Publications by authors named "Nardo J M van der Meer"

29 Publications

  • Page 1 of 1

Risk factors for adverse outcomes during mechanical ventilation of 1152 COVID-19 patients: a multicenter machine learning study with highly granular data from the Dutch Data Warehouse.

Intensive Care Med Exp 2021 Jun 28;9(1):32. Epub 2021 Jun 28.

ICU, Maasstad Ziekenhuis Rotterdam, Rotterdam, The Netherlands.

Background: The identification of risk factors for adverse outcomes and prolonged intensive care unit (ICU) stay in COVID-19 patients is essential for prognostication, determining treatment intensity, and resource allocation. Previous studies have determined risk factors on admission only, and included a limited number of predictors. Therefore, using data from the highly granular and multicenter Dutch Data Warehouse, we developed machine learning models to identify risk factors for ICU mortality, ventilator-free days and ICU-free days during the course of invasive mechanical ventilation (IMV) in COVID-19 patients.

Methods: The DDW is a growing electronic health record database of critically ill COVID-19 patients in the Netherlands. All adult ICU patients on IMV were eligible for inclusion. Transfers, patients admitted for less than 24 h, and patients still admitted at time of data extraction were excluded. Predictors were selected based on the literature, and included medication dosage and fluid balance. Multiple algorithms were trained and validated on up to three sets of observations per patient on day 1, 7, and 14 using fivefold nested cross-validation, keeping observations from an individual patient in the same split.

Results: A total of 1152 patients were included in the model. XGBoost models performed best for all outcomes and were used to calculate predictor importance. Using Shapley additive explanations (SHAP), age was the most important demographic risk factor for the outcomes upon start of IMV and throughout its course. The relative probability of death across age values is visualized in Partial Dependence Plots (PDPs), with an increase starting at 54 years. Besides age, acidaemia, low P/F-ratios and high driving pressures demonstrated a higher probability of death. The PDP for driving pressure showed a relative probability increase starting at 12 cmHO.

Conclusion: Age is the most important demographic risk factor of ICU mortality, ICU-free days and ventilator-free days throughout the course of invasive mechanical ventilation in critically ill COVID-19 patients. pH, P/F ratio, and driving pressure should be monitored closely over the course of mechanical ventilation as risk factors predictive of these outcomes.
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http://dx.doi.org/10.1186/s40635-021-00397-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236316PMC
June 2021

Effect of a Lower vs Higher Positive End-Expiratory Pressure Strategy on Ventilator-Free Days in ICU Patients Without ARDS: A Randomized Clinical Trial.

JAMA 2020 12;324(24):2509-2520

Department of Intensive Care and Laboratory of Experimental Intensive Care and Anesthesiology, Amsterdam UMC, Location AMC, Amsterdam, the Netherlands.

Importance: It is uncertain whether invasive ventilation can use lower positive end-expiratory pressure (PEEP) in critically ill patients without acute respiratory distress syndrome (ARDS).

Objective: To determine whether a lower PEEP strategy is noninferior to a higher PEEP strategy regarding duration of mechanical ventilation at 28 days.

Design, Setting, And Participants: Noninferiority randomized clinical trial conducted from October 26, 2017, through December 17, 2019, in 8 intensive care units (ICUs) in the Netherlands among 980 patients without ARDS expected not to be extubated within 24 hours after start of ventilation. Final follow-up was conducted in March 2020.

Interventions: Participants were randomized to receive invasive ventilation using either lower PEEP, consisting of the lowest PEEP level between 0 and 5 cm H2O (n = 476), or higher PEEP, consisting of a PEEP level of 8 cm H2O (n = 493).

Main Outcomes And Measures: The primary outcome was the number of ventilator-free days at day 28, with a noninferiority margin for the difference in ventilator-free days at day 28 of -10%. Secondary outcomes included ICU and hospital lengths of stay; ICU, hospital, and 28- and 90-day mortality; development of ARDS, pneumonia, pneumothorax, severe atelectasis, severe hypoxemia, or need for rescue therapies for hypoxemia; and days with use of vasopressors or sedation.

Results: Among 980 patients who were randomized, 969 (99%) completed the trial (median age, 66 [interquartile range {IQR}, 56-74] years; 246 [36%] women). At day 28, 476 patients in the lower PEEP group had a median of 18 ventilator-free days (IQR, 0-27 days) and 493 patients in the higher PEEP group had a median of 17 ventilator-free days (IQR, 0-27 days) (mean ratio, 1.04; 95% CI, 0.95-∞; P = .007 for noninferiority), and the lower boundary of the 95% CI was within the noninferiority margin. Occurrence of severe hypoxemia was 20.6% vs 17.6% (risk ratio, 1.17; 95% CI, 0.90-1.51; P = .99) and need for rescue strategy was 19.7% vs 14.6% (risk ratio, 1.35; 95% CI, 1.02-1.79; adjusted P = .54) in patients in the lower and higher PEEP groups, respectively. Mortality at 28 days was 38.4% vs 42.0% (hazard ratio, 0.89; 95% CI, 0.73-1.09; P = .99) in patients in the lower and higher PEEP groups, respectively. There were no statistically significant differences in other secondary outcomes.

Conclusions And Relevance: Among patients in the ICU without ARDS who were expected not to be extubated within 24 hours, a lower PEEP strategy was noninferior to a higher PEEP strategy with regard to the number of ventilator-free days at day 28. These findings support the use of lower PEEP in patients without ARDS.

Trial Registration: ClinicalTrials.gov Identifier: NCT03167580.
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http://dx.doi.org/10.1001/jama.2020.23517DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726701PMC
December 2020

[Perspectives of stakeholders on technology use in the care of community-living older adults with dementia].

Tijdschr Gerontol Geriatr 2020 Sep 25;51(3). Epub 2020 Jul 25.

Departement Tranzo, Tilburg University, Tilburg, The Netherlands.

