<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04401345</url>
  </required_header>
  <id_info>
    <org_study_id>IRC/1603/019</org_study_id>
    <nct_id>NCT04401345</nct_id>
  </id_info>
  <brief_title>Effect of Glycopyrrolate on Vasopressors Requirement for Non-elective Caesarean Section Under Spinal Anaesthesia</brief_title>
  <official_title>Effect of Glycopyrrolate on Vasopressors Requirement for Non-elective Caesarean Section Under Spinal Anaesthesia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Rajesh Deshar</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>B.P. Koirala Institute of Health Sciences</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is prospective randomised double blind study conducted in parturients planned for&#xD;
      non-elective caesarean section under spinal anaesthesia. Glycopyrrolate group will receive&#xD;
      0.2 mg of Glycopyrrolate before start of phenylephrine infusion. Control group will receive&#xD;
      0.2 ml of Normal Saline before start of phenylephrine infusion. Total amount of vasopressors&#xD;
      required i.e. ephedrine or phenylephrine will recorded in the form of phenylephrine&#xD;
      equivalent during intraoperative period.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Intravenous glycopyrrolate has been investigated for its effect on haemodynamic changes after&#xD;
      spinal anesthesia for caesarean delivery. Results from previous studies are conflicting as&#xD;
      glycopyrrolate has shown to reduce, increase or had no effect on incidence of maternal&#xD;
      hypotension and/or vasopressor requirement after spinal anaesthesia. A recent meta-analysis&#xD;
      found that prophylactic glycopyrrolate does not prevent the incidence of spinal-induced&#xD;
      hypotension; however, it reduces the total vasopressor requirement during elective caesarean&#xD;
      delivery under spinal anaesthesia. Therefore, the aim of this study is to find out whether&#xD;
      the use of glycopyrrolate decreases the amount of vasopressors required to manage hypotension&#xD;
      induced by spinal anaesthesia in non-elective CS.&#xD;
&#xD;
      Methodology:&#xD;
&#xD;
      After approval from Institutional Review committee of B.P. Koirala Institute of Health&#xD;
      Sciences, the trial will be registered at clinical trial.gov. Parturient planned for&#xD;
      non-elective caesarian of ASA PS grade II fulfilling the inclusion criteria will be informed&#xD;
      about the study and written consent will be obtained either in labour room or in obstetric&#xD;
      emergency ward. The eligible patients will be randomly assigned to Glycopyrrolate (GP group)&#xD;
      or normal saline (NS group). The study will be conducted in accordance with the ethical&#xD;
      principles of the 1964 Declaration of Helsinki. Before patient is shifted to the operating&#xD;
      room (OR), ranitidine 50 mg and metoclopramide 10 mg will be administered intravenously via&#xD;
      18 G cannula. In the operating table, patients will be laid supine with a wedge placed in the&#xD;
      right hip. Standard anaesthesia monitoring including 3-lead electrocardiography, heart rate&#xD;
      (HR), noninvasive blood pressure (NIBP) and pulse oximetry (Sp02) will be done. A mean value&#xD;
      of three measurements of systolic blood pressure (SBP) and HR will be recorded as baseline&#xD;
      parameters. Patency of the vein will be maintained with the infusion of Ringer's lactate&#xD;
      solution at a minimal rate.&#xD;
&#xD;
      Before the patient is placed in sitting position for SA,she will receive the study drug&#xD;
      according to the randomization. After free flow of CSF is observed, 0.5 % hyperbaric&#xD;
      bupivacaine (2.2 ml) with 10 µg fentanyl will be injected intrathecally over 30 s using a&#xD;
      25-gauge Quinke needle at the L3-4 or L4-L5 interspace. Patients will then be immediately&#xD;
      placed in supine while maintaining 15 degree left lateral tilt. Co-loading of 1000 ml ringers&#xD;
      lactate solution will be initiated at the start of spinal anaesthesia using a pressure bag&#xD;
      and it will be completed within 10 min. Immediately after the spinal injection, phenylephrine&#xD;
      infusion will be initiated at a rate of 25 µg/min and it will be titrated to maintain&#xD;
      maternal SBP within 20 % of baseline.&#xD;
&#xD;
      The sensory level of anaesthesia will be checked using loss of cold sensation. Surgery will&#xD;
      be allowed once the bilateral sensory block height at T6 is achieved. Oxygen at 40% will be&#xD;
      administered via nasal cannula at 2-4 L/min until delivery.&#xD;
&#xD;
      Hemodynamic parameters will be recorded at following time intervals: baseline, after the&#xD;
      study drug in given IV, immediately after spinal anaesthesia, every minute for first 10 min,&#xD;
      and then at 2.5 min until end of surgery. Post-spinal hypotension will be defined as SBP &lt;&#xD;
      80% of baseline reading or SBP &lt; 100 mmHg before delivery of baby. Post-delivery hypotension&#xD;
      is defined as SBP &lt; 80% of baseline reading or SBP &lt; 100 mmHg after delivery of the baby. It&#xD;
      will be treated with phenylephrine 100 µg bolus and rapid infusion of Ringer's lactate 200&#xD;
      ml. Infusion of phenylephrine will be stopped if bradycardia (HR&lt; 55/min) occurs without&#xD;
      hypotension. If bradycardia (HR&lt; 55/min) is associated with hypotension, IV ephedrine 6 mg&#xD;
      will be administered. If these measures fail and bradycardia is still persistent then an IV&#xD;
      atropine 0.5 mg will be given. If reactive hypertension (defined as SBP &gt; 120% of baseline&#xD;
      reading) occurs, the infusion of phenylephrine will be stopped and restarted only when the&#xD;
