Postoperative Nausea and Vomiting
Conditions
Brief summary
This study will compare two different drug regimens (oral dronabinol versus intravenous ondanseteron) for the prevention of post-operative nausea and vomiting (PONV).
Detailed description
Anesthesia has become remarkably safe during the past two decades, yet postoperative nausea and vomiting (PONV) continues to be a vexing problem with an unacceptably high incidence. Multiple factors including age, gender, type of surgery and anesthetic agents, perioperative opioid use and duration of anesthesia have been implicated in the cause of PONV. Several new drugs have been introduced during the last two decades to minimize PONV; however the incidence still remains significantly high, ranging from 30% during the first 24 postoperatively to 35% post discharge. Unrelenting PONV results in delayed discharge which is particularly significant after outpatient surgery. The proposed study will examine the anti-emetic properties of orally administered dronabinol given immediately prior to surgery with standard of care intravenous ondansetron given at the end of a surgical procedure in an effort to assess the need for cost effective prophylaxis of PONV. The chemoreceptor trigger zone (CTZ) functions as emetic chemoreceptor for the vomiting centers. Many antiemetic drugs acting at the level of the CTZ are responsible for vomiting in patients receiving chemotherapy and postoperative patients. Our regimen of oral dronabinol has been proven to reduce the incidence of PONV in patients receiving chemotherapy. We intend to prove that a regimen that has been utilized in patients receiving chemotherapeutic drugs will work in patients with a high risk for developing PONV following surgery. We hypothesize that a regimen of preoperative low dose of dronabinol is superior in efficacy to a standard antiemetic in preventing the incidence of PONV, and thus will not only improve patient satisfaction but will also reduce length of stay in patients undergoing outpatient surgery. Specific Objectives 1. Reduction of postoperative and postdischarge nausea and vomiting in ambulatory surgery patients. 2. Reduce rate of hospital admissions and length of inpatient stay after outpatient surgery. 3. Improve patient satisfaction after outpatient surgery. Procedure After informed consent, surgical patients scheduled for outpatient abdominal surgery at the Central Arkansas Veterans Healthcare System (CAVHS) who are at high risk for developing PONV following their procedure will be randomized to receive either the study drug ( preoperative oral dronabinol-5 mg) or standard therapy ( 4 mg ondansetron intravenously at the end of surgery). The outcome measures will be the presence or absence of PONV, the severity and number of such episodes, the event count of rescue antiemetic use and patient satisfaction. All data will be recorded by personnel who are blinded to the drug regimen. Relevance: At CAVHS, 2/3 of our patients are scheduled for outpatient surgical procedure everyday. Our regimen will minimize postoperative and postdischarge nausea and vomiting, improve post-operative care unit (PACU) length of stay, minimize unnecessary hospital admissions, provide patient satisfaction and cost containment. The potential for application of this inexpensive intervention to other surgeries is enormous. Reducing the incidence of PONV could have a significant impact on patient satisfaction. The intervention is very low-risk, efficacious, and could substantially impact on the experience and the outcome of the Veteran undergoing surgery.
Interventions
Dronabinol (5mg) will be administered orally (p.o.) 20-60 min pre-operatively.
Ondansetron (4mg) will be administered intravenously (iv) intraoperatively in those patients not receiving Dronabinol.
Sponsors
Study design
Eligibility
Inclusion criteria
* The patients undergoing outpatient operations for intra-abdominal or abdominal wall procedures (e.g. hernias) under general anesthesia. * Patients that are at increased risk for PONV based on the Koivuranta risk scoring system, with inclusion of patients having a Koivuranta risk score (K score) of 2 or more. * Ability to give informed consent. * Veteran eligible for treatment.
