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  1. Artikel ; Online: Evaluation of an aPTT guided versus a multimodal heparin monitoring approach in patients on extra corporeal membrane oxygenation: A retrospective cohort study.

    Taha, Diman / Drop, Joppe G / Wildschut, Enno D / De Hoog, Matthijs / van Ommen, C Heleen / Reis Miranda, Dinis Dos

    Perfusion

    2024  , Seite(n) 2676591241253474

    Abstract: Introduction: Bleeding and thrombotic complications are common in extracorporeal membrane oxygenation (ECMO) patients and are associated with increased mortality and morbidity. The optimal anticoagulation monitoring protocol in these patients is unknown. ...

    Abstract Introduction: Bleeding and thrombotic complications are common in extracorporeal membrane oxygenation (ECMO) patients and are associated with increased mortality and morbidity. The optimal anticoagulation monitoring protocol in these patients is unknown. This study aims to compare the incidence of thrombotic and hemorrhagic complications before and after a protocol change. In addition, the association between hemostatic complications, coagulation tests and risk factors is evaluated.
    Methods: This is a retrospective single center cohort study of adult ECMO patients. We collected demographics, ECMO parameters and coagulation test results. Outcomes of the aPTT guided and multimodal protocol, including aPTT, anti-Xa assay and rotational thromboelastometry were compared and the association between coagulation tests, risk factors and hemostatic complications was determined using a logistic regression analysis for repeated measurements.
    Results: In total, 250 patients were included, 138 in the aPTT protocol and 112 in the multimodal protocol. The incidence of thrombosis (aPTT: 14%; multimodal: 12%) and bleeding (aPTT: 36%; multimodal: 40%), did not significantly differ between protocols. In the aPTT guided protocol, the aPTT was associated with thrombosis (Odds Ratio [OR] 1.015; 95% confidence interval [CI] 1.004-1.027). In both protocols, surgical interventions were risk factors for bleeding and thrombotic complications (aPTT: OR 93.2, CI 39.9-217.6; multimodal OR 17.5, CI 6.5-46.9).
    Discussion: The incidence of hemostatic complications was similar between both protocols and surgical interventions were a risk factor for hemostatic complications. Results from this study help to elucidate the role of coagulation tests and risk factors in predicting hemostatic complications in patients undergoing ECMO support.
    Sprache Englisch
    Erscheinungsdatum 2024-05-13
    Erscheinungsland England
    Dokumenttyp Journal Article ; Review
    ZDB-ID 645038-6
    ISSN 1477-111X ; 0267-6591
    ISSN (online) 1477-111X
    ISSN 0267-6591
    DOI 10.1177/02676591241253474
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: Bacteria in Extracorporeal Membrane Oxygenation Circuit Clots of a Patient With Persistent Bacteremia: A Case Report.

    Drop, Joppe G / Verhage, Latisha / van Westreenen, Mireille / Wildschut, Enno D / de Hoog, Matthijs / van Beusekom, Heleen / van Ommen, C Heleen

    ASAIO journal (American Society for Artificial Internal Organs : 1992)

    2023  Band 69, Heft 11, Seite(n) e463–e466

    Abstract: 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, ... ...

    Abstract 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. A circuit change was performed due to buildup of thrombotic material and disseminated intravascular coagulation (DIC) inside the circuit. Thrombus formation was more extensive in the first than the second circuit. Gram-positive diplococci were present in all initial circuit clots and gram-positive masses surrounded by fibrin were found inside thrombi of the second circuit. Scanning electron microscopy (SEM) revealed a dense fibrin network with embedded red blood cells and bacteria in the first circuit. In the second circuit, SEM analysis revealed scattered micro thrombi. Polymerase chain reaction for identification of bacteria in the thrombus of the first circuit showed the same bacteria as found in blood cultures and did not achieve a sufficient signal in the second circuit. This case report shows that bacteria can nestle in thrombi of an ECMO circuit and that there is a rationale for a circuit change in a patient with persistent positive blood cultures and DIC.
    Mesh-Begriff(e) Infant, Newborn ; Humans ; Extracorporeal Membrane Oxygenation/adverse effects ; Thrombosis/etiology ; Fibrin ; Bacteria ; Bacteremia/complications ; Anti-Bacterial Agents/therapeutic use
    Chemische Substanzen Fibrin (9001-31-4) ; Anti-Bacterial Agents
    Sprache Englisch
    Erscheinungsdatum 2023-05-17
    Erscheinungsland United States
    Dokumenttyp Case Reports ; Journal Article
    ZDB-ID 759982-1
    ISSN 1538-943X ; 0162-1432 ; 1058-2916
    ISSN (online) 1538-943X
    ISSN 0162-1432 ; 1058-2916
    DOI 10.1097/MAT.0000000000001980
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel: Pro-opiomelanocortin and ACTH-cortisol dissociation during pediatric cardiac surgery.

