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Nitric oxide (NO) can be safely delivered through the sweep gas to the oxygenator of an extracorporeal membrane oxygenation (ECMO) circuit. It has theoretical benefits such as preventing platelet adhesion to surfaces, mitigating inflammatory response and protection against ischemia-reperfusion injury. In this uncontrolled before-after study of children on ECMO, the outcomes of those who received NO were compared with those who did not. Among 393 ECMO runs (from 337 patients), 192 of 393 (49%) received NO and 201 of 393 (51%) did not. The use of NO was associated with a 37% reduction in circuit change (adjusted risk ratio [aRR]: 0.63, 95% confidence interval [CI]: 0.42-0.93). The aRR (95% CI) for risk of neurologic injury was 0.72 (0.47-1.11). We observed potential heterogeneity of treatment effect for the risk of neurologic injury in children who had cardiac surgery: the risk with NO was lower in those who had cardiac surgery (aRR: 0.50, 95% CI: 0.26-0.96). There was no difference in survival between the study groups. In children managed with NO delivered through the ECMO circuit, we report a reduction in observed rate of circuit change and lower risk of neurologic injury in children who underwent cardiac surgery. Nitric oxide therapy on ECMO warrants prospective evaluation in children., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2024.)

Peripheral veno-artertial extracorporeal membrane oxygenation (VA-ECMO) is commonly used in the paediatric population for intractable respiratory and cardiac failure. One of the devastating complications of VA-ECMO is severe brain damage due to ischemia or haemorrhage. We describe a case of peripheral cervical VA-ECMO complicated by evolving right cerebral ischemia which was rescued with rapid conversion from peripheral to central VA-ECMO support. Notably, the patient had a complete circle of Willis. Following conversion, we observed complete resolution of neurological symptoms with full functional recovery., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: To investigate changes in von Willebrand factor (VWF) concentration, function, and multimers during pediatric extracorporeal membrane oxygenation (ECMO) and determine whether routine monitoring of VWF during ECMO would be useful in predicting bleeding., Design: Prospective observational study of pediatric ECMO patients from April 2017 to May 2019., Setting: The PICU in a large, tertiary referral pediatric ECMO center., Patients: Twenty-five neonates and children (< 18 yr) supported by venoarterial ECMO., Interventions: None., Measurements and Main Results: Arterial blood samples were collected within 24 hours pre-ECMO, daily for the first 5 days of ECMO, every second day until decannulation, and 24 hours post-ECMO. The STA R Max analyzer was used to measure VWF antigen (VWF:Ag) and ristocetin cofactor (VWF:RCo) activity. VWF collagen binding (VWF:CB) was measured using an enzyme-linked immunosorbent assay. VWF multimers were measured using the semi-automated Hydragel 11 VWF Multimer assay. Corresponding clinical data for each patient was also recorded. A total of 25 venoarterial ECMO patients were recruited (median age, 73 d; interquartile range [IQR], 3 d to 1 yr). The median ECMO duration was 4 days (IQR, 3-8 d) and 15 patients had at least one major bleed during ECMO. The percentage of high molecular weight multimers (HMWM) decreased and intermediate molecular weight multimers increased while patients were on ECMO, irrespective of a bleeding status. VWF:Ag increased and the VWF:RCo/VWF:Ag and VWF:CB/VWF:Ag ratios decreased while patients were on ECMO compared with the baseline pre-ECMO samples and healthy children., Conclusions: Neonates and children on ECMO exhibited a loss of HMWM and lower VWF:CB/VWF:Ag and VWF:RCo/VWF:Ag ratios compared with healthy children, irrespective of major bleeding occurring. Therefore, monitoring VWF during ECMO would not be useful in predicting bleeding in these patients and changes to other hemostatic factors should be investigated to further understand bleeding during ECMO., Competing Interests: Ms. Van Den Helm’s, Ms. Letunica’s, Mr. McCafferty’s, and Drs. Ignjatovic’s and Monagle’s institutions received funding from the Australian National Health and Medical Research Council. Dr. MacLaren disclosed that he serves on the Board of Directors of the Extracorporeal Life Support Organization. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

