Clinical trial NCT01414777: Intravenous Ondansetron to Attenuate the Hypotensive, Bradycardic Response to Spinal Anesthesia in Healthy Parturients
Official title: IRB-HSR# 14583: Intravenous Ondansetron to Attenuate the Hypotensive, Bradycardic Response to Spinal Anesthesia in Healthy Parturients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Hypotension
Pregnancy
Keywords: c-section
Hypotension after spinal anesthesia for C-section
Lead sponsor: University of Virginia
Sponsor class: OTHER
First posted: 2011-08-11
Enrollment: 68
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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).

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 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

Primary outcomes:
measure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability"
timeFrame: day 1
Secondary outcomes:
measure: dosage of vasopressors administered
timeFrame: day one
measure: number of episodes of nausea
timeFrame: 24 hours after surgery
measure: occurrence & intensity of itching
timeFrame: 24 hours after surgery
measure: pain scores reported by the patient
timeFrame: 24 hours after surgery
measure: dosage of anticholinergics administered
timeFrame: 24 hours after surgery
Other outcomes:
Locations:
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
Study officials:
affiliation: University of Virginia Anesthesiology
name: Jordan Hackworth, MD
role: PRINCIPAL_INVESTIGATOR
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