Effect of glycopyrrolate on vasopressor requirements for non-elective cesarean section under spinal anesthesia: a randomized, double-blind, placebo-controlled trial

Rajesh Deshar, Asish Subedi, Krishna Pokharel, Birendra Prasad Sah, Jagat Narayan Prasad, Rajesh Deshar, Asish Subedi, Krishna Pokharel, Birendra Prasad Sah, Jagat Narayan Prasad

Abstract

Background: The study aimed to investigate whether prophylactic use of glycopyrrolate decreases the vasopressor requirements to prevent hypotension following spinal anesthesia during non-elective cesarean section.

Method: In this double-blind randomized clinical trial, 258 patients undergoing non-elective cesarean section were randomly assigned (1:1) to receive intravenous 0.2 mg glycopyrrolate or normal saline (placebo) before spinal anesthesia. The primary outcome was phenylephrine equivalent needed intraoperatively. Secondary outcomes included incidences of maternal hypotension, reactive hypertension, bradycardia, need for atropine, tachycardia, intraoperative nausea/vomiting, shivering, pruritus, dry mouth, dizziness; neonatal APGAR score at 1 min and 5 min, neonatal resuscitation needed, NICU admission and neonatal death.

Results: Three patients withdrew from the study due to failed spinal anesthesia. 128 patients in the glycopyrrolate group and 127 patients in the placebo group were analyzed. The mean phenylephrine equivalent needed was 1108.96 μg in the glycopyrrolate group and 1103.64 μg in the placebo group (mean difference, 5.32 μg [95% CI - 67.97 to 78.62]; P = 0.88). Hypotension occurred in 38 patients (30%) in the glycopyrrolate group as compared with 49 patients (39%) in the placebo group (P = 0.13). Tachycardia was reported in 70% of the participants in the glycopyrrolate group and 57% of those in the placebo group (P = 0.04). No statistically significant difference was noted in hypotensive episodes > 1, reactive hypertension, bradycardia, need for atropine, nausea, vomiting, shivering, and dry mouth between the two groups. Neonatal outcomes were similar in the two groups.

Conclusion: Prophylactic use of glycopyrrolate does not decrease the requirements of vasopressor to prevent hypotension in non-elective cesarean section under spinal anesthesia.

Trial registration: Registration number: NCT04401345. Date of registration: 26/05/2020. Website: https://clinicaltrials.gov.

Keywords: Cesarean section; Glycopyrrolate; Hypotension; Spinal anesthesia; Vasopressor.

Conflict of interest statement

The authors declare that they have no competing interests.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Patient enrollment, randomization, and analysis
Fig. 2
Fig. 2
Intraoperative mean phenylephrine equivalent consumed in glycopyrrolate and saline group. Error bar indicating 95% confidence interval