      SBP reaches the target range (SBP is within 120% of baseline SBP). The amount of ephedrine&#xD;
      used will be converted to phenylephrine equivalent based on potency of phenylephrine to&#xD;
      ephedrine as 81:1 ratio.(31)&#xD;
&#xD;
      After delivery of the baby, 2 U of oxytocin will be administered IV over 5-10 sec followed by&#xD;
      an infusion of 10 U/hr (oxytocin 20 U in 500 ml of Hartmann's solution). Phenylephrine&#xD;
      infusion will be gradually tapered after delivery of the baby keeping the SBP within the&#xD;
      target level. The total amount of intraoperative IV fluids administered and estimated blood&#xD;
      loss will be measured. Intraoperative use of other uterotonic agent or blood transfusion will&#xD;
      be recorded. The attending pediatrician will assess neonatal Apgar scores at 1 and 5 minutes&#xD;
      after delivery.&#xD;
&#xD;
      Patients will be asked to report the occurrence of intraoperative nausea and rate its&#xD;
      severity using an 11-point verbal rating scale (0=no nausea, 10=worst possible nausea).&#xD;
      Intraoperative nausea or vomiting (IONV) will be treated with ondansetron 4 mg IV. After 5&#xD;
      min, if nausea and vomiting is still persisted, IV dexamethasone 4 mg will be administered.&#xD;
      IONV incidence and its time of occurrence from intrathecal injection (whether associated with&#xD;
      hypotension) and antiemetic needed will be recorded. Incidence of intraoperative pruritus,&#xD;
      shivering, dizziness and dry mouth will also be recorded. Grading of intraoperative shivering&#xD;
      is as follows: 0 no shivering, 1 one or more of the following: piloerection, peripheral&#xD;
      vasoconstriction, peripheral cyanosis without other cause, but without visible muscular&#xD;
      activity; 2 visible muscular activity confined to one muscle group; 3 visible muscular&#xD;
      activity in more than one muscle group; and 4 gross muscular activity involving the whole&#xD;
      body. If the shivering score is ≥3, IV meperidine 20 mg will be given.&#xD;
&#xD;
      The primary outcome will be the total amount of phenylephrine used to maintain blood pressure&#xD;
      intraoperatively. The secondary outcome measures will include incidence of maternal&#xD;
      hypotension, reactive hypertension, bradycardia, other side-effects (IONV, shivering,&#xD;
      pruritus, dry mouth,dizziness), changes in maternal SBP and heart rate and neonatal outcome&#xD;
      (Apgar scores at 1 min and 5 min, requirement of neonatal resuscitation, need for neonatal&#xD;
      ICU admission and neonatal death within 30 days).&#xD;
&#xD;
      Data collection:&#xD;
&#xD;
      Baseline data (gestational age, uterine incision to delivery time, hemodynamic parameters)&#xD;
      and outcome parameters will be collected in the paper case record form and entered in windows&#xD;
      Microsoft excel spreadsheet for analysis.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 1, 2020</start_date>
  <completion_date type="Actual">January 31, 2021</completion_date>
  <primary_completion_date type="Actual">January 31, 2021</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Experimental Group (GP): In the experimental group patients will receive 0.2 mg (1 ml) glycopyrrolate before phenylephrine infusion is initiated.&#xD;
Placebo Group (NS): In the placebo group patients will receive 1 ml normal saline (0.9%) before phenylephrine infusion is initiated.</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <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.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Total vasopressors requirement intraoperatively</measure>
    <time_frame>immediately after spinal anaesthesia till the end of the surgery</time_frame>
    <description>Total vasopressors required to prevent hypotension during the period of surgery</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The incidence of hypotension</measure>
    <time_frame>after spinal anaesthesia till the end of the surgery</time_frame>
    <description>Hypotension is defined as systolic blood pressure &lt; 80% of baseline reading or systolic blood pressure &lt; 100 mmHg</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The incidence of reactive hypertension</measure>
    <time_frame>after spinal anaesthesia till the end of the surgery</time_frame>
    <description>defined as systolic blood pressure &gt; 120% of baseline reading</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The incidence of maternal bradycardia</measure>
    <time_frame>after spinal anaesthesia till the end of the surgery</time_frame>
    <description>heart rate &lt; 55/min</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The incidence of maternal tachycardia</measure>
    <time_frame>after spinal anaesthesia till the end of the surgery</time_frame>
    <description>Heart rate &gt; 100/min</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The incidence of nausea</measure>
    <time_frame>after spinal anaesthesia till the end of the surgery</time_frame>
    <description>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).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The incidence of vomiting</measure>
    <time_frame>after spinal anaesthesia till the end of the surgery</time_frame>
    <description>incidence of vomiting</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The incidence of shivering</measure>
    <time_frame>after spinal anaesthesia till the end of the surgery</time_frame>
    <description>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</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The incidence of dry mouth, intraoperative pruritus and dizziness</measure>
    <time_frame>after spinal anaesthesia till the end of the surgery</time_frame>
    <description>incidence of dry mouth, intraoperative pruritus and dizziness</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maternal heart rate and</measure>
