Prophylactic Ondansetron in Post-op Cardiac Surgery Patients to Prevent Post-operative Nausea and Vomiting

A Double-blinded, Randomized Control Trial of Prophylactic Ondansetron in a Post-operative Cardiac Surgery Population for Post-operative Nausea and Vomiting

To evaluate the effectiveness of a prophylactic dose of ondansetron in decreasing the incidence of post-operative nausea and vomiting in cardiac surgery patients after cessation of post-operative sedation. In patients who have undergone open heart surgery, a single prophylactic dose of ondansetron 4 mg IV given at the time of discontinuing propofol sedation will result in a 50% reduction of the rate of post-operative nausea and vomiting in the first 24 post-operative hours compared to placebo.

Study Overview

• Status: Completed
• Conditions: Postoperative Nausea and Vomiting
• Intervention / Treatment: Drug: Ondansetron; Drug: Saline

Detailed Description

Post-operative nausea and vomiting (PONV) is a significant source of morbidity for patients undergoing general anesthesia, and in particular, patients undergoing cardiac anesthesia. Despite its common occurrence, literature on PONV prophylaxis in the cardiac surgical population is limited relative to other surgical populations.

A rational approach to preventing PONV would be to administer prophylaxis prior to extubation once post-operative sedation has ceased. This timing of administration would be more standardized across patients, as duration of surgery and time of extubation after surgery can vary considerably, rendering plasma levels of PONV prophylaxis agents highly variable across patients.

At St. Paul's Hospital, PONV prophylaxis has not been a routine part of cardiac anesthesia care. Furthermore, there are no standardized guidelines, and practice varies between care providers. Following surgery, patients recover from anesthesia and are extubated in the cardiac surgery ICU (CSICU). They are usually sedated on a propofol infusion for one to four hours after surgery until they are ready for extubation. When PONV occurs, the first line drug for treatment is ondansetron 4 mg. The investigators therefore propose the use of a single, prophylactic dose of ondansetron (4 mg IV), given at the time of propofol cessation. A randomized, double blinded placebo controlled model will be utilized

• Study Type: Interventional
• Enrollment (Actual): 186
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 1Y6
      • St. Paul's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Elective (outpatient) and urgent (inpatient) cardiac surgery procedures requiring cardiopulmonary bypass, including:

  • Coronary artery bypass grafting (CABG)
  • Valve surgery (ie. repair and/or replacement)
  • CABG and valve surgery

Exclusion Criteria:

• Undergoing 'off-pump' CABG (not involving the cardiopulmonary bypass machine)
• With a contraindication to the study drug - including but not limited to congenital Long QT Syndrome, allergy to ondansetron, or a history of migraines
• Unable to understand the consent process, either due to language limitations or cognitive limitations if a translator or substitute decision maker is not available
• Receiving heart transplants, ventricular assist devices or on extra-corporeal membrane oxygenation (ECMO)
• Intubated for more than 12 hours post-operatively
• With a known history of PONV
• Sedated with dexmedatomine instead of propofol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ondansetron; Ondansetron 4mg IV at time of discontinuation of Propofol Infusion	Drug: Ondansetron; Ondansetron/Zofran is an antiemetic drug used to prevent and treat nausea and vomiting.; Other Names: Zofran
Placebo Comparator: Saline; 2 mL IV Normal Saline at time of discontinuation of Propofol Infusion	Drug: Saline; Normal saline is salt water and is acting as a placebo in this study. A placebo is an inactive substance that looks identical to the test drug, but it contains no therapeutic ingredient.; Other Names: Placebo Comparator: Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of Post-operative Nausea and Vomiting (PONV)	Measured by asking the patient hourly to assess their post operative nausea and vomiting using a 10-point verbal Likert rating scale.	First 24 hours post-extubation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Rescue PONV medication administration	How many participants received rescue post-operative nausea and vomiting medication post-extubation after surgery.	First 24 hours post-extubation
Time to first dose of rescue PONV medication	Time of administration of first dose of rescue post-operative nausea and vomiting medication	First 24 hours post-extubation
Dose of any Rescue PONV medication	Dose of administered rescue post-operative nausea and vomiting medication after extubation.	First 24 hours post-extubation
Time to first report of nausea or first vomit post-operatively	Time to first report of any nausea or vomiting after extubation post-operatively.	First 24 hours post-extubation
Incidence of Post-operative nausea without vomiting	Nurses both asked patients' for a nausea severity rating and recorded any vomiting hourly.	First 24 hours post-extubation
Severity Post-operative nausea without vomiting	Severity of post-operative nausea without vomiting based on a 10-point likert scale, recorded hourly.	First 24 hours post-extubation
Incidence of ventricular arrhythmias	Any sustained Ventricular Arrhythmias (i.e. lasting greater than 30 seconds)	first 24 hours post-extubation

Collaborators and Investigators

• Sponsor: University of British Columbia
• Investigators: Principal Investigator: Matthew Coley, MD, University of British Columbia; Study Chair: Erica Wang, PharmD, University of British Columbia; Study Chair: Cynthia Yarnold, MD, University of British Columbia; Study Chair: Stephan Schwarz, MD, University of British Columbia

Publications and helpful links

General Publications

• Wang EHZ, Sunderland S, Edwards NY, Chima NS, Yarnold CH, Schwarz SKW, Coley MA. A Single Prophylactic Dose of Ondansetron Given at Cessation of Postoperative Propofol Sedation Decreases Postoperative Nausea and Vomiting in Cardiac Surgery Patients: A Randomized Controlled Trial. Anesth Analg. 2020 Oct;131(4):1164-1172. doi: 10.1213/ANE.0000000000004730.

Study record dates

Study Major Dates

• Study Start (Actual): March 6, 2018
• Primary Completion (Actual): July 11, 2018
• Study Completion (Actual): July 11, 2018

Study Registration Dates

• First Submitted: October 25, 2016
• First Submitted That Met QC Criteria: November 14, 2016
• First Posted (Estimate): November 17, 2016

Study Record Updates

• Last Update Posted (Actual): October 15, 2018
• Last Update Submitted That Met QC Criteria: October 10, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: Postoperative Nausea and Vomiting; PONV; CSICU; post-cardiac surgery; cardiac intensive care unit
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Signs and Symptoms, Digestive; Nausea; Vomiting; Postoperative Nausea and Vomiting; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Dermatologic Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Serotonin Antagonists; Anti-Anxiety Agents; Antipruritics; Ondansetron
• Other Study ID Numbers: H15-00675

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No