Norepinephrine intravenous prophylactic bolus versus rescue bolus to prevent and treat maternal hypotension after combined spinal and epidural anesthesia during cesarean delivery: a sequential dose-finding study

Background: As a relatively new drug in obstetrical anesthesia, norepinephrine is less likely to induce bradycardia and decrease cardiac output, which makes it a potential alternative to phenylephrine. The purpose of this study was to determine the optimal norepinephrine bolus dose needed to either prevent or reverse hypotension after the use of combined spinal and epidural (CSE) anesthesia in 90% of women during elective cesarean delivery (CD). Methods: Eighty women undergoing elective CD were randomly allocated into either a prophylactic group or a rescue group in this dose finding study. If the women’s systolic blood pressure (SBP) was maintained above 80% of their baseline, the next patient had an 8/9th chance of receiving the same dose or a 1/9th chance of receiving a lower dose. If the patient’s SBP was not maintained, a higher dose was used for next patient. The primary outcome was the successful use of the norepinephrine bolus dose to maintain SBP above 80% of the baseline until after delivery. Secondary outcomes included nausea, vomiting, breathlessness, dizziness, hypertension, bradycardia due to hypotension and supplemental use of atropine and norepinephrine, upper sensory level of anesthesia, umbilical vein (UV) blood gases, and 1- and 5-minute Apgar scores. The 90% effective dose (ED90) and 95% confidence interval (95% CI) were estimated using isotonic regression methods. Results: The estimated ED90 of the norepinephrine prophylactic bolus was 10.85 µg (95% CI, 9.20–11.67 µg) and that of the norepinephrine rescue bolus was 12.3 µg (95% CI, 10.0–12.8 µg) using isotonic regression methods. Conclusions: For norepinephrine, either a prophylactic bolus dose of 11 µg or a rescue bolus dose of 12 µg was recommended for clinical practices.