To test the feasibility and safety of a randomized controlled trial (RCT) delivering nitric oxide into the sweep gas of extracorporeal membrane oxygenation (ECMO) circuits (sNO) in critically ill children. Second, we explored whether use of sNO may influence clinical outcomes. Prospective pilot single-center open-label RCT (trial registration number ACTRN12619001518156). Single-center, tertiary PICU with enrollment between July 2020 and July 2023. Patients from birth to 16 years requiring venoarterial or venovenous ECMO support were enrolled. Randomization to sweep flow with an oxygen/nitrogen mix vs. a mix of oxygen, nitrogen and sNO (20 parts per milliion). Randomization was stratified by type of ECMO support (venoarterial vs. venovenous). Of 60 eligible patients 53 underwent randomization. The median (interquartile range [IQR]) was 1 month (0.1-33.5 mo) and 6.2 months (0.5-120.2 mo) for the intervention and control arms, respectively. Venoarterial and venovenous support were used in 35 of 53 (65%) and 18 of 53 (35%) patients, respectively. In all, 17 of 53 (32%) received pulmonary, 23 of 53 (43%) cardiac and 13 of 53 (25%) extracorporeal cardiopulmonary resuscitation support. Median (IQR) survival free of ECMO and survival free of PICU censored at 30 and 90 days were similar: 18.2 days (0-25.2 d) and 69.1 days (0-85.2 d) vs. 20.8 days (0-26.3 d) and 77.7 days (0-85.9 d) with an effect estimate of -3.2 days (-16.6 to 10.1 d) and -8.8 days (-54.2 to 36.6 d) between the intervention and standard care arm. Blood product use, circuit duration to replacement, free plasma hemoglobin, degree of oxygenator thrombus, and incidence of methemoglobinemia were similar between the two groups. No major adverse events occurred related to the treatment allocation or intervention. This single-center pilot RCT of sNO vs. standard sweep flow in the ECMO circuit demonstrated that such a trial is safe and feasible. However, given no effect of sNO on clinical outcomes was detected further exploration of dose and route of administration of NO should be undertaken before larger, definitive trials are conducted.

BackgroundBronchiolitis is the most common lower respiratory tract infection in infants under 1 year of age. Although outcomes are generally good in neonates, preterm infants may experience rapid clinical deterioration and require extracorporeal membrane oxygenation (ECMO) as a rescue therapy.ObjectiveTo describe the characteristics and clinical outcomes of neonates requiring ECMO for acute bronchiolitis over the past decade.MethodsAn observational, retrospective, single-center study conducted in a level IIIC neonatal unit. All neonates admitted between 2013 and 2022 who required ECMO for bronchiolitis-related respiratory failure were included. Demographic, clinical, and outcome variables were analyzed.ResultsSix patients were included: five (83%) were preterm, with a median gestational age of 28.6 weeks (IQR 27.1-29.6). Respiratory syncytial virus was isolated in four patients, rhinovirus in one and influenza A in one. At ECMO initiation, median age was 48.5 days (IQR 34-120), median postmenstrual age was 38 weeks (IQR 35-41.8), and median weight was 2490g (IQR 1800-2900). The median duration of ECMO was 14 days (IQR 9-24). Two patients (33%) died, both preterm with RSV infection. All survivors were followed up by pediatric pulmonologists and neurologists. Two required home oxygen, and three showed neurodevelopmental disorders.ConclusionIn our cohort, the two non-survivors were preterm, RSV positive, and required prolonged ECMO support. Among survivors, respiratory and neurodevelopmental complications were common, underscoring the need for structured long-term follow-up. Neurodevelopmental impairment was the most frequent sequela observed.

The Use of Extracorporeal Membrane Oxygenation in Neonates With Congenital Renal Failure.

