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Objective: To compare the level of agreement between proximal (near the subject) and distal (inside the ventilator) measured airway occlusion pressure at 100 ms (P0.1) and occlusion pressure (ΔPocc), and to study the correlation between ΔPocc and peak-to-trough esophageal pressure (ΔPes)., Design: Secondary analysis of prospectively collected physiology dataset (2021-2022)., Setting: Medical-surgical 20-bed PICU., Patients: Children younger than 18 years with and without acute lung injury ventilated greater than 24 hours and spontaneously breathing with appropriate triggering of the ventilator., Interventions: None., Measurements and Main Results: Data from three expiratory hold maneuvers (with a maximum of three breaths during each maneuver) in 74 subjects (118 measurements) with median age 3 months (interquartile range 1-17), and primary respiratory failure due to a pulmonary infection in 41/74 (55.4%) were studied. The median proximal ∆Pocc was 6.7 cm H2O (3.1-10.7) and median P0.1 4.9 cm H2O (4.1-6.0) for the first breath from the maneuver; both increased significantly (p < 0.001) with the subsequent two breaths during the same maneuver. Median distal ∆Pocc was 6.8 (2.9-10.8) and P0.1 4.6 (3.9-5.6) cm H2O; both increased significantly (p < 0.001) with the two subsequent breaths. Proximal and distal ΔPocc (r > 0.99, p < 0.001) and P0.1 (r > 0.80, p < 0.001) were correlated. Correlation between ventilator displayed and Y-piece measured ΔPocc (r > 0.99) and P0.1 (r = 0.85) was good. Mean (sd) difference for ΔPocc was 0.13 (0.21); levels of agreement were -0.28 and 0.54. For P0.1, mean (sd) difference was -0.36 (1.14) and levels of agreement -2.61 and 1.88. There was a high correlation between ΔPes and ∆Pocc (r = 0.92) for the same breath and a good correlation with ΔPes from the preceding breath (r = 0.76). There was a poor correlation with the transpulmonary pressure (r = 0.37)., Conclusions: ΔPocc is not affected by measurement site, whereas P0.1 may be overestimated or underestimated. ΔPocc was highly correlated with the peak-to-trough esophageal pressure, supporting the concept that inspiratory effort can also be quantified noninvasively by measuring ΔPocc., Competing Interests: Dr. Rudolph’s institution received funding from ZonMW (project number 848041002); she received support for article research from ZonMW. Dr. Kneyber received funding from Getinge, Chiesi, and Metran. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2025 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

To describe outcomes of a cohort of patients with paediatric acute liver failure (PALF) treated with either one of two extracorporeal therapies (ECT) - continuous renal replacement therapy (CRRT) and molecular adsorbent recirculatory system (MARS®). Retrospective, observational, cohort study at two European paediatric intensive care units (PICUs) - UK (2006-2017, CRRT) and the Netherlands (2003-2017, MARS® and CRRT). Patients were children (0-18 years) admitted to the PICU with PALF who required CRRT or MARS®. Between each group, we compared baseline characteristics, biochemical parameters at 0 and 24 h after commencing MARS®/CRRT, and clinical outcomes. In total, 95 patients (23 MARS®, 72 CRRT) were included. The median age at admission for the whole cohort was 4.3 years (interquartile range (IQR) 1.0-12.1), and 47/95 (49.5%) of patients had an indeterminate aetiology. A lower proportion of patients in the MARS® group were on inotropes or were ventilated at admission, and they had a lower Pediatric Index of Mortality 3 risk % than the CRRT group (14.5% (7.5-22) vs 20.4% (16.8-26.4), p = 0.002). After treatment, there were no significant differences detected between groups in survival with native liver, or overall survival (15/23 (65.2%) for MARS® and 49/72 (68.1%) for CRRT, p = 0.998)., Conclusion: We did not detect a significant difference in clinical outcomes between PALF patients treated with CRRT or MARS®, despite a relatively sicker cohort in the CRRT group. Further high-quality evidence is necessary regarding the role of extracorporeal therapies in PALF, with consideration of clinical outcomes, feasibility, and cost., What Is Known: • Outcomes for children with paediatric acute liver failure (PALF) have improved in recent years secondary to improved supportive care aimed at avoiding liver transplantation. • Extracorporeal therapies, in particular continuous renal replacement therapy (CRRT), are increasingly applied in the management of these children; however few studies have compared outcomes between different extracorporeal therapies., What Is New: • In this retrospective study across two centres, outcomes between patients with PALF treated with CRRT were compared to patients treated with MARS®. • There was no significant difference in key clinical outcomes between groups, including survival with native liver and overall survival., Competing Interests: Declarations. Competing interests: AkD is Chair of Scientific Affairs of the European Society of Paediatric and Neonatal Intensive Care (ESPNIC) and Chair of the Working Group for Liver Failure in ESPNIC. MK is Medical President of ESPNIC. All other authors have no conflicts of interest to declare., (© 2025. The Author(s).)

