injury. Failure to normalize the cerebrovascular profile may be a parameter of poor outcome. TI - Middle cerebral artery flow, the critical closing pressure, and the optimal mean arterial pressure in comatose cardiac arrest survivors-An observational study EP - 89 SN - 0300-9572 SP - 85 JF - Resuscitation VL - vol. 110 DO - https://doi.org/10.1016/j.resuscitation.2016.10.022 ER - TY - JOUR AU - Muilwijk, E.W. AU - Dekkers, B.G.J. AU - Henriet, S.S.V. AU - Verweij, P.E. AU - Witjes, B. AU - Lashof, A. AU - Groeneveld, G.H. AU - Hoeven, J.G. van der AU - Alffenaar, J.W.C. AU - Russel, F.G. AU - Veerdonk, F.L. van de AU - Bruggemann, R.J.M. PY - 2017 UR - https://hdl.handle.net/2066/177025 AB - Combining voriconazole and flucloxacillin is indicated in patient cohorts experiencing both invasive aspergillosis and Gram-positive infections (e.g., patients with chronic granulomatous disease or postinfluenza pulmonary aspergillosis). We report a highly relevant interaction between voriconazole and flucloxacillin, resulting in subtherapeutic plasma voriconazole concentrations in more than 50% of patients, that poses a severe threat if not managed properly. TI - Flucloxacillin Results in Suboptimal Plasma Voriconazole Concentrations SN - 0066-4804 IS - iss. 9 JF - Antimicrobial Agents and Chemotherapy VL - vol. 61 DO - https://doi.org/10.1128/AAC.00915-17 ER - TY - JOUR AU - Douw, G. AU - Huisman-de Waal, G.J. AU - Zanten, A.R. van AU - Hoeven, J.G. van der AU - Schoonhoven, L. PY - 2017 UR - https://hdl.handle.net/2066/177311 AB - AIMS AND OBJECTIVES: To determine the predictive value of individual and combined dutch-early-nurse-worry-indicator-score indicators at various Early Warning Score levels, differentiating between Early Warning Scores reaching the trigger threshold to call a rapid response team and Early Warning Score levels not reaching this point. BACKGROUND: Dutch-early-nurse-worry-indicator-score comprises nine indicators underlying nurses' 'worry' about a patient's condition. All indicators independently show significant association with unplanned intensive care/high dependency unit admission or unexpected mortality. Prediction of this outcome improved by adding the dutch-early-nurse-worry-indicator-score indicators to an Early Warning Score based on vital signs. DESIGN: An observational cohort study was conducted on three surgical wards in a tertiary university-affiliated teaching hospital. METHODS: Included were surgical, native-speaking, adult patients. Nurses scored presence of 'worry' and/or dutch-early-nurse-worry-indicator-score indicators every shift or when worried. Vital signs were measured according to the prevailing protocol. Unplanned intensive care/high dependency unit admission or unexpected mortality was the composite endpoint. Percentages of 'worry' and dutch-early-nurse-worry-indicator-score indicators were calculated at various Early Warning Score levels in control and event groups. Entering all dutch-early-nurse-worry-indicator-score indicators in a multiple logistic regression analysis, we calculated a weighted score and calculated sensitivity, specificity, positive predicted value and negative predicted value for each possible total score. RESULTS: In 3522 patients, 102 (2.9%) had an unplanned intensive care/high dependency unit admissions (n = 97) or unexpected mortality (n = 5). Patients with such events and only slightly changed vital signs had significantly higher percentages of 'worry' and dutch-early-nurse-worry-indicator-score indicators expressed than patients in the control group. Increasing number of dutch-early-nurse-worry-indicator-score indicators showed higher positive predictive values. CONCLUSIONS: Dutch-early-nurse-worry-indicator-score indicators alert in an early stage of deterioration, before reaching the trigger threshold to call a rapid response team and can improve interdisciplinary communication on surgical wards during regular rounds, and when calling for assistance. RELEVANCE TO CLINICAL PRACTICE: Dutch-early-nurse-worry-indicator-score structures communication and recording of signs known to be associated with a decline in a patient's condition and can empower nurses to call assistance on the 'worry' criterion in an early stage of deterioration. TI - Capturing early signs of deterioration: the dutch-early-nurse-worry-indicator-score and its value in the Rapid Response System EP - 2613 SN - 0962-1067 IS - iss. 17-18 SP - 2605 JF - Journal of Clinical Nursing VL - vol. 26 DO - https://doi.org/10.1111/jocn.13648 ER - TY - JOUR AU - Witjes, M. AU - Kotsopoulos, A. AU - Herold, I.H.F. AU - Otterspoor, L. AU - Simons, K.S. AU - Vliet, J. van AU - Blauw, M. de AU - Festen, B. AU - Eijkenboom, J.J. AU - Jansen, N.E. AU - Hoeven, J.G. van der AU - Abdo, W.F. PY - 2017 UR - https://hdl.handle.net/2066/177480 AB - Many patients with acute devastating brain injury die outside intensive care units and could go unrecognized as potential organ donors. We conducted a prospective observational study in seven hospitals in the Netherlands to define the number of unrecognized potential organ donors outside intensive care units, and to identify the effect that end-of-life care has on organ donor potential. Records of all patients who died between January 2013 and March 2014 were reviewed. Patients were included if they died within 72 h after hospital admission outside the intensive care unit due to devastating brain injury, and fulfilled the criteria for organ donation. Physicians of included patients were interviewed using a standardized questionnaire regarding logistics and medical decisions related to end-of-life care. Of the 5170 patients screened, we found 72 additional potential organ donors outside intensive care units. Initiation of end-of-life care in acute settings and lack of knowledge and experience in organ donation practices outside intensive care units can result in under-recognition of potential donors equivalent to 11-34% of the total pool of organ donors. Collaboration with the intensive care unit and adjusting the end-of-life path in these patients is required to increase the likelihood of organ donation. TI - The Influence of End-of-Life Care on Organ Donor Potential EP - 1927 SN - 1600-6135 IS - iss. 7 SP - 1922 JF - American Journal of Transplantation VL - vol. 17 DO - https://doi.org/10.1111/ajt.14286 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/177480/177480.pdf?sequence=1 ER - TY - JOUR AU - Hopman, J. AU - Tostmann, A. AU - Wertheim, H.F.L. AU - Bos, M. AU - Kolwijck, E. AU - Akkermans, R.P. AU - Sturm, P.D.J. AU - Voss, A. AU - Pickkers, P. AU - Hoeven, H. van der PY - 2017 UR - https://hdl.handle.net/2066/174295 AB - BACKGROUND: Sinks in patient rooms are associated with hospital-acquired infections. The aim of this study was to evaluate the effect of removal of sinks from the Intensive Care Unit (ICU) patient rooms and the introduction of 'water-free' patient care on gram-negative bacilli colonization rates. METHODS: We conducted a 2-year pre/post quasi-experimental study that compared monthly gram-negative bacilli colonization rates pre- and post-intervention using segmented regression analysis of interrupted time series data. Five ICUs of a tertiary care medical center were included. Participants were all patients of 18 years and older admitted to our ICUs for at least 48 h who also received selective digestive tract decontamination during the twelve month pre-intervention or the twelve month post-intervention period. The effect of sink removal and the introduction of 'water-free' patient care on colonization rates with gram-negative bacilli was evaluated. The main outcome of this study was the monthly colonization rate with gram-negative bacilli (GNB). Yeast colonization rates were used as a 'negative control'. In addition, colonization rates were calculated for first positive culture results from cultures taken >/=3, >/=5, >/=7, >/=10 and >/=14 days after ICU-admission, rate ratios (RR) were calculated and differences tested with chi-squared tests. RESULTS: In the pre-intervention period, 1496 patients (9153 admission days) and in the post-intervention period 1444 patients (9044 admission days) were included. Segmented regression analysis showed that the intervention was followed by a statistically significant immediate reduction in GNB colonization in absence of a pre or post intervention trend in GNB colonization. The overall GNB colonization rate dropped from 26.3 to 21.6 GNB/1000 ICU admission days (colonization rate ratio 0.82; 95%CI 0.67-0.99; P = 0.02). The reduction in GNB colonization rate became more pronounced in patients with a longer ICU-Length of Stay (LOS): from a 1.22-fold reduction (>/=2 days), to a 1.6-fold (>/=5 days; P = 0.002), 2.5-fold (for >/=10 days; P < 0.001) to a 3.6-fold (>/=14 days; P < 0.001) reduction. CONCLUSIONS: Removal of sinks from patient rooms and introduction of a method of 'water-free' patient care is associated with a significant reduction of patient colonization with GNB, especially in patients with a longer ICU length of stay. TI - Reduced rate of intensive care unit acquired gram-negative bacilli after removal of sinks and introduction of 'water-free' patient care SN - 2047-2994 JF - Antimicrobial Resistance and Infection Control VL - vol. 6 DO - https://doi.org/10.1186/s13756-017-0213-0 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/174295/174295.pdf?sequence=1 ER - TY - JOUR AU - Osinski, A. AU - Vreugdenhil, G. AU - Koning, J. de AU - Hoeven, J.G. van der PY - 2017 UR - https://hdl.handle.net/2066/177573 AB - Discussing do-not-resuscitate (DNR) orders is part of daily hospital practice in oncology departments. Several medical factors and patient characteristics are associated with issuing DNR orders in cancer patients. DNR orders are often placed late in the disease process. This may be a cause for disagreements between doctors and between doctors and patients and may cause for unnecessary treatments and admissions. In addition, DNR orders on itself may influence the rest of the medical treatment for patients. We present recommendations for discussing DNR orders and medical futility in practice through shared decision-making. Prospective studies are needed to investigate in which a patient's cardiopulmonary resuscitation (CPR) is futile and whether or not DNR orders influence the medical care of patients. TI - Do-not-resuscitate orders in cancer patients: a review of literature EP - 685 SN - 0941-4355 IS - iss. 2 SP - 677 JF - Supportive Care in Cancer VL - vol. 25 DO - https://doi.org/10.1007/s00520-016-3459-9 ER - TY - JOUR AU - Veerdonk, F.L. van de AU - Kolwijck, E. AU - Lestrade, P.P.A. AU - Hodiamont, C.J. AU - Rijnders, B.J. AU - Paassen, J. van AU - Haas, P.J. AU - Santos, C. dos AU - Kampinga, G.A. AU - Bergmans, D.C. AU - Dijk, K van AU - Haan, A.F.J. de AU - Dissel, J. van AU - Hoeven, H. van der AU - Verweij, P.E. PY - 2017 UR - https://hdl.handle.net/2066/182506 TI - Influenza-Associated Aspergillosis in Critically Ill Patients EP - 527 SN - 1073-449X IS - iss. 4 SP - 524 JF - American Journal of Respiratory and Critical Care Medicine VL - vol. 196 DO - https://doi.org/10.1164/rccm.201612-2540LE ER - TY - JOUR AU - Geense, W.W. AU - Zegers, M. AU - Vermeulen, H. AU - Boogaard, M.H.W.A. van den AU - Hoeven, J.G. van der PY - 2017 UR - https://hdl.handle.net/2066/182346 AB - INTRODUCTION: Due to advances in critical care medicine, more patients survive their critical illness. However, intensive care unit (ICU) survivors often experience long-term physical, cognitive and mental problems, summarised as post-intensive care syndrome (PICS), impacting their health-related quality of life (HRQoL). In what frequency PICS occurs, and to what extent this influences ICU survivors' HRQoL, is mostly unknown. The aims of this study are therefore to study the: (1) 5-year patient outcomes, (2) predictors for PICS, (3) ratio between HRQoL of ICU survivors and healthcare-related costs, and (4) care and support needs. METHODS: The MONITOR-IC study is a multicentre prospective controlled cohort study, carried out in ICUs in four Dutch hospitals. Patients will be included between July 2016 and July 2021 and followed for 5 years. We estimated to include 12000 ICU patients. Outcomes are the HRQoL, physical, cognitive and mental symptoms, ICU survivors' care and support needs, healthcare use and related costs. A control cohort of otherwise seriously ill patients will be assembled to compare long-term patient-reported outcomes. We will use a mixed methods design, including questionnaires, medical data from patient records, cost data from health insurance companies and interviews with patients and family members. ETHICS AND DISSEMINATION: Insights from this study will be used to inform ICU patients and their family members about long-term consequences of ICU care, and to develop prediction and screening instruments to detect patients at risk for PICS. Subsequently, tailored interventions can be developed and implemented to prevent and mitigate long-term consequences. Additionally, insights into the ratio between HRQoL of ICU patients and related healthcare costs during 5 years after ICU admission can be used to discuss the added value of ICU care from a community perspective. The study has been approved by the research ethics committee of the Radboud University Medical Center (2016-2724). CLINICAL TRIAL REGISTRATION: NCT03246334. TI - MONITOR-IC study, a mixed methods prospective multicentre controlled cohort study assessing 5-year outcomes of ICU survivors and related healthcare costs: a study protocol SN - 2044-6055 IS - iss. 11 JF - BMJ Open VL - vol. 7 DO - https://doi.org/10.1136/bmjopen-2017-018006 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/182346/182346.pdf?sequence=1 ER - TY - JOUR AU - Koch, R.M. AU - Kox, M. AU - Jonge, M.I. de AU - Hoeven, J.G. van der AU - Ferwerda, G. AU - Pickkers, P. PY - 2017 UR - https://hdl.handle.net/2066/170576 AB - Immunosuppression renders the host increased susceptible for secondary infections. It is becoming increasingly clear that not only bacterial sepsis, but also respiratory viruses with both severe and mild disease courses such as influenza, respiratory syncytial virus, and the human rhinovirus may induce immunosuppression. In this review, the current knowledge on (mechanisms of) bacterial- and virus-induced immunosuppression and the accompanying susceptibility toward various secondary infections is described. In addition, the frequently encountered secondary pathogens and their preferred localizations are presented. Finally, future perspectives in the context of the development of diagnostic markers and possibilities for personalized therapy to improve the diagnosis and treatment of immunocompromised patients are discussed. TI - Patterns in Bacterial- and Viral-Induced Immunosuppression and Secondary Infections in the ICU EP - 12 SN - 1073-2322 IS - iss. 1 SP - 5 JF - Shock VL - vol. 47 DO - https://doi.org/10.1097/SHK.0000000000000731 ER - TY - JOUR AU - Doorduin, J. AU - Nollet, J.L. AU - Roesthuis, L.H. AU - Hees, H.W.H. van AU - Brochard, L.J. AU - Sinderby, C.A. AU - Hoeven, J.G. van der AU - Heunks, L.M.A. PY - 2017 UR - https://hdl.handle.net/2066/176006 AB - RATIONALE: Controlled mechanical ventilation is used to deliver lung-protective ventilation in patients with acute respiratory distress syndrome. Despite recognized benefits, such as preserved diaphragm activity, partial support ventilation modes may be incompatible with lung-protective ventilation due to high Vt and high transpulmonary pressure. As an alternative to high-dose sedatives and controlled mechanical ventilation, pharmacologically induced neuromechanical uncoupling of the diaphragm should facilitate lung-protective ventilation under partial support modes. OBJECTIVES: To investigate whether partial neuromuscular blockade can facilitate lung-protective ventilation while maintaining diaphragm activity under partial ventilatory support. METHODS: In a proof-of-concept study, we enrolled 10 patients with lung injury and a Vt greater than 8 ml/kg under pressure support ventilation (PSV) and under sedation. After baseline measurements, rocuronium administration was titrated to a target Vt of 6 ml/kg during neurally adjusted ventilatory assist (NAVA). Thereafter, patients were ventilated in PSV and NAVA under continuous rocuronium infusion for 2 hours. Respiratory parameters, hemodynamic parameters, and blood gas values were measured. MEASUREMENTS AND MAIN RESULTS: Rocuronium titration resulted in significant declines of Vt (mean +/- SEM, 9.3 +/- 0.6 to 5.6 +/- 0.2 ml/kg; P < 0.0001), transpulmonary pressure (26.7 +/- 2.5 to 10.7 +/- 1.2 cm H2O; P < 0.0001), and diaphragm electrical activity (17.4 +/- 2.3 to 4.5 +/- 0.7 muV; P < 0.0001), and could be maintained under continuous rocuronium infusion. During titration, pH decreased (7.42 +/- 0.02 to 7.35 +/- 0.02; P < 0.0001), and mean arterial blood pressure increased (84 +/- 6 to 99 +/- 6 mm Hg; P = 0.0004), as did heart rate (83 +/- 7 to 93 +/- 8 beats/min; P = 0.0004). CONCLUSIONS: Partial neuromuscular blockade facilitates lung-protective ventilation during partial ventilatory support, while maintaining diaphragm activity, in sedated patients with lung injury. TI - Partial Neuromuscular Blockade during Partial Ventilatory Support in Sedated Patients with High Tidal Volumes EP - 1042 SN - 1073-449X IS - iss. 8 SP - 1033 JF - American Journal of Respiratory and Critical Care Medicine VL - vol. 195 DO - https://doi.org/10.1164/rccm.201605-1016OC ER - TY - JOUR AU - Haerkens, M.H.T.M. AU - Leeuwen, W. van AU - Sexton, J.B. AU - Pickkers, P. AU - Hoeven, J.G. van der PY - 2016 UR - https://hdl.handle.net/2066/171911 AB - BACKGROUND: As the first objective of caring for patients is to do no harm, patient safety is a priority in delivering clinical care. An essential component of safe care in a clinical department is its safety climate. Safety climate correlates with safety-specific behaviour, injury rates, and accidents. Safety climate in healthcare can be assessed by the Safety Attitudes Questionnaire (SAQ), which provides insight by scoring six dimensions: Teamwork Climate, Job Satisfaction, Safety Climate, Stress Recognition, Working Conditions and Perceptions of Management. The objective of this study was to assess the psychometric properties of the Dutch language version of the SAQ in a variety of clinical departments in Dutch hospitals. METHODS: The Dutch version (SAQ-NL) of the SAQ was back translated, and analyzed for semantic characteristics and content. From October 2010 to November 2015 SAQ-NL surveys were carried out in 17 departments in two university and seven large non-university teaching hospitals in the Netherlands, prior to a Crew Resource Management human factors intervention. Statistical analyses were used to examine response patterns, mean scores, correlations, internal consistency reliability and model fit. Cronbach's alpha's and inter-item correlations were calculated to examine internal consistency reliability. RESULTS: One thousand three hundred fourteen completed questionnaires were returned from 2113 administered to health care workers, resulting in a response rate of 62 %. Confirmatory Factor Analysis revealed the 6-factor structure fit the data adequately. Response patterns were similar for professional positions, departments, physicians and nurses, and university and non-university teaching hospitals. The SAQ-NL showed strong internal consistency (alpha = .87). Exploratory analysis revealed differences in scores on the SAQ dimensions when comparing different professional positions, when comparing physicians to nurses and when comparing university to non-university hospitals. CONCLUSIONS: The SAQ-NL demonstrated good psychometric properties and is therefore a useful instrument to measure patient safety climate in Dutch clinical work settings. As removal of one item resulted in an increased reliability of the Working Conditions dimension, revision or deletion of this item should be considered. The results from this study provide researchers and practitioners with insight into safety climate in a variety of departments and functional positions in Dutch hospitals. TI - Validation of the Dutch language version of the Safety Attitudes Questionnaire (SAQ-NL) SN - 1472-6963 IS - iss. a SP - 385 JF - BMC Health Services Research VL - vol. 16 DO - https://doi.org/10.1186/s12913-016-1648-3 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/171911/171911.pdf?sequence=1 ER - TY - JOUR AU - Simons, K.S. AU - Laheij, R.J. AU - Boogaard, M. van den AU - Moviat, M.A. AU - Paling, A.J. AU - Polderman, F.N. AU - Rozendaal, F.W. AU - Salet, G.A. AU - Hoeven, J.G. van der AU - Pickkers, P. AU - Jager, C.P. de PY - 2016 UR - https://hdl.handle.net/2066/172369 AB - BACKGROUND: Disturbed circadian rhythm is a potentially modifiable cause of delirium among patients in intensive-care units (ICUs). Bright-light therapy in the daytime can realign circadian rhythm and reduce the incidence of delirium. We investigated whether a high-intensity dynamic light application (DLA) would reduce ICU-acquired delirium. METHODS: This was a randomised, controlled, single-centre trial of medical and surgical patients admitted to the ICU of a teaching hospital in the Netherlands. Patients older than 18 years, expected to stay in the ICU longer than 24 h and who could be assessed for delirium were randomised to DLA or normal lighting (control), according to a computer-generated schedule. The DLA was administered through ceiling-mounted fluorescent tubes that delivered bluish-white light up to 1700 lux between 0900 h and 1600 h, except for 1130-1330 h, when the light was dimmed to 300 lux. The light could only be turned off centrally by investigators. Control light levels were 300 lux and lights could be turned on and off from inside the room. The primary endpoint was the cumulative incidence of ICU-acquired delirium. Analyses were by intention to treat and per protocol. The study was terminated prematurely after an interim analysis for futility. This study is registered with Clinicaltrials.gov, number NCT01274819. FINDINGS: Between July 1, 2011, and Sept 9, 2013, 734 patients were enrolled, 361 in the DLA group and 373 in the control group. Delirium occurred in 137 (38%) of 361 DLA patients and 123 (33%) of 373 control patients (odds ratio 1.24, 95% CI 0.92-1.68, p=0.16). No adverse events were noted in patients or staff. INTERPRETATION: DLA as a single intervention does not reduce the cumulative incidence of delirium. Bright-light therapy should be assessed as part of a multicomponent strategy. FUNDING: None. TI - Dynamic light application therapy to reduce the incidence and duration of delirium in intensive-care patients: a randomised controlled trial EP - 202 SN - 2213-2600 IS - iss. 3 SP - 194 JF - Lancet Respiratory Medicine VL - vol. 4 DO - https://doi.org/10.1016/S2213-2600(16)00025-4 ER - TY - JOUR AU - Haerkens, M.H.T.M. AU - Tan, E.C.T.H. AU - Bleeker, C.P. AU - Hoeven, J.G. van der PY - 2016 UR - https://hdl.handle.net/2066/165859 AB - The recent terror attacks in Paris and Brussels have made the subject of injuries caused by explosives, also known as 'blast injuries', a very current one. The Netherlands has limited experience with terrorist attacks. This means that Dutch medical care providers possibly do not have sufficient knowledge about dealing with blast injuries. After explaining the mechanisms of explosions and the effects that these have on the human body, we go on to provide 15 tips on the main principles of treating blast injuries. These tips will help healthcare providers to deal with the complex requirements of victims of terror. TI - [How to deal with blast injuries. 15 tips for healthcare providers] J2 - Wat te doen bij een bomaanslag? 15 tips SN - 0028-2162 JF - Nederlands Tijdschrift voor Geneeskunde VL - vol. 160 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/165859/165859.pdf?sequence=1 ER - TY - JOUR AU - Vrancken, S.L.A.G. AU - Heijst, A.F.J. van AU - Hopman, J.C. AU - Liem, K.D. AU - Hoeven, J.G. van der AU - Boode, W.P. de PY - 2016 UR - https://hdl.handle.net/2066/168744 AB - OBJECTIVES: We investigated the accuracy of left-to-right shunt detection using transpulmonary ultrasound dilution (TPUD) and compared the agreement between pulmonary over systemic blood flow (Qp/Qs) ratio measured by TPUD [Qp/Qs(tpud)] and ultrasonic flow probes [Qp/Qs(ufp)]. METHODS: Seven newborn lambs under general anesthesia were connected to the TPUD monitor (COstatus) after insertion of arterial and central venous catheters. A Gore-Tex(R) shunt, inserted between the descending aorta and left pulmonary artery, was intermittently opened and closed while cardiac output was varied by blood withdrawals. Flow probes were placed around the main pulmonary artery (Qufp) and the descending aorta proximal (Qpre) and distal (Qpost) to the shunt insertion. Qp/Qs(ufp) was calculated as (Qufp+Qpre-Qpost)/Qufp. RESULTS: Seventy-two paired measurement sessions were analyzed. Shunts were detected by TPUD with a positive predictive value of 86%, a negative predictive value of 100%, a sensitivity of 100% and a specificity of 83%. The Bland-Altman analysis comparing Qp/Qs(tpud) and Qp/Qs(ufp) showed an overall mean bias (SD) of 0.1 (0.3), limits of agreement (LOA) of +/-0.6 and a percentage error of 34.8%. CONCLUSIONS: The qualitative diagnostic accuracy of TPUD for shunt detection is high. Modification of the algorithm seems required as shunt quantification by TPUD is accurate, but not yet very precise. TI - Detection and quantification of left-to-right shunting using transpulmonary ultrasound dilution (TPUD): a validation study in neonatal lambs EP - 932 SN - 0300-5577 IS - iss. 8 SP - 925 JF - Journal of Perinatal Medicine VL - vol. 44 DO - https://doi.org/10.1515/jpm-2015-0310 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/168744/168744.pdf?sequence=1 ER - TY - JOUR AU - Kiers, H.D. AU - Scheffer, G.J. AU - Hoeven, J.G. van der AU - Eltzschig, H.K. AU - Pickkers, P. AU - Kox, M. PY - 2016 UR - https://hdl.handle.net/2066/172742 AB - Hypoxia and immunity are highly intertwined at clinical, cellular, and molecular levels. The prevention of tissue hypoxia and modulation of systemic inflammation are cornerstones of daily practice in the intensive care unit. Potentially, immunologic effects of hypoxia may contribute to outcome and represent possible therapeutic targets. Hypoxia and activation of downstream signaling pathways result in enhanced innate immune responses, aimed to augment pathogen clearance. On the other hand, hypoxia also exerts antiinflammatory and tissue-protective effects in lymphocytes and other tissues. Although human data on the net immunologic effects of hypoxia and pharmacologic modulation of downstream pathways are limited, preclinical data support the concept of tailoring the immune response through modulation of the oxygen status or pharmacologic modulation of hypoxia-signaling pathways in critically ill patients. TI - Immunologic Consequences of Hypoxia during Critical Illness EP - 249 SN - 0003-3022 IS - iss. 1 SP - 237 JF - Anesthesiology VL - vol. 125 DO - https://doi.org/10.1097/ALN.0000000000001163 ER - TY - JOUR AU - Stolk, R.F. AU - Poll, T. van der AU - Angus, D.C. AU - Hoeven, J.G. van der AU - Pickkers, P. AU - Kox, M. PY - 2016 UR - https://hdl.handle.net/2066/171219 AB - Septic shock is a major cause of death worldwide and a considerable healthcare burden in the twenty-first century. Attention has shifted from damaging effects of the proinflammatory response to the detrimental role of antiinflammation, a phenomenon known as sepsis-induced immunoparalysis. Sepsis-induced immunoparalysis may render patients vulnerable to secondary infections and is associated with impaired outcome. The immunoparalysis hypothesis compels us to reevaluate the current management of septic shock and to assess whether we are inadvertently compromising or altering the host immune response. In this perspective, we discuss the potential detrimental role of norepinephrine, the cornerstone treatment for septic shock, in sepsis-induced immunoparalysis. We provide a short overview of the current understanding of the immunologic pathophysiology of sepsis, followed by a detailed description of the immunomodulatory effects of norepinephrine and alternative vasopressors. We conclude that although the development of novel therapies aimed at reversing immunoparalysis is underway, the use of norepinephrine may aggravate the development, extent, and duration of sepsis-induced immunoparalysis. Current in vitro and animal data indicate that norepinephrine treatment exerts immunosuppressive and bacterial growth-promoting effects and may increase susceptibility toward infections. However, evidence in humans is circumstantial, as immunologic effects of norepinephrine have not been investigated properly in experimental or clinical studies. Alternatives such as vasopressin/selepressin, angiotensin II, and phenylephrine could have a fundamental advantage over norepinephrine with respect to their immunologic properties. However, also for these agents, in vivo immunologic data in humans are largely lacking. As such, human studies on the immunomodulatory properties of norepinephrine and viable alternatives are highly warranted. TI - Potentially Inadvertent Immunomodulation: Norepinephrine Use in Sepsis EP - 558 SN - 1073-449X IS - iss. 5 SP - 550 JF - American Journal of Respiratory and Critical Care Medicine VL - vol. 194 DO - https://doi.org/10.1164/rccm.201604-0862CP ER - TY - JOUR AU - Oerlemans, A.J.M. AU - Wollersheim, H.C.H. AU - Sluisveld, N. van AU - Hoeven, J.G. van der AU - Dekkers, W.J.M. AU - Zegers, M. PY - 2016 UR - https://hdl.handle.net/2066/171342 AB - BACKGROUND: Internationally, there is no consensus on how to best deal with admission requests in cases of full ICU bed occupancy. Knowledge about the degree of dissension and insight into the reasons for this dissension is lacking. Information about the opinion of ICU physicians can be used to improve decision-making regarding allocation of ICU resources. The aim of this study was to: Assess which factors play a role in the decision-making process regarding the admission of ICU patients; Assess the adherence to a Dutch guideline pertaining to rationing of ICU resources; Investigate factors influencing the adherence to this guideline. METHODS: In March 2013, an online questionnaire was sent to all ICU physician members (n = 761, in 90 hospitals) of the Dutch Society for Intensive Care. RESULTS: 166 physicians (21.8 %) working in 64 different Dutch hospitals (71.1 %) completed the questionnaire. Factors associated with a patient's physical condition and quality of life were generally considered most important in admission decisions. Scenario-based adherence to the Dutch guideline "Admission request in case of full ICU bed occupancy" was found to be low (adherence rate 50.0 %). There were two main reasons for this poor compliance: unfamiliarity with the guideline and disagreement with the fundamental approach underlying the guideline. CONCLUSIONS: Dutch ICU physicians disagree about how to deal with admission requests in cases of full ICU bed occupancy. The results of this study contribute to the discussion about the fundamental principles regarding admission of ICU patients in case of full bed occupancy. TI - Rationing in the intensive care unit in case of full bed occupancy: a survey among intensive care unit physicians SN - 1471-2253 JF - BMC Anesthesiology VL - vol. 16 DO - https://doi.org/10.1186/s12871-016-0190-5 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/171342/171342.pdf?sequence=1 ER - TY - JOUR AU - Velasquez, T. AU - Mackey, G. AU - Lusk, J. AU - Kyle, U.G. AU - Rood, P.J.T. AU - Frenzel, T. AU - Verhage, R. AU - Bonn, M. AU - Pickkers, P. AU - Hoeven, J.G. van der AU - Boogaard, M.H.W.A. van den AU - et al. PY - 2016 UR - https://hdl.handle.net/2066/172381 TI - ESICM LIVES 2016: part three : Milan, Italy. 1-5 October 2016. EP - 28 SN - 2197-425X IS - iss. 1 SP - 28 JF - Intensive Care Medicine Experimental VL - vol. 4 DO - https://doi.org/10.1186/s40635-016-0100-7 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/172381/172381.pdf?sequence=1 ER - TY - JOUR AU - Douw, G. AU - Huisman-de Waal, G.J. AU - Zanten, A.R. van AU - Hoeven, J.G. van der AU - Schoonhoven, L. PY - 2016 UR - https://hdl.handle.net/2066/171075 AB - BACKGROUND: Nurses' 'worry' is used as a calling criterion in many Rapid Response Systems, however it is valued inconsistently. Furthermore, barriers to call the Rapid Response Team can cause delay in escalating care. The literature identifies nine indicators which trigger nurses to worry about a patient's condition. OBJECTIVES: The objective of this study is to determine the significance of nurses' 'worry' and/or indicators underlying 'worry' to predict unplanned Intensive-Care/High-Dependency-Unit admission or unexpected mortality among surgical ward patients. DESIGN: A prospective cohort study. SETTINGS: A 500-bed tertiary University affiliated teaching hospital. PARTICIPANTS: Adult, native speaking surgical patients, admitted to three surgical wards (traumatology, vascular- and abdominal/oncological surgery). We excluded patients with a non-ICU policy or with no curative treatment. Mentally incapacitated patients were also excluded. METHODS: We developed a new clinical assessment tool, the Dutch-Early-Nurse-Worry-Indicator-Score (DENWIS) based on signs underlying 'worry'. Nurses systematically scored their 'worry' and the DENWIS once per shift or at any moment of 'worry'. DENWIS measurements were linked to routinely measured vital signs. The composite endpoint was unplanned Intensive-Care/High-Dependency-Unit admission or unexpected mortality. The DENWIS-indicators were included in a univariate and multivariate logistic regression analysis, subsequently inserting 'worry' and the Early Warning Score into the model. We calculated the area under the receiver-operating characteristics curve. RESULTS: In 3522 patients there were 102 (2.9%) patients with unplanned Intensive Care Unit/High Dependency Unit-admissions or unexpected mortality. 'Worry' (0.81) and the DENWIS-model (0.85) had a lower area under the receiver-operating characteristics curve than the Early Warning Score (0.86). Adding 'worry' and the Early Warning Score to the DENWIS-model resulted in higher areas under the receiver operating characteristics curves (0.87 and 0.91, respectively) compared with the Early Warning Score only based on vital signs. CONCLUSIONS: In this single-center study we showed that adding the Early Warning Score based on vital signs to the DENWIS-indicators improves prediction of unplanned Intensive-Care/High-Dependency-Unit admission or unexpected mortality. TI - Nurses' 'worry' as predictor of deteriorating surgical ward patients: A prospective cohort study of the Dutch-Early-Nurse-Worry-Indicator-Score EP - 140 SN - 0020-7489 SP - 134 JF - International Journal of Nursing Studies VL - vol. 59 DO - https://doi.org/10.1016/j.ijnurstu.2016.04.006 ER - TY - JOUR AU - Timmermans, K. AU - Kox, M. AU - Vaneker, M. AU - Berg, M. van den AU - John, A. AU - Laarhoven, A. van AU - Hoeven, H. van der AU - Scheffer, G.J. AU - Pickkers, P. PY - 2016 UR - https://hdl.handle.net/2066/171199 AB - PURPOSE: Danger-associated molecular patterns (DAMPs) released of trauma could contribute to an immune suppressed state that renders patients vulnerable towards nosocomial infections. We investigated DAMP release in trauma patients, starting in the prehospital phase, and assessed its relationship with immune suppression and nosocomial infections. METHODS: Blood was obtained from 166 adult trauma patients at the trauma scene, emergency room (ER), and serially afterwards. Circulating levels of DAMPs and cytokines were determined. Immune suppression was investigated by determination of HLA-DRA gene expression and ex vivo lipopolysaccharide-stimulated cytokine production. RESULTS: Compared with healthy controls, plasma levels of nuclear DNA (nDNA) and heat shock protein-70 (HSP70) but not mitochondrial DNA were profoundly increased immediately following trauma and remained elevated for 10 days. Plasma cytokines were increased at the ER, and levels of anti-inflammatory IL-10 but not of pro-inflammatory cytokines peaked at this early time-point. HLA-DRA expression was attenuated directly after trauma and did not recover during the follow-up period. Plasma nDNA (r = -0.24, p = 0.006) and HSP70 (r = -0.38, p < 0.0001) levels correlated negatively with HLA-DRA expression. Ex vivo cytokine production revealed an anti-inflammatory phenotype already at the trauma scene which persisted in the following days, characterized by attenuated TNF-alpha and IL-6, and increased IL-10 production. Finally, higher concentrations of nDNA and a further decrease of HLA-DRA expression were associated with infections. CONCLUSIONS: Plasma levels of DAMPs are associated with immune suppression, which is apparent within minutes/hours following trauma. Furthermore, aggravated immune suppression during the initial phase following trauma is associated with increased susceptibility towards infections. TI - Plasma levels of danger-associated molecular patterns are associated with immune suppression in trauma patients EP - 561 SN - 0342-4642 IS - iss. 4 SP - 551 JF - Intensive Care Medicine VL - vol. 42 DO - https://doi.org/10.1007/s00134-015-4205-3 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/171199/171199.pdf?sequence=1 ER - TY - JOUR AU - Koch, R.M. AU - Kox, M. AU - Rahamat-Langendoen, J.C. AU - Timmermans, K. AU - Hoeven, J.G. van der AU - Pickkers, P. PY - 2016 UR - https://hdl.handle.net/2066/172800 TI - Increased risk for secondary infections in trauma patients with viral reactivation. EP - 1829 SN - 0342-4642 IS - iss. 11 SP - 1828 JF - Intensive Care Medicine VL - vol. 42 DO - https://doi.org/10.1007/s00134-016-4474-5 ER - TY - JOUR AU - Vrancken, S.L.A.G. AU - Nusmeier, A. AU - Hopman, J.C. AU - Liem, K.D. AU - Hoeven, J.G. van der AU - Lemson, J. AU - Heijst, A.F.J. van AU - Boode, W.P. de PY - 2016 UR - https://hdl.handle.net/2066/168747 AB - Increased extravascular lung water (EVLW) may contribute to respiratory failure in neonates. Accurate measurement of EVLW in these patients is limited due to the lack of bedside methods. The aim of this pilot study was to investigate the reliability of the transpulmonary ultrasound dilution (TPUD) technique as a possible method for estimating EVLW in a neonatal animal model. Pulmonary edema was induced in 11 lambs by repeated surfactant lavages. In between the lavages, EVLW indexed by bodyweight was estimated by TPUD (EVLWItpud) and transpulmonary dye dilution (EVLWItpdd) (n = 22). Final EVLWItpud measurements were also compared with EVLWI estimations by gold standard post mortem gravimetry (EVLWIgrav) (n = 6). EVLWI was also measured in two additional lambs without pulmonary edema. Bland-Altman plots showed a mean bias between EVLWItpud and EVLWItpdd of -3.4 mL/kg (LOA +/- 25.8 mL/kg) and between EVLWItpud and EVLWIgrav of 1.7 mL/kg (LOA +/- 8.3 mL/kg). The percentage errors were 109 and 43 % respectively. The correlation between changes in EVLW measured by TPUD and TPDD was r2 = 0.22. Agreement between EVLWI measurements by TPUD and TPDD was low. Trending ability to detect changes between these two methods in EVLWI was questionable. The accuracy of EVLWItpud was good compared to the gold standard gravimetric method but the TPUD lacked precision in its current prototype. Based on these limited data, we believe that TPUD has potential for future use to estimate EVLW after adaptation of the algorithm. Larger studies are needed to support our findings. TI - Estimation of extravascular lung water using the transpulmonary ultrasound dilution (TPUD) method: a validation study in neonatal lambs EP - 994 SN - 1387-1307 IS - iss. 6 SP - 985 JF - Journal of Clinical Monitoring and Computing VL - vol. 30 DO - https://doi.org/10.1007/s10877-015-9803-7 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/168747/168747.pdf?sequence=1 ER - TY - JOUR AU - Kolwijck, E. AU - Hoeven, H. van der AU - Sevaux, R.G.L. de AU - Oever, J. ten AU - Rijstenberg, L.L. AU - Lee, H.A.L. van der AU - Zoll, J. AU - Melchers, W.J.G. AU - Verweij, P.E. PY - 2016 UR - https://hdl.handle.net/2066/166535 TI - Voriconazole-Susceptible and Voriconazole-Resistant Aspergillus fumigatus Coinfection EP - 929 SN - 1073-449X IS - iss. 8 SP - 927 JF - American Journal of Respiratory and Critical Care Medicine VL - vol. 193 DO - https://doi.org/10.1164/rccm.201510-2104LE ER - TY - JOUR AU - Schellekens, W.J. AU - Hees, H.W.H. van AU - Doorduin, J. AU - Roesthuis, L.H. AU - Scheffer, G.J. AU - Hoeven, J.G. van der AU - Heunks, L.M. PY - 2016 UR - https://hdl.handle.net/2066/168156 AB - Respiratory muscle dysfunction may develop rapidly in critically ill ventilated patients and is associated with increased morbidity, length of intensive care unit stay, costs, and mortality. This review briefly discusses the pathophysiology of respiratory muscle dysfunction in intensive care unit patients and then focuses on strategies that prevent the development of muscle weakness or, if weakness has developed, how respiratory muscle function may be improved. We propose a simple strategy for how these can be implemented in clinical care. TI - Strategies to optimize respiratory muscle function in ICU patients SN - 1466-609X IS - iss. 1 SP - 103 JF - Critical Care VL - vol. 20 DO - https://doi.org/10.1186/s13054-016-1280-y L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/168156/168156.pdf?sequence=1 ER - TY - JOUR AU - Doorduin, J. AU - Nollet, J.L. AU - Vugts, M.P. AU - Roesthuis, L.H. AU - Akankan, F. AU - Hoeven, J.G. van der AU - Hees, H.W.H. van AU - Heunks, L.M. PY - 2016 UR - https://hdl.handle.net/2066/168195 AB - BACKGROUND: Physiological dead space (VD/VT) represents the fraction of ventilation not participating in gas exchange. In patients with acute respiratory distress syndrome (ARDS), VD/VT has prognostic value and can be used to guide ventilator settings. However, VD/VT is rarely calculated in clinical practice, because its measurement is perceived as challenging. Recently, a novel technique to calculate partial pressure of carbon dioxide in alveolar air (PACO2) using volumetric capnography (VCap) was validated. The purpose of the present study was to evaluate how VCap and other available techniques to measure PACO2 and partial pressure of carbon dioxide in mixed expired air (PeCO2) affect calculated VD/VT. METHODS: In a prospective, observational study, 15 post-cardiac surgery patients and 15 patients with ARDS were included. PACO2 was measured using VCap to calculate Bohr dead space or substituted with partial pressure of carbon dioxide in arterial blood (PaCO2) to calculate the Enghoff modification. PeCO2 was measured in expired air using three techniques: Douglas bag (DBag), indirect calorimetry (InCal), and VCap. Subsequently, VD/VT was calculated using four methods: Enghoff-DBag, Enghoff-InCal, Enghoff-VCap, and Bohr-VCap. RESULTS: PaCO2 was higher than PACO2, particularly in patients with ARDS (post-cardiac surgery PACO2 = 4.3 +/- 0.6 kPa vs. PaCO2 = 5.2 +/- 0.5 kPa, P < 0.05; ARDS PACO2 = 3.9 +/- 0.8 kPa vs. PaCO2 = 6.9 +/- 1.7 kPa, P < 0.05). There was good agreement in PeCO2 calculated with DBag vs. VCap (post-cardiac surgery bias = 0.04 +/- 0.19 kPa; ARDS bias = 0.03 +/- 0.27 kPa) and relatively low agreement with DBag vs. InCal (post-cardiac surgery bias = -1.17 +/- 0.50 kPa; ARDS mean bias = -0.15 +/- 0.53 kPa). These differences strongly affected calculated VD/VT. For example, in patients with ARDS, VD/VTcalculated with Enghoff-InCal was much higher than Bohr-VCap (VD/VT Enghoff-InCal = 66 +/- 10 % vs. VD/VT Bohr-VCap = 45 +/- 7 %; P < 0.05). CONCLUSIONS: Different techniques to measure PACO2 and PeCO2 result in clinically relevant mean and individual differences in calculated VD/VT, particularly in patients with ARDS. Volumetric capnography is a promising technique to calculate true Bohr dead space. Our results demonstrate the challenges clinicians face in interpreting an apparently simple measurement such as VD/VT. TI - Assessment of dead-space ventilation in patients with acute respiratory distress syndrome: a prospective observational study SN - 1466-609X IS - iss. 1 SP - 121 JF - Critical Care VL - vol. 20 DO - https://doi.org/10.1186/s13054-016-1311-8 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/168195/168195.pdf?sequence=1 ER - TY - JOUR AU - Doorduin, J. AU - Hoeven, J.G. van der AU - Heunks, L.M. PY - 2016 UR - https://hdl.handle.net/2066/171711 AB - PURPOSE OF REVIEW: In this review, we discuss the causes for a failed weaning trial and specific diagnostic tests that could be conducted to identify the cause for weaning failure. We briefly highlight treatment strategies that may enhance the chance of weaning success. RECENT FINDINGS: Impaired respiratory mechanics, respiratory muscle dysfunction, cardiac dysfunction, cognitive dysfunction, and metabolic disorders are recognized causes for weaning failure. In addition, iatrogenic factors may be at play. Most studies have focused on respiratory muscle dysfunction and cardiac dysfunction. Recent studies demonstrate that both ultrasound and electromyography are valuable tools to evaluate respiratory muscle function in ventilated patients. Sophisticated ultrasound techniques and biomarkers such as B-type natriuretic peptide, are valuable tools to identify cardiac dysfunction as a cause for weaning failure. Once a cause for weaning failure has been identified specific treatment should be instituted. Concerning treatment, both strength training and endurance training should be considered for patients with respiratory muscle weakness. Inotropes and vasodilators should be considered in case of heart failure. SUMMARY: Understanding the complex pathophysiology of weaning failure in combination with a systematic diagnostic approach allows identification of the primary cause of weaning failure. This will help the clinician to choose a specific treatment strategy and therefore may fasten liberation from mechanical ventilation. TI - The differential diagnosis for failure to wean from mechanical ventilation EP - 157 SN - 0952-7907 IS - iss. 2 SP - 150 JF - Current Opinion in Anesthesiology VL - vol. 29 DO - https://doi.org/10.1097/ACO.0000000000000297 ER - TY - JOUR AU - Haerkens, M.H. AU - Kox, M. AU - Lemson, J. AU - Houterman, S. AU - Hoeven, J.G. van der AU - Pickkers, P. PY - 2015 UR - https://hdl.handle.net/2066/154903 AB - BACKGROUND: Human factors account for the majority of adverse events in both aviation and medicine. Human factors awareness training entitled "Crew Resource Management (CRM)" is associated with improved aviation safety. We determined whether implementation of CRM impacts outcome in critically ill patients. METHODS: We performed a prospective 3-year cohort study in a 32-bed ICU, admitting 2500-3000 patients yearly. At the end of the baseline year, all personnel received CRM training, followed by 1 year of implementation. The third year was defined as the clinical effect year. All 7271 patients admitted to the ICU in the study period were included. The primary outcome measure was ICU complication rate. Secondary outcome measures were ICU and hospital length of stay, and standardized mortality ratio. RESULTS: Occurrence of serious complications was 67.1/1000 patients and 66.4/1000 patients during the baseline and implementation year respectively, decreasing to 50.9/1000 patients in the post-implementation year (P = 0.03). Adjusted odds ratios for occurrence of complications were 0.92 (95% CI 0.71-1.19, P = 0.52) and 0.66 (95% CI 0.51-0.87, P = 0.003) in the implementation and post-implementation year. The incidence of cardiac arrests was 9.2/1000 patients and 8.3/1000 patients during the baseline and implementation year, decreasing to 3.5/1000 patients (P = 0.04) in the post-implementation year, while cardiopulmonary resuscitation success rate increased from 19% to 55% and 