Fentanyl Utilization During Extracorporeal Membrane Oxygenation and Risk of Methadone Treatment Among Pediatric ECMO Survivors

INTRODUCTION: Single center studies suggest utilization of fentanyl during extracorporeal membrane oxygenation (ECMO) may be associated with a higher risk of opioid withdrawal. This study evaluated fentanyl use during ECMO and subsequent methadone or buprenorphine treatment among pediatric ECMO survivors in a large multi-center cohort. METHODS: This retrospective study included children < 18y treated at 41 U.S. children's hospitals in the Pediatric Health Information System between 2013 and 2023. Multivariable hierarchical regression was used to assess the relationship between fentanyl exposure on ECMO and likelihood of receiving methadone or buprenorphine after ECMO, adjusting for covariates including other opioid exposures. RESULTS: Overall, 4,365 children were included (55.5% male; 47.9% neonatal). Median duration of ECMO was 5 (IQR: 3-8) days. Fentanyl exposure was categorized into quartiles:0-1 days, 2 days, 3-4 days, and ≥ 5 days. On multivariable regression, children in the 3-4 days quartile (OR 1.32; 95% CI: 1.05-1.65) and ≥ 5 days quartile (OR 2.21; 95% CI: 1.71-2.85) were more likely to receive methadone or buprenorphine after ECMO compared to those in the 0-1 days quartile. On bivariate comparison, children who received fentanyl during ECMO were found to have prolonged ventilator dependence, TPN use, and post-ECMO length of stay. CONCLUSION: Patients receiving fentanyl while on ECMO had an increased risk of receiving methadone or buprenorphine treatment post-ECMO, suggesting a higher risk of opioid withdrawal in patients receiving fentanyl while on ECMO. Our findings underscore a need for expanded opioid stewardship initiatives to utilize alternative pain management and minimize fentanyl prescribing for children undergoing ECMO.