Although technology has the potential to promote aging in place among community-living older adults with dementia, the use remains scarce. In this literature study we provide an overview of perspectives (i.e., needs, wishes, attitudes, possibilities, and difficulties) of different stakeholders on technology use in the care for community-living older adults with dementia. After selection, 46 studies were included. We mainly found perspectives of informal caregivers and, to a lesser extent, of persons with dementia and formal caregivers. Shared perspectives were, among other things, ease of use, stability and flexibility of technology, importance of privacy, and confidentiality. Among older adults, fun and pleasure, in addition to enhancing freedom and independence, facilitates technology use. Informal caregivers' peace of mind and relief of burden also appeared to be important in using technologies. Formal caregivers value the potential of technologies to improve monitoring and communication. Insight in perspectives of stakeholders are essential to enhance the use of technology in the care for community-living older adults with dementia.
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http://dx.doi.org/10.36613/tgg.1875-6832/2020.03.03DOI Listing
September 2020

Late histopathologic characteristics of critically ill COVID-19 patients: Different phenotypes without evidence of invasive aspergillosis, a case series.

J Crit Care 2020 10 8;59:149-155. Epub 2020 Jul 8.

Department of Pulmonology, Amphia Hospital, Breda, the Netherlands; Department of Intensive Care, Amphia Hospital, Breda, the Netherlands.

Purpose: Pathological data of critical ill COVID-19 patients is essential in the search for optimal treatment options.

Material And Methods: We performed postmortem needle core lung biopsies in seven patients with COVID-19 related ARDS. Clinical, radiological and microbiological characteristics are reported together with histopathological findings.

Measurement And Main Results: Patients age ranged from 58 to 83 years, five males and two females were included. Time from hospital admission to death ranged from 12 to 36 days, with a mean of 20 ventilated days. ICU stay was complicated by pulmonary embolism in five patients and positive galactomannan on bronchoalveolar lavage fluid in six patients, suggesting COVID-19 associated pulmonary aspergillosis. Chest CT in all patients showed ground glass opacities, commonly progressing to nondependent consolidations. We observed four distinct histopathological patterns: acute fibrinous and organizing pneumonia, diffuse alveolar damage, fibrosis and, in four out of seven patients an organizing pneumonia. None of the biopsy specimens showed any signs of invasive aspergillosis.

Conclusions: In this case series common late histopathology in critically ill COVID patients is not classic DAD but heterogeneous with predominant pattern of organizing pneumonia. Postmortem biopsy investigations in critically COVID-19 patients with probable COVID-19 associated pulmonary aspergillosis obtained no evidence for invasive aspergillosis.
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http://dx.doi.org/10.1016/j.jcrc.2020.07.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7340597PMC
October 2020

A 0.6-protamine/heparin ratio in cardiac surgery is associated with decreased transfusion of blood products.

Interact Cardiovasc Thorac Surg 2020 09;31(3):391-397

Department of Anaesthesiology and Intensive Care, Amphia Hospital, Breda, Netherlands.

Objectives: In cardiac surgery, adequate heparinization is necessary to prevent thrombus formation in the cardiopulmonary bypass (CPB). To counteract the heparin effect after weaning from CPB, protamine is administered. The optimal protamine/heparin ratio is still unknown.

Methods: In this before-after study, we evaluated the effect of a 0.6/1-protamine/heparin ratio implementation as of May 2017 versus a 0.8/1-protamine/heparin ratio on the 12-h postoperative blood loss and the amount of blood and blood component transfusions (fresh frozen plasma, packed red blood cells, fibrinogen concentrate, platelet concentrate and prothrombin complex concentrate) after cardiac surgery. A total of 2051 patients who underwent cardiac surgery requiring CPB between May 2016 and May 2018 were included.

Results: In the 0.6/1-protamine/heparin ratio group, only 28.8% of the patients received blood component transfusion, compared to 37.9% of the patients in the 0.8/1-ratio group (P < 0.001). The median 12-h postoperative blood loss was 230 ml (interquartile range 140-320) in the 0.6/1-ratio group versus 260 ml (interquartile range 155-365) in the 0.8/1-ratio group (P < 0.001).

Conclusions: A 0.6/1-protamine/heparin ratio after weaning from CPB is associated with a significantly reduced 12-h postoperative blood loss and blood components transfusion.
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http://dx.doi.org/10.1093/icvts/ivaa109DOI Listing
September 2020

Procedures Performed by Advanced Practice Providers Compared With Medical Residents in the ICU: A Prospective Observational Study.

Crit Care Explor 2020 Apr 29;2(4):e0101. Epub 2020 Apr 29.

Department of Health, TIAS School for Business and Society, Tilburg, The Netherlands.

To assess the frequency and safety of procedures performed by advanced practice providers and medical residents in a mixed-bed ICU.

Design: A prospective observational study where consecutive invasive procedures were studied over a period of 1 year and 8 months. The interventions were registered anonymously in an online database. Endpoints were success rate at first attempt, number of attempts, complications, level of supervision, and teamwork.

Setting: A 33-bedded mixed ICU.

Subjects: Advanced practice providers and medical residents.

Interventions: Registration of the performance of tracheal intubation, central venous and arterial access, tube thoracostomies, interhospital transportation, and electrical cardioversion.

