Opioid and benzodiazepine requirements in neonatal and pediatric patients undergoing venoarterial ECMO: insights from a predominantly cardiac cohort.

BACKGROUND

Managing sedation and analgesia in neonates and pediatric patients supported with extracorporeal membrane oxygenation (ECMO) is challenging due to altered pharmacokinetics, prolonged critical illness, and the need for deep sedation to maintain circuit integrity. Limited data describing cumulative opioid and benzodiazepine exposure and factors associated with dose escalation in pediatric ECMO populations.

METHODS

We conducted a retrospective cohort study of neonates and pediatric patients aged ≤14 years who received ≥72 h of venoarterial ECMO support in a pediatric cardiac surgical intensive care unit between 2019 and 2023. Exclusions included early mortality, neurological conditions requiring altered sedation strategies, or sedation primarily used for seizure management. Opioid and benzodiazepine doses administered during ECMO were converted to intravenous morphine and midazolam equivalents. Cumulative (mg/kg) and average daily (mg/kg/day) exposures were calculated. Multivariable regression analyses were performed to identify clinical predictors of sedative and analgesic dose requirements and associations with outcomes.

RESULTS

Eighty patients were included, with postoperative cardiac disease accounting for 68.8% of primary diagnoses. All patients received opioids, and 96.3% received benzodiazepines; 66.3% received adjunctive sedative agents. Median cumulative opioid and benzodiazepine exposures were 7.33 mg/kg and 15.75 mg/kg, respectively. Prolonged ICU length of stay and ECMO duration were independently associated with higher cumulative opioid exposure (Coeff = 0.02; 95% CI: 0.01 to 0.03; p = 0.001 and Coeff = 0.02; 95% CI: 0.01 to 0.04; p = 0.001, respectively). Furthermore, multivariable analysis demonstrated that higher in-hospital mortality was significantly associated with prolonged ICU length of stay (Coeff = 0.73; 95% CI: 0.12 to 1.34; p = 0.02), higher average opioid doses (Coeff = 1.75; 95% CI: 0.11 to 3.39; p = 0.04), acute kidney injury (Coeff = 3.34; 95% CI: 0.32 to 6.35; p = 0.03), and longer ECMO duration (Coeff = 0.43; 95% CI: 0.06 to 0.80; p = 0.02).

CONCLUSION

Prolonged ICU stays and ECMO courses in neonatal and pediatric patients significantly increase cumulative opioid burdens. Crucially, higher average opioid doses, acute kidney injury, and extended ICU and ECMO durations serve as key clinical predictors of increased in-hospital mortality. These findings highlight the need for individualized, physiology-informed sedation strategies and structured weaning approaches to optimize outcomes in this high-risk population.