67% (P = 0.02). Standardized mortality ratio decreased from 0.72 (95% CI 0.63-0.81) in the baseline year to 0.60 (95% CI 0.53-0.67) in the post-implementation year (P = 0.04). CONCLUSION: Our data indicate an association between CRM implementation and reduction in serious complications and lower mortality in critically ill patients. TI - Crew Resource Management in the Intensive Care Unit: a prospective 3-year cohort study EP - 1329 SN - 0001-5172 IS - iss. 10 SP - 1319 JF - Acta Anaesthesiologica Scandinavica VL - vol. 59 DO - http://dx.doi.org/10.1111/aas.12573 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/154903/154903.pdf?sequence=1 ER - TY - JOUR AU - Abdo, W.F. AU - Hoeven, J.G. van der PY - 2015 UR - https://hdl.handle.net/2066/154100 TI - An unusual journey of a pulmonary artery catheter through the heart EP - 917 SN - 0342-4642 IS - iss. 5 SP - 916 JF - Intensive Care Medicine VL - vol. 41 DO - http://dx.doi.org/10.1007/s00134-014-3587-y ER - TY - JOUR AU - Kluge, G.H. AU - Brinkman, S. AU - Berkel, G. van AU - Hoeven, J.G. van der AU - Jacobs, C AU - Snel, Y.E. AU - Vogelaar, J.P. AU - Keizer, N.F. de AU - Boon, E.S. PY - 2015 UR - https://hdl.handle.net/2066/154146 AB - PURPOSE: The relationship between the number of patients admitted to an intensive care unit (ICU) volume and mortality is currently the subject of debate. After implementation of a national guideline in 2006, all Dutch ICUs have been classified into three levels based on ICU size, patient volume, ventilation days, and staffing. The goal of this study is to investigate the association between ICU level and mortality of ICU patients in the Netherlands. METHODS: We analyzed data from 132,159 patients admitted to 87 ICUs between January 1, 2009 and October 1, 2011. Logistic GEE analyses were performed to assess the influence of ICU level on in-hospital mortality and 90-day mortality in the total ICU population and in different ICU subgroups while adjusting for severity of illness by APACHE IV. Results : No significant differences were found in the adjusted in-hospital mortality of the total ICU population and in different subgroups admitted to level 1, 2 and 3 ICUs. In-hospital mortality in level 2 and 3 ICUs as opposed to level 1 ICUs was 1.06 (0.93-1.22) and 1.10 (0.94-1.29), respectively, and 90-day mortality was 0.92 (0.80-1.06) and 1.01 (0.88-1.17). CONCLUSION: We demonstrated that ICU level was not associated with significant differences in the case-mix adjusted in-hospital and long-term mortality of ICU patients. This finding is in contrast with some earlier studies suggesting a volume-outcome relationship. Our results may be explained by the successful implementation of nationwide mandatory quality requirements and adequate staffing in all three levels of ICUs over the last years. TI - The association between ICU level of care and mortality in the Netherlands EP - 311 SN - 0342-4642 IS - iss. 2 SP - 304 JF - Intensive Care Medicine VL - vol. 41 DO - http://dx.doi.org/10.1007/s00134-014-3620-1 ER - TY - JOUR AU - Aman, J. AU - Koppenhagen, L. van AU - Snoek, A.M. AU - Hoeven, J.G. van der AU - Lely, A.J. van der PY - 2015 UR - https://hdl.handle.net/2066/154732 TI - Cerebral fat embolism after bone fractures SN - 0140-6736 IS - iss. 10001 SP - e16 JF - The Lancet (London) VL - vol. 386 DO - https://doi.org/10.1016/S0140-6736(15)60064-2 ER - TY - JOUR AU - Schellekens, W.J.M. AU - Hees, H.W.H. van AU - Linkels, M. AU - Dekhuijzen, P.N.R. AU - Scheffer, G.J. AU - Hoeven, J.G. van der AU - Heunks, L.M.A. PY - 2015 UR - https://hdl.handle.net/2066/153276 AB - INTRODUCTION: Controlled mechanical ventilation and endotoxemia are associated with diaphragm muscle atrophy and dysfunction. Oxidative stress and activation of inflammatory pathways are involved in the pathogenesis of diaphragmatic dysfunction. Levosimendan, a cardiac inotrope, has been reported to possess anti-oxidative and anti-inflammatory properties. The aim of the present study was to investigate the effects of levosimendan on markers for diaphragm nitrosative and oxidative stress, inflammation and proteolysis in a mouse model of endotoxemia and mechanical ventilation. METHODS: Three groups were studied: (1) unventilated mice (CON, n =8), (2) mechanically ventilated endotoxemic mice (MV LPS, n =17) and (3) mechanically ventilated endotoxemic mice treated with levosimendan (MV LPS + L, n =17). Immediately after anesthesia (CON) or after 8 hours of mechanical ventilation, blood and diaphragm muscle were harvested for biochemical analysis. RESULTS: Mechanical ventilation and endotoxemia increased expression of inducible nitric oxide synthase (iNOS) mRNA and cytokine levels of interleukin (IL)-1beta, IL-6 and keratinocyte-derived chemokine, and decreased IL-10, in the diaphragm; however, they had no effect on protein nitrosylation and 4-hydroxy-2-nonenal protein concentrations. Levosimendan decreased nitrosylated proteins by 10% (P <0.05) and 4-hydroxy-2-nonenal protein concentrations by 13% (P <0.05), but it augmented the rise of iNOS mRNA by 47% (P <0.05). Levosimendan did not affect the inflammatory response in the diaphragm induced by mechanical ventilation and endotoxemia. CONCLUSIONS: Mechanical ventilation in combination with endotoxemia results in systemic and diaphragmatic inflammation. Levosimendan partly decreased markers of nitrosative and oxidative stress, but did not affect the inflammatory response. TI - Levosimendan affects oxidative and inflammatory pathways in the diaphragm of ventilated endotoxemic mice SN - 1466-609X IS - iss. 1 SP - 69 JF - Critical Care VL - vol. 19 DO - https://doi.org/10.1186/s13054-015-0798-8 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/153276/153276.pdf?sequence=1 ER - TY - JOUR AU - Dorresteijn, M.J. AU - Paine, A. AU - Zilian, E. AU - Fenten, M.G.E. AU - Frenzel, E. AU - Janciauskiene, S. AU - Figueiredo, C. AU - Eiz-Vesper, B. AU - Blasczyk, R. AU - Dekker, D. AU - Pennings, B. AU - Scharstuhl, A. AU - Smits, P. AU - Larmann, J. AU - Theilmeier, G. AU - Hoeven, J.G. van der AU - Wagener, F.A.D.T.G. AU - Pickkers, P. AU - Immenschuh, S. PY - 2015 UR - https://hdl.handle.net/2066/154724 AB - Heme oxygenase (HO)-1 is the inducible isoform of the heme-degrading enzyme HO, which is upregulated by multiple stress stimuli. HO-1 has major immunomodulatory and anti-inflammatory effects via its cell-type-specific functions in mononuclear cells. Contradictory findings have been reported on HO-1 regulation by the Toll-like receptor (TLR) 4 ligand lipopolysaccharide (LPS) in these cells. Therefore, we reinvestigated the effects of LPS on HO-1 gene expression in human and murine mononuclear cells in vitro and in vivo. Remarkably, LPS downregulated HO-1 in primary human peripheral blood mononuclear cells (PBMCs), CD14(+) monocytes, macrophages, dendritic cells, and granulocytes, but upregulated this enzyme in primary murine macrophages and human monocytic leukemia cell lines. Furthermore, experiments with human CD14(+) monocytes revealed that activation of other TLRs including TLR1, -2, -5, -6, -8, and -9 decreased HO-1 mRNA expression. LPS-dependent downregulation of HO-1 was specific, because expression of cyclooxygenase-2, NADP(H)-quinone oxidoreductase-1, and peroxiredoxin-1 was increased under the same experimental conditions. Notably, LPS upregulated expression of Bach1, a critical transcriptional repressor of HO-1. Moreover, knockdown of this nuclear factor enhanced basal and LPS-dependent HO-1 expression in mononuclear cells. Finally, downregulation of HO-1 in response to LPS was confirmed in PBMCs from human individuals subjected to experimental endotoxemia. In conclusion, LPS downregulates HO-1 expression in primary human mononuclear cells via a Bach1-mediated pathway. As LPS-dependent HO-1 regulation is cell-type- and species-specific, experimental findings in cell lines and animal models need careful interpretation. TI - Cell-type-specific downregulation of heme oxygenase-1 by lipopolysaccharide via Bach1 in primary human mononuclear cells EP - 232 SN - 0891-5849 SP - 224 JF - Free Radical Biology and Medicine VL - vol. 78 DO - https://doi.org/10.1016/j.freeradbiomed.2014.10.579 ER - TY - JOUR AU - Kiers, H.D. AU - Gerretsen, J. AU - Janssen, E. AU - John, A. AU - Groeneveld, R. AU - Hoeven, J.G. van der AU - Scheffer, G.J. AU - Pickkers, P. AU - Kox, M. PY - 2015 UR - https://hdl.handle.net/2066/152722 AB - Oxygen therapy to maintain tissue oxygenation is one of the cornerstones of critical care. Therefore, hyperoxia is often encountered in critically ill patients. Epidemiologic studies have demonstrated that hyperoxia may affect outcome, although mechanisms are unclear. Immunologic effects might be involved, as hyperoxia was shown to attenuate inflammation and organ damage in preclinical models. However, it remains unclear whether these observations can be ascribed to direct immunosuppressive effects of hyperoxia or to preserved tissue oxygenation. In contrast to these putative anti-inflammatory effects, hyperoxia may elicit an inflammatory response and organ damage in itself, known as oxygen toxicity. Here, we demonstrate that, in the absence of systemic inflammation, short-term hyperoxia (100% O2 for 2.5 hours in mice and 3.5 hours in humans) does not result in increased levels of inflammatory cytokines in both mice and healthy volunteers. Furthermore, we show that, compared with room air, hyperoxia does not affect the systemic inflammatory response elicited by administration of bacterial endotoxin in mice and man. Finally, neutrophil phagocytosis and ROS generation are unaffected by short-term hyperoxia. Our results indicate that hyperoxia does not exert direct anti-inflammatory effects and temper expectations of using it as an immunomodulatory treatment strategy. TI - Short-term hyperoxia does not exert immunologic effects during experimental murine and human endotoxemia SN - 2045-2322 JF - Scientific Reports VL - vol. 5 DO - https://doi.org/10.1038/srep17441 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/152722/152722.pdf?sequence=1 ER - TY - JOUR AU - Kolwijck, E. AU - Scheper, H. AU - Beuving, J. AU - Kuijper, E.J. AU - Hoeven, J.G. van der AU - Verweij, P.E. PY - 2015 UR - https://hdl.handle.net/2066/154528 AB - BACKGROUND: Invasive pulmonary aspergillosis (IPA) is a life-threatening infection that occurs predominantly in severely immunocompromised patients. Recently, IPA is also increasingly seen in less severely immunocompromised patients, such as patients with COPD receiving glucocorticoids and patients on ventilation in an IC unit. CASE DESCRIPTION: Here we present the case of a 59-year-old male who died of influenza complicated by a superinfection with Aspergillus fumigatus. This patient had no known previous medical history, except schizophrenia. CONCLUSION: Since the 2009 influenza pandemic, IPA has been increasingly reported as a superinfection in patients with a severe influenza virus infection. This combined Aspergillus and influenza infection often has a fatal outcome. An Aspergillus sputum culture should be taken seriously in patients with severe influenza pneumonia, and treatment should be considered early in the disease course. TI - [Invasive pulmonary aspergillosis in influenza] SN - 0028-2162 IS - iss. 0 SP - A7431 JF - Nederlands Tijdschrift voor Geneeskunde VL - vol. 159 ER - TY - JOUR AU - Ramakers, B.P.C. AU - Giamarellos-Bourboulis, E.J. AU - Tasioudis, C. AU - Coenen, M.J. AU - Kox, M. AU - Vermeulen, H.H. AU - Groothuismink, J.M. AU - Hoeven, J.G. van der AU - Routsi, C. AU - Savva, A. AU - Prekates, A. AU - Diamantea, F. AU - Sinapidis, D. AU - Smits, P. AU - Toutouzas, K. AU - Riksen, N.P. AU - Pickkers, P. PY - 2015 UR - https://hdl.handle.net/2066/152177 AB - INTRODUCTION: Adenosine exerts anti-inflammatory and tissue-protective effects during systemic inflammation. While the tissue-protective effects might limit organ damage, its anti-inflammatory properties may induce immunoparalysis and impede bacterial clearance. The common 34C>T loss-of-function variant of AMPD1 (rs17602729) is associated with increased adenosine formation, but effects on immune function and outcome in sepsis patients are unknown. METHODS: The effects of the presence of the 34C>T variant on sepsis susceptibility, immune function, multi-organ dysfunction, and mortality in septic patients were studied. Patients suffering from community acquired pneumonia (CAP, initial cohort n = 285; replication cohort n = 212) and ventilator-associated pneumonia (VAP, n = 117; n = 33) and control patients without infection (n = 101) were enrolled. Genetic distributions of the AMPD1 SNP were CC 76%, CT 22%, and TT 2% in the initial cohort and CC 80%, CT 18%, and TT 2% in the replication cohort. RESULTS: The occurrence of septic CAP, but not septic VAP, was increased for the CT versus CC genotype (OR (95% CI) 2.0 (1.1-3.7); P = 0.02) in the initial cohort. The increased risk for the CT versus CC genotype was also observed in the replication cohort but did not reach statistical significance there (P = 0.38), resulting in an OR of the total group of 1.7 (95% CI 1.0-3.1), P = 0.07. In septic patients carrying the CT genotype, the ex vivo production of TNF-alpha by LPS-stimulated monocytes was attenuated (P = 0.005), indicative of a more pronounced immunoparalytic state in these patients. CONCLUSIONS: Presence of the AMPD1 34C>T variant is associated with higher infection susceptibility to CAP, but not to VAP. More pronounced immunoparalysis in these patients mediated by the anti-inflammatory effects of adenosine may account for this observation. TI - Effects of the 34C>T Variant of the AMPD1 Gene on Immune Function, Multi-Organ Dysfunction, and Mortality in Sepsis Patients EP - 547 SN - 1073-2322 IS - iss. 6 SP - 542 JF - Shock VL - vol. 44 DO - https://doi.org/10.1097/SHK.0000000000000456 ER - TY - JOUR AU - Sluisveld, P.H.J. van AU - Hesselink, G.J. AU - Hoeven, J.G. van der AU - Westert, G.P. AU - Wollersheim, H.C. AU - Zegers, M. PY - 2015 UR - https://hdl.handle.net/2066/153116 AB - PURPOSE: To systematically review and evaluate the effectiveness of interventions in order to improve the safety and efficiency of patient handover between intensive care unit (ICU) and general ward healthcare professionals at ICU discharge. METHODS: PubMed, CINAHL, PsycINFO, EMBASE, Web of Science, and the Cochrane Library were searched for intervention studies with the aim to improve clinical handover between ICU and general ward healthcare professionals that had been published up to and including June 2013. The methods for article inclusion and data analysis were pre-specified and aligned with recommendations outlined in the PRISMA guideline. Two reviewers independently extracted data (study purpose, setting, population, method of sampling, sample size, intervention characteristics, outcome, and implementation activities) and assessed the quality of the included studies. RESULTS: From the 6,591 citations initially extracted from the six databases, we included 11 studies in this review. Of these, six (55 %) reported statistically significant effects. Effective interventions included liaison nurses to improve communication and coordination of care and forms to facilitate timely, complete and accurate handover information. Effective interventions resulted in improved continuity of care (e.g., reduced discharge delay) and in reduced adverse events. Inconsistent effects were observed for use of care, namely, reduction of length of stay versus increase of readmissions to higher care. No statistically significant effects were found in the reduction of mortality. The overall methodological quality of the 11 studies reviewed was relatively low, with an average score of 4.5 out of 11 points. CONCLUSIONS: This review shows that liaison nurses and handover forms are promising interventions to improve the quality of patient handover between the ICU and general ward. More robust evidence is needed on the effectiveness of interventions aiming to improve ICU handover and supportive implementation strategies. TI - Improving clinical handover between intensive care unit and general ward professionals at intensive care unit discharge EP - 604 SN - 0342-4642 IS - iss. 4 SP - 589 JF - Intensive Care Medicine VL - vol. 41 DO - https://doi.org/10.1007/s00134-015-3666-8 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/153116/153116.pdf?sequence=1 ER - TY - JOUR AU - Kox, M. AU - Eijk, L.T.G.J. van AU - Verhaak, T. AU - Frenzel, T. AU - Kiers, H.D. AU - Gerretsen, J. AU - Hoeven, J.G. van der AU - Kornet, L. AU - Scheiner, A. AU - Pickkers, P. PY - 2015 UR - https://hdl.handle.net/2066/154339 AB - INTRODUCTION: Vagus nerve stimulation (VNS) exerts beneficial anti-inflammatory effects in various animal models of inflammation, including collagen-induced arthritis, and is implicated in representing a novel therapy for rheumatoid arthritis. However, evidence of anti-inflammatory effects of VNS in humans is very scarce. Transvenous VNS (tVNS) is a newly developed and less invasive method to stimulate the vagus nerve. In the present study, we determined whether tVNS is a feasible and safe procedure and investigated its putative anti-inflammatory effects during experimental human endotoxemia. METHODS: We performed a randomized double-blind sham-controlled study in healthy male volunteers. A stimulation catheter was inserted in the left internal jugular vein at spinal level C5-C7, adjacent to the vagus nerve. In the tVNS group (n = 10), stimulation was continuously performed for 30 minutes (0-10 V, 1 ms, 20 Hz), starting 10 minutes before intravenous administration of 2 ng kg(-1) Escherichia coli lipopolysaccharide (LPS). Sham-instrumented subjects (n = 10) received no electrical stimulation. RESULTS: No serious adverse events occurred throughout the study. In the tVNS group, stimulation of the vagus nerve was achieved as indicated by laryngeal vibration. Endotoxemia resulted in fever, flu-like symptoms, and hemodynamic changes that were unaffected by tVNS. Furthermore, plasma levels of inflammatory cytokines increased sharply during endotoxemia, but responses were similar between groups. Finally, cytokine production by leukocytes stimulated with LPS ex vivo, as well as neutrophil phagocytosis capacity, were not influenced by tVNS. CONCLUSIONS: tVNS is feasible and safe, but does not modulate the innate immune response in humans in vivo during experimental human endotoxemia. TRIAL REGISTRATION: Clinicaltrials.gov NCT01944228 . Registered 12 September 2013. TI - Transvenous vagus nerve stimulation does not modulate the innate immune response during experimental human endotoxemia: a randomized controlled study SN - 1478-6354 SP - 150 JF - Arthritis Research & Therapy VL - vol. 17 DO - https://doi.org/10.1186/s13075-015-0667-5 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/154339/154339.pdf?sequence=1 ER - TY - JOUR AU - Nusmeier, A. AU - Cecchetti, C. AU - Blohm, M. AU - Lehman, R. AU - Hoeven, J.G. van der AU - Lemson, J. PY - 2015 UR - https://hdl.handle.net/2066/153476 AB - OBJECTIVES: To define near-normal values of extravascular lung water indexed to body weight in children. DESIGN: Prospective multicenter observational study. SETTING: Medical/surgical PICUs of 5 multinational hospitals. PATIENTS: Fifty-eight children with a median age of 4 years (range 1 month to 17 year) with heterogeneous PICU admission diagnoses were included. Extravascular lung water measurements from these children were collected after resolution of their illness. Obtained values were indexed to actual body weight and height and subsequently related to age. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Extravascular lung water indexed to body weight correlated with age (r2 = 0.7) and could be categorized in three-age groups consisting of significantly different median extravascular lung water indexed to body weight values (5th-95th percentile): less than 1 year, 9-29 mL/kg; 1-5 years, 7-25 mL/kg; and 5-17 years, 5-13 mL/kg. Extravascular lung water indexed to height did not correlate to age and resulted in an age-independent near-normal value of less than 315 mL/m. CONCLUSIONS: Younger children have higher values of extravascular lung water indexed to actual body weight. Age categorized near-normal values of extravascular lung water indexed to body weight are presented for possible clinical use. Furthermore, we suggest to index extravascular lung water to height, which seems to be age independent. TI - Near-normal values of extravascular lung water in children EP - 33 SN - 1529-7535 IS - iss. 2 SP - e28 JF - Pediatric Critical Care Medicine VL - vol. 16 DO - https://doi.org/10.1097/PCC.0000000000000312 ER - TY - JOUR AU - Tilburgs, B. AU - Nijkamp, M.D. AU - Bakker, E.C. AU - Hoeven, H. van der PY - 2015 UR - https://hdl.handle.net/2066/152845 AB - OBJECTIVES: To determine the influence of instrumental, emotional and informative support on the quality of life of former intensive care unit (ICU) patients and to establish their preferred sources of social support. RESEARCH METHODOLOGY: In a cross-sectional survey, former intensive care patients (n=88) completed the "social support interactions/discrepancies list", the "RAND-36 Health Survey" and reported their preferred sources of the different types of social support. SETTING: A 35 bed intensive care unit in the Radboudumc university hospital in the Netherlands. MAIN OUTCOME MEASURES: Psychological, physical and social domains of quality of life and patient preferences regarding sources of social support. RESULTS: Instrumental and emotional support show a buffering effect on the physical dimension of the quality of life. The discrepancies between the expected and the received instrumental, informative and emotional support have a negative influence on psychological quality of life. Former ICU patients prefer receiving social support from family members rather than friends, professional caregivers or fellow former ICU patients. CONCLUSION: This study emphasises the buffering effect of social support on diminished quality of life in former intensive care patients. It is suggested that hospitals provide an intensive care after-care programme including both patients and relatives to help fulfilling this need for social support. TI - The influence of social support on patients' quality of life after an intensive care unit discharge: A cross-sectional survey EP - 342 SN - 0964-3397 IS - iss. 6 SP - 336 JF - Intensive and Critical Care Nursing VL - vol. 31 DO - https://doi.org/10.1016/j.iccn.2015.07.002 ER - TY - JOUR AU - Douw, G. AU - Schoonhoven, L. AU - Holwerda, T. AU - Huisman-de Waal, G.J. AU - Zanten, A.R. van AU - Achterberg, T. van AU - Hoeven, J.G. van der PY - 2015 UR - https://hdl.handle.net/2066/153532 AB - INTRODUCTION: Nurses often recognize deterioration in patients through intuition rather than through routine measurement of vital signs. Adding the 'worry or concern' sign to the Rapid Response System provides opportunities for nurses to act upon their intuitive feelings. Identifying what triggers nurses to be worried or concerned might help to put intuition into words, and potentially empower nurses to act upon their intuitive feelings and obtain medical assistance in an early stage of deterioration. The aim of this systematic review is to identify the signs and symptoms that trigger nurses' worry or concern about a patient's condition. METHODS: We searched the databases PubMed, CINAHL, Psychinfo and Cochrane Library (Clinical Trials) using synonyms related to the three concepts: 'nurses', 'worry/concern' and 'deterioration'. We included studies concerning adult patients on general wards in acute care hospitals. The search was performed from the start of the databases until 14 February 2014. RESULTS: The search resulted in 4,006 records, and 18 studies (five quantitative, nine qualitative and four mixed-methods designs) were included in the review. A total of 37 signs and symptoms reflecting the nature of the criterion worry or concern emerged from the data and were summarized in 10 general indicators. The results showed that worry or concern can be present with or without change in vital signs. CONCLUSIONS: The signs and symptoms we found in the literature reflect the nature of nurses' worry or concern, and nurses may incorporate these signs in their assessment of the patient and their decision to call for assistance. The fact that it is present before changes in vital signs suggests potential for improving care in an early stage of deterioration. TI - Nurses' worry or concern and early recognition of deteriorating patients on general wards in acute care hospitals: a systematic review SN - 1466-609X SP - 230 JF - Critical Care VL - vol. 19 DO - https://doi.org/10.1186/s13054-015-0950-5 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/153532/153532.pdf?sequence=1 ER - TY - JOUR AU - Lansdorp, B. AU - Lemson, J. AU - Hoeven, J.G. van der AU - Pickkers, P. PY - 2015 UR - https://hdl.handle.net/2066/154147 TI - The authors reply SN - 0090-3493 IS - iss. 2 SP - e53 JF - Critical Care Medicine VL - vol. 43 DO - https://doi.org/10.1097/CCM.0000000000000808 ER - TY - JOUR AU - Vrancken, S.L.A.G. AU - Heijst, A.F.J. van AU - Hopman, J.C.W. AU - Liem, K.D. AU - Hoeven, J.G. van der AU - Boode, W.P. de PY - 2015 UR - https://hdl.handle.net/2066/152964 AB - To analyze changes in cardiac output and hemodynamic volumes using transpulmonary ultrasound dilution (TPUD) in a neonatal animal model under different hemodynamic conditions. 7 lambs (3.5-8.3 kg) under general anesthesia received arterial and central venous catheters. A Gore-Tex((R)) shunt was surgically inserted between the descending aorta and the left pulmonary artery to mimic a patent ductus arteriosus. After shunt opening and closure, induced hemorrhagic hypotension (by repetitive blood withdrawals) and repetitive volume challenges, the following parameters were assessed using TPUD: cardiac output, active circulating volume index (ACVI), central blood volume index (CBVI) and total end-diastolic volume index (TEDVI). 27 measurement sessions were analyzed. After shunt opening, there was a significant increase in TEDVI and a significant decrease in cardiac output with minimal change in CBVI and ACVI. With shunt closure, these results reversed. After progressive hemorrhage, cardiac output and all volumes decreased significantly, except for ACVI. Following repetitive volume resuscitation, cardiac output increased and all hemodynamic volumes increased significantly. Correlations between changes in COufp and changes in hemodynamic volumes (ACVI 0.83; CBVI 0.84 and TEDVI 0.78 respectively) were (slightly) better than between changes in COufp and changes in heart rate (0.44) and central venous pressure (0.7). Changes in hemodynamic volumes using TPUD were as expected under different conditions. Hemodynamic volumetry using TPUD might be a promising technique that has the potential to improve the assessment and interpretation of the hemodynamic status in critically ill newborns and children. TI - Hemodynamic volumetry using transpulmonary ultrasound dilution (TPUD) technology in a neonatal animal model EP - 652 SN - 1387-1307 IS - iss. 5 SP - 643 JF - Journal of Clinical Monitoring and Computing VL - vol. 29 DO - https://doi.org/10.1007/s10877-014-9647-6 ER - TY - JOUR AU - Bartels, R.H.M.A. AU - Meijer, F.J.A. AU - Hoeven, H. van der AU - Edwards, M.J. AU - Prokop, M. PY - 2015 UR - https://hdl.handle.net/2066/152480 AB - BACKGROUND: Traumatic acute subdural hematoma has a high mortality despite intensive treatment. Despite the existence of several prediction models, it is very hard to predict an outcome. We investigated whether a specific combination of initial head CT-scan findings is a factor in predicting outcome, especially non-survival. METHODS: We retrospectively studied admission head CT scans of all adult patients referred for a traumatic acute subdural hematoma between April 2009 and April 2013. Chart review was performed for every included patient. Midline shift and thickness of the hematoma were measured by two independent observers. The difference between midline shift and thickness of the hematoma was calculated. These differences were correlated with outcome. IRB has approved the study. RESULTS: A total of 59 patients were included, of whom 29 died. We found a strong correlation between a midline shift exceeding the thickness of the hematoma by 3 mm or more, and subsequent mortality. For each evaluation, specificity was 1.0 (95 % CI: 0.85-1 for all evaluations), positive predictive value 1.0 (95 % CI between 0.31-1 and 0.56-1), while sensitivity ranged from 0.1 to 0.23 (95 % CI between 0.08-0.39 and 0.17-0.43), and negative predictive value varied from 0.52 to 0.56 (95 % CI between 0.38-0.65 and 0.41-0.69). CONCLUSIONS: In case of a traumatic acute subdural hematoma, a difference between the midline shift and the thickness of the hematoma >/= 3 mm at the initial CT predicted mortality in all cases. This is the first time that such a strong correlation was reported. Especially for the future development of prediction models, the relation between midline shift and thickness of the hematoma could be included as a separate factor. TI - Midline shift in relation to thickness of traumatic acute subdural hematoma predicts mortality SN - 1471-2377 SP - 220 JF - BMC Neurology VL - vol. 15 DO - https://doi.org/10.1186/s12883-015-0479-x L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/152480/152480.pdf?sequence=1 ER - TY - JOUR AU - Timmermans, K. AU - Kox, M. AU - Gerretsen, J. AU - Peters, E. AU - Scheffer, G.J. AU - Hoeven, J.G. van der AU - Pickkers, P. AU - Hoedemaekers, C.W.E. PY - 2015 UR - https://hdl.handle.net/2066/154124 AB - OBJECTIVES: After cardiac arrest, patients are highly vulnerable toward infections, possibly due to a suppressed state of the immune system called "immunoparalysis." We investigated if immunoparalysis develops following cardiac arrest and whether the release of danger-associated molecular patterns could be involved. DESIGN: Observational study. SETTING: ICU of a university medical center. PATIENTS: Fourteen post-cardiac arrest patients treated with mild therapeutic hypothermia for 24 hours and 11 control subjects. MEASUREMENTS AND MAIN RESULTS: Plasma cytokines showed highest levels within 24 hours after cardiac arrest and decreased during the next 2 days. By contrast, ex vivo production of cytokines interleukin-6, tumor necrosis factor-alpha, and interleukin-10 by lipopolysaccharide-stimulated leukocytes was severely impaired compared with control subjects, with most profound effects observed at day 0, and only partially recovering afterward. Compared with incubation at 37 degrees C, incubation at 32 degrees C resulted in higher interleukin-6 and lower interleukin-10 production by lipopolysaccharide-stimulated leukocytes of control subjects, but not of patients. Plasma nuclear DNA, used as a marker for general danger-associated molecular pattern release, and the specific danger-associated molecular patterns (EN-RAGE and heat shock protein 70) were substantially higher in patients at days 0 and 1 compared with control subjects. Furthermore, plasma heat shock protein 70 levels were negatively correlated with ex vivo production of inflammatory mediators interleukin-6, tumor necrosis factor-alpha, and interleukin-10. Extracellular newly identified receptor for advanced glycation end products-binding protein levels only showed a significant negative correlation with ex vivo production of interleukin-6 and tumor necrosis factor-alpha and a borderline significant inverse correlation with interleukin-10. No significant correlations were observed between plasma nuclear DNA levels and ex vivo cytokine production. INTERVENTIONS: None. CONCLUSIONS: Release of danger-associated molecular patterns during the first days after cardiac arrest is associated with the development of immunoparalysis. This could explain the increased susceptibility toward infections in cardiac arrest patients. TI - The Involvement of Danger-Associated Molecular Patterns in the Development of Immunoparalysis in Cardiac Arrest Patients EP - 2338 SN - 0090-3493 IS - iss. 11 SP - 2332 JF - Critical Care Medicine VL - vol. 43 DO - https://doi.org/10.1097/CCM.0000000000001204 ER - TY - JOUR AU - Wal, S.E.I. van der AU - Vaneker, M. AU - Steegers, M.A.H. AU - Berkum, B. van AU - Kox, M. AU - Laak, J.A. van der AU - Hoeven, J.G. van der AU - Vissers, K. AU - Scheffer, G.J. PY - 2015 UR - https://hdl.handle.net/2066/153279 AB - BACKGROUND: Mechanical ventilation (MV) induces an inflammatory response that may result in (acute) lung injury. Lidocaine, an amide local anesthetic, has anti-inflammatory properties in vitro and in vivo, possibly due to an attenuation of pro-inflammatory cytokines, intracellular adhesion molecule-1 (ICAM-1), and reduction of neutrophils influx. We hypothesized an attenuation of MV-induced inflammatory response with intravenously administered lidocaine. METHODS: Lidocaine (Lido) (2, 4, and 8 mg/kg/h) was intravenously administered during 4 h of MV with a tidal volume of 8 ml/kg, positive end expiratory pressure 1,5 cmH2O and FiO2 0.4. We used one ventilated control (CON) group receiving vehicle. After MV, mice were euthanized, and lungs and blood were immediately harvested, and cytokine levels and ICAM-1 levels were measured in plasma and lung homogenates. Pulmonary neutrophils influx was determined in LEDER-stained slices of lungs. Anesthetic need was determined by painful hind paw stimulation. RESULTS: Lidocaine-treated animals (Lido 2, 4 and 8 mg/kg/h) showed higher interleukin (IL)-10 plasma levels compared to control animals. Lidocaine treatment with 8 mg/kg/h (Lido 8) resulted in higher IL-10 in lung homogenates. No differences were observed in pro-inflammatory cytokines, ICAM-1, and pulmonary influx between the different ventilated groups. CONCLUSIONS: Intravenously administered lidocaine increases levels of plasma IL-10 with infusion from 2, 4, and 8 mg/kg/h and pulmonary levels of IL-10 with 8 mg/kg/h in a murine mechanical ventilation model. Intravenously administered lidocaine appears to reduce anesthetic need in mice. TI - Lidocaine increases the anti-inflammatory cytokine IL-10 following mechanical ventilation in healthy mice EP - 55 SN - 0001-5172 IS - iss. 1 SP - 47 JF - Acta Anaesthesiologica Scandinavica VL - vol. 59 DO - https://doi.org/10.1111/aas.12417 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/153279/153279.pdf?sequence=1 ER - TY - JOUR AU - Heunks, L.M.A. AU - Doorduin, J. AU - Hoeven, J.G. van der PY - 2015 UR - https://hdl.handle.net/2066/153420 AB - PURPOSE OF REVIEW: The present review summarizes developments in the field of respiratory muscle monitoring, in particular in critically ill patients. RECENT FINDINGS: Patients admitted to the ICU may develop severe respiratory muscle dysfunction in a very short time span. Among other factors, disuse and sepsis have been associated with respiratory muscle dysfunction in these patients. Because weakness is associated with adverse outcome, including prolonged mechanical ventilation and mortality, it is surprising that respiratory muscle dysfunction largely develops without being noticed by the clinician. Respiratory muscle monitoring is not standard of care in most ICUs. Improvements in technology have opened windows for monitoring the respiratory muscles in critically ill patients. Diaphragm electromyography and esophageal pressure measurement are feasible techniques for respiratory muscle monitoring, although the effect on outcome remains to be investigated. SUMMARY: Respiratory muscle dysfunction develops rapidly in selected critically ill patients and is associated with adverse outcome. Recent technological advances allow real-time monitoring of respiratory muscle activity in these patients. Although this field is in its infancy, from a physiological perspective, it is reasonable to assume that monitoring respiratory muscle activity improves outcome in these patients. TI - Monitoring and preventing diaphragm injury EP - 41 SN - 1070-5295 IS - iss. 1 SP - 34 JF - Current Opinion in Critical Care VL - vol. 21 DO - https://doi.org/10.1097/MCC.0000000000000168 ER - TY - JOUR AU - Doorduin, J. AU - Leentjens, J. AU - Kox, M. AU - Hees, H.W.H. van AU - Hoeven, J.G. van der AU - Pickkers, P. AU - Heunks, L.M.A. PY - 2015 UR - https://hdl.handle.net/2066/155091 AB - INTRODUCTION: Systemic inflammation is a well-known risk factor for respiratory muscle weakness. Studies using animal models of inflammation have shown that endotoxin administration induces diaphragm dysfunction. However, the effects of in vivo endotoxin administration on diaphragm function in humans have not been studied. Our aim was to evaluate diaphragm function in a model of systemic inflammation in healthy subjects. METHODS: Two groups of 12 male volunteers received an intravenous bolus of 2 ng/kg of Escherichia coli lipopolysaccharide (LPS) and were monitored until 8 h after LPS administration. In the first group, the twitch transdiaphragmatic pressure (Pditw) and compound muscle action potential of the diaphragm (CMAPdi) were measured. In addition, plasma levels of cytokines, heart rate, and arterial blood pressure were measured. In the second group, catecholamines as well as respiratory rate and blood gas values were measured. Diaphragm ultrasonography was performed in four subjects with severe shivering. RESULTS: Lipopolysaccharide administration resulted in flulike symptoms, hemodynamic alterations, and increased plasma levels of cytokines. The Pditw increased after LPS administration from 31.2 +/- 2.0 cmH2O (baseline) to 38.8 +/- 2.0 cmH2O (t = 1 h) and 35.4 +/- 2.0 cmH2O (t = 1.5 h). There was no correlation between cytokine plasma levels and the Pditw. We found a trend toward a gradual decrease in the CMAPdi from 0.78 +/- 0.07 mV (baseline) to 0.58 +/- 0.05 mV (t = 2 h). Respiratory rate increased after LPS administration from 16.8 +/- 0.5 breaths/min (baseline) to 20.3 +/- 0.6 breaths/min (t = 4 h), with a resulting decrease in PaCO2 of 0.5 +/- 0.1 kPa. Plasma levels of epinephrine peaked at t = 1.5 h, with an increase of 1.3 +/- 0.3 nmol/L from baseline. Rapid diaphragm contractions consistent with shivering were observed. CONCLUSIONS: This study shows that, in contrast to diaphragm dysfunction observed in animal models of inflammation, in vivo diaphragm contractility is augmented in the early phase after low-dose endotoxin administration in humans. TI - Effects of experimental human endotoxemia on diaphragm function EP - 322 SN - 1073-2322 IS - iss. 4 SP - 316 JF - Shock VL - vol. 44 DO - https://doi.org/10.1097/SHK.0000000000000435 ER - TY - JOUR AU - Doorduin, J. AU - Sinderby, C.A. AU - Beck, J. AU - Hoeven, J.G. van der AU - Heunks, L.M. PY - 2015 UR - https://hdl.handle.net/2066/151946 AB - BACKGROUND: In patients with acute respiratory distress syndrome (ARDS), the use of assisted mechanical ventilation is a subject of debate. Assisted ventilation has benefits over controlled ventilation, such as preserved diaphragm function and improved oxygenation. Therefore, higher level of "patient control" of ventilator assist may be preferable in ARDS. However, assisted modes may also increase the risk of high tidal volumes and lung-distending pressures. The current study aims to quantify how differences in freedom to control the ventilator affect lung-protective ventilation, breathing pattern variability, and patient-ventilator interaction. METHODS: Twelve patients with ARDS were ventilated in a randomized order with assist pressure control ventilation (PCV), pressure support ventilation (PSV), and neurally adjusted ventilatory assist (NAVA). Transpulmonary pressure, tidal volume, diaphragm electrical activity, and patient-ventilator interaction were measured. Respiratory variability was assessed using the coefficient of variation of tidal volume. RESULTS: During inspiration, transpulmonary pressure was slightly lower with NAVA (10.3 +/- 0.7, 11.2 +/- 0.7, and 9.4 +/- 0.7 cm H2O for PCV, PSV, and NAVA, respectively; P < 0.01). Tidal volume was similar between modes (6.6 [5.7 to 7.0], 6.4 [5.8 to 7.0], and 6.0 [5.6 to 7.3] ml/kg for PCV, PSV, and NAVA, respectively), but respiratory variability was higher with NAVA (8.0 [6.4 to 10.0], 7.1 [5.9 to 9.0], and 17.0 [12.0 to 36.1] % for PCV, PSV, and NAVA, respectively; P < 0.001). Patient-ventilator interaction improved with NAVA (6 [5 to 8] % error) compared with PCV (29 [14 to 52] % error) and PSV (12 [9 to 27] % error); P < 0.0001. CONCLUSION: In patients with mild-to-moderate ARDS, increasing freedom to control the ventilator maintains lung-protective ventilation in terms of tidal volume and lung-distending pressure, but it improves patient-ventilator interaction and preserves respiratory variability. TI - Assisted Ventilation in Patients with Acute Respiratory Distress Syndrome: Lung-distending Pressure and Patient-Ventilator Interaction EP - 190 SN - 0003-3022 IS - iss. 1 SP - 181 JF - Anesthesiology VL - vol. 123 DO - https://doi.org/10.1097/ALN.0000000000000694 ER - TY - JOUR AU - Felten-Barentsz, K.M. AU - Haans, A.J.C. AU - Slutsky, A.S. AU - Heunks, L.M.A. AU - Hoeven, J.G. van der PY - 2015 UR - https://hdl.handle.net/2066/155272 TI - Feasibility and safety of hydrotherapy in critically ill ventilated patients EP - 477 SN - 1073-449X IS - iss. 4 SP - 476 JF - American Journal of Respiratory and Critical Care Medicine VL - vol. 191 DO - https://doi.org/10.1164/rccm.201408-1559LE ER - TY - JOUR AU - Bisschops, L.L.A. AU - Pop, G.A.M. AU - Teerenstra, S. AU - Struijk, P.C. AU - Hoeven, J.G. van der AU - Hoedemaekers, C.W.E. PY - 2014 UR - https://hdl.handle.net/2066/136280 AB - OBJECTIVES: To determine blood viscosity in adult comatose patients treated with mild therapeutic hypothermia after cardiac arrest and to assess the relation between blood viscosity, cerebral blood flow, and cerebral oxygen extraction. DESIGN: Observational study. SETTING: Tertiary care university hospital. PATIENTS: Ten comatose patients with return of spontaneous circulation after out-of-hospital cardiac arrest. INTERVENTION: Treatment with mild therapeutic hypothermia for 24 hours followed by passive rewarming to normothermia. MEASUREMENTS AND MAIN RESULTS: Median viscosity at shear rate 50/s was 5.27 mPa . s (4.29-5.91 mPa . s) at admission; it remained relatively stable during the first 12 hours and decreased significantly to 3.00 mPa . s (2.72-3.58 mPa . s) at 72 hours (p < 0.001). Median mean flow velocity in the middle cerebral artery was low (27.0 cm/s [23.8-30.5 cm/s]) at admission and significantly increased to 63.0 cm/s (51.0-80.0 cm/s) at 72 hours. Median jugular bulb saturation at the start of the study was 61.5% (55.5-75.3%) and significantly increased to 73.0% (69.0-81.0%) at 72 hours. Median hematocrit was 0.41 L/L (0.36-0.44 L/L) at admission and subsequently decreased significantly to 0.32 L/L (0.27-0.35 L/L) at 72 hours. Median C-reactive protein concentration was low at admission (2.5 mg/L [2.5-6.5 mg/L]) and increased to 101 mg/L (65-113.3 mg/L) in the following hours. Median fibrinogen concentration was increased at admission 2,795 mg/L (2,503-3,565 mg/L) and subsequently further increased to 6,195 mg/L (5,843-7,368 mg/L) at 72 hours. There was a significant negative association between blood viscosity and the mean flow velocity in the middle cerebral artery (p = 0.0008). CONCLUSIONS: Changes in blood viscosity in vivo are associated with changes in flow velocity in the middle cerebral artery. High viscosity early after cardiac arrest may reduce cerebral blood flow and may contribute to secondary brain injury. Further studies are needed to determine the optimal viscosity during the different stages of the postcardiac arrest syndrome. TI - Effects of viscosity on cerebral blood flow after cardiac arrest EP - 637 SN - 0090-3493 IS - iss. 3 SP - 632 JF - Critical Care Medicine VL - vol. 42 DO - http://dx.doi.org/10.1097/CCM.0000000000000027 ER - TY - JOUR AU - Bles, C. AU - Hoeven, J.G. van der AU - Hoedemaekers, C.W.E. PY - 2014 UR - https://hdl.handle.net/2066/138809 TI - Acetozolamide induced hyperammonaemia: a case report and review of the literature EP - 27 SN - 1569-3511 IS - iss. 1 SP - 25 JF - Netherlands Journal of Critical Care VL - vol. 18 ER - TY - JOUR AU - Hoedemaekers, C.W. AU - Hoeven, J.G. van der PY - 2014 UR - https://hdl.handle.net/2066/138359 TI - Is alpha-stat or pH-stat the best strategy during hypothermia after cardiac arrest?* EP - 1951 SN - 0090-3493 IS - iss. 8 SP - 1950 JF - Critical Care Medicine VL - vol. 42 DO - http://dx.doi.org/10.1097/CCM.0000000000000377 ER - TY - JOUR AU - Dieperink, P. AU - Hoeven, J.G. van der AU - Niesten, E.D. PY - 2014 UR - https://hdl.handle.net/2066/137785 TI - A misdiagnosed case of symptomatic hyponatraemia EP - 421 SN - 0310-057X IS - iss. 3 SP - 420 JF - Anaesthesia and Intensive Care VL - vol. 42 ER - TY - JOUR AU - Verlaat, C.W.M. AU - Heesen, G.P. AU - Vet, N.J. AU - Hoog, M. de AU - Hoeven, J.G. van der AU - Kox, M. AU - Pickkers, P. PY - 2014 UR - https://hdl.handle.net/2066/133867 AB - AIM: To study the feasibility of daily interruption of sedatives in critically ill children. METHODS: Prospective randomized controlled open-label trial, performed in a pediatric intensive care unit of a tertiary care teaching and referring hospital. 