This study analyzed the outcomes of neonates undergoing a second run of extracorporeal membrane oxygenation (ECMO) to determine whether there is a benefit to a repeated run. We used Extracorporeal Life Support Organization data to compare neonates undergoing a single versus two runs of ECMO from 2009 to 2019. Baseline characteristics of single-run patients were compared with the first run in two-run patients to identify clinical predictors of a second run of ECMO. Furthermore, we compared overall survival outcomes and ECMO-related complications in single-run and two-run patients, with propensity score matching to adjust for baseline differences between the groups. A total of 12,292 patients undergoing 12,668 ECMO runs met criteria. Neonates requiring a second run had a shorter duration of the first ECMO run (p < 0.001) and were more likely to have had venoarterial cannulation (p < 0.001) than single-run patients. Overall, 33.8% of patients undergoing a second run survived until discharge, compared with 62.9% of patients undergoing a single run only. Propensity score matched analysis demonstrated that patients undergoing two runs were more likely to die, irrespective of underlying physiologic status or ECMO indication (odds ratio [OR] = 3.53, 95% confidence interval [CI] = 2.75-4.56). Nevertheless, nearly a third of patients undergoing two ECMO runs survived until discharge, indicating that recannulation may be beneficial in certain patient cohorts.

This study aimed to assess whether the proinflammatory markers procalcitonin (PCT), C-reactive protein (CRP), or interleukin 6 (IL-6) are associated with mortality in neonates with congenital diaphragmatic hernia (CDH) requiring extracorporeal membrane oxygenation (ECMO). Congenital diaphragmatic hernia neonates receiving venovenous ECMO between December 2012 and June 2022 were retrospectively reviewed and grouped by survival status. Longitudinal CRP, PCT, and IL-6 levels during the first 10 days on ECMO were analyzed using the Mann-Whitney U test. A PCT cut-off was determined to define a "high inflammatory response group," further evaluated with Kaplan-Meier curves and the log-rank test. Independent mortality risk factors were identified using Cox regression. Among nonsurvivors, PCT values were significantly higher on day 2 (p = 0.028), day 3 (p = 0.028), day 6 (p = 0.031), and day 10 (p = 0.017) after ECMO initiation. Infants in the high inflammatory response group had significantly shorter survival time (p = 0.006). C-Reactive protein and IL-6 were not significantly associated with mortality. In multivariable Cox regression analysis, high PCT on day 2 of ECMO (hazard ratio: 1.022; 95% confidence interval [CI]: 1.004-1.040) and severe pulmonary hypertension (hazard ratio: 3.270; 95% CI: 1.245-8.588) were independently associated with mortality. High PCT in CDH neonates receiving ECMO is significantly associated with increased mortality and reduced survival time.

Central or Peripheral Venoarterial Extracorporeal Membrane Oxygenation for Neonates and Children With Septic Shock.

Extracorporeal membrane oxygenation (ECMO) can act as a bridge to recovery in both pre- and postoperative patients with transposition of the great arteries (TGA). However, literature on its use in these patients is scarce. Retrospective single-centre cohort study encompassing all TGA patients who received ECMO between January 2009 and March 2024. Twenty-two neonates received ECMO during the study period, with an overall median age and weight at time of ECMO cannulation of 6.5 (1.8-10) days and 3.7 (3.3-4.0) kg, respectively. Twelve neonates received ECMO prior to the arterial switch operation because of severe persistent pulmonary hypertension (83%), respiratory failure due to severe pulmonary atelectasis (8%) or hypoxia after pulmonary arterial banding procedure (8%). Postoperative ECMO was used in 11 patients; of these, 1 (9%) had also received ECMO preoperatively. Postoperative indications for the remaining patients included failure to wean from cardiopulmonary bypass (50%), low cardiac output in Intensive Care Unit (20%), or after cardiopulmonary arrest (30%). Overall, median ECMO duration for all TGA patients was 75 (45-171) h, with a survival rate of 59% to hospital discharge. Among the preoperative ECMO patients, 5 patients (42%) died (4 preoperatively, 1 postoperatively performed while on ECMO). In the postoperative ECMO group, survival rate was 60%. In this single-centre retrospective study, TGA neonates received ECMO preoperatively primarily for severe pulmonary hypertension and postoperatively for failure to wean from cardiopulmonary bypass. This study showed a 58% and 60% survival to hospital discharge in ECMO patients supported preoperatively and those supported postoperatively, respectively.