References

    1. Klöhr S, Roth R, Hofmann T, Rossaint R, Heesen M. Definitions of hypotension after spinal anaesthesia for caesarean section: literature search and application to parturients. Acta Anaesthesiol Scand. 2010;54:909–921. doi: 10.1111/j.1399-6576.2010.02239.x.
    1. Corke BC, Datta S, Ostheimer GW, Weiss JB, Alper MH. Spinal anaesthesia for caesarean section. The influence of hypotension on neonatal outcome. Anaesthesia. 1982;37:658–662. doi: 10.1111/j.1365-2044.1982.tb01278.x.
    1. Fitzgerald JP, Fedoruk KA, Jadin SM, Carvalho B, Halpern SH. Prevention of hypotension after spinal anaesthesia for caesarean section: a systematic review and network meta-analysis of randomised controlled trials. Anaesthesia. 2020;75:109–121. doi: 10.1111/anae.14841.
    1. Kinsella SM, Carvalho B, Dyer RA, et al. International consensus statement on the management of hypotension with vasopressors during caesarean section under spinal anaesthesia. Anaesthesia. 2018;73:71–92. doi: 10.1111/anae.14080.
    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. Anesth Analg. 2010;111:1230–1237. doi: 10.1213/ANE.0b013e3181f2eae1.
    1. Dyer RA, Reed AR, van Dyk D, Arcache MJ, et al. Hemodynamic effects of ephedrine, phenylephrine, and the coadministration of phen- ylephrine with oxytocin during spinal anesthesia for elective cesarean delivery. Anesthesiology. 2009;111:753–765. doi: 10.1097/ALN.0b013e3181b437e0.
    1. Robson SC, Boys RJ, Rodeck C, Morgan B. Maternal and fetal haemodynamic effects of spinal and extradural anaesthesia for elective caesarean section. Br J Anaesth. 1992;68:54–59. doi: 10.1093/bja/68.1.54.
    1. Ngan Kee WD, Lee SW, Khaw KS, Ng FF. Haemodynamic effects of glycopyrrolate pre-treatment before phenylephrine infusion during spinal anaesthesia for caesarean delivery. Int J Obstet Anesth. 2013;22:179–187. doi: 10.1016/j.ijoa.2013.03.008.
    1. Yoon HJ, Cho HJ, Lee IH, Jee YS, Kim SM. Comparison of hemodynamic changes between phenylephrine and combined phenylephrine and glycopyrrolate groups after spinal anesthesia for cesarean delivery. Korean J Anesthesiol. 2012;62:35–39. doi: 10.4097/kjae.2012.62.1.35.
    1. Ali-Melkkilä T, Kanto J, Iisalo E. Pharmacokinetics and related pharmacodynamics of anticholinergic drugs. Acta Anaesthesiol Scand. 1993;37:633–642. doi: 10.1111/j.1399-6576.1993.tb03780.x.
    1. Ure D, James KS, McNeill M, Booth JV. Glycopyrrolate reduces nausea during spinal anaesthesia for caesarean section without affecting neonatal outcome. Br J Anaesth. 1999;82:277–279. doi: 10.1093/bja/82.2.277.
    1. Yentis SM, Jenkins CS, Lucas DN, Barnes PK. The effect of prophylactic glycopyrrolate on maternal haemodynamics following spinal anaesthesia for elective caesarean section. Int J Obstet Anesth. 2000;9:156–159. doi: 10.1054/ijoa.1999.0376.
    1. Patel SD, Habib AS, Phillips S, Carvalho B, Sultan P. The effect of Glycopyrrolate on the incidence of hypotension and vasopressor requirement during spinal anesthesia for cesarean delivery: a Meta-analysis. Anesth Analg. 2018;126:552–558. doi: 10.1213/ANE.0000000000002274.
    1. Yentis SM, Richards NA. Classification of urgency of caesarean section. Obstet Gynaecol Reprod Med. 2008;18:139–140. doi: 10.1016/j.ogrm.2008.03.005.
    1. Saravanan S, Kocarev M, Wilson RC, Watkins E, Columb MO, Lyons G. Equivalent dose of ephedrine and phenylephrine in the prevention of post-spinal hypotension in caesarean section. Br J Anaesth. 2006;96:95–99. doi: 10.1093/bja/aei265.
    1. Tsai YC, Chu KS. A comparison of tramadol, amitriptyline, and meperidine for postepidural anesthetic shivering in parturients. Anesth Analg. 2001;93:1288–1292. doi: 10.1097/00000539-200111000-00052.
    1. Chamchad D, Horrow JC, Nakhamchik L, Sauter J, Roberts N, Aronzon B, et al. Prophylactic glycopyrrolate prevents bradycardia after spinal anesthesia for cesarean section: a randomized, double-blinded, placebo-controlled prospective trial with heart rate variability correlation. J Clin Anesth. 2011;23:361–366. doi: 10.1016/j.jclinane.2010.12.008.
    1. Mirakhur RK, Dundee JW. Glycopyrrolate: pharmacology and clinical use. Anaesthesia. 1983;38:1195–1204. doi: 10.1111/j.1365-2044.1983.tb12525.x.
    1. Peck T, Hill S, Williams M. Pharmacology for Anaesthesia and Intensive Care. 3. New York: Cambridge University Press; 2008. Sympathomimetics; pp. 197–216.
    1. Allen TK, George RB, White WD, Muir HA, Habib AS. A double-blind, placebo-controlled trial of four fixed rate infusion regimens of phenylephrine for hemodynamic support during spinal anesthesia for cesarean delivery. Anesth Analg. 2010;111:1221–1229. doi: 10.1213/ANE.0b013e3181e1db21.
    1. Quinney NF, Murphy PG. The effect of pretreatment with glycopyrrolate on emetic and hypotensive problems during caesarean section conducted under spinal anaesthesia. Int J Obstet Anesth. 1995;4:66–67. doi: 10.1016/0959-289X(95)82784-8.
    1. Balki M, Carvalho JC. Intraoperative nausea and vomiting during cesarean section under regional anesthesia. Int J Obstet Anesth. 2005;14:230–241. doi: 10.1016/j.ijoa.2004.12.004.

Source: PubMed

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