Prophylactic norepinephrine combined with 6% hydroxyethyl starch (130/0.4) co-load infusion for preventing postspinal anesthesia hypotension during cesarean section: a randomized, controlled, dose-finding trial.

Abstract

Colloid and/or co-load may be more effective than crystalloid for preventing postspinal anesthesia hypotension. We tested five different prophylactic norepinephrine dosages combined with colloid co-load infusion in patients receiving cesarean section and spinal anesthesia. Patients were randomly allocated to receive different prophylactic norepinephrine dosages (0 [NE 0 group], 0.025 [NE 25 group], 0.05 [NE 50 group], 0.075 [NE 75 group], or 0.1 [NE 100 group] µg/kg/min) combined with 500mL 6% hydroxyethyl starch (130/0.4) immediately following spinal anesthesia (n = 35 per group). The primary endpoint was the incidence of postspinal anesthesia hypotension (systolic blood pressure [SBP] < 80% of baseline). Secondary endpoints included severe hypotension, bradycardia, nausea or vomiting, hypertension, SBP stability control versus baseline, the 50% (effective dose, ED50) and 90% (ED90) dose effective for preventing postspinal anesthesia hypotension, Apgar scores, and umbilical cord blood gases. The incidence of postspinal anesthesia hypotension was 48.6%, 31.3%, 17.1%, 14.3%, and 5.7% in the respective groups. As the prophylactic norepinephrine dosage increased, the incidence of postspinal anesthesia hypotension declined (p < 0.001), and SBP remained stable relative to baseline (median performance error [MDPE], p < 0.001; median absolute performance error [MDAPE], p = 0.001). The ED50 and ED90 values were -0.006 (95% CI -0.046-0.013) and 0.081 (95% CI 0.063-0.119) µg/kg/min. Other endpoints were comparable across the groups. An initial prophylactic norepinephrine dosage of 0.05µg/kg/min combined with 500mL 6% hydroxyethyl starch (130/0.4) co-load infusion was optimal for preventing postspinal anesthesia hypotension during cesarean section. NCT05133817, registration date: 12 Nov, 2021.