Intravenous Ondansetron to Attenuate the Hypotensive, Bradycardic Response to Spinal Anesthesia in Healthy Parturients

March 9, 2022 updated by: Mohamed Tiouririne, MD, University of Virginia

IRB-HSR# 14583: Intravenous Ondansetron to Attenuate the Hypotensive, Bradycardic Response to Spinal Anesthesia in Healthy Parturients

The investigators hypothesize that given prophylactically, intravenous ondansetron will attenuate the drop in blood pressure and heart rate frequently seen after spinal anesthesia.

Eighty-six American Society of Anesthesiologists (ASA) physical status I or II in preoperative patient assessment, parturients age of 18 to 45 years scheduled to undergo elective caesarean section will be enrolled.

Patients will be randomized to 2 groups: the ondansetron group, receiving 8 mg intravenous ondansetron diluted in 10 mL of saline; or the placebo group, who were administered 10 mL of saline given 5 minutes prior to performing the spinal anesthetic. Investigational Pharmacy will randomize and dispense study drug.

Baseline measurements of vital signs will be taken. Otherwise standard management will then be used:

  • Patients must be NPO for 8 hours
  • Pulse oximetry, EKG monitoring, noninvasive blood pressure at a minimum of every 3 minutes, more frequently if decided by the provider.
  • Standard lumbar puncture in a sitting position the L3-L4 or L4-L5
  • Whitacre pencil-point, 25 gauge
  • Injectate: 2 mL of 0.75% hyperbaric bupivacaine, 100 mcg preservative free morphine, 20 mcg fentanyl
  • Immediately after completing the subarachnoid injection, patients will be laid supine with left lateral uterine displacement

The sensory level of anesthesia will be assessed in the standard fashion every five minutes using ice. The motor component will tested using the Bromage scale for spinal anesthesia (0, no paralysis; 1, inability to lift the thigh [only knee/feet]; 2, inability to flex the knee [only feet]; 3, inability to move any joint in the legs).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Over the last 30 years, regional anesthesia has emerged as the method of choice for elective caesarean section because it avoids risks involved in managing the airway of the parturient and has the added significant benefit of mother being awake for the birth of her child. Indeed, this changing practice patterns is thought to have lead to a significant drop in anesthesia related maternal morbidity and mortality.

At the same time, regional anesthesia is associated with both minor and significant risk.

Most common among these effects is hypotension and bradycardia, occurring in 33% and 13% of cases, respectively. In the pregnant patient, supine positioning required for surgery is associated hypotension due to aortocaval compression by the gravid uterus in 8% of patients, even without spinal anesthesia. During caesarean section, the combination of these factors can lead to hypotension include decreased placental blood flow, impaired fetal oxygenation and fetal acidosis. Maternal symptoms of low blood pressures include nausea, vomiting, dizziness, and decreased consciousness. This situation has lead to dozens of publications seeking to prevent or minimize the hypotensive response.

Hypotension after a spinal is initially due to a blockade of sympathetic fibers leading to a drop in systemic vascular resistance. Spinal-induced bradycardia is multifactorial but is in part due to the Bezold-Jarisch Reflex (BJR). This reflex is mediated by serotonin receptors within the wall of the ventricle in response to systemic hypotension. These receptors, the 5HT3 subtype, cause an increase efferent vagal signaling when bound by serotonin released during hypovolemic states, clinically leading to bradycardia and further hypotension.

Ondansetron, a widely used anti-emetic and serotonin antagonist, has been safely used to blunt the BJR, resulting in less bradycardia and hypotension first in animals and later in humans undergoing spinal anesthesia. ,

Use During Pregnancy:

The FDA labels ondansetron as a class B. Studies in pregnant rats and rabbits at doses up to 70 times higher than clinically used doses revealed no evidence of impaired fertility or harm to the fetus due to ondansetron. There are, however, few prospective studies in pregnant women. Nevertheless, the drug is widely used has a long safety history for use in pregnancy and during anesthesia for caesarean section.

Study Type

Interventional

Enrollment (Actual)

68

Phase

  • Phase 2
  • Phase 3

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

  • United States
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • University of Virginia Health System

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

16 years to 43 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Elective Caesarean section
  • Consent to be in the study
  • Age 18-45
  • ASA 1 or 2

Exclusion Criteria:

  • Patient refusal
  • Patients with known allergy to ondansetron will be excluded

  • Contraindications to spinal anesthetic

    • Known Coagulopathy (acquired e.g. anticoagulation or existing such as liver disease; using patient history, physical examination to determine bleeding risks, a platelet count under 100 or a PT INR over 1.4)
    • Severely altered anatomy (e.g. post surgical changes)
    • Existing neurological deficits (Women with a history of migraine or tension headache will be allowed to enroll. More severe conditions with daily life limiting symptoms will be excluded. Examples include epilepsy, pseudotumor cerebri, prior stroke with persistent neurologic deficits, or any motor or sensory neuropathy with existing deficits)
    • Skin infection overlying site

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: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: ondansetron
ondansetron 8 mg IV will be administered prior to placement of the spinal anesthesia
Drug: ondansetron
Ondansetron 8mg IV or placebo will be administered prior to placement of the spinal anesthetic
Other Names:
  • epidural
Placebo Comparator: Placebo
Ondansetron 8 mg IV or Placebo will be administered prior to placement of the spinal anesthestic
Drug: placebo
placebo or ondansetron 8mg IV will be administered prior to placement of the spinal anesthetic
Other Names:
  • epidural

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants with Adverse Events as a Measure of Safety and Tolerability"
Time Frame: day 1
hypotension & bradycardia will be recorded from the placement of the spinal through the end of surgical c-section
day 1

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
dosage of vasopressors administered
Time Frame: day one
vasopressors administered during surgery
day one
number of episodes of nausea
Time Frame: 24 hours after surgery
24 hours after surgery
occurrence & intensity of itching
Time Frame: 24 hours after surgery
24 hours after surgery
pain scores reported by the patient
Time Frame: 24 hours after surgery
24 hours after surgery
dosage of anticholinergics administered
Time Frame: 24 hours after surgery
24 hours after surgery

Collaborators and Investigators

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

Sponsor

University of Virginia

Investigators

  • Principal Investigator: Jordan Hackworth, MD, University of Virginia Anesthesiology

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

November 1, 2009

Primary Completion (Actual)

June 1, 2011

Study Completion (Actual)

June 1, 2011

Study Registration Dates

First Submitted

September 16, 2010

First Submitted That Met QC Criteria

August 10, 2011

First Posted (Estimate)

August 11, 2011

Study Record Updates

Last Update Posted (Actual)

March 24, 2022

Last Update Submitted That Met QC Criteria

March 9, 2022

Last Verified

March 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 14583

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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