Sweep Gas Nitric Oxide During Extracorporeal Membrane Oxygenation in Neonates and Children (NECTAR Trial): A Single-Center, Pilot Randomized Controlled Trial.

Predictability model of the need for extracorporeal membrane oxygenation in neonates with meconium aspiration syndrome treated with inhaled nitric oxide

Cannulation for repeat extracorporeal membrane oxygenation (ECMO) in neonates with respiratory failure may be associated with technical difficulties, especially after the ligation of both the carotid artery and internal jugular vein. In a newborn who required repeat ECMO, the previously reconstructed right carotid artery was used for arterial access. The right atrium was cannulated through a small submammary thoracotomy incision after the internal jugular vein was found to be thrombosed. This approach is relatively simple, provides excellent bypass flow, and is not associated with significant bleeding.

To determine current rates, risk factors, and causal organisms related to infections acquired during extracorporeal membrane oxygenation (ECMO). A descriptive and retrospective case-control study. ECMO centers belonging to the Extracorporeal Life Support Organization. The Extracorporeal Life Support Organization Registry was queried for data related to all ECMO cases from 1998 through 2008. All culture-proven infections obtained from any site during ECMO support and not believed preexisting were included. Infection rates were analyzed by age category (i.e., neonatal, pediatric, adult), indication for ECMO (i.e., respiratory, cardiac, cardiopulmonary resuscitation), mode of ECMO (e.g., venovenous), and duration of ECMO support. Infected and noninfected ECMO patients were compared. None. A total of 2,418 infections were reported during 20,741 (11.7%) ECMO cases for a rate of 15.4 per 1,000 ECMO days. Rates were highest in the adult vs. the pediatric and neonatal populations (30.6 vs. 20.8 vs. 10.1 infections per 1,000 ECMO days, respectively) and in those necessitating extracorporeal cardiopulmonary resuscitation (24.7 infections per 1,000 ECMO days). In each age category, venoarterial ECMO was the mode of support associated with the highest rate of infection. Prevalence of infection increased with duration of ECMO support from 6.1% of those requiring bypass for ≤ 7 days to 30.3% of those requiring ECMO for >14 days (p < .001). Coagulase-negative staphylococci (15.9%) were the most common organisms cultured followed by species of Candida (12.7%), and Pseudomonas (10.5%). Those with an infection acquired during ECMO support were significantly older, had a longer duration of ECMO, a longer duration of post-ECMO ventilatory support, and a higher prevalence of death than those without. Infections acquired during ECMO are common and can have significant associated consequences. Knowledge of high-risk patients and common causal organisms may improve strategies for treatment and prevention, but further work to develop strategies and guidelines for prevention of these infections is urgently needed.

Hybrid and parallel extracorporeal membrane oxygenation circuits

Severe cases of coronavirus disease 2019 (COVID-19) cannot be adequately managed with mechanical ventilation alone. The role and outcome of extracorporeal membrane oxygenation (ECMO) in the management of COVID-19 is currently unclear. Eight COVID-19 patients have received ECMO support in Shanghai with seven with venovenous (VV) ECMO support and one veno arterial (VA) ECMO during cardiopulmonary resuscitation. As of March 25, 2020, four patients died (50% mortality), three patients (37.5%) were successfully weaned off ECMO after 22, 40, and 47 days support, respectively, but remain on mechanical ventilation. One patient is still on VV ECMO with mechanical ventilation. The partial pressure of oxygen/fractional of inspired oxygen ratio before ECMO initiation was between 54 and 76, and all were well below 100. The duration of mechanical ventilation before ECMO ranged from 4 to 21 days. Except the one emergent VA ECMO during cardiopulmonary resuscitation, other patients were on ECMO support for between 18 and 47 days. In conclusion, ensuring effective, timely, and safe ECMO support in COVID-19 is key to improving clinical outcomes. Extracorporeal membrane oxygenation support might be an integral part of the critical care provided for COVID-19 patients in centers with advanced ECMO expertise.

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

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.

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.

Veno-arterial extracorporeal membrane oxygenation is well-established for pediatric patients with post-cardiotomy heart failure. However, extracorporeal membrane oxygenation support is associated with major complications, that is, hemorrhage and thromboembolism. We seek to report our experience with delayed systemic heparinization during neonatal cardiac extracorporeal membrane oxygenation and its impact on bleeding and thromboembolism. We retrospectively identified 15 consecutive neonates who were placed on extracorporeal membrane oxygenation after congenital heart surgery during a period of 3 years (2015-2017). Our anticoagulation protocol consisted of full heparin reversal by protamine after switching from cardiopulmonary bypass to extracorporeal membrane oxygenation (target activated clotting time: 120 ± 20 seconds). Administration of systemic heparinization was delayed until postoperative drainage volume declined to <1 mL/kg/h. Primary study endpoints were thromboembolism, bleeding, and requirement of blood products on extracorporeal membrane oxygenation. Our cohort (mean age: 13 ± 2.6 days; mean weight: 3.1 ± 0.3 kg; 66.7% male) required post-cardiotomy extracorporeal membrane oxygenation with a mean support time of 4.5 ± 2.2 days. Systemic heparinization was delayed averagely for 18.1 ± 9.3 hours. No thromboembolic events were observed on extracorporeal membrane oxygenation or after weaning. Relevant surgical site bleeding occurred in two patients (13.3%) requiring re-thoracotomy on the first postoperative day. Analysis of transfusion volumes revealed 24.5 ± 21.9 mL/kg/d mean packed red blood cells, 9.6 ± 7.1 mL/kg/d mean fresh frozen plasma, and 7.5 ± 5.7 mL/kg/d mean platelets. In-hospital survival was 86.6% (n = 13). In this retrospective analysis, the results of delayed systemic heparinization in neonatal post-cardiotomy extracorporeal membrane oxygenation could lead one to conclude that this routine is safe and favorable with low risk for thromboembolic events, reduced postoperative hemorrhage, and reduced blood product utilization.