    Téblick, Arno / Vanhorebeek, Ilse / Derese, Inge / Jacobs, An / Haghedooren, Renata / Maebe, Sofie / Zeilmaker-Roest, Gerdian A / Wildschut, Enno D / Langouche, Lies / Van den Berghe, Greet

    Endocrine connections

    2024  

    Abstract: 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 ... ...

    Abstract 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. From 53 patients (0-36 months), plasma was obtained pre-operatively, intraoperatively and on post-operative day 1 and 2. Plasma was also collected from 24 healthy children. In patients, POMC was supra-normal pre-operatively (p<0.0001) but no longer thereafter (p<0.05). ACTH was never high in patients. While in glucocorticoid-naive patients ACTH became suppressed by post-operative day 1 (p<0.0001), glucocorticoid-treated patients had suppressed ACTH already intraoperatively (p≤0.0001). Pre-operatively high POMC, not accompanied by increased plasma ACTH, suggests a centrally-activated HPA-axis with reduced pituitary processing of POMC into ACTH. Increasing systemic glucocorticoid availability with glucocorticoid treatment accelerated the suppression of plasma ACTH.
    Sprache Englisch
    Erscheinungsdatum 2024-04-01
    Erscheinungsland England
    Dokumenttyp Journal Article
    ZDB-ID 2668428-7
    ISSN 2049-3614
    ISSN 2049-3614
    DOI 10.1530/EC-24-0078
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  4. Artikel: The Pharmacokinetics of Beta-Lactam Antibiotics Using Scavenged Samples in Pediatric Intensive Care Patients: The EXPAT Kids Study Protocol.

    Schouwenburg, Stef / Wildschut, Enno D / de Hoog, M / Koch, Birgit C P / Abdulla, Alan

    Frontiers in pharmacology

    2021  Band 12, Seite(n) 750080

    Abstract: Background: ...

    Abstract Background:
    Sprache Englisch
    Erscheinungsdatum 2021-12-10
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article ; Review
    ZDB-ID 2587355-6
    ISSN 1663-9812
    ISSN 1663-9812
    DOI 10.3389/fphar.2021.750080
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  5. Artikel ; Online: Acquired von Willebrand disease in children undergoing extracorporeal membrane oxygenation: a prospective observational study.

    Drop, Joppe G / Wildschut, Enno D / de Maat, Moniek P M / van Rosmalen, Joost / de Boode, Willem P / de Hoog, Matthijs / Heleen van Ommen, C

    Journal of thrombosis and haemostasis : JTH

    2023  Band 21, Heft 12, Seite(n) 3383–3392

    Abstract: 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) ...

    Abstract 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.
    Objective: To study the incidence and longitudinal profile of AVWD during the first 14 days of ECMO support in children and to investigate the association between AVWD and bleeding complications.
    Methods: This prospective observational study included pediatric patients (0-17 years) receiving ECMO. Blood was sampled prior to and after ECMO start, daily and 12 to 24 hours after stopping ECMO. von Willebrand factor (VWF) parameters and multimer patterns were determined. Clinical data were collected for each patient. AVWD was defined as loss of high-molecular weight multimers (ie, decreased compared with baseline) or a VWF:collagen binding/VWF: antigen (Ag) ratio or VWF:activity/VWF:Ag ratio below 0.7.
    Results: All of 50 (100%) patients developed AVWD during ECMO. The VWF:collagen binding /VWF:Ag ratio, VWF:activity/VWF:Ag ratio, and high-molecular weight multimers decreased during the initial days and recovered to baseline level within 24 hours after stopping ECMO. The incidence and longitudinal profile of AVWD were similar in patients with and without major bleeding complications.
    Conclusion: Children receiving ECMO support commonly develop AVWD. AVWD develops rapidly after ECMO initiation and recovers quickly after ECMO cessation. Importantly, AVWD appears to be independent of major bleeding.
    Mesh-Begriff(e) Child ; Humans ; Collagen ; Extracorporeal Membrane Oxygenation/adverse effects ; Hemorrhage/complications ; von Willebrand Diseases/diagnosis ; von Willebrand Diseases/epidemiology ; von Willebrand Factor/metabolism ; Prospective Studies
    Chemische Substanzen Collagen (9007-34-5) ; von Willebrand Factor
    Sprache Englisch
    Erscheinungsdatum 2023-08-12
    Erscheinungsland England
    Dokumenttyp Observational Study ; Journal Article
    ZDB-ID 2112661-6
    ISSN 1538-7836 ; 1538-7933
    ISSN (online) 1538-7836
    ISSN 1538-7933
    DOI 10.1016/j.jtha.2023.08.007
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  6. Artikel ; Online: A Population Pharmacokinetic Model of Pentobarbital for Children with Status Epilepticus and Severe Traumatic Brain Injury.

