A randomised dose-response study of prophylactic Methoxamine infusion for preventing spinal-induced hypotension during Cesarean delivery

BACKGROUND: α-receptor agonists have been reported to be safe and effective for treating or preventing spinal-induced hypotension during cesarean delivery. As a pure α(1) adrenergic agonist, methoxamine has potential advantages of reducing myocardial oxygen consumption and protecting the heart in obstetric patients compared to phenylephrine. The aim of this study was to determine the optimal prophylactic methoxamine infusion dose that would be effective for preventing spinal-induced hypotension in 50% (ED(50)) and 95% (ED(95)) of parturients. METHODS: Eighty parturients with a singleton pregnancy scheduled for elective cesarean delivery were randomly allocated to receive prophylactic methoxamine infusion at one of four different fixed-rates: 1 μg/kg/min (group M1), 2 μg/kg/min (group M2), 3 μg/kg/min (group M3), or 4 μg/kg/min (group M4). An adequate response was defined as absence of hypotension (maternal SBP < 80% of baseline or SBP < 90 mmHg). The values for ED(50) and ED(95) of prophylactic methoxamine infusion were determined by probit regression model. The outcomes of maternal hemodynamics and fetal status were compared among the groups. RESULTS: The calculated ED(50) and ED(95) (95% confidence interval) of prophylactic methoxamine infusion dose were 2.178 (95% CI 1.564 to 2.680) μg/kg/min and 4.821 (95% CI 3.951 to 7.017) μg/kg/min, respectively. The incidence of hypotension decreased with increasing methoxamine infusion dose (15/20, 11/20, 7/20 and 2/20 in group M1, M2, M3 and M4 respectively, P < 0.001). 1-min Apgar scores and umbilical arterial PaO2 were lower but umbilical arterial PaCO2 was higher in Group M1. No difference was found in the other incidence of adverse effects and neonatal outcomes among groups. CONCLUSIONS: Under the conditions of this study, when prophylactic methoxamine infusion was given at a fixed-rate based on body weight for preventing spinal-induced hypotension in obstetric patients, the values for ED(50) and ED(95) were 2.178 μg/kg/min and 4.821 μg/kg/min respectively. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR), registry number of clinical trial: ChiCTR-1,800,018,988, date of registration: October 20, 2018.