Introduction: Neonates with congenital diaphragmatic hernia (CDH) who undergo repair while on extracorporeal membrane oxygenation (ECMO) are at risk of developing post-operative bleeding complications. Balanced anticoagulation is critical to maintain ECMO flow and avoid bleeding. Heparin has historically been our first-line anticoagulant; however, recently, we transitioned to bivalirudin, a direct thrombin inhibitor. The objective of this pilot study was to compare post-operative surgical bleeding complications between the two groups. Methods: We performed a single center retrospective cohort study of patients who underwent CDH repair while on ECMO between 2008 and 2023. Neonates were stratified based on the type of anticoagulant initiated after CDH repair. Outcomes included bleeding requiring surgical re-operation, intracranial hemorrhage, volume of blood products transfused, number of circuit changes, days on ECMO, and overall survival. Results: Among 62 neonates with CDH who underwent repair on ECMO, 44 (71%) were managed post-CDH repair with heparin and 18 (29%) with bivalirudin. One (5.6%) neonate managed with bivalirudin underwent re-operation following CDH repair for a bleeding complication compared to 17 (38.6%) managed with heparin (p = 0.022). In addition, the bivalirudin cohort utilized half of the total blood product volume compared to the heparin cohort (p = 0.020). Despite these benefits, there were no significant differences between groups for incidence of intracranial hemorrhage, number of circuit changes, days on ECMO, and overall survival. Conclusion: Anticoagulation with bivalirudin in neonates who underwent CDH repair while on ECMO was associated with decreased surgical bleeding complications and less total blood product transfused. This pilot analysis is the first to compare heparin to bivalirudin and stresses the importance of a multicenter study.

Background: Despite surgical advances, neonatal truncus arteriosus repair remains high risk and approximately 10% of patients receive perioperative extracorporeal membrane oxygenation (ECMO). We aimed to assess factors and outcomes associated with the use of perioperative ECMO in infants undergoing truncus arteriosus repair. Methods: We conducted a retrospective cohort study of patients who underwent truncus arteriosus repair between 2004 and 2019, using administrative data from the Pediatric Health Information System database. Results: We identified 1,645 neonates and infants who underwent truncus arteriosus repair at 49 centers, of which 141 (8.6%) received ECMO. Prematurity (adjusted odds ratio [aOR], 2.06; 95% CI, 1.38-3.06; P < .001), truncal valve intervention (aOR, 4.69; 95% CI, 2.56-8.59; P < .001), and interrupted aortic arch repair (aOR, 1.80; 95% CI, 0.96-3.38; P = .07) were associated with perioperative ECMO. Hospital mortality occurred in 87 of 141 (62%) patients who received ECMO compared with 77/1504 (5.1%) who did not require ECMO(aOR, 13.39; 95% CI, 8.70-20.61; P < .001). In the 1,481 patients who survived to hospital discharge, ECMO was associated with higher rates of postoperative length of stay >30 days (63% [34/54] vs 28% [400/1427]; aOR 2.65; 95% CI, 1.24-5.64, P = .012) and hospital readmission within 90 days (61% [33/54 [ vs 33% [474/1427] [; aOR, 2.66; 95% CI, 1.47-4.82; P = .001). Conclusions: Prematurity, truncal valve intervention, and interrupted aortic arch repair are important risk factors that could help predict the use of perioperative ECMO. Extracorporeal membrane oxygenation utilization is strongly associated with greater odds of hospital mortality, prolonged postoperative length of stay, and higher rates of hospital readmission in surviving patients.

Some critically ill neonates with congenital diaphragmatic hernia (CDH) require extracorporeal membrane oxygenation (ECMO) during the perioperative period. Neonates on ECMO face a significantly increased risk of thrombotic events. Thrombosis management varies across centers and may include anticoagulation, thrombolysis, or thrombectomy. We present our experience using low molecular weight heparin (LMWH) to treat a right atrial thrombus (RAT) following ECMO in a neonate with CDH.