30 children (0-12 years) receiving mechanically ventilation for >24 h were included. In the intervention group, all sedatives were stopped daily and restarted when COMFORT-behavior score >/=17. The control group received standard care. Primary end points were amounts of sedatives and number of bolus medications in the first 3 days after enrollment and number of (near) incidents. Secondary end points were duration of mechanical ventilation, length of stay in pediatric intensive care, and changes in COMFORT-behavior score. Results : Midazolam and morphine use were lower in the intervention group compared with the control group (P = 0.007 and P = 0.02, respectively), whereas the number of bolus medications did not differ between groups. Two complications were recorded: one patient (intervention group) lost his intravenous line, and one patient (control group) had an unplanned extubation. Duration of mechanical ventilation was significantly shorter in the intervention group compared with the control group (median [interquartile range] of 4 [3-8] and 9 [4-10] days, respectively, P = 0.03). Length of stay in the PICU in the intervention group was significantly shorter than in the control group (median [interquartile range] of 6 [4-9] and 10 [7-15] days, respectively, P = 0.01). CONCLUSIONS: Daily interruption of sedatives in critically ill children is feasible, results in decreased use of sedation, earlier extubation, and shorter length of stay. TI - Randomized controlled trial of daily interruption of sedatives in critically ill children EP - 156 SN - 1155-5645 IS - iss. 2 SP - 151 JF - Paediatric Anaesthesia VL - vol. 24 DO - http://dx.doi.org/10.1111/pan.12245 ER - TY - JOUR AU - Schellekens, W.J.M. AU - Hees, H.W.H. van AU - Kox, M. AU - Linkels, M. AU - Acuna, G.L. AU - Dekhuijzen, P.N.R. AU - Scheffer, G.J. AU - Hoeven, J.G. van der AU - Heunks, L.M.A. PY - 2014 UR - https://hdl.handle.net/2066/134064 AB - INTRODUCTION: Diaphragm weakness induced by prolonged mechanical ventilation may contribute to difficult weaning from the ventilator. Hypercapnia is an accepted side effect of low tidal volume mechanical ventilation, but the effects of hypercapnia on respiratory muscle function are largely unknown. The present study investigated the effect of hypercapnia on ventilator-induced diaphragm inflammation, atrophy and function. METHODS: Male Wistar rats (n = 10 per group) were unventilated (CON), mechanically ventilated for 18 hours without (MV) or with hypercapnia (MV + H, Fico2 = 0.05). Diaphragm muscle was excised for structural, biochemical and functional analyses. RESULTS: Myosin concentration in the diaphragm was decreased in MV versus CON, but not in MV + H versus CON. MV reduced diaphragm force by approximately 22% compared with CON. The force-generating capacity of diaphragm fibers from MV + H rats was approximately 14% lower compared with CON. Inflammatory cytokines were elevated in the diaphragm of MV rats, but not in the MV + H group. Diaphragm proteasome activity did not significantly differ between MV and CON. However, proteasome activity in the diaphragm of MV + H was significantly lower compared with CON. LC3B-II a marker of lysosomal autophagy was increased in both MV and MV + H. Incubation of MV + H diaphragm muscle fibers with the antioxidant dithiothreitol restored force generation of diaphragm fibers. CONCLUSIONS: Hypercapnia partly protects the diaphragm against adverse effects of mechanical ventilation. TI - Hypercapnia attenuates ventilator-induced diaphragm atrophy and modulates dysfunction SN - 1466-609X IS - iss. 1 SP - R28 JF - Critical Care VL - vol. 18 DO - https://doi.org/10.1186/cc13719 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/134064/134064.pdf?sequence=1 ER - TY - JOUR AU - Boogaard, M.H.W.A. van den AU - Schoonhoven, L. AU - Maseda, E. AU - Plowright, C. AU - Jones, C. AU - Luetz, A. AU - Sackey, P.V. AU - Jorens, P.G. AU - Aitken, L.M. AU - Haren, F.M.P. van AU - Donders, R. AU - Hoeven, J.G. van der AU - Pickkers, P. PY - 2014 UR - https://hdl.handle.net/2066/136662 AB - PURPOSE: Recalibration and determining discriminative power, internationally, of the existing delirium prediction model (PRE-DELIRIC) for intensive care patients. METHODS: A prospective multicenter cohort study was performed in eight intensive care units (ICUs) in six countries. The ten predictors (age, APACHE-II, urgent and admission category, infection, coma, sedation, morphine use, urea level, metabolic acidosis) were collected within 24 h after ICU admission. The confusion assessment method for the intensive care unit (CAM-ICU) was used to identify ICU delirium. CAM-ICU screening compliance and inter-rater reliability measurements were used to secure the quality of the data. RESULTS: A total of 2,852 adult ICU patients were screened of which 1,824 (64 %) were eligible for the study. Main reasons for exclusion were length of stay <1 day (19.1 %) and sustained coma (4.1 %). CAM-ICU compliance was mean (SD) 82 +/- 16 % and inter-rater reliability 0.87 +/- 0.17. The median delirium incidence was 22.5 % (IQR 12.8-36.6 %). Although the incidence of all ten predictors differed significantly between centers, the area under the receiver operating characteristic (AUROC) curve of the eight participating centers remained good: 0.77 (95 % CI 0.74-0.79). The linear predictor and intercept of the prediction rule were adjusted and resulted in improved re-calibration of the PRE-DELIRIC model. CONCLUSIONS: In this multinational study, we recalibrated the PRE-DELIRIC model. Despite differences in the incidence of predictors between the centers in the different countries, the performance of the PRE-DELIRIC-model remained good. Following validation of the PRE-DELIRIC model, it may facilitate implementation of strategies to prevent delirium and aid improvements in delirium management of ICU patients. TI - Recalibration of the delirium prediction model for ICU patients (PRE-DELIRIC): a multinational observational study EP - 369 SN - 0342-4642 IS - iss. 3 SP - 361 JF - Intensive Care Medicine VL - vol. 40 DO - https://doi.org/10.1007/s00134-013-3202-7 ER - TY - JOUR AU - Eijk, L.T.G.J. van AU - Pluijm, R.W. van der AU - Ramakers, B.P.C. AU - Dorresteijn, M.J. AU - Hoeven, J.G. van der AU - Kox, M. AU - Pickkers, P. PY - 2014 UR - https://hdl.handle.net/2066/133915 AB - A higher body mass index (BMI) appears to be associated with lower mortality in critically ill patients, possibly explained by an altered innate immune response. However, the precise relationship between BMI and the innate immune response in humans in vivo is unknown. We investigated the relationship between BMI and the systemic cytokine response during experimental human endotoxemia. Endotoxemia was induced in 112 healthy male volunteers by intravenous administration of 2 ng/kg Escherichia coli endotoxin. Plasma concentrations of TNF-alpha, IL-6, IL-10 and IL-1RA were serially determined. The relationship between BMI and the cytokine response, as well as body temperature, was investigated. The BMIs of the participants ranged from 18.3 to 33.6 kg/m(2), (median: 22.7 kg/m(2)). All participants showed a marked increase in plasma cytokine levels [median (interquartile range)] peak levels: TNF-alpha 509 (353-673) pg/ml; IL-6 757 (522-1098) pg/ml; IL-10 271 (159-401) pg/ml; IL-1RA 4882 (3927-6025) pg/ml; and an increase in body temperature [1.8(1.4-2.2)] during endotoxemia. No significant correlations were found between BMI and levels of any of the cytokines or body temperature. No relationship between BMI and the cytokine response was found in healthy volunteers subjected to experimental endotoxemia. These data question the relationship between BMI and cytokine responses in critical illness. TI - Body mass index is not associated with cytokine induction during experimental human endotoxemia EP - 67 SN - 1753-4259 IS - iss. 1 SP - 61 JF - Innate Immunity VL - vol. 20 DO - https://doi.org/10.1177/1753425913481821 ER - TY - JOUR AU - Eijk, L.T.G.J. van AU - John, A.S. AU - Schwoebel, F. AU - Summo, L. AU - Vauleon, S. AU - Zollner, S. AU - Laarakkers, C.M. AU - Kox, M. AU - Hoeven, J.G. van der AU - Swinkels, D.W. AU - Riecke, K. AU - Pickkers, P. PY - 2014 UR - https://hdl.handle.net/2066/136275 AB - Increased hepcidin production is key to the development of anemia of inflammation. We investigated whether lexaptepid, an antihepcidin l-oligoribonucleotide, prevents the decrease in serum iron during experimental human endotoxemia. This randomized, double-blind, placebo-controlled trial was carried out in 24 healthy males. At T = 0 hours, 2 ng/kg Escherichia coli lipopolysaccharide was intravenously administered, followed by an intravenous injection of 1.2 mg/kg lexaptepid or placebo at T = 0.5 hours. The lipopolysaccharide-induced inflammatory response was similar in subjects treated with lexaptepid or placebo regarding clinical and biochemical parameters. At T = 9 hours, serum iron had increased by 15.9 +/- 9.8 micromol/L from baseline in lexaptepid-treated subjects compared with a decrease of 8.3 +/- 9.0 micromol/L in controls (P < .0001). This study delivers proof of concept that lexaptepid achieves clinically relevant hepcidin inhibition enabling investigations in the treatment of anemia of inflammation. This trial was registered at www.clinicaltrial.gov as #NCT01522794. TI - Effect of the antihepcidin Spiegelmer lexaptepid on inflammation-induced decrease in serum iron in humans EP - 2646 SN - 0006-4971 IS - iss. 17 SP - 2643 JF - Blood VL - vol. 124 DO - https://doi.org/10.1182/blood-2014-03-559484 ER - TY - JOUR AU - Eijk, L.T.G.J. van AU - Heemskerk, S. AU - Pluijm, R.W. van der AU - Wijk, S.M. van AU - Peters, W.H.M. AU - Hoeven, J.G. van der AU - Kox, M. AU - Swinkels, D.W. AU - Pickkers, P. PY - 2014 UR - https://hdl.handle.net/2066/136110 AB - In this double-blind randomized placebo-controlled trial involving 30 healthy male volunteers we investigated the acute effects of iron loading (single dose of 1.25 mg/kg iron sucrose) and iron chelation therapy (single dose of 30 mg/kg deferasirox) on iron parameters, oxidative stress, the innate immune response, and subclinical organ injury during experimental human endotoxemia. The administration of iron sucrose induced a profound increase in plasma malondialdehyde 1 h after administration (433+/-37% of baseline; P<0.0001), but did not potentiate the endotoxemia-induced increase in malondialdehyde, as was seen 3 h after endotoxin administration in the placebo group (P=0.34) and the iron chelation group (P=0.008). Endotoxemia resulted in an initial increase in serum iron levels and transferrin saturation that was accompanied by an increase in labile plasma iron, especially when transferrin saturation reached levels above 90%. Thereafter, serum iron decreased to 51.6+/-9.7% of baseline at T=8 h in the placebo group versus 84+/-15% and 60.4+/-8.9% of baseline at 24 h in the groups treated with iron sucrose and deferasirox, respectively. No significant differences in the endotoxemia-induced cytokine response (TNF-alpha, IL-6, IL-10 and IL-1RA), subclinical vascular injury and kidney injury were observed between groups. However, vascular reactivity to noradrenalin was impaired in the 6 subjects in whom labile plasma iron was elevated during endotoxemia as opposed to those in whom no labile plasma iron was detected (P=0.029). In conclusion, a single dose of iron sucrose does not affect the innate immune response in a model of experimental human endotoxemia, but may impair vascular reactivity when labile plasma iron is formed. (Clinicaltrials.gov identifier:01349699). TI - The effect of iron loading and iron chelation on the innate immune response and subclinical organ injury during human endotoxemia: a randomized trial EP - 587 SN - 0390-6078 IS - iss. 3 SP - 579 JF - Haematologica VL - vol. 99 DO - https://doi.org/10.3324/haematol.2013.088047 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/136110/136110.pdf?sequence=1 ER - TY - JOUR AU - Kox, M. AU - Eijk, L.T.G.J. van AU - Zwaag, J. AU - Wildenberg, J. van den AU - Sweep, C.G.J. AU - Hoeven, J.G. van der AU - Pickkers, P. PY - 2014 UR - https://hdl.handle.net/2066/133920 AB - Excessive or persistent proinflammatory cytokine production plays a central role in autoimmune diseases. Acute activation of the sympathetic nervous system attenuates the innate immune response. However, both the autonomic nervous system and innate immune system are regarded as systems that cannot be voluntarily influenced. Herein, we evaluated the effects of a training program on the autonomic nervous system and innate immune response. Healthy volunteers were randomized to either the intervention (n = 12) or control group (n = 12). Subjects in the intervention group were trained for 10 d in meditation (third eye meditation), breathing techniques (i.a., cyclic hyperventilation followed by breath retention), and exposure to cold (i.a., immersions in ice cold water). The control group was not trained. Subsequently, all subjects underwent experimental endotoxemia (i.v. administration of 2 ng/kg Escherichia coli endotoxin). In the intervention group, practicing the learned techniques resulted in intermittent respiratory alkalosis and hypoxia resulting in profoundly increased plasma epinephrine levels. In the intervention group, plasma levels of the anti-inflammatory cytokine IL-10 increased more rapidly after endotoxin administration, correlated strongly with preceding epinephrine levels, and were higher. Levels of proinflammatory mediators TNF-alpha, IL-6, and IL-8 were lower in the intervention group and correlated negatively with IL-10 levels. Finally, flu-like symptoms were lower in the intervention group. In conclusion, we demonstrate that voluntary activation of the sympathetic nervous system results in epinephrine release and subsequent suppression of the innate immune response in humans in vivo. These results could have important implications for the treatment of conditions associated with excessive or persistent inflammation, such as autoimmune diseases. TI - Voluntary activation of the sympathetic nervous system and attenuation of the innate immune response in humans EP - 7384 SN - 0027-8424 IS - iss. 20 SP - 7379 JF - Proceedings of the National Academy of Sciences USA VL - vol. 111 DO - https://doi.org/10.1073/pnas.1322174111 ER - TY - JOUR AU - Nusmeier, A. AU - Vrancken, S.L. AU - Boode, W.P. de AU - Hoeven, J.G. van der AU - Lemson, J. PY - 2014 UR - https://hdl.handle.net/2066/137171 AB - OBJECTIVE: The measurement of extravascular lung water using the transpulmonary thermodilution technique enables the bedside quantification of the amount of pulmonary edema. Children have higher indexed to body weight values of extravascular lung water compared with adults. Transpulmonary thermodilution measurements of extravascular lung water in children have not yet been validated. The purpose of this study was to validate the extravascular lung water measurements with the transpulmonary thermodilution method over a wide range of lung water values in a pediatric animal model. DESIGN: Experimental animal intervention study. SETTING: Animal laboratory at the Radboud University Nijmegen, The Netherlands. SUBJECTS: Eleven lambs. INTERVENTION: Pulmonary edema was induced using a surfactant washout model. MEASUREMENTS AND MAIN RESULTS: Between the lavages, extravascular lung water index was estimated using transpulmonary single and double indicator dilution. Two additional lambs were used to estimate extravascular lung water index in lungs without pulmonary edema. The final extravascular lung water index results were compared with the extravascular lung water index estimations by postmortem gravimetry (EVLWIG). The results were analyzed using both correlation and Bland-Altman statistics. Extravascular lung water index by transpulmonary thermodilution (EVLWITPTD) correlated significantly with either EVLWIG (r = 0.88) or with extravascular lung water index by transpulmonary double indicator dilution (EVLWITPDD) (r = 0.98). The mean bias with EVLWIG was 12.2 mL/kg (limits of agreement +/- 10.9 mL/kg) and with EVLWITPDD 2.4 mL/kg (limits of agreement +/- 3.8 mL/kg). The percentage errors were 41% and 14%, respectively. The bias became more positive when the mean of EVLWITPTD and EVLWIG increased (r = 0.72; p = 0.003). CONCLUSIONS: EVLWITPTD was significantly correlated to the postmortem gravimetric gold standard, although a significant overestimation was demonstrated with increasing pulmonary edema. TI - Validation of extravascular lung water measurement by transpulmonary thermodilution in a pediatric animal model EP - 33 SN - 1529-7535 IS - iss. 5 SP - e226 JF - Pediatric Critical Care Medicine VL - vol. 15 DO - https://doi.org/10.1097/PCC.0000000000000104 ER - TY - JOUR AU - Hofhuizen, C.M. AU - Lansdorp, B. AU - Hoeven, J.G. van der AU - Scheffer, G.J. AU - Lemson, J. PY - 2014 UR - https://hdl.handle.net/2066/133916 AB - INTRODUCTION: Nexfin (Edwards Lifesciences, Irvine, CA) allows for noninvasive continuous monitoring of blood pressure (ABPNI) and cardiac output (CONI) by measuring finger arterial pressure (FAP). To evaluate the accuracy of FAP in measuring ABPNI and CONI as well as the adequacy of detecting changes in ABP and CO, we compared FAP to intra-arterially measured blood pressure (ABPIA) and transpulmonary thermodilution(COTD) in post cardiac surgery patients during a fluid challenge (FC). METHODS: Twenty sedated patients post cardiac surgery were included, and 28 FCs were performed. Measurements of ABP and CO were simultaneously collected before and after an FC, and we compared CO and blood pressure. RESULTS: Finger arterial pressure was obtainable in all patients.When comparing ABPNI with ABPIA, bias was2.7 mm Hg (limits of agreement [LOA], +/- 22.2), 4.9 mm Hg (LOA, +/- 13.6), and 4.2 mm Hg (LOA, +/-13.7) for systolic,diastolic, and mean arterial pressure, respectively. Concordance between changes in ABPNI and ABPIA was 100%.Mean bias between CONI and COTD was -0.26 (LOA, +/- 2.2), with a percentage error of 38.9%. Concordance between changes in CONI vs COTD and was 100%. CONCLUSION: Finger arterial pressure reliably measures ABP and adequately tracks changes in ABP. Although CONI is not interchangeable with COTD, it follows changes in CO closely. TI - Validation of noninvasive pulse contour cardiac output using finger arterial pressure in cardiac surgery patients requiring fluid therapy EP - 165 SN - 0883-9441 IS - iss. 1 SP - 161 JF - Journal of Critical Care VL - vol. 29 DO - https://doi.org/10.1016/j.jcrc.2013.09.005 ER - TY - JOUR AU - Lavieren, M. van AU - Veelenturf, J. AU - Hofhuizen, C.M. AU - Kolk, M. van der AU - Hoeven, J.G. van der AU - Pickkers, P. AU - Lemson, J. AU - Lansdorp, B. PY - 2014 UR - https://hdl.handle.net/2066/136266 AB - BACKGROUND: Optimizing cardiac stroke volume during major surgery is of interest to many as a therapeutic target to decrease the incidence of postoperative complications. Because dynamic preload indicators are strongly correlated with stroke volume, it is suggested that these indices can be used for goal directed fluid therapy. However, threshold values of these indicators depend on many factors that are influenced by surgery, including opening of the abdomen. The aim of this study was therefore to assess the effect of opening the abdomen on arterial pressure variations in patients undergoing abdominal surgery. METHODS: Blood pressure and bladder pressure were continuously recorded just before and after opening of the abdomen in patients undergoing elective laparotomy. Based on waveform analysis of the non-invasively derived blood pressure, the stroke volume index, pulse pressure variation (PPV) and stroke volume variation (SVV) were calculated off-line. RESULTS: Thirteen patients were included. After opening the abdomen, PPV and SVV decreased from 11.5 +/- 5.8% to 6.4 +/- 2.9% (p < 0.005, a relative decrease of 40 +/- 19%) and 12.7 +/- 6.1% to 4.8 +/- 1.6% (p < 0.05, a relative decrease of 53 +/- 26%), respectively. Although mean arterial pressure and stroke volume index tended to increase (41 +/- 6 versus 45 +/- 4 ml/min/m2, p = 0.14 and 41 +/- 6 versus 45 +/- 4 ml/min/m2, p = 0.05), and heart rate tended to decrease (73 +/- 15 versus 68 +/- 11 1/min, p = 0.05), no significant change was found. No significant change was found in respiratory parameter (tidal volume, respiratory rate or inspiratory pressure; p = 0.36, 0.34 and 0.17, respectively) or bladder pressure (6.0 +/- 3.7 versus 5.6 +/- 2.7 mmHg, p = 0.6) either. CONCLUSIONS: Opening of the abdomen decreases PPV and SVV. During goal directed therapy, current thresholds for fluid responsiveness should be changed accordingly. TI - Dynamic preload indicators decrease when the abdomen is opened SN - 1471-2253 JF - BMC Anesthesiology VL - vol. 14 DO - https://doi.org/10.1186/1471-2253-14-90 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/136266/136266.pdf?sequence=1 ER - TY - JOUR AU - Lansdorp, B. AU - Hofhuizen, C.M. AU - Lavieren, M. van AU - Swieten, H.A. van AU - Lemson, J. AU - Putten, M.J.A.M. van AU - Hoeven, J.G. van der AU - Pickkers, P. PY - 2014 UR - https://hdl.handle.net/2066/133826 AB - OBJECTIVE: Mechanical ventilation causes cyclic changes in the heart's preload and afterload, thereby influencing the circulation. However, our understanding of the exact physiology of this cardiopulmonary interaction is limited. We aimed to thoroughly determine airway pressure distribution, how this is influenced by tidal volume and chest compliance, and its interaction with the circulation in humans during mechanical ventilation. DESIGN: Intervention study. SETTING: ICU of a university hospital. PATIENTS: Twenty mechanically ventilated patients following coronary artery bypass grafting surgery. INTERVENTION: Patients were monitored during controlled mechanical ventilation at tidal volumes of 4, 6, 8, and 10 mL/kg with normal and decreased chest compliance (by elastic binding of the thorax). MEASUREMENTS AND MAIN RESULTS: Central venous pressure, airway pressure, pericardial pressure, and pleural pressure; pulse pressure variations, systolic pressure variations, and stroke volume variations; and cardiac output were obtained during controlled mechanical ventilation at tidal volume of 4, 6, 8, and 10 mL/kg with normal and decreased chest compliance. With increasing tidal volume (4, 6, 8, and 10 mL/kg), the change in intrathoracic pressures increased linearly with 0.9 +/- 0.2, 0.5 +/- 0.3, 0.3 +/- 0.1, and 0.3 +/- 0.1 mm Hg/mL/kg for airway pressure, pleural pressure, pericardial pressure, and central venous pressure, respectively. At 8 mL/kg, a decrease in chest compliance (from 0.12 +/- 0.07 to 0.09 +/- 0.03 L/cm H2O) resulted in an increase in change in airway pressure, change in pleural pressure, change in pericardial pressure, and change in central venous pressure of 1.1 +/- 0.7, 1.1 +/- 0.8, 0.7 +/- 0.4, and 0.8 +/- 0.4 mm Hg, respectively. Furthermore, increased tidal volume and decreased chest compliance decreased stroke volume and increased arterial pressure variations. Transmural pressure of the superior vena cava decreased during inspiration, whereas the transmural pressure of the right atrium did not change. CONCLUSIONS: Increased tidal volume and decreased chest wall compliance both increase the change in intrathoracic pressures and the value of the dynamic indices during mechanical ventilation. Additionally, the transmural pressure of the vena cava is decreased, whereas the transmural pressure of the right atrium is not changed. TI - Mechanical ventilation-induced intrathoracic pressure distribution and heart-lung interactions* EP - 1990 SN - 0090-3493 IS - iss. 9 SP - 1983 JF - Critical Care Medicine VL - vol. 42 DO - https://doi.org/10.1097/CCM.0000000000000345 ER - TY - JOUR AU - Simmes, F. AU - Schoonhoven, L. AU - Mintjes-de Groot, A.J. AU - Adang, E.M. AU - Hoeven, J.G. van der PY - 2014 UR - https://hdl.handle.net/2066/138038 AB - RATIONALE, AIMS AND OBJECTIVES: Rapid response systems (RRSs) are recommended by the Institute for Healthcare Improvement and implemented worldwide. Our study on the effects of an RRS showed a non-significant decrease in cardiac arrest and/or unexpected death from 0.5% to 0.25%. Unplanned intensive care unit (ICU) admissions increased significantly from 2.5% to 4.2% without a decrease in APACHE II scores. In this study, we estimated the mean costs of an RRS per patient day and tested the hypothesis that admitting less severely ill patients to the ICU reduces costs. METHODS: A cost analysis of an RRS on a surgical ward, including costs for implementation, a 1-day training programme for nurses, nursing time for extra vital signs observation, medical emergency team (MET) consults and differences in unplanned ICU days before and after RRS implementation. To test the hypothesis, we performed a scenario analysis with a mean APACHE II score of 14 points instead of the empirical 17.6 points for the unplanned ICU admissions, including 33% extra MET consults and 22% extra unplanned ICU admissions. RESULTS: Mean RRS costs were euro26.87 per patient-day: implementation euro0.33 (1%), training euro0.90 (3%), nursing time spent on extended observation of vital signs euro2.20 (8%), MET consults euro0.57 (2%) and increased number of unplanned ICU days after RRS implementation euro22.87 (85%). In the scenario analysis mean costs per patient-day were euro10.18. CONCLUSIONS: The costs for extra unplanned ICU days were relatively high but the remaining RRS costs were relatively low. The 'APACHE II 14' scenario confirmed the hypothesis that costs for the number of unplanned ICU days can be reduced if less severely ill patients are referred to the ICU. Based upon these findings, our hospital stimulates earlier referral to the ICU, although further implementation strategies are needed to achieve these aims. TI - Financial consequences of the implementation of a rapid response system on a surgical ward EP - 347 SN - 1356-1294 IS - iss. 4 SP - 342 JF - Journal of Evaluation in Clinical Practice VL - vol. 20 DO - https://doi.org/10.1111/jep.12134 ER - TY - JOUR AU - Vliet, M. van AU - Burgt, M.P.E.M. van der AU - Velden, W.J.F.M. van der AU - Hoeven, J.G. van der AU - Haan, A.F.J. de AU - Donnelly, J.P. AU - Pickkers, P. AU - Blijlevens, N.M.A. PY - 2014 UR - https://hdl.handle.net/2066/137127 AB - BACKGROUND: Because of the assumed dismal prognosis there is still reluctance to admit haematological patients to the intensive care unit (ICU). This study was conducted to determine trends in outcome of allogeneic haematopoietic stem cell transplant (HSCT) recipients transferred to the intensive care unit in a Dutch tertiary care hospital. METHODS: All patients who received allogeneic HSCT between 2004-2010 were included in the analyses. Baseline and outcome characteristics were compared and risk factors for ICU admission and survival were identified. Changes in outcome over time of three cohorts of HSCT recipients were investigated. RESULTS: Of 319 consecutive HSCT recipients, 49 (15%) were transferred to the ICU for a median (IQR) of 10 (6-45) days following their transplantation, of whom 43% were severely neutropenic and 90% had received systemic immunosuppressive therapy for graft-versus-host disease prophylaxis. Univariate logistic regression showed that transplantation from an unrelated donor and myeloablative conditioning were significant risk factors for ICU admission. Prolonged use of vasopressors, invasive mechanical ventilation and male gender were significant predictors for ICU mortality, while neutropenia and graft-versus-host disease were not. Over the years, APACHE-II severity of illness scores remained unchanged (21.0+/-7.1, 20.1+/-5.6, 21.2+/-6.6), while 100-day post-transplant mortality of patients who had been transferred to the ICU decreased significantly from 78% (2004/2005) to 57% (2006/2007), and 35% (2008/2009). CONCLUSIONS: While for allogeneic HSCT patients the severity of illness on admission to the ICU did not change, the 100-day post-transplant survival improved. These data indicate that reluctance to submit haematological patients to the ICU is not warranted. TI - Trends in the outcomes of Dutch haematological patients receiving intensive care support EP - 112 SN - 0300-2977 IS - iss. 2 SP - 107 JF - Netherlands Journal of Medicine VL - vol. 72 ER - TY - JOUR AU - Wal, S.E.I. van der AU - Vaneker, M. AU - Kox, M. AU - Braak, G. AU - Hees, H.W.H. van AU - Brink, I. van den AU - Pol, F.M. van de AU - Heunks, L.M.A. AU - Hoeven, J.G. van der AU - Joosten, L.A.B. AU - Vissers, K.C.P. AU - Scheffer, G.J. PY - 2014 UR - https://hdl.handle.net/2066/136061 AB - BACKGROUND: Mechanical ventilation (MV) can result in inflammation and subsequent lung injury. Toll-like receptor (TLR)4 and NF-kappaB are proposed to play a crucial role in the MV-induced inflammatory response. Resveratrol (RVT) exhibits anti-inflammatory effects in vitro and in vivo supposedly by interfering with TLR4 signaling and NF-kappaB. In the present study, we investigated the role of RVT in MV-induced inflammation in mice. METHODS: RVT (10 mg/kg, 20 mg/kg and 40 mg/kg) or vehicle was intraperitoneally administered 1 h before start of MV (4 h, tidal volume 8 ml/kg, positive end-expiratory pressure 1,5 cmH2 O and FiO2 0.4). Blood and lungs were harvested for cytokine analysis. DNA binding activity of transcription factor NF-kappaB was measured in lung homogenates. RESULTS: MV resulted in elevated pulmonary concentrations of IL-1beta, IL-6, keratinocyte-derived chemokine (KC) and NF-kappaB DNA-binding activity. RVT at 10, 20 and 40 mg/kg reduced NF-kappaB's DNA-binding activity following MV compared with ventilated controls. However, no differences in cytokine release were found between RVT-treated and control ventilated mice. Similarly, in plasma, MV resulted in elevated concentrations of TNF-alpha, KC and IL-6, but RVT did not affect cytokine levels. CONCLUSIONS: RVT abrogates the MV-induced increase in pulmonary NF-kappaB activity but does not attenuate cytokine levels. This implies a less prominent role for NF-kappaB in MV-induced inflammation than previously assumed. TI - Resveratrol attenuates NF-kappaB-binding activity but not cytokine production in mechanically ventilated mice EP - 494 SN - 0001-5172 IS - iss. 4 SP - 487 JF - Acta Anaesthesiologica Scandinavica VL - vol. 58 DO - https://doi.org/10.1111/aas.12276 ER - TY - JOUR AU - Simons, K.S. AU - Workum, J.D. AU - Slooter, A.J. AU - Boogaard, M.H.W.A. van den AU - Hoeven, J.G. van der AU - Pickkers, P. PY - 2014 UR - https://hdl.handle.net/2066/137886 AB - PURPOSE: It is assumed that there is a relation between light exposure and delirium incidence. The aim of our study was to determine the effect of prehospital light exposure on the incidence of intensive care unit (ICU)-acquired delirium. MATERIALS AND METHODS: Data from 3 ICUs in the Netherlands were analyzed retrospectively. Delirium was assessed with the Confusion Assessment Method for the ICU. Daily light intensity data were obtained from meteorological stations in the vicinity of the 3 hospitals. The association between light intensity and delirium incidence was analyzed using logistic regression analysis adjusting for known covariates for delirium. RESULTS: Data of 3198 patients, aged (mean +/- SD) 61.9 +/- 15.3 years with Acute Physiology and Chronic Health Evaluation II score 16.4 +/- 6.6 were analyzed. Delirium incidence was 31.2% and did not vary significantly throughout the year. Twenty-eight-day preadmission photoperiod was highest in spring and lowest in winter; however, no association between light exposure and delirium incidence was found (odds ratio, 1.00; 95% confidence interval, 0.99-1.00; P = 0.72). Furthermore, delirium was significantly associated with age, infection, use of sedatives, Acute Physiology and Chronic Health Evaluation II score, and diagnosis of neurological disease or trauma. CONCLUSIONS: The incidence of delirium does not differ per season and prior sunlight exposure does not play a role of importance in the development of ICU-acquired delirium. TI - Effect of preadmission sunlight exposure on intensive care unit-acquired delirium: a multicenter study EP - 286 SN - 0883-9441 IS - iss. 2 SP - 283 JF - Journal of Critical Care VL - vol. 29 DO - https://doi.org/10.1016/j.jcrc.2013.10.027 ER - TY - JOUR AU - Pickkers, P. AU - Hoeven, J.G. van der PY - 2013 UR - https://hdl.handle.net/2066/119053 AB - If an intensive care unit (ICU) is managed by intensivists, the prognosis of critically ill patients improves. Some retrospective analyses of patient databases suggest that critically ill patients admitted to the ICU during off-hours suffer a higher mortality rate compared to patients admitted during office hours. While this suggests that this difference might be related to the presence/absence of experienced intensivists at night, differences in case mix of patients admitted during the day/night may play an important role. Recently, the first prospective randomized controlled trial was published on this issue. Alternating every 7 nights an intensivist was present in the hospital or was available for consultation by telephone. No effect on ICU-length of stay, mortality or any of the secondary end points was found. Despite the compelling face value of nighttime intensivist staffing this practice should not be recommended in the absence of experimental evidence of its effectiveness. TI - [Is nighttime intensivist staffing beneficial?] SN - 0028-2162 IS - iss. 33 SP - A6596 JF - Nederlands Tijdschrift voor Geneeskunde VL - vol. 157 ER - TY - JOUR AU - Pop, G.A.M. AU - Bisschops, L.L.A. AU - Iliev, B. AU - Struijk, P.C. AU - Hoeven, J.G. van der AU - Hoedemaekers, C.W.E. PY - 2013 UR - https://hdl.handle.net/2066/118896 AB - Blood viscosity is an important determinant of microvascular hemodynamics and also reflects systemic inflammation. Viscosity of blood strongly depends on the shear rate and can be characterized by a two parameter power-law model. Other major determinants of blood viscosity are hematocrit, level of inflammatory proteins and temperature. In-vitro studies have shown that these major parameters are related to the electrical impedance of blood. A special central venous catheter was developed to measure electrical impedance of blood in-vivo in the right atrium. Considering that blood viscosity plays an important role in cerebral blood flow, we investigated the feasibility to monitor blood viscosity by electrical bioimpedance in 10 patients during the first 3 days after successful resuscitation from a cardiac arrest. The blood viscosity-shear rate relationship was obtained from arterial blood samples analyzed using a standard viscosity meter. Non-linear regression analysis resulted in the following equation to estimate in-vivo blood viscosity (Viscosity(imp)) from plasma resistance (R(p)), intracellular resistance (R(i)) and blood temperature (T) as obtained from right atrium impedance measurements: Viscosity(imp)=(-15.574+15.576R(p)T)SR ((-.138RpT-.290Ri)). This model explains 89.2% (R(2)=.892) of the blood viscosity-shear rate relationship. The explained variance was similar for the non-linear regression model estimating blood viscosity from its major determinants hematocrit and the level of fibrinogen and C-reactive protein (R(2)=.884). Bland-Altman analysis showed a bias between the in-vitro viscosity measurement and the in-vivo impedance model of .04 mPa s at a shear rate of 5.5s(-1) with limits of agreement between -1.69 mPa s and 1.78 mPa s. In conclusion, this study demonstrates the proof of principle to monitor blood viscosity continuously in the human right atrium by a dedicated central venous catheter equipped with an impedance measuring device. No safety problems occurred and there was good agreement with in-vitro measurements of blood viscosity. TI - On-line blood viscosity monitoring in vivo with a central venous catheter, using electrical impedance technique EP - 601 SN - 0956-5663 SP - 595 JF - Biosensors and Bioelectronics VL - vol. 41 DO - http://dx.doi.org/10.1016/j.bios.2012.09.033 ER - TY - JOUR AU - Kolk, A. van der AU - Yang, K.G. AU - Tamminga, R. AU - Hoeven, H. van der PY - 2013 UR - https://hdl.handle.net/2066/125830 AB - The aim of this study was to determine the effect of radial extracorporeal shock-wave therapy (rESWT) on patients with chronic tendinitis of the rotator cuff. This was a randomised controlled trial in which 82 patients (mean age 47 years (24 to 67)) with chronic tendinitis diagnosed clinically were randomly allocated to a treatment group who received low-dose rESWT (three sessions at an interval 10 to 14 days, 2000 pulses, 0.11 mJ/mm(2), 8 Hz) or to a placebo group, with a follow-up of six months. The patients and the treating orthopaedic surgeon, who were both blinded to the treatment, evaluated the results. A total of 44 patients were allocated to the rESWT group and 38 patients to the placebo group. A visual analogue scale (VAS) score for pain, a Constant-Murley (CMS) score and a simple shoulder test (SST) score significantly improved in both groups at three and six months compared with baseline (all p 48 h that received SDD (n=2045), SOD (n=1904) or SC (n=1990). INTERVENTIONS: SDD or SOD. PRIMARY AND SECONDARY OUTCOME MEASURES: Effects were based on hospital survival, expressed as crude Life Years Gained (cLYG). The incremental cost-effectiveness ratio (ICER) was calculated, with corresponding cost acceptability curves. Sensitivity analyses were performed for discount rates, costs of SDD, SOD and mechanical ventilation. RESULTS: Total costs per patient were euro41 941 for SC (95% CI euro40 184 to euro43 698), euro40 433 for SOD (95% CI euro38 838 to euro42 029) and euro41 183 for SOD (95% CI euro39 408 to euro42 958). SOD and SDD resulted in crude LYG of +0.04 and +0.25, respectively, as compared with SC, implying that both SDD and SOD are dominant (ie, cheaper and more beneficial) over SC. In cost-effectiveness acceptability curves probabilities for cost-effectiveness, compared with standard care, ranged from 89% to 93% for SOD and from 63% to 72% for SDD, for acceptable costs for 1 LYG ranging from euro0 to euro20 000. Sensitivity analysis for mechanical ventilation and discount rates did not change interpretation. Yet, if costs of the topical component of SDD and SOD would increase 40-fold to euro400/day and euro40/day (maximum values based on free market prices in 2012), the estimated ICER as compared with SC for SDD would be euro21 590 per LYG. SOD would remain cost-saving. CONCLUSIONS: SDD and SOD were both effective and cost-saving in Dutch ICUs. TI - Selective decontamination of the digestive tract and selective oropharyngeal decontamination in intensive care unit patients: a cost-effectiveness analysis SN - 2044-6055 IS - iss. 3 JF - BMJ Open VL - vol. 3 DO - https://doi.org/10.1136/bmjopen-2012-002529 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/117631/117631.pdf?sequence=1 ER - TY - JOUR AU - Boogaard, M. van den AU - Schoonhoven, L. AU - Achterberg, T. van AU - Hoeven, J.G. van der AU - Pickkers, P. PY - 2013 UR - https://hdl.handle.net/2066/125507 AB - ABSTRACT: INTRODUCTION: Delirium is associated with increased morbidity and mortality. We implemented a delirium prevention policy in intensive care unit (ICU) patients with a high risk of developing delirium, and evaluated if our policy resulted in quality improvement of relevant delirium outcome measures. METHODS: This study was a before/after evaluation of a delirium prevention project using prophylactic treatment with haloperidol. Patients with a predicted risk for delirium of >/= 50%, or with a history of alcohol abuse or dementia, were identified. According to the prevention protocol these patients received haloperidol 1 mg/8 h. Evaluation was primarily focused on delirium incidence, delirium free days without coma and 28-day mortality. Results of prophylactic treatment were compared with a historical control group and a contemporary group that did not receive haloperidol prophylaxis mainly due to non-compliance to the protocol mostly during the implementation phase. RESULTS: In 12 months, 177 patients received haloperidol prophylaxis. Except for sepsis, patient characteristics were comparable between the prevention and the historical (n = 299) groups. Predicted chance to develop delirium was 75 +/- 19% and 73 +/- 22%, respectively. Haloperidol prophylaxis resulted in a lower delirium incidence (65% vs. 75%, P = 0.01), and more delirium-free-days (median 20 days (IQR 8 to 27) vs. median 13 days (3 to 27), P = 0.003) in the intervention group compared to the control group. Cox-regression analysis adjusted for sepsis showed a hazard rate of 0.80 (95% confidence interval 0.66 to 0.98) for 28-day mortality. Beneficial effects of haloperidol appeared most pronounced in the patients with the highest risk for delirium. Furthermore, haloperidol prophylaxis resulted in less ICU re-admissions (11% vs. 18%, P = 0.03) and unplanned removal of tubes/lines (12% vs. 19%, P = 0.02). Haloperidol was stopped in 12 patients because of QTc-time prolongation (n = 9), renal failure (n = 1) or suspected neurological side-effects (n = 2). No other side-effects were reported. Patients who were not treated during the intervention period (n = 59) showed similar results compared to the untreated historical control group. CONCLUSIONS: Our evaluation study suggests that prophylactic treatment with low dose haloperidol in critically ill patients with a high risk for delirium probably has beneficial effects. These results warrant confirmation in a randomized controlled trial. TRIAL REGISTRATION: clinicaltrial.gov Identifier: NCT01187667. TI - Haloperidol prophylaxis in critically ill patients with a high risk for delirium SN - 1466-609X IS - iss. 1 SP - R9 JF - Critical Care VL - vol. 17 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/125507/125507.pdf?sequence=1 ER - TY - JOUR AU - Oostdijk, E.A. AU - Smet, A.M. de AU - Bonten, M.J. AU - Kalkman, C.J. AU - Joore, C. AU - Hall, M.A. AU - Blok, H.E. AU - Kluytmans, J.A. AU - Meer, J.W.M. van der AU - Mascini, E.M. AU - Kaasjager, K. AU - Bosch, F.H. AU - Benus, R.F. AU - Werf, T.S. van der AU - Arends, J.P. AU - Hoeven, J.G. van der AU - Pickkers, P. AU - Sturm, P.D. AU - Voss, A. AU - Bernards, A.T. AU - Kuijper, E.J. AU - Harinck, H.I. AU - Bindels, A.J. AU - Jansz, A.R. AU - Wesseling, R.M. AU - Jongh, B.M. de AU - Dennesen, P.J. AU - Asselt, G.J. van AU - et al. PY - 2013 UR - https://hdl.handle.net/2066/142734 TI - Effects of decontamination of the digestive tract and oropharynx in intensive care unit patients on 1-year survival EP - 120 SN - 1073-449X IS - iss. 1 SP - 117 JF - American Journal of Respiratory and Critical Care Medicine VL - vol. 188 ER - TY - JOUR AU - Boogaard, M. van den AU - Slooter, A.J. AU - Bruggemann, R.J.M. AU - Schoonhoven, L. AU - Kuiper, M.A. AU - Voort, P.H. van der AU - Hoogendoorn, M.E. AU - Beishuizen, A. AU - Schouten, J.A. AU - Spronk, P.E. AU - Houterman, S. AU - Hoeven, J.G. van der AU - Pickkers, P. PY - 2013 UR - https://hdl.handle.net/2066/125795 AB - BACKGROUND: Delirium is a frequent disorder in intensive care unit (ICU) patients with serious consequences. Therefore, preventive treatment for delirium may be beneficial. Worldwide, haloperidol is the first choice for pharmacological treatment of delirious patients. In daily clinical practice, a lower dose is sometimes used as prophylaxis. Some studies have shown the beneficial effects of prophylactic haloperidol on delirium incidence as well as on mortality, but evidence for effectiveness in ICU patients is limited. The primary objective of our study is to determine the effect of haloperidol prophylaxis on 28-day survival. Secondary objectives include the incidence of delirium and delirium-related outcome and the side effects of haloperidol prophylaxis. METHODS: This will be a multicenter three-armed randomized, double-blind, placebo-controlled, prophylactic intervention study in critically ill patients. We will include consecutive non-neurological ICU patients, aged >/=18 years with an expected ICU length of stay >1 day. To be able to demonstrate a 15% increase in 28-day survival time with a power of 80% and alpha of 0.05 in both intervention groups, a total of 2,145 patients will be randomized; 715 in each group. The anticipated mortality rate in the placebo group is 12%. The intervention groups will receive prophylactic treatment with intravenous haloperidol 1 mg/q8h or 2 mg/q8h, and patients in the control group will receive placebo (sodium chloride 0.9%), both for a maximum period of 28-days. In patients who develop delirium, study medication will be stopped and patients will subsequently receive open label treatment with a higher (therapeutic) dose of haloperidol. We will use descriptive summary statistics as well as Cox proportional hazard regression analyses, adjusted for covariates. DISCUSSION: This will be the first large-scale multicenter randomized controlled prevention study with haloperidol in ICU patients with a high risk of delirium, adequately powered to demonstrate an effect on 28-day survival. