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Background: Extracorporeal membrane oxygenation (ECMO) is used in critically ill children with cardiac and/or respiratory failure. Use is increasing in children with high‐risk comorbidities. Reasons children do not survive ECMO are poorly described. Aims: Describe characteristics and cause of death, compare mortality in children with high‐risk comorbidities, evaluate mortality trends over a decade. Method: All children <18 years old who received ECMO at this institution from 1 January 2011 to 31 December 2020 were described and categorised by outcome: died on or <48 h post‐ECMO, died ≥48 h post‐ECMO, survived to hospital discharge. Children who did not survive ECMO (DNSE) were categorised to: ECMO withdrawal for irrecoverable original condition, withdrawal for poor prognosis neurological condition, brain death, withdrawal for poor prognosis with multiple complex conditions, and unsupportable. Poison regression was used to analyse survival trends. Results: Four hundred twenty‐eight children received ECMO, 19% DNSE, 14% died ≥48 h post‐ECMO and 67% survived. ECMO was electively withdrawn for irrecoverable original condition (39%), poor prognosis for neurological condition (32%) or multiple complex conditions (18%). One hundred twenty‐two children had ≥1 high‐risk comorbidity. Children with genetic syndromes (58%), risk‐adjusted congenital heart surgery score‐1 ≥4 (53%), primary immunodeficiency (50%) had lower hospital survival. No children with malignancy/bone marrow transplant survived to hospital discharge. Overall hospital survival was 67%, with no significant change during the study period (P‐trend = 0.99). Conclusion: Children who DNSE have therapy electively withdrawn for irrecoverable disease or poor prognosis. Children with high‐risk comorbidities have a reasonable chance of survival. This study informs clinicians ECMO may be a therapeutic option. [ABSTRACT FROM AUTHOR]

Introduction: Hemolysis is a common complication of extracorporeal membrane oxygenation (ECMO). There are few data on whether carboxyhemoglobin (COHb), a potential marker of hemolysis, are elevated during ECMO support. Methods: We conducted a single-center, retrospective study comparing peak COHb levels of children pre-, during, and post-ECMO from January 2017 to August 2020. Results: There were 154 ECMO runs in 147 children (154 PICU admissions) included in the study. The median age was 3.5 (IQR 0.2, 39.2) months. Veno-arterial ECMO was the predominant mode: 146/154 (94.8%). Eighty-seven children (56.5%) underwent cardiac surgery. Peak COHb levels during ECMO were statistically significantly higher compared to pre ECMO (COHb 1.8% (IQR 1.4, 2.6) vs COHb 1.2% (IQR 0.7, 1.7), p < 0.001) and post ECMO (COHb 1.6% (IQR 1.3, 2.2), p = 0.009). Children with COHb ⩾2% were younger and had longer duration of ECMO support. Plasma hemoglobin weakly correlated with COHb level (r = 0.14; p = 0.04). Conclusions: Carboxyhemoglobin levels increased during ECMO support compared to the pre and post ECMO period. Younger age and longer ECMO duration were associated with COHb levels ⩾2%. Plasma hemoglobin weakly correlated with COHb level. [ABSTRACT FROM AUTHOR]

During hypoxia or acidosis, S -nitrosoglutathione (GSNO) has been shown to protect the cardiomyocyte from ischemia-reperfusion injury. In a randomized double-blinded control study of a porcine model of paediatric cardiopulmonary bypass (CPB), we aimed to evaluate the effects of 2 different doses (low and high) of GSNO. Pigs weighing 15-20 kg were exposed to CPB with 1 hour of aortic cross-clamp. Prior to and during CPB, animals were randomized to receive low-dose (up to 20 nmol/kg/min) GSNO (n = 8), high-dose (up to 60 nmol/kg/min) GSNO (n = 6), or normal saline (n = 7). Standard cardiac intensive care management was continued for 4 hours post-bypass. There was a reduction in myocyte apoptosis after administration of GSNO (P =.04) with no difference between low- and high-dose GSNO. The low-dose GSNO group had lower pulmonary vascular resistance post-CPB (P =.007). Mitochondrial complex I activity normalized to citrate synthase activity was higher after GSNO compared with control (P =.02), with no difference between low- and high-dose GSNO. In a porcine model of CPB, intravenous administration of GSNO limits myocardial apoptosis through preservation of mitochondrial complex I activity, and improves pulmonary vascular resistance. There appears to be a dose-dependent effect to this protection. [ABSTRACT FROM AUTHOR]