Paediatric critical care units are designed for children at a vulnerable stage of development, yet the evidence base for practice and policy in paediatric critical care remains scarce. In this Health Policy, we present a roadmap providing strategic guidance for international paediatric critical care trials. We convened a multidisciplinary group of 32 paediatric critical care experts from six continents representing paediatric critical care research networks and groups. The group identified key challenges to paediatric critical care research, including lower patient numbers than for adult critical care, heterogeneity related to cognitive development, comorbidities and illness or injury, consent challenges, disproportionately little research funding for paediatric critical care, and poor infrastructure in resource-limited settings. A seven-point roadmap was proposed: (1) formation of an international paediatric critical care research network; (2) development of a web-based toolkit library to support paediatric critical care trials; (3) establishment of a global paediatric critical care trial repository, including systematic prioritisation of topics and populations for interventional trials; (4) development of a harmonised trial minimum set of trial data elements and data dictionary; (5) building of infrastructure and capability to support platform trials; (6) funder advocacy; and (7) development of a collaborative implementation programme. Implementation of this roadmap will contribute to the successful design and conduct of trials that match the needs of globally diverse paediatric populations., Competing Interests: Declaration of interests LJS received grants from the Swiss Personalized Health Network, Personalized Health-Related Technologies Switzerland, Nomis Foundation, Thomas & Doris Ammann Foundation, National Institutes of Health (NIH), National Health and Medical Research Council, and Medical Research Future Funds. KSG received support from a National Health and Medical Research Council Emerging Leader Fellowship. BMM received grants from EuroQoL and the Society of Critical Care Medicine; and serves as President of the World Federation of Pediatric Intensive and Critical Care Societies and the Critical Care Society of South Africa. NN received grants from Actuated Medical and Philips Respironics. AA received travel support from the WHO. JHL received grants from the Thrasher Foundation (USA) and the National Research Medical Council (Singapore). MJP received grants from the National Institute for Health and Care Research Health Technology Assessment and serves on the general funding committee. JF-S received grants from the Universidad de La Sabana. HRF received a grant from NIH. PF received grants from the Canadian Institutes of Health Research. MCJK received a grant from NIH and consultancy fees from Metran. KM received funding from the Children's Hospital of Eastern Ontario Foundation; and is chair of the Canadian Critical Care Trials Group., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Objectives: Intravenous midazolam is widely used for sedation in critically ill children. Sometimes, these children develop a paediatric delirium (PD). Our aim was to determine the relationship between midazolam serum concentration and the development of new PD in critically ill children., Design: Prospective observational pilot study., Setting: Paediatric Intensive Care Unit (PICU), Groningen, the Netherlands., Patients: All children admitted to the PICU from October-December 2019 who received continuous midazolam administration., Interventions: None., Measurements and Main Results: Twenty-five percent (n = 7) of the included patients (n = 28) developed new PD. In most patients, PD occurred following midazolam dose reduction. The median cumulative midazolam dose was higher in patients who developed PD compared to those without PD. We analysed 104 blood samples to determine the midazolam concentrations. To determine whether patients had PD, the Sophia Observation withdrawal Symptoms-Paediatric Delirium (SOS-PD) score was used. Patients suffering PD (n = 7) had a lower median midazolam concentration on that day compared with the day prior to PD detection. Analysis of the active metabolites, 1-hydroxymidazolam and 1-hydroxymidazolam glucuronide, showed similar results., Conclusions: PD may be linked to a sudden and significant reduction in the midazolam concentration in critically ill children. Further investigation in larger patient populations is necessary to validate our findings.

Invasive mechanical ventilation (MV) is one of the most practiced interventions in the intensive care unit (ICU) and is unmistakably lifesaving for children with acute respiratory failure (ARF). However, if delivered inappropriately (i.e. ignoring the respiratory system mechanics and not targeted to the need of the individual patient at a specific time point in the disease trajectory), the side effects will outweigh the benefits. Decades of experimental and clinical investigations have resulted in a better understanding of three important detrimental effects of MV. These are ventilation-induced lung injury (VILI), patient self-inflicted lung injury (P-SILI), and ventilation-induced diaphragmatic injury (VIDD). VILI, P-SILI, and VIDD have in common that they occur when there is either too much or too little ventilatory assistance.Conclusion: The purpose of this review is to give the paediatrician an overview of the challenges to prevent these detrimental effects and titrate MV to the individual patient needs., (© 2024. The Author(s).)

Background: The 2023 International Pediatric Ventilator Liberation Clinical Practice Guidelines provided evidence-based recommendations to guide pediatric critical care providers on how to perform daily aspects of ventilator liberation. However, because of the lack of high-quality pediatric studies, most recommendations were conditional based on very low to low certainty of evidence., Research Question: What are the research gaps related to pediatric ventilator liberation that can be studied to strengthen the evidence for future updates of the guidelines?, Study Design and Methods: We conducted systematic reviews of the literature in eight predefined Population, Intervention, Comparator, Outcome (PICO) areas related to pediatric ventilator liberation to generate recommendations. Subgroups responsible for each PICO question subsequently identified major research gaps by synthesizing the literature. These gaps were presented at an international symposium at the Pediatric Acute Lung Injury and Sepsis Investigators meeting in spring 2022 for open discussion. Feedback was incorporated, and final evaluation of research gaps are summarized herein. Although randomized controlled trials (RCTs) represent the highest level of evidence, the panel sought to highlight areas where alternative study designs also may be appropriate, given challenges with conducting large multicenter RCTs in children., Results: Significant research gaps were identified in six broad areas related to pediatric ventilator liberation. Several of these areas necessitate multicenter RCTs to provide definitive results, whereas other gaps can be addressed with multicenter