Prospective, randomised, double-blind, dose-finding study of norepinephrine for preventing spinal-induced hypotension during caesarean delivery under combined spinal–epidural anaesthesia

BACKGROUND: During caesarean delivery under spinal anaesthesia hypotension may be managed by norepinephrine in preference to phenylephrine due a perception of less bradycardia and fewer reductions in cardiac output. OBJECTIVE: As the optimum prophylactic dose of norepinephrine is unclear, we aimed to investigate its dose-response for preventing postspinal hypotension in caesarean delivery. DESIGN: A randomised, double-blinded, dose-finding study. SETTING: Jiaxing University affiliated Women and Children Hospital, Jiaxing, China. PATIENTS: Ninety-nine patients undergoing elective caesarean delivery from 1 February to 5 August: excluding patients with ASA III or above, preeclampsia or hypertension, pre-existing or gestational diabetes, BMI more than 35 kg m, height less than 150 cm or with more than 175 cm, or with contraindications to local anaesthesia. INTERVENTIONS: Patients received 0, 0.04, 0.05, 0.06 or 0.07 mug kg min preventive norepinephrine infusions immediately after intrathecal injection of 10 mg bupivacaine with 5 mug sufentanil. MAIN OUTCOME MEASURES: The norepinephrine (Median effective dose) or (95% effective dose) ED50 and ED95, which were estimated using Probit analysis to compare haemodynamic changes associated with the different doses. RESULTS: The incidence of hypotension was 70, 47.4, 40, 20 and 15% in the 0, 0.04, 0.05, 0.06 and 0.07 mug kg min groups, respectively. The ED50, ED80 and ED95 values were 0.029 (95% CI 0.008 to 0.042 mug kg min), 0.068 (95% CI 0.055 to 0.099 mug kg min) and 0.105 mug kg min (95% CI 0.082 to 0.172 mug kg min), respectively. Apgar scores or umbilical arterial pH were similar among groups. CONCLUSION: The ED50, ED80 and ED95 were 0.029, 0.068 and 0.105 mug kg min respectively. A 0.07 mug kg min norepinephrine infusion may be optimum for preventing postspinal hypotension after intrathecal injection of 10 mg bupivacaine combined with 5 mug sufentanil. TRIAL REGISTRATION: Chinese Clinical Trial Registry (identifier: ChiCTR-TRC-1800014614).