Pain, Postoperative, Postoperative Nausea and Vomiting
Conditions
Brief summary
Postoperative nausea and vomiting (PONV) and pain are the most common causes of Post Anesthesia Care Unit (PACU) discharge delay, with untreated PONV occurring in 20-30% of post-surgical patients. The effect of guanfacine (GF) administration on pain and nausea scores will be assessed with two groups. One group will receive 1 mg of GF to take orally and the other group will receive a similar appearing placebo (containing no drug) to take orally.
Detailed description
Pain after surgery is commonly treated with narcotics which can potentiate PONV, further delaying PACU discharge. In multiple studies, alpha-2 agonists such as clonidine and dexmedetomidine reduce both the incidence of PONV and post-op pain, as well as requirements for postoperative analgesics. These actions are mediated via central alpha-2A receptors (A2AR). Of the A2AR agonists, guanfacine, though a weak antihypertensive agent, has the highest selectivity for the A2AR, but to date is untested for its potential to treat either PONV or post-operative pain.
Interventions
DRUGGuanfacine
Patients will receive 1 mg of guanfacine to take orally.
DRUGPlacebo
Patients will receive a placebo containing no drug that appears similarly to guanfacine to take orally.
Sponsors
Vanderbilt University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* VUMC patients undergoing sinus surgery in MCE OR
Exclusion criteria
* Inability to read and freely consent * Patients who take alpha-2 agonists routinely (guanfacine, clonidine, tizanidine) * Patients undergoing sinus surgery planned for greater than 3 hours * Patients with significant pre-existing pain, on chronic pain (opioid, methadone) therapy, severe fibromyalgia or other pre-existing pain condition in any body part * Patients with preoperative nausea/vomiting at baseline. * Pregnant or lactating women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Comparison of PONV Score of Assessments Done at 15 Minutes After Arrival in PACU Using 11-point Nausea Scale (nVRS) | 15 minutes after arriving in PACU | Comparison of PONV Score of assessments done at 15 minutes after arrival in PACU using the nVRS when 0 is no nausea and 10 is worst nausea |
| Comparison of PONV Score of Assessments Done at 30 Minutes After Arrival in PACU Using 11-point Nausea Scale (nVRS) | 30 minutes after arriving in PACU | Comparison of PONV Score of assessments done at 30 minutes after arrival in PACU using the nVRS when 0 is no nausea and 10 is worst nausea |
| Comparison of PONV Score of Assessments Done at 60 Minutes After Arrival in PACU Using 11-point Nausea Scale (nVRS) | 60 minutes after arriving in PACU | Comparison of PONV Score of assessments done at 60 minutes after arrival in PACU using the nVRS when 0 is no nausea and 10 is worst nausea |
| Postoperative Nausea Assessment Using 11-point Nausea Scale (nVRS) | 24 hours post op | PONV assessed using nVRS at 24 hours postop when 0 is no nausea and 10 is worst nausea. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Postoperative Pain Assessment Using 11-point Visual/Verbal Analog (VAS) | 15, 30, 60 minutes after arriving in PACU | Maximum postoperative pain assessment assessed in PACU at 15, 30 and 60 minutes after PACU arrival using VAS when 0 is no pain and 10 is worst pain |
| PACU Length of Stay in Minutes | Time frame between arrival and discharge in PACU, approximately 90 minutes | — |
| Postoperative Pain Assessment Using 11-point Visual/Verbal Analog (VAS) | 24 hours postop | Postoperative pain assessment using VAS at 24 hours postop when 0 is no pain and 10 is worst pain |
| Total Narcotic Requirement in PACU | Time frame between arrival and discharge in PACU, approximately 90 minutes | Total narcotic requirement in PACU tallied in morphine equivalents during PACU stay |
| Number of Doses of PONV Treatment Administered in PACU | Time frame between arrival and discharge in PACU, approximately 90 minutes | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Guanfacine Guanfacine 1 mg capsule by mouth, one time prior to surgery.
