The Efficacy and Safety of Norepinephrine and Its Feasibility as a Replacement for Phenylephrine to Manage Maternal Hypotension during Elective Cesarean Delivery under Spinal Anesthesia

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

Abstract

Maternal hypotension commonly occurs during spinal anesthesia for cesarean delivery, with a decrease of systemic vascular resistance recognized as a significant contributor. Accordingly, counteracting this effect with a vasopressor that constricts arterial vessels is appropriate, and the pure α-adrenergic receptor agonist phenylephrine is the current gold standard for treatment. However, phenylephrine is associated with dose-dependent reflex bradycardia and decreased cardiac output, which can endanger the mother and fetus in certain circumstances. In recent years, the older, traditional vasopressor norepinephrine has attracted increasing attention owing to its mild β-adrenergic effects in addition to its α-adrenergic effects. We search available literature for papers directly related to norepinephrine application in spinal anesthesia for elective cesarean delivery. Nine reports were found for norepinephrine use either alone or compared to phenylephrine. Results show that norepinephrine efficacy in rescuing maternal hypotension is similar to that of phenylephrine without obvious maternal or neonatal adverse outcomes, and with a lower incidence of bradycardia and greater cardiac output. In addition, either computer-controlled closed loop feedback infusion or manually-controlled variable-rate infusion of norepinephrine provides more precise blood pressure management than equipotent phenylephrine infusion or norepinephrine bolus. Thus, based on the limited available literature, norepinephrine appears to be a promising alternative to phenylephrine; however, before routine application begins, more favorable high-quality studies are warranted.

Figures

Figure 1
Figure 1
Flowchart of studies included. Footnote: The excluded two articles that neither editorial nor review are as follows: Selim MF. Norepinephrine versus ephedrine to maintain arterial blood pressure during spinal anesthesia for cesarean delivery: a prospective double-blinded trial. Anesthesia, essays, and researches 2018; 12: 92-97. Ngan Kee WD. Norepinephrine for maintaining blood pressure during spinal anaesthesia for caesarean section: a 12-month review of individual use. Int J Obstet Anesth 2017; 30: 73-74.