OBJECTIVES Open in new tab Download slide Open in new tab Download slide Levosimendan use is associated with more successful decannulation from veno-arterial extracorporeal membrane oxygenation (VA ECMO) in adults. We sought to determine the role of levosimendan in children who required VA ECMO after cardiac surgery. METHODS This observational study compares the outcomes of children who required VA ECMO after cardiac surgery and received levosimendan for weaning with those who did not receive the drug. A doubly robust estimation methodology (inverse probability of treatment weighting with regression adjustment) was used to balance study covariates (age, weight, sex, lactate pre-ECMO, vasoactive-inotropic score pre-ECMO, ECMO indication, ECMO modality, Risk Adjustment for Congenital Heart Surgery-1 category), and the final model was further adjusted for duration of ECMO. RESULTS Between January 2012 and December 2018, 118 eligible children received 145 ECMO runs [failed weaning from cardiopulmonary bypass, 67/145 (46%); low cardiac output state, 30/145 (21%); extracorporeal cardiopulmonary resuscitation, 47/145 (32%); other reasons in 1]. Levosimendan was administered before decannulation in 54/145 (37%) runs. The median time to start levosimendan after ECMO cannulation was 39 h (interquartile range, 14–83 h). The unadjusted rates of weaning failure in the levosimendan vs control group were 7% (4/54) vs 19% (17/91). In the controlled analysis, levosimendan was associated with decreased risk of weaning failure [adjusted relative risk (95% confidence interval), 0.20 (0.07–0.57)] and decreased risk of in-hospital mortality [adjusted relative risk (95% confidence interval), 0.45 (0.26–0.76)]. CONCLUSIONS Levosimendan administration in children requiring VA ECMO after cardiac surgery was associated with decreased risk of weaning failure and decreased in-hospital mortality. [ABSTRACT FROM AUTHOR]

Background: The surviving sepsis campaign recommends consideration for extracorporeal membrane oxygenation (ECMO) in refractory septic shock. We aimed to define the benefit threshold of ECMO in pediatric septic shock.Methods: Retrospective binational multicenter cohort study of all ICUs contributing to the Australian and New Zealand Paediatric Intensive Care Registry. We included patients < 16 years admitted to ICU with sepsis and septic shock between 2002 and 2016. Sepsis-specific risk-adjusted models to establish ECMO benefit thresholds with mortality as the primary outcome were performed. Models were based on clinical variables available early after admission to ICU. Multivariate analyses were performed to identify predictors of survival in children treated with ECMO.Results: Five thousand sixty-two children with sepsis and septic shock met eligibility criteria, of which 80 (1.6%) were treated with veno-arterial ECMO. A model based on 12 clinical variables predicted mortality with an AUROC of 0.879 (95% CI 0.864-0.895). The benefit threshold was calculated as 47.1% predicted risk of mortality. The observed mortality for children treated with ECMO below the threshold was 41.8% (23 deaths), compared to a predicted mortality of 30.0% as per the baseline model (16.5 deaths; standardized mortality rate 1.40, 95% CI 0.89-2.09). Among patients above the benefit threshold, the observed mortality was 52.0% (13 deaths) compared to 68.2% as per the baseline model (16.5 deaths; standardized mortality rate 0.61, 95% CI 0.39-0.92). Multivariable analyses identified lower lactate, the absence of cardiac arrest prior to ECMO, and the central cannulation (OR 0.31, 95% CI 0.10-0.98, p = 0.046) as significant predictors of survival for those treated with VA-ECMO.Conclusions: This binational study demonstrates that a rapidly available sepsis mortality prediction model can define thresholds for survival benefit in children with septic shock considered for ECMO. Survival on ECMO was associated with central cannulation. Our findings suggest that a fully powered RCT on ECMO in sepsis is unlikely to be feasible. [ABSTRACT FROM AUTHOR]