    Ketharanathan, Naomi / Lili, Anastasia / de Vries, Julia M Penning / Wildschut, Enno D / de Hoog, Matthijs / Koch, Birgit C P / de Winter, Brenda C M

    Clinical pharmacokinetics

    2023  Band 62, Heft 7, Seite(n) 1011–1022

    Abstract: Background: Pentobarbital pharmacokinetics (PK) remain elusive and the therapeutic windows narrow. Administration is frequent in critically ill children with refractory status epilepticus (SE) and severe traumatic brain injury (sTBI).: Objectives: To ...

    Abstract Background: Pentobarbital pharmacokinetics (PK) remain elusive and the therapeutic windows narrow. Administration is frequent in critically ill children with refractory status epilepticus (SE) and severe traumatic brain injury (sTBI).
    Objectives: To investigate pentobarbital PK in SE and sTBI patients admitted to the paediatric intensive care unit (PICU) with population-based PK (PopPK) modelling and dosing simulations.
    Methods: Develop a PopPK model with non-linear mixed-effects modelling (NONMEM
    Results: A one-compartment PK model with allometrically scaled weight on clearance (CL; 0.75) and volume of distribution (V
    Conclusions: The one-compartment PK model of intravenous pentobarbital described data well whereby serum creatinine and CRP significantly correlated with pentobarbital CL. Dosing simulations formulated adjusted dosing advice in patients with elevated creatinine and/or CRP. Prospective PK studies with pharmacodynamic endpoints, are imperative to optimise pentobarbital dosing in terms of safety and clinical efficacy in critically ill children.
    Mesh-Begriff(e) Humans ; Child ; Infant ; Anti-Bacterial Agents/pharmacokinetics ; Pentobarbital ; Creatinine ; Critical Illness ; Retrospective Studies ; Prospective Studies ; Brain Injuries, Traumatic/drug therapy ; Status Epilepticus/drug therapy
    Chemische Substanzen Anti-Bacterial Agents ; Pentobarbital (I4744080IR) ; Creatinine (AYI8EX34EU)
    Sprache Englisch
    Erscheinungsdatum 2023-05-29
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article
    ZDB-ID 197627-8
    ISSN 1179-1926 ; 0312-5963
    ISSN (online) 1179-1926
    ISSN 0312-5963
    DOI 10.1007/s40262-023-01249-z
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  7. Artikel ; Online: Withdrawal of Life-Sustaining Therapies in Children With Severe Traumatic Brain Injury.

    Ketharanathan, Naomi / Hunfeld, Maayke A W / de Jong, Marcus C / van der Zanden, Lineke J / Spoor, Jochem K H / Wildschut, Enno D / de Hoog, Matthijs / Tibboel, Dick / Buysse, Corinne M P

    Journal of neurotrauma

    2023  Band 40, Heft 13-14, Seite(n) 1388–1401

    Abstract: 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, ... ...

