Intravenous Ondansetron to Attenuate the Hypotensive, Bradycardic Response to Spinal Anesthesia in Healthy Parturients
|ClinicalTrials.gov Identifier: NCT01414777|
Recruitment Status : Unknown
Verified August 2011 by University of Virginia.
Recruitment status was: Enrolling by invitation
First Posted : August 11, 2011
Last Update Posted : August 11, 2011
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 or disease||Intervention/treatment||Phase|
|Hypotension Pregnancy||Drug: ondansetron Drug: placebo||Phase 2 Phase 3|
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 (Clinical Trial)|
|Estimated Enrollment :||68 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Care Provider, Investigator)|
|Official Title:||IRB-HSR# 14583: Intravenous Ondansetron to Attenuate the Hypotensive, Bradycardic Response to Spinal Anesthesia in Healthy Parturients|
|Study Start Date :||November 2009|
ondansetron 8 mg IV will be administered prior to placement of the spinal anesthesia
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
placebo or ondansetron 8mg IV will be administered prior to placement of the spinal anesthetic
Other Name: epidural
- 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
- dosage of vasopressors administered [ Time Frame: day one ]vasopressors administered during surgery
- number of episodes of nausea [ Time Frame: 24 hours after surgery ]
- occurrence & intensity of itching [ Time Frame: 24 hours after surgery ]
- pain scores reported by the patient [ Time Frame: 24 hours after surgery ]
- dosage of anticholinergics administered [ Time Frame: 24 hours after surgery ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01414777
|United States, Virginia|
|University of Virginia Health System|
|Charlottesville, Virginia, United States, 22908|
|Principal Investigator:||Jordan Hackworth, MD||University of Virginia Anesthesiology|