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

February 18, 2021 updated by: Rajesh Deshar
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Intravenous glycopyrrolate has been investigated for its effect on haemodynamic changes after spinal anesthesia for caesarean delivery. Results from previous studies are conflicting as glycopyrrolate has shown to reduce, increase or had no effect on incidence of maternal hypotension and/or vasopressor requirement after spinal anaesthesia. A recent meta-analysis found that prophylactic glycopyrrolate does not prevent the incidence of spinal-induced hypotension; however, it reduces the total vasopressor requirement during elective caesarean delivery under spinal anaesthesia. Therefore, the aim of this study is to find out whether the use of glycopyrrolate decreases the amount of vasopressors required to manage hypotension induced by spinal anaesthesia in non-elective CS.

Methodology:

After approval from Institutional Review committee of B.P. Koirala Institute of Health Sciences, the trial will be registered at clinical trial.gov. Parturient planned for non-elective caesarian of ASA PS grade II fulfilling the inclusion criteria will be informed about the study and written consent will be obtained either in labour room or in obstetric emergency ward. The eligible patients will be randomly assigned to Glycopyrrolate (GP group) or normal saline (NS group). The study will be conducted in accordance with the ethical principles of the 1964 Declaration of Helsinki. Before patient is shifted to the operating room (OR), ranitidine 50 mg and metoclopramide 10 mg will be administered intravenously via 18 G cannula. In the operating table, patients will be laid supine with a wedge placed in the right hip. Standard anaesthesia monitoring including 3-lead electrocardiography, heart rate (HR), noninvasive blood pressure (NIBP) and pulse oximetry (Sp02) will be done. A mean value of three measurements of systolic blood pressure (SBP) and HR will be recorded as baseline parameters. Patency of the vein will be maintained with the infusion of Ringer's lactate solution at a minimal rate.

Before the patient is placed in sitting position for SA,she will receive the study drug according to the randomization. After free flow of CSF is observed, 0.5 % hyperbaric bupivacaine (2.2 ml) with 10 µg fentanyl will be injected intrathecally over 30 s using a 25-gauge Quinke needle at the L3-4 or L4-L5 interspace. Patients will then be immediately placed in supine while maintaining 15 degree left lateral tilt. Co-loading of 1000 ml ringers lactate solution will be initiated at the start of spinal anaesthesia using a pressure bag and it will be completed within 10 min. Immediately after the spinal injection, phenylephrine infusion will be initiated at a rate of 25 µg/min and it will be titrated to maintain maternal SBP within 20 % of baseline.

The sensory level of anaesthesia will be checked using loss of cold sensation. Surgery will be allowed once the bilateral sensory block height at T6 is achieved. Oxygen at 40% will be administered via nasal cannula at 2-4 L/min until delivery.

Hemodynamic parameters will be recorded at following time intervals: baseline, after the study drug in given IV, immediately after spinal anaesthesia, every minute for first 10 min, and then at 2.5 min until end of surgery. Post-spinal hypotension will be defined as SBP < 80% of baseline reading or SBP < 100 mmHg before delivery of baby. Post-delivery hypotension is defined as SBP < 80% of baseline reading or SBP < 100 mmHg after delivery of the baby. It will be treated with phenylephrine 100 µg bolus and rapid infusion of Ringer's lactate 200 ml. Infusion of phenylephrine will be stopped if bradycardia (HR< 55/min) occurs without hypotension. If bradycardia (HR< 55/min) is associated with hypotension, IV ephedrine 6 mg will be administered. If these measures fail and bradycardia is still persistent then an IV atropine 0.5 mg will be given. If reactive hypertension (defined as SBP > 120% of baseline reading) occurs, the infusion of phenylephrine will be stopped and restarted only when the SBP reaches the target range (SBP is within 120% of baseline SBP). The amount of ephedrine used will be converted to phenylephrine equivalent based on potency of phenylephrine to ephedrine as 81:1 ratio.(31)

After delivery of the baby, 2 U of oxytocin will be administered IV over 5-10 sec followed by an infusion of 10 U/hr (oxytocin 20 U in 500 ml of Hartmann's solution). Phenylephrine infusion will be gradually tapered after delivery of the baby keeping the SBP within the target level. The total amount of intraoperative IV fluids administered and estimated blood loss will be measured. Intraoperative use of other uterotonic agent or blood transfusion will be recorded. The attending pediatrician will assess neonatal Apgar scores at 1 and 5 minutes after delivery.

Patients will be asked to report the occurrence of intraoperative nausea and rate its severity using an 11-point verbal rating scale (0=no nausea, 10=worst possible nausea). Intraoperative nausea or vomiting (IONV) will be treated with ondansetron 4 mg IV. After 5 min, if nausea and vomiting is still persisted, IV dexamethasone 4 mg will be administered. IONV incidence and its time of occurrence from intrathecal injection (whether associated with hypotension) and antiemetic needed will be recorded. Incidence of intraoperative pruritus, shivering, dizziness and dry mouth will also be recorded. Grading of intraoperative shivering is as follows: 0 no shivering, 1 one or more of the following: piloerection, peripheral vasoconstriction, peripheral cyanosis without other cause, but without visible muscular activity; 2 visible muscular activity confined to one muscle group; 3 visible muscular activity in more than one muscle group; and 4 gross muscular activity involving the whole body. If the shivering score is ≥3, IV meperidine 20 mg will be given.