    Abstract 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. This retrospective, single center observational study included patients <18 years admitted to the pediatric intensive care unit (PICU) of Erasmus MC-Sophia (a tertiary university hospital) between 2012 and 2020 with sTBI defined as a Glasgow Coma Scale (GCS) ≤8 and requiring intracranial pressure (ICP) monitoring. Clinical, neuroimaging, and electroencephalogram data were reviewed. Multi-disciplinary follow-up included the Pediatric Cerebral Performance Category (PCPC) score, educational level, and commonly cited complaints. Seventy-eight children with sTBI were included (median age 10.5 years; interquartile range [IQR] 5.0-14.1; 56% male; 67% traffic-related accidents). Median ICP monitoring was 5 days (IQR 3-8), 19 (24%) underwent decompressive craniectomy. PICU mortality was 21% (16/78): clinical brain death (5/16), WLST due to poor neurological prognosis (WLST_neuro, 11/16). Significant differences (
    Mesh-Begriff(e) Humans ; Child ; Male ; Female ; Persistent Vegetative State/complications ; Retrospective Studies ; Brain Death ; Brain Injuries, Traumatic/therapy ; Brain Injuries, Traumatic/complications ; Brain Injuries/complications
    Sprache Englisch
    Erscheinungsdatum 2023-02-27
    Erscheinungsland United States
    Dokumenttyp Observational Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 645092-1
    ISSN 1557-9042 ; 0897-7151
    ISSN (online) 1557-9042
    ISSN 0897-7151
    DOI 10.1089/neu.2022.0321
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  8. Artikel: Model-Informed Precision Dosing of Antibiotics in Pediatric Patients: A Narrative Review.

    Abdulla, Alan / Edwina, Elma E / Flint, Robert B / Allegaert, Karel / Wildschut, Enno D / Koch, Birgit C P / de Hoog, Matthijs

    Frontiers in pediatrics

    2021  Band 9, Seite(n) 624639

    Abstract: 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- ... ...

    Abstract 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., disease state, inflammation, organ failure, co-morbidity, co-medication and extracorporeal systems), antibiotic pharmacokinetics is highly variable in pediatric patients and difficult to predict without using population pharmacokinetics models. The intra- and inter-individual variability can result in under- or overexposure in a significant proportion of patients. Therapeutic drug monitoring typically covers assessment of pharmacokinetics and pharmacodynamics, and concurrent dose adaptation after initial standard dosing and drug concentration analysis. Model-informed precision dosing (MIPD) captures drug, disease, and patient characteristics in modeling approaches and can be used to perform Bayesian forecasting and dose optimization. Incorporating MIPD in the electronic patient record system brings pharmacometrics to the bedside of the patient, with the aim of a consisted and optimal drug exposure. In this narrative review, we evaluated studies assessing optimization of antibiotic pharmacotherapy using MIPD in pediatric populations. Four eligible studies involving amikacin and vancomycin were identified from 418 records. Key articles, independent of year of publication, were also selected to highlight important attributes of MIPD. Although very little research has been conducted until this moment, the available data on vancomycin indicate that MIPD is superior compared to conventional dosing strategies with respect to target attainment. The utility of MIPD in pediatrics needs to be further confirmed in frequently used antibiotic classes, particularly aminoglycosides and beta-lactams.
    Sprache Englisch
    Erscheinungsdatum 2021-02-23
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article ; Review
    ZDB-ID 2711999-3
    ISSN 2296-2360
    ISSN 2296-2360
    DOI 10.3389/fped.2021.624639
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  9. Artikel ; Online: Intermittent intravenous paracetamol versus continuous morphine in infants undergoing cardiothoracic surgery: a multi-center randomized controlled trial.

    Zeilmaker-Roest, Gerdien / de Vries-Rink, Christine / van Rosmalen, Joost / van Dijk, Monique / de Wildt, Saskia N / Knibbe, Catherijne A J / Koomen, Erik / Jansen, Nicolaas J G / Kneyber, Martin C J / Maebe, Sofie / Van den Berghe, Greet / Haghedooren, Renata / Vlasselaers, Dirk / Bogers, Ad J J C / Tibboel, Dick / Wildschut, Enno D

    Critical care (London, England)

    2024  Band 28, Heft 1, Seite(n) 143

    Abstract: Background: To determine whether intermittent intravenous (IV) paracetamol as primary analgesic would significantly reduce morphine consumption in children aged 0-3 years after cardiac surgery with cardiopulmonary bypass.: Methods: Multi-center, ... ...