Aims: Vancomycin is frequently used in critically ill children in whom the drug pharmacokinetics are significantly altered as a result of changes in renal clearance and volume of distribution. Therapeutic drug monitoring (TDM) is recommended to achieve vancomycin trough concentrations between 10 and 20 mg/L. In this study we reviewed vancomycin dosing, TDM and treatment outcomes in paediatric and neonatal intensive care unit patients. Methods: We reviewed the medical records of all patients receiving intravenous vancomycin in a tertiary paediatric and neonatal intensive care unit over a 10‐month period. Demographic, vancomycin dosing, TDM and drug‐related adverse effects data were collected. Results: In total, 115 children received 126 courses of vancomycin and had at least 1 TDM blood sample taken at steady state. In only 38/126 (30%) courses was the target concentration (10–20 mg/L) achieved at the initial steady state trough sample. Of the 88 courses that had initial trough concentrations outside the target range, the dose was adjusted in only 49 (56%). Overall, minimum doses of 30 mg/kg/day in neonates with a corrected gestational age of <35 weeks, and 50 mg/kg/day in older children, were required to achieve target vancomycin concentrations. Vancomycin‐attributable nephrotoxicity occurred in 10/126 (8%) courses and there were no episodes of red man syndrome. Conclusion: In critically ill children, individualised dosing is needed. In the absence of Bayesian model‐based dosing, in children with normal renal function, empiric vancomycin doses of at least 30 mg/kg/day in neonates of <35 weeks corrected gestational age, and 50 mg/kg/day in older children, should be considered. Optimisation of TDM practices through the development of protocols, ideally built into electronic medical records, should be considered. [ABSTRACT FROM AUTHOR]

Objective: To describe the effect of extracorporeal membrane oxygenation (ECMO) on survival and cardiac outcome of neonates with myocardial failure secondary to severe enterovirus (EV) myocarditis.Design: Retrospective case series.Setting: A 15-bed cardiac paediatric intensive care unit (ICU).Patients: We describe the clinical presentations, cardiac findings, ECMO characteristics and outcome of seven neonates with severe EV myocarditis. Additionally, 35 previously reported cases of EV myocarditis supported with ECMO are presented.Interventions: Extracorporeal membrane oxygenation.Results: Seven neonates presented with cardiovascular collapse within the first 10 days after birth and required ECMO support. Echocardiography showed left ventricular dysfunction in all and additional right ventricular dysfunction in four patients. ECG showing widespread ST changes as well as elevated troponin I indicated myocardial damage. All patients were cannulated onto ECMO shortly after ICU admission. None of the patients suffered cardiac arrest prior to ECMO initiation. Four patients survived ECMO and three survived to hospital discharge. All three survivors showed complete cardiac recovery after a median follow-up of 34 months. The survival rate in 35 previously reported cases was 34% (12/35) and including our seven cases 36% (15/42).Conclusions: In this case series, ECMO initiation prevented further deterioration and cardiac arrest in neonates with severe EV myocarditis and not responding to conventional medical therapies. Moreover, complete cardiac recovery occurred in survivors. However, these neonates may need long ECMO runs and are at increased risk for mechanical complications. Furthermore, mortality remains high due to greater disease severity. [ABSTRACT FROM AUTHOR]

