Norepinephrine or phenylephrine during spinal anaesthesia for Caesarean delivery: a randomised double-blind pragmatic non-inferiority study of neonatal outcome

Abstract

Background: Norepinephrine is an effective vasopressor during spinal anaesthesia for Caesarean delivery. However, before it can be fully recommended, possible adverse effects on neonatal outcome should be excluded. We aimed to test the hypothesis that umbilical arterial cord pH is at least as good (non-inferior) when norepinephrine is used compared with phenylephrine for treatment of hypotension. Methods: We enrolled 668 subjects having elective and non-elective Caesarean delivery under spinal or combined spinaleepidural anaesthesia in this randomised, double-blind, two-arm parallel, non-inferiority clinical trial. Arterial blood pressure was maintained using norepinephrine 6 mg ml À1 or phenylephrine 100 mg ml À1 according to the practice of the anaesthetist, either prophylactically or therapeutically, as an infusion or bolus. The primary outcome was umbilical arterial pH with a chosen non-inferiority margin of 0.01 units. Results: Of 664 subjects (531 elective and 133 non-elective) who completed the study, umbilical arterial cord blood was analysed for 351 samples from 332 subjects in the norepinephrine group and 343 samples from 332 subjects in the phenylephrine group. Umbilical arterial pH was non-inferior in the norepinephrine group (mean, 7.289; 95% confidence interval [CI], 7.284e7.294) compared with the phenylephrine group (mean, 7.287; 95% CI, 7.281e7.292) (mean difference between groups, 0.002; 95% CI, e0.005 to 0.009; P¼0.017). Subgroup analysis confirmed the non-inferiority of norepinephrine for elective cases but was inconclusive for non-elective cases. Conclusions: Norepinephrine was non-inferior to phenylephrine for neonatal outcome assessed by umbilical arterial pH. These results provide high-quality evidence supporting the fetal safety of norepinephrine in obstetric anaesthesia. Clinical trial registration: ChiCTR-IPR-15006235.

A systematic review of phenylephrine vs. noradrenaline for the management of hypotension associated with neuraxial anaesthesia in women undergoing caesarean section

“…. The latter included more than 600 elective and non‐elective caesarean sections, a variety of pathologies including pre‐eclamptic women and healthy women, and allowing for prophylactic or therapeutic vasopressor use; it found no difference in the rate of fetal acidosis between noradrenaline and phenylephrine .…”

“…Table also gives the incidences of fetal acidosis found in studies of pre‐eclamptic women , after therapeutic vasopressor use , and in a pragmatic study by Ngan Kee et al. . The latter included more than 600 elective and non‐elective caesarean sections, a variety of pathologies including pre‐eclamptic women and healthy women, and allowing for prophylactic or therapeutic vasopressor use; it found no difference in the rate of fetal acidosis between noradrenaline and phenylephrine .…”

“…After removal of duplicates, 536 reports were left over from an initial 1096. We identified 14 relevant reports . Three abstracts from recent obstetric anaesthesia meetings (Society for Obstetric Anesthesia and Perinatology 2019, Obstetric Anaesthetists’ Association 2019) and one from the European Society of Regional Anaesthesia meeting 2018 were also included.…”

“…was an abstract that did not give information relevant to all risks of bias. For other abstract publications , we obtained information from the corresponding author. Study details are given in Table .…”

“…Ngan Kee et al. studied elective and non‐elective cases and included all women undergoing caesarean section under spinal or combined spinal‐epidural anaesthesia, including those with pre‐eclampsia, multiple and preterm gestation; this was a pragmatic design, and the anaesthetists were free to use the vasopressor either prophylactically or therapeutically.…”