    Abstract Background: To determine whether intermittent intravenous (IV) paracetamol as primary analgesic would significantly reduce morphine consumption in children aged 0-3 years after cardiac surgery with cardiopulmonary bypass.
    Methods: Multi-center, randomized, double-blinded, controlled trial in four level-3 Pediatric Intensive Care Units (PICU) in the Netherlands and Belgium. Inclusion period; March 2016-July 2020. Children aged 0-3 years, undergoing cardiac surgery with cardiopulmonary bypass were eligible. Patients were randomized to continuous morphine or intermittent IV paracetamol as primary analgesic after a loading dose of 100 mcg/kg morphine was administered at the end of surgery. Rescue morphine was given if numeric rating scale (NRS) pain scores exceeded predetermined cutoff values. Primary outcome was median weight-adjusted cumulative morphine dose in mcg/kg in the first 48 h postoperative. For the comparison of the primary outcome between groups, the nonparametric Van Elteren test with stratification by center was used. For comparison of the proportion of patients with one or more NRS pain scores of 4 and higher between the two groups, a non-inferiority analysis was performed using a non-inferiority margin of 20%.
    Results: In total, 828 were screened and finally 208 patients were included; parents of 315 patients did not give consent and 305 were excluded for various reasons. Fourteen of the enrolled 208 children were withdrawn from the study before start of study medication leaving 194 patients for final analysis. One hundred and two patients received intermittent IV paracetamol, 106 received continuous morphine. The median weight-adjusted cumulative morphine consumption in the first 48 h postoperative in the IV paracetamol group was 5 times lower (79%) than that in the morphine group (median, 145.0 (IQR, 115.0-432.5) mcg/kg vs 692.6 (IQR, 532.7-856.1) mcg/kg; P < 0.001). The rescue morphine consumption was similar between the groups (p = 0.38). Non-inferiority of IV paracetamol administration in terms of NRS pain scores was proven; difference in proportion - 3.1% (95% CI - 16.6-10.3%).
    Conclusions: In children aged 0-3 years undergoing cardiac surgery, use of intermittent IV paracetamol reduces the median weight-adjusted cumulative morphine consumption in the first 48 h after surgery by 79% with equal pain relief showing equipoise for IV paracetamol as primary analgesic. Trial Registration Clinicaltrials.gov, Identifier: NCT05853263; EudraCT Number: 2015-001835-20.
    Mesh-Begriff(e) Humans ; Morphine/therapeutic use ; Morphine/administration & dosage ; Acetaminophen/therapeutic use ; Acetaminophen/administration & dosage ; Male ; Female ; Infant ; Double-Blind Method ; Pain, Postoperative/drug therapy ; Analgesics, Opioid/administration & dosage ; Analgesics, Opioid/therapeutic use ; Belgium ; Netherlands ; Infant, Newborn ; Administration, Intravenous ; Cardiac Surgical Procedures/methods ; Child, Preschool ; Analgesics, Non-Narcotic/administration & dosage ; Analgesics, Non-Narcotic/therapeutic use ; Intensive Care Units, Pediatric/organization & administration ; Intensive Care Units, Pediatric/statistics & numerical data ; Pain Measurement/methods
    Chemische Substanzen Morphine (76I7G6D29C) ; Acetaminophen (362O9ITL9D) ; Analgesics, Opioid ; Analgesics, Non-Narcotic
    Sprache Englisch
    Erscheinungsdatum 2024-04-30
    Erscheinungsland England
    Dokumenttyp Journal Article ; Randomized Controlled Trial ; Multicenter Study ; Research Support, Non-U.S. Gov't
    ZDB-ID 2041406-7
    ISSN 1466-609X ; 1364-8535
    ISSN (online) 1466-609X
    ISSN 1364-8535
    DOI 10.1186/s13054-024-04905-3
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  10. Artikel: Challenges in Maintaining the Hemostatic Balance in Children Undergoing Extracorporeal Membrane Oxygenation: A Systematic Literature Review.

    Drop, Joppe G F / Wildschut, Enno D / Gunput, Sabrina T G / de Hoog, Matthijs / van Ommen, C Heleen

    Frontiers in pediatrics

    2020  Band 8, Seite(n) 612467

    Abstract: Background: ...

    Abstract Background:
    Sprache Englisch
    Erscheinungsdatum 2020-12-16
    Erscheinungsland Switzerland
    Dokumenttyp Systematic Review
    ZDB-ID 2711999-3
    ISSN 2296-2360
    ISSN 2296-2360
    DOI 10.3389/fped.2020.612467
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