This systematic review summarizes the major developments in extracorporeal membrane oxygenation (ECMO) circuitry in pediatrics over the past 20 years and demonstrates the impacts of those developments on clinical outcomes. This systematic review followed structured Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A total of 1987 studies were retrieved, of which 82 were included in the final analysis. Over the past 20 years, ECMO pumps have shifted from roller pumps to centrifugal pumps. Silicone and polypropylene hollow fiber membrane oxygenators were initially used but have been replaced by polymethylpentene hollow fiber membrane oxygenators, with other ECMO components poorly reported. Considerable variability in mortality was found across studies and there was no statistical difference in mortality rates across different periods. The duration of ECMO and other outcome measures were inconsistently reported across studies. This systematic review demonstrated technological developments in pumps and oxygenators over the last two decades, although patient mortality rates remained unchanged. This could be because of ECMO support applied to patients in more critical conditions over the years. We also highlighted the limitations of methodology information disclosure and outcome measures in current ECMO studies, showing the need of reporting standardization for future ECMO studies., Competing Interests: Disclosure: G.M. is on the Board of Directors of ELSO (unpaid). The other authors have no conflicts of interest to report., (Copyright © ASAIO 2022.)

Objectives: To investigate platelet pathophysiology associated with pediatric extracorporeal membrane oxygenation (ECMO)., Design: Prospective observational study of neonatal and pediatric ECMO patients from September 1, 2016, to December 31, 2019., Setting: The PICU in a large tertiary referral pediatric ECMO center., Patients: Eighty-seven neonates and children (< 18 yr) supported by ECMO., Interventions: None., Measurements and Main Results: Arterial blood samples were collected on days 1, 2, and 5 of ECMO and were analyzed by whole blood flow cytometry. Corresponding clinical data for each patient was also recorded. A total of 87 patients were recruited (median age, 65 d; interquartile range [IQR], 7 d to 4 yr). The median duration of ECMO was 5 days (IQR, 3-8 d) with a median length of stay in PICU and hospital of 18 days (IQR, 10-29 d) and 35 days (IQR, 19-75 d), respectively. Forty-two patients (48%) had at least one major bleed according to a priori determined definitions, and 12 patients (14%) had at least one thrombotic event during ECMO. Platelet fibrinogen receptor expression decreased (median fluorescence intensity [MFI], 29,256 vs 26,544; p = 0.0005), while von Willebrand Factor expression increased (MFI: 7,620 vs 8,829; p = 0.0459) from day 2 to day 5 of ECMO. Platelet response to agonist, Thrombin Receptor Activator Peptide 6, also decreased from day 2 to day 5 of ECMO, as measured by binding with anti-P-selectin, PAC-1 (binds activated GPIIb/IIIa), and anti-CD63 monoclonal antibodies (P-selectin area under the curve [AUC]: 63.46 vs 42.82, respectively, p = 0.0022; PAC-1 AUC: 93.75 vs 74.46, p = 0.0191; CD63 AUC: 55.69 vs 41.76, p = 0.0020)., Conclusions: The loss of platelet response over time may contribute to bleeding during ECMO. These novel insights may be useful in understanding mechanisms of bleeding in pediatric ECMO and monitoring platelet markers clinically could allow for prediction or early detection of bleeding and thrombosis., Competing Interests: Dr. d’Udekem’s institution received funding from Actelion (Janssen) and from Berlin Heart. Drs. Ignjatovic’s and Mongale’s institutions received funding from the National Health and Medical Research Council (grant APP1129317). The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Background: In 2011 we reported unfavourable outcomes of second-run extracorporeal life support (ECLS) in children. We wanted to investigate whether this previous report affected our strategy and modified our long-term outcomes., Methods: Between 1988 and 2015, 31 patients underwent a second-run ECLS. Median age at the time of first support was 9days (0-16 years). Median length of support for the first and second runs were 4.7days (0.1-10) and 3.6days (0.5-8.7) respectively, with an interval of 1.8days (0.1-66) between supports., Results: There was an increasing trend in the number of patients undergoing second-run ECLS after our report: 21 patients between 1988 and mid-2010 (0.9 patients/year) and 10 between mid-2010 and 2015 (two patients/year) (p=0.06). However, among all the patients who underwent ECLS, the proportion of second-run ECLS was not different before and after 2010 (4% vs. 4.2% respectively, p=0.92). While 58% of patients (18/31) survived weaning of support, only 23% (7/31) survived to hospital discharge and 14% (5/31) were still alive after hospital discharge at a median of 6.5 years (1.2-11.6). The three patients who had positive long-term outcomes had the second-run ECLS instituted to allow for major cardiac operations., Conclusions: Compassionate use of second-run ECLS is difficult to refuse but one should be aware that its outcomes are dismal. In our centre, benefits seem to be limited to cases where the second-run ECLS allows for a major cardiac intervention., (Copyright © 2018 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Objective: The aim of this review is to highlight an emerging problem with anticoagulation-related complications in neonatal and paediatric ECMO, to explore for flaws in the currently recommended anticoagulation management responsible for these problems and to discuss possible strategies mitigating further escalation of the issue., Data Sources: Pertinent neonatal and paediatric literature on the topic of interest and international Extracorporeal Life Support Organisation (ELSO) registry data request., Conclusions: The international ELSO registry data reveals increasing rates of anticoagulation-related complications during neonatal and paediatric ECMO worldwide. The causes are multifactorial and the proposed solution to the problem is to match anticoagulation management to the pathophysiological complexity of haemostasis on ECMO., (© The Author(s) 2015.)