Measurement And Main Results: A full-time advanced practice provider performed an average of 168 procedures and a medical resident an average of 68. The advanced practice provider inserted significant more radial, brachial, and femoral artery catheters (66% vs 74%, = 0.17; 15% vs 12%, = 0.14; 18% vs 14%, = 0.14, respectively). The median number of attempts needed to successfully insert an arterial catheter was lower, and the success rate at first attempt was higher in the group treated by advanced practice providers (1.30 [interquartile range, 1-1.82] vs 1.53 [interquartile range, 1-2.27], < 0.0001; and 71% vs 54%, < 0.0001). The advanced practice providers inserted more central venous catheters (247 vs 177) with a lower median number of attempts (1.20 [interquartile range, 1-1.71] vs 1.33 [interquartile range, 1-1.86]) and a higher success rate at first attempt (81% vs 70%; < 0.005). The number of intubations by advanced practice providers was 143 and by medical residents was 115 with more supervision by the advanced practice provider (10% vs 0%; = 0.01). Team performance, as reported by nursing staff, was higher during advanced practice provider procedures compared with medical resident procedures (median, 4.85 [interquartile range, 4.85-5] vs 4.73 [interquartile range, 4.22-5]). Other procedures were also more often performed by advanced practice providers. The complication rate in the advanced practice provider-treated patient group was lower than that in the medical resident group.

Conclusions: Advanced practice providers in critical care performed procedures safe and effectively when compared with medical residents. Advanced practice providers appear to be a valuable addition to the professional staff in critical care when it comes to invasive procedures.
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http://dx.doi.org/10.1097/CCE.0000000000000101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7188435PMC
April 2020

Shared decision making in older patients with symptomatic severe aortic stenosis: a systematic review.

Heart 2020 05 30;106(9):647-655. Epub 2020 Jan 30.

TIAS, School for Business and Society, Tilburg University, Tilburg, The Netherlands.

This review provides an overview of the status of shared decision making (SDM) in older patients regarding treatment of symptomatic severe aortic stenosis (SSAS). The databases Embase, Medline Ovid, Cinahl and Cochrane Dare were searched for relevant studies from January 2002 to May 2018 regarding perspectives of professionals, patients and caregivers; aspects of decision making; type of decision making; application of the six domains of SDM; barriers to and facilitators of SDM. The systematic search yielded 1842 articles, 15 studies were included. Experiences of professionals and informal caregivers with SDM were scarcely found. Patient refusal was a frequently reported result of decision making, but often no insight was given into the decision process. Most studies investigated the 'decision' and 'option' domains of SDM, yet no study took all six domains into account. Problem analysis, personalised treatment aims, use of decision aids and integrating patient goals in decisions lacked in all studies. Barriers to and facilitators of SDM were 'individualised formal and informal information support' and 'patients' opportunity to use their own knowledge about their health condition and preferences for SDM'. In conclusion, SDM is not yet common practice in the decision making process of older patients with SSAS. Moreover, the six domains of SDM are not often applied in this process. More knowledge is needed about the implementation of SDM in the context of SSAS treatment and how to involve patients, professionals and informal caregivers.
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http://dx.doi.org/10.1136/heartjnl-2019-316055DOI Listing
May 2020

The ecological effects of selective decontamination of the digestive tract (SDD) on antimicrobial resistance: a 21-year longitudinal single-centre study.

Crit Care 2019 Jun 7;23(1):208. Epub 2019 Jun 7.

Department of Intensive Care, OLVG Hospital, Oosterpark 9, 1091 AC, Amsterdam, The Netherlands.

Background: The long-term ecological effects on the emergence of antimicrobial resistance at the ICU level during selective decontamination of the digestive tract (SDD) are unknown. We determined the incidence of newly acquired antimicrobial resistance of aerobic gram-negative potentially pathogenic bacteria (AGNB) during SDD.

Methods: In a single-centre observational cohort study over a 21-year period, all consecutive patients, treated with or without SDD, admitted to the ICU were included. The antibiotic regime was unchanged over the study period. Incidence rates for ICU-acquired AGNB's resistance for third-generation cephalosporins, colistin/polymyxin B, tobramycin/gentamicin or ciprofloxacin were calculated per year. Changes over time were tested by negative binomial regression in a generalized linear model.

Results: Eighty-six percent of 14,015 patients were treated with SDD. Most cultures were taken from the digestive tract (41.9%) and sputum (21.1%). A total of 20,593 isolates of AGNB were identified. The two most often found bacteria were Escherichia coli (N = 6409) and Pseudomonas (N = 5269). The incidence rate per 1000 patient-day for ICU-acquired resistance to cephalosporins was 2.03, for polymyxin B/colistin 0.51, for tobramycin 2.59 and for ciprofloxacin 2.2. The incidence rates for ICU-acquired resistant microbes per year ranged from 0 to 4.94 per 1000 patient-days, and no significant time-trend in incidence rates were found for any of the antimicrobials. The background prevalence rates of resistant strains measured on admission for cephalosporins, polymyxin B/colistin and ciprofloxacin rose over time with 7.9%, 3.5% and 8.0% respectively.

Conclusions: During more than 21-year SDD, the incidence rates of resistant microbes at the ICU level did not significantly increase over time but the background resistance rates increased. An overall ecological effect of prolonged application of SDD by counting resistant microorganisms in the ICU was not shown in a country with relatively low rates of resistant microorganisms.
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http://dx.doi.org/10.1186/s13054-019-2480-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6555978PMC
June 2019

Perspectives of Stakeholders on Technology Use in the Care of Community-Living Older Adults with Dementia: A Systematic Literature Review.

Healthcare (Basel) 2019 May 28;7(2). Epub 2019 May 28.

Department Tranzo, Tilburg School of Social and Behavioral Sciences, Tilburg University, 5000 LE Tilburg, The Netherlands.

Although technology has the potential to promote aging in place, the use of technology remains scarce among community-living older adults with dementia. A reason might be that many stakeholders are involved who all have a different perspective on technology use (i.e., needs, wishes, attitudes, possibilities, and difficulties). We systematically searched the literature in order to provide an overview of perspectives of different stakeholders on technology use among community-living older adults with dementia. After selection, 46 studies were included. We mainly found perspectives of informal caregivers and, to a lesser extent, of persons with dementia and formal caregivers. Perspectives of suppliers of technology were not present. Shared perspectives among persons with dementia and informal and formal caregivers were, among other things, ease of use, stability and flexibility of technology, importance of privacy, and confidentiality. We also found that among older persons, fun and pleasure, in addition to enhancing freedom and independence, facilitates technology use. Informal caregivers' peace of mind and relief of burden also appeared to be important in using technologies. Formal caregivers value the potential of technologies to improve monitoring and communication. Insight in shared, and conflicting perspectives of stakeholders are essential to enhance the use of technology.
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http://dx.doi.org/10.3390/healthcare7020073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6628181PMC
May 2019

Minimally Invasive Mitral Valve Surgery With Endoaortic Balloon Requires Cerebral Monitoring.

