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      Does an Earlier or Late Intravenous Injection of Ondansetron Affect the Dose of Phenylephrine Needed to Prevent Spinal-Anesthesia Induced Hypotension in Cesarean Sections?

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          Abstract

          Background

          There was controversy about ondansetron can reduce the incidence of spinal-induced hypotension and decrease the consumption of vasopressor in cesarean delivery with spinal anesthesia. We hypothesized that different timing of ondansetron administration may contribute to the controversy. Therefore, we aimed to determine the effect of different timing of ondansetron administration on the dose requirement of preventing phenylephrine via comparing the ED 50 of prophylactic phenylephrine.

          Methods

          Seventy-five parturients were finally enrolled in this prospective, randomized, double-blinded dose finding study. Ondansetron or placebo was administered 5 min or 15 min before intrathecal injection. Up-down allocation method was used to determine the dose of prophylactic phenylephrine for each parturient in the three groups. The initial infusion rate of first patient was 0.5 µg/kg/min. Then, the rate for next patient was varied with increasing or decreasing of 0.05 μg/kg/min according to the response of the previous patient. An effective dose was defined as no hypotension occurred during the study period. An ineffective dose was defined as hypotension occurred during the study period. Study period in this study is from intrathecal injection to neonatal delivery. ED 50 of phenylephrine infusion was calculated by probit regression.

          Results

          The ED 50 of intravenous phenylephrine calculated by probit analysis was 0.33 (95% CI 0.20 to 0.38) µg/kg/min and 0.36 (95% CI 0.32 to 0.38) µg/kg/min in group A and B, and 0.41 (95% CI 0.37 to 0.44) µg/kg/min in group C for patients undergoing cesarean delivery with combined spinal-epidural anesthesia.

          Conclusion

          An earlier administration of 4 mg prophylactic ondansetron contributed no benefits for lowing the dose of prophylactic phenylephrine compared to a late administration, but can decrease the dose of preventing phenylephrine in patients undergoing cesarean delivery with combined spinal-epidural anesthesia. This finding may be useful for clinical practice and further studies.

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          Most cited references 18

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          Advances in and limitations of up-and-down methodology: a précis of clinical use, study design, and dose estimation in anesthesia research.

          Sequential design methods for binary response variables exist for determination of the concentration or dose associated with the 50% point along the dose-response curve; the up-and-down method of Dixon and Mood is now commonly used in anesthesia research. There have been important developments in statistical methods that (1) allow the design of experiments for the measurement of the response at any point (quantile) along the dose-response curve, (2) demonstrate the risk of certain statistical methods commonly used in literature reports, (3) allow the estimation of the concentration or dose-the target dose-associated with the chosen quantile without the assumption of the symmetry of the tolerance distribution, and (4) set bounds on the probability of response at this target dose. This article details these developments, briefly surveys current use of the up-and-down method in anesthesia research, reanalyzes published reports using the up-and-down method for the study of the epidural relief of pain during labor, and discusses appropriate inferences from up-and-down method studies.
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            International consensus statement on the management of hypotension with vasopressors during caesarean section under spinal anaesthesia

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              Staircase bioassay: The up-and-down method

               W.J. Dixon (1991)
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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                DDDT
                dddt
                Drug Design, Development and Therapy
                Dove
                1177-8881
                16 July 2020
                2020
                : 14
                : 2789-2795
                Affiliations
                [1 ]Department of Anesthesia, Jiaxing University Affiliated Women and Children Hospital , Jiaxing, People’s Republic of China
                [2 ]Department of Obstetrics, Jiaxing University Affiliated Women and Children Hospital , Jiaxing, People’s Republic of China
                Author notes
                Correspondence: Xiufeng Zheng Department of Obstetrics, Jiaxing University Affiliated Women and Children Hospital , Jiaxing, People’s Republic of ChinaTel +86573-83963131 Email zxffybjy@163.com
                Fei Xiao Department of Anesthesia, Jiaxing University Affiliated Women and Children Hospital , Jiaxing, People’s Republic of ChinaTel +86573-83963131 Email 13706597501@163.com
                Article
                257880
                10.2147/DDDT.S257880
                7371998
                © 2020 Qian et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                Page count
                Figures: 3, Tables: 2, References: 19, Pages: 7
                Categories
                Original Research

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