B Learning Objectives: b Despite improvements in early recognition and treatment of infections, sepsis remains a frequent causes of childhood mortality worldwide. Sepsis-specific adjusted models to predict baseline mortality were performed to compare sepsis cases treated with ECMO versus cases not treated with ECMO. We were able to demonstrate a threshold for survival benefit of ECMO in children with sepsis using a sepsis mortality prediction model. [Extracted from the article]

• Performance of individualized vancomycin dosing assessed using an online model-based dosing calculator (Vanc App) • Of 40 young infants, 75% achieved a target trough concentration of 10-20 mg/L at first steady-state concentration • 83% of young infants achieved a target AUC 0-24 of 400-650 mg/L.h Empiric vancomycin dosing regimens fail to achieve recommended target trough concentrations of 10-20 mg/L in the majority of infants. This study assessed the performance of a model-based dosing calculator (Vanc App) in achieving target vancomycin concentrations at first steady-state level. This was a multicenter prospective study in four tertiary pediatric hospitals over an 18-month period. Infants aged 0-90 days with suspected Gram-positive sepsis requiring empiric vancomycin treatment were included if they did not meet any of the exclusion criteria: post-menstrual age (PMA) <25 weeks, weight <500 g, glycopeptide allergy, receiving extracorporeal membrane oxygenation, vancomycin use within the previous 72 h, and renal impairment. The Vanc App used a published population pharmacokinetic model to generate a dose based on the infant's PMA, weight, creatinine, and target vancomycin concentration. A total of 40 infants were included; 40% were female, median (range) weight was 2505 (700-4460) g and median (range) PMA was 37.4 (25.7-49.0) weeks. The median (range) vancomycin dose was 45 (24-79) mg/kg/day. All infants had trough vancomycin concentrations measured at steady-state (24-<48 hours) and 30 (75%) infants achieved target concentrations. Five infants had supratherapeutic (median 25, range 21-38 mg/L) and five had subtherapeutic (median 6, range <5-9 mg/L) concentrations. An area under the concentration-time curve (AUC 0-24) of 400-650 mg/L.h was achieved in 33 (83%) infants. There were no infusion-related reactions or nephrotoxicity. Individualized intermittent vancomycin dosing using a model-based online calculator resulted in 75% and 83% of infants achieving target trough and AUC 0-24 , respectively, at first steady-state level. There were no vancomycin-related nephrotoxicity or infusion-related reactions. [ABSTRACT FROM AUTHOR]

Objective: To characterize surface-bound proteins and to measure the thickness of fibrin fibers bound to extracorporeal membrane oxygenation (ECMO) circuits used in children., Design: Single-center observational prospective study, April to November 2021., Setting: PICU, Royal Children's Hospital, Melbourne, Australia., Patients: Patients aged less than 18 years on venoarterial ECMO and without preexisting disorder., Interventions: None., Measurements and Main Results: ECMO circuits were collected from six patients. Circuit samples were collected from five different sites, and subsequently processed for proteomic and scanning electron microscopy (SEM) studies. The concentration of proteins bound to ECMO circuit samples was measured using a bicinchoninic acid protein assay, whereas characterization of the bound proteome was performed using data-independent acquisition mass spectrometry. The Reactome Over-representation Pathway Analyses tool was used to identify functional pathways related to bound proteins. For the SEM studies, ECMO circuit samples were prepared and imaged, and the thickness of bound fibrin fibers was measured using the Fiji ImageJ software, version 1.53c (https://imagej.net/software/fiji/). Protein binding to ECMO circuit samples and fibrin networks showed significant intra-circuit and interpatient variation. The median (range) total protein concentration was 19.0 (0-76.9) μg/mL, and the median total number of proteins was 2011 (1435-2777). A total of 933 proteins were commonly bound to ECMO circuit samples from all patients and were functionally involved in 212 pathways, with signal transduction, cell cycle, and metabolism of proteins being the top three pathway categories. The median intra-circuit fibrin fiber thickness was 0.20 (0.15-0.24) μm, whereas the median interpatient fibrin fiber thickness was 0.18 (0.15-0.21) μm., Conclusions: In this report, we have characterized proteins and fiber fibrin thickness bound to ECMO circuits in six children. The techniques and approaches may be useful for investigating interactions between blood, coagulation, and the ECMO circuit and have the potential for circuit design., Competing Interests: Drs. McCafferty and Monagle’s institution received funding from the National Health and Medical Research Council (NHMRC) grant APP1129317. Dr. Attard’s institution received funding from the National Blood Authority, Bayer, and Janssen; he received funding from Anthos; he received support for article research from the NHMRC. Dr. MacLaren reported that he serves on the board of directors of the Extracorporeal Life Support Organization (unpaid). The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Competing Interests: Disclosure: G.M. is the President of the Extracorporeal Life Support Organization (ELSO) (unpaid). The other authors have no conflicts of interest to report. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants, or patents received or pending royalties.