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01785290.EudraCT number: 2012-004012-66. TI - Prevention of ICU delirium and delirium-related outcome with haloperidol: a study protocol for a multicenter randomized controlled trial SN - 1745-6215 JF - Trials VL - vol. 14 DO - https://doi.org/10.1186/1745-6215-14-400 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/125795/125795.pdf?sequence=1 ER - TY - JOUR AU - Goeij, M. de AU - Eijk, L.T.G.J. van AU - Vanelderen, P. AU - Wilder-Smith, O.H.G. AU - Vissers, K.C.P. AU - Hoeven, J.G. van der AU - Kox, M. AU - Scheffer, G.J. AU - Pickkers, P. PY - 2013 UR - https://hdl.handle.net/2066/126296 AB - BACKGROUND: Hyperalgesia is a well recognized hallmark of disease. Pro-inflammatory cytokines have been suggested to be mainly responsible, but human data are scarce. Changes in pain threshold during systemic inflammation evoked by human endotoxemia, were evaluated with three quantitative sensory testing methods. METHODS AND RESULTS: Pressure pain thresholds, electrical pain thresholds and tolerance to the cold pressor test were measured before and 2 hours after the intravenous administration of 2 ng/kg purified E. coli endotoxin in 27 healthy volunteers. Another 20 subjects not exposed to endotoxemia served as controls. Endotoxemia led to a rise in body temperature and inflammatory symptom scores and a rise in plasma TNF-alpha, IL-6, IL-10 and IL-1RA. During endotoxemia, pressure pain thresholds and electrical pain thresholds were reduced with 20+/-4 % and 13+/-3 %, respectively. In controls only a minor decrease in pressure pain thresholds (7+/-3 %) and no change in electrical pain thresholds occurred. Endotoxin-treated subjects experienced more pain during the cold pressor test, and fewer subjects were able to complete the cold pressor test measurement, while in controls the cold pressor test results were not altered. Peak levels and area under curves of each individual cytokine did not correlate to a change in pain threshold measured by one of the applied quantitative sensory testing techniques. CONCLUSIONS AND SIGNIFICANCE: In conclusion, this study shows that systemic inflammation elicited by the administration of endotoxin to humans, results in lowering of the pain threshold measured by 3 quantitative sensory testing techniques. The current work provides additional evidence that systemic inflammation is accompanied by changes in pain perception. TI - Systemic inflammation decreases pain threshold in humans in vivo SN - 1932-6203 IS - iss. 12 JF - PLoS One VL - vol. 8 DO - https://doi.org/10.1371/journal.pone.0084159 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/126296/126271.pdf?sequence=1 ER - TY - JOUR AU - Kiers, H.D. AU - Boogaard, M.H.W.A. van den AU - Schoenmakers, M.C.J. AU - Hoeven, J.G. van der AU - Swieten, H.A. van AU - Heemskerk, S. AU - Pickkers, P. PY - 2013 UR - https://hdl.handle.net/2066/118182 AB - BACKGROUND: Cardiac surgery-related acute kidney injury (CS-AKI) results in increased morbidity and mortality. Different models have been developed to identify patients at risk of CS-AKI. While models that predict dialysis and CS-AKI defined by the RIFLE criteria are available, their predictive power and clinical applicability have not been compared head to head. METHODS: Of 1388 consecutive adult cardiac surgery patients operated with cardiopulmonary bypass, risk scores of eight prediction models were calculated. Four models were only applicable to a subgroup of patients. The area under the receiver operating curve (AUROC) was calculated for all levels of CS-AKI and for need for dialysis (AKI-D) for each risk model and compared for the models applicable to the largest subgroup (n = 1243). RESULTS: The incidence of AKI-D was 1.9% and for CS-AKI 9.3%. The models of Rahmanian, Palomba and Aronson could not be used for preoperative risk assessment as postoperative data are necessary. The three best AUROCs for AKI-D were of the model of Thakar: 0.93 [95% confidence interval (CI) 0.91-0.94], Fortescue: 0.88 (95% CI 0.87-0.90) and Wijeysundera: 0.87 (95% CI 0.85-0.89). The three best AUROCs for CS-AKI-risk were 0.75 (95% CI 0.73-0.78), 0.74 (95% CI 0.71-0.76) and 0.70 (95% CI 0.73-0.78), for Thakar, Mehta and both Fortescue and Wijeysundera, respectively. The model of Thakar performed significantly better compared with the models of Mehta, Rahmanian, Fortescue and Wijeysundera (all P-values <0.01) at different levels of severity of CS-AKI. CONCLUSIONS: The Thakar model offers the best discriminative value to predict CS-AKI and is applicable in a preoperative setting and for all patients undergoing cardiac surgery. TI - Comparison and clinical suitability of eight prediction models for cardiac surgery-related acute kidney injury EP - 351 SN - 0931-0509 IS - iss. 2 SP - 345 JF - Nephrology, Dialysis, Transplantation VL - vol. 28 ER - TY - JOUR AU - Nusmeier, A. AU - Vrancken, S.L. AU - Boode, W.P. de AU - Hoeven, J.G. van der AU - Lemson, J. PY - 2013 UR - https://hdl.handle.net/2066/117883 AB - BACKGROUND: /st> The transpulmonary thermodilution (TPTD) technique is widely used in clinical practice for measuring cardiac output (CO). This study was designed to investigate the influence of various levels of pulmonary oedema on the reliability of CO measurements by the TPTD method. METHODS: /st> In 11 newborn lambs pulmonary oedema was induced using a surfactant washout technique. Serial CO measurements using TPTD (COTPTD) were performed at various amounts of lung water. Simultaneously, CO was measured by an ultrasound flow probe around the main pulmonary artery (COMPA) and used as the standard reference. CO was divided by the body surface area to calculate cardiac index (CI). Data were analysed using correlational statistics and Bland-Altman analysis. RESULTS: /st> One lamb died prematurely. A total of 56 measurements in 10 lambs were analysed with a median CIMPA of 2.95 (IQR 1.04) litre min(-1) m(-2). Mean percentage increase in extravascular lung water (EVLW) between the start and the end of the study was 126.4% (sd 40.4). Comparison of the two CO methods showed a mean bias CI of -0.16 litre min(-1) m(-2) (limits of agreement +/-0.73 litre min(-1) m(-2)) and a percentage error of 23.8%. Intraclass correlation coefficients were 0.91 (95% CI 0.81-0.95) for absolute agreement and 0.92 (95% CI 0.87-0.95) for consistency. Acceptable agreement was confirmed by a tolerability-agreement ratio of 0.39. The within-subject correlation between the amount of EVLWI and the bias between the two methods was not significant (-0.02; P=0.91). CONCLUSIONS: /st> CO measurements by the transpulmonary thermodilution technique over a wide range of CI values are not affected by the presence of high EVLWI. The slight underestimation of the CO is independent of the amount of pulmonary oedema. TI - Transpulmonary thermodilution cardiac output measurement is not affected by severe pulmonary oedema: a newborn animal study EP - 292 SN - 0007-0912 IS - iss. 2 SP - 286 JF - British Journal of Anaesthesia VL - vol. 111 DO - https://doi.org/10.1093/bja/aet021 ER - TY - JOUR AU - Sluisveld, P.H. van AU - Zegers, M. AU - Westert, G.P. AU - Hoeven, J.G. van der AU - Wollersheim, H.C. PY - 2013 UR - https://hdl.handle.net/2066/118558 AB - BACKGROUND: To use intensive care unit (ICU) facilities efficiently and ensure high quality of care, an optimal patient flow is necessary. Discharging patients relieves the pressure on ICU beds but the risk of premature discharge must be managed carefully. Suboptimal patient discharge may result in ICU readmissions and in patients' death.The aim of this study is to obtain insight into the safety and efficiency of current ICU discharge practices and into barriers and facilitators to the implementation of effective ICU discharge interventions, and to develop an implementation strategy tailored to the barriers and facilitators identified. METHODS/DESIGN: This study exists of five phases. Phase A: analysis of routinely registered data on variation in ICU readmissions and hospital mortality after ICU discharge of all ICUs participating in the Dutch National Intensive Care Evaluation registry (n=83). Phase B: systematic review of effective interventions aiming to improve the efficiency and safety of the ICU discharge process. Phase C: assessing the intervention adherence with a questionnaire survey among all Dutch ICUs (n=90). Phase D: assessing barriers and facilitators to the implementation of effective ICU discharge interventions with a questionnaire survey among all Dutch intensivists (n=700). The questionnaire will be based on barriers and facilitators identified by focus groups (n=4) and individual interviews with professionals of ICUs and general wards and adult discharged ICU patients (n=25 to 30). Phase E: systematic development of an implementation strategy based on the sampled data in phase A to D, and effective implementation strategies from the literature using the intervention mapping method. DISCUSSION: Using theory and empirical data, an implementation strategy will be developed to improve the safety and efficiency of the ICU discharge process. The developed strategy will be evaluated in a subsequent study. The knowledge obtained in this study should be used for further implementation of ICU discharge interventions, and can be used for implementation of handover interventions in other healthcare transition settings. TI - A strategy to enhance the safety and efficiency of handovers of ICU patients: study protocol of the pICUp study EP - 67 SN - 1748-5908 SP - 67 JF - Implementation Science VL - vol. 8 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/118558/118558.pdf?sequence=1 ER - TY - JOUR AU - Moviat, M. AU - Boogaard, M. van den AU - Intven, F. AU - Voort, P. van der AU - Hoeven, H. van der AU - Pickkers, P. PY - 2013 UR - https://hdl.handle.net/2066/126275 AB - PURPOSE: This study aimed to describe Stewart parameters in critically ill patients with an apparently normal acid-base state and to determine the incidence of mixed metabolic acid-base disorders in these patients. MATERIALS AND METHODS: We conducted a prospective, observational multicenter study of 312 consecutive Dutch intensive care unit patients with normal pH (7.35 18 years) admitted to the ICU were included. Results: During the 47-month study period, 9279 patients were admitted to our ICU, of which 3753 patients had an APACHE II score ≤15. Of the latter group of patients, 131 (3.5%) died during their hospital stay. Their median (IQR) APACHE II was 12 (11-14) and their main reason for ICU admission was respiratory insufficiency (47%). Both in patients with and without limited therapy, haemodynamic insufficiency was the main cause of death (50 and 69%, respectively). Three patients died directly related to medical interventions. Conclusion: Most patients with an APACHE II score lower than 15 who died were admitted to the ICU because of respiratory insufficiency. The main cause of death was haemodynamic insufficiency following limited therapy because of an unfavourable prognosis. In less than one out of 1000 cases of this low-risk group of patients death was related to iatrogenic injury. TI - Causes of death in intensive care patients with a low APACHE II score EP - 459 SN - 0300-2977 IS - iss. 10 SP - 455 JF - Netherlands Journal of Medicine VL - vol. 70 ER - TY - JOUR AU - Bisschops, L.L.A. AU - Hoedemaekers, C.W.E. AU - Mollnes, T.E. AU - Hoeven, J.G. van der PY - 2012 UR - https://hdl.handle.net/2066/109405 AB - OBJECTIVES: The aim of this study was to simultaneously analyze the key components of the cerebral and systemic inflammatory response over time in cardiac arrest patients during mild therapeutic hypothermia and rewarming. DESIGN AND SETTING: Clinical observational study in a tertiary care university hospital. PATIENTS: Ten comatose patients after out-of-hospital cardiac arrest. INTERVENTIONS: All patients were cooled to 32-34 degrees C for 24 hrs. After 24 hrs patients were passively rewarmed to normothermia. MEASUREMENTS AND MAIN RESULTS: On admission and at 3, 6, 12, 24, and 48 hrs blood samples were taken from the arterial and jugular bulb catheter. Proinflammatory and anti-inflammatory cytokines and chemokines (interleukin-1ra, interleukin-1beta, interleukin-6, interleukin-8, interleukin-10, interleukin-18, monocyte chemotactic protein-1, high-mobility group box-1 and tumor necrosis factor-alpha), complement activation products (C4d, Bb, C3a, and terminal complement complex), and the adhesion molecule soluble intercellular adhesion molecule were measured. Mean temperatures at the start of the study and at 12 and 24 hrs were 33.7 +/- 0.9 degrees C, 32.7 +/- 0.92 degrees C, and 34.5 +/- 1.5 degrees C, respectively. Passive rewarming resulted in a temperature of 37.8 +/- 0.5 degrees C at 48 hrs. The proinflammatory cytokine interleukin-6 increased from 12 to 24 hrs and returned to baseline levels after 48 hrs. In contrast, the chemokines interleukin-8 and monocyte chemotactic protein-1 stayed relatively high from the start and during the hypothermia period, decreasing to baseline levels after 48 hrs. The anti-inflammatory cytokines interleukin-10 and interleukin-1ra did not significantly change during mild therapeutic hypothermia and rewarming, although low values of interleukin-10 were observed after rewarming. A significant increase after rewarming was demonstrated on high-mobility group box-1 concentrations in the jugular bulb, whereas soluble intercellular adhesion molecule increased significantly during hypothermia and remained at this level after rewarming. Complement activation was increased on admission and decreased after induction of hypothermia, followed by a secondary increase during rewarming. No significant differences between any of the biomarkers were found between samples from the arterial and jugular bulb catheter. CONCLUSIONS: Complement activation occurs during rewarming from mild therapeutic hypothermia after cardiac arrest. Interleukin-6 increased already from 12 to 24 hrs, concomitantly with a significant increase in the temperature seen during this period of mild therapeutic hypothermia. The optimal rate of rewarming is unknown. Additional clinical studies are needed to determine the optimal rewarming rate and strategy. TI - Rewarming after hypothermia after cardiac arrest shifts the inflammatory balance. EP - 1142 SN - 0090-3493 IS - iss. 4 SP - 1136 JF - Critical Care Medicine VL - vol. 40 N1 - 1 april 2012 DO - https://doi.org/10.1097/CCM.0b013e3182377050 ER - TY - JOUR AU - van Iersel, F.M. AU - Slooter, A.J. AU - Vroegop, R. AU - Wolters, A.E. AU - Tiemessen, C.A. AU - Rosken, R.H. AU - van der Hoeven, J.G. AU - Peelen, L.M. AU - Hoedemaekers, C.W.E. PY - 2012 UR - https://hdl.handle.net/2066/109415 AB - PURPOSE: To identify risk factors for hypoglycaemia in neurocritical care patients receiving intensive insulin therapy (IIT). METHODS: We performed a nested case-control study. All first episodes of hypoglycaemia (glucose <80 mg/dL, <4.4 mmol/L) in neurocritical care patients between 1 March 2006 and 31 December 2007 were identified. Patients were treated according to the local IIT protocol, with target blood glucose levels between 4.5 and 6.0 mmol/L (81.0-108.0 mg/dL). The first hypoglycaemic event of every patient (index moment) was used to match to a control patient. Possible risk factors preceding the index moment were scored using hospital records and analysed with conditional logistic regression. RESULTS: Of 786 neurocritical care patients, 449 developed hypoglycaemia (57.1 %). Independent risk factors for hypoglycaemia were lowering nutrition 6 h before the index moment without insulin dose reduction (odds ratio (OR) 5.25, 95 % confidence interval (95 % CI) 1.32-20.88), mechanical ventilation (OR 2.59, 95 % CI 1.56-4.29), lowering the dosage of norepinephrine 3 h before the index moment (OR 2.44, 95 % CI 1.07-5.55), a hyperglycaemic event (>10 mmol/L, >180.0 mg/dL) in the 24 h preceding the index moment (OR 2.40, 95 % CI 1.26-4.58), gastric residual in the 6 h preceding the index moment without insulin dose reduction (OR 1.76, 95 % CI 1.05-2.96) and dosage of insulin at the index moment (OR 0.83, 95 % CI 0.76-0.90). CONCLUSION: Hypoglycaemia occurs in a considerable proportion of neurocritical care patients. We recommend the identification of these risk factors in these patients to avoid the occurrence of hypoglycaemia. TI - Risk factors for hypoglycaemia in neurocritical care patients EP - 2006 SN - 0342-4642 IS - iss. 12 SP - 1999 JF - Intensive Care Medicine VL - vol. 38 DO - https://doi.org/10.1007/s00134-012-2681-2 ER - TY - JOUR AU - Kox, M. AU - Vrouwenvelder, M.Q. AU - Pompe, J.C. AU - Hoeven, J.G. van der AU - Pickkers, P. AU - Hoedemaekers, C.W.E. PY - 2012 UR - https://hdl.handle.net/2066/109810 AB - Brain injury and its related increased intracranial pressure (ICP) may lead to increased vagus nerve activity and the subsequent suppression of innate immunity via the cholinergic anti-inflammatory pathway. This may explain the observed increased susceptibility to infection in these patients. In the present study, we investigated the association between brain injury, vagus nerve activity, and innate immunity. We determined heart rate variability (HRV) as a measure of vagus nerve activity, plasma cytokines, and cytokine production of ex vivo lipopolysaccharide-stimulated whole blood in the first 4 days of admission to the neurological intensive care unit (ICU) in 34 patients with various forms of brain damage. HRV, immune parameters, and the correlations between these measures were analyzed in the entire group of patients and in subgroups of patients with conditions associated with high (intracranial hemorrhage [ICH]) and normal ICP (subarachnoid hemorrhage [SAH] with an extraventricular drain alleviating ICP). Healthy volunteers were used for comparison. HRV total spectral power and ex vivo-stimulated cytokine production were severely depressed in patients compared with healthy volunteers (p<0.05). Furthermore, HRV analysis showed that normalized units of high-frequency power (HFnu, corresponding with vagus nerve activity) was higher, and the low-frequency:high-frequency ratio (LF:HF, corresponding with sympathovagal balance) was lower in patients compared to healthy volunteers (p<0.05). HFnu correlated inversely with ex vivo-stimulated tumor necrosis factor-alpha (TNF-alpha) production (r=-0.22, p=0.025). The most pronounced suppression of ex vivo-stimulated cytokine production was observed in the ICH group. Furthermore, in ICH patients, HFnu correlated strongly with lower plasma TNF-alpha levels (r=-0.73, p=0.002). Our data suggest that brain injury, and especially conditions associated with increased ICP, is associated with vagus nerve-mediated immune suppression. TI - The effects of brain injury on heart rate variability and the innate immune response in critically ill patients. EP - 755 SN - 0897-7151 IS - iss. 5 SP - 747 JF - Journal of Neurotrauma VL - vol. 29 DO - https://doi.org/10.1089/neu.2011.2035 ER - TY - JOUR AU - Haren, F.M.P. van AU - Sleigh, J. AU - Boerma, E.C. AU - Pine, M. La AU - Bahr, M. AU - Pickkers, P. AU - Hoeven, J.G. van der PY - 2012 UR - https://hdl.handle.net/2066/108182 AB - We assessed the short-term effects of hypertonic fluid versus isotonic fluid administration in patients with septic shock. This was a double-blind, prospective randomized controlled trial in a 15-bed intensive care unit. Twenty-four patients with septic shock were randomized to receive 250 mL 7.2% NaCl/6% hydroxyethyl starch (HT group) or 500 mL 6% hydroxyethyl starch (IT group). Hemodynamic measurements included mean arterial blood pressure (MAP), central venous pressure, stroke volume index, stroke volume variation, intrathoracic blood volume index, gastric tonometry, and sublingual microcirculatory flow as assessed by sidestream dark field imaging. Systolic tissue Doppler imaging velocities of the medial mitral annulus were measured using echocardiography to assess left ventricular contractility. Log transformation of the ratio MAP divided by the norepinephrine infusion rate (log MAP/NE) quantified the combined effect on both parameters. Compared with the IT group, hypertonic solution treatment resulted in an improvement in log MAP/NE (P = 0.008), as well as an increase in systolic tissue Doppler imaging velocities (P = 0.03) and stroke volume index (P = 0.017). No differences between the groups were found for preload parameters (central venous pressure, stroke volume variation, intrathoracic blood volume index) or for afterload parameters (systemic vascular resistance index, MAP). Hypertonic solution treatment decreased the need for ongoing fluid resuscitation (P = 0.046). No differences between groups were observed regarding tonometry or the sublingual microvascular variables. In patients with septic shock, hypertonic fluid administration did not promote gastrointestinal mucosal perfusion or sublingual microcirculatory blood flow in comparison to isotonic fluid. Independent of changes in preload or afterload, hypertonic fluid administration improved the cardiac contractility and vascular tone compared with isotonic fluid. The need for ongoing fluid resuscitation was also reduced. TI - Hypertonic fluid administration in patients with septic shock: a prospective randomized controlled pilot study. EP - 275 SN - 1073-2322 IS - iss. 3 SP - 268 JF - Shock VL - vol. 37 N1 - 1 maart 2012 DO - https://doi.org/10.1097/SHK.0b013e31823f152f ER - TY - JOUR AU - Pickkers, P. AU - Heemskerk, S. AU - Schouten, J.A. AU - Laterre, P.F. AU - Vincent, J.L. AU - Beishuizen, A. AU - Jorens, P.G. AU - Spapen, H. AU - Bulitta, M. AU - Peters, W.H.M. AU - Hoeven, J.G. van der PY - 2012 UR - https://hdl.handle.net/2066/108970 AB - INTRODUCTION: To evaluate whether alkaline phosphatase (AP) treatment improves renal function in sepsis-induced acute kidney injury (AKI), a prospective, double-blind, randomized, placebo-controlled study in critically ill patients with severe sepsis or septic shock with evidence of AKI was performed. METHODS: Thirty-six adult patients with severe sepsis or septic shock according to Systemic Inflammatory Response Syndrome criteria and renal injury defined according to the AKI Network criteria were included. Dialysis intervention was standardized according to Acute Dialysis Quality Initiative consensus. Intravenous infusion of alkaline phosphatase (bolus injection of 67.5 U/kg body weight followed by continuous infusion of 132.5 U/kg/24 h for 48 hours, or placebo) starting within 48 hours of AKI onset and followed up to 28 days post-treatment. The primary outcome variable was progress in renal function variables (endogenous creatinine clearance, requirement and duration of renal replacement therapy, RRT) after 28 days. The secondary outcome variables included changes in circulating inflammatory mediators, urinary excretion of biomarkers of tubular injury, and safety. RESULTS: There was a significant (P = 0.02) difference in favor of AP treatment relative to controls for the primary outcome variable. Individual renal parameters showed that endogenous creatinine clearance (baseline to Day 28) was significantly higher in the treated group relative to placebo (from 50 +/- 27 to 108 +/- 73 mL/minute (mean +/- SEM) for the AP group; and from 40 +/- 37 to 65 +/- 30 mL/minute for placebo; P = 0.01). Reductions in RRT requirement and duration did not reach significance. The results in renal parameters were supported by significantly more pronounced reductions in the systemic markers C-reactive protein, Interleukin-6, LPS-binding protein and in the urinary excretion of Kidney Injury Molecule-1 and Interleukin-18 in AP-treated patients relative to placebo. The Drug Safety Monitoring Board did not raise any issues throughout the trial. CONCLUSIONS: The improvements in renal function suggest alkaline phosphatase is a promising new treatment for patients with severe sepsis or septic shock with AKI. TRIAL REGISTRATION: www.clinicaltrials.gov: NCTNCT00511186. TI - Alkaline phosphatase for treatment of sepsis-induced acute kidney injury: a prospective randomized double-blind placebo-controlled trial. EP - R14 SN - 1466-609X IS - iss. 1 SP - R14 JF - Critical Care VL - vol. 16 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/108970/108970.pdf?sequence=1 ER - TY - JOUR AU - Oostdijk, E.A. AU - Smet, A.M. de AU - Kesecioglu, J. AU - Bonten, M.J. AU - Hoeven, J.G. van der AU - Pickkers, P. AU - Sturm, P.D. AU - Voss, A. AU - et al. PY - 2012 UR - https://hdl.handle.net/2066/110798 AB - OBJECTIVES: Prevalences of cephalosporin-resistant Enterobacteriaceae are increasing globally, especially in intensive care units (ICUs). The effect of selective digestive tract decontamination (SDD) on the eradication of cephalosporin-resistant Enterobacteriaceae from the intestinal tract is unknown. We quantified eradication rates of cephalosporin-resistant and cephalosporin-susceptible Enterobacteriaceae during SDD in patients participating in a 13 centre cluster-randomized study and from a single-centre cohort. METHODS: All SDD patients colonized with Enterobacteriaceae in the intestinal tract at ICU admission were included. Cephalosporin resistance was defined as resistance to ceftazidime, cefotaxime or ceftriaxone and aminoglycoside resistance as resistance to tobramycin or gentamicin. Duration of rectal colonization was determined by screening twice weekly during ICU stay. Swabs were inoculated on selective medium supplemented with tobramycin or cefotaxime. RESULTS: Five hundred and seven (17%) of 2959 SDD patients with at least one rectal sample were colonized with Enterobacteriaceae at ICU admission: 77 (15%) with cephalosporin-resistant Enterobacteriaceae and 50 (10%) with aminoglycoside-resistant Enterobacteriaceae. Fifty-six (73%) patients colonized with cephalosporin-resistant Enterobacteriaceae were successfully decontaminated before ICU discharge, as were 343 (80%) patients colonized with cephalosporin-susceptible Enterobacteriaceae (P = 0.17). For aminoglycoside resistance, 31 (62%) patients were decontaminated, as were 368 patients (81%) colonized with aminoglycoside-susceptible Enterobacteriaceae (P < 0.01). On average, decolonization was demonstrated after 4 days if colonized with cephalosporin-susceptible Enterobacteriaceae and aminoglycoside-susceptible Enterobacteriaceae, and after 5 and 5.5 days if colonized with cephalosporin-resistant Enterobacteriaceae and aminoglycoside-resistant Enterobacteriaceae, respectively (log-rank test P = 0.053 for cephalosporin resistance and P = 0.03 for aminoglycoside resistance). If eradication failed, no associations were found with increased resistance in time (P > 0.05 for all comparisons). CONCLUSIONS: SDD can successfully eradicate cephalosporin-resistant Enterobacteriaceae from the intestinal tract. TI - Decontamination of cephalosporin-resistant Enterobacteriaceae during selective digestive tract decontamination in intensive care units EP - 2253 SN - 0305-7453 IS - iss. 9 SP - 2250 JF - Journal of Antimicrobial Chemotherapy VL - vol. 67 DO - https://doi.org/10.1093/jac/dks187 ER - TY - JOUR AU - Spoelstra-de Man, A.M. AU - Hoeven, J.G. van der AU - Heunks, L.M.A. PY - 2012 UR - https://hdl.handle.net/2066/111045 TI - Effect of do-not-resuscitate orders on the penumbra of care. EP - 727 SN - 0342-4642 IS - iss. 4 SP - 726 JF - Intensive Care Medicine VL - vol. 38 N1 - 1 april 2012 DO - https://doi.org/10.1007/s00134-011-2461-4 ER - TY - JOUR AU - Boogaard, M.H.W.A. van den AU - Schoonhoven, L. AU - Evers, A.W. AU - Hoeven, J.G. van der AU - Achterberg, T. van AU - Pickkers, P. PY - 2012 UR - https://hdl.handle.net/2066/110811 TI - Delirium in critically ill patients: Impact on long-term health-related quality of life and cognitive functioning. EP - 118 SN - 0090-3493 IS - iss. 1 SP - 112 JF - Critical Care Medicine VL - vol. 40 DO - https://doi.org/10.1097/CCM.0b013e31822e9fc9 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/110811/110811.pdf?sequence=1 ER - TY - JOUR AU - Boogaard, M.W. van den AU - Pickkers, P. AU - Slooter, A.J. AU - Kuiper, M.A. AU - Spronk, P.E. AU - Voort, P.H. van der AU - Hoeven, J.G. van der AU - Donders, R. AU - Achterberg, T. van AU - Schoonhoven, L. PY - 2012 UR - https://hdl.handle.net/2066/110861 AB - OBJECTIVES: To develop and validate a delirium prediction model for adult intensive care patients and determine its additional value compared with prediction by caregivers. DESIGN: Observational multicentre study. SETTING: Five intensive care units in the Netherlands (two university hospitals and three university affiliated teaching hospitals). PARTICIPANTS: 3056 intensive care patients aged 18 years or over. MAIN OUTCOME MEASURE: Development of delirium (defined as at least one positive delirium screening) during patients' stay in intensive care. RESULTS: The model was developed using 1613 consecutive intensive care patients in one hospital and temporally validated using 549 patients from the same hospital. For external validation, data were collected from 894 patients in four other hospitals. The prediction (PRE-DELIRIC) model contains 10 risk factors-age, APACHE-II score, admission group, coma, infection, metabolic acidosis, use of sedatives and morphine, urea concentration, and urgent admission. The model had an area under the receiver operating characteristics curve of 0.87 (95% confidence interval 0.85 to 0.89) and 0.86 after bootstrapping. Temporal validation and external validation resulted in areas under the curve of 0.89 (0.86 to 0.92) and 0.84 (0.82 to 0.87). The pooled area under the receiver operating characteristics curve (n=3056) was 0.85 (0.84 to 0.87). The area under the curve for nurses' and physicians' predictions (n=124) was significantly lower at 0.59 (0.49 to 0.70) for both. CONCLUSION: The PRE-DELIRIC model for intensive care patients consists of 10 risk factors that are readily available within 24 hours after intensive care admission and has a high predictive value. Clinical prediction by nurses and physicians performed significantly worse. The model allows for early prediction of delirium and initiation of preventive measures. Trial registration Clinical trials NCT00604773 (development study) and NCT00961389 (validation study). TI - Development and validation of PRE-DELIRIC (PREdiction of DELIRium in ICu patients) delirium prediction model for intensive care patients: observational multicentre study. EP - e420 SN - 0959-535X SP - e420 JF - Bmj. British Medical Journal (Compact Ed.) VL - vol. 344 ER - TY - JOUR AU - Haerkens, M.H.T.M. AU - Jenkins, D.H. AU - van der Hoeven, J.G. PY - 2012 UR - https://hdl.handle.net/2066/110739 AB - Intensive care frequently results in unintentional harm to patients and statistics don't seem to improve. The ICU environment is especially unforgiving for mistakes due to the multidisciplinary, time-critical nature of care and vulnerability of the patients. Human factors account for the majority of adverse events and a sound safety climate is therefore essential. This article reviews the existing literature on aviation-derived training called Crew Resource Management (CRM) and discusses its application in critical care medicine. CRM focuses on teamwork, threat and error management and blame free discussion of human mistakes. Though evidence is still scarce, the authors consider CRM to be a promising tool for culture change in the ICU setting, if supported by leadership and well-designed follow-up. TI - Crew resource management in the ICU: the need for culture change EP - 39 SN - 2110-5820 IS - iss. 1 SP - 39 JF - Annals of Intensive Care VL - vol. 2 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/110739/110739.pdf?sequence=1 ER - TY - JOUR AU - Boogaard, M.W. van den AU - Schoonhoven, L. AU - Hoeven, J.G. van der AU - Achterberg, T. van AU - Pickkers, P. PY - 2012 UR - https://hdl.handle.net/2066/108309 AB - BACKGROUND: Delirium is a serious and frequent psycho-organic disorder in critically ill patients. Reported incidence rates vary to a large extent and there is a paucity of data concerning delirium incidence rates for the different subgroups of intensive care unit (ICU) patients and their short-term health consequences. OBJECTIVES: To determine the overall incidence and duration of delirium, per delirium subtype and per ICU admission diagnosis. Furthermore, we determined the short-term consequences of delirium. DESIGN: Prospective observational study. PARTICIPANTS AND SETTING: All adult consecutive patients admitted in one year to the ICU of a university medical centre. METHODS: Delirium was assessed using the Confusion Assessment Method-ICU three times a day. Delirium was divided in three subtypes: hyperactive, hypoactive and mixed subtype. As measures for short-term consequences we registered duration of mechanical ventilation, re-intubations, incidence of unplanned removal of tubes, length of (ICU) stay and in-hospital mortality. RESULTS: 1613 patients were included of which 411 (26%) developed delirium. The incidence rate in the neurosurgical (10%) and cardiac surgery group (12%) was the lowest, incidence was intermediate in medical patients (40%), while patients with a neurological diagnosis had the highest incidence (64%). The mixed subtype occurred the most (53%), while the hyperactive subtype the least (10%). The median delirium duration was two days [IQR 1-7], but significantly longer (P<0.0001) for the mixed subtype. More delirious patients were mechanically ventilated and for a longer period of time, were more likely to remove their tube and catheters, stayed in the ICU and hospital for a longer time, and had a six times higher chance of dying compared to non-delirium ICU patients, even after adjusting for their severity of illness score. Delirium was associated with an extended duration of mechanical ventilation, length of stay in the ICU and in-hospital, as well as with in-hospital mortality. CONCLUSIONS: The delirium incidence in a mixed ICU population is high and differs importantly between ICU admission diagnoses and the subtypes of delirium. Patients with delirium had a significantly higher incidence of short-term health problems, independent from their severity of illness and this was most pronounced in the mixed subtype of delirium. Delirium is significantly associated with worse short-term outcome. TI - Incidence and short-term consequences of delirium in critically ill patients: A prospective observational cohort study. EP - 783 SN - 0020-7489 IS - iss. 7 SP - 775 JF - International Journal of Nursing Studies VL - vol. 49 N1 - 1 juli 2012 DO - https://doi.org/10.1016/j.ijnurstu.2011.11.016 ER - TY - JOUR AU - Ramakers, B.P.C. AU - Wever, K.E. AU - Kox, M. AU - Broek, P.L.C. van den AU - Mbuyi, F. AU - Rongen, G.A. AU - Masereeuw, R. AU - Hoeven, J.G. van der AU - Smits, P. AU - Riksen, N.P. AU - Pickkers, P. PY - 2012 UR - https://hdl.handle.net/2066/108157 AB - OBJECTIVE: : Adenosine modulates inflammation and prevents associated organ injury by activation of its receptors. During sepsis, the extracellular adenosine concentration increases rapidly, but the underlying mechanism in humans is unknown. We aimed to determine the changes in adenosine metabolism and signaling both in vivo during experimental human endotoxemia and in vitro. DESIGN: : We studied subjects participating in three different randomized double-blind placebo-controlled trials. In order to prevent confounding by the different pharmacological interventions in these trials, analyses were performed on data of placebo-treated subjects only. SETTING: : Intensive care research unit at the Radboud University Nijmegen Medical Center. SUBJECTS: : In total, we used material of 24 healthy male subjects. INTERVENTIONS: : Subjects received 2 ng/kg Escherichia coli endotoxin (lipopolysaccharide) intravenously. MEASUREMENTS AND MAIN RESULTS: : Following experimental endotoxemia, endogenous adenosine concentrations increased. Expression of 5'ectonucleotidase messenger RNA was upregulated (p = .01), whereas adenosine deaminase messenger RNA was downregulated (p = .02). Furthermore, both adenosine deaminase and adenosine kinase activity was significantly diminished (both p 7 ml kg(-1) with correction for TV, calculated breath-by-breath, and with exclusion of arrhythmias [area under the curve (AUC)=0.95, 0.93, and 0.90 for PPV, SPV, and SVV, respectively]. Including patients ventilated with lower TVs decreased the predictive value of all dynamic indices, while calculating dynamic indices over 30 s and not excluding cardiac arrhythmias further reduced the AUC to 0.51, 0.63, and 0.51 for PPV, SPV, and SVV, respectively. CONCLUSIONS: PPV, SPV, and SVV are the only reliable predictors of fluid responsiveness under strict conditions. In routine clinical practice, factors including low TV, cardiac arrhythmias, and the calculation method can substantially reduce their predictive value. TI - Dynamic indices do not predict volume responsiveness in routine clinical practice. EP - 401 SN - 0007-0912 IS - iss. 3 SP - 395 JF - British Journal of Anaesthesia VL - vol. 108 N1 - 1 maart 2012 ER - TY - JOUR AU - Moviat, M. AU - Terpstra, A.M. AU - Hoeven, J.G. van der AU - Pickkers, P. PY - 2012 UR - https://hdl.handle.net/2066/108244 AB - PURPOSE: Urinary excretion of chloride corrects metabolic acidosis, but this may be hampered in patients with impaired renal function. We explored the effects of renal function on acid-base characteristics and urinary strong ion excretion using the Stewart approach in critically ill patients with metabolic acidosis. MATERIALS AND METHODS: We examined the plasma and urine chemistry in 65 critically ill (mixed medical and surgical) patients with metabolic acidosis. The apparent strong ion difference, effective strong ion difference, strong ion gap, and urinary simplified strong ion difference (urinary SID) were calculated. Linear regression analyses were used (1) to assess whether plasma creatinine concentrations were related to urinary SIDs values, adjusted for blood pH levels, and (2) to determine whether urinary SID values were associated with blood pH levels. RESULTS: Creatinine concentrations were positively and significantly (P < .001) associated with urinary SIDs values, adjusted for pH levels. Urinary simplified strong ion difference values were inversely and significantly (P < .001) related to pH levels. CONCLUSIONS: In critically ill patients with metabolic acidosis, impaired renal function was associated with greater urinary SIDs. Subsequently, the higher urinary SIDs values were related to lower pH levels, illustrating the importance of renal chloride excretion to correct for acidosis. TI - Impaired renal function is associated with greater urinary strong ion differences in critically ill patients with metabolic acidosis. EP - 260 SN - 0883-9441 IS - iss. 3 SP - 255 JF - Journal of Critical Care VL - vol. 27 N1 - 1 juni 2012 DO - https://doi.org/10.1016/j.jcrc.2011.05.028 ER - TY - JOUR AU - Simmes, F. AU - Schoonhoven, L. AU - Mintjes-de Groot, A.J. AU - Fikkers, B.G. AU - Hoeven, J.G. van der PY - 2012 UR - https://hdl.handle.net/2066/108311 AB - ABSTRACT: BACKGROUND: Rapid response systems (RRSs) are considered an important tool for improving patient safety. We studied the effect of an RRS on the incidence of cardiac arrests and unexpected deaths. METHODS: Retrospective before- after study in a university medical centre. We included 1376 surgical patients before (period 1) and 2410 patients after introduction of the RRS (period 2). Outcome measures were corrected for the baseline covariates age, gender and ASA. RESULTS: The number of patients who experienced a cardiac arrest and/or who died unexpectedly decreased non significantly from 0.50% (7/1376) in period 1 to 0.25% (6/2410) in period 2 (odds ratio (OR) 0.43, CI 0.14-1.30). The individual number of cardiac arrests decreased non-significantly from 0.29% (4/1367) to 0.12% (3/2410) (OR 0.38, CI 0.09-1.73) and the number of unexpected deaths decreased non-significantly from 0.36% (5/1376) to 0.17% (4/2410) (OR 0.42, CI 0.11-1.59). In contrast, the number of unplanned ICU admissions increased from 2.47% (34/1376) in period 1 to 4.15% (100/2400) in period 2 (OR 1.66, CI 1.07-2.55). Median APACHE ll score at unplanned ICU admissions was 16 in period 1 versus 16 in period 2 (NS). Adherence to RRS procedures. Observed abnormal early warning scores 8, or 4) they did not satisfy the Simplified Acute Physiology Score II inclusion criteria. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 13,962 patients were admitted to an intensive care unit following cardiac arrest. In total 8,645 patients were excluded, 5,544 because of a Glasgow Coma Scale score of >8. Of the resultant 5,317 patients, 1,547 patients were treated before and 3,770 patients after implementation of mild therapeutic hypothermia. Patients admitted after implementation of mild therapeutic hypothermia had lower minimal and maximal temperatures (p < .0001) during the first 24 hrs on the intensive care unit compared to patients admitted before implementation of mild therapeutic hypothermia. The adjusted odds ratio of the hospital mortality of patients treated after implementation of mild therapeutic hypothermia was 0.80 (95% confidence interval of 0.65-0.98, p = .029). CONCLUSION: The results of this retrospective, observational survey suggest that implementation of mild therapeutic hypothermia in Dutch intensive care units is associated with a 20% relative reduction of hospital mortality in cardiac arrest patients. TI - Influence of mild therapeutic hypothermia after cardiac arrest on hospital mortality EP - 88 SN - 0090-3493 IS - iss. 1 SP - 84 JF - Critical Care Medicine VL - vol. 39 DO - https://doi.org/10.1097/CCM.0b013e3181fd6aef ER - TY - JOUR AU - Haren, F.M.P. van AU - Sleigh, J. AU - Cursons, R. AU - Pine, M. La AU - Pickkers, P. AU - Hoeven, J.G. van der PY - 2011 UR - https://hdl.handle.net/2066/98426 AB - ABSTRACT: OBJECTIVE: This study was designed to investigate the effect of hypertonic fluid administration on inflammatory mediator gene expression in patients with septic shock. DESIGN AND SETTING: Prospective, randomized, controlled, double-blind clinical study in a 15-bed mixed intensive care unit in a tertiary referral teaching hospital. INTERVENTIONS: Twenty-four patients, who met standard criteria for septic shock, were randomized to receive a bolus of hypertonic fluid (HT, 250 ml 6% HES/7.2% NaCl) or isotonic fluid (IT, 500 ml 6% HES/0.9% NaCl) administered over 15 minutes. Randomization and study fluid administration was within 24 hours of ICU admission for all patients. This trial is registered with ANZCTR.org.au as ACTRN12607000259448. RESULTS: Blood samples were taken immediately before and 4, 8, 12, and 24 hours after fluid administration. Real-time reverse transcriptase polymerase chain reaction (RT rtPCR) was used to quantify mRNA expression of different inflammatory mediators in peripheral leukocytes. In the HT group, compared with the IT group, levels of gene expression of MMP9 and L-selectin were significantly suppressed (p = 0.0002 and p = 0.007, respectively), and CD11b gene expression tended to be elevated (p = NS). No differences were found in the other mediators examined. CONCLUSIONS: In septic shock patients, hypertonic fluid administration compared with isotonic fluid may modulate expression of genes that are implicated in leukocyte-endothelial interaction and capillary leakage.The study was performed at the Intensive Care Department, Waikato Hospital, and at the Molecular Genetics Laboratory, University of Waikato, Hamilton, New Zealand. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12607000259448. TI - The effects of hypertonic fluid administration on the gene expression of inflammatory mediators in circulating leucocytes in patients with septic shock: a preliminary study EP - 44 SN - 2110-5820 IS - iss. 1 SP - 44 JF - Annals of Intensive Care VL - vol. 1 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/98426/98426.pdf?sequence=1 ER - TY - JOUR AU - Tiemessen, C.A. AU - Hoedemaekers, C.W.E. AU - Iersel, F.M. van AU - Rosken, G.H. AU - Hoeven, J.G. van der AU - Biessels, G.J. AU - Slooter, A.J. PY - 2011 UR - https://hdl.handle.net/2066/96024 AB - BACKGROUND: Intensive insulin therapy protocols are widely used in intensive care medicine. A disadvantage of these protocols may be the occurrence of hypoglycemic episodes. Neurocritical care patients are particularly vulnerable to the effects of hypoglycemia. We aimed to study the risk of hypoglycemia in neurocritical care patients in relation to intensive insulin therapy. METHODS: To determine the effects of 2 different intensive insulin therapy protocols on glucose levels and hypoglycemia incidence, we collected data before and after implementation of the protocols in 2 university hospitals. The risk of hypoglycemia (blood glucose level below 3.0 mmol/L) was studied retrospectively with logistic regression analyses. RESULTS: In hospital A, data were obtained on 152 patients before implementation of the protocol and on 649 patients after implementation of the protocol. In hospital B, data were obtained on 111 patients before implementation of the protocol and on 118 patients thereafter. Implementation of intensive insulin therapy protocols increased the time spent in the desired blood glucose range of 4.6 to 6.0 mmol/L in both hospitals, but increased the risk of hypoglycemia: the absolute risk of hypoglycemia during intensive care unit admission increased in hospital A from 14.5% to 20.3% (adjusted odds ratio=1.3; 95% confidence interval: 0.8-2.3) and in hospital B from 3.6% to 29.7% (adjusted odds ratio=28.6; 95% confidence interval: 5.9-138.9). CONCLUSIONS: Implementation of intensive insulin therapy protocols in neurocritical care patients not only seems to increase the time spent in the desired blood glucose range, but also seems to increase the risk of hypoglycemia. The risk of hypoglycemia strongly depends on characteristics of the intensive insulin therapy protocol. TI - Intensive insulin therapy increases the risk of hypoglycemia in neurocritical care patients EP - 214 SN - 0898-4921 IS - iss. 3 SP - 206 JF - Journal of Neurosurgical Anesthesiology VL - vol. 23 DO - https://doi.org/10.1097/ANA.0b013e31821aa6f2 ER - TY - JOUR AU - Boogaard, M.W. van den AU - Kox, M. AU - Quinn, K.L. AU - Achterberg, T. van AU - Hoeven, J.G. van der AU - Schoonhoven, L. AU - Pickkers, P. PY - 2011 UR - https://hdl.handle.net/2066/98557 TI - Biomarkers associated with delirium in critically ill patients and their relation with long-term subjective cognitive dysfunction; indications for different pathways governing delirium in inflamed and non-inflamed patients. SN - 1466-609X IS - iss. 15 JF - Critical Care VL - vol. 29 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/98557/98557.pdf?sequence=1 ER - TY - JOUR AU - Oostdijk, E.A. AU - Smet, A.M. de AU - Kesecioglu, J. AU - Bonten, M.J. AU - Kalkman, C.J. AU - Joore, H.C. AU - Hoeven, J.G. van der AU - Pickkers, P. AU - Sturm, P.D.J. AU - Voss, A. AU - et al. PY - 2011 UR - https://hdl.handle.net/2066/98459 AB - OBJECTIVE: Selective digestive tract decontamination aims to eradicate gram-negative bacteria in both the intestinal tract and respiratory tract and is combined with a 4-day course of intravenous cefotaxime. Selective oropharyngeal decontamination only aims to eradicate respiratory tract colonization. In a recent study, selective digestive tract decontamination and selective oropharyngeal decontamination were associated with lower day-28 mortality, when compared to standard care. Furthermore, selective digestive tract decontamination was associated with a lower incidence of intensive care unit-acquired bacteremia caused by gram-negative bacteria. We quantified the role of intestinal tract carriage with gram-negative bacteria and intensive care unit-acquired gram-negative bacteremia. DESIGN: Data from a cluster-randomized and a single-center observational study. SETTING: Intensive care unit in The Netherlands. PATIENTS: Patients with intensive care unit stay of >48 hrs that received selective digestive tract decontamination (n = 2,667), selective oropharyngeal decontamination (n = 2,166) or standard care (n = 1,945). INTERVENTIONS: Selective digestive tract decontamination or selective oropharyngeal decontamination. MEASUREMENTS AND MAIN RESULTS: Incidence densities (episodes/1000 days) of intensive care unit-acquired gram-negative bacteremia were 4.5, 3.0, and 1.4 during standard care, selective oropharyngeal decontamination, and selective digestive tract decontamination, respectively, and the daily risk for developing intensive care unit-acquired gram-negative bacteria bacteremia increased until days 36, 33, and 31 for selective digestive tract decontamination, standard care, and selective oropharyngeal decontamination and was always lowest during selective digestive tract decontamination. Rectal colonization with gram-negative bacteria was present in 26% and 71% of patient days during selective digestive tract decontamination and selective oropharyngeal decontamination, respectively (p < .01). Irrespective of interventions, incidence densities of intensive care unit-acquired gram-negative bacteremia was 4.5 during patient days with both intestinal and respiratory tract gram-negative bacteria carriage. These incidence densities reduced with 33% (to 3.1) during days with intestinal gram-negative bacteria carriage only and with another 45% (to 1.0) during days without gram-negative bacteria carriage at both sites. CONCLUSIONS: Respiratory tract decolonization was associated with a 33% and intestinal tract decolonization was associated with a 45% reduction in the occurrence of intensive care unit-acquired gram-negative bacteremia. TI - The role of intestinal colonization with gram-negative bacteria as a source for intensive care unit-acquired bacteremia EP - 966 SN - 0090-3493 IS - iss. 5 SP - 961 JF - Critical Care Medicine VL - vol. 39 DO - https://doi.org/10.1097/CCM.0b013e318208ee26 ER - TY - JOUR AU - Ramakers, B.P.C. AU - Riksen, N.P. AU - Broek, P.H.H. van den AU - Franke, B. AU - Peters, W.H.M. AU - Hoeven, J.G. van der AU - Smits, P. AU - Pickkers, P. PY - 2011 UR - https://hdl.handle.net/2066/95720 AB - INTRODUCTION: Preclinical studies have shown that the endogenous nucleoside adenosine prevents excessive tissue injury during systemic inflammation. We aimed to study whether endogenous adenosine also limits tissue injury in a human in vivo model of systemic inflammation. In addition, we studied whether subjects with the common 34C > T nonsense variant (rs17602729) of adenosine monophosphate deaminase (AMPD1), which predicts increased adenosine formation, have less inflammation-induced injury. METHODS: In a randomized double-blinded design, healthy male volunteers received 2 ng/kg E. Coli LPS intravenously with (n = 10) or without (n = 10) pretreatment with the adenosine receptor antagonist caffeine (4 mg/kg body weight). In addition, lipopolysaccharide (LPS) was administered to 10 subjects heterozygous for the AMPD1 34C > T variant. RESULTS: The increase in adenosine levels tended to be more pronounced in the subjects heterozygous for the AMPD1 34C > T variant (71 +/- 22%, P=0.04), compared to placebo- (59 +/- 29%, P=0.012) and caffeine-treated (53 +/- 47%, P=0.29) subjects, but this difference between groups did not reach statistical significance. Also the LPS-induced increase in circulating cytokines was similar in the LPS-placebo, LPS-caffeine and LPS-AMPD1-groups. Endotoxemia resulted in an increase in circulating plasma markers of endothelial activation [intercellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM)], and in subclinical renal injury, measured by increased urinary excretion of tubular injury markers. The LPS-induced increase of these markers did not differ between the three groups. CONCLUSIONS: Human experimental endotoxemia induces an increase in circulating cytokine levels and subclinical endothelial and renal injury. Although the plasma adenosine concentration is elevated during systemic inflammation, co-administration of caffeine or the presence of the 34C > T variant of AMPD1 does not affect the observed subclinical organ damage, suggesting that adenosine does not affect the inflammatory response and subclinical endothelial and renal injury during human experimental endotoxemia. TRIAL REGISTRATION: ClinicalTrials (NCT): NCT00513110. TI - Circulating adenosine increases during human experimental endotoxemia but blockade of its receptor does not influence the immune response and subsequent organ injury EP - R3 SN - 1466-609X IS - iss. 1 SP - R3 JF - Critical Care VL - vol. 15 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/95720/95720.pdf?sequence=1 ER - TY - JOUR AU - Kox, M. AU - Ramakers, B.P.C. AU - Pompe, J.C. AU - Hoeven, J.G. van der AU - Hoedemaekers, C.W. AU - Pickkers, P. PY - 2011 UR - https://hdl.handle.net/2066/98032 TI - Interplay between the acute inflammatory response and heart rate variability in healthy human volunteers. EP - 120 SN - 1073-2322 IS - iss. 2 SP - 115 JF - Shock VL - vol. 36 DO - https://doi.org/10.1097/SHK.0b013e31821c2330 ER - TY - JOUR AU - Bisschops, L.L.A. AU - Alfen, N. van AU - Bons, S. AU - Hoeven, J.G. van der AU - Hoedemaekers, C.W.E. PY - 2011 UR - https://hdl.handle.net/2066/97242 AB - INTRODUCTION: Outcome studies in patients with anoxic-ischemic encephalopathy focus on the early and reliable prediction of an outcome no better than a vegetative state or severe disability. We determined the effect of mild therapeutic hypothermia on the validity of the currently used clinical practice parameters. METHODS: We conducted a retrospective cohort study of adult comatose patients after cardiac arrest treated with hypothermia. All data were collected from medical