observational studies or quality improvement initiatives. Furthermore, a need for some physiologic studies in several areas remains, particularly regarding newer diagnostic methods to improve identification of patients at high risk of extubation failure., Interpretation: Although pediatric ventilator liberation guidelines have been created, the certainty of evidence remains low and multiple research gaps exist that should be bridged through high-quality RCTs, multicenter observational studies, and quality improvement initiatives., Competing Interests: Financial/Nonfinancial Disclosures None declared., (Copyright © 2024 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Objectives: Respiratory management for pediatric acute respiratory distress syndrome (PARDS) remains largely supportive without data to support one approach over another, including supine versus prone positioning (PP) and conventional mechanical ventilation (CMV) versus high-frequency oscillatory ventilation (HFOV)., Design: We present the research methodology of a global, multicenter, two-by-two factorial, response-adaptive, randomized controlled trial of supine versus PP and CMV versus HFOV in high moderate-severe PARDS, the Prone and Oscillation Pediatric Clinical Trial ( PROSpect , www.ClinicalTrials.gov , NCT03896763)., Setting: Approximately 60 PICUs with on-site extracorporeal membrane oxygenation support in North and South America, Europe, Asia, and Oceania with experience using PP and HFOV in the care of patients with PARDS., Patients: Eligible pediatric patients (2 wk old or older and younger than 21 yr) are randomized within 48 h of meeting eligibility criteria occurring within 96 h of endotracheal intubation., Interventions: One of four arms, including supine/CMV, prone/CMV, supine/HFOV, or prone/HFOV. We hypothesize that children with high moderate-severe PARDS treated with PP or HFOV will demonstrate greater than or equal to 2 additional ventilator-free days (VFD)., Measurements and Main Results: The primary outcome is VFD through day 28; nonsurvivors receive zero VFD. Secondary and exploratory outcomes include nonpulmonary organ failure-free days, interaction effects of PP with HFOV on VFD, 90-day in-hospital mortality, and among survivors, duration of mechanical ventilation, PICU and hospital length of stay, and post-PICU functional status and health-related quality of life. Up to 600 patients will be randomized, stratified by age group and direct/indirect lung injury. Adaptive randomization will first occur 28 days after 300 patients are randomized and every 100 patients thereafter. At these randomization updates, new allocation probabilities will be computed based on intention-to-treat trial results, increasing allocation to well-performing arms and decreasing allocation to poorly performing arms. Data will be analyzed per intention-to-treat for the primary analyses and per-protocol for primary, secondary, and exploratory analyses., Conclusions: PROSpect will provide clinicians with data to inform the practice of PP and HFOV in PARDS., (Copyright © 2024 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Objectives: To derive systematic-review informed, modified Delphi consensus regarding prophylactic transfusions in neonates and children supported with extracorporeal membrane oxygenation (ECMO) from the Pediatric ECMO Anticoagulation CollaborativE., Data Sources: A structured literature search was performed using PubMed, EMBASE, and Cochrane Library (CENTRAL) databases from January 1988 to May 2020, with an update in May 2021., Study Selection: Included studies assessed use of prophylactic blood product transfusion in pediatric ECMO., Data Extraction: Two authors reviewed all citations independently, with a third independent reviewer resolving conflicts. Thirty-three references were used for data extraction and informed recommendations. Evidence tables were constructed using a standardized data extraction form., Measurements and Main Results: The evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation system. Forty-eight experts met over 2 years to develop evidence-informed recommendations and, when evidence was lacking, expert-based consensus statements or good practice statements for prophylactic transfusion strategies for children supported with ECMO. A web-based modified Delphi process was used to build consensus via the Research And Development/University of California Appropriateness Method. Consensus was based on a modified Delphi process with agreement defined as greater than 80%. We developed two good practice statements, 4 weak recommendations, and three expert consensus statements., Conclusions: Despite the frequency with which pediatric ECMO patients are transfused, there is insufficient evidence to formulate evidence-based prophylactic transfusion strategies., Competing Interests: The Executive Committee (Drs. Alexander, Muszynski, Bembea, Cheifetz, Steiner, and Barbaro) served as arbitrators for conflict of interest management. Dr. Alexander’s institution received funding from Novartis (consultant on the end-point adjudication committee for Prospective Trial to Assess the Angiotensin Receptor Blocker Neprilysin Inhibitor LCZ696 Versus Angiotensin-Converting Enzyme Inhibitor for the Medical Treatment of Pediatric HF [PANORAMA-HF] clinical trial). Dr. Sloan commenced employment with CSL Behring after the consensus process was complete. Dr. Kneyber received funding from Metran. Drs. Alexander and Muszynski’s institutions received funding from the National Institutes of Health (NIH); they received support for article research from the NIH. Dr. Alexander’s institution received funding from the Extracorporeal Life Support Organization and Novartis. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Objectives: To present recommendations and consensus statements with supporting literature for the clinical management of neonates and children supported with extracorporeal membrane oxygenation (ECMO) from the Pediatric ECMO Anticoagulation CollaborativE (PEACE) consensus conference., Data Sources: Systematic review was performed using PubMed, Embase, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021, followed by serial meetings of international, interprofessional experts in the management ECMO for critically ill children., Study Selection: The management of ECMO anticoagulation for critically ill children., Data Extraction: Within each of eight subgroup, two authors reviewed all citations independently, with a third independent reviewer resolving any conflicts., Data Synthesis: A systematic review was conducted using MEDLINE, Embase, and Cochrane Library databases, from January 1988 to May 2021. Each panel developed evidence-based and, when evidence was insufficient, expert-based statements for the clinical management of anticoagulation for children supported with ECMO. These statements were reviewed and ratified by 48 PEACE experts. Consensus was obtained using the Research and Development/UCLA Appropriateness Method. Results were summarized using the Grading of Recommendations Assessment, Development, and Evaluation method. We developed 23 recommendations, 52 expert consensus statements, and 16 good practice statements covering