SummaryWe conducted a systematic review to determine the harm and benefit associated with prophylactic phenylephrine for caesarean section under spinal anaesthesia. We included 21 randomised controlled trials with 1504 women. The relative risk (95% CI) of hypotension with phenylephrine infusion -as defined by authors -before delivery was 0.36 (0.18-0.73) vs placebo, p = 0.004; 0.58 (0.39-0.88) vs an ephedrine infusion, p = 0.009; and 0.73 (0.55-0.96) when added to an ephedrine infusion, p = 0.02. After delivery, the relative risks of hypotension and nausea and vomiting with phenylephrine compared with placebo were 0.37 (0.19-0.71), p = 0.003, and 0.39 (0.17-0.91), p = 0.03, respectively. There was no evidence that hypertension, bradycardia or neonatal endpoints were affected. Phenylephrine reduced the risk for hypotension and nausea and vomiting after spinal doses of bupivacaine generally exceeding 8 mg, but there was no evidence that it reduced other maternal or neonatal morbidities. Phenylephrine is the a-agonist recommended to treat hypotension that affects approximately half of caesarean sections under spinal anaesthesia [1,2]. Phenylephrine is associated with a lower rate of fetal acidosis compared with ephedrine [3]. Prophylactic administration of a vasopressor has been recommended [4] and in some institutions it is routine, but it is unclear whether any benefit might be outweighed by harm [5,6]. The aim of this systematic review was to determine the harm and the benefit associated with prophylactic phenylephrine infusion.
MethodsWe searched PubMed, Embase, CINAHL, LILACS, CENTRAL and ISI WOS from inception to February 26th, 2013 (Appendix). We also screened the reference lists of retrieved studies. We included randomised controlled trials (RCTs) of prophylactic phenylephrine vs placebo or other intervention started before, during or after neuraxial blockade. We included any dose or mode of phenylephrine administration, as well as its combination with another vasopressor. Two authors (MH, SS) independently assessed as adequate, unclear or inadequate the risk of bias in the following domains: selection (random sequence generation, allocation concealment); performance (blinding of participant and personnel); detection (blinding of assessor). We excluded studies categorised as at high risk of selection bias and also studies with more than one of the following categor- ised as inadequate: patient blinding; operator blinding; or assessor blinding. We recorded maternal rates of hypotension, hypertension, bradycardia and nausea or vomiting, using the authors' definitions for each, which therefore varied between studies. We also recorded uterine circulatory variables, arterial and venous umbilical pH and base excess, and neonatal Apgar scores. We focused on hypotension before delivery as most cases of hypotension occur in the first 15 min after spinal injection [7], whilst haemodynamic changes after delivery do not directly influence fetal outcome.We calculated pooled estimates for comparisons with two or more RCT...