    <time_frame>after spinal anaesthesia till the end of the surgery</time_frame>
    <description>to record the heart rate of the patient during surgery</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maternal systolic blood pressure</measure>
    <time_frame>after spinal anaesthesia till the end of the surgery</time_frame>
    <description>to record systolic blood pressure of the patient during surgery</description>
  </secondary_outcome>
  <other_outcome>
    <measure>The APGAR outcome of baby</measure>
    <time_frame>at 1 and 5 min after delivery</time_frame>
    <description>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</description>
  </other_outcome>
  <other_outcome>
    <measure>Need for neonatal resuscitation</measure>
    <time_frame>immediately after delivery</time_frame>
    <description>resuscitation needed for baby</description>
  </other_outcome>
  <other_outcome>
    <measure>Admission to neonatal ICU (NICU)</measure>
    <time_frame>after delivery</time_frame>
    <description>the need for ICU admission</description>
  </other_outcome>
  <other_outcome>
    <measure>Neonatal death</measure>
    <time_frame>within 30 days of delivery</time_frame>
    <description>if there is neonatal death or not</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">258</enrollment>
  <condition>Glycopyrrolate</condition>
  <condition>Post-spinal Hypotension</condition>
  <condition>Effect of Drug</condition>
  <condition>Hemodynamic Instability</condition>
  <arm_group>
    <arm_group_label>Experimental Group (GP)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will receive 0.2 mg (1 ml) glycopyrrolate before phenylephrine infusion is initiated at 25mcg/min.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Group(NS)</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>patients will receive 1 ml normal saline (0.9%) before phenylephrine infusion is initiated at 25 mcg/min</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Glycopyrrolate 0.2 MG/ML</intervention_name>
    <description>In this group, the patients will receive glycopyrrolate 0.2 mg in 1 ml</description>
    <arm_group_label>Experimental Group (GP)</arm_group_label>
    <other_name>Glycopyrronium bromide</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Normal saline</intervention_name>
    <description>In this group, the patients will receive 1 ml of 0.9% normal saline</description>
    <arm_group_label>Placebo Group(NS)</arm_group_label>
    <other_name>0.9% NS</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age between 18-40 years&#xD;
&#xD;
          -  All parturients at term (gestational weeks ≥ 37)&#xD;
&#xD;
          -  ASA (American society of Anaesthesiologist) PS (Physical status) grade II&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Age &gt;40 year&#xD;
&#xD;
          -  ASA PS Grade &gt;2&#xD;
&#xD;
          -  Maternal bradycardia (baseline HR&lt; 60/min) or tachycardia (baseline HR&gt; 100/min)&#xD;
&#xD;
          -  Pregnancy induced hypertension&#xD;
&#xD;
          -  Gestational hypertension&#xD;
&#xD;
          -  Known fetal abnormalities&#xD;
&#xD;
          -  Intrauterine growth retardation (IUGR)&#xD;
&#xD;
          -  Intrauterine fetal death (IUFD)&#xD;
&#xD;
          -  Contraindications to spinal anaesthesia&#xD;
&#xD;
          -  Contraindications to glycopyrrolate&#xD;
&#xD;
          -  Multiple pregnancy&#xD;
&#xD;
          -  BMI: &gt; 30 kg/m2&#xD;
&#xD;
          -  Height: &lt;150cm&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>B.P.Koirala Institute of Health Sciences</name>
      <address>
        <city>Dharān Bāzār</city>
        <state>Province 1</state>
        <zip>56700</zip>
        <country>Nepal</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Nepal</country>
  </location_countries>
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  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>28704246</PMID>
  </results_reference>
  <results_reference>
    <citation>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. Erratum In: Anesth Analg. 2011 Oct;113(4):800.</citation>
    <PMID>20495139</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>30738019</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>30905688</PMID>
  </results_reference>
  <results_reference>
    <citation>Bruntion L (ed), Chabner B (ed), Knollman B (ed). Goodman &amp; Gilman's The Pharmacological Basis of Therapeutics. 12th ed. New York: The McGraw Hill Companies; 2011.</citation>
  </results_reference>
  <verification_date>February 2021</verification_date>
  <study_first_submitted>May 20, 2020</study_first_submitted>
  <study_first_submitted_qc>May 20, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 26, 2020</study_first_posted>
  <last_update_submitted>February 18, 2021</last_update_submitted>
  <last_update_submitted_qc>February 18, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 21, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>B.P. Koirala Institute of Health Sciences</investigator_affiliation>
    <investigator_full_name>Rajesh Deshar</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>caesarean section</keyword>
  <keyword>hypotension</keyword>
  <keyword>spinal anaesthesia</keyword>
  <keyword>glycopyrrolate</keyword>
  <keyword>post-spinal anaesthesia</keyword>
  <keyword>vasopressors</keyword>
  <keyword>non-elective caesarean section</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypotension</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Glycopyrrolate</mesh_term>
    <mesh_term>Bromides</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04401345
org study id: IRC/1603/019
nct id: NCT04401345
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
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.