Outcomes of Post-Cardiotomy Extracorporeal Membrane Oxygenation in Neonates and Paediatric Patients

Hemolysis during Venovenous Extracorporeal Membrane Oxygenation in Neonates with Congenital Diaphragmatic Hernia: A Prospective Observational Study

ObjectiveExtracorporeal membrane oxygenation (ECMO) has been increasingly used for severe neonatal respiratory failure refractory to conventional treatments. This paper summarizes our operation experience of neonatal ECMO via cannulation of the internal jugular vein and carotid artery.MethodsThe clinical data of 12 neonates with severe respiratory failure who underwent ECMO via the internal jugular vein and carotid artery in our hospital from January 2021 to October 2022 were collected.ResultsAll neonates were successfully operated on. The size of arterial intubation was 8 F, and the size of venous intubation was 10 F. The operation time was 29 (22–40) minutes. ECMO was successfully removed in 8 neonates. Surgeons successfully reconstructed the internal jugular vein and carotid artery of these neonates. Arterial blood flow was unobstructed in 5 patients, mild stenosis was present in 2 patients, and moderate stenosis was present in 1 patient. Venous blood flow was unobstructed in 6 patients, mild stenosis was present in 1 patient, and moderate stenosis was present in 1 patient. The complications were as follows: 1 case had poor neck incision healing after ECMO removal. No complications, such as incisional bleeding, incisional infection, catheter-related blood infection, cannulation accidentally pulling away, vascular laceration, thrombosis, cerebral haemorrhage, cerebral infarction, or haemolysis, occurred in any of the patients.ConclusionCannulation of the internal jugular vein and carotid artery can quickly establish effective ECMO access for neonates with severe respiratory failure. Careful, skilled and delicate operation was essential. In addition, during the cannulation process, we should pay special attention to the position of cannulation, firm fixation and strict aseptic operation.

Percutaneous, ultrasound-guided single- and multisite cannulation for veno-venous extracorporeal membrane oxygenation in neonates.

BackgroundExtracorporeal membrane oxygenation (ECMO) provides support for the pulmonary or cardiovascular function of children in whom the predicted mortality risk remains very high. The inevitable host inflammatory response and activation of the coagulation cascade due to the extracorporeal circuit contribute to additional morbidity and mortality in these patients. Mixing nitric oxide (NO) into the sweep gas of ECMO circuits may reduce the inflammatory and coagulation cascade activation during ECMO support.ObjectiveThe purpose of this study is to test the feasibility and safety of mixing NO into the sweep gas of ECMO systems and assess its effect on inflammation and coagulation system activation through a pilot randomized controlled trial.MethodsThe Nitric Oxide on Extracorporeal Membrane Oxygenation in Neonates and Children (NECTAR) trial is an open-label, parallel-group, pilot randomized controlled trial to be conducted at a single center. Fifty patients who require ECMO support will be randomly assigned to receive either NO mixed into the sweep gas of the ECMO system at 20 ppm for the duration of ECMO or standard care (no NO) in a 1:1 ratio, with stratification by support type (veno-venous vs veno-arterial ECMO).ResultsOutcome measures will focus on feasibility (recruitment rate and consent rate, and successful inflammatory marker measurements), the safety of the intervention (oxygenation and carbon dioxide control within defined parameters and methemoglobin levels), and proxy markers of efficacy (assessment of cytokines, chemokines, and coagulation factors to assess the impact of NO on host inflammation and coagulation cascade activation, clotting of ECMO components, including computer tomography scanning of oxygenators for clot assessments), bleeding complications, as well as total blood product use. Survival without ECMO and the length of stay in the pediatric intensive care unit (PICU) are clinically relevant efficacy outcomes. Long-term outcomes include neurodevelopmental assessments (Ages and Stages Questionnaire, Strength and Difficulties Questionnaire, and others) and quality of life (Pediatric Quality of Life Inventory and others) measured at 6 and 12 months post ECMO cannulation. Analyses will be conducted on an intention-to-treat basis.ConclusionsThe NECTAR study investigates the safety and feasibility of NO as a drug intervention during extracorporeal life support and explores its efficacy. The study will investigate whether morbidity and mortality in patients treated with ECMO can be improved with NO. The intervention targets adverse outcomes in patients who are supported by ECMO and who have high expected mortality and morbidity. The study will be one of the largest randomized controlled trials performed among pediatric patients supported by ECMO.Trial RegistrationAustralian New Zealand Clinical Trials Registry ACTRN12619001518156; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=376869International Registered Report Identifier (IRRID)DERR1-10.2196/43760