The continuous contact between blood and the foreign surface of the extracorporeal membrane oxygenation (ECMO) circuit contributes to hemostatic, inflammatory, and other physiological disturbances observed during ECMO. Although previous studies have extensively investigated blood samples from patients on ECMO, cell adsorption to the ECMO circuit as an additional factor that could potentially influence clinical outcomes, has largely been overlooked. Here we provide a detailed immunofluorescence (IF) protocol designed to characterize cellular binding on ECMO circuits collected from patients. Extracorporeal membrane oxygenation circuits were collected from three pediatric patients and an albumin primed-only ECMO circuit was used as control. Circuit samples from five different sites within each ECMO circuit were collected and processed for the IF protocol. CD14 and CD42a antibodies were used to identify platelets and leukocytes bound to each ECMO circuit sample and images captured using inverted fluorescence microscopy. The protocol enables the comprehensive characterization of platelet and leukocyte binding to ECMO circuits collected from patients, which could in turn extend our knowledge of the characteristics of circuit binding and may provide guidance for improved ECMO circuit design., Competing Interests: G.M. is the president of the Extracorporeal Life Support Organization (ELSO). The other authors have no conflicts of interest to report., (Copyright © ASAIO 2024.)

Objectives: The Gaps in the Congenital Diaphragmatic Hernia (CDH) Journey Priority Setting Partnership (PSP) was developed in collaboration with CDH Australia, James Lind Alliance (JLA) and the Murdoch Children's Research Institute to identify research priorities for people with CDH, their families and healthcare workers in Australasia., Design: Research PSP in accordance with the JLA standardised methodology., Setting: Australian community and institutions caring for patients with CDH and their families., Patients: CDH survivors, families of children born with CDH (including bereaved) and healthcare professionals including critical care physicians and nurses (neonatal and paediatric), obstetric, surgical, allied health professionals (physiotherapists, speech pathologists and speech therapists) and general practitioners., Main Outcome Measure: Top 10 research priorities for CDH., Results: 377 questions, from a community-based online survey, were categorised and collated into 50 research questions. Through a further prioritisation process, 21 questions were then discussed at a prioritisation workshop where they were ranked by 21 participants (CDH survivors, parents of children born with CDH (bereaved and not) and 11 multidisciplinary healthcare professionals) into their top 10 research priorities., Conclusion: Stakeholders' involvement identified the top 10 CDH-related research questions, spanning from antenatal care to long-term functional outcomes, that should be prioritised for future research to maximise meaningful outcomes for people with CDH and their families., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Sepsis and septic shock in newborns causes mortality and morbidity depending on the organism and primary site. ECMO provides cardiorespiratory support to allow adequate organ perfusion during the time for antibiotics and source control surgery (if needed) to occur. ECMO mode and cannulation site vary depending on support required and local preference. Earlier and more aggressive use of ECMO can improve survival., (Copyright © 2020 Butt and Chiletti.)