Comparative Dose–Response Study on the Infusion of Norepinephrine Combined with Crystalloid Coload versus Colloid Coload for Preventing Hypotension During Spinal Anesthesia for Cesarean Delivery

Background: Although the optimal infusion dose of norepinephrine combined with crystalloid coload for preventing spinal anesthesia-induced hypotension (SAIH) for cesarean delivery has been established, the infusion regimen of norepinephrine combined with colloid coload has not been fully quantifed. The objective of this study was to compare and determine the median effective dose ([ED.sub.50]) and 90% effective dose ([ED.sub.90]) of norepinephrine infusion combined with crystalloid coload versus colloid coload for preventing SAIH during cesarean delivery. Methods: Two hundred parturients were randomly assigned to receive norepinephrine infusion at 0.02, 0.04, 0.06, 0.08, or 0.10 [micro]g/kg/min in combination with 10 mL/kg crystalloid coload or colloid coload to prevent SAIH. The study period was defined as the interval from the commencement of intrathecal injection to delivery of the neonate. The primary outcome was non-occurrence of hypotension, defined as systolic blood pressure (SBP) less than 80% of the baseline before delivery. The [ED.sub.50] and [ED.sub.90] of norepinephrine infusion dose were determined using probit regression analysis. By calculating the 95% confidence intervals (CIs) of relative median potency to determine whether the prophylactic infusion of norepinephrine requirement was different between the two groups. Results: The derived [ED.sub.50] and [ED.sub.90] of norepinephrine infusion combined with crystalloid coload were 0.030 (95% CIs 0.020 to 0.038) and 0.097 (95% CIs 0.072 to 0.157) [micro]g/kg/min, respectively. The [ED.sub.50] and [ED.sub.90] of norepinephrine infusion combined with colloid coload were 0.021 (95% CIs 0.013 to 0.029) and 0.070 (95% CIs 0.053 to 0.107) [micro]g/kg/min, respectively. The estimate of relative median potency for norepinephrine between the two groups was 1.37 (95% CIs 0.94 to 2.23). Conclusion: Under the conditions of this study, 10 mL/kg colloid coload reduced the dose of prophylactic norepinephrine infusion by approximately 30% in parturients during spinal anesthesia for cesarean delivery compared with the crystalloid coload. Keywords: norepinephrine, hypotension, the dose-response relationship, crystalloid, colloid, [ED.sub.50], [ED.sub.90]