title: A randomised double-blind trial of phenylephrine and metaraminol infusions for prevention of hypotension during spinal and combined spinal-epidural anaesthesia for elective caesarean section.
abstract: Prophylactic vasopressor administration is commonly recommended to reduce maternal hypotension during spinal anaesthesia for caesarean section. Metaraminol has undergone limited investigation in obstetric anaesthesia for this purpose, particularly in comparison with phenylephrine. In this multicentre, randomised, double-blind, non-inferiority study, we compared prophylactic phenylephrine or metaraminol infusions, started immediately after spinal anaesthesia, in 185 women who underwent elective caesarean section. Phenylephrine was initially infused at 50 μg.min-1, and metaraminol at 250 μg.min-1. The primary outcome was the difference in umbilical arterial pH between groups; secondary outcomes included other neonatal acid-base measures, and maternal haemodynamic changes. The mean (SD) umbilical arterial pH was 7.28 (0.06) in the phenylephrine group vs. 7.31 (0.04) in the metaraminol group (p = 0.0002). The estimated mean (95%CI) pH difference of 0.03 (0.01-0.04) was above the pre-determined lower boundary of clinical non-inferiority, and also met the criterion for superiority. Umbilical artery lactate concentration was 2.8 (1.2) mmol.l-1in the phenylephrine group vs. 2.3 (0.7) mmol.l-1in the metaraminol group (p = 0.0018). Apgar scores did not significantly differ between groups. There was a higher incidence of hypotension, defined as systolic arterial pressure < 90% baseline, in the phenylephrine group; there was a higher incidence of hypertension and severe hypertension (systolic arterial pressure > 110% and > 120% baseline, respectively) in the metaraminol group. There was no significant difference between groups in the incidence of nausea, vomiting or maternal bradycardia. We conclude that, when used as an infusion to prevent hypotension after spinal anaesthesia for elective caesarean section, metaraminol is at least non-inferior to phenylephrine with respect to neonatal acid-base outcomes.
authors.affiliation: School of Medicine and Pharmacology, The University of Western Australia, Perth, Australia.|School of Women's and Infants Health, The University of Western Australia, Perth, Australia.
authors.forename: N J
authors.initials: NJ
authors.lastname: McDonnell
authors.affiliation: School of Medicine and Pharmacology, The University of Western Australia, Perth, Australia.
authors.forename: M J
authors.initials: MJ
authors.lastname: Paech
authors.affiliation: St Michael's Hospital, Bristol, UK.
authors.forename: N A
authors.initials: NA
authors.lastname: Muchatuta
authors.affiliation: Rockingham General Hospital, Rockingham, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Hillyard
authors.affiliation: Biostatistics and Research Design Unit, Women and Infants Research Foundation, Perth, Australia.
authors.forename: E A
authors.initials: EA
authors.lastname: Nathan
mesh_terms: D000136:Acid-Base Equilibrium; D000328:Adult; D000767:Anesthesia, Epidural / Q000009:adverse effects*; D000773:Anesthesia, Obstetrical / Q000009:adverse effects*; D000775:Anesthesia, Spinal / Q000009:adverse effects*; D002585:Cesarean Section / Q000379:methods*; D004311:Double-Blind Method; D017558:Elective Surgical Procedures; D005260:Female; D006801:Humans; D007022:Hypotension / Q000517:prevention & control*; D007231:Infant, Newborn; D007262:Infusions, Intravenous; D019344:Lactic Acid / Q000097:blood; D008680:Metaraminol / Q000008:administration & dosage; D010656:Phenylephrine / Q000008:administration & dosage / Q000627:therapeutic use*; D020250:Postoperative Nausea and Vomiting / Q000453:epidemiology; D011247:Pregnancy; D016896:Treatment Outcome; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D019344:Lactic Acid; D008680:Metaraminol
keywords: cardiovascular effects; fetal blood gas values; neuraxial anaesthesia; spinal hypotension; treatment; uterine blood flow determinants