Exclusion criteria
* Patients \<18 years old * Patients with a history of hypersensitivity to cannabinoids or sesame oil --Patients with current substance abuse. Substance abuse will be identified meeting one or both of the following criteria: * a) Review the participant's medical chart to identify inpatient, residential, or outpatient treatment for alcohol or drug dependence as recorded in the Veterans Health Administration Computerized Patient Record system (CPRS) within the preceding six months. OR * b) Patient report. Exclude patients who report current marijuana or cocaine use within the past 30 days. If a drug screen is clinically indicated and is positive the patient will NOT be entered into the study. * Patients taking medications known to have significant drug-drug interactions with the prescribed drug and study drugs, Dronabinol and Ondansetron, will be reviewed in Micromedex. Micromedex is a medication database used by Central Arkansas Veterans Healthcare System (CAVHS). If the drug could have a drug-drug interaction with either dronabinol or ondansetron the patients will NOT be entered into the study. If a drug is confirmed via Micromedex not to have a drug-drug interaction, the patient will be eligible for study participation. * Pregnant women * Patients with prolonged QTC intervals on electrocardiogram (EKG). * Patients enrolled in another clinical trial at the time of randomization. * Inability to adhere to study protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Postoperative Nausea and Vomiting | Post-operative Care Unit (PACU) length of stay on day of surgery (time from end of surgery to transfer to discharge unit or other hospital unit) | The incidence of postoperative nausea (PON) and postoperative vomiting (POV) was assessed during Post-operative Care Unit (PACU) stay. |
| Maximum Reported Post-Operative Nausea Scores on Visual Analog Scale (VAS) Scale | Post-operative Care Unit (PACU) stay from end of surgery to transfer to ambulatory unit | VAS Scale: 0=no nausea, 1-3=mild nausea, 4-6= moderate nausea, 7-9= severe nausea, 10=extreme nausea usually accompanied with vomiting. VAS nausea score were obtained every 30 min from entry into post-operative care unit (PACU) for first 2 hrs. and then hourly until time of transfer out of PACU. |
| Post-operative Nausea and Vomiting (PONV) Incidence 24-48 Hours Post Surgery | 24-48 hrs post surgery | Participants were queried for presence of postoperative nausea (PON) or postoperative vomiting (POV) during the 24-48 hr window post surgery. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patient Satisfaction: Willingness to Take Pre-operative Medication for Post-operative Nausea and/or Vomiting | Post operative follow up interviews 24 hrs to 6 wks | Percent of participants who responded that they would be willing to take preemptive medication for nausea and vomiting for subsequent surgeries when queried during post-operative follow-up interviews at 24-48 hrs or 2-6 weeks. |
| Post-Operative Care Unit Length of Stay (Min) | Day of surgery (time from end of surgery to transfer to ambulatory pre-discharge unit or other unit) | Length of time in PACU (minutes) measured from end of surgery to time of transfer to ambulatory care prior to home discharge or time to hospital admission if applicable. |
| Patient Satisfaction 2: Willingness to Pay Extra Money for Post-Operative Nausea and Vomiting (PONV) Preventive Medication | Post-operative follow-up interviews 24 hr to 6 weeks post surgery | Percent of participants willing to pay extra money for preemptive medication for PONV for subsequent surgical procedures when queried at post-operative 24-48 hr. and at 2-6 wk. follow-up interviews. |
| Post-Surgery Hospital Admissions (All Cause) After Out-patient Abdominal Procedure | Post-operative Day of Surgery (DOS) | Number of all-cause hospital admissions on day of elective out-patient surgery . |
| Post-operative Antiemetic Use | End of surgery to 48 hr post surgery | Percentage of participants requiring post-operative anti-emetic medications.. Anti-emetic medication need was assessed during a) post-operative care unit (PACU) stay and b)during the first 48 hrs. following discharge from PACU to home or if applicable to in-patient unit. |
Countries
United States
Participant flow
Recruitment details
Recruitment period was from 12-02-2009 to 11-20-2013. Participants were recruited during pre-surgery or preanesthesia clinic visits for elective outpatient abdominal surgery lasting at least 1 hr. Inclusion criteria included high risk for post-operative nausea and vomiting (PONV) as measured by a Koivuranta score (K score) of 2 or more.
