Extracorporeal membrane oxygenation support in COVID-19: an international cohort study of the Extracorporeal Life Support Organization registry.

BACKGROUND: Multiple major health organisations recommend the use of extracorporeal membrane oxygenation (ECMO) support for COVID-19-related acute hypoxaemic respiratory failure. However, initial reports of ECMO use in patients with COVID-19 described very high mortality and there have been no large, international cohort studies of ECMO for COVID-19 reported to date. METHODS: We used data from the Extracorporeal Life Support Organization (ELSO) Registry to characterise the epidemiology, hospital course, and outcomes of patients aged 16 years or older with confirmed COVID-19 who had ECMO support initiated between Jan 16 and May 1, 2020, at 213 hospitals in 36 countries. The primary outcome was in-hospital death in a time-to-event analysis assessed at 90 days after ECMO initiation. We applied a multivariable Cox model to examine whether patient and hospital factors were associated with in-hospital mortality. FINDINGS: Data for 1035 patients with COVID-19 who received ECMO support were included in this study. Of these, 67 (6%) remained hospitalised, 311 (30%) were discharged home or to an acute rehabilitation centre, 101 (10%) were discharged to a long-term acute care centre or unspecified location, 176 (17%) were discharged to another hospital, and 380 (37%) died. The estimated cumulative incidence of in-hospital mortality 90 days after the initiation of ECMO was 37·4% (95% CI 34·4-40·4). Mortality was 39% (380 of 968) in patients with a final disposition of death or hospital discharge. The use of ECMO for circulatory support was independently associated with higher in-hospital mortality (hazard ratio 1·89, 95% CI 1·20-2·97). In the subset of patients with COVID-19 receiving respiratory (venovenous) ECMO and characterised as having acute respiratory distress syndrome, the estimated cumulative incidence of in-hospital mortality 90 days after the initiation of ECMO was 38·0% (95% CI 34·6-41·5). INTERPRETATION: In patients with COVID-19 who received ECMO, both estimated mortality 90 days after ECMO and mortality in those with a final disposition of death or discharge were less than 40%. These data from 213 hospitals worldwide provide a generalisable estimate of ECMO mortality in the setting of COVID-19. FUNDING: None.

Impairment of Venous Drainage on Extracorporeal Membrane Oxygenation Secondary to Air Trapping in Acute Asphyxial Asthma.

The inability to adequately support a patient on extracorporeal membrane oxygenation (ECMO) due to impaired drainage is not an uncommon occurrence during support. Typically, the causes include hypovolemia, kinks in the circuit, cannula malposition, or inadequate cannula size. In this report we present an uncommon etiology of this problem. A 3-year-old female presented to our hospital in status asthmaticus and pulseless electrical activity (PEA). This was a result of dynamic hyperinflation of the lungs causing physical obstruction of venous return to the heart. Upon initiating venoarterial (VA) ECMO, we experienced inadequate drainage that did not improve despite multiple interventions. This resolved with the addition of an inhaled anesthetic gas to treat this patient's severe bronchospasm. This case illustrates the importance of considering a patient's physiology or disease state and how that may affect the mechanics of ECMO support.

Initial experience with recombinant antithrombin to treat antithrombin deficiency in patients on extracorporeal membrane oxygenation.

Acquired antithrombin (AT) deficiency has been associated with patients on extracorporeal membrane oxygenation (ECMO) as a result of hemodilution, blood coagulation activation, and the use of heparin. Replacement of AT has been typically utilized through the use of fresh-frozen plasma or AT concentrate. Antithrombin alfa (ATryn) is a recombinant form of AT (rAT) with an identical amino acid sequence as that of plasma-derived antithrombin. The primary objective of this study is to examine the relationship of rAT dose to measured plasma antithrombin activity in a small series of patients who received rAT while on ECMO. A retrospective chart review was performed of all patients at Medical City Children's Hospital who received ATryn while supported on ECMO between December 2011 and April 2012. Five patients were identified and the patients' weight, bolus dose of ATryn, drip rate of ATryn, and AT blood levels were collected for analysis. The median age of these patients was 1 month (range, 1 day to 3.75 years). Because no dosing guidelines exist for pediatric ECMO, a starting dose of ATryn was chosen based on the manufacturer's labeled indication (prevention of thromboembolic events in patients with AT hereditary deficiency). The median dose of rAT was 368 IU/kg/day (range, 104-520 IU/kg/day) to obtain AT activity level of 80-120%. The average time to reach the targeted AT activity level (80-120%) was 12.7 hours (range, 11-17 hours). Our findings suggest that the published ATryn dose may be inadequate to reach desired AT activity concentrations for pediatric patients on ECMO. Difference in patient population, use of extracorporeal circuits, and the use of heparin are likely explanations for this finding. We would also recommend frequent checking of AT levels while delivering this drug because making timely adjustments is necessary for achieving and maintaining the target AT activity level.