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.
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.
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes 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.
measure: Total vasopressors requirement intraoperatively
time frame: immediately after spinal anaesthesia till the end of the surgery
description: Total vasopressors required to prevent hypotension during the period of surgery
measure: The incidence of hypotension
time frame: after spinal anaesthesia till the end of the surgery
description: Hypotension is defined as systolic blood pressure < 80% of baseline reading or systolic blood pressure < 100 mmHg
measure: The incidence of reactive hypertension
time frame: after spinal anaesthesia till the end of the surgery
description: defined as systolic blood pressure > 120% of baseline reading
measure: The incidence of maternal bradycardia
time frame: after spinal anaesthesia till the end of the surgery
description: heart rate < 55/min
measure: The incidence of maternal tachycardia
time frame: after spinal anaesthesia till the end of the surgery
description: Heart rate > 100/min
measure: The incidence of nausea
time frame: after spinal anaesthesia till the end of the surgery
description: 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).
measure: The incidence of vomiting
time frame: after spinal anaesthesia till the end of the surgery
description: incidence of vomiting
measure: The incidence of shivering
time frame: after spinal anaesthesia till the end of the surgery
description: 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
measure: The incidence of dry mouth, intraoperative pruritus and dizziness
time frame: after spinal anaesthesia till the end of the surgery
description: incidence of dry mouth, intraoperative pruritus and dizziness
measure: Maternal heart rate and
time frame: after spinal anaesthesia till the end of the surgery
description: to record the heart rate of the patient during surgery
measure: Maternal systolic blood pressure
time frame: after spinal anaesthesia till the end of the surgery
description: to record systolic blood pressure of the patient during surgery
measure: The APGAR outcome of baby
time frame: at 1 and 5 min after delivery
description: 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
measure: Need for neonatal resuscitation
time frame: immediately after delivery
description: resuscitation needed for baby
measure: Admission to neonatal ICU (NICU)
time frame: after delivery
description: the need for ICU admission
measure: Neonatal death
time frame: within 30 days of delivery
description: if there is neonatal death or not
arm group label: Experimental Group (GP)
arm group type: Experimental
description: Patients will receive 0.2 mg (1 ml) glycopyrrolate before phenylephrine infusion is initiated at 25mcg/min.
arm group label: Placebo Group(NS)
arm group type: Placebo Comparator
description: patients will receive 1 ml normal saline (0.9%) before phenylephrine infusion is initiated at 25 mcg/min
intervention type: Drug
intervention name: Glycopyrrolate 0.2 MG/ML
description: In this group, the patients will receive glycopyrrolate 0.2 mg in 1 ml
arm group label: Experimental Group (GP)
other name: Glycopyrronium bromide
intervention type: Drug
intervention name: Normal saline
description: In this group, the patients will receive 1 ml of 0.9% normal saline
arm group label: Placebo Group(NS)
other name: 0.9% NS
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 40 Years
healthy volunteers: No
facility: 
country: Nepal
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PMID: 22323952
citation: 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
citation: 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. Erratum In: Anesth Analg. 2011 Oct;113(4):800.
PMID: 20495139
citation: 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
citation: 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
citation: 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.
responsible party type: Sponsor-Investigator
investigator affiliation: B.P. Koirala Institute of Health Sciences
investigator full name: Rajesh Deshar
investigator title: Principal Investigator
mesh term: Hypotension
mesh term: Glycopyrrolate
mesh term: Bromides
sharing ipd: No