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

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.

Condition:

Hypotension

Treatment:

ondansetron

Start Date:

November 2009

Sponsor:

University of Virginia

For More Information:

https://clinicaltrials.gov/show/NCT01414777