Effect of Glycopyrrolate on Vasopressors Requirement for Non-elective Caesarean Section Under Spinal Anaesthesia
Condition: Glycopyrrolate; Post-spinal Hypotension; Effect of Drug; Hemodynamic Instability
MeSH terms: Hypotension
Study type: Interventional
Phase: Phase 4

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.
    

Intervention name(s): Glycopyrrolate 0.2 MG/ML; Normal saline
Intervention type(s): Drug; Drug
Intervention description(s): In this group, the patients will receive glycopyrrolate 0.2 mg in 1 ml; In this group, the patients will receive 1 ml of 0.9% normal saline
Other intervention name(s): Glycopyrronium bromide; 0.9% NS
Intervention MeSH terms: Glycopyrrolate; Bromides
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention 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: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: caesarean section; hypotension; spinal anaesthesia; glycopyrrolate; post-spinal anaesthesia; vasopressors; non-elective caesarean section