Ann Thorac Surg 2018 12 29;106(6):e295-e296. Epub 2018 May 29.

Department of Anaesthesiology and Intensive Care, Amphia Hospital Breda, Breda, The Netherlands.

After induction of anesthesia, an extra right radial artery catheter and cerebral oximetry were placed for minimally invasive mitral valve surgery. An anterolateral minithoracotomy, endoaortic balloon, and left atriotomy allowed visualization of the mitral valve. During the procedure, we observed a drop of the right cerebral oximetry saturation without a drop in right radial artery pressure. We suspected an aberrant right subclavian artery. After the endoaortic balloon was repositioned, right cerebral oximetry recovered. A postoperative computed tomography scan revealed an aberrant right subclavian artery. In this case, bilateral upper extremity arterial pressure monitoring would not have detected cerebral hypoperfusion.
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http://dx.doi.org/10.1016/j.athoracsur.2018.04.075DOI Listing
December 2018

Effect of On-Demand vs Routine Nebulization of Acetylcysteine With Salbutamol on Ventilator-Free Days in Intensive Care Unit Patients Receiving Invasive Ventilation: A Randomized Clinical Trial.

JAMA 2018 03;319(10):993-1001

Department of Intensive Care, Academic Medical Center, University of Amsterdam, the Netherlands.

Importance: It remains uncertain whether nebulization of mucolytics with bronchodilators should be applied for clinical indication or preventively in intensive care unit (ICU) patients receiving invasive ventilation.

Objective: To determine if a strategy that uses nebulization for clinical indication (on-demand) is noninferior to one that uses preventive (routine) nebulization.

Design, Setting, And Participants: Randomized clinical trial enrolling adult patients expected to need invasive ventilation for more than 24 hours at 7 ICUs in the Netherlands.

Interventions: On-demand nebulization of acetylcysteine or salbutamol (based on strict clinical indications, n = 471) or routine nebulization of acetylcysteine with salbutamol (every 6 hours until end of invasive ventilation, n = 473).

Main Outcomes And Measures: The primary outcome was the number of ventilator-free days at day 28, with a noninferiority margin for a difference between groups of -0.5 days. Secondary outcomes included length of stay, mortality rates, occurrence of pulmonary complications, and adverse events.

Results: Nine hundred twenty-two patients (34% women; median age, 66 (interquartile range [IQR], 54-75 years) were enrolled and completed follow-up. At 28 days, patients in the on-demand group had a median 21 (IQR, 0-26) ventilator-free days, and patients in the routine group had a median 20 (IQR, 0-26) ventilator-free days (1-sided 95% CI, -0.00003 to ∞). There was no significant difference in length of stay or mortality, or in the proportion of patients developing pulmonary complications, between the 2 groups. Adverse events (13.8% vs 29.3%; difference, -15.5% [95% CI, -20.7% to -10.3%]; P < .001) were more frequent with routine nebulization and mainly related to tachyarrhythmia (12.5% vs 25.9%; difference, -13.4% [95% CI, -18.4% to -8.4%]; P < .001) and agitation (0.2% vs 4.3%; difference, -4.1% [95% CI, -5.9% to -2.2%]; P < .001).

Conclusions And Relevance: Among ICU patients receiving invasive ventilation who were expected to not be extubated within 24 hours, on-demand compared with routine nebulization of acetylcysteine with salbutamol did not result in an inferior number of ventilator-free days. On-demand nebulization may be a reasonable alternative to routine nebulization.

Trial Registration: clinicaltrials.gov Identifier: NCT02159196.
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http://dx.doi.org/10.1001/jama.2018.0949DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5885882PMC
March 2018

Does a Platelet Transfusion Independently Affect Bleeding and Adverse Outcomes in Cardiac Surgery?

Anesthesiology 2017 03;126(3):441-449

From the Center for Clinical Transfusion Research, Sanquin/Leiden University Medical Center, Leiden, The Netherlands (F.M.A.v.H., E.K.H., J.G.v.d.B., A.B., L.M.G.v.d.W.); Department of Cardiac Anesthesiology and CU (P.M.J.R., N.J.M.v.d.M.) and Department of Cardiothoracic Surgery (M.B.), Amphia Hospital, Breda, The Netherlands; Department of Clinical Epidemiology (F.M.A.v.H., J.G.v.d.B.) and Department of Anesthesiology (E.L.A.v.D.), Leiden University Medical Center, The Netherlands; Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, The Netherlands (N.v.G.); Department of Anesthesia, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands (E.K.H.); and TIAS/Tilburg University, Tilburg, The Netherlands (N.J.M.v.d.M.).

Background: Conflicting results have been reported concerning the effect of platelet transfusion on several outcomes. The aim of this study was to assess the independent effect of a single early intraoperative platelet transfusion on bleeding and adverse outcomes in cardiac surgery patients.

Methods: For this observational study, 23,860 cardiac surgery patients were analyzed. Patients who received one early (shortly after cardiopulmonary bypass while still in the operating room) platelet transfusion, and no other transfusions, were defined as the intervention group. By matching the intervention group 1:3 to patients who received no early transfusion with most comparable propensity scores, the reference group was identified.

