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

This study is enrolling participants by invitation only.
Sponsor:
Information provided by:
University of Virginia
ClinicalTrials.gov Identifier:
NCT01414777
First received: September 16, 2010
Last updated: August 10, 2011
Last verified: August 2011
  Purpose

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).


Condition Intervention Phase
Hypotension
Pregnancy
Drug: ondansetron
Drug: placebo
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Prevention
Official Title: IRB-HSR# 14583: Intravenous Ondansetron to Attenuate the Hypotensive, Bradycardic Response to Spinal Anesthesia in Healthy Parturients

Resource links provided by NLM:


Further study details as provided by University of Virginia:

Primary Outcome Measures:
  • Number of Participants with Adverse Events as a Measure of Safety and Tolerability" [ Time Frame: day 1 ] [ Designated as safety issue: No ]
    hypotension & bradycardia will be recorded from the placement of the spinal through the end of surgical c-section


Secondary Outcome Measures:
  • dosage of vasopressors administered [ Time Frame: day one ] [ Designated as safety issue: No ]
    vasopressors administered during surgery

  • number of episodes of nausea [ Time Frame: 24 hours after surgery ] [ Designated as safety issue: No ]
  • occurrence & intensity of itching [ Time Frame: 24 hours after surgery ] [ Designated as safety issue: No ]
  • pain scores reported by the patient [ Time Frame: 24 hours after surgery ] [ Designated as safety issue: No ]
  • dosage of anticholinergics administered [ Time Frame: 24 hours after surgery ] [ Designated as safety issue: No ]

Estimated Enrollment: 68
Study Start Date: November 2009
Arms Assigned Interventions
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 Name: 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 Name: epidural

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.

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01414777

Locations
United States, Virginia
University of Virginia Health System
Charlottesville, Virginia, United States, 22908
Sponsors and Collaborators
University of Virginia
Investigators
Principal Investigator: Jordan Hackworth, MD University of Virginia Anesthesiology
  More Information

Publications:

Responsible Party: Jordan Hackworth, MD, UVA Department of Anesthesiology
ClinicalTrials.gov Identifier: NCT01414777     History of Changes
Other Study ID Numbers: 14583
Study First Received: September 16, 2010
Last Updated: August 10, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by University of Virginia:
c-section
Hypotension after spinal anesthesia for C-section

Additional relevant MeSH terms:
Hypotension
Cardiovascular Diseases
Vascular Diseases
Anesthetics
Antihypertensive Agents
Ondansetron
Anti-Anxiety Agents
Antiemetics
Antipruritics
Antipsychotic Agents
Autonomic Agents
Cardiovascular Agents
Central Nervous System Agents
Central Nervous System Depressants
Dermatologic Agents
Gastrointestinal Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Serotonin Agents
Serotonin Antagonists
Therapeutic Uses
Tranquilizing Agents

ClinicalTrials.gov processed this record on October 23, 2014