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

Primary Purpose

Glycopyrrolate, Post-spinal Hypotension, Effect of Drug

Status

Completed

Phase

Phase 4

Locations

Nepal

Study Type

Interventional

Intervention

Glycopyrrolate 0.2 MG/ML

Normal saline

About this trial

This is an interventional prevention trial for Glycopyrrolate focused on measuring caesarean section, hypotension, spinal anaesthesia, glycopyrrolate, post-spinal anaesthesia, vasopressors, non-elective caesarean section

Eligibility Criteria

18 Years - 40 Years (Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

B.P.Koirala Institute of Health Sciences

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Experimental Group (GP)

Placebo Group(NS)

Arm Description

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

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

Outcomes

Primary Outcome Measures

Total vasopressors requirement intraoperatively

Total vasopressors required to prevent hypotension during the period of surgery

Secondary Outcome Measures

The incidence of hypotension

Hypotension is defined as systolic blood pressure < 80% of baseline reading or systolic blood pressure < 100 mmHg

The incidence of reactive hypertension

defined as systolic blood pressure > 120% of baseline reading

The incidence of maternal bradycardia

heart rate < 55/min

The incidence of maternal tachycardia

Heart rate > 100/min

The incidence of nausea

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).

The incidence of vomiting

incidence of vomiting

The incidence of shivering

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

The incidence of dry mouth, intraoperative pruritus and dizziness

incidence of dry mouth, intraoperative pruritus and dizziness

Maternal heart rate and

to record the heart rate of the patient during surgery

Maternal systolic blood pressure

to record systolic blood pressure of the patient during surgery

Full Information

NCT ID

NCT04401345

First Posted

May 20, 2020

Last Updated

February 18, 2021

Sponsor

Rajesh Deshar

1. Study Identification

Unique Protocol Identification Number

NCT04401345

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

February 2021

Overall Recruitment Status

Completed

Study Start Date

June 1, 2020 (Actual)

Primary Completion Date

January 31, 2021 (Actual)

Study Completion Date

January 31, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Rajesh Deshar

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

Keywords

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

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Model Description

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.

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Masking Description

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.

Allocation

Randomized

Enrollment

258 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Experimental Group (GP)

Arm Type

Experimental

Arm Description

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

Arm Title

Placebo Group(NS)

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Glycopyrrolate 0.2 MG/ML

Other Intervention Name(s)

Glycopyrronium bromide

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Normal saline

Other Intervention Name(s)

0.9% NS

Intervention Description

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

Primary Outcome Measure Information:

Title

Total vasopressors requirement intraoperatively

Description

Total vasopressors required to prevent hypotension during the period of surgery

Time Frame

immediately after spinal anaesthesia till the end of the surgery

Secondary Outcome Measure Information:

Title

The incidence of hypotension

Description

Hypotension is defined as systolic blood pressure < 80% of baseline reading or systolic blood pressure < 100 mmHg

Time Frame