We aimed to determine the prevalence of electrographic seizures and associated odds of adverse outcomes of electrographic seizures in neonates with congenital diaphragmatic hernia (CDH) receiving extracorporeal membrane oxygenation (ECMO). Retrospective, descriptive case series. Neonatal ICU (NICU) in a quaternary care institution. All neonates with CDH receiving ECMO undergoing continuous electroencephalographic monitoring (CEEG) and follow-up between January 2012 and December 2019. None. All eligible neonates with CDH receiving ECMO underwent CEEG (n = 75). Electrographic seizures occurred in 14 of 75 (19%): they were exclusively electrographic-only in nine of 14, both electrographic-only and electroclinical in three of 14, and electroclinical only in two of 14. Two neonates developed status epilepticus. We identified an association between presence of seizures, rather than not, and longer duration of initial session of CEEG monitoring (55.7 hr [48.2-87.3 hr] vs 48.0 hr [43.0-48.3 hr]; p = 0.001). We also found an association between presence of seizures, rather than not, and greater odds of use of a second CEEG monitoring (12/14 vs 21/61; odds ratio [OR], 11.43 [95% CI, 2.34-55.90; p = 0.0026). Most neonates with seizures (10/14), experienced their onset of seizures more than 96 hours after the start of ECMO. Overall, the presence of electrographic seizures, compared with not, was associated with lower odds of survival to NICU discharge (4/14 vs 49/61; OR 0.10 [95% CI 0.03 to 0.37], p = 0.0006). Also, the presence of seizures-rather than not-was associated with greater odds of a composite of death and all abnormal outcomes on follow-up (13/14 vs 26/61; OR, 17.5; 95% CI, 2.15-142.39; p = 0.0074). Nearly one in five neonates with CDH receiving ECMO developed seizures during the ECMO course. Seizures were predominantly electrographic-only and when present were associated with great odds of adverse outcomes. The current study provides evidence to support standardized CEEG in this population.

Extracorporeal membrane oxygenation is a modern therapeutic strategy aimed to stabilize vital function in a patient suffering from severe circulatory failure and refractory hypoxia.Purpose. To describe two clinical cases of venoarterial extracorporeal membrane oxygenation in neonates with mеconium aspiration syndrome, complicated by persistent pulmonary hypertension and refractory hypoxia during medical evacuation.Material and methods. The authors performed a comprehensive analysis of the condition specifics based on clinical and instrumental work up.Results. We demonstrated that early application of venoarterial extracorporeal membrane oxygenation in neonates with meconium aspiration syndrome promotes the quickest possible stabilization and reverse of hypoxia and low cardiac output.Conclusion. Venoarterial extracorporeal membrane oxygenation in neonates with meconium aspiration syndrome and refractory hypoxemia is a life-saving procedure, that can be applied during medical evacuation by qualified medical staff.