the management of ECMO anticoagulation in three broad categories: general care and monitoring; perioperative care; and nonprocedural bleeding or thrombosis. Gaps in knowledge and research priorities were identified, along with three research focused good practice statements., Conclusions: The 91 statements focused on clinical care will form the basis for standardization and future clinical trials., Competing Interests: Drs. Alexander’s and Muszynski’s institutions received funding from the National Institutes of Health (NIH). Drs. Alexander, Bembea, Himebauch, Barbaro, and Muszynski received support for article research from the NIH. Drs. Alexander’s and Bembea’s institutions received funding from the Extracorporeal Life Support Organization (ELSO). Dr. Alexander’s institution received funding from Novartis (Prospective Trial to Assess the Angiotensin Receptor Blocker Neprilysin Inhibitor LCZ696 Versus Angiotensin-Converting Enzyme Inhibitor for the Medical Treatment of Pediatric HF [PANORAMA-HF]). Dr. Alexander disclosed that she is Treasurer of the Board of Directors of ELSO, past Co-Chair of Pediatric Extracorporeal Membrane Oxygenation (Pedi-ECMO). Dr. Bembea’s institution received funding from the National Institute of Neurologic Disorders and Stroke and a Grifols Investigator Sponsored Research Grant. Dr. Cheifetz received funding from UptoDate. Dr. Dalton received funding from Innovative Extracorporeal Membrane Oxygenation (ECMO) Concepts, Medtronic, Entegrion, and Hemocue. Drs. Dalton, Ozment, Barbaro, Almond, Brandão, Baumann Kreuziger, Paden, and Ryerson disclosed the off-label product use of pediatric ECMO-related medications for anticoagulation. Dr. Himebauch’s institution received funding from the National Heart, Lung, and Blood Institute (NHLBI) (K23HL153759). Drs. Karam’s and Nellis’s institutions received funding from the NHBLI (R34HL159119). Dr. Ozment received funding from Kaufman & Canoles, Social Cascade, and Wiseman Ashworth Law Group. Dr. Steiner’s institution received funding from the Department of Defense (DoD); she received funding from Medtronic and Octapharma; she disclosed that she is a Pumps for Kids, Infantsand Neonates (PumpKIN) trial Data Safety and Monitoring Board member. Dr. Alexander’s and Thiagarajan’s institution received funding from the DoD Clinical Trial Award for Trial of Indication-Based Transfusion of RBCs in ECMO trial (W81XWH2210301). Dr. Thiagarajan received funding from Society of Critical Care Medicine and ELSO. Dr. Zantek disclosed that she is a Board Member and Vice President of the North American Specialized Coagulation Laboratory Association and Board Member of the American Society for Apheresis, the External Quality Assurance in Thrombosis and Hemostasis, and Blood Network subgroup of Pediatric Acute Lung Injury and Sepsis Investigators groups; she disclosed that her spouse is an employee of Boston Scientific and owns stock in Endo International PLC. Dr. Barbaro’s institution received funding from the NHLBI (R01 HL153519 and K12 HL138039); he disclosed that he is ELSO Board of Directors and Pedi-ECMO Co-Chair. Dr. Emani received funding from Chiesi Pharma. Dr. Hyslop disclosed he is Co-Chair of ELSO Registry Database Development Committee and Coordinator Liaison to ELSO Steering Committee. Dr. Baumann Kreuziger received funding from the Health Resources and Services Administration Vaccine Injury Compensation Program. Dr. Paden disclosed that he is past president and board member of ELSO. Dr. Ryerson received an honorarium from Instrumentation Laboratory for consultation work. Dr. Sloan commenced employment with CSL Behring after the consensus process was complete. Dr. Patregnani received funding from Mallinckrodt; he discloses consultation payments from MNK pharmaceuticals and Pfizer. The Executive Committee (Drs. Alexander, Muszynski, Bembea, Cheifetz, Steiner, and Barbaro) served as arbitrators for conflict-of-interest management. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Background: The implementation of the approved respiratory syncytial virus (RSV) preventive interventions in immunisation programmes is advancing rapidly. Insight into healthcare costs of RSV-related paediatric intensive care unit (PICU) admissions is lacking, but of great importance to evaluate the impact of implementation. Therefore, this study aimed to determine the total annual RSV-related paediatric intensive care healthcare costs in the Netherlands., Methods: A nationwide prospective, observational, multicenter study was performed from September 2021 until June 2023. The total annual RSV-related healthcare costs on PICUs in the Netherlands were calculated using RSV-related costs (subgroup I) and consequential costs (subgroup II and III). Subgroup I comprised all PICU admitted infants ≤12 months of age with laboratory-confirmed RSV infection. Subgroup II and III consisted of postponed elective PICU admissions and refused acute PICU admissions due to RSV-related lack of PICU capacity., Findings: A total of 424 infants with RSV-related PICU admission were included. Median age at PICU admission was 46 days (IQR 25-89). The median length of PICU admission was 5 days (IQR 3-8). The total RSV-related PICU costs are € 3,826,386 in 2021-2022, and € 3,183,888 in 2022-2023. Potential costs averted by RSV preventive interventions is € 1.9 to € 2.6 million depending on season, and the duration of protection., Interpretation: RSV-related PICU admissions cost €3.1 to €3.8 million in the Netherlands during one season. The introduction of new RSV preventive interventions into the Dutch immunisation programme will generate significant cost-savings on PICUs and decreases the admission burden of PICUs., Funding: None., Competing Interests: EP, CB, MH, MK, SM, AN, MR, RWA, JvW and GF have no competing interests to declare. LB has regular interaction with pharmaceutical and other industrial partners. He has not received personal fees or other personal benefits. UMCU has received major funding (>€100,000 per industrial partner) for investigator initiated studies from AstraZeneca, Sanofi, Janssen, Pfizer, MSD and MeMed Diagnostics. UMCU has received major funding from the Bill and Melinda Gates Foundation. UMCU has received major funding as part of the public private partnership IMI-funded RESCEU and PROMISE projects with partners GSK, Novavax, Janssen, AstraZeneca, Pfizer and Sanofi. UMCU has received major funding by Julius Clinical for participating in clinical studies sponsored by AstraZeneca, Merck and Pfizer. UMCU received minor funding (€1000–25,000 per industrial partner) for consultation, DSMB membership or invited lectures by Ablynx, Bavaria Nordic, GSK, Novavax, Pfizer, Moderna, Astrazeneca, MSD, Sanofi, Janssen. LB is the founding chairman of the ReSViNET Foundation. JGW has been an investigator for clinical trials sponsored by pharmaceutical companies including AstraZeneca, Merck, Pfizer, Sanofi, and Janssen and an investigator for clinical trials funded by IMI/Horizon2020 and ZonMw. All funds have been paid to the institution (UMCU). JGW participated in advisory boards of Janssen and Sanofi and was a speaker at a Sanofi sponsored symposium with fees paid to the institution (UMCU)., (© 2024 The Author(s).)