charts and laboratory files and analyzed from the day of admission to the intensive care unit until day 7, discharge from the intensive care unit or death using the Utstein definitions for the registration of the data. RESULTS: We analyzed the data of 103 patients. The combination of an M1 or M2 on the Glasgow Coma Scale or absent pupillary reactions or absent corneal reflexes on day 3 was present in 80.6% of patients with an unfavourable and 11.1% of patients with a favourable outcome. The combination of M1 or M2 and absent pupillary reactions to light and absent corneal reflexes on day 3 was present in 14.9% of patients with an unfavourable and none of the patients with a favourable outcome. None of the patients with a favourable outcome had a bilaterally absent somatosensory evoked potential of the median nerve. The value of electroencephalogram patterns in predicting outcome was low, except for reactivity to noxious stimuli. CONCLUSIONS: No single clinical or electrophysiological parameter has sufficient accuracy to determine prognosis and decision making in patients after cardiac arrest, treated with hypothermia. TI - Predictors of poor neurologic outcome in patients after cardiac arrest treated with hypothermia: a retrospective study EP - 701 SN - 0300-9572 IS - iss. 6 SP - 696 JF - Resuscitation VL - vol. 82 DO - https://doi.org/10.1016/j.resuscitation.2011.02.020 ER - TY - JOUR AU - Bisschops, L.L.A. AU - Alfen, N. van AU - Hoeven, J.G. van der AU - Hoedemaekers, C.W.E. PY - 2011 UR - https://hdl.handle.net/2066/98232 TI - Predictive value of neurologic prognostic indicators in hypothermia after cardiac arrest EP - 7 SN - 0364-5134 IS - iss. 1 SP - 176; reply 176 JF - Annals of Neurology VL - vol. 70 ER - TY - JOUR AU - Nusmeier, A. AU - Boode, W.P. de AU - Hopman, J.C.W. AU - Schoof, P.H. AU - Hoeven, J.G. van der AU - Lemson, J. PY - 2011 UR - https://hdl.handle.net/2066/96696 AB - BACKGROUND: The transpulmonary thermodilution (TPTD) technique for measuring cardiac output (CO) has never been validated in the presence of a left-to-right shunt. METHODS: In this experimental, paediatric animal model, nine lambs with a surgically constructed aorta-pulmonary left-to-right shunt were studied under various haemodynamic conditions. CO was measured with closed and open shunt using the TPTD technique (CO(TPTD)) with central venous injections of ice-cold saline. An ultrasound transit time perivascular flow probe around the main pulmonary artery served as the standard reference measurement (CO(MPA)). RESULTS: Seven lambs were eligible for further analysis. Mean (sd) weight was 6.6 (1.6) kg. The mean CO(MPA) was 1.21 litre min(-1) (range 0.61-2.06 l min(-1)) with closed shunt and 0.93 litre min(-1) (range 0.48-1.45 litre min(-1)) with open shunt. The open shunt resulted in a mean Q(p)/Q(s) ratio of 1.8 (range 1.6-2.4). The bias between the two CO methods was 0.17 litre min(-1) [limits of agreement (LOA) of 0.27 litre min(-1)] with closed shunt and 0.14 litre min(-1) (LOA of 0.32 litre min(-1)) with open shunt. The percentage errors were 22% with closed shunt and 34% with open shunt. The correlation (r) between the two methods was 0.93 (P<0.001) with closed shunt and 0.86 (P<0.001) with open shunt. The correlation (r) between the two methods in tracking changes in CO (DeltaCO) during the whole experiment was 0.94 (P<0.0001). CONCLUSIONS: The TPTD technique is a feasible method of measuring CO in paediatric animals with a left-to-right shunt. TI - Cardiac output can be measured with the transpulmonary thermodilution method in a paediatric animal model with a left-to-right shunt EP - 343 SN - 0007-0912 IS - iss. 3 SP - 336 JF - British Journal of Anaesthesia VL - vol. 107 DO - https://doi.org/10.1093/bja/aer127 ER - TY - JOUR AU - Nusmeier, A. AU - Hoeven, J.G. van der AU - Lemson, J. PY - 2011 UR - https://hdl.handle.net/2066/97058 TI - Interpretation of the transpulmonary thermodilution curve in the presence of a left-to-right shunt EP - 1; author reply 552-3 SN - 0342-4642 IS - iss. 3 SP - 550 JF - Intensive Care Medicine VL - vol. 37 DO - https://doi.org/10.1007/s00134-010-2107-y ER - TY - JOUR AU - Ramakers, B.P.C. AU - Riksen, N.P. AU - Hoeven, J.G. van der AU - Smits, P. AU - Pickkers, P. PY - 2011 UR - https://hdl.handle.net/2066/97122 AB - In the past decades, increased concentrations of the signaling molecule adenosine have been shown to play an important role in the prevention of tissue damage evoked by several stressful circumstances. During systemic inflammation, the circulating adenosine concentration increases rapidly, even up to 10-fold in septic shock patients. By binding to specific adenosine receptor subtypes, designated A1, A2a, A2b, and A3, adenosine exerts a wide variety of immunomodulating and (cyto)protective effects. Only recently, several specific adenosine receptor agonists and other drugs that modulate adenosine metabolism have been developed for human use. Importantly, correct interpretation of the effects of adenosine is highly related to the model of inflammation used, e.g., administration of endotoxin or live bacteria. This review will discuss the potential role for adenosine as an immunomodulating and cytoprotective signaling molecule and will discuss its potential role in the treatment of the patient suffering from sepsis. TI - Modulation of innate immunity by adenosine receptor stimulation EP - 215 SN - 1073-2322 IS - iss. 3 SP - 208 JF - Shock VL - vol. 36 DO - https://doi.org/10.1097/SHK.0b013e318225aee4 ER - TY - JOUR AU - Ramakers, B.P.C. AU - Riksen, N.P. AU - Stal, T.H. AU - Heemskerk, S. AU - Broek, P van den AU - Peters, W.H. AU - Hoeven, J.G. van der AU - Smits, P. AU - Pickkers, P. PY - 2011 UR - https://hdl.handle.net/2066/95812 TI - Dipyridamole augments the anti-inflammatory response during human endotoxemia. EP - R289 SN - 1466-609X SP - R289 JF - Critical Care VL - vol. 15 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/95812/95812.pdf?sequence=1 ER - TY - JOUR AU - Lansdorp, B. AU - Ouweneel, D. AU - Keijzer, A. de AU - Hoeven, J.G. van der AU - Lemson, J. AU - Pickkers, P. PY - 2011 UR - https://hdl.handle.net/2066/98155 AB - BACKGROUND: Pulse pressure variation (PPV) and systolic pressure variation (SPV) are reliable predictors of fluid responsiveness in patients undergoing controlled mechanical ventilation. Currently, PPV and SPV are measured invasively and it is unknown if an arterial pressure (AP) signal obtained with a finger cuff can be used as an alternative. The aim of this study was to validate PPV and SPV measured using a finger cuff. METHODS: Patients receiving mechanical ventilation under sedation after cardiac artery bypass graft (CABG) surgery were included after arrival on the intensive care unit. AP was measured invasively in the radial artery and non-invasively using the finger cuff of the Nexfin monitor. I.V. fluid challenges were administered according to clinical need. The mean value of PPV and SVV was calculated before and after administration of a fluid challenge. Agreement of the calculated PPV and SPV from both methods was assessed using the Bland-Altman analysis. RESULTS: Nineteen patients were included and 28 volume challenges were analysed. Correlation between the two methods for PPV and SPV [mean (sd)=6.9 (4.3)% and 5.3 (2.6)%, respectively] was r=0.96 (P<0.0001) and r=0.95 (P<0.0001), respectively. The mean bias was -0.95% for PPV and -0.22% for SPV. Limits of agreement were -4.3% and 2.4% for PPV and -2.2% and 1.7% for SPV. The correlation between changes in PPV and SPV as a result of volume expansion measured by the two different methods was r=0.88 (P<0.0001) and r=0.87 (P<0.0001), respectively. CONCLUSIONS: In patients receiving controlled mechanical ventilation after CABG, PPV and SPV can be measured reliably non-invasively using the inflatable finger cuff of the Nexfin monitor. TI - Non-invasive measurement of pulse pressure variation and systolic pressure variation using a finger cuff corresponds with intra-arterial measurement EP - 545 SN - 0007-0912 IS - iss. 4 SP - 540 JF - British Journal of Anaesthesia VL - vol. 107 DO - https://doi.org/10.1093/bja/aer187 ER - TY - JOUR AU - Eijk, L.T.G.J. van AU - Kroot, J.J.C. AU - Tromp, M. AU - Hoeven, J.G. van der AU - Swinkels, D.W. AU - Pickkers, P. PY - 2011 UR - https://hdl.handle.net/2066/98009 AB - INTRODUCTION: Anemia is a frequently encountered problem during inflammation. Hepcidin is an interleukin-6 (IL-6)-induced key modulator of inflammation-associated anemia. Human sepsis is a prototypical inflammatory syndrome, often complicated by the development of anemia. However, the association between inflammation, hepcidin release and anemia has not been demonstrated in this group of patients. Therefore, we explored the association between hepcidin and sepsis-associated anemia. METHODS: 92 consecutive patients were enrolled after presentation on the emergency ward of a university hospital with sepsis, indicated by the presence of a proven or suspected infection and >/= 2 extended systemic inflammatory response syndrome (SIRS) criteria. Blood was drawn at day 1, 2 and 3 after admission for the measurement of IL-6 and hepcidin-25. IL-6 levels were correlated with hepcidin concentrations. Hemoglobin levels and data of blood transfusions during 14 days after hospitalisation were retrieved and the rate of hemoglobin decrease was correlated to hepcidin levels. RESULTS: 53 men and 39 women with a mean age of 53.3 +/- 1.8 yrs were included. Hepcidin levels were highest at admission (median[IQR]): 17.9[10.1 to 28.4]nmol/l and decreased to normal levels in most patients within 3 days (9.5[3.4 to 17.9]nmol/l). Hepcidin levels increased with the number of extended SIRS criteria (P = 0.0005). Highest IL-6 levels were measured at admission (125.0[46.3 to 330.0]pg/ml) and log-transformed IL-6 levels significantly correlated with hepcidin levels at admission (r = 0.28, P = 0.015), day 2 (r = 0.51, P < 0.0001) and day 3 (r = 0.46, P < 0.0001). Twelve patients received one or more blood transfusions during the first 2 weeks of admission, not related to active bleeding. These patients had borderline significant higher hepcidin level at admission compared to non-transfused patients (26.9[17.2 to 53.9] vs 17.9[9.9 to 28.8]nmol/l, P = 0.052). IL-6 concentrations did not differ between both groups. Correlation analyses showed significant associations between hepcidin levels on day 2 and 3 and the rate of decrease in hemoglobin (Spearman's r ranging from -0.32, P = 0.03 to -0.37, P = 0.016, respectively). CONCLUSIONS: These data suggest that hepcidin-25 may be an important modulator of anemia in septic patients with systemic inflammation. TI - Inflammation-induced hepcidin-25 is associated with the development of anemia in septic patients: an observational study EP - R9 SN - 1466-609X IS - iss. 1 SP - R9 JF - Critical Care VL - vol. 15 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/98009/98009.pdf?sequence=1 ER - TY - JOUR AU - Kox, M. AU - Kleijn, S. de AU - Pompe, J.C. AU - Ramakers, B.P.C. AU - Netea, M.G. AU - Hoeven, J.G. van der AU - Hoedemaekers, C.W.E. AU - Pickkers, P. PY - 2011 UR - https://hdl.handle.net/2066/96819 TI - Differential ex vivo and in vivo endotoxin tolerance kinetics following human endotoxemia EP - 1870 SN - 0090-3493 IS - iss. 8 SP - 1866 JF - Critical Care Medicine VL - vol. 39 DO - https://doi.org/10.1097/CCM.0b013e3182190d5d ER - TY - JOUR AU - Hoedemaekers, C.W.E. AU - Klein Gunnewiek, J.M.T. AU - Hoeven, J.G. van der PY - 2010 UR - https://hdl.handle.net/2066/89711 TI - Point-of-care glucose measurement systems should be used with great caution in critically ill intensive care unit patients. EP - 40 SN - 0090-3493 IS - iss. 1 SP - 339; author reply 339 JF - Critical Care Medicine VL - vol. 38 N1 - 1 januari 2010 ER - TY - JOUR AU - Dorresteijn, M.J. AU - Draisma, A. AU - Hoeven, J.G. van der AU - Pickkers, P. PY - 2010 UR - https://hdl.handle.net/2066/87263 AB - A widely applied method to study the activation of the innate immune system is in vitro stimulation of whole blood using lipopolysaccharide (LPS). However, it is unclear if in vitro cytokine production relates to in vivo cytokine levels elicited during experimental endotoxemia or sepsis. To determine the correlation between in vitro cytokine production and the in vivo inflammatory response, blood was obtained from 15 healthy volunteers for in vitro incubation with Escherichia coli LPS, immediately followed by experimental E. coli endotoxemia. Correlations of in vitro and peak in vivo cytokine concentrations were determined using Pearson correlation coefficient. In stimulated whole blood, tumor necrosis factor (TNF)-alpha, Interleukin (IL)-1beta, IL-6, IL-10 and interferon (IFN)-gamma were induced to 279 +/- 53, 392 +/- 64, 5312 +/- 624, 83 +/- 20 and 343 +/- 85 pg/ml, respectively, whereas in vivo cytokine induction led to cytokine levels of 603 +/- 123, 11 +/- 1, 4999 +/- 1228, 167 +/- 25 and 194 +/- 40 pg/ml, respectively. Correlation coefficients between the in vitro and in vivo cytokine concentrations were for TNF-alpha, IL-1beta, IL-6, IL-10 and IFN-gamma -0.10 (P = 0.7), 0.09 (P = 0.8), 0.36 (P = 0.2), 0.19 (P = 0.5) and 0.40 (P = 0.1), respectively. Comparison between in vitro and in vivo stimulation with LPS shows no correlation between the amount of cytokines produced. In vitro cytokine production, therefore, does not predict the in vivo inflammatory response. TI - Lipopolysaccharide-stimulated whole blood cytokine production does not predict the inflammatory response in human endotoxemia. EP - 253 SN - 1753-4259 IS - iss. 4 SP - 248 JF - Innate Immunity VL - vol. 16 N1 - 1 augustus 2010 DO - http://dx.doi.org/10.1177/1753425909339923 ER - TY - CHAP AU - Fukuda, K. AU - Hoeven, J.G. van der AU - Joswig, M. AU - Takayama, N. AU - Urban, J. AU - Hoder, K. AU - Voronkov, A. PY - 2010 UR - https://hdl.handle.net/2066/83733 PB - Berlin : Springer TI - Evaluation of Automated Theorem Proving on the Mizar Mathematical Library EP - 166 SN - 9783642155826 SP - 155 CT - Fukuda, K. (ed.), Mathematical Software – ICMS 2010 : Third International Congress on Mathematical Software, Kobe, Japan, September 13-17, 2010. Proceedings DO - http://dx.doi.org/10.1007/978-3-642-15582-6_30 ER - TY - JOUR AU - Draisma, A. AU - Dorresteijn, M.J. AU - Bouw, M.P.W.J.M. AU - Hoeven, J.G. van der AU - Pickkers, P. PY - 2010 UR - https://hdl.handle.net/2066/87722 AB - Sepsis is characterized by a blunted vascular responses due to impairment of endothelial function. The aim of our study was to assess endothelial function and the role of cytokines and nitric oxide (NO). Endotoxin tolerance was induced in 14 healthy volunteers by intravenous injection of 2 ng.kg.d lipopolysaccharide on 5 consecutive days. Forearm blood flow (FBF) was measured by strain-gauge plethysmography during dose-response curves of endothelium-dependent vasodilator acetylcholine and endothelium-independent vasodilator sodium nitroprusside before and 4 hours after LPS administration on days 1 and 5. In another study, 7 healthy volunteers were given selective inducible NO synthase inhibitor aminoguanidine intravenous continuously from 1 hour after a single LPS administration until 5 hours. FBF showed an attenuation of ACh-induced vasodilatory response with 67% (45%-72%) 4 hours after the first LPS administration (P = 0.01) with an unchanged dose-response curve to sodium nitroprusside. This attenuation to ACh infusion did not occur in the presence of aminoguanidine (P = 0.21) and also did not occur when tolerance was present on day 5 (P = 0.45). Our data demonstrate that endothelial dysfunction caused by endotoxemia does not occur when endotoxin tolerance develops, indicated by the absence of cytokine production and during administration of selective inducible NO synthase inhibitor aminoguanidine in vivo. TI - The role of cytokines and inducible nitric oxide synthase in endotoxemia-induced endothelial dysfunction. EP - 600 SN - 0160-2446 IS - iss. 6 SP - 595 JF - Journal of Cardiovascular Pharmacology VL - vol. 55 N1 - 1 juni 2010 DO - http://dx.doi.org/10.1097/FJC.0b013e3181da774b ER - TY - JOUR AU - Lemson, J. AU - Die, L. van AU - Hemelaar, A.E.A. AU - Hoeven, J.G. van der PY - 2010 UR - https://hdl.handle.net/2066/88622 AB - INTRODUCTION: Extravascular lung water index (EVLWI) can be measured at the bedside using the transpulmonary thermodilution technique (TPTD). The goal of this study was to compare EVLWI values with a chest x-ray score of pulmonary edema and markers of oxygenation in critically ill children. METHODS: This was a prospective observational study in a pediatric intensive care unit of a university hospital. We included 27 critically ill children with an indication for advanced invasive hemodynamic monitoring. No specific interventions for the purpose of the study were carried out. Measurements included EVLWI and other relevant hemodynamic variables. Blood gas analysis, ventilator parameters, chest x-ray and TPTD measurements were obtained within a three-hour time frame. Two radiologists assessed the chest x-ray and determined a score for pulmonary edema. RESULTS: A total of 103 measurements from 24 patients were eligible for final analysis. Mean age was two years (range: two months to eight years). Median cardiac index was 4.00 (range: 1.65 to 10.85) l/min/m2. Median EVLWI was 16 (range: 6 to 31) ml/kg. The weighted kappa between the chest x-ray scores of the two radiologists was 0.53. There was no significant correlation between EVLWI or chest x-ray score and the number of ventilator days, severity of illness or markers of oxygenation. There was no correlation between EVLWI and the chest x-ray score. EVLWI was significantly correlated with age and length (r2 of 0.47 and 0.67 respectively). CONCLUSIONS: The extravascular lung water index in critically ill children does not correlate with a chest x-ray score of pulmonary edema, nor with markers of oxygenation. TI - Extravascular lung water index measurement in critically ill children does not correlate with a chest x-ray score of pulmonary edema. EP - R105 SN - 1466-609X IS - iss. 3 SP - R105 JF - Critical Care VL - vol. 14 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/88622/88622.pdf?sequence=1 ER - TY - JOUR AU - Heunks, L.M.A. AU - Bruin, C.J. de AU - Hoeven, J.G. van der AU - Heijden, H.F.M. van der PY - 2010 UR - https://hdl.handle.net/2066/89809 AB - PURPOSE: Bronchoscopy is an indispensable tool for invasive pulmonary evaluation with high diagnostic yield and low incidence of major complications. However, hypoxemia increases the risk of complications, in particular after bronchoalveolar lavage. Non-invasive positive pressure ventilation may prevent hypoxemia associated with bronchoalveolar lavage. The purpose of this study is to present a modified total face mask to aid bronchoscopy during non-invasive positive pressure ventilation. METHODS: A commercially available full face mask was modified to allow introduction of the bronchoscope without interfering with the ventilator circuit. Bronchoscopy with bronchoalveolar lavage was performed in 12 hypoxemic non-ICU patients during non-invasive positive pressure ventilation in the ICU. Results : Patients had severely impaired oxygen uptake as indicated by PaO(2)/FiO(2) ratio 192 +/- 23 mmHg before bronchoscopy. Oxygenation improved after initiation of non-invasive positive pressure ventilation. In all patients the procedure could be completed without subsequent complications, although in one patient SpO(2) decreased until 86% during bronchoscopy. A microbiological diagnosis could be established in 8 of 12 patients with suspected for infection. CONCLUSIONS: Our modified face mask for non-invasive positive pressure ventilation is a valuable tool to aid diagnostic bronchoscopy in hypoxemic patients. TI - Non-invasive mechanical ventilation for diagnostic bronchoscopy using a new face mask: an observational feasibility study. EP - 147 SN - 0342-4642 IS - iss. 1 SP - 143 JF - Intensive Care Medicine VL - vol. 36 N1 - 1 januari 2010 DO - http://dx.doi.org/10.1007/s00134-009-1662-6 ER - TY - JOUR AU - Hofhuizen, C.M. AU - Lemson, J. AU - Hemelaar, A.E.A. AU - Settels, J.J. AU - Schraa, O. AU - Singh, S.K. AU - Hoeven, J.G. van der AU - Scheffer, G.J. PY - 2010 UR - https://hdl.handle.net/2066/88974 AB - BACKGROUND: Continuous non-invasive measurement of finger arterial pressure (FAP) is a reliable technology in adults. FAP is measured with an inflatable cuff around the finger and simultaneously converted to a reconstructed brachial artery pressure waveform (reBAP) by the Nexfin device. We assessed the adequacy of a prototype device (Nexfin-paediatric), designed for a paediatric population, for detecting rapid arterial pressure changes in children during cardiac surgery. METHODS: Thirteen anaesthetized children with a median age of 11 months (2 months-7 yr) undergoing congenital cardiac surgery were included in the study. reBAP and intra-arterial pressure (IAP) were recorded simultaneously during the surgical procedure. To assess the accuracy of reBAP in tracking arterial pressure changes, the four largest IAP variations within a 5 min time interval were identified from each procedure. These variations were compared offline with reBAP during a 10 s control period before and a 10 s period after an arterial pressure change had occurred. RESULTS: In 10 out of 13 children, a non-invasive arterial pressure recording could be obtained. Therefore, recordings from these 10 children were eligible for further analysis, resulting in 40 data points. The correlation coefficient between reBAP and IAP in tracking mean arterial pressure (MAP) changes was 0.98. reBAP followed changes in IAP with a mean bias for systolic, diastolic arterial pressure, and MAP of 0.0 mm Hg (sd 5.8), 0.1 (sd 2.8), and 0.19 (sd 2.7), respectively. CONCLUSIONS: The prototype device closely follows arterial pressure changes in children. However, in a considerable number of attempts, obtaining a signal was time-consuming or unsuccessful. This technique seems promising but requires further technical development. TI - Continuous non-invasive finger arterial pressure monitoring reflects intra-arterial pressure changes in children undergoing cardiac surgery. EP - 500 SN - 0007-0912 IS - iss. 4 SP - 493 JF - British Journal of Anaesthesia VL - vol. 105 N1 - 1 oktober 2010 DO - https://doi.org/10.1093/bja/aeq201 ER - TY - JOUR AU - Dorresteijn, M.J. AU - Visser, T. AU - Cox, L.A. AU - Bouw, M.P.W.J.M. AU - Pillay, J. AU - Koenderman, A.H. AU - Strengers, P.F.W. AU - Leenen, L.P.H. AU - Hoeven, J.G. van der AU - Koenderman, L. AU - Pickkers, P. PY - 2010 UR - https://hdl.handle.net/2066/88360 AB - OBJECTIVE: Besides its role in regulation of the complement and contact system, C1-esterase inhibitor has other immunomodulating effects that could prove beneficial in patients with acute inflammation such as during sepsis or after trauma. We examined the immunomodulating properties of C1-esterase inhibitor during human experimental endotoxemia, in which the innate immune system is activated in the absence of activation of the classic complement pathway. DESIGN: Double-blind placebo-controlled study. SETTING: Research intensive care unit of the Radboud University Nijmegen Medical Centre. SUBJECTS: Twenty healthy volunteers. INTERVENTIONS: Intravenous injection of 2 ng/kg Escherichia coli lipopolysaccharide. Thirty minutes thereafter (to prevent binding of lipopolysaccharide), C1-esterase inhibitor concentrate (100 U/kg, n = 10) or placebo (n = 10) was infused. MEASUREMENTS AND MAIN RESULTS: Pro- and anti-inflammatory mediators, markers of endothelial and complement activation, hemodynamics, body temperature, and symptoms were measured. C1-esterase inhibitor reduced the release of proinflammatory cytokines as well as C-reactive protein (peak levels of: interleukin-6 1521 +/- 209 vs. 932 +/- 174 pg/mL [p = .04], tumor necrosis factor-alpha 1213 +/- 187 vs. 827 +/- 167 pg/mL [p = .10], monocyte chemotactic protein-1 6161 +/- 1302 vs. 3373 +/- 228 pg/mL [p = .03], interleukin-1beta 34 +/- 5 vs. 23 +/- 2 pg/mL [p < .01], C-reactive protein 39 +/- 4 vs. 29 +/- 2 mg/L [p = .02]). In contrast, release of the anti-inflammatory cytokine interleukin-10 was increased by C1-esterase inhibitor (peak level 73 +/- 11 vs. 121 +/- 18 pg/mL, p = .02). The increase in interleukin-1 receptor antagonist tended to be smaller in the C1-esterase inhibitor group, but this effect did not reach statistical significance (p = .07). Markers for endothelial activation were increased after lipopolysaccharide infusion, but no significant differences between groups were observed. The lipopolysaccharide-induced changes in heart rate, blood pressure, body temperature, and symptoms (all p < .001 over time) were not influenced by C1-esterase inhibitor. Complement fragment C4 was not increased after lipopolysaccharide challenge. CONCLUSIONS: This study is the first to demonstrate that C1-esterase inhibitor exerts anti-inflammatory effects in the absence of classic complement activation in humans. TI - C1-esterase inhibitor attenuates the inflammatory response during human endotoxemia. EP - 2145 SN - 0090-3493 IS - iss. 11 SP - 2139 JF - Critical Care Medicine VL - vol. 38 N1 - 1 november 2010 DO - https://doi.org/10.1097/CCM.0b013e3181f17be4 ER - TY - JOUR AU - Haren, F.M.P. van AU - Pickkers, P. AU - Foudraine, N. AU - Heemskerk, S. AU - Sleigh, J. AU - Hoeven, J.G. van der PY - 2010 UR - https://hdl.handle.net/2066/88917 AB - OBJECTIVE: We prospectively studied the effect of methylene blue (MB) infusion on gastric mucosal metabolism perfusion ratio, assessed by gastric tonometry, and on mucosal cell damage, assessed by urinary levels of intestinal fatty acid binding protein, in septic shock patients. METHODS: Methylene blue (MB) infusion (1 mg/kg per hour) during 4 hours in 10 consecutive patients with a proven or suspected bacterial infection and with severe vasodilatory shock, defined as a mean arterial pressure 70 mm Hg or lower for at least 1 hour despite adequate volume resuscitation and norepinephrine infusion at a rate >or=0.2 microg/kg per minute. RESULTS: Methylene blue infusion did not significantly change the P(g-a)CO(2) gradient (P = .16). Post hoc analysis of the subgroup of patients with an elevated baseline P(g-a)CO(2) gradient, defined as >or=20 mm Hg, showed that the median P(g-a)CO(2) gradient (interquartile range [IQR]) decreased from 45 (41-56) mm Hg before infusion to 41 (28-52) at the end of the 4-hour infusion and decreased further to 32 (26-36) mm Hg 2 hours after cessation of MB infusion (P = .012). The median urinary intestinal fatty acid binding protein concentration at baseline was elevated (210 [79-437] pg/mumol creatinine) and did not change significantly after 24 hours (116 [53-601] pg/mumol creatinine, P = .15). The median mean arterial blood pressure (IQR) increased from 70 (69-71) mm Hg at baseline to 77 (67-83) mm Hg after 1 hour (P = .04), the norepinephrine dose did not change significantly. The median (IQR) cardiac index decreased from 4.4 (3.2-5.5) L min(-1) m(-2) at baseline to 3.6 (3.3-4.7) L min(-1) m(-2) after 2 h, returning back to baseline values after cessation of MB infusion P = .02). CONCLUSION: Although MB infusion in patients with septic shock and advanced multi-organ failure increases mean arterial blood pressure and decreases cardiac index, it does not compromise the gastric mucosal perfusion metabolism ratio as indicated by tonometry, and by the release of a mucosal cellular injury marker. TI - The effects of methylene blue infusion on gastric tonometry and intestinal fatty acid binding protein levels in septic shock patients. EP - 7 SN - 0883-9441 IS - iss. 2 SP - 358.e1 JF - Journal of Critical Care VL - vol. 25 N1 - 1 juni 2010 ER - TY - JOUR AU - Bisschops, L.L.A. AU - Hoedemaekers, C.W.E. AU - Simons, K.S. AU - Hoeven, J.G. van der PY - 2010 UR - https://hdl.handle.net/2066/89670 AB - OBJECTIVE: Although mild hypothermia improves outcome in patients after out-of-hospital cardiac arrest, the cardiodepressive effects of hypothermia may lead to secondary brain damage. This study was performed to assess the cerebral blood flow, cerebral oxygen extraction, and cerebrovascular reactivity to changes in partial pressure of carbon dioxide in the arterial blood in comatose patients after out-of-hospital cardiac arrest treated with mild hypothermia. DESIGN: Observational study. SETTING: Tertiary care university hospital. PATIENTS: Ten comatose patients after out-of-hospital cardiac arrest. INTERVENTIONS: All patients were cooled to 32-34 degrees C for 24 hrs. Cerebrovascular reactivity to changes in carbon dioxide in the arterial blood was measured after increasing or decreasing the minute ventilation by 20%. MEASUREMENTS AND MAIN RESULTS: Mean flow velocity in the middle cerebral artery and pulsatility index were measured by transcranial Doppler at 0, 3, 6, 9, 12, 18, 24, and 48 hrs after admission. Jugular bulb oxygenation was measured at the same intervals. Cerebrovascular reactivity to changes in carbon dioxide in the arterial blood was studied on admission to the intensive care unit and at 6, 12, 18, and 24 hrs by measurement of mean flow velocity in the middle cerebral artery and jugular bulb oxygenation. Mean flow velocity in the middle cerebral artery was low (30.3+/-9.5 cm/sec) on admission and remained relatively stable for the first 24 hrs. After rewarming, it increased to 67.5+/-33.0 cm/sec at 48 hrs after admission from 30.3+/-9.5 at admission (p=.009). Jugular bulb oxygenation at the start of the study was 66.2+/-8.5% and gradually increased to 82.9+/-4.9% at 48 hrs (p<.001). Regression analysis showed a significant correlation between changes in carbon dioxide in the arterial blood, mean flow velocity in the middle cerebral artery (p<.001) and jugular bulb oxygenation (p<.001). The mean percentage change in mean flow velocity in the middle cerebral artery was 3.6+/-2.9% per 1-mm Hg change of carbon dioxide in the arterial blood. CONCLUSIONS: The mean flow velocity in the middle cerebral artery, as a parameter of cerebral blood flow, was low during mild hypothermia, whereas cerebral oxygen extraction remained normal, suggesting decreased cerebral metabolic activity. We demonstrated that CO2 reactivity is preserved during hypothermia in these patients. TI - Preserved metabolic coupling and cerebrovascular reactivity during mild hypothermia after cardiac arrest. EP - 1547 SN - 0090-3493 IS - iss. 7 SP - 1542 JF - Critical Care Medicine VL - vol. 38 N1 - 1 juli 2010 DO - https://doi.org/10.1097/CCM.0b013e3181e2cc1e ER - TY - JOUR AU - Boogaard, M.H.W.A. van den AU - Peters, S.A. AU - Hoeven, J.G. van der AU - Dagnelie, P.C. AU - Leffers, P. AU - Pickkers, P. AU - Schoonhoven, L. PY - 2010 UR - https://hdl.handle.net/2066/87836 AB - INTRODUCTION: Predictive models, such as acute physiology and chronic health evaluation II (APACHE-II), are widely used in intensive care units (ICUs) to estimate mortality. Although the presence of delirium is associated with a higher mortality in ICU patients, delirium is not part of the APACHE-II model. The aim of the current study was to evaluate whether delirium, present within 24 hours after ICU admission, improves the predictive value of the APACHE-II score. METHODS: In a prospective cohort study 2116 adult patients admitted between February 2008 and February 2009 were screened for delirium with the confusion assessment method-ICU (CAM-ICU). Exclusion criteria were sustained coma and unable to understand Dutch. Logistic regression analysis was used to estimate the predicted probabilities in the model with and without delirium. Calibration plots and the Hosmer-Lemeshow test (HL-test) were used to assess calibration. The discriminatory power of the models was analyzed by the area under the receiver operating characteristics curve (AUC) and AUCs were compared using the Z-test. RESULTS: 1740 patients met the inclusion criteria, of which 332 (19%) were delirious at the time of ICU admission or within 24 hours after admission. Delirium was associated with in-hospital mortality in unadjusted models, odds ratio (OR): 3.22 (95% confidence interval [CI]: 2.23 - 4.66). The OR between the APACHE-II and in-hospital mortality was 1.15 (95% CI 1.12 - 1.19) per point. The predictive accuracy of the APACHE-II did not improve after adding delirium, both in the total group as well as in the subgroup without cardiac surgery patients. The AUC of the APACHE model without delirium was 0.77 (0.73 - 0.81) and 0.78 (0.74 - 0.82) when delirium was added to the model. The z-value was 0.92 indicating no improvement in discriminative power, and the HL-test and calibration plots indicated no improvement in calibration. CONCLUSIONS: Although delirium is a significant predictor of mortality in ICU patients, adding delirium as an additional variable to the APACHE-II model does not result in an improvement in its predictive estimates. TI - The impact of delirium on the prediction of in-hospital mortality in intensive care patients. EP - R146 SN - 1466-609X IS - iss. 4 SP - R146 JF - Critical Care VL - vol. 14 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/87836/87836.pdf?sequence=1 ER - TY - JOUR AU - Boode, W.P. de AU - Heijst, A.F.J. van AU - Hopman, J.C.W. AU - Tanke, R.B. AU - Hoeven, J.G. van der AU - Liem, K.D. PY - 2010 UR - https://hdl.handle.net/2066/88152 AB - OBJECTIVE: To assess agreement between a new method of cardiac output monitoring, using ultrasound dilution technology and ultrasound transit time-based measurement of pulmonary blood flow in a piglet model. DESIGN: Prospective, experimental juvenile animal study. SETTING: Animal laboratory of a university hospital. SUBJECTS: Nine random-bred piglets. INTERVENTIONS: After the animals received general anesthesia, we placed intravascular arterial and central venous catheters with the tip positioned in the abdominal aorta and the right atrium, respectively. The catheters were connected to the ultrasound dilution cardiac output monitor. An ultrasound transit time perivascular flow probe was positioned around the common pulmonary artery and served as the standard reference measurement. Cardiac output was manipulated during the experiment by creating hemorrhagic hypotension. Ultrasound dilution cardiac output was measured intermittently with injection volumes of 0.5 mL/kg and 1.0 mL/kg of isotonic saline at body temperature. MEASUREMENTS AND MAIN RESULTS: Ultrasound dilution cardiac output (Q) measurement was compared with pulmonary blood flow (Q). Bias, defined as Q minus Q, was calculated for each measurement. Mean bias with standard deviation was calculated for measurements with volumes of injected saline, 0.5 mL/kg and 1.0 mL/kg, and compared using the Mann-Whitney U test. Mean bias (sd) between Q and Q was 0.040 (0.132) and 0.058 (0.136) L/min for measurement with 0.5 mL/kg and 1.0 mL/kg of isotonic saline, respectively (no statistically significant difference). CONCLUSIONS: Ultrasound dilution cardiac output measurement is reliable in piglets with the use of a small volume of a nontoxic indicator (isotonic saline). TI - Cardiac output measurement using an ultrasound dilution method: a validation study in ventilated piglets. EP - 108 SN - 1529-7535 IS - iss. 1 SP - 103 JF - Pediatric Critical Care Medicine VL - vol. 11 N1 - 1 januari 2010 DO - https://doi.org/10.1097/PCC.0b013e3181b064ea ER - TY - JOUR AU - Boode, W.P. de AU - Hopman, J.C.W. AU - Wijnen, M.H.W.A. AU - Tanke, R.B. AU - Hoeven, J.G. van der AU - Liem, K.D. PY - 2010 UR - https://hdl.handle.net/2066/88160 AB - BACKGROUND: It remains a great challenge to measure systemic blood flow in critically ill newborns. In a former study we validated the modified carbon dioxide Fick (mCO(2)F) method for measurement of cardiac output in a newborn lamb model. In this new study we studied the influence of a left-to-right shunt on the accuracy of the mCO(2)F method. OBJECTIVE: To analyze the influence of a left-to-right shunt on the agreement between cardiac output measurement with the mCO(2)F method and ultrasonic transit time pulmonary blood flow in a lamb model. METHODS: The study was approved by the Ethical Committee on Animal Research of the Radboud University Nijmegen and performed in 8 random-bred lambs. A Gore-Tex shunt was placed between the left pulmonary artery and the descending aorta. This aortopulmonary shunt was intermittently opened and closed, while cardiac output was manipulated by creating hemorrhagic hypotension. Cardiac output measurement with the mCO(2)F method (Q(mCO2F)) was compared with pulmonary blood flow obtained by a transit time ultrasonic flow probe positioned around the common pulmonary artery (Q(APC)). RESULTS: Bias, defined as Q(mCO2F) - Q(APC), was calculated for each measurement. With an open shunt there was a significant left-to-right shunt (mean Qp/Qs ratio 2.26; range 1.56-3.69). Mean bias (SD) was -12.3 (50.4) ml x kg(-1) x min(-1) and -12.3 (42.7) ml x kg(-1) x min(-1) for measurements with a closed and open shunt, respectively (no statistical significant difference). CONCLUSIONS: Cardiac output measurement with the mCO(2)F method is reliable and easily applicable in ventilated newborn lambs, also in the presence of a significant left-to-right shunt. TI - Cardiac output measurement in ventilated lambs with a significant left-to-right shunt using the modified carbon dioxide fick method. EP - 131 SN - 1661-7800 IS - iss. 2 SP - 124 JF - Neonatology VL - vol. 97 DO - https://doi.org/10.1159/000237223 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/88160/88160.pdf?sequence=1 ER - TY - JOUR AU - Boode, W.P. de AU - Heijst, A.F.J. van AU - Hopman, J.C.W. AU - Tanke, R.B. AU - Hoeven, J.G. van der AU - Liem, K.D. PY - 2010 UR - https://hdl.handle.net/2066/88270 AB - OBJECTIVE: Analysis of cerebral and systemic hemodynamic consequences of ultrasound dilution cardiac output measurements. DESIGN: : Prospective, experimental piglet study. SETTING: Animal laboratory. SUBJECTS: Nine piglets. INTERVENTIONS: Ultrasound dilution cardiac output measurements were performed in ventilated, anesthetized piglets. Interventions that are required for ultrasound dilution cardiac output measurement were evaluated for its effect on cerebral and systemic circulation and oxygenation. MEASUREMENTS AND MAIN RESULTS: DeltacHbD and DeltactHb, representing changes in cerebral blood flow and cerebral blood volume, respectively, were measured with near infrared spectrophotometry. Pulmonary artery (Q) and left carotid artery (Q) blood flow were assessed with transit time flow probes. Starting and/or stopping blood flowing through the arteriovenous loop did not cause relevant hemodynamic changes. Fast injection of isotonic saline caused a biphasic change in DeltacHbD and DeltactHb. After injection of 0.5 mL/kg, the mean (sd) increase in DeltacHbD and DeltactHb was 0.175 (0.213) micromol/L and 0.122 (0.148) micromol/L, respectively, with a subsequent mean decrease of -0.191 (0.299) micromol/L and -0.312 (0.266) micromol/L. Injection of 1.0 mL/kg caused a mean increase in DeltacHbD and DeltactHb of 0.237 (0.203) micromol/L and 0.179 (0.162) followed by a mean decrease of -0.334 (0.407) micromol/L and -0.523 (0.335) micromol/L, respectively. Q and Q changed shortly with a mean increase of 5.9 (3.0) mL/kg/min and 0.23 (0.10) mL/kg/min after injection of 0.5 mL/kg and with 12.0 (4.2) mL/kg/min and 0.44 (0.18) mL/kg/min after injection of 1.0 mL/kg, respectively. The observed changes were more profound after an injection volume of 1.0 mL/kg compared with 0.5 mL/kg for DeltacHbD (p = .06), DeltactHb (p = .09), Q, and Q (p < .01). No relevant changes in mean arterial blood pressure or heart rate were detected in response to the indicator injection. CONCLUSIONS: Cardiac output measurement by ultrasound dilution does not cause clinically relevant changes in cerebral and systemic circulation and oxygenation in a piglet model. TI - Application of ultrasound dilution technology for cardiac output measurement: Cerebral and systemic hemodynamic consequences in a juvenile animal model. EP - 623 SN - 1529-7535 IS - iss. 5 SP - 616 JF - Pediatric Critical Care Medicine VL - vol. 11 N1 - 1 september 2010 DO - https://doi.org/10.1097/PCC.0b013e3181c517b3 ER - TY - JOUR AU - Besselink-Lobanova, A. AU - Maandag, N.J. AU - Voermans, N.C. AU - Heijden, E. van der AU - Hoeven, J.G. van der AU - Heunks, L.M.A. PY - 2010 UR - https://hdl.handle.net/2066/87644 TI - Trachea rupture in tenascin-X-deficient type Ehlers-Danlos syndrome. EP - 749 SN - 0003-3022 IS - iss. 3 SP - 746 JF - Anesthesiology VL - vol. 113 N1 - 1 september 2010 DO - https://doi.org/10.1097/ALN.0b013e3181e19c0f ER - TY - JOUR AU - Lansdorp, B. AU - Brule, J.M. van den AU - Hoeven, J.G. van der AU - Pickkers, P. PY - 2010 UR - https://hdl.handle.net/2066/87802 TI - The influence of pacing on the pre-ejection period. EP - 4 SN - 0001-5172 IS - iss. 1 SP - 123; author reply 123 JF - Acta Anaesthesiologica Scandinavica VL - vol. 54 N1 - 1 januari 2010 ER - TY - JOUR AU - Fick, I.W. AU - Tijdink, M.M. AU - Halbertsma, F.J. AU - Hoeven, J.G. van der AU - Pickkers, P. PY - 2010 UR - https://hdl.handle.net/2066/89384 AB - PURPOSE: The aim of the study is to determine which factors are associated with the deterioration of Pao(2)/fraction of inspired oxygen (Fio(2)) ratio in patients with normal oxygenation at admission and ventilated according to a lung protective ventilation strategy. MATERIALS AND METHODS: Retrospective cohort study of ventilated (>/=3 days) intensive care unit patients with an admission Pao(2)/Fio(2) ratio of 300 mm Hg or higher (n = 105). Patients who developed lung injury (Pao(2)/Fio(2) ratio, <300 mm Hg) on day 7 (n = 37) were compared to those who did not (n = 68), with regard to ventilator settings, gas exchange variables, and lung injury risk factors. RESULTS: Mean +/- SD of administered tidal volume was 7.9 +/- 1.3 mL/kg. Patients who developed lung injury were older (P = .019), had lower Pao(2) (P = .009), higher Paco(2) (P = .045), and lower Pao(2)/Fio(2) ratio (P = .002) at admission. Postoperative state (Hazard risk [HR], 5.1) and controlled ventilation mode (HR, 4.3) were identified as independent risk factors. Lung injury-free time was shorter in patients with low initial Pao(2)/Fio(2) ratio (odds ratio, 1.7; P = .039). This effect was not only caused by the baseline difference, as the decrease in Pao(2)/Fio(2) ratio was more pronounced in patients who developed lung injury compared to those who did not (P = .008). CONCLUSIONS: Lung injury exacerbates during mechanical ventilation. In patients treated with a mean tidal volume of 7.9 mL/kg, controlled ventilation is a major risk factor. TI - Risk factors for the deterioration of oxygenation ratio in ventilated intensive care unit patients: a retrospective cohort study. EP - 9 SN - 0883-9441 IS - iss. 1 SP - 3 JF - Journal of Critical Care VL - vol. 25 N1 - 1 maart 2010 DO - https://doi.org/10.1016/j.jcrc.2009.04.007 ER - TY - JOUR AU - Halbertsma, F.J. AU - Vaneker, M. AU - Pickkers, P. AU - Neeleman, C. AU - Scheffer, G.J. AU - Hoeven, J.G. van der PY - 2010 UR - https://hdl.handle.net/2066/87344 AB - INTRODUCTION: Recruitment maneuvers (RMs) are advocated to prevent pulmonary collapse during low tidal volume ventilation and improve oxygenation. However, convincing clinical evidence for improved outcome is lacking. Recent experimental studies demonstrate that RMs translocate pulmonary inflammatory mediators into the circulation. To determine whether a single RM in ventilated children affects pulmonary and systemic cytokine levels, we performed a prospective intervention study. METHODS: Cardiorespiratory stable ventilated patients (0.5-45 months, n = 7) with acute lung injury were subjected to an RM determining opening and closing pressures (peak inspiratory pressure < or =45 cmH(2)O, positive end expiratory pressure (PEEP) < or =30 cmH(2)O). Before and after RM, cardiorespiratory parameters and ventilator settings were recorded, blood gas analysis performed, and bronchoalveolar lavage fluid and plasma TNF-alpha, IL-1beta, IL-6, IL-8, and IL-10 concentrations were determined. RESULTS: Fifteen minutes after the RM, an increase was observed in plasma tumor necrosis factor-alpha (400% +/- 390% of baseline, P = .04), IL-6 (120% +/- 35%, P = .08), and IL-1beta (520% +/- 535%, P = .04), which decreased at T = 60 minutes, hence indicative of translocation. Recruitment maneuver did not change the plasma levels of the anti-inflammatory IL-10 (105% +/- 12%, P = .5). Apart from a nonsignificant increase of IL-8 after 360 minutes (415% +/- 590%,P = .1), bronchoalveolar cytokine levels were not influenced by the RM. No increase in oxygenation or improvement of lung kinetics was observed. CONCLUSIONS: A single RM can translocate pro-inflammatory cytokines from the alveolar space into the systemic circulation in ventilated critically ill children. TI - A single recruitment maneuver in ventilated critically ill children can translocate pulmonary cytokines into the circulation. EP - 15 SN - 0883-9441 IS - iss. 1 SP - 10 JF - Journal of Critical Care VL - vol. 25 N1 - 1 maart 2010 DO - https://doi.org/10.1016/j.jcrc.2009.01.006 ER - TY - JOUR AU - Neeleman, C. AU - Verhagen, M. AU - Deuren, M. van AU - Willemsen, M.A.A.P. AU - Hoeven, H. van der AU - Yntema, J.L. AU - Weemaes, C.M.R. AU - Heijdra, Y.F. PY - 2010 UR - https://hdl.handle.net/2066/89555 TI - Pulmonary function tests in patients with ataxia-telangiectasia: obstructive or restrictive lung dysfunction? EP - 4; author reply 1045 SN - 8755-6863 IS - iss. 10 SP - 1043 JF - Pediatric Pulmonology VL - vol. 45 N1 - 1 oktober 2010 DO - https://doi.org/10.1002/ppul.21276 ER - TY - JOUR AU - Boogaard, M.H.W.A. van den AU - Ramakers, B.P.C. AU - Alfen, N. van AU - Werf, S.P. van der AU - Fick, W.F. AU - Hoedemaekers, C.W.E. AU - Verbeek, M.M. AU - Schoonhoven, L. AU - Hoeven, J.G. van der AU - Pickkers, P. PY - 2010 UR - https://hdl.handle.net/2066/88680 AB - INTRODUCTION: Effects of systemic inflammation on cerebral function are not clear, as both inflammation-induced encephalopathy as well as stress-hormone mediated alertness have been described. METHODS: Experimental endotoxemia (2 ng/kg Escherichia coli lipopolysaccharide [LPS]) was induced in 15 subjects, whereas 10 served as controls. Cytokines (TNF-alpha, IL-6, IL1-RA and IL-10), cortisol, brain specific proteins (BSP), electroencephalography (EEG) and cognitive function tests (CFTs) were determined. RESULTS: Following LPS infusion, circulating pro- and anti-inflammatory cytokines, and cortisol increased (P < 0.0001). BSP changes stayed within the normal range, in which neuron specific enolase (NSE) and S100-beta changed significantly. Except in one subject with a mild encephalopathic episode, without cognitive dysfunction, endotoxemia induced no clinically relevant EEG changes. Quantitative EEG analysis showed a higher state of alertness detected by changes in the central region, and peak frequency in the occipital region. Improved CFTs during endotoxemia was found to be due to a practice effect as CFTs improved to the same extent in the reference group. Cortisol significantly correlated with a higher state of alertness detected on the EEG. Increased IL-10 and the decreased NSE both correlated with improvement of working memory and with psychomotor speed capacity. No other significant correlations between cytokines, cortisol, EEG, CFT and BSP were found. CONCLUSIONS: Short-term systemic inflammation does not provoke or explain the occurrence of septic encephalopathy, but primarily results in an inflammation-mediated increase in cortisol and alertness. TRIAL REGISTRATION: NCT00513110. TI - Endotoxemia-induced inflammation and the effect on the human brain. EP - R81 SN - 1466-609X IS - iss. 3 SP - R81 JF - Critical Care VL - vol. 14 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/88680/88680.pdf?sequence=1 ER - TY - JOUR AU - Hoedemaekers, C.W.E. AU - Deuren, M. van AU - Sprong, T. AU - Pickkers, P. AU - Mollnes, T.E. AU - Klasen, I.S. AU - Hoeven, J.G. van der PY - 2010 UR - https://hdl.handle.net/2066/88964 