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      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

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          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.

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            Randomized double-blinded comparison of norepinephrine and phenylephrine for maintenance of blood pressure during spinal anesthesia for cesarean delivery.

            During spinal anesthesia for cesarean delivery, phenylephrine can cause reflexive decreases in maternal heart rate and cardiac output. Norepinephrine has weak β-adrenergic receptor agonist activity in addition to potent α-adrenergic receptor activity and therefore may be suitable for maintaining blood pressure with less negative effects on heart rate and cardiac output compared with phenylephrine.
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              The dose-dependent effects of phenylephrine for elective cesarean delivery under spinal anesthesia.

              Hypotension is the most common serious side effect of spinal anesthesia for cesarean delivery. There has been a move recently toward the use of phenylephrine as a vasopressor infusion to improve maternal cardiovascular stability and fetal outcome. Although it seems safe in the elective setting, there have been concerns about its propensity for causing an increase in afterload and a baroreceptor-mediated bradycardia in the mother, with a consequent reduction in maternal cardiac output (CO). Using a noninvasive measure of CO, our aim was to investigate whether there were any dose-dependent effects of phenylephrine on maternal cardiovascular stability and, if so, any impact on fetal outcome. In this randomized, double-blind study, 75 women scheduled for elective cesarean delivery were allocated to receive a phenylephrine infusion at 25 μg/min, 50 μg/min, or 100 μg/min. This infusion was titrated to maintain maternal baseline systolic blood pressure (SBP), from induction of spinal anesthesia until delivery. The maternal cardiovascular variables recorded included heart rate (HR) and SBP. A suprasternal Doppler monitor measured CO and stroke volume, as well as measures of venous return (corrected flow time) and contractility, at baseline, and then every 5 minutes for 20 minutes after initiation of spinal anesthesia. Apgar scores and umbilical cord blood gases were recorded. SBP control was satisfactory in all groups; however, the group receiving phenylephrine 100 μg/min required significantly higher doses to achieve arterial blood pressure control compared with the lower infusion rates. There were no significant differences in the number of times SBP decreased below 80% of baseline, or the numbers of boluses of ephedrine or phenylephrine required to maintain SBP above 80% of baseline. There were significant time and dose-dependent reductions in HR and CO with phenylephrine, such that HR and CO were seen to decrease with time in each group, and also with increasing concentrations of phenylephrine. Stroke volume remained stable throughout. Apgar scores and umbilical cord blood gases were similar among groups. By infusing a higher concentration (100 μg/min), we subject the mother and fetus to a much higher dose of phenylephrine, with significant effects on maternal HR and CO (up to a 20% reduction). Future investigation is required to determine whether this reduction in maternal CO has detrimental effects when providing anesthesia for an emergency cesarean delivery for a compromised fetus.
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                Author and article information

                Contributors
                Journal
                Biomed Res Int
                Biomed Res Int
                BMRI
                BioMed Research International
                Hindawi
                2314-6133
                2314-6141
                2018
                31 December 2018
                : 2018
                : 1869189
                Affiliations
                1Department of Anesthesiology, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, China
                2Department of Anesthesiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
                3Nanjing Medical University, Nanjing, China
                Author notes

                Academic Editor: Kazunori Uemura

                Author information
                http://orcid.org/0000-0003-3922-9358
                http://orcid.org/0000-0002-6957-7137
                http://orcid.org/0000-0002-3833-575X
                Article
                10.1155/2018/1869189
                6330831
                de84a49f-b80c-4003-a702-d1e952851665
                Copyright © 2018 Xian Wang et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 19 September 2018
                : 17 November 2018
                : 4 December 2018
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                Review Article

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