Results: The intervention group comprised 169 patients and the reference group 507. No difference between the groups was observed concerning reinterventions, thromboembolic complications, infections, organ failure, and mortality. However, patients in the intervention group experienced less blood loss and required vasoactive medication 139 of 169 (82%) versus 370 of 507 (74%; odds ratio, 1.65; 95% CI, 1.05 to 2.58), prolonged mechanical ventilation 92 of 169 (54%) versus 226 of 507 (45%; odds ratio, 1.47; 94% CI, 1.03 to 2.11), prolonged intensive care 95 of 169 (56%) versus 240 of 507 (46%; odds ratio, 1.49; 95% CI, 1.04 to 2.12), erythrocytes 75 of 169 (44%) versus 145 of 507 (34%; odds ratio, 1.55; 95% CI, 1.08 to 2.23), plasma 29 of 169 (17%) versus 23 of 507 (7.3%; odds ratio, 2.63; 95% CI, 1.50-4.63), and platelets 72 of 169 (43%) versus 25 of 507 (4.3%; odds ratio, 16.4; 95% CI, 9.3-28.9) more often compared to the reference group.

Conclusions: In this retrospective analysis, cardiac surgery patients receiving platelet transfusion in the operating room experienced less blood loss and more often required vasoactive medication, prolonged ventilation, prolonged intensive care, and blood products postoperatively. However, early platelet transfusion was not associated with reinterventions, thromboembolic complications, infections, organ failure, or mortality.
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http://dx.doi.org/10.1097/ALN.0000000000001518DOI Listing
March 2017

Effectiveness of pericardial lavage with or without tranexamic acid in cardiac surgery patients receiving intravenous tranexamic acid: a randomized controlled trial.

Eur J Cardiothorac Surg 2016 Dec 21;50(6):1124-1131. Epub 2016 Jun 21.

Department of Anesthesiology, Amphia Hospital, Breda, Netherlands

Objectives: Pericardial lavage with saline, with or without tranexamic acid (TA), is still not evidence-based within current clinical practice as a part of a blood conservation strategy in cardiac surgery patients receiving intravenous TA administration. The objective was to determine whether intravenous TA combined with pericardial lavage with saline, with or without TA, reduces blood loss by 25% after cardiac surgery measured in the first 12 h postoperatively.

Methods: In this single-centre, randomized controlled, multiple-armed, parallel study, individual patients were randomly assigned to receive either topical administration of 2 g TA diluted in 200 ml of saline (TA group), 200 ml of saline (placebo group) or no topical administration at all (control group). Eligible participants were all adults aged 18 or older and scheduled for elective cardiac surgery on cardiopulmonary bypass. All patients received 2 g TA intravenously before sternal incision and 2 g TA after cardiopulmonary bypass. The main outcome measure was the 12-h postoperative blood loss.

Results: In total, 739 individuals were analysed according to intention-to-treat analyses (TA group, n = 245 patients; placebo group, n = 249 patients; control group, n = 245 patients). There was no difference in the median 12-h postoperative blood loss between the three groups [TA group, 290 (IQR 190-430) ml; placebo group, 290 (IQR 210-440) ml; control group, 300 (IQR 190-450) ml, P= 0.759].

Conclusions: Pericardial lavage, with or without TA, does not result in a statistically significant difference in the 12-h postoperative blood loss in cardiac surgery patients receiving intravenous TA administration. Pericardial lavage with saline, with or without TA, should not be a part of a blood conservation strategy.
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http://dx.doi.org/10.1093/ejcts/ezw214DOI Listing
December 2016

The long-term reform in the Netherlands: what is the scientific rational for the WMO?

Health Policy 2016 Jul 17;120(7):862-4. Epub 2016 May 17.

HealthLab, TIAS school for Business and Society, Tilburg University, Tilburg, The Netherlands. Electronic address:

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http://dx.doi.org/10.1016/j.healthpol.2016.05.007DOI Listing
July 2016

Pilot Study of the Pharmacokinetics of Cefotaxime in Critically Ill Patients with Acute Kidney Injury Treated with Continuous Renal Replacement Therapy.

Antimicrob Agents Chemother 2016 06 23;60(6):3587-90. Epub 2016 May 23.

Department of Intensive Care, Amphia Hospital Breda, Oosterhout, and Etten-Leur, Breda, The Netherlands Tias School for Business and Society, Tilburg University, Tilburg, The Netherlands.

The objective of this study was to describe the pharmacokinetics of cefotaxime (CTX) in critically ill patients with acute kidney injury (AKI) when treated with continuous renal replacement therapy (CRRT) in the intensive care unit (ICU). This single-center prospective observational pilot study was performed among ICU-patients with AKI receiving ≥48 h concomitant CRRT and CTX. CTX was administered intravenously 1,000 mg (bolus) every 6 h for 4 days. CRRT was performed as continuous venovenous hemofiltration (CVVH). Plasma concentrations of CTX and its active metabolite desacetylcefotaxime (DAC) were measured during CVVH treatment. CTX plasma levels and patient data were used to construct concentration-time curves. By using this data, the duration of plasma levels above 4 mg/liter (four times the MIC) was calculated and analyzed. Twenty-seven patients were included. The median CTX peak level was 55 mg/liter (range, 19 to 98 mg/liter), the median CTX trough level was 12 mg/liter (range, 0.8 to 37 mg/liter), and the median DAC plasma level was 15 mg/liter (range, 1.5 to 48 mg/liter). Five patients (19%) had CTX plasma levels below 4 mg/liter at certain time points during treatment. In at least 83% of the time any patient was treated with CTX, the CTX plasma level stayed above 4 mg/liter. A dosing regimen of 1,000 mg of CTX given four times daily is likely to achieve adequate plasma levels in patients with AKI treated with CVVH. Dose reduction might be a risk for suboptimal treatment.
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http://dx.doi.org/10.1128/AAC.02888-15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4879359PMC
June 2016

Intraoperative Anemia and Single Red Blood Cell Transfusion During Cardiac Surgery: An Assessment of Postoperative Outcome Including Patients Refusing Blood Transfusion.

