Effective Dose of Ephedrine for Treatment of Hypotension After Induction of General Anaesthesia in Neonates and Infants Less Than 6 Months of Age: a Multicentre Randomised, Controlled, Open Label, Dose Escalation Trial

Background: The recommended dose of ephedrine in adults (0.1 mg kg) frequently fails to treat hypotension after induction of general anaesthesia in neonates and infants less than 6 months of age. The aim of this study was to determine the optimal dose of ephedrine in this population for the treatment of hypotension after induction of general anaesthesia with sevoflurane.

Methods: We conducted a multicentre, prospective, randomised, open-label, controlled, dose-escalation trial. Subjects were randomised if presenting a >20% change from baseline in MAP. Six cohorts of 20 subjects each were enrolled. Ten subjects in the first cohort received 0.1 mg kg i. v. (reference dose). For each subsequent cohort, 10 subjects were assigned to the next higher dose (consecutively 0.6, 0.8, 1, 1.2, and 1.4 mg kg i. v.), and the other subjects were assigned to one or more doses already investigated in previous cohorts. The primary outcome was the return of MAP to >80% of baseline at least once within 10 min after ephedrine administration.

Results: A total of 119 infants (25% females), with a mean age (standard deviation) of 2.7 (1.3) months, received their allocated dose of ephedrine. The optimal dose of ephedrine was 1.2 mg kg, with a percentage of success of 65.5% (95% confidence interval, 35.6-86.4). The doses of ephedrine investigated did not induce adverse events.

Conclusions: Doses of ephedrine much higher (∼10-fold) than those used in adults are necessary in neonates and infants for the treatment of hypotension after induction of general anaesthesia with sevoflurane.

Clinical Trial Registration: NCT02384876.