Effect of Glycopyrrolate on Vasopressors Requirement for Non-elective Caesarean Section Under Spinal Anaesthesia

NCT04401345 | Completed Phase 4

• 1 other identifier: IRC/1603/019
• Study Type: interventional
• Target: 258
• Locations: 1 country
• Sites: 1

Brief Summary

This is prospective randomised double blind study conducted in parturients planned for non-elective caesarean section under spinal anaesthesia. Glycopyrrolate group will receive 0.2 mg of Glycopyrrolate before start of phenylephrine infusion. Control group will receive 0.2 ml of Normal Saline before start of phenylephrine infusion. Total amount of vasopressors required i.e. ephedrine or phenylephrine will recorded in the form of phenylephrine equivalent during intraoperative period.

Conditions

Glycopyrrolate; Post-spinal Hypotension; Effect of Drug; Hemodynamic Instability

Keywords

caesarean section; hypotension; spinal anaesthesia; glycopyrrolate; post-spinal anaesthesia; vasopressors; non-elective caesarean section

Outcome Measures

Primary Outcomes (1)

• Total vasopressors requirement intraoperatively

  Total vasopressors required to prevent hypotension during the period of surgery

  immediately after spinal anaesthesia till the end of the surgery

Secondary Outcomes (10)

• The incidence of hypotension

  after spinal anaesthesia till the end of the surgery

• The incidence of reactive hypertension

  after spinal anaesthesia till the end of the surgery

• The incidence of maternal bradycardia

  after spinal anaesthesia till the end of the surgery

• The incidence of maternal tachycardia

  after spinal anaesthesia till the end of the surgery

• The incidence of nausea

  after spinal anaesthesia till the end of the surgery

Other Outcomes (4)

• The APGAR outcome of baby

  at 1 and 5 min after delivery

• Need for neonatal resuscitation

  immediately after delivery

• Admission to neonatal ICU (NICU)

  after delivery

Study Arms (2)

Experimental Group (GP)

EXPERIMENTAL

Patients will receive 0.2 mg (1 ml) glycopyrrolate before phenylephrine infusion is initiated at 25mcg/min.

Drug: Glycopyrrolate 0.2 MG/ML

Placebo Group(NS)

PLACEBO COMPARATOR

patients will receive 1 ml normal saline (0.9%) before phenylephrine infusion is initiated at 25 mcg/min

Drug: Normal saline

Interventions

Glycopyrrolate 0.2 MG/ML DRUG

In this group, the patients will receive glycopyrrolate 0.2 mg in 1 ml

Also known as: Glycopyrronium bromide

Experimental Group (GP)

Normal saline DRUG

In this group, the patients will receive 1 ml of 0.9% normal saline

Also known as: 0.9% NS

Placebo Group(NS)

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age between 18-40 years
• All parturients at term (gestational weeks ≥ 37)
• ASA (American society of Anaesthesiologist) PS (Physical status) grade II

You may not qualify if:

• Age \>40 year
• ASA PS Grade \>2
• Maternal bradycardia (baseline HR\< 60/min) or tachycardia (baseline HR\> 100/min)
• Pregnancy induced hypertension
• Gestational hypertension
• Known fetal abnormalities
• Intrauterine growth retardation (IUGR)
• Intrauterine fetal death (IUFD)
• Contraindications to spinal anaesthesia
• Contraindications to glycopyrrolate
• Multiple pregnancy
• BMI: \> 30 kg/m2
• Height: \<150cm

Sponsors & Collaborators

• Rajesh Deshar: lead

Study Sites (1)

B.P.Koirala Institute of Health Sciences

Dharān, Koshi, 56700, Nepal

Location

Related Publications (32)

• 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 Jul;9(3):156-9. doi: 10.1054/ijoa.1999.0376.

  PMID: 15321086 BACKGROUND

• 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 Jan;96(1):95-9. doi: 10.1093/bja/aei265. Epub 2005 Nov 25.

  PMID: 16311286 BACKGROUND

• Somboonviboon W, Kyokong O, Charuluxananan S, Narasethakamol A. Incidence and risk factors of hypotension and bradycardia after spinal anesthesia for cesarean section. J Med Assoc Thai. 2008 Feb;91(2):181-7.

  PMID: 18389982 RESULT

• Dyer RA, Biccard BM. Ephedrine for spinal hypotension during elective caesarean section: the final nail in the coffin? Acta Anaesthesiol Scand. 2012 Aug;56(7):807-9. doi: 10.1111/j.1399-6576.2012.02719.x. No abstract available.