J Cardiothorac Vasc Anesth 2016 Apr 2;30(2):363-72. Epub 2015 Nov 2.

Amphia Hospital, Department of Anesthesia and Intensive Care, Breda, Netherlands; TIAS, Tilburg University, Tilburg, Netherlands.

Objectives: Increasing evidence suggests benefits from restrictive red blood cell transfusion (RBC) thresholds in major surgery and critically ill patients. However, these benefits are not obvious in cardiac surgery patients with intraoperative anemia. The authors examined the association between uncorrected hemoglobin (Hb) levels and selected postoperative outcomes as well as the effects of RBCs.

Design: Cohort study with prospectively collected data from a cardiac surgery registry.

Setting: A major cardiac surgical hospital within the Netherlands, which is also a referral center for Jehovah's Witnesses.

Participants: Patients (23,860) undergoing cardiac surgery between 1997 and 2013.

Interventions: Comparisons were done in patients with intraoperative nadir Hb<8 g/dL and/or an Hb decrease ≥ 50%. Comparison (A) between Jehovah's Witnesses (Witnesses) and matched non-Jehovah's Witnesses (non-Witnesses) transfused with 1 unit of RBC, and comparison (B) between patients given 1 unit of RBC intraoperatively versus matched non-transfused patients.

Measurements And Main Results: Postoperative outcomes were myocardial infarction, renal replacement therapy, stroke, and death. With propensity matching, the authors optimized exchangeability of the compared groups. Adverse outcomes increased with a decreasing Hb both among Witnesses and among non-Witnesses. The incidence of postoperative complications did not differ between Witnesses and matched non-Witnesses who received RBC (adjusted odds ratio 1.44, 95% confidence interval 0.63-3.29). Similarly, postoperative complications did not differ between patients who received a red cell transfusion and matched patients who did not (adjusted odds ratio 0.94, confidence interval 0.72-1.23).

Conclusion: Intraoperative anemia is associated with adverse outcomes after cardiac surgery, and a single RBC transfusion does not seem to influence these outcomes.
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http://dx.doi.org/10.1053/j.jvca.2015.10.021DOI Listing
April 2016

Preventive nebulization of mucolytic agents and bronchodilating drugs in invasively ventilated intensive care unit patients (NEBULAE): study protocol for a randomized controlled trial.

Trials 2015 Sep 2;16:389. Epub 2015 Sep 2.

Department of Intensive Care, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.

Background: Preventive nebulization of mucolytic agents and bronchodilating drugs is a strategy aimed at the prevention of sputum plugging, and therefore atelectasis and pneumonia, in intubated and ventilated intensive care unit (ICU) patients. The present trial aims to compare a strategy using the preventive nebulization of acetylcysteine and salbutamol with nebulization on indication in intubated and ventilated ICU patients.

Methods/design: The preventive nebulization of mucolytic agents and bronchodilating drugs in invasively ventilated intensive care unit patients (NEBULAE) trial is a national multicenter open-label, two-armed, randomized controlled non-inferiority trial in the Netherlands. Nine hundred and fifty intubated and ventilated ICU patients with an anticipated duration of invasive ventilation of more than 24 hours will be randomly assigned to receive either a strategy consisting of preventive nebulization of acetylcysteine and salbutamol or a strategy consisting of nebulization of acetylcysteine and/or salbutamol on indication. The primary endpoint is the number of ventilator-free days and surviving on day 28. Secondary endpoints include ICU and hospital length of stay, ICU and hospital mortality, the occurrence of predefined pulmonary complications (acute respiratory distress syndrome, pneumonia, large atelectasis and pneumothorax), and the occurrence of predefined side effects of the intervention. Related healthcare costs will be estimated in a cost-benefit and budget-impact analysis.

Discussion: The NEBULAE trial is the first randomized controlled trial powered to investigate whether preventive nebulization of acetylcysteine and salbutamol shortens the duration of ventilation in critically ill patients.

Trial Registration: NCT02159196, registered on 6 June 2014.
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http://dx.doi.org/10.1186/s13063-015-0865-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4557315PMC
September 2015

Defining indications for selective chest radiography in the first 24 hours after cardiac surgery.

J Thorac Cardiovasc Surg 2015 Jul 21;150(1):225-9. Epub 2015 Apr 21.

Department of Anesthesiology and Intensive Care, Amphia Hospital, Breda, Oosterhout, and Etten-Leur, The Netherlands; TIAS School for Business and Society, Tilburg University, Tilburg, The Netherlands.

Objective: In the intensive-care unit (ICU), chest radiographs (CXRs) are frequently obtained routinely for postoperative cardiac surgery patients, despite the fact that the efficacy of routine CXRs is known to be low. We investigated the efficacy and safety of CXRs performed after cardiac surgery for specified indications only.

Methods: In this observational cohort study, we prospectively included all patients who underwent conventional major cardiac surgery by median sternotomy in the year 2012. On-demand CXRs could be obtained during the first postoperative period for specified indications only. A routine control CXR was performed on the morning of the first postoperative day for all patients who had not undergone a CXR before that time. The diagnostic and therapeutic efficacy values were calculated for all CXRs. Differences were tested using Fisher's exact test or χ(2) analysis.

Results: A total of 1102 consecutive cardiac surgery patients were included in this study. The diagnostic efficacy of CXRs for major abnormalities was higher for the postoperative on-demand CXRs (n = 301; 27%) than for the routine CXRs taken the morning after surgery (n = 801; 73%) (6.6% vs 2.7%, P = .004). The therapeutic efficacy was higher for the on-demand CXRs, whereas the need for intervention after the next-morning, routine CXRs was limited to 5 patients (4.0% vs 0.6%, P < .001). None of these patients experienced a major adverse event.

