Up-Down Determination of the 90% Effective Dose of Phenylephrine for the Treatment of Spinal Anesthesia-Induced Hypotension in Parturients Undergoing Cesarean Delivery

Abstract

Hypotension frequently complicates spinal anesthesia for cesarean delivery, and vasopressors are the mainstay for treatment. The most effective dose of phenylephrine for the treatment of spinal anesthesia-induced hypotension has not been estimated. Healthy nonlaboring women undergoing a cesarean delivery were recruited. All women received spinal anesthesia using hyperbaric bupivacaine 12 mg with fentanyl and morphine. Each subject received an i.v. crystalloid fluid bolus before and at the time of initiation of spinal anesthesia (preload and coload). An up-down sequential allocation method using the biased-coin design was used to estimate the 90% effective dose (ED(90)) of phenylephrine. The assigned phenylephrine dose was based on the response of the preceding subject. If the systolic blood pressure (SBP) decreased > 20% of baseline (i.e., SBP 20%) or to an SBP < 90 mm Hg, the assigned dose of phenylephrine was administered. If the SBP returned to within 20% of baseline or > or = 90 mm Hg within 1 min, this was considered a success, otherwise it was a failure. The initial dose of phenylephrine was 100 microg. The ED(90) with 95% confidence intervals (CIs) was calculated using the maximum likelihood estimation and Firth logistic regression. Sixty-nine subjects were screened to participate, of whom 66 subjects consented. Forty-five of the enrolled subjects experienced spinal anesthesia-induced hypotension and received a blinded dose of phenylephrine. Those subjects who developed hypotension received doses of phenylephrine between 80 and 180 microg. No subjects experienced hypertension. Determined with the maximum likelihood estimation method, the ED(90) of phenylephrine was 147 microg (95% CI, 98-222 microg). With Firth regression, the probability of a successful response at 150 microg is 90.5% (95% CI, 66.0%-99.0%). In this study, we estimated that the ED(90) of phenylephrine required to treat spinal anesthesia-induced hypotension in cesarean delivery is approximately 150 microg.