Guanfacine: Patients will receive 1 mg of guanfacine to take orally. | 39 |
| Placebo Placebo with a similar appearance to guanfacine by mouth one time prior to surgery
Placebo: Patients will receive a placebo containing no drug that appears similarly to guanfacine to take orally. | 41 |
| Total | 80 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 2 |
| Overall Study | Physician Decision | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo | Total | Guanfacine |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 7 Participants | 12 Participants | 5 Participants |
| Age, Categorical Between 18 and 65 years | 34 Participants | 68 Participants | 34 Participants |
| Age, Continuous | 48.7 years STANDARD_DEVIATION 15.4 | 45.3 years STANDARD_DEVIATION 16.5 | 42 years STANDARD_DEVIATION 16.9 |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment United States | 41 participants | 80 participants | 39 participants |
| Sex: Female, Male Female | 19 Participants | 40 Participants | 21 Participants |
| Sex: Female, Male Male | 22 Participants | 40 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 40 | 0 / 44 |
| other Total, other adverse events | 0 / 40 | 0 / 44 |
| serious Total, serious adverse events | 0 / 40 | 0 / 44 |
Outcome results
Primary
Comparison of PONV Score of Assessments Done at 15 Minutes After Arrival in PACU Using 11-point Nausea Scale (nVRS)
Comparison of PONV Score of assessments done at 15 minutes after arrival in PACU using the nVRS when 0 is no nausea and 10 is worst nausea
Time frame: 15 minutes after arriving in PACU
Population: 15 minute nVRS datapoint was not available for 2 participants in the Placebo group
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Guanfacine | Comparison of PONV Score of Assessments Done at 15 Minutes After Arrival in PACU Using 11-point Nausea Scale (nVRS) | None (nVRS 0) | 35 Participants |
| Guanfacine | Comparison of PONV Score of Assessments Done at 15 Minutes After Arrival in PACU Using 11-point Nausea Scale (nVRS) | Mild (nVRS 1-5) | 1 Participants |
| Guanfacine | Comparison of PONV Score of Assessments Done at 15 Minutes After Arrival in PACU Using 11-point Nausea Scale (nVRS) | Moderate/Severe (nVRS 6-10) | 3 Participants |
| Placebo | Comparison of PONV Score of Assessments Done at 15 Minutes After Arrival in PACU Using 11-point Nausea Scale (nVRS) | None (nVRS 0) | 33 Participants |
| Placebo | Comparison of PONV Score of Assessments Done at 15 Minutes After Arrival in PACU Using 11-point Nausea Scale (nVRS) | Mild (nVRS 1-5) | 2 Participants |
| Placebo | Comparison of PONV Score of Assessments Done at 15 Minutes After Arrival in PACU Using 11-point Nausea Scale (nVRS) | Moderate/Severe (nVRS 6-10) | 4 Participants |
Primary
Comparison of PONV Score of Assessments Done at 30 Minutes After Arrival in PACU Using 11-point Nausea Scale (nVRS)
Comparison of PONV Score of assessments done at 30 minutes after arrival in PACU using the nVRS when 0 is no nausea and 10 is worst nausea
Time frame: 30 minutes after arriving in PACU
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Guanfacine | Comparison of PONV Score of Assessments Done at 30 Minutes After Arrival in PACU Using 11-point Nausea Scale (nVRS) | None (nVRS 0) | 34 Participants |
| Guanfacine | Comparison of PONV Score of Assessments Done at 30 Minutes After Arrival in PACU Using 11-point Nausea Scale (nVRS) | Mild (nVRS 1-5) | 4 Participants |
| Guanfacine | Comparison of PONV Score of Assessments Done at 30 Minutes After Arrival in PACU Using 11-point Nausea Scale (nVRS) | Moderate/Severe (nVRS 6-10) | 1 Participants |
| Placebo | Comparison of PONV Score of Assessments Done at 30 Minutes After Arrival in PACU Using 11-point Nausea Scale (nVRS) | None (nVRS 0) | 34 Participants |
| Placebo | Comparison of PONV Score of Assessments Done at 30 Minutes After Arrival in PACU Using 11-point Nausea Scale (nVRS) | Mild (nVRS 1-5) | 5 Participants |