Conclusions: Defining clear indications for selective CXRs after cardiac surgery is effective and seems to be safe. This approach may significantly reduce the total number of CXRs performed, and will increase their efficacy.
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http://dx.doi.org/10.1016/j.jtcvs.2015.04.026DOI Listing
July 2015

Why intensivists want chest radiographs.

Crit Care 2015 Mar 5;19:100. Epub 2015 Mar 5.

Department of Healthcare, Tias Nimbas Business School, Tilburg University, Warandelaan 2, Tilburg, 5037 AB, The Netherlands.

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http://dx.doi.org/10.1186/s13054-015-0816-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4350790PMC
March 2015

The value of routine chest radiographs after minimally invasive cardiac surgery: an observational cohort study.

J Cardiothorac Surg 2014 Nov 11;9:174. Epub 2014 Nov 11.

Department of Anesthesiology & Intensive Care, Amphia Hospital, Molengracht 21, 4818, CK, Breda, The Netherlands.

Background: Chest radiographs (CXRs) are obtained frequently in postoperative cardiac surgery patients. The diagnostic and therapeutic efficacy of routine CXRs is known to be low and the discussion regarding the safety of abandoning these CXRs after cardiac surgery is still ongoing. We investigated the value of routine CXRs directly after minimally invasive cardiac surgery.

Methods: We prospectively included all patients who underwent minimally invasive cardiac surgery by port access, ministernotomy or bilateral video-assisted thoracoscopy (VATS) in the year 2012. A direct postoperative CXR was performed on all patients at ICU arrival. All CXR findings were noted, including whether they led to an intervention or not. The results were compared to the postoperative CXR results in patients who underwent conventional cardiac surgery by full median sternotomy over the same period.

Main Results: A total of 249 consecutive patients were included. Most of these patients underwent valve surgery, rhythm surgery or a combination of both. The diagnostic efficacy for minor findings was highest in the port access and bilateral VATS groups (56% and 63% versus 28% and 45%) (p < 0.005). The diagnostic efficacy for major findings was also higher in these groups (8.9% and 11% versus 4.3% and 3.8%) (p = 0.010). The need for an intervention was most common after minimally invasive surgery by port access, although this difference was not statistically significant (p = 0.056).

Conclusions: The diagnostic efficacy of routine CXRs performed after minimally invasive cardiac surgery by port access or bilateral VATS is higher than the efficacy of CXRs performed after conventional cardiac surgery. A routine CXR after these procedures should still be considered.
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http://dx.doi.org/10.1186/s13019-014-0174-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4232684PMC
November 2014

Association of perioperative troponin and atrial fibrillation after coronary artery bypass grafting.

Interact Cardiovasc Thorac Surg 2013 Oct 20;17(4):608-14. Epub 2013 Jun 20.

Department of Cardiac Anesthesiology and Intensive Care, Amphia Hospital Breda and Oosterhout, Breda, Netherlands.

Objectives: Prediction of atrial fibrillation (AF) after coronary artery bypass grafting (CABG) may lead to preventive or early treatment and improved outcome. We investigated the association of serial perioperative cardiac troponin T (cTNT) measurements with postoperative AF in patients undergoing CABG.

Methods: In a retrospective analysis of prospectively collected data, 3148 patients undergoing elective CABG were evaluated. cTNT values were routinely determined before the start of surgery (cTNT0), at arrival on the intensive care unit (cTNT1) and 8-12 h later (cTNT2). Measurement of cTNT was continued until the peak value was reached. The development of AF during hospital stay was scored. The association between cTNT (cTNT0, cTNT1, cTNT2 and cTNTmax in first 48 h) and AF was calculated in univariable and multivariable analysis.

Results: AF occurred in 1080 (34%) patients. cTNT0, cTNT2 and cTNTmax were significantly and positively associated with postoperative AF (P < 0.001) in a univariable analysis, whereas a trend was seen for cTNT1 (P = 0.051). Advanced age, inotropic support and postoperative infection were independently associated with postoperative AF after logistic regression analysis, but cTNT was not. Categorizing patients by inotropic support into categories of inotropic support duration (none, <48 h, >48 h), the mean cTNT values were significantly higher among patients with AF in each category (all P < 0.001). Perioperative cTNT was significantly higher in patients with postoperative complications, longer hospital stay and reduced in-hospital survival.

Conclusions: Perioperative cTNT is univariably associated with postoperative AF after CABG, but not independently. Further, no clinically useful cut-off point for preventive or early treatment could be identified. Both perioperative cTNT and postoperative AF are associated with negative outcome and prolonged hospital stay.
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http://dx.doi.org/10.1093/icvts/ivt259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3781790PMC
October 2013

Löffler endocarditis: a rare cause of acute cardiac failure.

J Cardiothorac Surg 2012 Oct 10;7:109. Epub 2012 Oct 10.

Department of Internal Medicine, Erasmus Medical Centre, Rotterdam, the Netherlands, P,O, Box 2040, , 3000, CA, Rotterdam, the Netherlands.

We describe a patient with acute cardiogenic shock due to cardiac involvement in idiopathic hypereosinophilic syndrome (Löffler endocarditis). At the echocardiography, there was a huge mass in the left ventricular cavity, resulting in inflow- and outflow tract obstruction. The posterior leaflet of the mitral valve apparatus was completely embedded in a big (organized) thrombus mass. The patient was treated with high dose corticosteroids, however without effect. Partial remission was achieved after treatment with hydroxycarbamide. He was also treated with anticoagulants and high dose beta-blockers. The patient's condition improved remarkably after correction of the mitral valve insufficiency by a mitral valve bioprosthesis.
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http://dx.doi.org/10.1186/1749-8090-7-109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3493299PMC
October 2012

[Possibly fewer donors due to decreasing hospital mortality rates].

Ned Tijdschr Geneeskd 2012 ;156(40):A4418

Amphia Ziekenhuis, Breda, the Netherlands.