  PMID: 22780437 RESULT

• Kinsella SM, Tuckey JP. Perioperative bradycardia and asystole: relationship to vasovagal syncope and the Bezold-Jarisch reflex. Br J Anaesth. 2001 Jun;86(6):859-68. doi: 10.1093/bja/86.6.859.

  PMID: 11573596 RESULT

• Dobson PM, Caldicott LD, Gerrish SP, Cole JR, Channer KS. Changes in haemodynamic variables during transurethral resection of the prostate: comparison of general and spinal anaesthesia. Br J Anaesth. 1994 Mar;72(3):267-71. doi: 10.1093/bja/72.3.267.

  PMID: 8130043 RESULT

• Ali S, Athar M, Ahmed SM. Basics of CPB. Indian J Anaesth. 2019;49:257-62.

  RESULT

• Lee AJ, Landau R. Aortocaval Compression Syndrome: Time to Revisit Certain Dogmas. Anesth Analg. 2017 Dec;125(6):1975-1985. doi: 10.1213/ANE.0000000000002313.

  PMID: 28759487 RESULT

• Dick WF. Anaesthesia for caesarean section (epidural and general): effects on the neonate. Eur J Obstet Gynecol Reprod Biol. 1995 May;59 Suppl:S61-7. doi: 10.1016/0028-2243(95)02075-4.

  PMID: 7556827 RESULT

• Kuhn JC, Hauge TH, Rosseland LA, Dahl V, Langesaeter E. Hemodynamics of Phenylephrine Infusion Versus Lower Extremity Compression During Spinal Anesthesia for Cesarean Delivery: A Randomized, Double-Blind, Placebo-Controlled Study. Anesth Analg. 2016 Apr;122(4):1120-9. doi: 10.1213/ANE.0000000000001174.

  PMID: 26991619 RESULT

• Cyna AM, Andrew M, Emmett RS, Middleton P, Simmons SW. Techniques for preventing hypotension during spinal anaesthesia for caesarean section. Cochrane Database Syst Rev. 2006 Oct 18;(4):CD002251. doi: 10.1002/14651858.CD002251.pub2.

  PMID: 17054153 RESULT

• Lee AJ, Landau R, Mattingly JL, Meenan MM, Corradini B, Wang S, Goodman SR, Smiley RM. Left Lateral Table Tilt for Elective Cesarean Delivery under Spinal Anesthesia Has No Effect on Neonatal Acid-Base Status: A Randomized Controlled Trial. Anesthesiology. 2017 Aug;127(2):241-249. doi: 10.1097/ALN.0000000000001737.

  PMID: 28598894 RESULT

• Ripolles Melchor J, Espinosa A, Martinez Hurtado E, Casans Frances R, Navarro Perez R, Abad Gurumeta A, Calvo Vecino JM. Colloids versus crystalloids in the prevention of hypotension induced by spinal anesthesia in elective cesarean section. A systematic review and meta-analysis. Minerva Anestesiol. 2015 Sep;81(9):1019-30. Epub 2014 Dec 11.

  PMID: 25501602 RESULT

• Mercier FJ. Cesarean delivery fluid management. Curr Opin Anaesthesiol. 2012 Jun;25(3):286-91. doi: 10.1097/ACO.0b013e3283530dab.

  PMID: 22459983 RESULT

• Banerjee A, Stocche RM, Angle P, Halpern SH. Preload or coload for spinal anesthesia for elective Cesarean delivery: a meta-analysis. Can J Anaesth. 2010 Jan;57(1):24-31. doi: 10.1007/s12630-009-9206-7. Epub 2009 Oct 27.

  PMID: 19859776 RESULT

• Sharwood-Smith G, Drummond GB. Hypotension in obstetric spinal anaesthesia: a lesson from pre-eclampsia. Br J Anaesth. 2009 Mar;102(3):291-4. doi: 10.1093/bja/aep003. No abstract available.

  PMID: 19218369 RESULT

• Hwang J, Min S, Kim C, Gil N, Kim E, Huh J. Prophylactic glycopyrrolate reduces hypotensive responses in elderly patients during spinal anesthesia: a randomized controlled trial. Can J Anaesth. 2014 Jan;61(1):32-8. doi: 10.1007/s12630-013-0064-y. Epub 2013 Dec 18.

  PMID: 24347351 RESULT

• McDonnell NJ, Paech MJ, Muchatuta NA, Hillyard S, Nathan EA. A randomised double-blind trial of phenylephrine and metaraminol infusions for prevention of hypotension during spinal and combined spinal-epidural anaesthesia for elective caesarean section. Anaesthesia. 2017 May;72(5):609-617. doi: 10.1111/anae.13836. Epub 2017 Mar 3.

