It’s amazing how low you go to get high – John Lennon
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. Anaesthesia
Caesarean section is one of the most common surgical procedures and approximately 80-90% are performed under spinal or CSE. Maternal hypotension is a frequent side-effect that can result in adverse outcomes, and it is therefore recommended practice to use a prophylactic vasopressor to avoid this. Phenylephrine has previously been shown to produce less fetal acidosis than ephedrine, and this paper proposed that the use of a metaraminol infusion (with its alpha and beta effects) would be at least non-inferior to phenylephrine.
The study was a randomized, controlled, double-blind, multi-centre, non-inferiority trial comparing the effects of an infusion of phenylephrine vs an infusion of metaraminol. 188 patients were initially recruited, and after dropouts and incomplete data, 77 and 74 patients were analysed in the phenylephrine and metaraminol groups respectively. All patients recruited were ASA I or II, and elective. They were excluded if there was any history of cardiovascular disease, cerebrovascular disease, diabetes, or pre-eclampsia. The protocol involved a pre-prepared syringe of either 100mcg/ml of phenylephrine or 500mcg/ml of metaraminol and an infusion of 30ml/hr was started following the spinal injection of 2.2-2.5ml of 0.5% bupivicaine (plus 25mcg fentanyl). These infusions were increased if hypotension occurred (<90% baseline) or decreased if hypertension occurred (>110% baseline). The primary outcome was umbilical artery pH, and a non-inferiority difference of <0.03 was agreed upon prior to the study. Secondary outcomes included severe maternal hypotension, nausea, bradycardia, hypertension, and the total dose of vasopressor used.
The mean umblical pH in the phenylephrine group was 7.28 (0.06 SD) and 7.31 (0.04 SD) in the metaraminol group. The lower bound 95% CI was 0.014, which was above the predetermined level of -0.03 pH difference. The analysed groups were similar in term of their characteristics, age, BMI, and height of block. The authors argued that this demonstrated metaraminol to be non-inferior to phenylephrine in the elective LSCS population. In terms of secondary outcomes, there was more hypotension in the phenylephrine group (87%) vs metaraminol (71%) with a p-value of 0.006. Conversely there was more hypertension in the meteraminol group (90% vs 67%, with a p-value of 0.0002). The other secondary outcomes were not statistically significant.
At the doses used in this study, and in the elective low-risk LSCS population, metaraminol is said to be non-inferior to phenylephrine. There is a slightly increased incidence of hypertension with metaraminol and an slightly increased incidence of hypotension in the phenylephrine group. The incidence of both however, was high in both groups.
- There was no explanation about recruitment into the two groups and what happened to the remaining patients who underwent LSCS during the 15 month period.
- As the authors point out, significant questions remain about the equipotency of the two groups. A phenylephrine to metaraminol ratio of 5:1 was used and other studies have used ratios with much more phenylephrine (e.g 15:1)
- The protocol was designed to alter rates of infusion if BP went above or below 10%, arguably a clinically insignificant amount. This may have been over-sensitive and may have partly contributed to the high incidence of hyper and hypotension in both groups.
- The authors did suggest that an advantage of metaraminol would be the reduced risk of drug error as there is only a single dilution rather than multiple.
- Overall our group agreed that this study would not change our practice significantly as some questions remained unanswered
- However, it was thought that in an emergency situation, a metaraminol infusion would be a temporary and quick alternative if phenylephrine wasn’t available
Summary by Dr Stephen Barrett