AB - BACKGROUND: The complement system is a key component in the inflammatory response after coronary artery bypass grafting (CABG). The routes of complement activation and deactivation after cardiac surgery are not clear. The aim of this study was to analyze routes of complement activation after uncomplicated CABG. METHODS: Complement components and activation products were measured in 20 nondiabetic adult patients undergoing elective CABG at several times postoperatively starting at admission to the intensive care unit. RESULTS: Complement activation after uncomplicated CABG showed a biphasic pattern. In the first 8 hours after admission to the intensive care unit, complement activation was initiated by the classical lectin pathway and augmented by the alternative pathway. Ultimately, this resulted in terminal pathway activation and formation of terminal complement complex. In the second phase, starting at 8 hours after the operation, complement was still activated by the classical lectin pathway, but there was no augmentation by the alternative pathway and no terminal complement complex formation. This implies that during this second stage, inhibitory mechanisms beyond C3b are engaged. CONCLUSIONS: Complement activation after cardiac surgery is regulated in a complex biphasic way, with additional inhibitory mechanisms engaged from 8 hours postoperatively onward. TI - The complement system is activated in a biphasic pattern after coronary artery bypass grafting. EP - 716 SN - 0003-4975 IS - iss. 3 SP - 710 JF - Annals of Thoracic Surgery VL - vol. 89 N1 - 1 maart 2010 DO - https://doi.org/10.1016/j.athoracsur.2009.11.049 ER - TY - JOUR AU - Simons, K.S. AU - Pickkers, P. AU - Bleeker-Rovers, C.P. AU - Oyen, W.J.G. AU - Hoeven, J.G. van der PY - 2010 UR - https://hdl.handle.net/2066/88623 AB - PURPOSE: To assess the value of F-18-fluorodeoxyglucose positron emission tomography (FDG-PET) combined with CT in critically ill patients suspected of having an infection. METHODS: FDG-PET CT scans requested for evaluation of a suspected infection or inflammatory process in critically ill, mechanically ventilated patients were analyzed (blinded for the final clinical diagnosis) and compared with clinical follow-up. RESULTS: Thirty-five FDG-PET/CT scans performed in 33 ICU patients (28 adults and 5 children), median age 58 years (range 1 month-72 years), were analyzed. Twenty-one FDG-PET/CT scans were true positive. Three FDG-PET/CT scans were considered false positive, in one case leading to additional diagnostic procedures (specificity 79%). Additionally, 11 true negatives were found (sensitivity 100%), leading to an overall accuracy of 91%. CONCLUSIONS: FDG-PET/CT scanning is of additional value in the evaluation of suspected infection in critically ill patients in whom conventional diagnostics did not lead to a diagnosis. Apart from the high accuracy, in this study it appeared that, in addition to conventional diagnostic techniques that were routinely performed, a normal FDG-PET/CT ruled out important infections requiring prolonged antibiotic therapy or drainage. Since sensitivity is lower in highly metabolic active tissues (e.g., endocarditis, meningitis), the FDG-PET/CT scan is not suited to detect infections in these tissues. TI - F-18-fluorodeoxyglucose positron emission tomography combined with CT in critically ill patients with suspected infection. EP - 511 SN - 0342-4642 IS - iss. 3 SP - 504 JF - Intensive Care Medicine VL - vol. 36 N1 - 1 maart 2010 DO - https://doi.org/10.1007/s00134-009-1697-8 ER - TY - JOUR AU - Draisma, A. AU - Pickkers, P. AU - Bouw, M.P.W.J.M. AU - Hoeven, J.G. van der PY - 2009 UR - https://hdl.handle.net/2066/80340 AB - OBJECTIVE: Endotoxin (lipopolysaccharide [LPS]) tolerance is characterized by a reduced responsiveness to a subsequent LPS challenge. In animal and human in vitro experiments, LPS tolerance is associated with an attenuated response of proinflammatory cytokines and an enhanced production of anti-inflammatory cytokines. It is unclear if this mechanism accounts for the development of LPS tolerance in humans in vivo. DESIGN: Clinical experimental study. SETTING: Intensive care research unit. PATIENTS: Fourteen healthy male volunteers. INTERVENTIONS: Intravenous injections of 2 ng/kg/day Escherichia coli LPS on 5 consecutive days. MEASUREMENTS AND MAIN RESULTS: Symptom scores, vital signs, leukocyte (elastase) and endothelial cell activation (von Willebrand factor [vWF]), and circulating cytokine levels. On day 1, the symptom score increased to 6.1 +/- 3.1, temperature to 37.8 +/- 0.4 degrees C, heart rate to 103 +/- 6/min (p < 0.0001 for all parameters) compared with 0.3 +/- 0.6, 36.2 +/- 0.5 degrees C, 79 +/- 4/min on day 5, respectively (p < 0.0001 between days 1 and 5). On day 1, elastase, vWF, and all cytokine levels increased significantly (p < 0.001 for all, except transforming growth factor (TGF)-beta, p = 0.02), whereas on day 5, this increase was significantly attenuated (p < 0.001) for elastase (61% +/- 6%), vWF (68% +/- 5%), tumor necrosis factor (97% +/- 3%), interleukin (IL)-6 (88% +/- 8%), IL-10 (87% +/- 7%), and IL-1ra (93% +/- 9% p = 0.018) but not for TGF-beta (5% +/- 22% p = 0.22). The tumor necrosis factor-alpha/IL-10 ratio showed an initial proinflammatory phase, followed by an anti-inflammatory phase on the first day. The proinflammatory phase was attenuated with 95% +/- 2%, whereas the reduction of the anti-inflammatory phase, without TGF-beta levels, was 99% +/- 1% on day 5 (p = 0.13 between phases). CONCLUSIONS: Endotoxin tolerance developed during five consecutive LPS administrations as demonstrated by the attenuated release of proinflammatory cytokines on the fifth day and was associated with less leukocyte and endothelial activation. In contrast to animal and human in vitro data, the attenuated response was not limited to the proinflammatory response, as a similar reduction in the anti-inflammatory cytokines was observed, with the exception of TGF-beta. TI - Development of endotoxin tolerance in humans in vivo. EP - 1267 SN - 0090-3493 IS - iss. 4 SP - 1261 JF - Critical Care Medicine VL - vol. 37 DO - http://dx.doi.org/10.1097/CCM.0b013e31819c3c67 ER - TY - JOUR AU - Kox, M. AU - Velzen, J.F. van AU - Pompe, J.C. AU - Hoedemaekers, C.W.E. AU - Hoeven, J.G. van der AU - Pickkers, P. PY - 2009 UR - https://hdl.handle.net/2066/80663 AB - The vagus nerve can limit inflammation via the alpha7 nicotinic acetylcholine receptor (alpha7nAChR). Selective pharmacological stimulation of the alpha7nAChR may have therapeutic potential for the treatment of inflammatory conditions. We determined the anti-inflammatory potential of GTS-21, an alpha7nAChR-selective partial agonist, on primary human leukocytes and compared it with nicotine, the nAChR agonist widely used for research into the anti-inflammatory effects of alpha7nAChR stimulation. Furthermore, we investigated whether the effects of both nicotinic agonists were restricted to specific Toll-like receptors (TLRs) stimulated and explored the mechanism behind the anti-inflammatory effect of GTS-21. GTS-21 and nicotine inhibited the release of pro-inflammatory cytokines in peripheral blood mononuclear cells (PBMCs), monocytes and whole blood independent of the TLR stimulated, with higher potency/efficacy for GTS-21 compared to nicotine. The anti-inflammatory cytokine IL-10 was relatively unaffected by both nicotinic agonists. The effects of GTS-21 and nicotine could not be reversed by nAChR antagonists, while the JAK2 inhibitor AG490 abolished the anti-inflammatory effects. GTS-21 downregulated monocyte cell-surface expression of TLR2, TLR4 and CD14. qPCR analysis demonstrated that the anti-inflammatory effect of GTS-21 is mediated at the transcriptional level and involves JAK2-STAT3 activation. In conclusion, GTS-21 has a profound anti-inflammatory effect in human leukocytes and that GTS-21 is more potent/efficacious than nicotine. The absence of a blocking effect of nAChR antagonists in human leukocytes might indicate different pharmacological properties of the alpha7nAChR in human leukocytes compared to other cell types. GTS-21 may be promising from a therapeutic perspective because of its suitability for human use. TI - GTS-21 inhibits pro-inflammatory cytokine release independent of the Toll-like receptor stimulated via a transcriptional mechanism involving JAK2 activation. EP - 872 SN - 0006-2952 IS - iss. 7 SP - 863 JF - Biochemical Pharmacology VL - vol. 78 DO - http://dx.doi.org/10.1016/j.bcp.2009.06.096 ER - TY - JOUR AU - Lemson, J. AU - Backx, A.P.C.M. AU - Oort, A.M. van AU - Bouw, M.P.W.J.M. AU - Hoeven, J.G. van der PY - 2009 UR - https://hdl.handle.net/2066/80712 AB - OBJECTIVE: Measurement of extravascular lung water (EVLW) may be useful in the treatment of critically ill children and can be performed at the bedside using the transpulmonary thermodilution technique (TPTD). There are currently no data to verify the accuracy of these measurements in (small) children. We compared the results of TPTD measurement with the clinical gold standard transpulmonary double indicator dilution (TPDD) measurement in young children. DESIGN: Prospective clinical study in children. SETTING: Catheterization laboratory of a university hospital. PATIENTS AND METHODS: Twelve children (<2 yrs or <12 kg) under general anesthesia. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Measurements were performed using injections of ice-cold indicator (saline or dye) through a central venous catheter. Mean cardiac index was 3.91 L/min/m, mean intrathoracic blood volume index (ITBVITPDD) was 614.9 mL/m, and mean extravascular lung water index (EVLWITPDD) was 11.7 mL/kg. The correlation coefficient between EVLWITPDD and EVLWITPTD is 0.96 (95% confidence interval: 0.87-0.99; p < 0.0001). Bland-Altman analysis for EVLW measurements showed a mean bias of 2.34 mL/kg (18.13%) and limits of agreement +/-2.97 mL/kg (19.78%). The difference between measurements via the right atrium compared with the femoral vein was 2.8% for cardiac output, 8.2% for global end-diastolic volume, and 0.1% for EVLW. CONCLUSION: Clinical measurement of EVLW in young children can be performed using the TPTD with the injection catheter inserted in the femoral vein. Further studies are needed to clarify the clinical value of these measurements. TI - Extravascular lung water measurement using transpulmonary thermodilution in children. EP - 233 SN - 1529-7535 IS - iss. 2 SP - 227 JF - Pediatric Critical Care Medicine VL - vol. 10 DO - http://dx.doi.org/10.1097/PCC.0b013e3181937227 ER - TY - JOUR AU - Pompe, J.C. AU - Kox, M. AU - Hoedemaekers, C.W.E. AU - Hoeven, J.G. van der AU - Pickkers, P. PY - 2009 UR - https://hdl.handle.net/2066/81215 TI - Nitric oxide inhalation and glucocorticoids as combined treatment in human experimental endotoxemia: It takes not always two to tango. EP - 7 SN - 0090-3493 IS - iss. 9 SP - 2676; author reply 2676 JF - Critical Care Medicine VL - vol. 37 ER - TY - JOUR AU - Draisma, A. AU - Goeij, M. de AU - Wouters, C.W. AU - Riksen, N.P. AU - Oyen, W.J.G. AU - Rongen, G.A.P.J.M. AU - Boerman, O.C. AU - Deuren, M. van AU - Hoeven, J.G. van der AU - Pickkers, P. PY - 2009 UR - https://hdl.handle.net/2066/80768 AB - Animal studies have shown that previous exposure to lipopolysaccharide (LPS) can limit ischemia-reperfusion injury. We tested whether pretreatment with LPS also protects against ischemia-reperfusion injury in humans in vivo. Fourteen volunteers received bolus injections of incremental dosages of LPS on 5 consecutive days (LPS group). Before the first and 1 day after the last LPS administration, the forearm circulation of the non-dominant arm was occluded for 10 min, with concomitant intermittent handgripping to induce transient ischemia. After reperfusion, 0.1 mg of ( 99m)Tc-labeled annexin A5 (400 MBq) was injected intravenously to detect phosphatidylserine expression as an early marker of ischemia-reperfusion injury. Similarly, the control group (n = 10) underwent the ischemic exercise twice, but without pretreatment with LPS. Annexin A5 targeting was expressed as the percentage difference in radioactivity in the thenar muscle between both hands. Endotoxin tolerance developed during 5 consecutive days of LPS administration. Annexin A5 targeting was 12.1 +/- 2.2% and 10.4 +/- 2.1% before LPS treatment at 1 h and 4 h after reperfusion, compared to 12.2 +/- 2.4% and 8.9 +/- 2.1% at 1 h and 4 h after reperfusion on day 5 (P = 1.0 and 0.6, respectively). Also, no significant changes in annexin A5 targeting were found in the control group. So, in this model, LPS-tolerance does not protect against ischemia-reperfusion injury in humans in vivo. TI - Endotoxin tolerance does not limit mild ischemia-reperfusion injury in humans in vivo. EP - 367 SN - 1753-4259 IS - iss. 6 SP - 360 JF - Innate Immunity VL - vol. 15 DO - http://dx.doi.org/10.1177/1753425909105548 ER - TY - JOUR AU - Hilkens, M. AU - Pickkers, P. AU - Peters, W.H.M. AU - Hoeven, J.G. van der PY - 2009 UR - https://hdl.handle.net/2066/81242 AB - Hepatocellular toxicity is a putative side-effect of amiodarone. The hepatic detoxification enzyme glutathione S-transferase-A1-1 (GSTA1-1) is a sensitive indicator of hepatocellular damage. We investigated the occurrence of subclinical liver injury, as measured by plasma GSTA1-1 in intensive care unit patients with atrial fibrillation receiving amiodarone. Sixteen haemodynamically stable intensive care unit patients with atrial fibrillation were treated with amiodarone intravenously. Patients were given a loading dose of 150 mg followed by another 150 mg followed by a continuous infusion of 1200 mg/hour if atrial fibrillation persisted. Blood samples for GSTA1-1 (measured by an enzyme-linked immunosorbent assay) were taken at zero, one, three, six, 12 and 24 hours, transaminases and bilirubin at zero, six, 12 and 24 hours. Blood pressure and heart rate were continuously monitored. Effects were analysed for time-dependent changes (one-way analysis of variance for repeated measures). Blood pressure increased from 125 +/- 8/60 +/- 3 mmHg at t = 0 to 144 +/- 9/66 +/- 4 mmHg at t = 24 hours (P < 0.05), heart rate decreased from atrial fibrillation 124 +/- 5 to sinus rhythm 86 +/- 6 beats per minute (P < 0.05). There was no significant elevation of GSTA1-1, transaminases or bilirubin during the observation period of 24 hours. Amiodarone does not cause elevation of GSTA1-1 as a marker of subclinical liver injury in haemodynamically stable intensive care unit patients with atrial fibrillation. TI - No elevation of glutathione S-transferase-a1-1 by amiodarone loading in intensive care unit patients with atrial fibrillation. EP - 285 SN - 0310-057X IS - iss. 2 SP - 281 JF - Anaesthesia and Intensive Care VL - vol. 37 ER - TY - JOUR AU - Heemskerk, S. AU - Masereeuw, R. AU - Moesker, O. AU - Bouw, M.P.W.J.M. AU - Hoeven, J.G. van der AU - Peters, W.H.M. AU - Russel, F.G.M. AU - Pickkers, P. PY - 2009 UR - https://hdl.handle.net/2066/75218 AB - OBJECTIVE: Alkaline phosphatase (AP) attenuates inflammatory responses by lipopolysaccharide detoxification and may prevent organ damage during sepsis. To investigate the effect of AP in patients with severe sepsis or septic shock on acute kidney injury. DESIGN AND SETTING: A multicenter double-blind, randomized, placebo-controlled phase IIa study (2:1 ratio). PATIENTS: Thirty-six intensive care unit patients (20 men/16 women, mean age 58 +/- 3 years) with a proven or suspected Gram-negative bacterial infection, >or=2 systemic inflammatory response syndrome criteria (<24 hours), and <12 hours end-organ dysfunction onset were included. INTERVENTION: An initial bolus intravenous injection (67.5 U/kg body weight) over 10 minutes of AP or placebo, followed by continuous infusion (132.5 U/kg) over the following 23 hours and 50 minutes. MEASUREMENTS AND MAIN RESULTS: Median plasma creatinine levels declined significantly from 91 (73-138) to 70 (60-92) micromol/L only after AP treatment. Pathophysiology of nitric oxide (NO) production and subsequent renal damage were assessed in a subgroup of 15 patients. A 42-fold induction (vs. healthy subjects) in renal inducible NO synthase expression was reduced by 80% +/- 5% after AP treatment. In AP-treated patients, the increase in cumulative urinary NO metabolite excretion was attenuated, whereas the opposite occurred after placebo. Reduced excretion of NO metabolites correlated with the proximal tubule injury marker glutathione S-transferase A1-1 in urine, which decreased by 70 (50-80)% in AP-treated patients compared with an increase by 200 (45-525)% in placebo-treated patients. CONCLUSIONS: In severe sepsis and septic shock, infusion of AP inhibits the upregulation of renal inducible NO synthase, leading to subsequent reduced NO metabolite production, and attenuated tubular enzymuria. This mechanism may account for the observed improvement in renal function. TI - Alkaline phosphatase treatment improves renal function in severe sepsis or septic shock patients. EP - 23, e1 SN - 0090-3493 IS - iss. 2 SP - 417 JF - Critical Care Medicine VL - vol. 37 DO - http://dx.doi.org/10.1097/CCM.0b013e31819598af ER - TY - JOUR AU - Heijden, M. van der AU - Pickkers, P. AU - Nieuw Amerongen, G.P. van AU - Hinsbergh, V.W.H. van AU - Bouw, M.P.W.J.M. AU - Hoeven, J.G. van der AU - Groeneveld, A.B. PY - 2009 UR - https://hdl.handle.net/2066/79899 AB - PURPOSE: To investigate whether angiopoietin-2, von Willebrand factor (VWF) and angiopoietin-1 relate to surrogate indicators of vascular permeability, pulmonary dysfunction and intensive care unit (ICU) mortality throughout the course of septic shock. METHODS: In 50 consecutive mechanically ventilated septic shock patients, plasma angiopoietin-2, VWF and angiopoietin-1 levels and fluid balance, partial pressure of oxygen/inspiratory oxygen fraction and the oxygenation index as indicators of vascular permeability and pulmonary dysfunction, respectively, were measured until day 28. RESULTS: Angiopoietin-2 positively related to the fluid balance and pulmonary dysfunction, was higher in non-survivors than in survivors and independently predicted non-survival throughout the course of septic shock. VWF inversely related to the fluid balance and pulmonary dysfunction throughout the course of septic shock, was comparable between survivors and non-survivors and predicted non-survival on day 0 only. Angiopoietin-1 positively related to pulmonary dysfunction throughout the course, but did not differ between survivors and non-survivors. CONCLUSIONS: In contrast to VWF, plasma angiopoietin-2 positively relates to fluid balance, pulmonary dysfunction and mortality throughout the course of septic shock, in line with a suggested mediator role of the protein. TI - Circulating angiopoietin-2 levels in the course of septic shock: relation with fluid balance, pulmonary dysfunction and mortality. EP - 1574 SN - 0342-4642 IS - iss. 9 SP - 1567 JF - Intensive Care Medicine VL - vol. 35 DO - https://doi.org/10.1007/s00134-009-1560-y ER - TY - JOUR AU - Lemson, J. AU - Hofhuizen, C.M. AU - Schraa, O. AU - Settels, J.J. AU - Scheffer, G.J. AU - Hoeven, J.G. van der PY - 2009 UR - https://hdl.handle.net/2066/81204 AB - INTRODUCTION: Continuous noninvasive arterial blood pressure can be measured in finger arteries using an inflatable finger cuff (FINAP) with a special device and has proven to be feasible and reliable in adults. We studied prototype pediatric finger cuffs and pediatric software to compare this blood pressure measurement with intraarterially measured blood pressure (IAP) in critically ill children. METHODS: We included sedated and mechanically ventilated children admitted to our pediatric intensive care unit. We performed simultaneous arterial blood pressure measurements during a relatively stable hemodynamic period and compared FINAP, IAP, and the noninvasive blood pressure oscillometric technique. We also compared IAP to a reconstruction of brachial pressure from finger pressure. RESULTS: Thirty-five children between 2 and 22 kg body weight were included. In total, 152 attempts to record a FINAP pressure were performed of which 4.6% were unsuccessful. When comparing FINAP to IAP, bias was -16.2, -7.7, and -10.2 mm Hg for systolic arterial blood pressure, diastolic arterial blood pressure, and mean arterial blood pressure. Limits of agreement (LOA) were respectively 26.1%, 30.1%, and 22.6%. When reconstruction of brachial pressure from finger pressure was compared to IAP, these results were -11.8, 0.6, and -0.9 mm Hg for bias and 21.7%, 8.9%, and 8.9% for LOA. When noninvasive blood pressure oscillometric technique was compared to IAP, the results were: -6.8, -0.9, and -3.8 mm Hg for bias and 18.2%, 38.6%, and 22.1% for LOA. CONCLUSION: Beta type continuous noninvasive arterial blood pressure monitoring using a finger cuff with brachial arterial waveform reconstruction seems reliable in hemodynamically stable critically ill children. TI - The reliability of continuous noninvasive finger blood pressure measurement in critically ill children. EP - 821 SN - 0003-2999 IS - iss. 3 SP - 814 JF - Anesthesia and Analgesia VL - vol. 108 DO - https://doi.org/10.1213/ane.0b013e318194f401 ER - TY - JOUR AU - Hietbrink, F. AU - Besselink, M.G. AU - Renooij, W. AU - Smet, M.B. de AU - Draisma, A. AU - Hoeven, H. van der AU - Pickkers, P. PY - 2009 UR - https://hdl.handle.net/2066/81438 AB - Although the gut is often considered the motor of sepsis, the relation between systemic inflammation and intestinal permeability in humans is not clear. We analyzed intestinal permeability during experimental endotoxemia in humans. Before and during experimental endotoxemia (Escherichia coli LPS, 2 ng/kg), using polyethylene glycol (PEG) as a permeability marker, intestinal permeability was analyzed in 14 healthy subjects. Enterocyte damage was determined by intestinal fatty acid binding protein. Endotoxemia induced an inflammatory response. Urinary PEGs 1,500 and 4,000 recovery increased from 38.8 +/- 6.3 to 63.1 +/- 12.5 and from 0.58 +/- 0.31 to 3.11 +/- 0.93 mg, respectively (P < 0.05). Intestinal fatty acid binding protein excretion was not affected by endotoxemia. The peak serum IL-10 concentrations correlated with the increase in PEG 1,500 recovery (r = 0.48, P = 0.027). Systemic inflammation results in an increased intestinal permeability. The increase in intestinal permeability is most likely caused by inflammation-induced paracellular permeability, rather than ischemia-mediated enterocyte damage. TI - Systemic inflammation increases intestinal permeability during experimental human endotoxemia. EP - 378 SN - 1073-2322 IS - iss. 4 SP - 374 JF - Shock VL - vol. 32 DO - https://doi.org/10.1097/SHK.0b013e3181a2bcd6 ER - TY - JOUR AU - Struck, J. AU - Strebelow, M. AU - Tietz, S. AU - Alonso, C. AU - Morgenthaler, N.G. AU - Hoeven, J.G. van der AU - Pickkers, P. AU - Bergmann, A. PY - 2009 UR - https://hdl.handle.net/2066/79571 AB - BACKGROUND: Procalcitonin (PCT) is an established marker for diagnosing and monitoring bacterial infections. Full-length PCT [116 amino acids that make up procalcitonin (PCT1-116)] can be truncated, leading to des-Ala-Pro-PCT (des-Alanin-Prolin-Procalcitonin; PCT3-116). Current immunoassays for PCT ("total PCT") use antibodies directed against internal epitopes and are unable to distinguish amino-terminal PCT variants. Here we describe the development of monoclonal antibodies recognizing the amino-termini of PCT1-116 and PCT3-116 and their use in the selective measurement of these PCT species. METHODS: With newly developed monoclonal antibodies against the amino-termini of PCT1-116 and PCT3-116, and an antibody against the katacalcin moiety of PCT, we developed and characterized immunoluminometric assays for the 2 PCT peptides. We comparatively assessed the kinetics of PCT variants in a human endotoxemia model. RESULTS: Monoclonal antibodies against the amino-termini of PCT1-116 and PCT3-116 showed <1% cross-reactivity with other PCT-related peptides. The sandwich assays for PCT1-116 and PCT3-116 had functional assay sensitivities of 5 and 1.2 pmol/L, respectively, and exhibited recoveries within 20% of expected values. Plasma PCT1-116 was stable for 6 h at 22 degrees C and 24 h at 4 degrees C, and PCT3-116 was stable for at least 24 h at both temperatures. During experimental endotoxemia in healthy people, both PCT1-116 and PCT3-116 increased early in parallel with total PCT, but further increases in PCT1-116 were significantly slower than for PCT3-116 (P = 0.0049) and total PCT (P = 0.0024). CONCLUSIONS: The new assays selectively measure PCT1-116 and PCT3-116. Both PCT species increase early during endotoxemia but differ in their kinetics thereafter. The selective measurement of PCT species with different in vivo kinetics may be useful in improving PCT-guided therapies. TI - Method for the selective measurement of amino-terminal variants of procalcitonin. EP - 1679 SN - 0009-9147 IS - iss. 9 SP - 1672 JF - Clinical Chemistry VL - vol. 55 DO - https://doi.org/10.1373/clinchem.2008.123018 ER - TY - JOUR AU - Draisma, A. AU - Bemelmans, R. AU - Hoeven, J.G. van der AU - Spronk, P. AU - Pickkers, P. PY - 2009 UR - https://hdl.handle.net/2066/79594 AB - The purpose of the study was to investigate microcirculation and vascular reactivity during experimental endotoxemia and endotoxin tolerance in humans by comparing different methods of approach. Endotoxin tolerance was induced in nine healthy volunteers by intravenous injection of 2 ng . kg(-1) . d(-1) LPS for 5 consecutive days. Microcirculation and vascular reactivity were monitored before and after LPS administrations on days 1 and 5 by near-infrared spectroscopy, sidestream dark-field imaging, and forearm blood flow by venous occlusion strain-gauge plethysmography during local intra-arterial infusion of endothelial-dependent vasodilator acetylcholine (0.5, 2, and 8 microg . min(-1) . dL(-1)). LPS administration induced a significant rise in all measured cytokines. During subsequent LPS administrations, the increase in cytokine levels was almost completely abolished, indicating the development of tolerance. Near-infrared spectroscopy showed 79% (interquartile range [IQR], 62%-92%) attenuation of recovery slope after ischemia 2 h after LPS administration on day 1 (P = 0.04), which was absent on day 5 (P = 0.72). Sidestream dark-field imaging showed 33% (IQR, 14%-40%) and 30% (IQR, 10%-33%) diminished flow in medium and large microvessels, respectively, 2 h after LPS administration on day 1 (P = 0.07 and 0.04, respectively), which was absent on day 5 (P = 0.47 for both vessels). Forearm blood flow measurements showed an attenuation of acetylcholine-induced vasodilatory response, with 67% (IQR, 45%-72%) 4 h after the first LPS administration (P = 0.01), but not when tolerance was present on day 5 (P = 0.61). Human endotoxemia results in endothelial dysfunction that can be adequately detected with different methods and was restored with development of LPS tolerance. TI - Microcirculation and vascular reactivity during endotoxemia and endotoxin tolerance in humans. EP - 585 SN - 1073-2322 IS - iss. 6 SP - 581 JF - Shock VL - vol. 31 DO - https://doi.org/10.1097/SHK.0b013e318193e187 ER - TY - JOUR AU - Pickkers, P. AU - Snellen, F. AU - Rogiers, P. AU - Bakker, J. AU - Jorens, P. AU - Meulenbelt, J. AU - Spapen, H. AU - Tulleken, J.E. AU - Lins, R. AU - Ramael, S. AU - Bulitta, M. AU - Hoeven, J.G. van der PY - 2009 UR - https://hdl.handle.net/2066/79632 AB - PURPOSE: To evaluate the clinical pharmacology of exogenous alkaline phosphatase (AP). METHODS: Randomized, double-blind, placebo-controlled sequential protocols of (1) ascending doses and infusion duration (volunteers) and (2) fixed dose and duration (patients) were conducted at clinical pharmacology and intensive care units. A total of 103 subjects (67 male volunteers and 36 patients with severe sepsis) were administered exogenous, 10-min IV infusions (three ascending doses) or 24-72 h continuous (132.5-200 U kg(-1) 24 h(-1)) IV infusion with/without preceding loading dose and experimental endotoxemia for evaluations of pharmacokinetics, pharmacodynamics, safety parameters, antigenicity, inflammatory markers, and outcomes. RESULTS: Linearity and dose-proportionality were shown during 10-min infusions. The relatively short elimination half-life necessitated a loading dose to achieve stable enzyme levels. Pharmacokinetic parameters in volunteers and patients were similar. Innate immunity response was not significantly influenced by AP, while renal function significantly improved in sepsis patients. CONCLUSIONS: The pharmacokinetics of exogenous AP is linear, dose-proportional, exhibit a short half-life, and are not influenced by renal impairment or dialysis. TI - Clinical pharmacology of exogenously administered alkaline phosphatase. EP - 402 SN - 0031-6970 IS - iss. 4 SP - 393 JF - European Journal of Clinical Pharmacology VL - vol. 65 DO - https://doi.org/10.1007/s00228-008-0591-6 ER - TY - JOUR AU - Smet, A.M. de AU - Kluytmans, J.A. AU - Cooper, B.S. AU - Mascini, E.M. AU - Benus, R.F. AU - Werf, T.S. van der AU - Hoeven, J.G. van der AU - Pickkers, P. AU - Bogaers-Hofman, D. AU - Meer, N.J. van der AU - Bernards, A.T. AU - Kuijper, E.J. AU - Joore, J.C. AU - Leverstein-van Hall, M.A. AU - Bindels, A.J. AU - Jansz, A.R. AU - Wesselink, R.M. AU - Jongh, B.M. de AU - Dennesen, P.J. AU - Asselt, G.J. van AU - Velde, L.F. te AU - Frenay, I.H. AU - Kaasjager, K.A. AU - Bosch, F.H. AU - Iterson, M. van AU - Thijsen, S.F. AU - Kluge, G.H. AU - Pauw, W. AU - Vries, J.W. de AU - Kaan, J.A. AU - Arends, J.P. AU - Aarts, L.P. AU - Sturm, P.D.J. AU - Harinck, H.I. AU - Voss, A. AU - Uijtendaal, E.V. AU - Blok, H.E. AU - Thieme Groen, E.S. AU - Pouw, M.E. AU - Kalkman, C.J. AU - Bonten, M.J. PY - 2009 UR - https://hdl.handle.net/2066/79996 AB - BACKGROUND: Selective digestive tract decontamination (SDD) and selective oropharyngeal decontamination (SOD) are infection-prevention measures used in the treatment of some patients in intensive care, but reported effects on patient outcome are conflicting. METHODS: We evaluated the effectiveness of SDD and SOD in a crossover study using cluster randomization in 13 intensive care units (ICUs), all in The Netherlands. Patients with an expected duration of intubation of more than 48 hours or an expected ICU stay of more than 72 hours were eligible. In each ICU, three regimens (SDD, SOD, and standard care) were applied in random order over the course of 6 months. Mortality at day 28 was the primary end point. SDD consisted of 4 days of intravenous cefotaxime and topical application of tobramycin, colistin, and amphotericin B in the oropharynx and stomach. SOD consisted of oropharyngeal application only of the same antibiotics. Monthly point-prevalence studies were performed to analyze antibiotic resistance. RESULTS: A total of 5939 patients were enrolled in the study, with 1990 assigned to standard care, 1904 to SOD, and 2045 to SDD; crude mortality in the groups at day 28 was 27.5%, 26.6%, and 26.9%, respectively. In a random-effects logistic-regression model with age, sex, Acute Physiology and Chronic Health Evaluation (APACHE II) score, intubation status, and medical specialty used as covariates, odds ratios for death at day 28 in the SOD and SDD groups, as compared with the standard-care group, were 0.86 (95% confidence interval [CI], 0.74 to 0.99) and 0.83 (95% CI, 0.72 to 0.97), respectively. CONCLUSIONS: In an ICU population in which the mortality rate associated with standard care was 27.5% at day 28, the rate was reduced by an estimated 3.5 percentage points with SDD and by 2.9 percentage points with SOD. (Controlled Clinical Trials number, ISRCTN35176830.) TI - Decontamination of the digestive tract and oropharynx in ICU patients. EP - 31 SN - 0028-4793 IS - iss. 1 SP - 20 JF - The New England Journal of Medicine VL - vol. 360 DO - https://doi.org/10.1056/NEJMoa0800394 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/79996/79996.pdf?sequence=1 ER - TY - JOUR AU - Boogaard, M.H.W.A. van den AU - Pickkers, P. AU - Hoeven, J.G. van der AU - Roodbol, G.J.M. AU - Achterberg, T. van AU - Schoonhoven, L. PY - 2009 UR - https://hdl.handle.net/2066/80336 AB - INTRODUCTION: In critically ill patients, delirium is a serious and frequent disorder that is associated with a prolonged intensive care and hospital stay and an increased morbidity and mortality. Without the use of a delirium screening instrument, delirium is often missed by ICU nurses and physicians. The effects of implementation of a screening method on haloperidol use is not known. The purpose of this study was to evaluate the implementation of the confusion assessment method-ICU (CAM-ICU) and the effect of its use on frequency and duration of haloperidol use. METHODS: We used a tailored implementation strategy focused on potential barriers. We measured CAM-ICU compliance, interrater reliability, and delirium knowledge, and compared the haloperidol use, as a proxy for delirium incidence, before and after the implementation of the CAM-ICU. RESULTS: Compliance and delirium knowledge increased from 77% to 92% and from 6.2 to 7.4, respectively (both, P < 0.0001). The interrater reliability increased from 0.78 to 0.89. More patients were treated with haloperidol (9.9% to 14.8%, P < 0.001), however with a lower dose (18 to 6 mg, P = 0.01) and for a shorter time period (5 [IQR:2-9] to 3 [IQR:1-5] days, P = 0.02). CONCLUSIONS: With a tailored implementation strategy, a delirium assessment tool was successfully introduced in the ICU with the main goals achieved within four months. Early detection of delirium in critically ill patients increases the number of patients that receive treatment with haloperidol, however with a lower dose and for a shorter time period. TI - Implementation of a delirium assessment tool in the ICU can influence haloperidol use. EP - R131 SN - 1466-609X IS - iss. 4 SP - R131 JF - Critical Care VL - vol. 13 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/80336/80336.pdf?sequence=1 ER - TY - JOUR AU - Ramakers, B.P.C. AU - Goeij, M. de AU - Hoeven, J.G. van der AU - Peters, W.H.M. AU - Pickkers, P. PY - 2009 UR - https://hdl.handle.net/2066/80200 AB - Because severe sepsis is frequently complicated by multiple organ failure, it is of importance to monitor organ function. Unfortunately, conventional liver function markers are either relatively unspecific or have a long half-life, which make them poor predictors of acute liver injury. Glutathione S-transferase A1-1 (GSTA1-1) has a relatively short half-life (1 h), is more specific, and is rapidly released into the blood after liver damage. In the present study, we measured plasma GSTA1-1 levels by enzyme-linked immunosorbent assay in seven healthy volunteers after repeated experimental endotoxemia induced by 2 ng kg Escherichia coli endotoxin per day (to investigate inflammation-induced hepatic injury) and in 21 patients within 12 h after the occurrence of severe sepsis/septic shock (to investigate its ability to predict an increase of transaminases on day 7). During repeated experimental endotoxemia in healthy volunteers, TNF-alpha and IL-6 levels increased from undetectable levels to 1,425 (474-1,949) and 1,739 (989-2,047) pg mL, respectively, whereas GSTA1-1 levels did not exceed the normal range, indicating that no (sub)clinical liver injury occurs in this model of inflammation. In septic patients, GSTA1-1 levels had a specificity of 88%, resulting in a positive predictive value for liver injury of 86% and a positive likelihood ratio of 6 to indicate an increase in transaminases on day 7. Furthermore, GSTA1-1 levels did not correlate with IL-6 levels but did with dobutamine infusion rate (Spearman r = 0.94; P = 0.02), suggesting that the extent of hemodynamic instability and not the degree of inflammation could be of importance for the occurrence of liver damage. In septic shock patients, GSTA1-1 may represent a useful marker for early liver injury. TI - Inflammation-induced hepatotoxicity in humans. EP - 156 SN - 1073-2322 IS - iss. 2 SP - 151 JF - Shock VL - vol. 31 DO - https://doi.org/10.1097/SHK.0b013e31818335ff ER - TY - JOUR AU - Boode, W.P. de AU - Hopman, J.C.W. AU - Wijnen, M.H.W.A. AU - Tanke, R.B. AU - Hoeven, J.G. van der AU - Liem, K.D. PY - 2009 UR - https://hdl.handle.net/2066/159360 TI - Cardiac Output Measurement in Ventilated Lambs with a Significant Left-to-Right Shunt Using the Modified Carbon Dioxide Fick Method. EP - 131 SN - 1661-7800 IS - iss. 2 SP - 124 JF - Neonatology VL - vol. 97 DO - https://doi.org/10.1159/000237223 ER - TY - JOUR AU - Vaneker, M. AU - Heunks, L.M.A. AU - Joosten, L.A.B. AU - Hees, J. van AU - Snijdelaar, D.G. AU - Halbertsma, F.J. AU - Egmond, J. van AU - Netea, M.G. AU - Hoeven, J.G. van der AU - Scheffer, G.J. PY - 2009 UR - https://hdl.handle.net/2066/79523 AB - BACKGROUND: Mechanical ventilation (MV) can induce lung injury. Proinflammatory cytokines have been shown to play an important role in the development of ventilator-induced lung injury. Previously, the authors have shown a role for Toll-like receptor 4 signaling. The current study aims to investigate the role of Toll/interleukin-1 receptor domain-containing adapter-inducing interferon-beta (TRIF), a protein downstream of Toll-like receptors, in the development of the inflammatory response after MV in healthy mice. METHODS: Wild-type C57BL6 and TRIF mutant mice were mechanically ventilated for 4 h. Lung tissue and plasma was used to investigate changes in cytokine profile, leukocyte influx, and nuclear factor-kappaB activity. In addition, experiments were performed to assess the role of TRIF in changes in cardiopulmonary physiology after MV. RESULTS: MV significantly increased messenger RNA expression of interleukin (IL)-1beta in wild-type mice, but not in TRIF mutant mice. In lung homogenates, MV increased levels of IL-1alpha, IL-1beta, and keratinocyte-derived chemokine in wild-type mice. In contrast, in TRIF mutant mice, only a minor increase in IL-1beta and keratinocyte-derived chemokine was found after MV. Nuclear factor-kappaB activity after MV was significantly lower in TRIF mutant mice compared with wild-type mice. In plasma, MV increased levels of IL-6 and keratinocyte-derived chemokine. In TRIF mutant mice, no increase of IL-6 was found after MV, and the increase in keratinocyte-derived chemokine appeared less pronounced. TRIF deletion did not affect cardiopulmonary physiology after MV. CONCLUSIONS: The current study supports a prominent role for TRIF in the development of the pulmonary and systemic inflammatory response after MV. TI - Mechanical ventilation induces a Toll/interleukin-1 receptor domain-containing adapter-inducing interferon beta-dependent inflammatory response in healthy mice. EP - 843 SN - 0003-3022 IS - iss. 4 SP - 836 JF - Anesthesiology VL - vol. 111 DO - https://doi.org/10.1097/ALN.0b013e3181b76499 ER - TY - JOUR AU - Vaneker, M. AU - Santosa, J.P. AU - Heunks, L.M.A. AU - Halbertsma, F.J. AU - Snijdelaar, D.G. AU - Egmond, J. van AU - Brink, W.A. van den AU - Pol, F.M. van de AU - Hoeven, J.G. van der AU - Scheffer, G.J. PY - 2009 UR - https://hdl.handle.net/2066/80045 AB - BACKGROUND: Mechanical ventilation (MV) induces an inflammatory response in healthy lungs. The resulting pro-inflammatory state is a risk factor for ventilator-induced lung injury and peripheral organ dysfunction. Isoflurane is known to have protective immunological effects on different organ systems. We tested the hypothesis that the MV-induced inflammatory response in healthy lungs is reduced by isoflurane. METHODS: Healthy C57BL6 mice (n=34) were mechanically ventilated (tidal volume, 8 ml/kg; positive end-expiratory pressure, 4 cmH(2)O; and fraction of inspired oxygen, 0.4) for 4 h under general anesthesia using a mix of ketamine, medetomidine and atropine (KMA). Animals were divided into four groups: (1) Unventilated control group; (2) MV group using KMA anesthesia; (3) MV group using KMA with 0.25 MAC isoflurane; (4) MV group using KMA with 0.75 MAC isoflurane. Cytokine levels were measured in lung homogenate and plasma. Leukocytes were counted in lung tissue. RESULTS: Lung homogenates: MV increased pro-inflammatory cytokines. In mice receiving KMA+ isoflurane 0.75 MAC, no significant increase in interleukin (IL)-1beta was found compared with non-ventilated control mice. PLASMA: MV induced a systemic pro-inflammatory response. In mice anesthetized with KMA+ isoflurane (both 0.25 and 0.75 MAC), no significant increase in tumor necrosis factor (TNF)-alpha was found compared with non-ventilated control mice. CONCLUSIONS: The present study is the first to show that isoflurane attenuates the pulmonary IL-1beta and systemic TNF-alpha response following MV in healthy mice. TI - Isoflurane attenuates pulmonary interleukin-1beta and systemic tumor necrosis factor-alpha following mechanical ventilation in healthy mice. EP - 748 SN - 0001-5172 IS - iss. 6 SP - 742 JF - Acta Anaesthesiologica Scandinavica VL - vol. 53 DO - https://doi.org/10.1111/j.1399-6576.2009.01962.x ER - TY - JOUR AU - Halbertsma, F.J. AU - Vaneker, M. AU - Pickkers, P. AU - Hoeven, J.G. van der PY - 2009 UR - https://hdl.handle.net/2066/81226 AB - OBJECTIVE: The objective of this study is to analyze the role of tidal volume (Vt) and positive end-expiratory pressure on the oxygenation ratio (OR) (Pao(2)/Fio(2)) during mechanical ventilation (MV) in children with a normal pulmonary gas exchange on admission. METHODS: A retrospective cohort study of children with an admission OR greater than 300 mm Hg and duration of MV greater than 48 hours (n = 96) was done. We analyzed Vt, Fio(2), Pao(2), and positive end-expiratory pressure and calculated Vt (mL/kg) and Pao(2)/Fio(2) based on the measured Vt and weight. Patients were divided into group 1, Vt less than 9 mL/kg (n = 24); 2, Vt 9 to 12 mL/kg (n = 58); and 3, Vt 12 mL/kg or higher (n = 14). RESULTS: Baseline characteristics and OR were comparable. Forty-one percent of patients developed OR less than 300 mm Hg. The proportion of patients developing an OR less than 300 mm Hg was lowest in group 1 and highest in group 3, and differences became more pronounced with longer MV duration: 56%, 58%, and 89% on day 5; 29%, 65%, and 100% on day 7 (P = .05); 0%, 40%, and 100% on day 10 (P = .03). In patients maintaining an OR greater than 300 mm Hg during 10 days of MV, Vt was 9.3 +/- 1.0 vs 12.7 +/- 4.8 mL/kg in patients developing an OR less than 300 mm Hg (P = .05). Mechanical ventilation duration was longer in children developing OR less than 300 mm Hg (P < .01). Positive end-expiratory pressure levels were not significantly different between groups. CONCLUSION: In ventilated children, Vt was greater than 9 mL/kg were associated with increased development of an OR less than 300 mm Hg and longer duration of MV. TI - The oxygenation ratio during mechanical ventilation in children: the role of tidal volume and positive end-expiratory pressure. EP - 226 SN - 0883-9441 IS - iss. 2 SP - 220 JF - Journal of Critical Care VL - vol. 24 DO - https://doi.org/10.1016/j.jcrc.2008.03.036 ER - TY - JOUR AU - Verhagen, M.M.M. AU - Deuren, M. van AU - Willemsen, M.A.A.P. AU - Hoeven, J.G. van der AU - Heijdra, Y.F. AU - Yntema, J.L. AU - Weemaes, C.M.R. AU - Neeleman, C. PY - 2009 UR - https://hdl.handle.net/2066/80298 TI - Ataxia-Telangiectasia and mechanical ventilation: a word of caution. EP - 102 SN - 8755-6863 IS - iss. 1 SP - 101 JF - Pediatric Pulmonology VL - vol. 44 DO - https://doi.org/10.1002/ppul.20957 ER - TY - JOUR AU - Lemson, J. AU - Driessen, J.J. AU - Hoeven, J.G. van der PY - 2008 UR - https://hdl.handle.net/2066/70798 AB - OBJECTIVE: To measure the effect of intense neuromuscular blockade (NMB) on oxygen consumption (VO(2)) in deeply sedated and mechanically ventilated children on the first day after complex congenital cardiac surgery. DESIGN: Prospective clinical interventional study. SETTING: Pediatric intensive care unit of an university medical centre. MEASUREMENTS AND RESULTS: Nine mechanically ventilated and sedated children (weight 2.8-8.7 kg) were included. All children were treated with vasoactive drugs. The level of sedation was quantified using the comfort score, Ramsay score and bispectral index (BIS). The intensity of NMB was quantified using acceleromyography and VO(2) was measured using indirect calorimetry. Analgo-sedation using various intravenous agents was targeted at a deep level (comfort score < 18, BIS < 60 and Ramsay score > 4). NMB was achieved by intravenous administration of rocuronium. All measurements were conducted before, during and after recovery from a period of intense NMB. Baseline values were VO(2) 6.1 ml/(kg min) (SD 1.3), comfort score 13 (SD 0.7), BIS 42.5 (SD 14.2), mean blood pressure 54.0 mmHg (SD 10.5), mean heart rate 129.9 bpm (SD 28.9) and mean core temperature 36.7 degrees C (SD 0.5). There were no significant differences in VO(2) or other parameters between baseline, during NMB and the recovery phase. CONCLUSION: Neuromuscular blocking agents do not reduce oxygen consumption in deeply sedated and mechanically ventilated children after congenital cardiac surgery. TI - The effect of neuromuscular blockade on oxygen consumption in sedated and mechanically ventilated pediatric patients after cardiac surgery. EP - 2272 SN - 0342-4642 IS - iss. 12 SP - 2268 JF - Intensive Care Medicine VL - vol. 34 DO - http://dx.doi.org/10.1007/s00134-008-1252-z ER - TY - JOUR AU - Hoedemaekers, C.W.E. AU - Deuren, M. van AU - Hoeven, J.G. van der PY - 2008 UR - https://hdl.handle.net/2066/71269 TI - Complement activation after cardiac surgery follows a biphasic pattern. EP - 1723; author reply 1723 SN - 0003-4975 IS - iss. 5 SP - 1723 JF - Annals of Thoracic Surgery VL - vol. 86 ER - TY - JOUR AU - Heemskerk, S. AU - Haren, F.M. van AU - Foudraine, N.A. AU - Peters, W.H.M. AU - Hoeven, J.G. van der AU - Russel, F.G.M. AU - Masereeuw, R. AU - Pickkers, P. PY - 2008 UR - https://hdl.handle.net/2066/71022 AB - OBJECTIVE: We previously demonstrated that upregulation of renal inducible nitric oxide synthase (iNOS) is associated with proximal tubule injury during systemic inflammation in humans. In this study we investigated the short-term effect of methylene blue (MB), an inhibitor of the NO pathway, on kidney damage and function in septic shock patients. DESIGN AND SETTING: A prospective clinical study conducted in an intensive care unit. PATIENTS: Nine patients (four men, five women, mean age 71 +/- 3 years) with confirmed or suspected bacterial infection and with refractory septic shock defined as a mean arterial pressure < or = 70 mmHg despite norepinephrine infusion > or = 0.2 microg/kg per minute. INTERVENTIONS: A 4 h continuous intravenous infusion of 1 mg/kg MB per hour. MEASUREMENTS AND RESULTS: The urinary excretion of NO metabolites decreased with median 90% (range 75-95%) from baseline to 6 h after MB administration. The first 24 h creatinine clearance improved by 51% (18-173%) after MB treatment but was still strongly impaired. During the first 6 h after the start of MB treatment both the urinary excretion of cytosolic glutathione S-transferase A1-1 and P1-1, markers for proximal and distal tubule damage, respectively, decreased by 45% (10-70%) and 70% (40-85) vs. baseline. After termination of the MB infusion the NO metabolites and markers of tubular injury returned to pretreatment levels. CONCLUSIONS: In septic patients with refractory shock short-term infusion of MB is associated with a decrease in NO production and an attenuation of the urinary excretion of renal tubular injury markers. TI - Short-term beneficial effects of methylene blue on kidney damage in septic shock patients. EP - 354 SN - 0342-4642 IS - iss. 2 SP - 350 JF - Intensive Care Medicine VL - vol. 34 DO - http://dx.doi.org/10.1007/s00134-007-0867-9 ER - TY - JOUR AU - Hoedemaekers, C.W.E. AU - Klein Gunnewiek, J.M.T. AU - Prinsen, M.A. AU - Willems, J.L. AU - Hoeven, J.G. van der PY - 2008 UR - https://hdl.handle.net/2066/69498 AB - OBJECTIVE: Implementation of strict glucose control in