Intravenous Ondansetron to Attenuate the Hypotensive, Bradycardic Response to Spinal Anesthesia in Healthy Parturients
Condition: Hypotension; Pregnancy
MeSH terms: Hypotension
Study type: Interventional
Phase: Phase 2/Phase 3

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.
    

Intervention name(s): ondansetron; placebo
Intervention type(s): Drug; Drug
Intervention description(s): Ondansetron 8mg IV or placebo will be administered prior to placement of the spinal anesthetic; placebo or ondansetron 8mg IV will be administered prior to placement of the spinal anesthetic
Other intervention name(s): epidural; epidural
Intervention MeSH terms: Ondansetron
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Prevention
Keywords: c-section; Hypotension after spinal anesthesia for C-section