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Created May 31, 2020, last updated almost 4 years ago.
Collection: 124, Score: 1157, Trend score: 0, Read count: 1506, Articles count: 10, Created: 2020-05-31 01:34:09 UTC. Updated: 2021-02-07 07:09:10 UTC.Notes
Although there is some evidence of different efficacy among commonly used vasopressors, translating this to clinically-significant outcome differences is still uncertain.
Singh's 2020 Bayesian network meta-analysis is the most comprehensive study to date investigating this issue. The researchers concluded that norepinephrine, metaraminol, and mephentermine showed the lowest probability of adverse neonatal acid-base effects, and ephedrine showed the greatest.
Previously phenylephrine infusion has been the consensus recommendation.
Nonetheless, other than ephedrine which should not be a first-choice pressor during Caesarean section, there is not enough evidence to strongly recommend one pressor over another. Clinical familiarity and institutional availability are probably the most important factors when choosing a vasopressor.
Daniel Jolley
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Collected Articles
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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.
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Recommendations from the guidelines:
- Hypotension following spinal or combined spinal-epidural anaesthesia at caesarean section causes both maternal and fetal/neonatal adverse effects.
- Hypotension is frequent – vasopressors should be used routinely and preferably prophylactically.
- α‐agonist drugs are the most appropriate agents to treat or prevent hypotension following spinal anaesthesia. Although those with a small amount of β‐agonist activity may have the best profile (noradrenaline (norepinephrine), metaraminol), phenylephrine is currently recommended due to the amount of supporting data. Single‐dilution techniques, and/or prefilled syringes should be considered.
- Left lateral uterine displacement and intravenous (i.v.) colloid pre‐loading or crystalloid coloading, should be used in addition to vasopressors.
- The aim should be to maintain systolic arterial pressure (SAP) at ≥ 90% of an accurate baseline obtained before spinal anaesthesia, and avoid a decrease to < 80% baseline. We recommend a variable rate prophylactic infusion of phenylephrine using a syringe pump. This should be started at 25–50 μg.min−1 immediately after the intrathecal local anaesthetic injection, and titrated to blood pressure and pulse rate. Top‐up boluses may be required.
- Maternal heart rate can be used as a surrogate for cardiac output if the latter is not being monitored; both tachycardia and bradycardia should be avoided.
- When using an α‐agonist as the first‐line vasopressor, small doses of ephedrine are suitable to manage SAP < 90% of baseline combined with a low heart rate. For bradycardia with hypotension, an anticholinergic drug (glycopyrronium (glycopyrrolate) or atropine) may be required. Adrenaline (epinephrine) should be used for circulatory collapse.
- The use of smart pumps and double (two drug) vasopressor infusions can lead to greater cardiovascular stability than that achieved with physician‐controlled infusions.
- Women with pre‐eclampsia develop less hypotension after spinal anaesthesia than healthy women. Abrupt decreases in blood pressure are undesirable because of the potential for decreased uteroplacental blood flow. A prophylactic vasopressor infusion may not be required but, if used, should be started at a lower rate than for healthy women.
- Women with cardiac disease should be assessed on an individual basis; some conditions are best managed with phenylephrine (an arterial constrictor without positive inotropic effect), whereas others respond best to ephedrine (producing positive inotropic and chronotropic effect).
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Review Meta Analysis
Prevention of hypotension after spinal anaesthesia for caesarean section: a systematic review and network meta-analysis of randomised controlled trials.
Why is this review important?
Although the importance of managing spinal anaesthesia-associated hypotension during caesarean section is well appreciated, there continues to be some debate over relative efficacy of interventions, whether vasopressors or fluid-loading.
Fitzgerald at al.'s review and network meta-analysis quantitatively compares a complete range of interventions across 109 studies.
What did they show?
Vasopressors were more effective at preventing intra-operative hypotension than fluid infusion techniques alone. Although there was no statistically significant difference in the incidence of hypotension among metaraminol, phenylephrine or noradrenaline/norepinephrine, metaraminol appeared the most effective (OR 0.04-0.26) and ephedrine the least (0.09-0.85). [vs Norepinephrine (OR 0.06-0.28), Phenylephrine (OR 0.11-0.29)]
Similarly, nausea and vomiting incidence was lower with vasopressors than other interventions. Phenylephrine more commonly caused bradycardia than other pressors, and ephedrine more commonly tachycardia. There was no significant difference in reactive hypertension.
The bottom-line...
The most effective way of preventing and managing maternal intraoperative hypotension is, as international guidelines already assert, alpha-agonist vasopressors. Using more complex protocols, such as phenylephrine or norepinephrine infusions, does not appear to offer benefit over metaraminol. Fluid infusions are at best a secondary intervention.
summary -
Int J Obstet Anesth · Feb 2019
Meta Analysis Comparative StudyEphedrine versus phenylephrine as a vasopressor for spinal anaesthesia-induced hypotension in parturients undergoing high-risk caesarean section: meta-analysis, meta-regression and trial sequential analysis.
Phenylephrine is the preferred vasopressor for the prevention and treatment of spinal anaesthesia-induced hypotension during caesarean section, because studies on low-risk elective patients found it to have a less detrimental effect on umbilical artery pH compared with ephedrine. However, limited data exist from high-risk parturients and parturients with uteroplacental insufficiency. ⋯ Despite several studies and a large number of patients there was insufficient evidence to make a recommendation for choice of vasopressor in high-risk caesarean section. Trials with adequate power to detect differences in the incidence of fetal acidosis between ephedrine and phenylephrine are required to provide evidence-based guidance.
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Int J Obstet Anesth · Aug 2019
Meta AnalysisMetaraminol use during spinal anaesthesia for caesarean section: a meta-analysis of randomised controlled trials.
Metaraminol is likely superior to ephedrine for managing hypotension due to spinal anaesthesia for Caesarean section, and non-inferior to phenylephrine.
pearl -
Cochrane Db Syst Rev · Oct 2006
ReviewTechniques for preventing hypotension during spinal anaesthesia for caesarean section.
No intervention has yet been shown to completely avoid maternal hypotension due to spinal anaesthesia for Caesarean section.
pearl -
Acta Anaesthesiol Scand · Aug 2012
Review Meta AnalysisVasopressors for the management of hypotension after spinal anesthesia for elective caesarean section. Systematic review and cumulative meta-analysis.
Phenylephrine use has been recommended over ephedrine for the management of hypotension after spinal anesthesia for elective caesarean section. The evidence for this is rather limited because in previous trials, pH was significantly lower after ephedrine, but absolute values were still within normal range. We pooled the available data to define maternal and neonatal effects of the two vasopressors. ⋯ Our analysis could clearly demonstrate a decreased risk of fetal acidosis associated with phenylephrine use. In addition with our findings for BE, this suggests a favorable effect of phenylephrine on fetal outcome parameters. The mechanism of pH depression is not related to pCO(2) .
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Cochrane Db Syst Rev · Aug 2017
ReviewTechniques for preventing hypotension during spinal anaesthesia for caesarean section.
No intervention has yet been shown to completely avoid maternal hypotension due to spinal anaesthesia for Caesarean section.
pearl -
Current evidence is too limited to conclude any significant difference between phenylephrine and noradrenaline for managing CS hypotension due to spinal anaesthesia.
pearl
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