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

Shiqin Xu, Xiaofeng Shen, Shijiang Liu, Jianjun Yang, Xian Wang, Shiqin Xu, Xiaofeng Shen, Shijiang Liu, Jianjun Yang, Xian Wang

Abstract

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.

Conflict of interest statement

The authors declare there is no conflicts of interest regarding the publication of this paper.

Figures

Figure 1
Figure 1
PRISM flowchart of studies enrollment.
Figure 2
Figure 2
Risk of bias summary, presented as percentages across all included trials.
Figure 3
Figure 3
Forest plots and effect sizes of maternal outcomes across all included trials for incidence of hypotension (A), hypertension (B), bradycardia (C), and intraoperative nausea and vomiting (IONV) (D). IONV = intraoperative nausea and vomiting.
Figure 4
Figure 4
Forest plots and effect sizes of neonatal outcomes, including incidence of Apgar 2 (D), PCO2 (E), and base excess (F).
Figure 5
Figure 5
Begg's funnel-plot assessment of publication bias in trials that examined incidence of hypotension (A), hypertension (B), bradycardia (D), and intraoperative nausea and vomiting (IONV) (D). IONV = intraoperative nausea and vomiting.

References

    1. Kinsella S, Carvalho B, Dyer R, et al. International consensus statement on the management of hypotension with vasopressors during caesarean section under spinal anaesthesia. Anaesthesia 2018;73:71–92.
    1. Lee A, Ngan Kee WD, Gin T. A quantitative, systematic review of randomized controlled trials of ephedrine versus phenylephrine for the management of hypotension during spinal anesthesia for cesarean delivery. Anesth Analg 2002;94:920–6.
    1. Habib AS. A review of the impact of phenylephrine administration on maternal hemodynamics and maternal and neonatal outcomes in women undergoing cesarean delivery under spinal anesthesia. Anesth Analg 2012;114:377–90.
    1. Thiele RH, Nemergut EC, Lynch C., 3rd The physiologic implications of isolated alpha(1) adrenergic stimulation. Anesth Analg 2011;113:284–96.
    1. Stewart A, Fernando R, McDonald S, et al. The dose-dependent effects of phenylephrine for elective cesarean delivery under spinal anesthesia. Anesth Analg 2010;111:1230–7.
    1. Chen D, Qi X, Huang X, et al. Efficacy and safety of different norepinephrine regimens for prevention of spinal hypotension in cesarean section: a randomized trial. Biomed Res Int 2018;2018:2708175.
    1. Ngan Kee WD. A random-allocation graded dose-response study of norepinephrine and phenylephrine for treating hypotension during spinal anesthesia for cesarean delivery. Anesthesiology 2017;127:934–41.
    1. Onwochei DN, Ngan Kee WD, Fung L, et al. Norepinephrine intermittent intravenous boluses to prevent hypotension during spinal anesthesia for cesarean delivery: a sequential allocation dose-finding study. Anesth Analg 2017;125:212–8.
    1. Ngan Kee WD, Lee SW, Ng FF, et al. Randomized double-blinded comparison of norepinephrine and phenylephrine for maintenance of blood pressure during spinal anesthesia for cesarean delivery. Anesthesiology 2015;122:736–45.
    1. Higgins JPT, Green S. (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from .
    1. Meader N, King K, Llewellyn A, et al. A checklist designed to aid consistency and reproducibility of GRADE assessments: development and pilot validation. Syst Rev 2014;3:82.
    1. Hozo SP, Djulbegovic B, Hozo I. Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol 2005;5:13.
    1. Vallejo M, Attaallah A, Elzamzamy O, et al. An open-label randomized controlled clinical trial for comparison of continuous phenylephrine versus norepinephrine infusion in prevention of spinal hypotension during cesarean delivery. Int J Obstet Anesth 2017;29:18–25.
    1. Ngan Kee WD, Khaw KS, Tam YH, et al. Performance of a closed-loop feedback computer-controlled infusion system for maintaining blood pressure during spinal anaesthesia for caesarean section: a randomized controlled comparison of norepinephrine versus phenylephrine. J Clin Monit Comput 2017;31:617–23.
    1. Sharkey AM, Siddiqui N, Downey K, et al. Comparison of intermittent intravenous boluses of phenylephrine and norepinephrine to prevent and treat spinal-induced hypotension in cesarean deliveries: randomized controlled trial. Anesth Analg 2018.
    1. Smiley RM. More perfect? Int J Obstet Anesth 2017;29:1–4.
    1. Sharwood-Smith G, Drummond GB. Hypotension in obstetric spinal anaesthesia: a lesson from pre-eclampsia. Br J Anaesth 2009;102:291–4.
    1. Benedict C, Fillenz M, Stanford C. Changes in plasma noradrenaline concentration as a measure of release rate. Br J Pharmacol 1978;64:305–9.
    1. Carvalho B, Dyer RA. Norepinephrine for spinal hypotension during cesarean delivery: another paradigm shift? Anesthesiology 2015;122:728–30.
    1. Ngan Kee WD, Lee SWY, Ng FF, et al. Prophylactic norepinephrine infusion for preventing hypotension during spinal anesthesia for cesarean delivery. Anesth Analg 2018;126:1989–94.
    1. Lecoq JP, Brichant JF, Lamy ML, et al. Norepinephrine and ephedrine do not counteract the increase in cutaneous microcirculation induced by spinal anaesthesia. Br J Anaesth 2010;105:214–9.
    1. Drugs., com. Levophed—FDA prescribing information, side effects and uses. Available at: ; Accesses on April 26, 2016.

Source: PubMed

スポンサーと協力者

医学的状態

薬物療法

3
購読する