Objective: Compared with fresh frozen plasma (FFP), Omniplasma has been attributed to an increased coagulation potential and an increased fibrinolytic potential. This study aimed to compare Omniplasma and FFP used for cardiopulmonary bypass (CPB) priming regarding the incidence of postoperative thrombotic or hemorrhagic complications and outcomes in pediatric patients undergoing cardiac surgery., Design: A retrospective observational cohort study SETTING: This single-center study was performed at the University Medical Center Groningen., Participant: All pediatric patients up to 10 kg undergoing cardiac surgery with CPB., Interventions: Procedures in which FFP was used for CPB priming were compared with those in which Omniplasma was used., Measurements and Main Results: The primary outcome parameter was a composite endpoint consisting of the following: (1) pediatric intensive care unit (PICU) mortality, (2) thromboembolic complications, and (3) hemorrhagic complications during PICU stay. The authors included 143 procedures in the analyses, 90 (63%) in the FFP group and 53 (37%) in the Omniplasma group. The occurrence of the combined primary endpoint (FFP 20% v Omniplasma 11%, p = 0.18) and its components did not differ between the used CPB priming agent). Omniplasma for CPB priming was associated with decreased unfractionated heparin administration per kg bodyweight (585 IU v 510 IU, p = 0.03), higher preoperative and postoperative activated clotting times (ACT) discrepancy (90% v 94%, p = 0.03), a lower postoperative ACT value (125 v 118 seconds, p = 0.01), and less red blood cell transfusion per kilogram bodyweight (78 v 55 mL, p = 0.02). However, none of the variables differed statistically significantly in the multivariate logistic regression analyses., Conclusions: The authors did not find an association between the plasma used for CPB priming and thromboembolic and hemorrhagic complications and death in neonates and infants undergoing cardiac surgery. Omniplasma seems to be safe to use in this population., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

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., (© 2024. The Author(s).)

Background: Lung volume optimization maneuvers (LVOM) are necessary to make physiologic use of high-frequency oscillatory ventilation (HFOV), but lung behavior during such maneuvers has not been studied to determine lung volume changes after initiation of HFOV, to quantify recruitment versus derecruitment during the LVOM and to calculate the time to stabilization after a pressure change., Methods: We performed a secondary analysis of prospectively collected data in subjects < 18 years on HFOV. Uncalibrated respiratory inductance plethysmography (RIP) tracings were used to quantify lung recruitment and derecruitment during the LVOM inflation and deflation. The time constant was calculated according to the Niemann model., Results: RIP data of 51 subjects (median age 3.5 [1.7-13.3] months) with moderate-to-severe pediatric acute respiratory distress syndrome (PARDS) in 85.4% were analyzed. Lung recruitment and derecruitment occurred during the LVOM inflation phase upon start of HFOV and between and within pressure changes. At 90% of maximum inflation pressure, lung derecruitment already started during the deflation phase. Time to stable lung volume (time constant) could only be calculated in 26.2% of all pressure changes during the inflation and in 21.4% during the deflation phase, independent of continuous distending pressure (CDP). Inability to calculate the time constant was due to lack of stabilization of the RIP signal or no change in any direction., Conclusions: Significant heterogeneity in lung behavior during a staircase incremental-decremental LVOM occurred, underscoring the need for higher initial inflation pressures when transitioning from conventional mechanical ventilation (CMV) and a longer time between pressure changes to allow for equilibration., (© 2024. The Author(s).)

Background: The underlying pathophysiological pathways how reverse triggering is being caused are not fully understood. Respiratory entrainment may be one of these mechanisms, but both terms are used interchangeably. We sought to characterize reverse triggering and the relationship with respiratory entrainment among mechanically ventilated children with and without acute lung injury., Methods: We performed a secondary phyiology analysis of two previously published data sets of invasively mechanically ventilated children < 18 years with and without lung injury mechanically ventilated in a continuous or intermittent mandatory ventilation mode. Ventilator waveforms, electrical activity of the diaphragm measured with surface electromyography and oesophageal tracings were analyzed for entrained and non-entrained reverse triggered breaths., Results: In total 102 measurements (3110 min) from 67 patients (median age 4.9 [1.8 ; 19,1] months) were analyzed. Entrained RT was identified in 12 (12%) and non-entrained RT in 39 (38%) recordings. Breathing variability for entrained RT breaths was lower compared to non-entrained RT breaths. We did not observe breath stacking during entrained RT. Double triggering often occurred during non-entrained RT and led to an increased tidal volume. Patients with respiratory entrainment related RT had a shorter duration of MV and length of PICU stay., Conclusions: Reverse triggering is not one entity but a clinical spectrum with different mechanisms and consequences., Trial Registration: Not applicable., (© 2024. The Author(s).)