Pre-assignment details
36 participants were withdrawn prior to assignment into a treatment arm: 8 participants voluntarily withdrew prior to surgery date, 2 did not meet inclusion criteria, 6 had exclusion criteria, 3 withdrawn when study was closed to enrollment, 17 were withdrawn due to cancellation or re-scheduled surgery incompatible with study schedules.
Participants by arm
| Arm | Count |
|---|---|
| Arm 1: Dronabinol dronabinol
Dronabinol: Dronabinol (5mg) will be administered po 20-60 min pre-operatively. | 64 |
| Arm 2: Ondansetron ondansetron
Ondansetron: Ondansetron (4mg) will be administered iv intraoperatively in those patients not receiving Dronabinol. | 57 |
| Total | 121 |
Baseline characteristics
| Characteristic | Arm 1: Dronabinol | Arm 2: Ondansetron | Total |
|---|---|---|---|
| Age, Continuous | 57.8 years STANDARD_DEVIATION 12.5 | 57.6 years STANDARD_DEVIATION 13.2 | 57.7 years STANDARD_DEVIATION 12.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 8 Participants | 14 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 58 Participants | 48 Participants | 106 Participants |
| Risk scores for PONV K score=2 | 44 participants | 35 participants | 79 participants |
| Risk scores for PONV K score >2 | 20 participants | 22 participants | 42 participants |
| Sex: Female, Male Female | 5 Participants | 2 Participants | 7 Participants |
| Sex: Female, Male Male | 59 Participants | 55 Participants | 114 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 92 | 6 / 88 |
| serious Total, serious adverse events | 13 / 92 | 10 / 88 |
Outcome results
Incidence of Postoperative Nausea and Vomiting
The incidence of postoperative nausea (PON) and postoperative vomiting (POV) was assessed during Post-operative Care Unit (PACU) stay.
Time frame: Post-operative Care Unit (PACU) length of stay on day of surgery (time from end of surgery to transfer to discharge unit or other hospital unit)
Population: Per protocol
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm 1:Dronabinol | Incidence of Postoperative Nausea and Vomiting | Incidence PACU PON | 34.4 percentage of participants |
| Arm 1:Dronabinol | Incidence of Postoperative Nausea and Vomiting | Incidence PACU POV | 12.5 percentage of participants |
| Arm 2:Ondansetron | Incidence of Postoperative Nausea and Vomiting | Incidence PACU PON | 29.8 percentage of participants |
| Arm 2:Ondansetron | Incidence of Postoperative Nausea and Vomiting | Incidence PACU POV | 7 percentage of participants |
Maximum Reported Post-Operative Nausea Scores on Visual Analog Scale (VAS) Scale
VAS Scale: 0=no nausea, 1-3=mild nausea, 4-6= moderate nausea, 7-9= severe nausea, 10=extreme nausea usually accompanied with vomiting. VAS nausea score were obtained every 30 min from entry into post-operative care unit (PACU) for first 2 hrs. and then hourly until time of transfer out of PACU.
