Ambulatory surgery is occurring with rapidly increasing frequency as surgical and anesthetic techniques have improved and pressure to reduce health-care costs has increased. While there are many benefits to recovering from surgery within the home, a significant disadvantage is the lack of rapid access to a healthcare provider when postoperative complications occur. Postoperative nausea and vomiting (PONV) are common after surgery and anesthesia, and recent studies have demonstrated a high incidence of post-discharge nausea and vomiting (PDNV) after ambulatory surgery, particularly in high-risk groups (female gender, age less than 50 years, history of PONV, opioid administration in the post-anesthesia care unit (PACU), and nausea in the PACU). Current practices known to reduce the risk of postoperative nausea and vomiting in the PACU, such as the avoidance of volatile anesthetics and the use of intraoperative ondansetron and steroids, have little effect on the risk of delayed PDNV. Novel strategies to prevent PDNV are needed. Orally administered olanzapine, which has been shown to decrease the incidence of chemotherapy-induced nausea and vomiting, demonstrates promise as a novel strategy for preventing PDNV. It has a long half-life, allowing for a single dose to be administered preoperatively. This study will evaluate whether there is a difference in the incidence and severity of PDNV between patients who receive oral olanzapine versus placebo prior to general anesthesia for ambulatory surgery.

Inclusion Criteria:

• Adults age ≥ 18 and ≤ 50 years old
• Patient scheduled to undergo ambulatory surgery under general anesthesia
• Willing and able to provide informed consent

Exclusion Criteria:

• Unable to swallow pills

• Current use of typical or atypical anti-psychotic medications

• History of allergy to olanzapine

• Pregnancy/Lactation (subjects of child-bearing potential will have a urine pregnancy test performed the day of surgery)

• History of QTc > 450ms or torsades de pointes

• 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 (NYHA) Class II or higher congestive heart failure.

• Postural hypotension or vasovagal syncope within 6 months of planned surgery.

• Hypotension on day of surgery, defined as a systolic blood pressure < 90mm Hg or a diastolic pressure < 60mm Hg.

• Seizure disorder

• Clinically active prolactinoma

• Hepatic disease

• Poorly controlled diabetes

• Pre-operative blood glucose > 250 mg/dL

• Narrow angle glaucoma

• Parkinson's disease

• Lewy body dementia

24 hours after discharge