Application of positive end-expiratory pressure (PEEP) targeted towards improving oxygenation is one of the components of the ventilatory management of pediatric acute respiratory distress syndrome (PARDS). Low end-expiratory airway pressures cause repetitive opening and closure of unstable alveoli, leading to surfactant dysfunction and parenchymal shear injury. Consequently, there is less lung volume available for tidal ventilation when there are atelectatic lung regions. This will increase lung strain in aerated lung areas to which the tidal volume is preferentially distributed. Pediatric critical care practitioners tend to use low levels of PEEP and inherently accept higher FiO 2 , but these practices may negatively affect patient outcome. The Pediatric Acute Lung Injury Consensus Conference (PALICC) suggests that PEEP should be titrated to oxygenation/oxygen delivery, hemodynamics, and compliance measured under static conditions as compared to other clinical parameters or any of these parameters in isolation in patients with PARDS, while limiting plateau pressure and/or driving pressure limits., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Accuracy of esophageal pressure measured by an air-filled esophageal balloon catheter is dependent on balloon filling volume. However, this has been understudied in mechanically ventilated children. We sought to study the optimal filling volume in children receiving ventilation by using previously reported calibration methods. Secondary objectives included to examine the difference in pressure measurements at individualized optimal filling volume versus a standardized inflation volume and to study if a static hold during calibration is required to identify the optimal filling volume., Methods: An incremental inflation calibration procedure was performed in children receiving ventilation, <18 y, instrumented with commercially available catheters (6 or 8 French) who were not breathing spontaneously. The balloon was manually inflated by 0.2 to 1.6 mL (6 French) or 2.6 mL (8 French). Esophageal pressure (P es ) and airway pressure tracings were recorded during the procedure. Data were analyzed offline by using 2 methods: visual determination of filling range with the calculation of the highest difference between expiratory and inspiratory P es and determination of a correctly filled balloon by calculating the esophageal elastance., Results: We enrolled 40 subjects with median (interquartile range [IQR]) age 6.8 (2-25) months. The optimal filling volume ranged from 0.2 to 1.2 mL (median [IQR] 0.6 [0.2-1.0] mL) in the subjects with a 6 French catheter and 0.2-2.0 mL (median [IQR] 0.7 [0.5-1.2] mL) for 8 French catheters. Inflating the balloon with 0.6 mL (median computed from the whole cohort) gave an absolute difference in transpulmonary pressure that ranged from -4 to 7 cm H 2 O compared with the personalized volume. P es calculated over 5 consecutives breaths differed with a maximum of 1 cm H 2 O compared to P es calculated during a single inspiratory hold. The esophageal elastance was correlated with weight, age, and sex., Conclusions: The optimal balloon inflation volume was highly variable, which indicated the need for an individual calibration procedure. P es was not overestimated when an inspiratory hold was not applied., (Copyright © 2024 by Daedalus Enterprises.)

Objectives: To describe the use and outcomes of the neurological wake-up test (NWT) in pediatric severe traumatic brain injury (pTBI)., Design: Retrospective single-center observational cohort study., Setting: Medical-surgical tertiary pediatric intensive care unit (PICU) in a university medical center and Level 1 Trauma Center., Patients: Children younger than 18 years with severe TBI [i.e., Glasgow Coma Scale (GCS) of ≤8] admitted between January 2010 and December 2020. Subjects with non-traumatic brain injury were excluded., Measurements and Main Results: Of 168 TBI patients admitted, 36 (21%) met the inclusion criteria. Median age was 8.5 years [2 months to 16 years], 5 patients were younger than 6 months. Median initial Glasgow Coma Scale (GCS) and Glasgow Motor Scale (GMS) was 6 [3-8] and 3 [1-5]. NWTs were initiated in 14 (39%) patients, with 7 (50%) labelled as successful. Fall from a height was the underlying injury mechanism in those seven. NWT-failure occurred in patients admitted after traffic accidents. Sedation use in both NWT-subgroups (successful vs. failure) was comparable. Cause of NWT-failure was non-arousal (71%) or severe agitation (29%). Subjects with NWT failure subsequently had radiological examination (29%), repeat NWT (43%), continuous interruption of sedation (14%) or intracranial pressure (ICP) monitoring (14%). The primary reason for not doing NWTs was intracranial hypertension in 59%. Compared to the NWT-group, the non-NWT group had a higher PRISM III score (18.9 vs. 10.6), lower GCS/GMS at discharge, more associated trauma, and circulatory support. Nine patients (25%) died during their PICU admission, none of them had an NWT., Conclusion: We observed limited use of NWTs in pediatric severe TBI. Patients who failed the NWT were indistinguishable from those without NWT. Both groups were more severely affected compared to the NWT successes. Therefore, our results may indicate that only a select group of severe pTBI patients qualify for the NWT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Mulder, Helfferich and Kneyber.)

Background: Mechanical power (MP) refers to the energy transmitted over time to the respiratory system and serves as a unifying determinant of ventilator-induced lung injury. MP normalization is required to account for developmental changes in children. We sought to examine the relationship between mechanical energy (ME BW ), MP normalized to body weight (MP BW ), and MP normalized to respiratory compliance (MP CRS ) concerning the severity and outcomes of pediatric acute respiratory distress syndrome (pARDS)., Method: In this retrospective study, children aged 1 month to 18 years diagnosed with pARDS who underwent pressure-control ventilation for at least 24 h between January 2017 and September 2020 were enrolled. We calculated MP using Becher's equation. Multivariable logistic regression analysis adjusted for age, pediatric organ dysfunction score, and oxygenation index (OI) was performed to determine the independent association of MP and its derivatives 24 h after diagnosing pARDS with 28-day mortality. The association was also studied for 28 ventilator-free days (VFD-28) and the severity of pARDS in terms of OI., Results: Out of 246 admitted with pARDS, 185 were eligible, with an overall mortality of 43.7%. Non-survivors exhibited higher severity of illness, as evidenced by higher values of MP, MP BW , and ME BW . Multivariable logistic regression analysis showed that only ME BW but not MP, MP BW , or MP CRS at 24 h was independently associated with mortality [adjusted OR: 1.072 (1.002-1.147), p  = 0.044]. However, after adjusting for the type of pARDS, ME BW was not independently associated with mortality [adjusted OR: 1.061 (0.992-1.136), p  = 0.085]. After adjusting for malnutrition, only MP at 24 h was found to be independently associated. Only MP CRS at 1-4 and 24 h but not MP, MP BW , or ME BW at 24 h of diagnosing pARDS was significantly correlated with VFD-28., Conclusions: Normalization of MP is better related to outcomes and severity of pARDS than non-normalized MP. Malnutrition can be a significant confounding factor in resource-limited settings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 Shaikh, Ramaswamy, Chirla, Venkataraman and Kneyber.)

