Postoperative Nausea and Vomiting
Conditions
Keywords
olanzapine, placebo-controlled, nausea, vomiting, ambulatory surgery procedures, antiemetic, general anesthesia
Brief summary
The primary objective of this phase 2 randomized controlled trial is to determine whether the pre-operative administration of olanzapine (5 mg PO) improves quality of recovery (assessed by the Quality of Recovery-40 (QoR-40) survey) on postoperative day 1 in patients having ambulatory surgery with general anesthesia. The secondary objectives of this study are to determine whether there are differences in quality of recovery on postoperative day 2, presence of post-discharge nausea, presence of severe post-discharge nausea, recovery room length of stay and opioid consumption in patients who receive the study drug versus placebo.
Detailed description
Up to 37% of patients undergoing ambulatory surgery experience postdischarge nausea and vomiting (PDNV), and PDNV represents a major barrier to improving a patient's quality of recovery. Because olanzapine has been shown to be an effective drug for PDNV prevention, but carries the risk of sedation, this study seeks to identify if the administration of olanzapine is an intervention that improves a patient's overall quality of recovery. The study population includes women between 18 and 50 years-old who are undergoing ambulatory (outpatient) surgery at Yale New Haven Hospital. This represents the population that is most susceptible to post-discharge nausea and vomiting (PDNV) and is therefore most likely to benefit from an intervention that reduces PDNV to impact overall quality of recovery.
Interventions
DRUGOlanzapine
5 mg of oral olanzapine one hour prior to ambulatory surgery
DRUGPlacebo
oral matched placebo one hour prior to ambulatory surgery
Sponsors
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* Provision of signed and dated informed consent form * Stated willingness to comply with all study procedures and availability for the duration of the study * Female aged 18-50 * Scheduled to undergo ambulatory surgery under general anesthesia * Access to smartphone device or computer with internet connection and has an email address
Exclusion criteria
* Non-English speaking * Unable to swallow pills * Current use of anti-psychotic medications * History of allergy to olanzapine * Pregnancy/Lactation * Current use of antihypertensive medication * Diabetes Mellitus * Clinically significant cardiovascular disease defined as follows: 1. Myocardial infarction or unstable angina within 6 months prior to the day of planned surgery. 2. History of serious ventricular arrhythmia (i.e.: ventricular tachycardia or ventricular fibrillation) or cardiac arrhythmias requiring anti-arrhythmic medications, except for atrial fibrillation that is well controlled on anti-arrhythmic medication. 3. New York Heart Association Class II or higher congestive heart failure. 4. Postural hypotension or vasovagal syncope within 6 months of planned surgery. * Hypotension on day of surgery, defined as a systolic blood pressure \< 90mmHg * Seizure disorder * Clinically active prolactinoma * Hepatic disease * Narrow angle glaucoma * Parkinson's disease * Lewy body dementia
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Quality of Recovery-40 (QoR-40) Survey to Assess Efficacy | post-operative day 1 | Quality of Recovery-40 (QoR-40) survey is a 40-item questionnaire that provides a global score across five dimensions: patient support, comfort, emotions, physical independence, and pain. The survey is scored on a 5-point Likert scale: for positive items: 1 = none of the time, 5 = all of the time; for negative items, the scoring was reversed. The QoR-40 has a possible score of 40 (extremely poor quality of recovery) to 200 (excellent quality of recovery). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Quality of Recovery-40 (QoR-40) Survey to Assess Efficacy | post-operative day 2 | Quality of Recovery-40 (QoR-40) survey is a 40-item questionnaire that provides a global score across five dimensions: patient support, comfort, emotions, physical independence, and pain. The survey is scored on a 5-point Likert scale: for positive items: 1 = none of the time, 5 = all of the time; for negative items, the scoring was reversed. The QoR-40 has a possible score of 40 (extremely poor quality of recovery) to 200 (excellent quality of recovery). |
| Participants With Any Nausea | post-operative day 1 | Nausea was assessed using a numerical rating scale from 0 to 10, where 0 indicated no nausea and 10 indicated the worst nausea imaginable. For this outcome measure, participants were classified as having any nausea if they reported a nausea score greater than 0 at any assessment during the specified time period. |
| Number of Participants With Severe Post-discharge Nausea | up to 24 hours post discharge | Severe post-discharge nausea defined as any numerical rating \> 3 on a 0-10 scale during the 24 hours after discharge |
| Recovery Room Length of Stay | From surgery end time to recovery room discharge, up to 23 hours | Recovery room length of stay in minutes |
| Recovery Room Opioid Consumption | From surgery end time to recovery room discharge, up to 23 hours | Recovery room opioid consumption in morphine milligram equivalents |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORJaime Hyman, MD
Yale University
Participant flow
Recruitment details
Participants were recruited to the trial from June 26, 2023 through December 6, 2025 at Yale New Haven Hospital in New Haven, CT and Shoreline Surgery Center in Guilford, CT
Pre-assignment details
398 patients were consented to participate in the trial. Twelve patients were withdrawn from the trial prior to randomization including: patient withdrew consent (n=4), surgery rescheduled (n=3), investigator unable to randomize (n=2), patient enrolled in a conflicting study (n=1), surgery cancelled (n=1), patient admission planned (n=1). Two patients were withdrawn after randomization but prior to receiving study medication including: vasovagal syncope (n = 1), patient withdrew consent (n = 1).
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 38 Years STANDARD_DEVIATION 8 |
| American Society of Anesthesiologists- Physical Status Classification (ASA-PS) 1 | 44 Participants |
| American Society of Anesthesiologists- Physical Status Classification (ASA-PS) 2 | 147 Participants |
| American Society of Anesthesiologists- Physical Status Classification (ASA-PS) 3 | 28 Participants |
| Apfel score 2 | 58 Participants |
| Apfel score 3 | 83 Participants |
| Apfel score 4 | 31 Participants |
| Body Mass Index | 29 kg/m^2 STANDARD_DEVIATION 8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 18 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 167 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 15 Participants |
| Race/Ethnicity, Customized Race Black | 15 Participants |
| Race/Ethnicity, Customized Race Other/Unknown | 22 Participants |
| Race/Ethnicity, Customized Race White | 299 Participants |
| Sex: Female, Male Female | 193 Participants |
| Sex: Female, Male Male | 0 Participants |
| Surgery procedure type Breast | 41 Participants |
| Surgery procedure type Hysteroscopy | 37 Participants |
| Surgery procedure type Laparoscopic gynecologic | 70 Participants |
| Surgery procedure type Other | 32 Participants |
| Surgery procedure type Otolaryngology | 28 Participants |
| Surgery procedure type Vaginal | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 191 | 0 / 193 |
| other Total, other adverse events | 5 / 191 | 5 / 193 |
| serious Total, serious adverse events | 1 / 191 | 3 / 193 |
Outcome results
None listed