ObjectivePost-cardiotomy extracorporeal membrane oxygenation (PC-ECMO) is a known rescue therapy for neonates and pediatric patients who failed to wean from cardiopulmonary bypass (CPB) or who deteriorate in intensive care unit (ICU) due to various reasons such as low cardiac output syndrome (LCOS), cardiac arrest and respiratory failure. We conducted a systematic review and meta-analysis to assess the survival in neonates and pediatric patients who require PC-ECMO and sought the difference in survivals by each indication for PC-ECMO.DesignSystematic review and meta-analysis.SettingMulti-institutional analysis.ParticipantsNeonates and pediatric patients who requires PC- ECMO.InterventionsECMO after open-heart surgery.ResultsTwenty-six studies were included in the analysis with a total of 186,648 patients and the proportion of the population who underwent PC-ECMO was 2.5% (2,683 patients). The overall pooled proportion of survival in this population was 43.3% [95% Confidence interval (CI): 41.3–45.3%; I2: 1%]. The survival by indications of PC-ECMO were 44.6% (95% CI: 42.6–46.6; I2: 0%) for CPB weaning failure, 47.3% (95% CI: 39.9–54.7%; I2: 5%) for LCOS, 37.6% (95% CI: 31.0–44.3%; I2: 32%) for cardiac arrest and 47.7% (95% CI: 32.5–63.1%; I2: 0%) for respiratory failure. Survival from PC-ECMO for single ventricle or biventricular physiology, was reported by 12 studies. The risk ratio (RR) was 0.74 for survival in patients with single ventricle physiology (95% CI: 0.63–0.86; I2: 40%, P < 0.001). Eight studies reported on the survival after PC-ECMO for genetic conditions. The RR was 0.93 for survival in patients with genetic condition (95% CI: 0.52–1.65; I2: 65%, P = 0.812).ConclusionsPC-ECMO is an effective modality to support neonates and pediatric patients in case of failed CPB weaning and deterioration in ICU. Even though ECMO seems to improve survival, mortality and morbidity remain high, especially in neonates and pediatric patients with single ventricle physiology. Most genetic conditions alone should not be considered a contraindication to ECMO support, further studies are needed to determine which genetic abnormalities are associated with favorable outcome.

Objective: The objective of the study is to evaluate the utility of real-time echocardiography (RTE) to provide objective hemodynamic guidance during decannulation of neonates from extracorporeal membrane oxygenation (ECMO).Design: Retrospective case series.Patients: Neonates with respiratory and circulatory failure who underwent venoarterial ECMO (VA-ECMO).Interventions: Use of RTE to assess cardiac function, pulmonary hypertension (PH), and readiness for decannulation from ECMO.Outcome measures: Data abstracted included clinical parameters, RTE data, and management decisions during weaning from VA-ECMO.Results: We used RTE during weaning in 12 of 33 patients between 2016 and 2019.Findings prompted inotrope titration in 10 (83%) patients and volume resuscitation in 10 patients.PH was present in 12 (100%) patients and prompted initiation of prostaglandin infusion (in 3 (25%) patients.Ten of 12 patients were successfully weaned off; in 2, RTE was instrumental in halting decannulation.Conclusions: RTE may serve as a valuable tool in clinical decision-making while weaning neonates from VA-ECMO and providing data to choose appropriate support for successful decannulation.

BackgroundCongenital diaphragmatic hernia (CDH) is a rare disease often requiring mechanical ventilation after birth. In severe cases, extracorporeal membrane oxygenation (ECMO) may be needed. This study analyzed the outcomes of patients with CDH treated with ECMO and investigated factors related to in-hospital mortality.MethodsAmong 254 newborns diagnosed with CDH between 2008 and 2020, 51 patients needed ECMO support. At Asan Medical Center, a multidisciplinary team approach has been applied for managing newborns with CDH since 2018. Outcomes were compared between hospital survivors and nonsurvivors.ResultsECMO was established at a median of 17 hours after birth. The mean birth weight was 3.1±0.5 kg. Twenty-three patients (23/51, 45.1%) were weaned from ECMO, and 16 patients (16/51, 31.4%) survived to discharge. The ECMO mode was veno-venous in 24 patients (47.1%) and veno-arterial in 27 patients (52.9%). Most cannulations (50/51, 98%) were accomplished through a transverse cervical incision. No significant between-group differences in baseline characteristics and prenatal indices were observed. The oxygenation index (1 hour before 90.0 vs. 51.0, p=0.005) and blood lactate level (peak 7.9 vs. 5.2 mmol/L, p=0.023) before ECMO were higher in nonsurvivors. Major bleeding during ECMO more frequently occurred in nonsurvivors (57.1% vs. 12.5%, p=0.007). In the multivariate analysis, the oxygenation index measured at 1 hour before ECMO initiation was identified as a significant risk factor for in-hospital mortality (odds ratio, 1.02; 95% confidence interval, 1.01–1.04; p=0.05).ConclusionThe survival of neonates after ECMO for CDH is suboptimal. Timely application of ECMO is crucial for better survival outcomes.