The extracorporeal membrane oxygenation circuit is made of a number of components that have been customized to provide adequate tissue oxygen delivery in patients with severe cardiac and/or respiratory failure for a prolonged period of time (days to weeks). A standard extracorporeal membrane oxygenation circuit consists of a mechanical blood pump, gas-exchange device, and a heat exchanger all connected together with circuit tubing. Extracorporeal membrane oxygenation circuits can vary from simple to complex and may include a variety of blood flow and pressure monitors, continuous oxyhemoglobin saturation monitors, circuit access sites, and a bridge connecting the venous access and arterial infusion limbs of the circuit. Significant technical advancements have been made in the equipment available for short- and long-term extracorporeal membrane oxygenation applications. Contemporary extracorporeal membrane oxygenation circuits have greater biocompatibility and allow for more prolonged cardiopulmonary support time while minimizing the procedure-related complications of bleeding, thrombosis, and other physiologic derangements, which were so common with the early application of extracorporeal membrane oxygenation. Modern era extracorporeal membrane oxygenation circuitry and components are simpler, safer, more compact, and can be used across a wide variety of patient sizes from neonates to adults.

This study aims to evaluate the impact of a change in extracorporeal membrane oxygenation (ECMO) technology on patient and circuit outcomes. A retrospective single-centre study of all ECMO runs from 1988 to 2006 was performed. Predictors of survival to hospital discharge (primary outcome measure) were evaluated in the entire cohort by univariate and multivariate analysis. A detailed subgroup univariate and multivariate analysis was performed in the cardiac and respiratory groups to identify predictors of survival to hospital discharge. A total of 275 patients underwent 294 extracorporeal support runs at a median (interquartile range) age of 40 (3-639) days and weight of 4.0 (3.1-10) kg. The primary indications for support were respiratory (41.8%), cardiac (45.6%) and sepsis (12.6%). Between the initial (Era 1) and most recent era (Era 3), cardiac support became the predominant ECMO indication (26 of 127 vs. 59 of 107; P<0.001). Survival to decannulation, intensive care and hospital discharge for the entire cohort and Era 3 patients were 50.0%, 48.9%, 44.4% and 71.7%, 55.6%, 52.6% (P<0.003), respectively. Treatment in Era 3 was associated with increased survival to intensive care discharge (P=0.02) for all ECMO patients. Cardiac survival was associated with treatment in Era 3 (P=0.04) and a lower complexity score (P<0.001). There was a significant reduction in mechanical circuit complications in the respiratory ECMO subgroup. A significant improvement in patient survival outcomes and reduction in mechanical circuit complications was noted in the current era. This improvement was associated with a change in ECMO technology.

A 13-year-old girl presented to the emergency department with fatigue, headaches and muscle stiffness after returning from a family camping trip. Within 24 h, she was transferred to ICU with general oedema and low saturations, where she had a cardio-respiratory arrest and was placed on veno-arterial extracorporeal membrane oxygenation (ECMO). The patient was successfully supported with ECMO for profound myocardial dysfunction and haemofiltration for rhabdomyolysis and acute renal failure. Patients who present with profound myocardial dysfunction and myoglobinuria as a consequence of viral infection can be successfully supported with ECMO.