A randomised double-blind dose–response study of weight-adjusted infusions of norepinephrine for preventing hypotension during combined spinal–epidural anaesthesia for Caesarean delivery

Abstract

Background: Norepinephrine infusion has been suggested as an effective method for preventing hypotension during spinal anaesthesia for Caesarean delivery. However, optimal dosing regimens for norepinephrine have not been well established. This study aimed to determine the doseeresponse characteristics of a weight-adjusted fixed-rate infusion of norepinephrine to prevent hypotension during neuraxial anaesthesia for Caesarean delivery. Methods: In a double-blind, randomised controlled trial, 80 parturients having elective Caesarean delivery received a prophylactic norepinephrine infusion at 0.025 mg kg À1 min À1 (Group N1), 0.05 mg kg À1 min À1 (Group N2), 0.075 mg kg À1 min À1 (Group N3), or 0.10 mg kg À1 min À1 (Group N4), starting immediately after induction of combined spinaleepidural anaesthesia.The primary outcome was non-occurrence of hypotension, defined as a decrease in systolic arterial pressure !20% below baseline value or to 90 mm Hg, before delivery. Values for 50% effective dose (ED 50 ) and ED 90 were calculated using probit regression. Results: The incidence of hypotension was 11/20 (55%), 6/20 (30%), 2/20 (10%), and 1/20 (5%) in Groups N1, N2, N3, and N4, respectively (P<0.0001). The ED 50 and ED 90 (95% confidence interval) of norepinephrine infusions for preventing hypotension were 0.029 (e0.002 to 0.043) and 0.080 (0.065e0.116) mg kg À1 min À1 , respectively. The incidence of reactive hypertension increased with increasing norepinephrine dose (P¼0.002). Other adverse effects were similar among groups.Conclusions: Under the conditions of this study, an infusion of norepinephrine 0.08 mg kg À1 min À1 was effective for preventing hypotension in 90% of patients. This information should provide a guide for initiating norepinephrine infusions. Clinical trial registration: ChiCTR1900022322 at the Chinese Clinical Trial Registry (http://www.chictr.org.cn/enindex.aspx).

Prophylactic norepinephrine infusion for postspinal anesthesia hypotension in patients undergoing cesarean section: A randomized, controlled, dose‐finding trial

“…The ED50, ED85, and ED95 values for a prophylactic dose of norepinephrine were 0.029 (95% CI 0.008–0.042), 0.068 (95% CI 0.055–0.099), and 0.105 (95% CI 0.082–0.172) µg/kg/min, respectively. A loading bolus of 6 μg norepinephrine was given before norepinephrine infusion, and only bupivacaine was administrated for spinal anesthesia in our study; however, we found similar results, though different prophylactic doses were employed by Wei et al 13 The prophylactic doses of norepinephrine employed in our study was in accordance with Hasanin et al 7 and Fu et al 12 Significantly, the work reported by Hasanin et al 7 provided us a good foundation without exploring the ED50 and ED90 values. In addition, we further explored the overall stability of SBP control versus baseline, including MDPE and MDAPE.…”

“…In clinical practice, norepinephrine has proven efficacy and safety as a prophylactic vasopressor drug infusion for obstetric anesthesia. Adverse outcomes, such as reactive hypertension and bradycardia, have a low probability of occurrence 12,13 . Onwochei et al 8 carried out a sequential allocation dose‐finding study and demonstrated that the ED90 of intermittent boluses of norepinephrine to prevent postspinal anesthesia hypotension was 5.8 μg (95% CI: 5.01–6.59).…”

“…In our study, the ED50 and ED90 values for a prophylactic dose of norepinephrine were 0.016 (95% CI: −0.014 to 0.033) and 0.088 (95% CI: 0.068-0.133) µg/kg/min, respectively. Fu et al12 compared four weight-adjusted doses (0.025, 0.05, 0.075, and 0.1 µg/kg/min) of norepinephrine for preventing hypotension during combined spinal-epidural anesthesia for cesarean delivery without a NS control group. After 10 mg of ropivacaine spinal anesthesia, the incidence of postspinal anesthesia hypotension was 55%, 30%, 10%, and 5%, respectively.…”

Comparison of two Norepinephrine rescue bolus for Management of Post-spinal Hypotension during Cesarean Delivery: a randomized controlled trial

“…Kg − 1 .min − 1 [12] and 0.08 mcg. Kg − 1 .min − 1 [18]); however, these studies were not available when we started our study.…”

Comparison of Hemodynamic Responses to Administration of Vasopressin and Norepinephrine Under General Anesthesia: A Systematic Review and Meta-analysis of Randomized Controlled Trials with Trial Sequential Analysis

“…3,4 Norepinephrine has been used to treat intraoperative hypotension, and its use has been studied extensively. [5][6][7] Norepinephrine regulates blood pressure and heart rate via activation of aand b-adrenergic receptors. However, norepinephrine has well-known side effects, such as increased myocardial oxygen consumption and arrhythmias, which may ultimately worsen prognosis despite positive hemodynamic effects.…”