Extracorporeal Life Support Organization Registry International Report 2022: 100,000 Survivors.

The Extracorporeal Life Support Organization (ELSO) maintains the world's largest extracorporeal membrane oxygenation (ECMO) registry by volume, center participation, and international scope. This 2022 ELSO Registry Report describes the program characteristics of ECMO centers, processes of ECMO care, and reported outcomes. Neonates (0-28 days), children (29 days-17 years), and adults (≥18 years) supported with ECMO from 2009 through 2022 and reported to the ELSO Registry were included. This report describes adjunctive therapies, support modes, treatments, complications, and survival outcomes. Data are presented descriptively as counts and percent or median and interquartile range (IQR) by year, group, or level. Missing values were excluded before calculating descriptive statistics. Complications are reported per 1,000 ECMO hours. From 2009 to 2022, 154,568 ECMO runs were entered into the ELSO Registry. Seven hundred and eighty centers submitted data during this time (557 in 2022). Since 2009, the median annual number of adult ECMO runs per center per year increased from 4 to 15, whereas for pediatric and neonatal runs, the rate decreased from 12 to 7. Over 50% of patients were transferred to the reporting ECMO center; 20% of these patients were transported with ECMO. The use of prone positioning before respiratory ECMO increased from 15% (2019) to 44% (2021) for adults during the coronavirus disease-2019 (COVID-19) pandemic. Survival to hospital discharge was greatest at 68.5% for neonatal respiratory support and lowest at 29.5% for ECPR delivered to adults. By 2022, the Registry had enrolled its 200,000th ECMO patient and 100,000th patient discharged alive. Since its inception, the ELSO Registry has helped centers measure and compare outcomes across its member centers and strategies of care. Continued growth and development of the Registry will aim to bolster its utility to patients and centers.

Perioperative opiate requirements in children with previous opiate infusion.

BACKGROUND: Critically ill children often require continuous opiate infusions. Tolerance may develop requiring a weaning strategy to prevent withdrawal symptoms. These children may also require subsequent surgical procedures. This is the first study to investigate whether previously opiate-tolerant patients require higher doses of opiates for adequate pain management perioperatively. METHODS: A retrospective study was conducted at a tertiary children's hospital to investigate whether children previously exposed to continuous opiates for 10 or more days with subsequent weaning from those opiates will have similar or increased perioperative opiate requirements when compared to opioid-naïve controls. Study patients included 31 children with previous continuous opiate exposure for 10 or more days followed by weaning and without signs of withdrawal for at least 72 h prior to the surgical procedure. Excluded were patients over 18 years of age, those whose surgical procedures would be unlikely to require perioperative opiates, oncological patients, burn patients, neurologically devastated patients, and patients who received regional anesthesia in addition to perioperative narcotics. The control group consisted of 31 age- and case-matched opiate-naïve patients who underwent a surgical procedure during a similar time frame as the study patient. The medication administration record was reviewed for the length of continuous opiate exposure, date of last opiate use prior to a subsequent surgical procedure, and opiate use during the perioperative period. Opiate use was calculated as morphine equivalents per kilogram body weight (MSEQ·kg(-1)). The Wilcoxon rank sum test was used for univariate comparisons between matched pairs, and P-values <0.05 were considered statistically significant. RESULTS: The perioperative opiate requirements in opiate-exposed patients (median, interquartile range: 0.14, 0.08-0.25 MSEQ·kg(-1)) were not significantly different from opiate-naïve patients (median, interquartile range 0.10, 0.05-0.2 MSEQ·kg(-1), P = 0.19). Pain scores indicated that patients were generally comfortable in the perioperative period. CONCLUSIONS: The perioperative opiate requirements of pediatric patients who were successfully weaned after prolonged opiate use were similar to opiate-naïve patients. A history of prolonged opiate use alone does not necessitate special pain management for future procedures.