The primary outcome will be the total amount of phenylephrine used to maintain blood pressure intraoperatively. The secondary outcome measures will include incidence of maternal hypotension, reactive hypertension, bradycardia, other side-effects (IONV, shivering, pruritus, dry mouth,dizziness), changes in maternal SBP and heart rate and neonatal outcome (Apgar scores at 1 min and 5 min, requirement of neonatal resuscitation, need for neonatal ICU admission and neonatal death within 30 days).

Data collection:

Baseline data (gestational age, uterine incision to delivery time, hemodynamic parameters) and outcome parameters will be collected in the paper case record form and entered in windows Microsoft excel spreadsheet for analysis.

Study Type

Interventional

Enrollment (Actual)

258

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Nepal
    • Province 1
      • Dharān Bāzār, Province 1, Nepal, 56700
        • B.P.Koirala Institute of Health Sciences

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 40 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

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

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Experimental Group (GP)
Patients will receive 0.2 mg (1 ml) glycopyrrolate before phenylephrine infusion is initiated at 25mcg/min.
Drug: Glycopyrrolate 0.2 MG/ML
In this group, the patients will receive glycopyrrolate 0.2 mg in 1 ml
Other Names:
  • Glycopyrronium bromide
Placebo Comparator: Placebo Group(NS)
patients will receive 1 ml normal saline (0.9%) before phenylephrine infusion is initiated at 25 mcg/min
Drug: Normal saline
In this group, the patients will receive 1 ml of 0.9% normal saline
Other Names:
  • 0.9% NS

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Total vasopressors requirement intraoperatively
Time Frame: immediately after spinal anaesthesia till the end of the surgery
Total vasopressors required to prevent hypotension during the period of surgery
immediately after spinal anaesthesia till the end of the surgery

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The incidence of hypotension
Time Frame: after spinal anaesthesia till the end of the surgery
Hypotension is defined as systolic blood pressure < 80% of baseline reading or systolic blood pressure < 100 mmHg
after spinal anaesthesia till the end of the surgery
The incidence of reactive hypertension
Time Frame: after spinal anaesthesia till the end of the surgery
defined as systolic blood pressure > 120% of baseline reading
after spinal anaesthesia till the end of the surgery
The incidence of maternal bradycardia
Time Frame: after spinal anaesthesia till the end of the surgery
heart rate < 55/min
after spinal anaesthesia till the end of the surgery
The incidence of maternal tachycardia
Time Frame: after spinal anaesthesia till the end of the surgery
Heart rate > 100/min
after spinal anaesthesia till the end of the surgery
The incidence of nausea
Time Frame: after spinal anaesthesia till the end of the surgery
Patients will be asked to report the occurrence of intraoperative nausea and rate its severity using an 11-point verbal rating scale (0=no nausea, 10=worst possible nausea).
after spinal anaesthesia till the end of the surgery
The incidence of vomiting
Time Frame: after spinal anaesthesia till the end of the surgery
incidence of vomiting
after spinal anaesthesia till the end of the surgery
The incidence of shivering
Time Frame: after spinal anaesthesia till the end of the surgery
Shivering will be graded as: 0 no shivering, 1 one or more of the following: piloerection, peripheral vasoconstriction, peripheral cyanosis without other cause, but without visible muscular activity; 2 visible muscular activity confined to one muscle group; 3 visible muscular activity in more than one muscle group; and 4 gross muscular activity involving the whole body
after spinal anaesthesia till the end of the surgery
The incidence of dry mouth, intraoperative pruritus and dizziness
Time Frame: after spinal anaesthesia till the end of the surgery
incidence of dry mouth, intraoperative pruritus and dizziness
after spinal anaesthesia till the end of the surgery
Maternal heart rate and
Time Frame: after spinal anaesthesia till the end of the surgery
to record the heart rate of the patient during surgery
after spinal anaesthesia till the end of the surgery
Maternal systolic blood pressure
Time Frame: after spinal anaesthesia till the end of the surgery
to record systolic blood pressure of the patient during surgery
after spinal anaesthesia till the end of the surgery

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
The APGAR outcome of baby
Time Frame: at 1 and 5 min after delivery
APGAR score comprises of 5 criteria : a) Appearance b) Pulse Rate c) Reflex d)Muscle tone e) Respiratory Effort with each criteria of score 0,1 or 2; making total score of 10. Score 7-10 is reassuring, 4-6 moderately normal, 0-3 is low and cause for immediate resuscitative efforts
at 1 and 5 min after delivery
Need for neonatal resuscitation
Time Frame: immediately after delivery
resuscitation needed for baby
immediately after delivery
Admission to neonatal ICU (NICU)
Time Frame: after delivery
the need for ICU admission
after delivery
Neonatal death
Time Frame: within 30 days of delivery
if there is neonatal death or not
within 30 days of delivery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Rajesh Deshar

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 1, 2020

Primary Completion (Actual)

January 31, 2021

Study Completion (Actual)

January 31, 2021

Study Registration Dates

First Submitted

May 20, 2020

First Submitted That Met QC Criteria

May 20, 2020

First Posted (Actual)

May 26, 2020

Study Record Updates

Last Update Posted (Actual)

February 21, 2021

Last Update Submitted That Met QC Criteria

February 18, 2021

Last Verified

February 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRC/1603/019

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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