BackgroundSurvival of neonates with intrauterine renal insufficiency and oligo- or anhydramnios correlates with the severity of secondary pulmonary hypoplasia. Early prenatal diagnosis together with repetitive amnioinfusions and modern intensive care treatment have improved the prognosis of these neonates. Extracorporeal membrane oxygenation is an established treatment option, mainly applied to neonates with pulmonary hypoplasia caused by congenital diaphragmatic hernia. However, a few case reports of extracorporeal membrane oxygenation in neonates with lower urinary tract obstruction have been published.Case presentationWe describe a case of a Caucasian male infant with prenatally diagnosed lower urinary tract obstruction and secondary pulmonary hypoplasia who was delivered spontaneously at 36 + 2 weeks of gestation. Venovenous extracorporeal membrane oxygenation was initiated on the first day of life for severe respiratory failure and consecutive hypoxemia despite treatment with inhaled nitric oxide and high-frequency oscillation. The patient was supported by extracorporeal membrane oxygenation for 10 days and extubated 6 weeks later. Hemofiltration was required on the second day of life because of renal insufficiency and was later replaced by peritoneal dialysis. The child was discharged after 4 months with nasal high-flow mild oxygen therapy and peritoneal dialysis.ConclusionNeonatal extracorporeal membrane oxygenation support is a possible treatment option for neonates with lower urinary tract obstruction and pulmonary hypoplasia.

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

The Right Ventricle During Veno-Venous Extracorporeal Membrane Oxygenation in Acute Respiratory Distress Syndrome: Can We Protect the Injured Ventricle?

To describe the clinical characteristics and outcomes of referrals for extracorporeal membrane oxygenation to a regional pediatric intensive care transport service, and identify clinical features at initial referral that predict the eventual need for extracorporeal membrane oxygenation. Retrospective analysis of prospectively collected data. Specialist pediatric intensive care transport service based at a large U.K. extracorporeal membrane oxygenation center. All referrals made for potential extracorporeal membrane oxygenation transport between January 2014 and July 2017. None. Demographic and clinical data at the time of referral, referral outcome, and 90-day mortality status were extracted. Univariate and multivariate analyses were used to identify clinical features at initial referral in neonates that predicted the need for extracorporeal membrane oxygenation. Of 253 extracorporeal membrane oxygenation referrals, 203 were included: 64 of 203 received extracorporeal membrane oxygenation (31.5%), 18 were accepted for extracorporeal membrane oxygenation but died before extracorporeal membrane oxygenation could be provided (8.8%), and 121 did not receive extracorporeal membrane oxygenation (59.6%). The transport team mobilized in 136 of 203 referrals (66.9%); conventional transport to an extracorporeal membrane oxygenation center was successful in 127 of 136 (93.4%), while nine of 136 were too unstable to transport. The 90-day mortality for the cohort was 17.7% (36/203). In logistic regression analysis, the odds ratio of requiring extracorporeal membrane oxygenation for diaphragmatic hernia was 12.0 (95% CI, 2.8-52.1) compared to meconium aspiration syndrome. Oxygenation index and Vasoactive-Inotropic Score were independent predictors of the need for extracorporeal membrane oxygenation in neonates. In this large cohort of neonatal and pediatric extracorporeal membrane oxygenation referrals to a pediatric intensive care transport service, a considerable portion of extracorporeal membrane oxygenation referrals (59.6%) continued on conventional management; however, 8.8% of the referrals died before extracorporeal membrane oxygenation could be provided. Earlier referral for extracorporeal membrane oxygenation; targeted referral triage using primary diagnosis, oxygenation index, and Vasoactive-Inotropic Score; and access to mobile extracorporeal membrane oxygenation services and faster mobilization of transport teams are important factors that could improve outcomes.

What is New in ECMO for COVID-19?

Objectives: Extracorporeal membrane oxygenation (ECMO) despite its common use in cases of severe cardiopulmonary failure in adult and pediatric patients still remains a challenge in modern intensive medicine. In this study, we analyzed our experience with ECMO support through cervical cannulation in infants and pediatric patients.