Efficacy and safety of norepinephrine versus phenylephrine for the management of maternal hypotension during cesarean delivery with spinal anesthesia: A systematic review and meta-analysis

BACKGROUND: Phenylephrine is the current “gold standard" vasopressor used to treat maternal hypotension in women undergoing cesarean delivery with spinal anesthesia. Since 2015, various studies have explored the use of norepinephrine to manage maternal hypotension. We conducted this systematic review and meta-analysis of available randomized controlled trials (RCTs) to compare the efficacy and safety of norepinephrine and phenylephrine for the prevention and treatment of maternal hypotension. METHODS: A systematic literature search was conducted using electronic databases, including PubMed, MEDLINE, Embase (Embase.com), and the Cochrane CENTRAL register of controlled trials. Parturients underwent cesarean delivery with spinal anesthesia and received norepinephrine to prevent or treat hypotension were considered. Maternal outcomes, including incidences of hypotension, hypertension, bradycardia, intraoperative nausea and vomiting (IONV), maternal cardiac output (CO), and blood pressure (BP) control precision, as well as neonatal Apgar scores and umbilical cord blood analyses, were compared between groups. RESULTS: Three RCTs in 4 reports published between 2015 and 2018 were finally identified with a total of 294 parturients. We found there was no difference in effectiveness between norepinephrine and phenylephrine for the treatment of maternal hypotension (odds ratio [OR] 0.64; 95% confidence interval [CI] 0.37–1.10, P = .11), and there was no difference in the occurrence of hypertension (OR 0.74; 95% CI 0.33–1.62, P = .45). Of note, compared to the phenylephrine group, parturients in the norepinephrine group were less likely to experience bradycardia (OR 0.29; 95% CI 0.12–0.68, P = .005) and IONV (OR 0.54; 95% CI, 0.29–0.99, P = .04). Further, we did not observe a difference between the two vasopressors in the incidence of neonatal Apgar scores < 7 at 1 and 5 minutes or in umbilical vein (UV) blood gas. However, evidence is insufficient to draw conclusions regarding the greater maternal CO and better BP control precision with the use of norepinephrine. CONCLUSION: This systematic review and meta-analysis shows norepinephrine provides similar efficacy to manage maternal hypotension compared to phenylephrine; additionally, showing advantage regarding certain side effects like bradycardia and IONV reduction. Accordingly, norepinephrine is a promising alternative to phenylephrine. However, before routine clinical application, more studies are warranted.