Purpose of Review: To discuss the role of ventilator induced lung injury (VILI) and patient self-inflicted lung injury in ventilated children supported on extracorporeal membrane oxygenation (ECMO)., Recent Findings: While extracorporeal life support is used routinely used every day around the globe to support neonatal, pediatric, and adult patients with refractory cardiac and/or respiratory failure, the optimal approach to mechanical ventilation, especially for those with acute respiratory distress syndrome (ARDS), remains unknown and controversial. Given the lack of definitive data in this population, one must rely on available evidence in those with ARDS not supported with ECMO and extrapolate adult observations. Ventilatory management should include, as a minimum standard, limiting inspiratory and driving pressures, providing a sufficient level of positive end-expiratory pressure, and setting a low rate to reduce mechanical power. Allowing for spontaneous breathing and use of pulmonary specific ancillary treatment modalities must be individualized, while balancing the risk and benefits. Future studies delineating the best strategies for optimizing MV during pediatric extracorporeal life support are much needed., Summary: Future investigations will hopefully provide the needed evidence and better understanding of the overall goal of reducing mechanical ventilation intensity to decrease risk for VILI and promote lung recovery for those supported with ECMO., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Effort of Breathing (EOB) calculations may be a reliable alternative to Work of Breathing (WOB) calculations in which Respiratory Inductance Plethysmography (RIP) replaces spirometry. We sought to compare EOB and WOB measurements in a nonhuman primate model of increasing extrathoracic inspiratory resistance simulating upper airway obstruction (UAO)., Methods: RIP, spirometry, and esophageal manometry were measured in spontaneously breathing, intubated Rhesus monkeys utilizing 11 calibrated resistors randomly applied for 2-min. EOB was calculated breath-by-breath as Pressure Rate Product (PRP) and Pressure Time Product (PTP). WOB was calculated from the Pressure-Volume curve based on spirometry (WOB SPIR ) or RIP flow (WOB RIP )., Results: WOB, PRP and PTP showed similar linear increases when exposed to higher levels of resistive loads. When comparing WOB SPIR to WOB RIP , a similar strong correlation was seen for both signals as resistance increased and there were no statistically significant differences., Conclusion: EOB and WOB parameters utilizing esophageal manometry and RIP, independent of spirometry, showed a strong correlation as a function of increasing inspiratory resistance in nonhuman primates. This allows several potential monitoring possibilities for non-invasively ventilated patients or situations where spirometry is not available., Impact: EOB and WOB parameters showed a strong correlation as a function of increasing inspiratory resistance in nonhuman primates. There was a strong correlation between spirometry-based WOB versus RIP-based WOB. To date, it has remained untested as to whether EOB is a reliable alternative for WOB and if RIP can replace spirometry in these measurements. Our results enable additional potential monitoring possibilities for non-invasively ventilated patients or situations where spirometry is not available. Where spirometry is not available, there is no need to apply a facemask post extubation to a spontaneously breathing, non-intubated infant to make objective EOB measurements., (© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Background and Objectives: To provide support to parents of critically ill children, it is important that physicians adequately respond to parents' emotions. In this study, we investigated emotions expressed by parents, physicians' responses to these expressions, and parents' emotions after the physicians' responses in conversations in which crucial decisions regarding the child's life-sustaining treatment had to be made., Methods: Forty-nine audio-recorded conversations between parents of 12 critically ill children and physicians working in the neonatal and pediatric intensive care units of 3 Dutch university medical centers were coded and analyzed by using a qualitative inductive approach., Results: Forty-six physicians and 22 parents of 12 children participated. In all 49 conversations, parents expressed a broad range of emotions, often intertwining, including anxiety, anger, devotion, grief, relief, hope, and guilt. Both implicit and explicit expressions of anxiety were prevalent. Physicians predominantly responded to parental emotions with cognition-oriented approaches, thereby limiting opportunities for parents. This appeared to intensify parents' expressions of anger and protectiveness, although their anxiety remained under the surface. In response to more tangible emotional expressions, for instance, grief when the child's death was imminent, physicians provided parents helpful support in both affect- and cognition-oriented ways., Conclusions: Our findings illustrate the diversity of emotions expressed by parents during end-of-life conversations. Moreover, they offer insight into the more and less helpful ways in which physicians may respond to these emotions. More training is needed to help physicians in recognizing parents' emotions, particularly implicit expressions of anxiety, and to choose helpful combinations of responses., (Copyright © 2023 by the American Academy of Pediatrics.)