Time frame: Post-operative Care Unit (PACU) stay from end of surgery to transfer to ambulatory unit
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm 1:Dronabinol | Maximum Reported Post-Operative Nausea Scores on Visual Analog Scale (VAS) Scale | Mild Nausea (VAS score=1-3) | 15.6 percentage of participants |
| Arm 1:Dronabinol | Maximum Reported Post-Operative Nausea Scores on Visual Analog Scale (VAS) Scale | Severe nausea (VAS score=7-9) | 7.8 percentage of participants |
| Arm 1:Dronabinol | Maximum Reported Post-Operative Nausea Scores on Visual Analog Scale (VAS) Scale | Moderate Nausea (VAS score =4-6) | 7.8 percentage of participants |
| Arm 1:Dronabinol | Maximum Reported Post-Operative Nausea Scores on Visual Analog Scale (VAS) Scale | Extreme nausea (VAS score=10) | 9.4 percentage of participants |
| Arm 1:Dronabinol | Maximum Reported Post-Operative Nausea Scores on Visual Analog Scale (VAS) Scale | No nausea (VAS score=0) | 59.4 percentage of participants |
| Arm 2:Ondansetron | Maximum Reported Post-Operative Nausea Scores on Visual Analog Scale (VAS) Scale | Extreme nausea (VAS score=10) | 8.8 percentage of participants |
| Arm 2:Ondansetron | Maximum Reported Post-Operative Nausea Scores on Visual Analog Scale (VAS) Scale | No nausea (VAS score=0) | 70.2 percentage of participants |
| Arm 2:Ondansetron | Maximum Reported Post-Operative Nausea Scores on Visual Analog Scale (VAS) Scale | Mild Nausea (VAS score=1-3) | 12.3 percentage of participants |
| Arm 2:Ondansetron | Maximum Reported Post-Operative Nausea Scores on Visual Analog Scale (VAS) Scale | Moderate Nausea (VAS score =4-6) | 1.8 percentage of participants |
| Arm 2:Ondansetron | Maximum Reported Post-Operative Nausea Scores on Visual Analog Scale (VAS) Scale | Severe nausea (VAS score=7-9) | 7.0 percentage of participants |
Post-operative Nausea and Vomiting (PONV) Incidence 24-48 Hours Post Surgery
Participants were queried for presence of postoperative nausea (PON) or postoperative vomiting (POV) during the 24-48 hr window post surgery.
Time frame: 24-48 hrs post surgery
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm 1:Dronabinol | Post-operative Nausea and Vomiting (PONV) Incidence 24-48 Hours Post Surgery | 24-48hr PON incidence | 23.4 percentage of participants |
| Arm 1:Dronabinol | Post-operative Nausea and Vomiting (PONV) Incidence 24-48 Hours Post Surgery | 24-48 hr POV incidence | 6.3 percentage of participants |
| Arm 2:Ondansetron | Post-operative Nausea and Vomiting (PONV) Incidence 24-48 Hours Post Surgery | 24-48hr PON incidence | 22.8 percentage of participants |
| Arm 2:Ondansetron | Post-operative Nausea and Vomiting (PONV) Incidence 24-48 Hours Post Surgery | 24-48 hr POV incidence | 3.5 percentage of participants |
Patient Satisfaction 2: Willingness to Pay Extra Money for Post-Operative Nausea and Vomiting (PONV) Preventive Medication
Percent of participants willing to pay extra money for preemptive medication for PONV for subsequent surgical procedures when queried at post-operative 24-48 hr. and at 2-6 wk. follow-up interviews.
Time frame: Post-operative follow-up interviews 24 hr to 6 weeks post surgery
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm 1:Dronabinol | Patient Satisfaction 2: Willingness to Pay Extra Money for Post-Operative Nausea and Vomiting (PONV) Preventive Medication | 24-48 hr. post-op | 80 percent of participants |
| Arm 1:Dronabinol | Patient Satisfaction 2: Willingness to Pay Extra Money for Post-Operative Nausea and Vomiting (PONV) Preventive Medication | 2-6 wk post-op | 73 percent of participants |
| Arm 2:Ondansetron | Patient Satisfaction 2: Willingness to Pay Extra Money for Post-Operative Nausea and Vomiting (PONV) Preventive Medication | 24-48 hr. post-op | 70 percent of participants |
| Arm 2:Ondansetron | Patient Satisfaction 2: Willingness to Pay Extra Money for Post-Operative Nausea and Vomiting (PONV) Preventive Medication | 2-6 wk post-op | 68 percent of participants |
Patient Satisfaction: Willingness to Take Pre-operative Medication for Post-operative Nausea and/or Vomiting
Percent of participants who responded that they would be willing to take preemptive medication for nausea and vomiting for subsequent surgeries when queried during post-operative follow-up interviews at 24-48 hrs or 2-6 weeks.