References

    1. Carvalho B., Dyer R. A. Norepinephrine for spinal hypotension during cesarean delivery: Another paradigm shift? Anesthesiology. 2015;122(4):728–730. doi: 10.1097/ALN.0000000000000602.
    1. Hasanin A. M., Amin S. M., Agiza N. A., et al. Norepinephrine infusion for preventing postspinal anesthesia hypotension during cesarean delivery: a randomized dose-finding trial. Anesthesiology. 2018 doi: 10.1097/ALN.0000000000002483.
    1. Ngan Kee W. D., Lee S. W. Y., Ng F. F., et al. Prophylactic norepinephrine infusion for preventing hypotension during spinal anesthesia for cesarean delivery. Anesthesia & Analgesia. 2018;126:1989–1994.
    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 Research International. 2018;2018:8. doi: 10.1155/2018/2708175.2708175
    1. Onwochei D. N., Ngan Kee W. D., Fung L., Downey K., Ye X. Y., Carvalho J. C. A. Norepinephrine intermittent intravenous boluses to prevent hypotension during spinal anesthesia for cesarean delivery: A sequential allocation dose-finding study. Anesthesia & Analgesia. 2017;125(1):212–218. doi: 10.1213/ANE.0000000000001846.
    1. Kee W. D. N. A random-allocation graded dose-response study of norepinephrine and phenylephrine for treating hypotension during spinal anesthesia for cesarean delivery. Anesthesiology. 2017;127(6):934–941. doi: 10.1097/ALN.0000000000001880.
    1. Vallejo M. C. An open-label randomized controlled clinical trial for comparison of continuous phenylephrine versus norepinephrine infusion in prevention of spinal hypotension during cesarean delivery. International Journal of Obstetric Anesthesia. 2017;29:18–25. doi: 10.1016/j.ijoa.2016.08.005.
    1. Ngan Kee W. D., Khaw K. S., Tam Y.-H., Ng F. F., Lee S. W. 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. Journal of Clinical Monitoring and Computing. 2017;31(3):617–623. doi: 10.1007/s10877-016-9883-z.
    1. Ngan Kee W. D., Lee S. W. Y., Ng F. F., Tan P. E., Khaw K. S. Randomized double-blinded comparison of norepinephrine and phenylephrine for maintenance of blood pressure during spinal anesthesia for cesarean delivery. Anesthesiology. 2015;122(4):736–745. doi: 10.1097/ALN.0000000000000601.
    1. Sharkey A. M., Siddiqui N., Downey K., Ye X. Y., Guevara J., Carvalho J. C. Comparison of intermittent intravenous boluses of phenylephrine and norepinephrine to prevent and treat spinal-induced hypotension in cesarean deliveries. Anesthesia & Analgesia. 2018 doi: 10.1213/ANE.0000000000003704.
    1. Benedict C. R., Fillenz M., Stanford C. Changes in plasma noradrenaline concentration as a measure of release rate. British Journal of Pharmacology. 1978;64(2):305–309. doi: 10.1111/j.1476-5381.1978.tb17305.x.
    1. Allen T. K., Muir H. A., George R. B., Habib A. S. A survey of the management of spinal-induced hypotension for scheduled cesarean delivery. International Journal of Obstetric Anesthesia. 2009;18(4):356–361. doi: 10.1016/j.ijoa.2009.03.014.
    1. Smiley R. M. More perfect? International Journal of Obstetric Anesthesia. 2017;29:1–4. doi: 10.1016/j.ijoa.2017.01.002.
    1. Lecoq J.-P. H., Brichant J.-F., Lamy M. L., Joris J. L. Norepinephrine and ephedrine do not counteract the increase in cutaneous microcirculation induced by spinal anaesthesia. British Journal of Anaesthesia. 2010;105(2):214–219. doi: 10.1093/bja/aeq145.
    1. , Levophed - FDA prescirbing information, side effects and uses. ; Accesses on April 2016.
    1. Marx G. F. Supine hypotension syndrome during cesarean section. Journal of the American Medical Association. 1969;207(10):1903–1905. doi: 10.1001/jama.1969.03150230117018.
    1. Holmes F. Spinal analgesia and caesarean section; maternal mortality. The Journal of Obstetrics and Gynaecology of the British Empire. 1957;64:229–232.
    1. Payne C., Wiffen P. J., Martin S. Interventions for fatigue and weight loss in adults with advanced progressive illness. Cochrane Database of Systematic Reviews. 2012;8 doi: 10.1002/14651858.CD008427
    1. Della Rocca G., Di Marco P., Beretta L., De Gaudio A. R., Ori C., Mastronardi R. Do we need to use sugammadex at the end of a general anesthesia to reverse the action of neuromuscular bloking agents? Position paper on sugammadex use. Minerva Anestesiologica. 2013;79(6):661–666.
    1. Sharwood-Smith G., Drummond G. B. Hypotension in obstetric spinal anaesthesia: A lesson from pre-eclampsia. British Journal of Anaesthesia. 2009;102(3):291–294. doi: 10.1093/bja/aep003.
    1. Langesæter E., Rosseland L. A., Stubhaug A. Continuous invasive blood pressure and cardiac output monitoring during cesarean delivery: A randomized, double-blind comparison of low-dose versus high-dose spinal anesthesia with intravenous phenylephrine or placebo infusion. Anesthesiology. 2008;109(5):856–863. doi: 10.1097/ALN.0b013e31818a401f.
    1. Dyer R. A., Reed A. R., Van Dyk D., et al. Hemodynamic effects of ephedrine, phenylephrine, and the coadministration of phenylephrine with oxytocin during spinal anesthesia for elective cesarean delivery. Anesthesiology. 2009;111(4):753–765. doi: 10.1097/ALN.0b013e3181b437e0.
    1. Ngan Kee W. D., Lau T. K., Khaw K. S., Lee B. B. Comparison of metaraminol and ephedrine infusions for maintaining arterial pressure during spinal anesthesia for elective cesarean section. Anesthesiology. 2001;95(2):307–313. doi: 10.1097/00000542-200108000-00009.
    1. Nag D. S., Samaddar D. P., Chatterjee A., et al. Vasopressors in obstetric anesthesia: a current perspective. World Journal of Clinical Cases. 2015;3:58–64.
    1. Veeser M., Hofmann T., Roth R., Klöhr S., Rossaint R., Heesen M. Vasopressors for the management of hypotension after spinal anesthesia for elective caesarean section. Systematic review and cumulative meta-analysis. Acta Anaesthesiologica Scandinavica. 2012;56(7):810–816. doi: 10.1111/j.1399-6576.2011.02646.x.
    1. Lee A., Ngan Kee W. D., 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. Anesthesia & Analgesia. 2002;94(4):920–926. doi: 10.1097/00000539-200204000-00028.
    1. Habib A. S. A review of the impact of phenylephrine administration on maternal hemodynamics and maternal and neonatal outcomes in women undergoing cesarean delivery under spinal anesthesia. Anesthesia & Analgesia. 2012;114(2):377–390. doi: 10.1213/ane.0b013e3182373a3e.
    1. Stewart A., Fernando R., McDonald S., Hignett R., Jones T., Columb M. The dose-dependent effects of phenylephrine for elective cesarean delivery under spinal anesthesia. Anesthesia & Analgesia. 2010;111(5):1230–1237. doi: 10.1213/ANE.0b013e3181f2eae1.
    1. Thiele R. H., Nemergut E. C., Lynch C., III The physiologic implications of isolated alpha1 adrenergic stimulation. Anesthesia & Analgesia. 2011;113(2):284–296. doi: 10.1213/ANE.0b013e3182124c0e.
    1. Johnson J. O. The autonomic nervous system. In: Miller R. D., editor. Miller’s Anesthesia. Phiadelphia, PA, USA: Elsevier; 2015. pp. 346–386.
    1. Stowe D. F., Ebert T. J. Sympathomimetic and sympatholytic drugs. In: Evers A., Maze M., Karasch E., editors. Anesthetic Pharmacology. Cambridge University Press; 2011. pp. 648–665.
    1. Mets B. Should norepinephrine, rather than phenylephrine, be considered the primary vasopressor in anesthetic practice? Anesthesia & Analgesia. 2016;122(5):1707–1714. doi: 10.1213/ANE.0000000000001239.
    1. Ngan Kee W. D., Khaw K. S., Tan P. E., Ng F. F., Karmakar M. K. Placental transfer and fetal metabolic effects of phenylephrine and ephedrine during spinal anesthesia for cesarean delivery. Anesthesiology. 2009;111(3):506–512. doi: 10.1097/aln.0b013e3181b160a3.
    1. Sodha R. J., Proegler M., Schneider H. Transfer and metabolism of norepinephrine studied from maternal-to-fetal and fetal-to-maternal sides in the in vitro perfused human placental lobe. American Journal of Obstetrics & Gynecology. 1984;148(4):474–481. doi: 10.1016/0002-9378(84)90729-4.
    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. Obstetric Anesthesia Digest. 2018;73:71–92. doi: 10.1097/01.aoa.0000547270.12467.06.

Source: PubMed

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