| Placebo | Comparison of PONV Score of Assessments Done at 30 Minutes After Arrival in PACU Using 11-point Nausea Scale (nVRS) | Moderate/Severe (nVRS 6-10) | 2 Participants |
Primary
Comparison of PONV Score of Assessments Done at 60 Minutes After Arrival in PACU Using 11-point Nausea Scale (nVRS)
Comparison of PONV Score of assessments done at 60 minutes after arrival in PACU using the nVRS when 0 is no nausea and 10 is worst nausea
Time frame: 60 minutes after arriving in PACU
Population: nVRS data was not available for 1 participant in the Guanfacine group
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Guanfacine | Comparison of PONV Score of Assessments Done at 60 Minutes After Arrival in PACU Using 11-point Nausea Scale (nVRS) | None (nVRS 0) | 33 Participants |
| Guanfacine | Comparison of PONV Score of Assessments Done at 60 Minutes After Arrival in PACU Using 11-point Nausea Scale (nVRS) | Mild (nVRS 1-5) | 2 Participants |
| Guanfacine | Comparison of PONV Score of Assessments Done at 60 Minutes After Arrival in PACU Using 11-point Nausea Scale (nVRS) | Moderate/Severe (nVRS 6-10) | 3 Participants |
| Placebo | Comparison of PONV Score of Assessments Done at 60 Minutes After Arrival in PACU Using 11-point Nausea Scale (nVRS) | None (nVRS 0) | 35 Participants |
| Placebo | Comparison of PONV Score of Assessments Done at 60 Minutes After Arrival in PACU Using 11-point Nausea Scale (nVRS) | Mild (nVRS 1-5) | 5 Participants |
| Placebo | Comparison of PONV Score of Assessments Done at 60 Minutes After Arrival in PACU Using 11-point Nausea Scale (nVRS) | Moderate/Severe (nVRS 6-10) | 1 Participants |
Primary
Postoperative Nausea Assessment Using 11-point Nausea Scale (nVRS)
PONV assessed using nVRS at 24 hours postop when 0 is no nausea and 10 is worst nausea.
Time frame: 24 hours post op
Population: Only 70 patients (32 in guanfacine arm; 38 in placebo arm) responded to follow-up phone call and provided PONV data at the 24 hour timepoint.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Guanfacine | Postoperative Nausea Assessment Using 11-point Nausea Scale (nVRS) | 0.00 score on a scale |
| Placebo | Postoperative Nausea Assessment Using 11-point Nausea Scale (nVRS) | 0.00 score on a scale |
Secondary
Maximum Postoperative Pain Assessment Using 11-point Visual/Verbal Analog (VAS)
Maximum postoperative pain assessment assessed in PACU at 15, 30 and 60 minutes after PACU arrival using VAS when 0 is no pain and 10 is worst pain
Time frame: 15, 30, 60 minutes after arriving in PACU
Population: Data unavailable for 2 participants in the placebo group at 15 minute time point, 1 participant in the placebo group at the 30 minute time point,
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Guanfacine | Maximum Postoperative Pain Assessment Using 11-point Visual/Verbal Analog (VAS) | 15 minutes after PACU admission | Mild (Pain nVRS 1-5) | 0 Participants |
| Guanfacine | Maximum Postoperative Pain Assessment Using 11-point Visual/Verbal Analog (VAS) | 30 minutes after PACU admission | Moderate/Severe (Pain nVRS 6-10) | 14 Participants |
| Guanfacine | Maximum Postoperative Pain Assessment Using 11-point Visual/Verbal Analog (VAS) | 30 minutes after PACU admission | None (Pain nVRS 0) | 18 Participants |
| Guanfacine | Maximum Postoperative Pain Assessment Using 11-point Visual/Verbal Analog (VAS) | 60 minutes after PACU admission | None (Pain nVRS 0) | 12 Participants |
| Guanfacine | Maximum Postoperative Pain Assessment Using 11-point Visual/Verbal Analog (VAS) | 15 minutes after PACU admission | Moderate/Severe (Pain nVRS 6-10) | 8 Participants |
| Guanfacine | Maximum Postoperative Pain Assessment Using 11-point Visual/Verbal Analog (VAS) | 60 minutes after PACU admission | Mild (Pain nVRS 1-5) | 6 Participants |
| Guanfacine | Maximum Postoperative Pain Assessment Using 11-point Visual/Verbal Analog (VAS) | 30 minutes after PACU admission | Mild (Pain nVRS 1-5) | 7 Participants |
| Guanfacine | Maximum Postoperative Pain Assessment Using 11-point Visual/Verbal Analog (VAS) | 60 minutes after PACU admission | Moderate/Severe (Pain nVRS 6-10) | 21 Participants |