Time frame: Post operative follow up interviews 24 hrs to 6 wks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm 1:Dronabinol | Patient Satisfaction: Willingness to Take Pre-operative Medication for Post-operative Nausea and/or Vomiting | 24-48 hr post-operative interview | 92 percent of participants |
| Arm 1:Dronabinol | Patient Satisfaction: Willingness to Take Pre-operative Medication for Post-operative Nausea and/or Vomiting | 2-6 week post-operative interview | 87 percent of participants |
| Arm 2:Ondansetron | Patient Satisfaction: Willingness to Take Pre-operative Medication for Post-operative Nausea and/or Vomiting | 24-48 hr post-operative interview | 89 percent of participants |
| Arm 2:Ondansetron | Patient Satisfaction: Willingness to Take Pre-operative Medication for Post-operative Nausea and/or Vomiting | 2-6 week post-operative interview | 75 percent of participants |
Post-operative Antiemetic Use
Percentage of participants requiring post-operative anti-emetic medications.. Anti-emetic medication need was assessed during a) post-operative care unit (PACU) stay and b)during the first 48 hrs. following discharge from PACU to home or if applicable to in-patient unit.
Time frame: End of surgery to 48 hr post surgery
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm 1:Dronabinol | Post-operative Antiemetic Use | Medication need during PACU stay | 25 percentage of participants |
| Arm 1:Dronabinol | Post-operative Antiemetic Use | Medication need for first 48 hrs after discharge t | 3 percentage of participants |
| Arm 2:Ondansetron | Post-operative Antiemetic Use | Medication need during PACU stay | 17 percentage of participants |
| Arm 2:Ondansetron | Post-operative Antiemetic Use | Medication need for first 48 hrs after discharge t | 4 percentage of participants |
Post-Operative Care Unit Length of Stay (Min)
Length of time in PACU (minutes) measured from end of surgery to time of transfer to ambulatory care prior to home discharge or time to hospital admission if applicable.
Time frame: Day of surgery (time from end of surgery to transfer to ambulatory pre-discharge unit or other unit)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm 1:Dronabinol | Post-Operative Care Unit Length of Stay (Min) | 99.5 minutes |
| Arm 2:Ondansetron | Post-Operative Care Unit Length of Stay (Min) | 97.0 minutes |
Post-Surgery Hospital Admissions (All Cause) After Out-patient Abdominal Procedure
Number of all-cause hospital admissions on day of elective out-patient surgery .
Time frame: Post-operative Day of Surgery (DOS)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm 1:Dronabinol | Post-Surgery Hospital Admissions (All Cause) After Out-patient Abdominal Procedure | DOS admission- urinary retension | 4 participants |
| Arm 1:Dronabinol | Post-Surgery Hospital Admissions (All Cause) After Out-patient Abdominal Procedure | DOS admission- low SpO2 | 1 participants |
| Arm 1:Dronabinol | Post-Surgery Hospital Admissions (All Cause) After Out-patient Abdominal Procedure | DOS admission-pain management | 1 participants |
| Arm 1:Dronabinol | Post-Surgery Hospital Admissions (All Cause) After Out-patient Abdominal Procedure | DOS admission -intractable nausea/vomitting | 0 participants |
| Arm 1:Dronabinol | Post-Surgery Hospital Admissions (All Cause) After Out-patient Abdominal Procedure | DOS admission-observation | 3 participants |
| Arm 2:Ondansetron | Post-Surgery Hospital Admissions (All Cause) After Out-patient Abdominal Procedure | DOS admission -intractable nausea/vomitting | 0 participants |
| Arm 2:Ondansetron | Post-Surgery Hospital Admissions (All Cause) After Out-patient Abdominal Procedure | DOS admission-observation | 3 participants |
| Arm 2:Ondansetron | Post-Surgery Hospital Admissions (All Cause) After Out-patient Abdominal Procedure | DOS admission- urinary retension | 3 participants |
| Arm 2:Ondansetron | Post-Surgery Hospital Admissions (All Cause) After Out-patient Abdominal Procedure | DOS admission-pain management | 1 participants |
| Arm 2:Ondansetron | Post-Surgery Hospital Admissions (All Cause) After Out-patient Abdominal Procedure | DOS admission- low SpO2 | 0 participants |