U.S. attitudes and perceived practice for noninvasive ventilation in pediatric acute respiratory failure.

OBJECTIVE: Few pediatric studies exist regarding the use of noninvasive positive-pressure ventilation for acute respiratory failure; however, those that do suggest a role. This study seeks to describe attitudes and perceived practices of pediatric intensivists regarding the use of noninvasive positive-pressure ventilation in children with acute respiratory failure. DESIGN: Electronic survey. SETTING: Medical institutions. PARTICIPANTS: Of the 932 physicians approached, 353 (38%) responded to the survey. Respondents included U.S. physicians practicing pediatric critical care (90%), pediatric anesthesia critical care (4%), pediatric pulmonary critical care (4%), and other disciplines (2%). INTERVENTIONS: Survey. MEASUREMENTS AND MAIN RESULTS: The survey contained questions regarding 1) practitioner demographics, 2) patient characteristics, and 3) clinical cases designed to assess noninvasive positive-pressure ventilation use in certain patient scenarios. Noninvasive positive-pressure ventilation was used by 99% of the respondents, with 60% using noninvasive positive-pressure ventilation as initial support >10% of the time. Respondents reported use of noninvasive positive-pressure ventilation for acute respiratory failure in lower airway disease (70%), asthma (51%), acute lung injury/acute respiratory distress syndrome (43%), and upper airway obstruction (31%). In clinical scenarios, respondents reported that the factors associated with nonuse of noninvasive positive-pressure ventilation as initial support were disease process (31%), oxygenation (19%), ventilation severity (15%), expectation that the patient was likely to worsen (12%), and age or inability to cooperate (11%). CONCLUSIONS: Noninvasive positive-pressure ventilation is widely used and most frequently utilized in patients with acute lower airway disease. Factors such as severe defects in oxygenation and ventilation, disease progression, and patient tolerability decreased the likelihood of use. These findings may help direct further studies of noninvasive positive-pressure ventilation in children with acute respiratory failure.

The Use of Recombinant Antithrombin III in Pediatric and Neonatal ECMO Patients.

A retrospective review of 77 pediatric and neonatal extracorporeal membranous oxygenation (ECMO) patients who received recombinant antithrombin III (ATIII) for ATIII activity greater than 80% was conducted. Anticoagulation management was per institutional protocol. An ATIII activity greater than 80% was targeted. Diagnosis, reason for ECMO cannulation, blood product usage, heparin dosing, ATIII activity and doses, thrombotic and bleeding complications, hours on ECMO, and mortality were recorded. We calculated patient-level summary statistics and assessed differences between groups using χ tests (categorical variables) and Wilcoxon rank sum tests (continuous variables). Hierarchical generalized linear models were developed to model bleeding and thrombotic complications. The majority (n = 75) received venoarterial ECMO and had cardiac diagnoses (n = 62). Antithrombin III activity was below 80% for an average of 5.2 hours per patient. Antithrombin III activity less than 80% was not associated with thrombotic complications (odds ratio [OR] = 1.02, 95% confidence interval [CI] = 0.97-1.06, p = 0.86). Antithrombin III activity greater than 80% was not associated with bleeding complications (OR = 1.06, 95% CI = 1.01-1.11, p = 0.44). Duration of ECMO was an independent predictor of thrombotic complications (OR = 1.08, 95% CI = 1.02-1.11, p = 0.02). There were no independent predictors of bleeding complications. Antithrombin III activity correlated with anti Xa activity (r = 0.367, p < 0.001) but not with other measures of anticoagulation or with heparin dose (r = 0.16, p = 0.165). ATIII activity was not associated with bleeding, thrombosis, or heparin dose. Antithrombin III activity was associated with anti Xa activity but not with traditional measures of anticoagulation. Antithrombin III replacement for an activity less than 80% did not increase bleeding.