Over the past ten years, the mortality rate at the Amphia Hospital in the Netherlands has decreased and the average age at death has increased significantly. This downward trend in hospital mortality rates is a national trend in the Netherlands. In addition, in recent years road traffic fatalities have steadily decreased. Both trends have had a significant impact on the availability of potential organ and tissue donors. Currently the main barriers to donation are the limited number of registrations in the donor registry and obtaining permission from relatives. To achieve the maximum number of donors, several initiatives must be undertaken. These include hospitals encouraging registration in the donor registry, training of professionals in communication skills concerning donation, increasing opportunities for organ donations in the emergency department and recruiting donors extramurally. If no measures are taken, a decreasing number of patients with end-stage organ failure will be able to profit from organ transplantation.
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December 2012

Appointing 'trained donation practitioners' results in a higher family consent rate in the Netherlands: a multicenter study.

Transpl Int 2011 Dec 8;24(12):1189-97. Epub 2011 Sep 8.

Dutch Transplant Foundation, Leiden, The Netherlands.

The consent process for organ and tissue donation is complex, both for families and professionals. To help professionals in broaching this subject we performed a multicenter study. We compared family consent to donation in three hospitals between December 2007 and December 2009. In the intervention hospital, trained donation practitioners (TDP) guided 66 families throughout the time in the ICU until a decision regarding donation had been reached. In the first control hospital, without any family guidance or training, 107 families were approached. In the second control hospital 'hostesses', who were not trained in donation questions, supported 99 families during admittance. A total of 272 families were requested to donate. We primarily compared consent rates, but also asked families about their experiences through a questionnaire. Family consent rate was significantly higher in the intervention hospital: 57.6% (38/66), than in the control hospitals: 34.6% (37/107) and 39.4% (39/99). The 69% response rate to the questionnaire -~5 months after death - showed no confounding variables that could have influenced the consent rate. Appointing TDPs in the intervention hospital to guide families during admittance and the donation decision-making process, results in higher family consent rates.
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http://dx.doi.org/10.1111/j.1432-2277.2011.01326.xDOI Listing
December 2011

The clinical value of routine chest radiographs in the first 24 hours after cardiac surgery.

Anesth Analg 2011 Jan 3;112(1):139-42. Epub 2010 Nov 3.

Department of Anesthesiology, Intensive Care and Pain Treatment, St. Antonius Hospital, Koekoekslaan 1, 3435 CM Nieuwegein, The Netherlands.

Background: Chest radiographs (CXRs) are obtained frequently in the intensive care unit (ICU). Whether these CXRs should be performed routinely or on clinical indication only is often debated. The aim of our study was to investigate the incidence and clinical significance of abnormalities found on routine postoperative CXRs in cardiac surgery patients and whether a restricted use of CXRs would influence the number of significant findings.

Methods: We prospectively included all consecutive patients who underwent cardiac surgery during a 2-month period. Two or three CXRs were performed in the first 24 hours of ICU stay. After ICU admission and after drain removal, a clinical assessment was performed before a CXR was obtained. All CXR abnormalities were noted and it was also noted whether they led to an intervention. For the admission CXR and the drain removal CXR, a comparison was made between CXRs clinically indicated by the physician and those not clinically indicated.

Results: Two hundred fourteen patients were included. The majority of patients underwent coronary arterial bypass grafting (60%), heart valve surgery (21%), or a combination of these (14%). In total, 534 CXRs were performed (2.5 per patient). Abnormalities were found on 179 CXRs (33.5%) and 13 CXR results led to an intervention (2.4%). The association between clinically indicated CXRs and the presence of CXR abnormalities was poor. For 32 (10%) of the 321 admission and drain removal CXRs, clinical indications were stated by the physician beforehand. If these CXRs would not have been performed routinely, 68 abnormalities would have been missed, of which 5 led to an intervention.

Conclusions: Partial elimination of routine CXRs in the first 24 hours after cardiac surgery seems possible for the majority of patients, but it is limited by the insensitivity of clinical assessment in predicting clinically important abnormalities detectable by CXRs.
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http://dx.doi.org/10.1213/ANE.0b013e3181fdf6b7DOI Listing
January 2011

Purpura in a patient receiving vancomycin: a leukoclastic vasculitis?

J Cardiothorac Vasc Anesth 2011 Apr 27;25(2):390-1. Epub 2010 Apr 27.

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http://dx.doi.org/10.1053/j.jvca.2010.02.027DOI Listing
April 2011

Persistent cortical blindness after a thoracic epidural test dose of bupivacaine.

Anesthesiology 2010 Feb;112(2):493-5

Department of Anesthesiology, Amphia Hospital, Breda, The Netherlands.

Thoracic epidural anesthesia is considered as an essential component of the perioperative care for patients undergoing lung resection. Although neurologic adverse events have been associated with this technique, permanent injury is rare. These events primarily involve the peripheral nervous system; for example, nerve root injury. We present a case of persistent cortical blindness after a test dose of bupivacaine was administered into an uneventfully placed thoracic epidural catheter.
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http://dx.doi.org/10.1097/ALN.0b013e3181c5387aDOI Listing
February 2010

Pneumatosis intestinalis with gastric pneumatosis and hepatoportal venous gas in blunt abdominal trauma: A case report.

Eur J Trauma Emerg Surg 2009 Oct 26;35(5):505. Epub 2008 Nov 26.

Department of Surgery, Amphia Hospital, Breda, The Netherlands.

A case of transient pneumatosis intestinalis with gastric pneumatosis and hepatoportal venous gas following blunt abdominal trauma is described. The presence of intramural gas mostly implies intestinal necrosis, which needs emergent surgical exploration. This case demonstrates that conservative management with close clinical observation and follow-up computed tomography scan can be safely applied in selected cases of pneumatosis intestinalis with gastric pneumatosis and hepatoportal venous gas.
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http://dx.doi.org/10.1007/s00068-008-8134-5DOI Listing
October 2009
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