most intensive care units has resulted in increased use of point-of-care glucose devices in the intensive care unit. The aim of this study was to determine the reliability of point-of-care testing glucose meters among critically ill patients under intensive insulin treatment. DESIGN: Prospective observational study. PATIENTS: Intensive care unit and non-intensive care unit patients in a tertiary care teaching hospital. MEASUREMENTS: A glucose oxidase method was used to validate the point-of-care testing devices. Three different point-of-care testing devices, Accu-Chek Sensor (Roche Diagnostics), Precision (Abbott Diagnostics), and HemoCue were tested. Glucose measurements were performed in duplicate by an experienced technician under standardized conditions in the hospital's laboratory, using arterial (intensive care unit patients) and arterial or venous (non-intensive care unit patients) heparinized whole blood samples. MAIN RESULTS: A strong correlation was found between the glucose oxidase method and the Accu-Chek device (r = .9596, p < 0.001). Mean absolute difference between the glucose oxidase and Accu-Chek was -0.32 mmol/L (95% confidence interval -0.84 to 1.48 mmol/L). Using the International Organization for Standardization (ISO) criteria, 27 of 197 samples (13.7%) were inaccurate. In all samples that failed to meet the ISO criteria, glucose values measured by the Accu-Chek device were higher compared with the glucose oxidase method. In another set of experiments among intensive care unit patients, strong positive correlations were also found between the other point-of-care testing devices and the glucose oxidase method. However, paired samples from Accu-Chek, HemoCue, and Precision failed the ISO criteria in 9 of 82 (11.0%), 4 of 82 (4.9%), and 11 of 82 (13.4%) of cases, respectively. In non-intensive care unit patients paired samples from Accu-Chek, HemoCue, and Precision failed the ISO criteria in 3 of 120 (2.5%), 11 of 120 (9.2%), and 16 of 120 (13.3%) cases, respectively. CONCLUSIONS: Under standardized conditions, glucose results from three point-of-care testing devices were inaccurate in both intensive care unit and non-intensive care unit patients. Among intensive care unit patients, inaccurate glucose readings were most frequently falsely elevated, resulting in misinterpretation of high glucose values with subsequent inappropriate insulin administration or masking of true hypoglycemia. TI - Accuracy of bedside glucose measurement from three glucometers in critically ill patients. EP - 3066 SN - 0090-3493 IS - iss. 11 SP - 3062 JF - Critical Care Medicine VL - vol. 36 DO - https://doi.org/10.1097/CCM.0b013e318186ffe6 ER - TY - JOUR AU - Bisschops, L.L.A. AU - Hoedemaekers, C.W.E. AU - Hoeven, J.G. van der PY - 2008 UR - https://hdl.handle.net/2066/69811 TI - Changes in cerebral blood flow and oxygen extraction during the post-resuscitation syndrome. EP - 415 SN - 0300-9572 IS - iss. 3 SP - 415 JF - Resuscitation VL - vol. 77 ER - TY - JOUR AU - Kox, M. AU - Pompe, J.C. AU - Pickkers, P. AU - Hoedemaekers, C.W.E. AU - Vugt, A.B. van AU - Hoeven, J.G. van der PY - 2008 UR - https://hdl.handle.net/2066/69752 AB - Traumatic brain injury (TBI) is a leading cause of death and disability, especially in the younger population. In the acute phase after TBI, patients are more vulnerable to infection, associated with a decreased immune response in vitro. The cause of this immune paralysis is poorly understood. Apart from other neurologic dysfunction, TBI also results in an increase in vagal activity. Recently, the vagus nerve has been demonstrated to exert an anti-inflammatory effect, termed the cholinergic anti-inflammatory pathway. The anti-inflammatory effects of the vagus nerve are mediated by the alpha 7 nicotinic acetylcholine receptor present on macrophages and other cytokine-producing cells. From these observations, we hypothesize that the immune paralysis observed in patients with TBI may, at least in part, result from augmented vagal activity and subsequent sustained effects of the cholinergic anti-inflammatory pathway. This pathway may counteract systemic proinflammation caused by the release of endogenous compounds termed alarmins as a result of tissue trauma. However, sustained activity of this pathway may severely impair the body's ability to combat infection. Since the cholinergic anti-inflammatory pathway can be pharmacologically modulated in humans, it could represent a novel approach to prevent infections in patients with TBI. TI - Increased vagal tone accounts for the observed immune paralysis in patients with traumatic brain injury. EP - 485 SN - 0028-3878 IS - iss. 6 SP - 480 JF - Neurology VL - vol. 70 DO - https://doi.org/10.1212/01.wnl.0000279479.69502.3e L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/69752/69752.pdf?sequence=1 ER - TY - JOUR AU - Dorresteijn, M.J. AU - Hoeven, J.G. van der AU - Pickkers, P. PY - 2008 UR - https://hdl.handle.net/2066/69408 TI - Volume therapy and innate immune response during systemic inflammation or sepsis. EP - 9 SN - 0090-3493 IS - iss. 3 SP - 1028; author reply 1028 JF - Critical Care Medicine VL - vol. 36 ER - TY - JOUR AU - Draisma, A. AU - Dorresteijn, M.J. AU - Pickkers, P. AU - Hoeven, H. van der PY - 2008 UR - https://hdl.handle.net/2066/70758 AB - The phenomenon of repeated exposure to endotoxin resulting in diminished release of pro-inflammatory cytokines is called endotoxin tolerance, in which there is a putative role for nitric oxide (NO). We investigated the effect of selective inducible NO-synthase (iNOS) inhibition during experimental human endotoxemia on the development of tolerance to various Toll-like receptor (TLR) agonists ex vivo. Volunteers received 2 ng/kg Escherichia coli endotoxin in the absence (n = 7) or presence (n = 7) of the selective iNOS inhibitor aminoguanidine (bolus 5 mM followed by a continuous infusion of 1.5 mmol/h). At 0, 2 and 4 h, blood samples were drawn for ex vivo stimulation with different TLR agonists. Experimental endotoxemia did not induce tolerance to TLR-2 and TLR-7 stimulation. In TLR-3, TLR-4 and TLR-5 stimulated whole blood, pro- and anti-inflammatory cytokine release was attenuated at 4 h, indicating that endotoxin-induced tolerance is not confined to subsequent TLR-4 stimulation alone. Aminoguanidine-treated subjects also developed tolerance to TLR-4 stimulation. In contrast, tolerance to TLR-3 stimulation did not occur for IL-10, and tolerance in TLR-5 stimulated blood did not develop for both pro- and anti-inflammatory cytokines. The role of NO in the development of tolerance is different for the various TLRs stimulated and pro- and anti-inflammatory cytokines measured. TI - The effect of systemic iNOS inhibition during human endotoxemia on the development of tolerance to different TLR-stimuli. EP - 159 SN - 1753-4259 IS - iss. 3 SP - 153 JF - Innate Immunity VL - vol. 14 DO - https://doi.org/10.1177/1753425908091959 ER - TY - JOUR AU - Heunks, L.M.A. AU - Hoeven, J.G. van der PY - 2008 UR - https://hdl.handle.net/2066/69435 TI - Ventilation strategies for acute lung injury and acute respiratory distress syndrome. EP - 41 SN - 0098-7484 IS - iss. 1 SP - 40 JF - Jama : Journal of the American Medical Association VL - vol. 300 N1 - author reply p. 42 ER - TY - JOUR AU - Vaneker, M. AU - Heunks, L.M.A. AU - Hoeven, J.G. van der AU - Scheffer, G.J. PY - 2008 UR - https://hdl.handle.net/2066/70661 TI - The role of poly (ADP-ribose) polymerase in ventilator-induced lung injury. EP - 431 SN - 1466-609X IS - iss. 5 SP - 431-1 JF - Critical Care VL - vol. 12 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/70661/70661.pdf?sequence=1 ER - TY - JOUR AU - Lemson, J. AU - Hoeven, J.G. van der PY - 2008 UR - https://hdl.handle.net/2066/69115 TI - Clinical value of an arterial pressure-based cardiac output measurement device. EP - 403; author reply 403 SN - 1466-609X IS - iss. 1 SP - 403 JF - Critical Care VL - vol. 12 DO - https://doi.org/10.1186/cc6219 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/69115/69115.pdf?sequence=1 ER - TY - JOUR AU - Ramakers, B.P.C. AU - Pickkers, P. AU - Deussen, A. AU - Rongen, G.A.P.J.M. AU - Broek, P. van den AU - Hoeven, J.G. van der AU - Smits, P. AU - Riksen, N.P. PY - 2008 UR - https://hdl.handle.net/2066/69181 AB - The endogenous nucleoside adenosine has profound tissue protective effects in situations of ischaemia or inflammation. Animal studies have shown that various drugs can activate this protective mechanism by interfering with the metabolism of adenosine. Translation of this concept to the clinical arena is hampered by the difficulties encountered in measuring the adenosine concentration, due to the rapid cellular uptake and degradation of adenosine, which continues unabated after blood sampling, and due to the metabolically active endothelial barrier for adenosine. In the current paper, we critically discuss the various methods to measure the adenosine concentration in humans in vivo. For the measurement of circulating adenosine, we conclude that the use of a pharmacological blocker solution (containing inhibitors of the enzymes ecto-5'-nucleotidase, adenosine deaminase, and adenosine kinase, and of the equilibrative nucleoside transporter) and a purpose-built syringe which mixes the blood with this solution immediately at the tip of the needle, seems to be the most sensitive technique. However, for the measurement of adenosine concentrations in interstitial tissue, microdialysis is a suitable method, when used with an appropriate method to determine the recovery of adenosine across the semipermeable membrane to calculate the absolute adenosine concentration. Consistent use of these methods could help in the comparison of the various studies focussed on endogenous adenosine and could help to facilitate the use of drugs that modulate the adenosine concentration to protect tissues in the clinical arena. TI - Measurement of the endogenous adenosine concentration in humans in vivo: methodological considerations. EP - 685 SN - 1389-2002 IS - iss. 8 SP - 679 JF - Current Drug Metabolism VL - vol. 9 DO - https://doi.org/10.2174/138920008786049249 ER - TY - JOUR AU - Lemson, J. AU - Boode, W.P. de AU - Hopman, J.C.W. AU - Singh, S.K. AU - Hoeven, J.G. van der PY - 2008 UR - https://hdl.handle.net/2066/69467 AB - OBJECTIVE: This study was undertaken to validate the transpulmonary thermodilution cardiac output measurement (CO(TPTD)) in a controlled newborn animal model under various hemodynamic conditions with special emphasis on low cardiac output. DESIGN: Prospective, experimental, pediatric animal study. SETTING: Animal laboratory of a university hospital. SUBJECTS: Twelve lambs. INTERVENTIONS: We studied 12 lambs under various hemodynamic conditions. Cardiac output was measured using the transpulmonary thermodilution technique with central venous injections of ice-cold saline. An ultrasound transit time perivascular flow probe around the main pulmonary artery served as the standard reference measurement (CO(UFP)). During the experiment, animals were resuscitated from hemodynamic shock using fluid boluses. Cardiac output measurements were performed throughout the experiment. MEASUREMENTS AND MAIN RESULTS: The correlation coefficient between CO(TPTD) and CO(UFP)was .97 (95% confidence interval .94-.98, p < .0001). Bland-Altman analysis showed a mean bias of 0.19 L/min with limits of agreement of -0.04 and 0.43 L/min (12.0% and +/-14.7%, respectively). The correlation coefficient between changes in CO(TPTD) and CO(UFP) during volume loading was .95 (95% confidence interval .91-.96, p < .0001). There was a significant correlation between changes in global end-diastolic volume and changes in stroke volume (r = .59) but not between changes in central venous pressure and changes in stroke volume (r = .03). CONCLUSIONS: The transpulmonary thermodilution technique is a reliable method of measuring cardiac output in newborn animals. It is also capable of tracking changes in cardiac output. TI - Validation of transpulmonary thermodilution cardiac output measurement in a pediatric animal model. EP - 319 SN - 1529-7535 IS - iss. 3 SP - 313 JF - Pediatric Critical Care Medicine VL - vol. 9 DO - https://doi.org/10.1097/PCC.0b013e31816c6fa1 ER - TY - JOUR AU - Eijk, L.T.G.J. van AU - Hoeven, J.G. van der AU - Pickkers, P. PY - 2008 UR - https://hdl.handle.net/2066/70357 TI - Endothelium-dependent vascular dysfunction in septic patients. EP - 5 SN - 0003-2409 IS - iss. 8 SP - 883-4; author reply 884 JF - Anaesthesia VL - vol. 63 ER - TY - JOUR AU - Moviat, M. AU - Terpstra, A.M. AU - Ruitenbeek, W. AU - Kluijtmans, L.A.J. AU - Pickkers, P. AU - Hoeven, J.G. van der PY - 2008 UR - https://hdl.handle.net/2066/71010 AB - OBJECTIVE: The physicochemical approach, described by Stewart to investigate the acid-base balance, includes the strong ion gap (SIG), a quantitative measure of "unmeasured" anions, which strongly correlates to the corrected anion gap. The chemical nature of these anions is for the most part unknown. We hypothesized that amino acids, uric acid, and organic acids could contribute to the SIG. DESIGN: Prospective observational study. SETTING: Intensive care department of an academic hospital. PATIENTS: Consecutive intensive care unit patients (n = 31) with metabolic acidosis, defined as a pH of < 7.35 and a base excess of < or = -5 mmol/L. INTERVENTIONS: A single arterial blood sample was collected. MEASUREMENTS: The SIG was calculated and two groups were compared: patients with SIG of < or = 2 mEq/L and patients with SIG of > or = 5 mEq/L. "Unmeasured" anions were examined by ion-exchange column chromatography, reverse-phase high-performance liquid chromatography, and gas chromatography/mass spectrometry measuring amino acids, uric acid, and organic acids, respectively. MAIN RESULTS: Comparison of patient characteristics of both SIG groups showed that age, sex, Acute Physiology and Chronic Health Evaluation II, pH, base excess, and lactate were not significantly different. Renal insufficiency and sepsis were more prevalent in the SIG > or = 5 mEq/L group (n = 12; median SIG, 8.3 mEq/L), associated with higher mortality. Concentrations of the anionic compounds aspartic acid, uric acid, succinic acid, pyroglutamic acid, p-hydroxyphenyllactic acid, and the semiquantified organic acid homovanillic acid were all statistically significantly elevated in the SIG > or = 5 mEq/L group compared with the SIG < or = 2 mEq/L group (n = 8; median SIG, 0.6 mEq/L). Overall, the averaged difference between both SIG groups in total anionic amino acids, uric acid, and organic acids concentrations contributed to the SIG for, respectively, 0.07% (5 microEq/L, p = not significant), 2.2% (169 microEq/L, p = .021), and 5.6% (430 microEq/L, p = .025). CONCLUSIONS: Amino acids, uric acid, and organic acids together accounted for only 7.9% of the SIG in intensive care unit patients with metabolic acidosis. TI - Contribution of various metabolites to the "unmeasured" anions in critically ill patients with metabolic acidosis. EP - 758 SN - 0090-3493 IS - iss. 3 SP - 752 JF - Critical Care Medicine VL - vol. 36 DO - https://doi.org/10.1097/CCM.0B013E31816443CB ER - TY - JOUR AU - Halbertsma, F.J. AU - Vaneker, M. AU - Pickkers, P. AU - Snijdelaar, D.G. AU - Egmond, J. van AU - Scheffer, G.J. AU - Hoeven, J.G. van der PY - 2008 UR - https://hdl.handle.net/2066/69935 AB - BACKGROUND: Mechanical ventilation with small tidal volumes reduces the development of ventilator-induced lung injury and mortality, but may increase PaCO2. It is not clear whether the beneficial effect of a lung-protective strategy results from reduced ventilation pressures/tidal volumes or is mediated by the effects of hypercapnic acidosis on the inflammatory response involved in the pathogenesis of ventilator-induced lung injury. OBJECTIVE: To analyze whether hypercapnic acidosis affects lung tissue cytokine levels and leukocyte influx in healthy ventilated mice. STUDY DESIGN: Analysis of lung tissue and plasma concentrations of interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha, IL-6, IL-10, and keratocyte-derived chemokine after 2 hrs of mechanical ventilation (V(t) 8 mL/kg, positive end-expiratory pressure 4 cm H2O) with 0.06% CO2 (room air), 2% CO2, or 4% CO2. SUBJECTS: Healthy C57BL6 mice (n = 40). MEASUREMENTS/RESULTS: PaCO2 and pH were within normal range when ventilated with 0.06% CO2 and significantly changed with 2% and 4% CO2: (mean +/- SD) pH 7.23 +/- 0.06 and 7.15 +/- 0.04, PaCO2 7.9 +/- 1.4 and 10.8 +/- 0.7 kPa, respectively (p < 0.005). Blood pressure remained within normal limits in all animals. Quantitative microscopic analysis showed a 4.7 +/- 3.7-fold increase (p < 0.01) in pulmonary leukocyte influx in normocapnic ventilated animals and a significant reduction in leukocyte influx of 57 +/- 32% (p < 0.01) and 67 +/- 22% (p < 0.01) when ventilated with 2% and 4% CO2, respectively. Normocapnic ventilation induced a significant elevation of lung tissue IL-1beta (1516 +/- 119 ng/mL), TNF-alpha (344 +/- 88 ng/mL), IL-6 (6310 +/- 807 ng/mL), IL-10 (995 +/- 152 ng/mL), and keratocyte-derived chemokine (36,966 +/- 15,294 ng/mL) (all p-values <0.01). Hypercapnic acidosis with 2% respectively 4% CO2 significantly attenuated this increase with 25 +/- 32% and 54 +/- 32% (IL-1beta, p < 0.01); 17 +/- 36% and 58 +/- 33% (TNF-alpha, p < 0.02); 22 +/- 34% and 89 +/- 6% (IL-6, p < 0.01); 20 +/- 31% and 67 +/- 17% (IL-10, p < 0.01) and 16 +/- 44% and 45 +/- 30% (keratocyte-derived chemokine, p = 0.07). CONCLUSION: Hypercapnic acidosis attenuates the mechanical ventilation-induced immune response independent from reduced tidal volumes/pressures and may protect the lung from ventilator induced lung injury. TI - Hypercapnic acidosis attenuates the pulmonary innate immune response in ventilated healthy mice. EP - 2406 SN - 0090-3493 IS - iss. 8 SP - 2403 JF - Critical Care Medicine VL - vol. 36 DO - https://doi.org/10.1097/CCM.0b013018180266e ER - TY - JOUR AU - Vaneker, M. AU - Joosten, L.A.B. AU - Heunks, L.M.A. AU - Snijdelaar, D.G. AU - Halbertsma, F.J. AU - Egmond, J. van AU - Netea, M.G. AU - Hoeven, J.G. van der AU - Scheffer, G.J. PY - 2008 UR - https://hdl.handle.net/2066/69078 AB - BACKGROUND: Mechanical ventilation (MV) can induce ventilator-induced lung injury. A role for proinflammatory pathways has been proposed. The current studies analyzed the roles of Toll-like receptor (TLR) 4 and TLR2 involvement in the inflammatory response after MV in the healthy lung. METHODS: Wild-type (WT) C57BL6, TLR4 knockout (KO), and TLR2 KO mice were mechanically ventilated for 4 h. Bronchoalveolar lavage fluid was analyzed for presence of endogenous ligands. Lung homogenates were used to investigate changes in TLR4 and TLR2 expression. Cytokines were measured in lung homogenate and plasma, and leukocytes were counted in lung tissue. RESULTS: MV significantly increased endogenous ligands for TLR4 in bronchoalveolar lavage fluid and relative messenger RNA expression of TLR4 and TLR2 in lung tissue. In lung homogenates, MV in WT mice increased levels of keratinocyte-derived chemokine, interleukin (IL)-1alpha, and IL-1beta. In TLR4 KO mice, MV increased IL-1alpha but not IL-1beta, and the increase in keratinocyte-derived chemokine was less pronounced. In plasma, MV in WT mice increased levels of IL-6, keratinocyte-derived chemokine, and tumor necrosis factor alpha. In TLR4 KO mice, MV did not increase levels of IL-6 or tumor necrosis factor alpha, and the response of keratinocyte-derived chemokine was less pronounced. MV in TLR2 KO mice did not result in different cytokine levels compared with WT mice. In WT and TLR2 KO mice, but not in TLR4 KO mice, MV increased the number of pulmonary leukocytes. CONCLUSIONS: The current study supports a role for TLR4 in the inflammatory reaction after short-term MV in healthy lungs. Increasing the understanding of the innate immune response to MV may lead to future treatment advances in ventilator-induced lung injury, in which TLR4 may serve as a therapeutic target. TI - Low-tidal-volume mechanical ventilation induces a toll-like receptor 4-dependent inflammatory response in healthy mice. EP - 472 SN - 0003-3022 IS - iss. 3 SP - 465 JF - Anesthesiology VL - vol. 109 DO - https://doi.org/10.1097/ALN.0b013e318182aef1 ER - TY - JOUR AU - Moviat, M. AU - Pickkers, P. AU - Ruitenbeek, W. AU - Hoeven, J.G. van der PY - 2008 UR - https://hdl.handle.net/2066/70719 TI - The nature of unmeasured anions in critically ill patients. EP - 416 SN - 1466-609X IS - iss. 2 SP - 416 JF - Critical Care VL - vol. 12 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/70719/70719.pdf?sequence=1 ER - TY - JOUR AU - Meer, W. van der AU - Pickkers, P. AU - Scott, C.S. AU - Hoeven, J.G. van der AU - Klein Gunnewiek, J.M.T. PY - 2007 UR - https://hdl.handle.net/2066/51625 AB - CD64 is a high-affinity Fc(gamma)RI receptor expressed by activated neutrophils that has been recently evaluated as a potential sepsis parameter. In the present study, the kinetics of neutrophil membrane CD64 expression were examined during a standardized inflammatory response, using a human endotoxemia model, and compared with hematological indices, CRP, cytokines and interleukins. Ten healthy subjects received 2 ng/kg intravenous Escherichia coli lipopolysaccharide (LPS). After administration of LPS, neutrophil CD64 showed a biphasic response, characterized by a first increase from 108.5 +/- 7.5 to 133 +/- 6 AFU after 1 h (P = 0.047) and a second increase that started at 6 h and reached its maximum of 167 +/- 13 AFU at 22 h (P < 0.0001). CRP concentrations increased to 40 +/- 5 mg/dl 22 h after the administration of LPS. The cytokines and interleukins reached their maximum response within 1-2 h. The maximum values of pro-inflammatory cytokines (TNF-alpha, IFN-gamma and IL-6) correlated with the CD64 expression at 22 h after LPS administration (r(2) = 0.76, r(2) = 0.78, r(2) = 0.81, respectively, all P < 0.05), whereas this correlation was not found for the anti-inflammatory IL-10 (r(2) = 0.058, P = 0.54), suggesting that neutrophil CD64 expression might be a quantitative marker for innate immunity that could easily be used in the clinical setting. TI - Hematological indices, inflammatory markers and neutrophil CD64 expression: comparative trends during experimental human endotoxemia. EP - 100 SN - 0968-0519 IS - iss. 2 SP - 94 JF - Journal of Endotoxin Research VL - vol. 13 DO - https://doi.org/10.1177/0968051907079101 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/51625/51625.pdf?sequence=1 ER - TY - JOUR AU - Schouten, J.A. AU - Bindels, A. AU - Pickkers, P. AU - Hoeven, J.G. van der PY - 2007 UR - https://hdl.handle.net/2066/52994 TI - Cardiac surgery for infective endocarditis, complicated by septic cardioembolic stroke. EP - e31 SN - 0039-2499 IS - iss. 6 SP - e31 JF - Stroke VL - vol. 38 DO - https://doi.org/10.1161/STROKEAHA.106.475848 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/52994/52994.pdf?sequence=1 ER - TY - JOUR AU - Haren, E.M. van AU - Sleight, J.W. AU - Pickkers, P. AU - Hoeven, J.G. van der PY - 2007 UR - https://hdl.handle.net/2066/53434 AB - Septic shock is characterised by vasodilation, myocardial depression and impaired microcirculatory blood flow, resulting in redistribution of regional blood flow. Animal and human studies have shown that gastrointestinal mucosal blood flow is impaired in septic shock. This is consistent with abnormalities found in many other microcirculatory vascular beds. Gastrointestinal mucosal microcirculatory perfusion deficits have been associated with gut injury and a decrease in gut barrier function, possibly causing augmentation of systemic inflammation and distant organ dysfunction. A range of techniques have been developed and used to quantify these gastrointestinal perfusion abnormalities. The following techniques have been used to study gastrointestinal perfusion in humans: tonometry, laser Doppler flowmetry, reflectance spectrophotometry, near-infrared spectroscopy, orthogonal polarisation spectral imaging, indocyanine green clearance, hepatic vein catheterisation and measurements of plasma D-lactate. Although these methods share the ability to predict outcome in septic shock patients, it is important to emphasise that the measurement results are not interchangeable. Different techniques measure different elements of gastrointestinal perfusion. Gastric tonometry is currently the most widely used technique because of its non-invasiveness and ease of use. Despite all the recent advances, the usefulness of gastrointestinal perfusion parameters in clinical decision-making is still limited. Treatment strategies specifically aimed at improving gastrointestinal perfuision have failed to actually correct mucosal perfusion abnormalities and hence not shown to improve important clinical endpoints. Current and future treatment strategies for septic shock should be tested for their effects on gastrointestinal perfusion; to further clarify its exact role in patient management, and to prevent therapies detrimental to gastrointestinal perfusion being implemented. TI - Gastrointestinal perfusion in septic shock. EP - 694 SN - 0310-057X IS - iss. 5 SP - 679 JF - Anaesthesia and Intensive Care VL - vol. 35 ER - TY - JOUR AU - Kox, M. AU - Hoedemaekers, C.W.E. AU - Pickkers, P. AU - Hoeven, J.G. van der AU - Pompe, J.C. PY - 2007 UR - https://hdl.handle.net/2066/51808 TI - A possible role for the cholinergic anti-inflammatory pathway in increased mortality observed in critically ill patients receiving nicotine replacement therapy. EP - 9; author reply 2469 SN - 0090-3493 IS - iss. 10 SP - 2468 JF - Critical Care Medicine VL - vol. 35 ER - TY - JOUR AU - Heemskerk, S. AU - Masereeuw, R. AU - Hoeven, J.G. van der AU - Pickkers, P. PY - 2007 UR - https://hdl.handle.net/2066/51557 TI - Renal effects of nitric oxide during sepsis: another two-edged sword? EP - 420 SN - 1073-449X IS - iss. 4 SP - 419 JF - American Journal of Respiratory and Critical Care Medicine VL - vol. 176 ER - TY - JOUR AU - Hoedemaekers, C.W.E. AU - Ezzahti, M. AU - Gerritsen, A. AU - Hoeven, J.G. van der PY - 2007 UR - https://hdl.handle.net/2066/52086 AB - BACKGROUND: Temperature management is used with increased frequency as a tool to mitigate neurological injury. Although frequently used, little is known about the optimal cooling methods for inducing and maintaining controlled normo- and hypothermia in the intensive care unit (ICU). In this study we compared the efficacy of several commercially available cooling devices for temperature management in ICU patients with various types of neurological injury. METHODS: Fifty adult ICU patients with an indication for controlled mild hypothermia or strict normothermia were prospectively enrolled. Ten patients in each group were assigned in consecutive order to conventional cooling (that is, rapid infusion of 30 ml/kg cold fluids, ice and/or coldpacks), cooling with water circulating blankets, air circulating blankets, water circulating gel-coated pads and an intravascular heat exchange system. In all patients the speed of cooling (expressed as degrees C/h) was measured. After the target temperature was reached, we measured the percentage of time the patient's temperature was 0.2 degrees C below or above the target range. Rates of temperature decline over time were analyzed with one-way analysis of variance. Differences between groups were analyzed with one-way analysis of variance, with Bonferroni correction for multiple comparisons. A p < 0.05 was considered statistically significant. RESULTS: Temperature decline was significantly higher with the water-circulating blankets (1.33 +/- 0.63 degrees C/h), gel-pads (1.04 +/- 0.14 degrees C/h) and intravascular cooling (1.46 +/- 0.42 degrees C/h) compared to conventional cooling (0.31 +/- 0.23 degrees C/h) and the air-circulating blankets (0.18 +/- 0.2 degrees C/h) (p < 0.01). After the target temperature was reached, the intravascular cooling device was 11.2 +/- 18.7% of the time out of range, which was significantly less compared to all other methods. CONCLUSION: Cooling with water-circulating blankets, gel-pads and intravascular cooling is more efficient compared to conventional cooling and air-circulating blankets. The intravascular cooling system is most reliable to maintain a stable temperature. TI - Comparison of cooling methods to induce and maintain normo- and hypothermia in intensive care unit patients: a prospective intervention study. EP - R91 SN - 1466-609X IS - iss. 4 SP - R91-1 JF - Critical Care VL - vol. 11 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/52086/52086.pdf?sequence=1 ER - TY - JOUR AU - Boode, W.P. de AU - Hopman, J.C.W. AU - Daniëls, O. AU - Hoeven, J.G. van der AU - Liem, K.D. PY - 2007 UR - https://hdl.handle.net/2066/52992 AB - Cardiac output can be measured using a modified carbon dioxide Fick (mCO2F) method. A validation study was performed comparing mCO2F method-derived cardiac output (Q(mCO2F)) with invasively measured pulmonary blood flow. In seven randomly bred ventilated newborn lambs, cardiac output was manipulated by creating hemorrhagic hypotension. When steady state was reached, Q(mCO2F) was measured. Gas analysis was performed in simultaneously obtained arterial and venous blood samples (right atrium [RA], superior vena cava [SVC], and inferior vena cava [IVC]). Carbon dioxide exchange and pulmonary blood flow was measured continuously using a CO2SMO Plus monitor and a pulmonary ultrasonic flow probe (Q), respectively. Mean bias, defined as Q(mCO2F) - Q(ufp), was small (respectively, -0.082 L.min, -0.085 Lx min(-1) and -0.183 Lxmin(-1) for venous sampling from RA, SVC, and IVC). The limits of agreement were -0.328 to 0.164 Lxmin(-1) (RA), -0.335 to 0.165 Lxmin(-1) (SVC), and 0.415 to 0.049 Lxmin(-1) (IVC). In conclusion, measurement of cardiac output with the mCO2F method is reliable and easily applicable in ventilated newborn lambs. For clinical use, the site of venous blood sampling is of minor importance. TI - Cardiac output measurement using a modified carbon dioxide Fick method: a validation study in ventilated lambs. EP - 283 SN - 0031-3998 IS - iss. 3 SP - 279 JF - Pediatric Research VL - vol. 61 DO - https://doi.org/10.1203/pdr.0b013e318030d0c6 ER - TY - JOUR AU - Eijk, L.T.G.J. van AU - Dorresteijn, M.J. AU - Smits, P. AU - Hoeven, J.G. van der AU - Netea, M.G. AU - Pickkers, P. PY - 2007 UR - https://hdl.handle.net/2066/53440 AB - OBJECTIVE: To determine gender differences in the innate immune response and vascular reactivity during human endotoxemia. DESIGN: Clinical experimental study. SETTING: University medical center intensive care research unit. SUBJECTS: Fifteen female and 15 male volunteers. INTERVENTIONS: Intravenous injection of 2 ng/kg Escherichia coli lipopolysaccharide. MEASUREMENTS AND MAIN RESULTS: C-reactive protein, leukocytes, and cytokines were measured at regular time intervals as indicators of inflammation. Heart rate and blood pressure were continuously monitored. Forearm blood flow and the responsiveness of forearm vessels to the intrabrachial infusion of norepinephrine (1-3-10-30 ng/min/dL) were measured before and 4 hrs after the administration of endotoxin using venous occlusion plethysmography. Differences were tested with repeated-measures analysis of variance.Females showed a more proinflammatory response to lipopolysaccharide than males, illustrated by a higher rise in C-reactive protein (42 +/- 3 vs. 29 +/- 3 mg/L, p = .002) and more leukocyte sequestration (leukopenia 1.8 +/- 0.1 x 10 vs. 2.4 +/- 0.1 x 10, p = .003). The increase in cytokine levels showed a more proinflammatory pattern in females as reflected by a higher increase in tumor necrosis factor-alpha (965 +/- 193 vs. 411 +/- 35 pg/mL, p < .0001), whereas the increase of the anti-inflammatory interleukin-10 was not significantly different (95 +/- 15 pg/mL in females vs. 129 +/- 15 pg/mL in males, p = .288). Females exhibited higher baseline levels (9.9 +/- 1.1 vs. 7.0 +/- 0.8 pg/mL in males, p = .042) and an augmented increase in lipopolysaccharide-binding protein, which may explain the more pronounced inflammatory response in females. The lipopolysaccharide-induced change in heart rate was not significantly different between the genders, whereas blood pressure decreased more in females (p < .0001). Lipopolysaccharide administration significantly attenuated the norepinephrine sensitivity in males (p = .002), whereas no lipopolysaccharide-induced effect was observed in females (p = .552; difference between groups, p = .045). CONCLUSIONS: During experimental human endotoxemia, females showed a more pronounced proinflammatory innate immune response associated with less attenuation of norepinephrine sensitivity. These findings may be relevant in view of the profound and incompletely explained differences in incidence and outcome of sepsis among male and female patients. TI - Gender differences in the innate immune response and vascular reactivity following the administration of endotoxin to human volunteers. EP - 1469 SN - 0090-3493 IS - iss. 6 SP - 1464 JF - Critical Care Medicine VL - vol. 35 DO - https://doi.org/10.1097/01.CCM.0000266534.14262.E8 ER - TY - JOUR AU - Halbertsma, F.J. AU - Vaneker, M. AU - Hoeven, J.G. van der PY - 2007 UR - https://hdl.handle.net/2066/53659 TI - Use of recruitment maneuvers during mechanical ventilation in pediatric and neonatal intensive care units in the Netherlands. EP - 1674 SN - 0342-4642 IS - iss. 9 SP - 1673 JF - Intensive Care Medicine VL - vol. 33 DO - https://doi.org/10.1007/s00134-007-0581-7 ER - TY - JOUR AU - Vaneker, M. AU - Halbertsma, F.J. AU - Egmond, J. van AU - Netea, M.G. AU - Dijkman, H.B.P.M. AU - Snijdelaar, D.G. AU - Joosten, L.A.B. AU - Hoeven, J.G. van der AU - Scheffer, G.J. PY - 2007 UR - https://hdl.handle.net/2066/52616 AB - BACKGROUND: Mechanical ventilation (MV) may activate the innate immune system, causing the release of cytokines. The resulting proinflammatory state is a risk factor for ventilator-induced lung injury. Cytokine increase results from direct cellular injury but may also result from cyclic stretch alone as demonstrated in vitro: mechanotransduction. To study mechanotransduction in vivo, the authors used an animal MV model with clinically relevant ventilator settings, avoiding alveolar damage. METHODS: Healthy C57BL6 mice (n = 82) were ventilated (tidal volume, 8 ml/kg; positive end-expiratory pressure, 4 cm H2O; fraction of inspired oxygen, 0.4) for 30, 60, 120, and 240 min. Assigned animals were allowed to recover for 2 days after MV. Both pulmonary tissue and plasma interleukin (IL)-1alpha, IL-1beta, tumor necrosis factor alpha, IL-6, IL-10, and keratinocyte-derived chemokine levels were measured. Histopathologic appearance of lung tissue was analyzed by light microscopy and electron microscopy. RESULTS: In lung tissue, all measured cytokines and keratinocyte-derived chemokine levels increased progressively with MV duration. Light microscopy showed increased leukocyte influx but no signs of alveolar leakage or albumin deposition. Electron microscopy revealed intact epithelial cell and basement membranes with sporadically minimal signs of partial endothelial detachment. In plasma, increased levels of IL-1alpha, tumor necrosis factor alpha, IL-6, and keratinocyte-derived chemokine were measured after MV. In the recovery animals, cytokine levels had normalized and no histologic alterations could be found. CONCLUSIONS: Mechanical ventilation induces reversible cytokine increase and leukocyte influx with preserved tissue integrity. This model offers opportunities to study the pathophysiologic mechanisms behind ventilator-induced lung injury and the contribution of MV to the "multiple-hit" concept. TI - Mechanical ventilation in healthy mice induces reversible pulmonary and systemic cytokine elevation with preserved alveolar integrity: an in vivo model using clinical relevant ventilation settings. EP - 426 SN - 0003-3022 IS - iss. 3 SP - 419 JF - Anesthesiology VL - vol. 107 DO - https://doi.org/10.1097/01.anes.0000278908.22686.01 ER - TY - JOUR AU - Derksen, R. AU - Scheffer, G.J. AU - Hoeven, J.G. van der PY - 2006 UR - https://hdl.handle.net/2066/50152 AB - Traditional theories of acid-base balance are based on the Henderson-Hasselbalch equation to calculate proton concentration. The recent revival of quantitative acid-base physiology using the Stewart model has increased our understanding of complicated acid-base disorders, but has also led to several new controversies. With the help of three patient histories, we show that the Henderson-Hasselbalch equation should be regarded as a simplified version of the more general Stewart model and not as something completely different. Therefore, both models may be useful at the bedside. TI - Quantitative acid-base physiology using the Stewart model. Does it improve our understanding of what is really wrong? EP - 333 SN - 0953-6205 IS - iss. 5 SP - 330 JF - European Journal of Internal Medicine VL - vol. 17 DO - https://doi.org/10.1016/j.ejim.2006.01.005 ER - TY - JOUR AU - Konijnenberg, A.Y. AU - Graeff-Meeder, E.R. de AU - Hoeven, J.G. van der AU - Buitelaar, J.K. AU - Kimpen, J.L.L. AU - Uiterwaal, C.S. PY - 2006 UR - https://hdl.handle.net/2066/50167 AB - CONTEXT: There is very little general evidence to support the clinical management, particularly diagnosis, of medically unexplained chronic pain (UCP) in children. OBJECTIVE: We sought to assess in children with UCP if clinical characteristics held important by general pediatricians help to accurately diagnose psychiatric morbidity and, alternatively, if the same can be achieved using dedicated questionnaires. METHODS: We used a cross-sectional diagnostic study in a pediatric outpatient clinic of a university hospital. Our participants were 134 patients, aged 8 to 18 years, who were referred for UCP. Performed were (1) diagnostic test reflecting the pediatricians' choice of clinical characteristics and (2) selected questionnaires. Classification was performed according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, by a child psychiatrist using the Diagnostic Interview Schedule for Children-Parent Version IV and the Semi-structured Clinical Interview for Children and Adolescents. Results were analyzed by logistic regression. RESULTS: Psychiatric morbidity was present in 80 of the children. A minority had a medical explanation for the pain (15% definite, 17% probable). The clinical diagnostic model included age, social-problem indicators, family structure, parental somatization, and school problems. In the quintile of children in whom this model predicted the highest risk, 93% indeed had psychiatric morbidity at reference testing. In the quintile with the lowest predicted risk, indeed only 27% had psychiatric morbidity. The Dutch Personality Inventory for Youth and the Child Behavior Checklist matched the pediatricians' choice of clinical characteristics. In the quintile of children with the highest predicted risk based on these questionnaires, 89% had psychiatric morbidity. In the quintile with the lowest predicted risk, only 15% had psychiatric morbidity. CONCLUSIONS: A pediatrician-chosen set of clinical characteristics of children with UCP proves useful in diagnosing psychiatric morbidity. Using selected questionnaire screening yields similar results. TI - Psychiatric morbidity in children with medically unexplained chronic pain: diagnosis from the pediatrician's perspective. EP - 897 SN - 0031-4005 IS - iss. 3 SP - 889 JF - Pediatrics (Evanston) VL - vol. 117 DO - https://doi.org/10.1542/peds.2005-0109 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/50167/50167.pdf?sequence=1 ER - TY - JOUR AU - Lemson, J. AU - Eijk, R.J.R. AU - Hoeven, J.G. van der PY - 2006 UR - https://hdl.handle.net/2066/50966 TI - The "cross-talk phenomenon" in transpulmonary thermodilution is flow dependent. EP - 1092 SN - 0342-4642 IS - iss. 7 SP - 1092 JF - Intensive Care Medicine VL - vol. 32 DO - https://doi.org/10.1007/s00134-006-0162-1 ER - TY - JOUR AU - Heemskerk, S. AU - Pickkers, P. AU - Bouw, M.P.W.J.M. AU - Draisma, A. AU - Hoeven, J.G. van der AU - Peters, W.H.M. AU - Smits, P. AU - Russel, F.G.M. AU - Masereeuw, R. PY - 2006 UR - https://hdl.handle.net/2066/50426 TI - Upregulation of renal inducible nitric oxide synthase during human endotoxemia and sepsis is associated with proximal tubule injury. EP - 862 SN - 1555-9041 IS - iss. 4 SP - 853 JF - Clinical Journal of the American Society of Nephrology VL - vol. 1 ER - TY - JOUR AU - Dorresteijn, M.J. AU - Smits, P. AU - Hoeven, J.G. van der AU - Pickkers, P. PY - 2006 UR - https://hdl.handle.net/2066/50161 TI - Role of potassium channel blockade in the treatment of sepsis-induced vascular hyporeactivity. EP - 2869 SN - 0090-3493 IS - iss. 11 SP - 2867 JF - Critical Care Medicine VL - vol. 34 ER - TY - JOUR AU - Pickkers, P. AU - Dorresteijn, M.J. AU - Bouw, M.P.W.J.M. AU - Hoeven, J.G. van der AU - Smits, P. PY - 2006 UR - https://hdl.handle.net/2066/51299 AB - BACKGROUND: During septic shock, the vasoconstrictor response to norepinephrine is seriously blunted. Animal experiments suggest that hyperpolarization of smooth muscle cells by opening of potassium (K) channels underlies this phenomenon. In the present study, we examined whether K-channel blockers and/or nitric oxide (NO) synthase inhibition could restore norepinephrine sensitivity during experimental human endotoxemia. METHODS AND RESULTS: Volunteers received 2 ng/kg Escherichia coli endotoxin intravenously. Forearm blood flow (FBF) was measured with venous occlusion plethysmography. Infusion of 4 dose steps of norepinephrine into the brachial artery decreased the FBF ratio (ratio of FBF in the experimental arm to FBF in the control arm) to 84 +/- 4%, 70 +/- 4%, 55 +/- 4%, and 38 +/- 4% (mean +/- SEM) of its baseline value. After endotoxin administration, norepinephrine-induced vasoconstriction was attenuated (FBF ratio, 101 +/- 4%, 92 +/- 4%, 83 +/- 6%, and 56 +/- 7%; n = 30; P = 0.0018; pooled data). Intrabrachial infusion of the K-channel blocker tetraethylammonium (TEA) completely restored the vasoconstrictor response to norepinephrine from 104 +/- 5%, 93 +/- 7%, 93 +/- 12%, and 69 +/- 12% to 89 +/- 9%, 73 +/- 4%, 59 +/- 5%, and 46 +/- 8% (n = 6; P = 0.045). Other K-channel blockers did not affect the response to norepinephrine. The NO synthase inhibitor N(G)-monomethyl-l-arginine (L-NMMA; 0.2 mg x min(-1) x dL(-1) intra-arterially) also restored the norepinephrine sensitivity. In the presence of L-NMMA, TEA did not have an additional effect on the norepinephrine-induced vasoconstriction (n = 6; P = 0.9). CONCLUSIONS: The K-channel blocker TEA restores the attenuated vasoconstrictor response to norepinephrine during experimental human endotoxemia. Coadministration of L-NMMA abolishes this potentiating effect of TEA, suggesting that NO mediates the endotoxin-induced effect on vascular K channels. In the absence of an effect of the selective adenosine triphosphate-dependent K-channel blocker tolbutamide, we conclude that the blunting effect of endotoxin on norepinephrine-induced vasoconstriction is caused by NO-mediated activation of calcium-activated K channels in the vascular wall. TI - In vivo evidence for nitric oxide-mediated calcium-activated potassium-channel activation during human endotoxemia. EP - 421 SN - 0009-7322 IS - iss. 5 SP - 414 JF - Circulation VL - vol. 114 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/51299/51299.pdf?sequence=1 ER - TY - JOUR AU - Ramakers, B.P.C. AU - Riksen, N.P. AU - Hoeven, J.G. van der AU - Smits, P. AU - Pickkers, P. PY - 2006 UR - https://hdl.handle.net/2066/50112 TI - Protective effects of adenosine A2A agonist during hemorrhagic shock: a simple intervention may result in a complex response. EP - 3059 SN - 0090-3493 IS - iss. 12 SP - 3059 JF - Critical Care Medicine VL - vol. 34 ER - TY - JOUR AU - Ramakers, B.P.C. AU - Riksen, N.P. AU - Rongen, G.A.P.J.M. AU - Hoeven, J.G. van der AU - Smits, P. AU - Pickkers, P. PY - 2006 UR - https://hdl.handle.net/2066/50998 AB - In the present study, we determined whether the immunomodulatory effect of adenosine receptor stimulation depends on the Toll-like Receptor (TLR) used for stimulation of cytokine release. Therefore, human mononuclear cells were stimulated by different TLR agonists in the absence and presence of A1 (CPA), A2a (CGS21680), and A3 (Cl-IB-MECA) adenosine receptor agonists. Effects of these agonists on Il-6, Il-10, IFN-gamma, TNF-alpha, and Il-1beta production were expressed as percentage inhibition/stimulation after TLR stimulation. CGS21680 inhibited TLR4-mediated TNF-alpha release and potentiated TLR3- and TLR5-mediated IL-6 release. Cl-IB-MECA inhibited TLR4-agonist-induced IFN-gamma release. Interestingly, CPA en Cl-IB-MECA tended to inhibit cytokine release only after TLR4 stimulation. In more detail, CPA potentiated TLR5-mediated IL-6 production, TLR3-mediated IFN-gamma production and TLR3-mediated Il-1beta-production compared to TLR4-mediated stimulation. Cl-IB-MECA potentiated TLR5-mediated IL-6 and Il-1beta formation as compared to TLR4-mediated stimulation. Finally, CGS21680 potentiated TLR5-mediated IL-6 production compared to TLR1-2 stimulation, and potentiated TLR3- and TLR5-mediated IL-10 production compared to TLR1-2-mediated stimulation. In conclusion, the effect of adenosine agonists on cytokine production depends on the specific TLR agonist used for stimulation. These findings suggest that well-known anti-inflammatory effects of adenosine agonists on LPS-induced inflammation cannot be extrapolated to situations in which stimulation of other TLR subtypes is involved. TI - The effect of adenosine receptor agonists on cytokine release by human mononuclear cells depends on the specific Toll-like receptor subtype used for stimulation. EP - 99 SN - 1043-4666 IS - iss. 1-2 SP - 95 JF - Cytokine VL - vol. 35 DO - https://doi.org/10.1016/j.cyto.2006.07.014 ER - TY - JOUR AU - Eijk, L.T.G.J. van AU - Nooteboom, A. AU - Hendriks, T. AU - Sprong, T. AU - Netea, M.G. AU - Smits, P. AU - Hoeven, J.G. van der AU - Pickkers, P. PY - 2006 UR - https://hdl.handle.net/2066/49698 AB - To gain insight in the pathogenesis of increased vascular permeability during sepsis, we studied the effect of plasma obtained during human experimental endotoxemia on the permeability of cultured endothelial monolayers. Eight healthy subjects received an i.v. dose of 2 ng/kg Escherichia coli O:113 lipopolysaccharide (LPS). The concentration of various plasma mediators that supposedly induce vascular permeability was measured over time. Plasmas that were obtained before, and 2 and 4 h after the administration of LPS were added to human umbilical venular endothelial cells that were cultured on semipermeable membranes.The permeability of the endothelial monolayers to fluorescein isothiocyanate-labeled bovine serum albumin was determined and expressed as the relative concentration of fluorescein isothiocyanate-bovine serum albumin when compared with that measured across empty Transwell-COL (Corning Life Sciences B.V., Schiphol-Rijk, The Netherlands) membranes (i.e., without endothelial monolayers). The permeability levels were correlated with the concentrations of various mediators.Experimental endotoxemia resulted in elevated levels of tumor necrosis factor alpha, interleukin (IL) 1beta, IL-6, IL-8, IL-10, and vascular endothelial growth factor and a moderate increase of IL-12 and IFN-gamma (all P values < 0.01). Incubation of human umbilical venular endothelial cells with plasma obtained 2 and 4 h after the administration of LPS increased the relative permeability from a baseline level (median) of 17% (range, 14% - 31%) to 23% (range, 12% - 39%; P = not significant) and 28% (range, 11% - 40%; P < 0.05), respectively. Plasma levels of vascular endothelial growth factor and IL-10, but not TNF-alpha or any other mediators, significantly correlated with the increase in endothelial permeability (r = 0.47, P = 0.038; r = 0.43, P = 0.038, respectively). The data presented here demonstrate that plasmas obtained from experimental human endotoxemia increase