Why is this important?

Hypotension associated with spinal anaesthesia for Caesarean section is common. Increased interested over the past decade has resulted in some consensus recommending phenylephrine infusions, however there are few studies that directly compare this to other vasopressors.

What did Singh and team do?

By analysing 52 high-to-moderate quality RCTs and over 4,000 patients, Singh performed a Bayesian network meta-analysis to indirectly compare various vasopressors.

It's notable that umbilical artery base excess was used as the primary outcome, although other neonatal and maternal outcomes (nausea, vomiting, bradycardia) were secondarily assessed. Nonetheless, this study prioritised the fetal effects of hypotension management.

"We selected umbilical arterial BE as our primary outcome because it is thought to represent the effect of pronounced fetal hypoxaemia, anaerobic metabolism, and accumulation of non-volatile acids, that is the metabolic component of acidaemia."

Ok, what's a Bayesian network meta-analysis anyway?

A network meta-analysis compares trial interventions indirectly, when researchers are interested in a comparison between two factors (eg. use of metaraminol vs phenylephrine) that have not been directly compared by included RCTs (eg. a study comparing metaraminol vs ephedrine, and a study of phenylepherine vs ephedrine). A Bayesian NMA allows simultaneous comparison of multiple-arm trials, considering prior probability along with the likelihood of outcome rank between interventions.

A Bayesian NMA acknowledges the uncertainty of research conclusions and the probabilistic nature of clinical decision making.

Singh concluded...

Norepinephrine (noradrenaline), metaraminol, and mephentermine showed the lowest likelihood of adverse neonatal acid-base effects, and ephedrine the greatest.

"...norepinephrine, metaraminol, and mephentermine had the lowest probability of adversely affecting the fetal acid-base status as assessed by their effect on umbilical arterial base excess (probability rank order: norepinephrine > mephentermine > metaraminol > phenylephrine > ephedrine)."

When combined, there was a 66% probability that norepinephrine & mephentermine are the best agents for supporting umbilical a. BE.

There was a 66% probability that metaraminol is the best treatment for optimising umbilical artery pH, an 85% combined-probability that metaraminol & norepinephrine are best for umbilical a. pCO₂, and 85% that they are the two best agents for avoiding maternal nausea and vomiting.

Be smart

Given the very nature of meta-analyses and the challenge of indirect comparison among agents from heterogenous studies, the conclusions are only suggestive of the benefits of phenylephrine alternatives. A large RCT is still needed! (And despite it's popularity in some countries, there are still only a small number of trials of metaraminol.)

Nevertheless, other than for bradycardia, ephedrine was most likely the worst for all outcomes, reinforcing past conclusions that there are better pressor choices.

summary

• Preet M Singh, Narinder P Singh, Matthew Reschke, Ngan Kee Warwick D WD Department of Anesthesiology, Sidra Medicine, Doha, Qatar., Arvind Palanisamy, and David T Monks.
• Department of Anesthesiology, Washington University in St. Louis, St. Louis, MO, USA. Electronic address: singh.p@wustl.edu.
• Br J Anaesth. 2020 Mar 1; 124 (3): e95-e107.

BackgroundThe optimal choice of vasopressor drugs for managing hypotension during neuraxial anaesthesia for Caesarean delivery is unclear. Although phenylephrine was recently recommended as a consensus choice, direct comparison of phenylephrine with vasopressors used in other healthcare settings is largely lacking. Therefore, we assessed this indirectly by collating data from relevant studies in this comprehensive network meta-analysis. Here, we provide the possible rank orders for these vasopressor agents in relation to clinically important fetal and maternal outcomes.MethodsRCTs were independently searched in MEDLINE, Web of Science, Embase, The Cochrane Central Register of Controlled Trials, and clinicaltrials.gov (updated January 31, 2019). The primary outcome assessed was umbilical arterial base excess. Secondary fetal outcomes were umbilical arterial pH and Pco2. Maternal outcomes were incidences of nausea, vomiting, and bradycardia.ResultsWe included 52 RCTs with a total of 4126 patients. Our Bayesian network meta-analysis showed the likelihood that norepinephrine, metaraminol, and mephentermine had the lowest probability of adversely affecting the fetal acid-base status as assessed by their effect on umbilical arterial base excess (probability rank order: norepinephrine > mephentermine > metaraminol > phenylephrine > ephedrine). This rank order largely held true for umbilical arterial pH and Pco2. With the exception of maternal bradycardia, ephedrine had the highest probability of being the worst agent for all assessed outcomes. Because of the inherent imprecision when collating direct/indirect comparisons, the rank orders suggested are possibilities rather than absolute ranks.ConclusionOur analysis suggests the possibility that norepinephrine and metaraminol are less likely than phenylephrine to be associated with adverse fetal acid-base status during Caesarean delivery. Our results, therefore, lay the scientific foundation for focused trials to enable direct comparisons between these agents and phenylephrine.Copyright © 2019 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

This article appears in the collection: Which is the best vasopressor to avoid hypotension during spinal anaesthesia for Caesarean section?.

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