  PMID: 28255987 RESULT

• Cardoso MM, Yamaguchi ET, Amaro AR, Mezzetti R, Torres MA. Fetal and maternal effects of bolus of phenylephrine or metaraminol during spinal anesthesia for cesarean delivery. Anesthesiology. 2005;102:A31--A31.

  RESULT

• Abboud TK, Read J, Miller F, Chen T, Valle R, Henriksen EH. Use of glycopyrrolate in the parturient: effect on the maternal and fetal heart and uterine activity. Obstet Gynecol. 1981 Feb;57(2):224-7.

  PMID: 7465128 RESULT

• Ali-Melkkila T, Kaila T, Kanto J, Iisalo E. Pharmacokinetics of glycopyrronium in parturients. Anaesthesia. 1990 Aug;45(8):634-7. doi: 10.1111/j.1365-2044.1990.tb14385.x.

  PMID: 2400072 RESULT

• Mirakhur RK, Dundee JW. Glycopyrrolate: pharmacology and clinical use. Anaesthesia. 1983 Dec;38(12):1195-204. doi: 10.1111/j.1365-2044.1983.tb12525.x.

  PMID: 6660460 RESULT

• 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 Feb;82(2):277-9. doi: 10.1093/bja/82.2.277.

  PMID: 10365009 RESULT

• Quiney 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. 2000;9:156-9.

  RESULT

• Chamchad D, Horrow JC, Nakhamchik L, Sauter J, Roberts N, Aronzon B, Gerson A, Medved M. 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 Aug;23(5):361-6. doi: 10.1016/j.jclinane.2010.12.008. Epub 2011 May 31.

  PMID: 21632228 RESULT

• 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 Jan;62(1):35-9. doi: 10.4097/kjae.2012.62.1.35. Epub 2012 Jan 25.

  PMID: 22323952 RESULT

• 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 Feb;126(2):552-558. doi: 10.1213/ANE.0000000000002274.

  PMID: 28704246 RESULT

• 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 Nov;111(5):1221-9. doi: 10.1213/ANE.0b013e3181e1db21. Epub 2010 May 21.

  PMID: 20495139 RESULT

• Wang X, Mao M, Liu S, Xu S, Yang J. A Comparative Study of Bolus Norepinephrine, Phenylephrine, and Ephedrine for the Treatment of Maternal Hypotension in Parturients with Preeclampsia During Cesarean Delivery Under Spinal Anesthesia. Med Sci Monit. 2019 Feb 9;25:1093-1101. doi: 10.12659/MSM.914143.

  PMID: 30738019 RESULT

• Chabicovsky M, Winkler S, Soeberdt M, Kilic A, Masur C, Abels C. Pharmacology, toxicology and clinical safety of glycopyrrolate. Toxicol Appl Pharmacol. 2019 May 1;370:154-169. doi: 10.1016/j.taap.2019.03.016. Epub 2019 Mar 21.

  PMID: 30905688 RESULT

• Bruntion L (ed), Chabner B (ed), Knollman B (ed). Goodman & Gilman's The Pharmacological Basis of Therapeutics. 12th ed. New York: The McGraw Hill Companies; 2011.

  RESULT

• Deshar R, Subedi A, Pokharel K, Sah BP, Prasad JN. Effect of glycopyrrolate on vasopressor requirements for non-elective cesarean section under spinal anesthesia: a randomized, double-blind, placebo-controlled trial. BMC Anesthesiol. 2022 Oct 25;22(1):327. doi: 10.1186/s12871-022-01882-4.

  PMID: 36284288 DERIVED

MeSH Terms

Conditions

Hypotension

Interventions

Glycopyrrolate; Saline Solution

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Quaternary Ammonium Compounds; Amines; Organic Chemicals; Onium Compounds; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Glycopyrrolate and normal saline will be administered as 1 ml clear fluid, and therefore, both patient and investigator will be blinded to the randomization and intervention.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Experimental Group (GP): In the experimental group patients will receive 0.2 mg (1 ml) glycopyrrolate before phenylephrine infusion is initiated. Placebo Group (NS): In the placebo group patients will receive 1 ml normal saline (0.9%) before phenylephrine infusion is initiated.

Study Record Dates

• First Submitted: May 20, 2020
• First Posted: May 26, 2020
• Study Start: June 1, 2020
• Primary Completion: January 31, 2021
• Study Completion: January 31, 2021
• Last Updated: February 21, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

NE (1)