ED95 of phenylephrine to prevent spinal-induced hypotension and/or nausea at elective cesarean delivery

Abstract

Background The purpose of this trial was to determine the 95% effective dose (ED95) of phenylephrine by intermittent i.v. bolus, to prevent spinal-induced hypotension and/or nausea at elective cesarean delivery. Methods The study was conducted in a double-blinded fashion in 50 patients undergoing elective cesarean delivery under spinal anesthesia. The dose of phenylephrine was determined using up-down sequential allocation, modified by a variation of the Narayana rule. Systolic pressure and heart rate were assessed every minute until uterine incision. The first patient was assigned a 40-μg dose, and the dose to subsequent patients varied by 10-μg increments or decrements. An adequate response was defined as absence of hypotension (systolic pressure <80% of baseline) and nausea. The study solution was given immediately after spinal administration, without prior pressure measurement, and thereafter when the systolic pressure was ⩽ control values. fell below baseline. The ED95 was determined by a logistic model with non-log-transformed doses, using Firth’s penalized maximum likelihood method with 95% confidence intervals based on penalized profile likelihood. Results The ED95 of phenylephrine was estimated as 159 μg (95% confidence interval: 122–371 μg), although the largest dose given in the study was only 120 μg. Hypertension (systolic blood pressure >120% of baseline) was observed in 14 cases, immediately after intrathecal injection and prophylactic phenylephrine administration in all cases. Conclusion The ED95 of phenylephrine, administered as intermittent boluses to prevent pre-delivery spinal-induced hypotension and/or nausea at elective cesarean delivery, is at least 122 μg (lower limit of the confidence interval). The safety of this dose warrants further studies.