endothelial albumin permeability in vitro. Thus, cultured human endothelial monolayers provide a model to study sepsis-associated vascular changes. TI - Plasma obtained during human endotoxemia increases endothelial albumin permeability in vitro. EP - 362 SN - 1073-2322 IS - iss. 4 SP - 358 JF - Shock VL - vol. 25 DO - https://doi.org/10.1097/01.shk.0000209527.35743.b0 ER - TY - JOUR AU - Moviat, M. AU - Pickkers, P. AU - Voort, P.H. van der AU - Hoeven, J.G. van der PY - 2006 UR - https://hdl.handle.net/2066/50014 AB - INTRODUCTION: Metabolic alkalosis is a commonly encountered acid-base derangement in the intensive care unit. Treatment with the carbonic anhydrase inhibitor acetazolamide is indicated in selected cases. According to the quantitative approach described by Stewart, correction of serum pH due to carbonic anhydrase inhibition in the proximal tubule cannot be explained by excretion of bicarbonate. Using the Stewart approach, we studied the mechanism of action of acetazolamide in critically ill patients with a metabolic alkalosis. METHODS: Fifteen consecutive intensive care unit patients with metabolic alkalosis (pH > or = 7.48 and HCO3- > or = 28 mmol/l) were treated with a single administration of 500 mg acetazolamide intravenously. Serum levels of strong ions, creatinine, lactate, weak acids, pH and partial carbon dioxide tension were measured at 0, 12, 24, 48 and 72 hours. The main strong ions in urine and pH were measured at 0, 3, 6, 12, 24, 48 and 72 hours. Strong ion difference (SID), strong ion gap, sodium-chloride effect, and the urinary SID were calculated. Data (mean +/- standard error were analyzed by comparing baseline variables and time dependent changes by one way analysis of variance for repeated measures. RESULTS: After a single administration of acetazolamide, correction of serum pH (from 7.49 +/- 0.01 to 7.46 +/- 0.01; P = 0.001) was maximal at 24 hours and sustained during the period of observation. The parallel decrease in partial carbon dioxide tension was not significant (from 5.7 +/- 0.2 to 5.3 +/- 0.2 kPa; P = 0.08) and there was no significant change in total concentration of weak acids. Serum SID decreased significantly (from 41.5 +/- 1.3 to 38.0 +/- 1.0 mEq/l; P = 0.03) due to an increase in serum chloride (from 105 +/- 1.2 to 110 +/- 1.2 mmol/l; P < 0.0001). The decrease in serum SID was explained by a significant increase in the urinary excretion of sodium without chloride during the first 24 hours (increase in urinary SID: from 48.4 +/- 15.1 to 85.3 +/- 7.7; P = 0.02). CONCLUSION: A single dose of acetazolamide effectively corrects metabolic alkalosis in critically ill patients by decreasing the serum SID. This effect is completely explained by the increased renal excretion ratio of sodium to chloride, resulting in an increase in serum chloride. TI - Acetazolamide-mediated decrease in strong ion difference accounts for the correction of metabolic alkalosis in critically ill patients. EP - R14 SN - 1466-609X IS - iss. 1 SP - R14-1 JF - Critical Care VL - vol. 10 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/50014/50014.pdf?sequence=1 ER - TY - JOUR AU - Fikkers, B.G. AU - Vugt, S. van AU - Hoeven, J.G. van der AU - Hoogen, F.J.A. van den AU - Marres, H.A.M. PY - 2005 UR - https://hdl.handle.net/2066/47420 TI - Emergency airway equipment and training EP - 292 SN - 0003-2409 IS - iss. 3 SP - 292 JF - Anaesthesia VL - vol. 60 ER - TY - JOUR AU - Konijnenberg, A.Y. AU - Uiterwaal, C.S. AU - Kimpen, J.L.L. AU - Hoeven, J.G. van der AU - Buitelaar, J.K. AU - Graeff-Meeder, E.R. de PY - 2005 UR - https://hdl.handle.net/2066/48659 AB - AIMS: To describe and quantify impairment in an outpatient population of children with chronic pain of unknown origin (UCP). METHODS: A total of 149 children who presented with pain of at least three months' duration and without a satisfactory explanation at presentation were studied. Number of somatic complaints (Children's Somatisation Inventory, CSI), pain intensity (VAS, 0-10 cm), functional disability (Child Health Questionnaire (CHQ-CF) and clinical history), and general health perceptions (CHQ) were determined. RESULTS: Mean age of the children was 11.8 years; 73% were girls. Overall, 72% suffered impairment in sports activities, 51% reported absence from school, 40% experienced limitations in social functioning, and 34% had problems with sleeping. Mean number of somatic symptoms differed significantly between boys (8.4) and girls (10.7). The CHQ-CF scores for physical functioning, role/social functioning, and general health perceptions were 76.4, 70.7, and 57.5, respectively, indicating substantial impairment on all domains. The mean pain intensity was 4.7 for current and 7.1 for worst pain. Children solely evaluated by a general practitioner prior to referral reported less, though still substantial, impairment. Low general health perceptions, impaired role/social functioning, high pain intensity, and having headache or musculoskeletal pain were independent predictors of having significant impairment. CONCLUSIONS: Referred children with UCP show substantial impairment on multiple domains in daily life. TI - Children with unexplained chronic pain: substantial impairment in everyday life. EP - 686 SN - 0003-9888 IS - iss. 7 SP - 680 JF - Archives of Disease in Childhood VL - vol. 90 DO - https://doi.org/10.1136/adc.2004.056820 ER - TY - JOUR AU - Staatsen, M AU - Bleeker, C.P. AU - Marres, H.A.M. AU - Hoeven, J.G. van der AU - Fikkers, B.G. PY - 2005 UR - https://hdl.handle.net/2066/48267 TI - Emergency cricothyroidotomy: a comparison of two different techniques among residents and paramedics. EP - S118 SN - 0342-4642 IS - iss. supplement 1 SP - S118 JF - Intensive Care Medicine VL - vol. 31 ER - TY - JOUR AU - Fikkers, B.G. AU - Vugt, S. van AU - Hoeven, J.G. van der AU - Hoogen, F.J.A. van den AU - Marres, H.A.M. PY - 2005 UR - https://hdl.handle.net/2066/48268 TI - Emergency cricothyrotomy EP - 413 SN - 0003-2409 IS - iss. 4 SP - 413 JF - Anaesthesia VL - vol. 60 ER - TY - JOUR AU - Kemna, E.H.J.M. AU - Pickkers, P. AU - Nemeth, E. AU - Hoeven, J.G. van der AU - Swinkels, D.W. PY - 2005 UR - https://hdl.handle.net/2066/48502 AB - Hepatic peptide hormone hepcidin is the key regulator of iron metabolism and the mediator of anemia of inflammation. Previous studies indicated that interleukin-6 (IL-6) mediates hepcidin increase and consequent hypoferremia during inflammation. Here we used an in vivo human endotoxemia model to analyze the effects of lipopolysaccharide (LPS) as a more upstream inflammation activator. The temporal associations between plasma cytokines, hepcidin levels, and serum iron parameters were studied in 10 healthy individuals after LPS injection. IL-6 was dramatically induced within 3 hours after injection, and urinary hepcidin peaked within 6 hours, followed by a significant decrease in serum iron. Serum prohepcidin showed no significant change within a 22-hour time frame. These in vivo human results confirm the importance of the IL-6-hepcidin axis in the development of hypoferremia in inflammation and highlight the rapid responsiveness of this iron regulatory system. TI - Time-course analysis of hepcidin, serum iron, and plasma cytokine levels in humans injected with LPS. EP - 1866 SN - 0006-4971 IS - iss. 5 SP - 1864 JF - Blood VL - vol. 106 DO - https://doi.org/10.1182/blood-2005-03-1159 ER - TY - JOUR AU - Dorresteijn, M.J. AU - Pickkers, P. AU - Netea, M.G. AU - Hoeven, J.G. van der PY - 2005 UR - https://hdl.handle.net/2066/47341 AB - Endotoxin administration to animals and humans is an accepted experimental model of Gram-negative sepsis, and endotoxin is believed to play a major role in triggering the activation of cytokines. In septic patients, the IL-12/IL-18/IFN-gamma axis is activated and correlates with mortality. Our aim was to investigate the effects of endotoxin administration in humans on the activation of the IL-12/IL-18/IFN-gamma axis. Seven healthy volunteers received E. coli endotoxin (O:113). Hemodynamics, temperature and the course of plasma concentrations of TNF-alpha, IL-1beta, IL-12, IL-18 and IFN-gamma were determined. Endotoxin administration resulted in the expected flu-like symptoms, a temperature of 38.8 +/- 0.3(o)C (p < 0.003), a decrease in mean arterial blood pressure of 14.8 +/- 1.8 mmHg (p < 0.0002) and an increase in heart rate of 27.5 +/- 4.8 bpm (p < 0.002) compared to baseline values. TNF-alpha increased from 16.6 +/- 8.2 to 927 +/- 187 pg/mL (p < 0.003). IL-1beta increased from 8.6 +/- 0.5 to 25.3 +/- 2.0 pg/mL (p < 0.0001). IL-12 showed no significant increase (8.2 +/- 0.2 to 9.3 +/- 0.8 pg/mL, p = 0.13), and all IL-18 measurements remained below the level of detection. In contrast, IFN-gamma showed an increase from 106.6 +/- 57.1 to 152.7 +/- 57.8 (p < 0.005). These results indicate that pathways other than the IL-12/IL-18 axis may induce IFN-gamma production in human endotoxemia. TI - IFN-gamma is not induced through increased plasma concentrations of interleukin-12/interleukin-18 during human endotoxemia. EP - 193 SN - 1148-5493 IS - iss. 3 SP - 191 JF - European Cytokine Network VL - vol. 16 ER - TY - JOUR AU - Merkx, M.A.W. AU - Hoeven, J.G. van der AU - Wilde, P.C.M. de PY - 2005 UR - https://hdl.handle.net/2066/48117 AB - To consider the value of prognostic factors in the development of a squamous cell carcinoma from a leukoplakia of the oral mucosa, a retrospective study was performed. Clinical and histological data of 104 patients with oral leukoplakia were analyzed. Leukoplastic lesions with dysplasia in the initial biopsy (n = 38) had been treated by excision (n = 28), by laser evaporation (n = 6) or a combination of these treatments (n = 4). Non-dysplastic lesions (n = 66) had been excised (n = 48), evaporised (n = 17) or treated by excision as well as laser evaporation (n = 1). During follow-up of maximal 6 years (mean 3.6 years), 12 patients had developed an infiltrative squamous cell carcinoma at the site of the primary lesion, 2 within a period of 24 months. No relation could be found between on the one hand size (p > 0.2), clinical aspect (p > 0.2), location (p > 0.45), and primary treatment (p > 0.15) of the lesion, and on the other hand the risk of developing a squamous cell carcinoma. Only a relation could be found between (the intensity of) dysplasia and the development of a squamous cell carcinoma (p < 0.001). It was concluded that because of the high risk of developing a squamous cell carcinoma, patients with a dysplastic mucosal oral lesion should be followed during a prolonged time. TI - [Premalignant lesions of the oral mucosa. Prognosis, treatment and follow-up] EP - 55 SN - 0028-2200 IS - iss. 2 SP - 51 JF - Nederlands Tijdschrift voor Tandheelkunde VL - vol. 112 ER - TY - JOUR AU - Hoedemaekers, C.W.E. AU - Pickkers, P. AU - Netea, M.G. AU - Deuren, M. van AU - Hoeven, J.G. van der PY - 2005 UR - https://hdl.handle.net/2066/47482 AB - ABSTRACT : INTRODUCTION : Strict control of plasma glucose in diabetic and non-diabetic patients has been shown to improve outcome in several clinical settings. There is extensive evidence that glucose can stimulate the production of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-alpha and IL-6, with no effect on the anti-inflammatory cytokine IL-10. We hypothesized that strict glucose regulation results in a change in cytokine balance from a pro-inflammatory state to a more balanced anti-inflammatory condition. In a randomized controlled trial we studied the effect of strict glycemic control on the local and systemic pro-inflammatory and anti-inflammatory balance in non-diabetic patients undergoing elective coronary artery bypass grafting with cardiopulmonary bypass. METHODS : After surgery patients were randomly assigned to intensive insulin therapy (blood glucose between 80 and 110 mg/dl) or conventional insulin therapy (blood glucose less than 200 mg/dl). At 0, 1, 2, 4, 8, 12, 16 and 24 hours after admission to the intensive care unit, plasma samples and samples from the mediastinal drains were obtained. We measured the concentrations of the pro-inflammatory cytokines TNF-alpha and IL-6 and the anti-inflammatory cytokine IL-10 by enzyme-linked immunosorbent assay. RESULTS : Both patient groups were comparable in demographics, clinical characteristics and peri-operative data. In the intensive treatment group, glucose levels were significantly lower than in the conventionally treated group. No differences were found between both groups in the concentrations of TNF-alpha, IL-6 and IL-10 in plasma samples or in fluid draining the mediastinal cavity. Levels of IL-6 and IL-10 were significantly higher in mediastinal fluid samples than in plasma samples, suggesting a compartmentalized production of cytokines. CONCLUSION : The protective effect of intensive insulin therapy in patients after cardiac surgery with cardiopulmonary bypass is not related to a change in cytokine balance from a pro-inflammatory to an anti-inflammatory pattern. Systemic cytokine levels are not representative of the local inflammatory response. TI - Intensive insulin therapy does not alter the inflammatory response in patients undergoing coronary artery bypass grafting: a randomized controlled trial [ISRCTN95608630]. EP - 7 SN - 1466-609X IS - iss. 6 SP - R790 JF - Critical Care VL - vol. 9 DO - https://doi.org/10.1186/cc3911 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/47482/47482.pdf?sequence=1 ER - TY - JOUR AU - Pickkers, P. AU - Sprong, T. AU - Eijk, L.T.G.J. van AU - Hoeven, J.G. van der AU - Smits, P. AU - Deuren, M. van PY - 2005 UR - https://hdl.handle.net/2066/48215 AB - Meningococcal septic shock is an important cause of morbidity and mortality in children and young adults worldwide and is the prototypical gram-negative septic shock. One of the key factors in the development of shock is increased microvascular permeability. Vascular endothelial growth factor (VEGF) is a central factor in angiogenesis and is an important mediator of vascular permeability. Thirteen patients with meningococcal infection (eight presenting with shock) were investigated in the early phase of invasive meningococcal disease. Cytokines, complement activation, and VEGF plasma concentrations were measured during the first 48 h on the pediatric intensive care unit. Increased cytokine concentrations and activation of the complement system were observed. VEGF plasma concentrations were increased (median 193 pg/mL, range 71-1082) and were highest in the presence of shock (208 pg/mL, 169-1082) compared with patients presenting without shock (92 pg/mL range 71-299). VEGF concentration at admission correlated with the severity of disease (pediatric risk of mortality score, R=0.90 [Spearman], P=0.0001) and the amount of fluids administered within the first 24 h (R=0.90, P<0.0001). In all patients, a decrease in VEGF was associated with a decrease in fluid intake during t=24 to 48 h. The results suggest that apart from correlation with IL-1 beta, -10, -12, and complement activation, microvascular permeability in sepsis is also closely linked to the plasma concentration of VEGF. The role of VEGF in sepsis-associated increased microvascular permeability needs further exploration and may represent a new therapeutic target. TI - Vascular endothelial growth factor is increased during the first 48 hours of human septic shock and correlates with vascular permeability. EP - 512 SN - 1073-2322 IS - iss. 6 SP - 508 JF - Shock VL - vol. 24 DO - https://doi.org/10.1097/01.shk.0000190827.36406.6e ER - TY - JOUR AU - Dorresteijn, M.J. AU - Eijk, L.T.G.J. van AU - Netea, M.G. AU - Smits, P. AU - Hoeven, J.G. van der AU - Pickkers, P. PY - 2005 UR - https://hdl.handle.net/2066/48621 AB - Clinical experience suggests that the administration of fluids in human endotoxemia reduces symptoms. In the present study, the effects of a standardised fluid protocol on symptoms, inflammatory and hemodynamic parameters in human endotoxemia are determined. With approval of the local ethics committee, 16 healthy volunteers received 2 ng/kg of Escherichia coli endotoxin (O:113). After an overnight fast, nine subjects received 1.5 l of 2.5% glucose/0.45% NaCl the hour prior to the endotoxin administration and 150 ml/h during the course of the experiment ('prehydrated group'). Seven subjects only received a continuous infusion of 75 ml/h during the experiment ('non-prehydrated group'). The course of inflammatory parameters and symptoms were determined and mean arterial pressure, heart rate and forearm blood flow were measured. In the prehydrated group, TNF-alpha increased to 522 +/- 63 pg/ml (mean +/- SEM) while the maximum in the non-prehydrated group was 927 +/- 187 pg/ml (P < 0.04). IL-10 increased similarly in both groups (non-prehydrated 117 +/- 18 pg/ml and prehydrated 99 +/- 18 pg/ml; P = NS). The prehydrated group had a significantly lower (P < 0.004) symptom score and recovered sooner (P = 0.004). Endotoxin-induced changes in hemodynamics revealed no significant differences between groups. We demonstrate that prehydration in experimental human endotoxemia significantly shifts the cytokine balance towards a more anti-inflammatory pattern. This effect is associated with a reduction in symptoms, whereas the changes in hemodynamic parameters are not influenced by prehydration. TI - Iso-osmolar prehydration shifts the cytokine response towards a more anti-inflammatory balance in human endotoxemia. EP - 293 SN - 0968-0519 IS - iss. 5 SP - 287 JF - Journal of Endotoxin Research VL - vol. 11 DO - https://doi.org/10.1179/096805105X58715 ER - TY - JOUR AU - Eijkenboom, J.J. AU - Eijk, L.T.G.J. van AU - Pickkers, P. AU - Peters, W.H.M. AU - Wetzels, J.F.M. AU - Hoeven, J.G. van der PY - 2005 UR - https://hdl.handle.net/2066/47876 AB - OBJECTIVE: Cardiac surgery is an important risk factor for the development of acute renal failure. Cytosolic enzymes glutathione S-transferase (GST) A1 and P1 are present selectively in proximal and distal tubular cells, respectively. We determined the extent and site of tubular injury and examined if GST excretion may predict a clinically relevant change in renal function. DESIGN AND SETTING: A prospective, observational study in 84 consecutive patients in the cardiac surgery intensive care unit of the University Medical Centre Nijmegen. MEASUREMENTS AND RESULTS: Urinary GST enzyme excretion was determined 0-4 h and 20-24 h after cardiac surgery by enzyme-linked immunosorbent assay. Data are expressed as median and 5-95% range. Urinary excretion of GSTA1 was increased: 1.25 microg/mmol [0.31-10.20] creatinine at t =0-4 h ( p <0.0001, compared with controls; 0.25 [0.1-0.8]) and returned to normal values at t =20-24 h. Excretion of GSTP1 was 2.11 microg/mmol [0.52-17.82] creatinine ( p <0.0001) at t =0-4 h and remained significantly elevated: 0.84 [0.30-16.86] at t =20-24 h ( p =0.01) compared with controls (0.5 [0.2-1.1]). The ten patients with the highest urinary excretion of GSTA1 or GSTP1 did not demonstrate a different plasma creatinine level on postoperative day 3, compared with the ten patients with the lowest urinary excretion of GSTA1 or GSTP1. CONCLUSION: Uncomplicated cardiac surgery results in a statistically significant increase in the urinary excretion of GSTA1 and GSTP1 as compared with healthy controls, indicating proximal and distal tubular damage. However, this small increase in urinary excretion of GSTs is not associated with clinically relevant renal injury. TI - Small increases in the urinary excretion of glutathione S-transferase A1 and P1 after cardiac surgery are not associated with clinically relevant renal injury. EP - 667 SN - 0342-4642 IS - iss. 5 SP - 664 JF - Intensive Care Medicine VL - vol. 31 DO - https://doi.org/10.1007/s00134-005-2608-2 ER - TY - JOUR AU - Eijk, L.T.G.J. van AU - Pickkers, P. AU - Smits, P. AU - Broek, W. van den AU - Bouw, M.P.W.J.M. AU - Hoeven, J.G. van der PY - 2005 UR - https://hdl.handle.net/2066/48813 AB - INTRODUCTION: Septic shock is associated with increased microvascular permeability. As a model for study of the pathophysiology of sepsis, endotoxin administration to humans has facilitated research into inflammation, coagulation and cardiovascular effects. The present study was undertaken to determine whether endotoxin administration to human volunteers can be used as a model to study the sepsis-associated increase in microvascular permeability. METHODS: In an open intervention study conducted in a university medical centre, 16 healthy volunteers were evaluated in the research unit of the intensive care unit. Eight were administered endotoxin intravenously (2 ng/kg Escherichia coli O113) and eight served as control individuals. Microvascular permeability was assessed before and 5 hours after the administration of endotoxin (n = 8) or placebo (n = 8) by three different methods: transcapillary escape rate of I(125)-albumin; venous occlusion strain-gauge plethysmography to determine the filtration capacity; and bioelectrical impedance analysis to determine the extracellular and total body water. RESULTS: Administration of endotoxin resulted in the expected increases in proinflammatory cytokines, temperature, flu-like symptoms and cardiovascular changes. All changes were significantly different from those in the control group. In the endotoxin group all microvascular permeability parameters remained unchanged from baseline: transcapillary escape rate of I(125)-albumin changed from 7.2 +/- 0.6 to 7.7 +/- 0.9%/hour; filtration capacity changed from 5.0 +/- 0.3 to 4.2 +/- 0.4 ml/min per 100 ml mmHg x 10(-3); and extracellular/total body water changed from 0.42 +/- 0.01 to 0.40 +/- 0.01 l/l (all differences not significant). CONCLUSION: Although experimental human endotoxaemia is frequently used as a model to study sepsis-associated pathophysiology, an endotoxin-induced increase in microvascular permeability in vivo could not be detected using three different methods. Endotoxin administration to human volunteers is not suitable as a model in which to study changes in microvascular permeability. TI - Microvascular permeability during experimental human endotoxemia: an open intervention study. EP - 64 SN - 1466-609X IS - iss. 2 SP - R157 JF - Critical Care VL - vol. 9 DO - https://doi.org/10.1186/cc3050 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/48813/48813.pdf?sequence=1 ER - TY - JOUR AU - Alp, E. AU - Hoeven, J.G. van der AU - Verweij, P.E. AU - Mouton †, J.W. AU - Voss, A. PY - 2005 UR - https://hdl.handle.net/2066/48812 TI - Duration of antibiotic treatment: are even numbers odd? EP - 442 SN - 0305-7453 IS - iss. 2 SP - 441 JF - Journal of Antimicrobial Chemotherapy VL - vol. 56 DO - https://doi.org/10.1093/jac/dki213 ER - TY - JOUR AU - Halbertsma, F.J. AU - Vaneker, M. AU - Scheffer, G.J. AU - Hoeven, J.G. van der PY - 2005 UR - https://hdl.handle.net/2066/48124 AB - BACKGROUND: Mechanical ventilation is known to induce and aggravate lung injury. One of the underlying mechanisms is biotrauma, an inflammatory response in which cytokines play a crucial role. OBJECTIVE: To review the literature on the role of cytokines in ventilator-induced lung injury (VILI) and multiple organ dysfunction syndrome (MODS). MATERIAL AND METHODS: 57 English written, peer-reviewed articles on cytokines in in-vitro settings (n=5), ex-vivo models (n=9) in-vitro models (n=19) and clinical trials (n=24). RESULTS: Mechanical ventilation (MV) can induce cytokine upregulation in both healthy and injured lungs. The underlying mechanisms include alveolar cellular responses to stretch with subsequent decompartimentalisation due to concomitant cellular barrier damage. The cytokines involved are interleukin (IL)-8 and CXC chemokines, and probably IL-6, IL-1beta and tumour necrosis factor (TNF)-alpha. Cytokines are important for signalling between inflammatory cells and recruiting leucocytes to the lung. There is strong circumstantial evidence that the release of cytokines into the systemic circulation contributes to the pathogenesis of MODS. Multiple studies demonstrate the relation between elevated proinflammatory cytokine concentrations and mortality. CONCLUSION: Cytokines are likely to play a role in the various interrelated processes that lead to VILI and other MV-related complications, such as MODS and possibly ventilatorassociated pneumonia. Cytokines are good surrogate endpoints in exploring the pathogenesis and pathophysiology of VILI in both experimental and clinical studies. TI - Cytokines and biotrauma in ventilator-induced lung injury: a critical review of the literature. EP - 392 SN - 0300-2977 IS - iss. 10 SP - 382 JF - Netherlands Journal of Medicine VL - vol. 63 ER - TY - JOUR AU - Halbertsma, F.J. AU - Hoeven, J.G. van der PY - 2005 UR - https://hdl.handle.net/2066/48725 AB - A literature review was conducted to assess the evidence for recruitment manoeuvres used in conventional mechanical positive pressure ventilation. A total of 61 studies on recruitment manoeuvres were identified: 13 experimental, 31 ICU, 6 PICU and 12 anaesthesia studies. Recruitment appears to be a continuous process during inspiration and expiration and is determined by peak inspiratory pressure (PIP) and positive end expiratory pressure (PEEP). Single or repeated recruitment manoeuvres may result in a statistically significant increase in oxygenation; however, this is short lasting and clinically irrelevant, especially in late ARDS and pneumonia. Temporary PIP elevation may be effective but only after PEEP loss (for example disconnection and tracheal suctioning). Continuous PEEP elevation and prone positioning can increase P(a)O2 significantly. Adverse haemodynamic or barotrauma effects are reported in various studies. No data exist on the effect of recruitment manoeuvres on mortality, morbidity, length of stay or duration of mechanical ventilation. Although recruitment manoeuvres can improve oxygenation, they can potentially increase lung injury, which eventually determines outcome. Based on the presently available literature, prone position and sufficient PEEP as part of a lung protective ventilation strategy seem to be the safest and most effective recruitment manoeuvres. As paediatric physiology is essentially different from adult, paediatric studies are needed to determine the role of recruitment manoeuvres in the PICU. TI - Lung recruitment during mechanical positive pressure ventilation in the PICU: what can be learned from the literature? EP - 790 SN - 0003-2409 IS - iss. 8 SP - 779 JF - Anaesthesia VL - vol. 60 DO - https://doi.org/10.1111/j.1365-2044.2005.04187.x ER - TY - JOUR AU - Meent, H. van de AU - Vos, P.E. AU - Schreuder, H.W.B. AU - Hoeven, J.G. van der PY - 2004 UR - https://hdl.handle.net/2066/59026 AB - Three men aged 18, 18 and 24 years, developed hypotension and bradycardia following an acute traumatic cervical or thoracic spinal cord injury. After treatment in intensive care and 1-12 months of rehabilitation they still suffered from considerable neurological disorders. Hypotension and bradycardia are common phenomena following acute traumatic cervical and thoracic spinal cord injury. Awareness of cardiovascular complications as a possible threat for functional recovery and adequate insight in the neurological cause of hypotension and bradycardia are important issues in the acute treatment of patients with spinal cord injury. It seems sensible to admit these patients to a medium-care or intensive-care department where they can be monitored and treated by a specialised team in accordance with an adequate protocol. TI - [Acute traumatic spinal cord injury and cardiovascular complications due to neurogenic shock: a possible threat for functional recovery] EP - 1106 SN - 0028-2162 IS - iss. 22 SP - 1103 JF - Nederlands Tijdschrift voor Geneeskunde VL - vol. 148 ER - TY - JOUR AU - Haren, F.M. van AU - Oudemans-van Straaten, H.M. AU - Mathus-Vliegen, E.M.H. AU - Tepaske, R. AU - Hoeven, J.G. van der PY - 2004 UR - https://hdl.handle.net/2066/58924 AB - Nutritional therapy in the intensive care unit exerts favourable effects on morbidity and mortality. Enteral nutrition is preferable to parenteral nutrition. Only perforation or total obstruction of the gastrointestinal tract, proven mesenteric ischaemia and toxic megacolon are absolute contra-indications to enteral nutrition. Early enteral nutrition is effective in decreasing infectious complications and reducing the length of stay in the hospital. Nutrition that is enriched with specific ingredients in order to modulate the immune response is referred to as immunonutrition. The use of immunonutrition, notably in surgical intensive care patients, has a favourable effect on the incidence of infectious complications, the duration of artificial respiration and the length of hospital stay. The addition of glutamine to parenteral nutrition may reduce mortality compared to standard parenteral nutrition. Implementation of a simple feeding algorithm in the intensive care unit, with special attention for the treatment of delayed gastric emptying, is cost-effective and leads to an improvement in the nutritional parameters. TI - [Nutrition and health--enteral nutrition in intensive care patients] EP - 1091 SN - 0028-2162 IS - iss. 22 SP - 1086 JF - Nederlands Tijdschrift voor Geneeskunde VL - vol. 148 ER - TY - JOUR AU - Pickkers, P. AU - Rosendaal, A.J. van AU - Hoeven, J.G. van der AU - Smits, P. PY - 2004 UR - https://hdl.handle.net/2066/57698 AB - Sepsis-induced vasodilation is characterized by an attenuated sensitivity to vasoconstrictor substances such as norepinephrine, possibly mediated by activation of vascular potassium channels. We determined whether vasodilation associated with potassium channel activation resulted in an attenuated vasoconstrictive response to norepinephrine in humans and whether the vasodilation associated with potassium channel activation could be inhibited by pharmacological potassium channel blockers. In 30 volunteers, the brachial artery was cannulated for infusion of drugs. Forearm blood flow (FBF) was measured in both arms using strain-gauge venous occlusion plethysmography. Forearm vascular resistance (FVR, mean arterial pressure/FBF) was calculated. The effects of vasodilation induced by sodium nitroprusside (SNP, nitric oxide donor) or diazoxide (activator of the ATP-dependent potassium channel) on norepinephrine-mediated vasoconstriction were examined. Also, the effects of potassium channel blockers on vasodilation associated with potassium channel activation were determined. Intraarterial SNP infusion (2 microg/min/dL) increased forearm blood flow by 235%, from (mean +/- SEM) 2.8 +/- 0.7 to 9.4 +/- 1.5 mL/min/dL (P < 0.0001). Subsequent norepinephrine infusion (10, 30, 100, 300, 1000 ng/min/dL) increased FVR dose-dependently from 13 +/- 4 AU to 249 +/- 45 AU at the highest norepinephrine infusion. Intraarterial diazoxide infusion (1 mg/min/dL) increased FBF by 209% from 2.2 +/- 0.3 to 6.8 +/- 1.0 mL/min/dL (P < 0.001). Subsequent norepinephrine infusion increased FVR from 18 +/- 5 to 51 +/- 6 AU at the highest norepinephrine infusion rate (n = 10), significantly different from the norepinephrine-induced effects during SNP coinfusion (P < 0.001). Diazoxide-induced fall in FVR in the infused forearm was inhibited by potassium channel blockers tetraethyl ammonium (1 mg/min/dL, n = 10, P = 0.004) and quinine (50 microg/min/dL, n = 10, P = 0.016). Vasodilation induced by vascular potassium channel activation is associated with an impressive reduction in the vasoconstrictor response to norepinephrine in humans. In accordance with animal experiments, this indicates that potassium channel activation could account for the diminished norepinephrine sensitivity in septic patients. Vasodilation associated with potassium channel activation can be inhibited by pharmacological potassium channel blockade. The possible role of potassium channel blockers during sepsis-induced potassium channel activation and vasodilation in humans needs further elucidation. TI - Activation of the ATP-dependent potassium channel attenuates norepinephrine-induced vasoconstriction in the human forearm. EP - 325 SN - 1073-2322 IS - iss. 4 SP - 320 JF - Shock VL - vol. 22 DO - https://doi.org/10.1097/01.shk.0000142250.85264.10 ER - TY - JOUR AU - Konijnenberg, A.Y. AU - Graeff-Meeder, E.R. de AU - Kimpen, J.L.L. AU - Hoeven, J.G. van der AU - Uiterwaal, C.S. PY - 2004 UR - https://hdl.handle.net/2066/59013 AB - OBJECTIVE: To investigate the opinions of general pediatricians regarding children with unexplained chronic pain (UCP), with respect to the presumed cause of the pain and the optimal diagnostic approach for these children. DESIGN: Diagnostic follow-up study. SETTING: Outpatient clinic of a university children's hospital. PARTICIPANTS: A total of 134 consecutive patients, 8 to 18 years of age, referred for pain of > or =3-month duration without a satisfactory explanation at presentation. METHODS: A full copy of the patient records from routine medical practice and data from standardized psychiatric assessments, standardized questionnaires, and standardized follow-up assessments were provided to 17 pediatricians assigned to 3 panels. MAIN OUTCOME MEASURES: Agreement regarding the presumed primary cause and diagnostic approach for children with UCP, with consensus being defined as > or =80% agreement among the pediatricians. RESULTS: The mean age of the children (73% girls) was 11.8 years (SD: 2.6 years). Psychiatric (co)morbidity was present for 60% of the children. Consensus regarding the presumed primary cause was reached for 43% of the patients (58 of 134 patients), ie, 72% (42 of 58 patients) primarily dysfunctional, 17% (10 of 58 patients) primarily psychologic, and 10% (6 of 58 patients) primarily somatic. Consensus regarding the diagnostic approach was reached for 63% of the children (84 of 134 children), leaving more than one-third of the children (37%) without diagnostic consensus. CONCLUSIONS: The relatively high rates of disagreement regarding the optimal diagnostic approach and presumed primary cause illustrate the difficulties of diagnostic evaluation and subsequent therapeutic strategy design for this patient group. Therefore, children with UCP might be at risk for suboptimal care. TI - Children with unexplained chronic pain: do pediatricians agree regarding the diagnostic approach and presumed primary cause? EP - 1226 SN - 0031-4005 IS - iss. 5 SP - 1220 JF - Pediatrics (Evanston) VL - vol. 114 DO - https://doi.org/10.1542/peds.2004-0355 ER - TY - JOUR AU - Fikkers, B.G. AU - Vugt, S. van AU - Hoeven, J.G. van der AU - Hoogen, F.J.A. van den AU - Marres, H.A.M. PY - 2004 UR - https://hdl.handle.net/2066/58606 AB - In a randomised crossover trial, we compared a wire-guided cricothyrotomy technique (Minitrach) with a catheter-over-needle technique (Quicktrach). Performance time, ease of method, accuracy in placement and complication rate were compared. Ten anaesthesiology and 10 ENT residents performed cricothyrotomies with both techniques on prepared pig larynxes. The catheter-over-needle technique was faster than the wire-guided (48 compared to 150 s, p < 0.001) and subjectively easier to perform (VAS-score 2.1 vs. 5.6, p < 0.001). Correct positioning of the cannula could be achieved in 95% and 85%, respectively (NS). There was one complication in the catheter-over-needle group compared to five in the wire-guided group. We conclude that the wire-guided minitracheotomy kit is unsuitable for emergency cricothyrotomies performed by inexperienced practitioners. On the other hand, the catheter-over-needle technique appears to be quick, safe and reliable. TI - Emergency cricothyrotomy: a randomised crossover trial comparing the wire-guided and catheter-over-needle techniques. EP - 1011 SN - 0003-2409 IS - iss. 10 SP - 1008 JF - Anaesthesia VL - vol. 59 DO - https://doi.org/10.1111/j.1365-2044.2004.03794.x ER - TY - JOUR AU - Renes, M.H. AU - Hoeven, J.G. van der PY - 2004 UR - https://hdl.handle.net/2066/57854 TI - Administration of nitric oxide synthase inhibitor 546c88 in septic shock. EP - 1626 SN - 0090-3493 IS - iss. 7 SP - 1625 JF - Critical Care Medicine VL - vol. 32 ER - TY - JOUR AU - Klein Gunnewiek, J.M.T. AU - Hoeven, J.G. van der PY - 2004 UR - https://hdl.handle.net/2066/58646 AB - PURPOSE OF THE REVIEW: Elevated levels of cardiac troponins, indicative of the presence of cardiac injury, have been reported in critically ill patients. In this review, the incidence, significance, and clinical relevance of elevated troponin levels among this group of patients will be discussed. RECENT FINDINGS: It has been shown that elevated cardiac troponin levels can be present among critically ill septic patients without evidence of myocardial ischemia. Recent studies show that elevated troponin levels are also present in a diverse group of critically ill patients without sepsis or septic shock. In addition, several but not all studies show that the mortality rate of troponin-positive patients is significantly higher compared with troponin-negative patients. SUMMARY: Elevated troponin levels are not only present in patients suffering from acute coronary syndromes but can also be present in critically ill patients. Even minor elevations are specific for myocardial injury. However, every elevated troponin level in the critically ill patient should not be rigorously diagnosed or treated as a myocardial infarction. TI - Cardiac troponin elevations among critically ill patients. EP - 346 SN - 1070-5295 IS - iss. 5 SP - 342 JF - Current Opinion in Critical Care VL - vol. 10 ER - TY - JOUR AU - Fikkers, B.G. AU - Veen, J.A. van AU - Kooloos, J.G.M. AU - Pickkers, P. AU - Hoogen, F.J.A. van den AU - Hillen, B. AU - Hoeven, J.G. van der PY - 2004 UR - https://hdl.handle.net/2066/58607 AB - STUDY OBJECTIVE: Part 1: To describe cases of emphysema (subcutaneous and/or mediastinal) and pneumothorax after percutaneous dilational tracheostomy (PDT) in a series of 326 patients, and to review the existing literature describing the incidence and possible mechanisms. Part 2: To analyze the potential mechanisms for the development of emphysema and pneumothorax in human cadaver models. DESIGN: A retrospective analysis of PDTs, in combination with an anatomic study in human cadavers. MATERIALS AND METHODS: Part 1: All ICU patients who underwent PDT between 1997 and 2002 were enrolled in the study. We analyzed the cases of emphysema and pneumothorax. Similar cases were retrieved from the literature and underwent a systematic review. Part 2: The relevant anatomic structures were studied. We simulated the clinical situation after PDT in a human pathologic study in order to induce subcutaneous emphysema and pneumothorax. MEASUREMENTS AND RESULTS: Part 1: Five cases of subcutaneous emphysema (1.5%) and two cases of pneumothorax (0.6%) are described. In the literature search, we found 41 cases of emphysema (1.4%) and 25 cases of pneumothorax (0.8%) in a total of 3,012 patients. Part 2: Subcutaneous emphysema could easily be induced in a human cadaver model by inflating air in the pretracheal tissues and after posterior tracheal wall laceration. Air leakage was also possible through a fenestrated cannula via the space between the inner nonfenestrated cannula and outer cannula and then through the fenestration. CONCLUSIONS: We conclude that one mechanism for the development of emphysema is an imperfect positioning of the fenestrated cannula, whereby the fenestration is extraluminal. For this reason, fenestrated cannulas should not be used immediately after placement of a PDT. Posterior tracheal wall laceration is another mechanism responsible for emphysema after PDT. After perforation of the posterior tracheal wall, the pleural space can be reached easily. This may result in a pneumothorax. TI - Emphysema and pneumothorax after percutaneous tracheostomy: case reports and an anatomic study. EP - 1814 SN - 0012-3692 IS - iss. 5 SP - 1805 JF - Chest VL - vol. 125 DO - https://doi.org/10.1378/chest.125.5.1805 ER - TY - JOUR AU - Fikkers, B.G. AU - Staatsen, M AU - Lardenoije, S.G. AU - Hoogen, F.J.A. van den AU - Hoeven, J.G. van der PY - 2004 UR - https://hdl.handle.net/2066/57948 AB - INTRODUCTION: To evaluate and compare the peri-operative and postoperative complications of the two most frequently used percutaneous tracheostomy techniques, namely guide wire dilating forceps (GWDF) and Ciaglia Blue Rhino (CBR). METHODS: A sequential cohort study with comparison of short-term and long-term peri-operative and postoperative complications was performed in the intensive care unit of the University Medical Centre in Nijmegen, The Netherlands. In the period 1997-2000, 171 patients underwent a tracheostomy with the GWDF technique and, in the period 2000-2003, a further 171 patients with the CBR technique. All complications were prospectively registered on a standard form. RESULTS: There was no significant difference in major complications, either peri-operative or postoperative. We found a significant difference in minor peri-operative complications (P < 0.01) and minor late complications (P < 0.05). CONCLUSION: Despite a difference in minor complications between GWDF and CBR, both techniques seem equally reliable. TI - Comparison of two percutaneous tracheostomy techniques, guide wire dilating forceps and Ciaglia Blue Rhino: a sequential cohort study. EP - 305 SN - 1466-609X IS - iss. 5 SP - R299 JF - Critical Care VL - vol. 8 DO - https://doi.org/10.1186/cc2907 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/57948/57948.pdf?sequence=1 ER - TY - JOUR AU - Fikkers, B.G. AU - Hoeven, J.G. van der PY - 2004 UR - https://hdl.handle.net/2066/59196 TI - Complications of percutaneous dilating tracheostomy. EP - 398 SN - 1466-609X IS - iss. 5 SP - 397 JF - Critical Care VL - vol. 8 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/59196/59196.pdf?sequence=1 ER - TY - JOUR AU - Eijk, L.T.G.J. van AU - Pickkers, P. AU - Smits, P. AU - Bouw, M.P.W.J.M. AU - Hoeven, J.G. van der PY - 2004 UR - https://hdl.handle.net/2066/57759 AB - OBJECTIVE: Endotoxin administration to humans is a common means to study systemic inflammation. Worldwide, thousands of volunteers have received endotoxin, and adverse events are rarely reported. The aim of this report was to increase awareness of specific risks of the intravenous administration of endotoxin to human volunteers. DESIGN: Report of four cases who developed severe bradycardia or protracted asystole after administration of endotoxin. Interviews with investigators at three large centers that conduct normal volunteer endotoxin studies. SETTING: Clinical research unit. CASES: Four subjects developed severe bradycardia or protracted asystole, approximately 1 h after administration of endotoxin. Further analyses revealed that the subjects had a history of vasovagal syncope or a positive head-tilt test, indicating increased vagal sensitivity. Relative volume depletion associated with fasting overnight may have predisposed these subjects to this condition. CONCLUSIONS: These responses are very rare and are likely due to the cardioinhibitory Bezold-Jarisch reflex. A thorough screening regarding a history of vagal sensitivity and liberal oral or intravenous fluid administration prior to and during the endotoxin challenge may decrease the risk of these events. TI - Severe vagal response after endotoxin administration in humans. EP - 2281 SN - 0342-4642 IS - iss. 12 SP - 2279 JF - Intensive Care Medicine VL - vol. 30 DO - https://doi.org/10.1007/s00134-004-2477-0 ER - TY - JOUR AU - Pickkers, P. AU - Hoedemaekers, C.W.E. AU - Netea, M.G. AU - Galan, B.E. de AU - Smits, P. AU - Hoeven, J.G. van der AU - Deuren, M. van PY - 2004 UR - https://hdl.handle.net/2066/58239 AB - Recent trials investigating the effects of strict glucose regulation in critically ill patients have shown impressive reductions in morbidity and mortality. Although the literature focuses on the possible toxic effects of high blood glucose levels, the underlying mechanism for this improvement is unclear. We hypothesise that strict glucose regulation results in modulation of cytokine production, leading to a shift towards a more anti-inflammatory pattern. This shift in the cytokine balance accounts for the reduction in morbidity and mortality. To support our hypothesis, effects of glucose and insulin on cytokine release and effects of glucose, insulin, and cytokines on host defence, cardiac function and coagulation will be reviewed. TI - Hypothesis: Normalisation of cytokine dysbalance explains the favourable effects of strict glucose regulation in the critically ill. EP - 150 SN - 0300-2977 IS - iss. 5 SP - 143 JF - Netherlands Journal of Medicine VL - vol. 62 ER - TY - JOUR AU - Hilkens, M. AU - Haren, F.H.F. van AU - Hoeven, J.G. van der PY - 2003 UR - https://hdl.handle.net/2066/185216 TI - Unexpected left main stem bronchus cardiac output measurement. SN - 0342-4642 SP - 1201 JF - Intensive Care Medicine VL - vol. 29 DO - http://dx.doi.org/10.1007/s00134-003-1816-x ER - TY - JOUR AU - Fikkers, B.G. AU - Fransen, G.A.J. AU - Hoeven, J.G. van der AU - Briede, I.S. AU - Hoogen, F.J.A. van den PY - 2003 UR - https://hdl.handle.net/2066/142738 AB - OBJECTIVE: To assess the frequency, timing, technique, and follow-up of tracheostomy for long-term ventilated patients in different intensive care units (ICUs) in The Netherlands. DESIGN AND SETTING: Postal questionnaire, survey on retrospective data. A questionnaire was sent to all ( n=63) ICUs with six or more beds suitable for mechanical ventilation and officially recognized by The Netherlands Intensive Care Society. Pediatric ICUs were excluded. MEASUREMENTS AND Results : There was an 87% ( n=55) response rate of contacted ICUs. The number of tracheostomies per year per unit varied widely (range 1-75), most ICUs (42%) performing between 11 and 25 tracheostomies per year. In 44% of ICUs ( n=24) tracheostomy was not performed on a routine basis. In 25% of ICUs ( n=14) tracheostomies were performed during the second week of ventilation. Surgical tracheostomy and percutaneous procedures were technique of first choice in 38% and 62% of ICUs, respectively. In only 7% of units were late follow-up protocols in use. Thirty-two units (58%) reported a total of 56 major complications. CONCLUSIONS: Timing and technique of tracheostomy varies widely in Dutch ICUs. The percutaneous technique is the procedure of choice for tracheostomy in most of these units. Late follow-up protocols are rarely in use. TI - Tracheostomy for long-term ventilated patients: a postal survey of ICU practice in The Netherlands. EP - 1393 SN - 0342-4642 IS - iss. 8 SP - 1390 JF - Intensive Care Medicine VL - vol. 29 DO - http://dx.doi.org/10.1007/s00134-003-1824-x ER - TY - JOUR AU - Egeraat, S.C.I. van AU - Munster, E.T.L. van AU - Bodewes, H.W. AU - Hoeven, J.G. van der PY - 2003 UR - https://hdl.handle.net/2066/186417 TI - Spinal cord infarction as a severe complication of meningococcal meningitis. EP - 385 SN - 0953-6205 SP - 383 JF - European Journal of Internal Medicine VL - vol. 14 ER - TY - JOUR AU - Haren, F.M. van AU - Rozendaal, F.W. AU - Hoeven, J.G. van der PY - 2003 UR - https://hdl.handle.net/2066/185191 TI - The effect of vasopressin on gastric perfusion in catecholamine-dependent septic shock patients. EP - 2260 SN - 0012-3692 SP - 2256 JF - Chest VL - vol. 124 DO - https://doi.org/10.1378/chest.124.6.2256 ER - TY - JOUR AU - Jongen-Lavrencic, M. AU - Schneeberger, P.M. AU - Hoeven, J.G. van der PY - 2003 UR - https://hdl.handle.net/2066/184977 TI - Ciprofloxacin-induced toxic epidermal necrolysis in a patient with systemic lupus erythematosus. EP - 429 SN - 0300-8126 SP - 428 JF - Infection VL - vol. 31 DO - https://doi.org/10.1007/s15010-003-2128-3 ER - TY - JOUR AU - Moviat, M. AU - Haren, F.M. van AU - Hoeven, J.G. van der PY - 2003 UR - https://hdl.handle.net/2066/184990 TI - Conventional or physicochemical approach in ICU patients with metabolic acidosis. EP - R45 SN - 1466-609X SP - R41 JF - Critical Care VL - vol. 7 DO - https://doi.org/10.1186/cc2184 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/184990/184990.pdf?sequence=1 ER -