Publications by authors named "Enno D Wildschut"

Article Synopsis
  • Bleeding and thrombotic complications are prevalent in ECMO patients, impacting mortality and morbidity; this study compares complication rates before and after a change in anticoagulation monitoring protocol.
  • A retrospective cohort study involved 250 adult ECMO patients, analyzing demographics, ECMO data, and coagulation tests to evaluate the effectiveness of the aPTT guided and multimodal protocols.
  • Results showed that complication rates were similar between the two protocols, and surgical interventions significantly increased the risk of both bleeding and thrombotic issues.
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Article Synopsis
  • The study aimed to see if using intermittent intravenous paracetamol instead of continuous morphine would help kids aged 0-3 years feel less pain after heart surgery.
  • It took place in special hospitals in the Netherlands and Belgium, and involved 208 children who had heart surgery, where they were split into two groups to compare pain relief methods.
  • The results showed that kids who received paracetamol used much less morphine (79% less) for pain relief in the first 48 hours after surgery than those who got only morphine.
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In critically ill adults, high plasma cortisol in face of low ACTH coincides with high pro-opiomelanocortin (POMC) levels. Glucocorticoids further lower ACTH without affecting POMC. We hypothesized that in pediatric cardiac surgery-induced critical illness, plasma POMC is elevated, plasma ACTH transiently rises intraoperatively but becomes suppressed post-operatively, and glucocorticoid administration amplifies this phenotype.

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Background: Extracorporeal membrane oxygenation (ECMO) provides cardiopulmonary support for children with severe cardiac and/or pulmonary failure. The incidence of bleeding complications during ECMO support is high. Acquired von Willebrand disease (AVWD) might contribute to the development of bleeding complications.

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Article Synopsis
  • The study focused on understanding the pharmacokinetics (PK) of pentobarbital, a medication often given to critically ill children with severe neurological conditions, using a population-based modeling approach.
  • A one-compartment model was developed based on data from 36 patients and validated with a separate group of 9, revealing that kidney function and inflammation significantly affect drug clearance.
  • The findings suggest that current dosing might lead to toxic levels in patients with elevated creatinine and C-reactive protein, highlighting the need for adjusted dosing strategies and further studies to improve safety and efficacy in this vulnerable population.
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A neonate with pulmonary hypertension was supported with extracorporeal membrane oxygenation (ECMO). During ECMO support, the patient developed Enterococcus faecalis bacteremia, treated with targeted antibiotics. Despite the maximum dose of antibiotics, routine blood cultures remained positive throughout the ECMO treatment.

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Neuroprognostication in severe traumatic brain injury (sTBI) is challenging and occurs in critical care settings to determine withdrawal of life-sustaining therapies (WLST). However, formal pediatric sTBI neuroprognostication guidelines are lacking, brain death criteria vary, and dilemmas regarding WLST persist, which lead to institutional differences. We studied WLST practice and outcome in pediatric sTBI to provide insight into WLST-associated factors and survivor recovery trajectory ≥1 year post-sTBI.

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Emerging evidence supports the importance of optimized antibiotic exposure in pediatric intensive care unit (PICU) patients. Traditional antibiotic dosing is not designed for PICU patients, as the extreme pharmacokinetic (PK) behavior of drugs threatens the achievement of optimal antibiotic treatment outcomes. Scavenged sampling is a sampling strategy which may have positive implications for routine TDM and PK research, as well as monitoring other biomarkers.

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Purpose: Innovative and sustainable sampling strategies for bioanalytical quantification of drugs and metabolites have gained considerable interest. Scavenging can be stratified as a sustainable sampling strategy using residual material because it aligns with the green principles of waste reduction and sampling optimization. Scavenged sampling includes all biological fluids' (eg, blood, liquor, and urine) leftover from standard clinical care.

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Background: The incidence of hemostatic complications in pediatric patients undergoing extracorporeal membrane oxygenation (ECMO) is high. The optimal anticoagulation strategy in children undergoing ECMO is unknown.

Objectives: To study the association between hemostatic complications, coagulation tests, and clinical parameters in pediatric patients undergoing ECMO and their effect on survival.

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Article Synopsis
  • Entrustable Professional Activities (EPAs) represent key competencies required in professional practice, which can be assigned to capable learners, and form the basis for specialty training curricula.
  • The study aimed to develop a set of nine EPAs for Dutch Pediatric Intensive Care Unit (PICU) fellows using a modified Delphi method involving multiple rounds of expert ratings regarding the importance and clarity of each EPA.
  • The results showed strong consensus among experts (93-100% agreement), confirming that the EPAs cover essential clinical tasks for PICU physicians, establishing a foundation for future assessment systems in PICU training.
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Optimal pharmacotherapy in pediatric patients with suspected infections requires understanding and integration of relevant data on the antibiotic, bacterial pathogen, and patient characteristics. Because of age-related physiological maturation and non-maturational covariates (e.g.