| Guanfacine | Maximum Postoperative Pain Assessment Using 11-point Visual/Verbal Analog (VAS) | 15 minutes after PACU admission | None (Pain nVRS 0) | 31 Participants |
| Placebo | Maximum Postoperative Pain Assessment Using 11-point Visual/Verbal Analog (VAS) | 60 minutes after PACU admission | Moderate/Severe (Pain nVRS 6-10) | 12 Participants |
| Placebo | Maximum Postoperative Pain Assessment Using 11-point Visual/Verbal Analog (VAS) | 15 minutes after PACU admission | None (Pain nVRS 0) | 24 Participants |
| Placebo | Maximum Postoperative Pain Assessment Using 11-point Visual/Verbal Analog (VAS) | 15 minutes after PACU admission | Mild (Pain nVRS 1-5) | 5 Participants |
| Placebo | Maximum Postoperative Pain Assessment Using 11-point Visual/Verbal Analog (VAS) | 15 minutes after PACU admission | Moderate/Severe (Pain nVRS 6-10) | 10 Participants |
| Placebo | Maximum Postoperative Pain Assessment Using 11-point Visual/Verbal Analog (VAS) | 30 minutes after PACU admission | None (Pain nVRS 0) | 20 Participants |
| Placebo | Maximum Postoperative Pain Assessment Using 11-point Visual/Verbal Analog (VAS) | 30 minutes after PACU admission | Mild (Pain nVRS 1-5) | 6 Participants |
| Placebo | Maximum Postoperative Pain Assessment Using 11-point Visual/Verbal Analog (VAS) | 30 minutes after PACU admission | Moderate/Severe (Pain nVRS 6-10) | 14 Participants |
| Placebo | Maximum Postoperative Pain Assessment Using 11-point Visual/Verbal Analog (VAS) | 60 minutes after PACU admission | None (Pain nVRS 0) | 16 Participants |
| Placebo | Maximum Postoperative Pain Assessment Using 11-point Visual/Verbal Analog (VAS) | 60 minutes after PACU admission | Mild (Pain nVRS 1-5) | 13 Participants |
Secondary
Number of Doses of PONV Treatment Administered in PACU
Time frame: Time frame between arrival and discharge in PACU, approximately 90 minutes
Population: Data missing for1 participants in the placebo group and 1 participant in the Guanfacine group.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Guanfacine | Number of Doses of PONV Treatment Administered in PACU | Zero doses | 26 Participants |
| Guanfacine | Number of Doses of PONV Treatment Administered in PACU | One dose | 8 Participants |
| Guanfacine | Number of Doses of PONV Treatment Administered in PACU | Two doses | 4 Participants |
| Placebo | Number of Doses of PONV Treatment Administered in PACU | Zero doses | 32 Participants |
| Placebo | Number of Doses of PONV Treatment Administered in PACU | One dose | 5 Participants |
| Placebo | Number of Doses of PONV Treatment Administered in PACU | Two doses | 3 Participants |
Secondary
PACU Length of Stay in Minutes
Time frame: Time frame between arrival and discharge in PACU, approximately 90 minutes
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Guanfacine | PACU Length of Stay in Minutes | 128 minutes |
| Placebo | PACU Length of Stay in Minutes | 110 minutes |
Secondary
Postoperative Pain Assessment Using 11-point Visual/Verbal Analog (VAS)
Postoperative pain assessment using VAS at 24 hours postop when 0 is no pain and 10 is worst pain
Time frame: 24 hours postop
Population: Based on only 71 participants to post operative questionnaire.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Guanfacine | Postoperative Pain Assessment Using 11-point Visual/Verbal Analog (VAS) | 3 score on a scale |
| Placebo | Postoperative Pain Assessment Using 11-point Visual/Verbal Analog (VAS) | 2 score on a scale |
Secondary
Total Narcotic Requirement in PACU
Total narcotic requirement in PACU tallied in morphine equivalents during PACU stay
Time frame: Time frame between arrival and discharge in PACU, approximately 90 minutes
Population: Data was not available for 1 participant in the placebo group.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Guanfacine | Total Narcotic Requirement in PACU | 8.75 morphine equivalents |
| Placebo | Total Narcotic Requirement in PACU | 7.50 morphine equivalents |