Objectives: To study the hemodynamic consequences of an open-lung high-frequency oscillatory ventilation (HFOV) strategy in patients with an underlying cardiac anomaly with or without intracardiac shunt or primary pulmonary hypertension with severe lung injury., Design: Secondary analysis of prospectively collected data., Setting: Medical-surgical PICU., Patients: Children less than 18 years old with cardiac anomalies (± intracardiac shunt) or primary pulmonary hypertension., Interventions: None., Measurements and Main Results: Data from 52 subjects were analyzed, of whom 39 of 52 with cardiac anomaly (23/39 with intracardiac shunt) and 13 of 52 with primary pulmonary hypertension. Fourteen patients were admitted postoperatively, and 26 patients were admitted with acute respiratory failure. Five subjects (9.6%) were canulated for ECMO (of whom four for worsening respiratory status). Ten patients (19.2%) died during PICU stay. Median conventional mechanical ventilation settings prior to HFOV were peak inspiratory pressure 30 cm H 2 O (27-33 cm H 2 O), positive end-expiratory pressure 8 cm H 2 O (6-10 cm H 2 O), and F io2 0.72 (0.56-0.94). After transitioning to HFOV, there was no negative effect on mean arterial blood pressure, central venous pressure, or arterial lactate. Heart rate decreased significantly over time ( p < 0.0001), without group differences. The percentage of subjects receiving a fluid bolus decreased over time ( p = 0.003), especially in those with primary pulmonary hypertension ( p = 0.0155) and without intracardiac shunt ( p = 0.0328). There were no significant differences in the cumulative number of daily boluses over time. Vasoactive Infusion Score did not increase over time. Pa co2 decreased ( p < 0.0002) and arterial pH significantly improved ( p < 0.0001) over time in the whole cohort. Neuromuscular blocking agents were used in all subjects switched to HFOV. Daily cumulative sedative doses were unchanged, and no clinically apparent barotrauma was found., Conclusions: No negative hemodynamic consequences occurred with an individualized, physiology-based open-lung HFOV approach in patients with cardiac anomalies or primary pulmonary hypertension suffering from severe lung injury., Competing Interests: Dr. Curley’s institution received funding from the National Heart, Lung, and Blood Institute and the National Institute of Child Health and Human Development; she received support for article research from the National Institutes of Health. Dr. Cheifetz received funding from Philips, Medtronic, Tim Peters and Co, and UptoDate. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Background: Mechanical power is a major contributor to lung injury and mortality in adults receiving mechanical ventilation. Recent advances in our understanding of mechanical power have allowed the different mechanical components to be isolated. The preterm lung shares many of the same similarities that would indicate mechanical power may be relevant in this group. To date, the role of mechanical power in neonatal lung injury is unknown. We hypothesise that mechanical power maybe useful in expanding our understanding of preterm lung disease. Specifically, that mechanical power measures may account for gaps in knowledge in how lung injury is initiated., Hypothesis-Generating Data Set: To provide a justification for our hypothesis, data in a repository at the Murdoch Children's Research Institute, Melbourne (Australia) were re-analysed. 16 preterm lambs 124-127d gestation (term 145d) who received 90 min of standardised positive pressure ventilation from birth via a cuffed endotracheal tube were chosen as each was exposed to three distinct and clinically relevant respiratory states with unique mechanics. These were (1) the respiratory transition to air-breathing from an entirely fluid-filled lung (rapid aeration and fall in resistance); (2) commencement of tidal ventilation in an acutely surfactant-deficient state (low compliance) and (3) exogenous surfactant therapy (improved aeration and compliance). Total, tidal, resistive and elastic-dynamic mechanical power were calculated from the flow, pressure and volume signals (200 Hz) for each inflation., Results: All components of mechanical power behaved as expected for each state. Mechanical power increased during lung aeration from birth to 5 min, before again falling immediately after surfactant therapy. Before surfactant therapy tidal power contributed 70% of total mechanical power, and 53.7% after. The contribution of resistive power was greatest at birth, demonstrating the initial high respiratory system resistance at birth., Conclusions: In our hypothesis-generating dataset, changes in mechanical power were evident during clinically important states for the preterm lung, specifically transition to air-breathing, changes in aeration and surfactant administration. Future preclinical studies using ventilation strategies designed to highlight different types of lung injury, including volu-, baro- and ergotrauma, are needed to test our hypothesis., (© 2023. The Author(s).)

Background: Common, operational definitions are crucial to assess interventions and outcomes related to pediatric mechanical ventilation. These definitions can reduce unnecessary variability among research and quality improvement efforts, to ensure findings are generalizable, and can be pooled to establish best practices., Research Question: Can we establish operational definitions for key elements related to pediatric ventilator liberation using a combination of detailed literature review and consensus-based approaches?, Study Design and Methods: A panel of 26 international experts in pediatric ventilator liberation, two methodologists, and two librarians conducted systematic reviews on eight topic areas related to pediatric ventilator liberation. Through a series of virtual meetings, we established draft definitions that were voted upon using an anonymous web-based process. Definitions were revised by incorporating extracted data gathered during the systematic review and discussed in another consensus meeting. A second round of voting was conducted to confirm the final definitions., Results: In eight topic areas identified by the experts, 16 preliminary definitions were established. Based on initial discussion and the first round of voting, modifications were suggested for 11 of the 16 definitions. There was significant variability in how these items were defined in the literature reviewed. The final round of voting achieved ≥ 80% agreement for all 16 definitions in the following areas: what constitutes respiratory support (invasive mechanical ventilation and noninvasive respiratory support), liberation and failed attempts to liberate from invasive mechanical ventilation, liberation from respiratory support, duration of noninvasive respiratory support, total duration of invasive mechanical ventilation, spontaneous breathing trials, extubation readiness testing, 28 ventilator-free days, and planned vs rescue use of post-extubation noninvasive respiratory support., Interpretation: We propose that these consensus-based definitions for elements of pediatric ventilator liberation, informed by evidence, be used for future quality improvement initiatives and research studies to improve generalizability and facilitate comparison., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Although aminoglycosides are frequently prescribed to neonates and children, the ability to reach effective and safe target concentrations with the currently used dosing regimens remains unclear. This study aims to evaluate the target attainment of the currently used dosing regimens for gentamicin in neonates and children. We conducted a retrospective single-center cohort study in neonates and children receiving gentamicin between January 2019 and July 2022, in the Beatrix Children's Hospital. The first gentamicin concentration used for therapeutic drug monitoring was collected for each patient, in conjunction with information on dosing and clinical status. Target trough concentrations were ≤1 mg/L for neonates and ≤0.5 mg/L for children. Target peak concentrations were 8-12 mg/L for neonates and 15-20 mg/L for children. In total, 658 patients were included (335 neonates and 323 children). Trough concentrations were outside the target range in 46.2% and 9.9% of neonates and children, respectively. Peak concentrations were outside the target range in 46.0% and 68.7% of neonates and children, respectively. In children, higher creatinine concentrations were associated with higher gentamicin trough concentrations. This study corroborates earlier observational studies showing that, with a standard dose, drug concentration targets were met in only approximately 50% of the cases. Our findings show that additional parameters are needed to improve target attainment.