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Despite advances in technology and clinical experience, the incidence of hemostatic complications, including bleeding and thrombosis, remains high in children supported with extracorporeal membrane oxygenation (ECMO). These hemostatic complications are important to prevent, since they are associated with increased morbidity and mortality. This systematic literature review aims to outline the most important risk factors for hemostatic complications in children undergoing ECMO treatment, to summarize the reported alternative anticoagulant drugs used in pediatric ECMO and to describe studied associations between coagulation tests and hemostatic complications.

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Background/purpose: Coagulation complications are frequent, unwanted occurrences in extracorporeal membrane oxygenation (ECMO) treatment, possibly influenced by the pump in the ECMO-circuit. We hypothesized that fewer complications would occur with a smaller, heparin-coated ECMO system with a centrifugal pump (CP) than with one with a roller pump (RP) and that after conversion, complication rates would decrease over time.

Methods: This single-center, retrospective chart study included all first neonatal and pediatric ECMO runs between 2009 and 2015.

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Bacterial and fungal infections are common and often contribute to death in patients undergoing extracorporeal membrane oxygenation (ECMO). Drug disposition is altered during ECMO, and adsorption in the circuit is an established causative factor. Vancomycin and voriconazole are widely used, despite the lack of evidence-based prescription guidelines.

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Objective: Hyperoxia is associated with adverse outcome in severe traumatic brain injury (TBI). This study explored differences in patient classification of oxygen exposure by PaO cutoff and cumulative area-under-the-curve (AUC) analysis.

Methods: Retrospective, explorative study including children (<18 years) with accidental severe TBI (2002-2015).

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Cardiopulmonary bypass (CPB) is often necessary for congenital cardiac surgery, but CPB can alter drug pharmacokinetic parameters resulting in underdosing. Inadequate plasma levels of antibiotics could lead to postoperative infections with increased morbidity. The influence of pediatric CPB systems on cefazolin and clindamycin plasma levels is not known.

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Objectives: To evaluate in vitro drug recovery in cardiopulmonary bypass (CPB) systems used for pediatric cardiac surgery.

Design: Observational in vitro study.

Setting: Single-center university hospital.

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Extracorporeal membrane oxygenation (ECMO) is a lifesaving support technology for potentially reversible neonatal cardiac and/or respiratory failure. As the survival and the overall outcome of patients rely on the treatment and reversal of the underlying disease, effective and preferentially evidence-based pharmacotherapy is crucial to target recovery. Currently limited data exist to support the clinicians in their every-day intensive care prescribing practice with the contemporary ECMO technology.

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Extracorporeal membrane oxygenation (ECMO) treatment alleviates systemic cardiorespiratory failure. However, it is unclear whether ECMO also improves microcirculatory function, as the microcirculation can be disturbed despite normal systemic hemodynamics. We therefore aimed to study the sublingual microcirculation (SMC) throughout neonatal and pediatric ECMO treatment.

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Evidence-based analgosedation in severe pediatric traumatic brain injury (pTBI) management is lacking, and improved pharmacological understanding is needed. This starts with increased knowledge of factors controlling the pharmacokinetics (PK) of unbound drug at the target site (brain) and related drug effect(s). This prospective, descriptive study tested a pediatric physiology-based pharmacokinetic software model by comparing actual plasma and brain extracellular fluid (brain) morphine concentrations with predicted concentration-time profiles in severe pTBI patients (Glasgow Coma Scale [GCS], ≤8).

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Background: Morphine is worldwide the analgesic of first choice after cardiac surgery in children. Morphine has unwanted hemodynamic and respiratory side effects. Therefore, post-cardiac surgery patients may potentially benefit from a non-opioid drug for pain relief.

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Background: Use of donor blood in congenital cardiac surgery increases the risk for post-operative morbidity and mortality. To reduce the need for allogenic blood transfusion a technique for peri-operative mechanical red cell salvage is applied. Blood from the operation site is collected in a reservoir, processed, passed through a lipophilic filter and returned to the patient.

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Data evaluating pharmacokinetic/pharmacodynamic (PK/PD) aspect in the pediatric population are scarce especially regarding the pediatric intensive care unit. Dosing of frequently used drugs (sedatives, analgesics, antibiotics and cardiovascular drugs) are mainly based on non "pediatric intensive care unit (PICU)" patients, and sometimes are translated from adult patients. Among PICU patients, the most complex patients are the ones who are critically ill and are receiving mechanical circulatory/respiratory support for cardiac and/or respiratory failure.

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Objective: The mainstay of pain treatment after paediatric cardiac surgery is the use of opioids. Current guidelines for its optimal use are based on small, non-randomised clinical trials, and data on the pharmacokinetics (PK) and pharmacodynamics (PD) of opioids are lacking. This study aims at providing an overview of international hospital practices on the treatment of pain and sedation after paediatric cardiac surgery.

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