Post-operative Pain
Conditions
Keywords
IV Acetaminophen, Ofirmev, Post-operative pain
Brief summary
The investigators' goal in this planned prospective, randomized, patient blinded study is to compare our standard of care as the control group to an experimental group in which patients receive preemptive IV acetaminophen dosing that is continued every 6 hours for a total of 8 doses in patients who have undergone major gynecologic surgery. The outcomes analyzed will include amount of rescue opioids required, time to return of bowel function, length of hospital stay, and patient satisfaction. The hypothesis is that the addition of IV acetaminophen will decrease the need for opioid rescue and thereby decrease the incidence of associated gastrointestinal side effects including nausea, vomiting, bloating, and constipation. The hope is that it will affect the final outcome of quicker return of bowel function, increased patient satisfaction, shortened hospital stay and prove to be an overall more effective postoperative pain management approach.
Detailed description
This is a patient-blinded prospective study in which patients that undergo major gynecologic surgery via an open abdominal approach will be randomized into two arms: 1. Control Group: Morphine patient-controlled-anesthesia (PCA) for the initial 24 hours post-operation with a low-dose basal rate (0.5mg/hr) and patient administered boluses prn. Oral oxycodone from 24-48 hours post-operation will be used prn for pain and then patients will be transitioned to oral combined oxycodone/acetaminophen for the remainder of their hospital stay. Normal saline 100cc IV will be infused as placebo every 6 hours for a total of eight doses with the first dose being given at time of anesthesia induction. 2. Experimental Group: Morphine PCA for the initial 24 hours post-operation with low-dose basal rate (0.5mg/hr) with patient administered boluses prn. IV acetaminophen 1,000mg will be given every six hours for a total of eight doses with the first dose being given at time of anesthesia induction. Oral oxycodone from 24-48 hours post-operation will be used prn and then patients will be transitioned to oral combined oxycodone/acetaminophen for the remainder of their hospital stay. Outcomes that will be analyzed include the amount of opioids used; time to return of bowel function designated as passage of flatus; time to first bowel movement if it occurs while inpatient; duration of hospital stay; and patient symptoms and satisfaction at the 24 and 48 hour marks as well as at time of discharge.
Interventions
DRUGPlacebo
Normal saline (100cc) will be given IV as the placebo medication every six hours for a total of eight doses with the first dose being given at time of anesthesia induction.
DRUGIV acetaminophen
IV acetaminophen (1,000mg) will be given every six hours for a total of eight doses with the first dose being given at time of anesthesia induction.
Sponsors
Aultman Health Foundation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
-Female patients undergoing major gynecologic surgery via an open abdominal approach. The included surgeries would be exploratory laparotomy with or without removal of uterus, fallopian tubes, or ovaries.
Exclusion criteria
* Patients with baseline preoperative liver function enzymes (AST and ALT) that are greater than twice the upper limit of normal would be excluded. * Patients with baseline CrCl \<30. * Patients that require intensive postoperative care and delayed extubation will typically require additional sedation which would impede adequate evaluation of the two study pain regimens as they are designed to be patient controlled. * Patients with complications unrelated to the pain regimens that prolong their stay would be excluded from the evaluation of hospital stay and cost effectiveness analyses. Examples would include but are not limited to pre-renal azotemia and acute renal failure; pneumonia; venous thromboembolism; or need for re-exploration laparotomy. * Allergy to acetaminophen would exclude those patients set to enter the experimental IV acetaminophen study arm. One exception would be if the allergy were trivial and related to route of administration such as mild nausea with oral acetaminophen. * Patients that undergo a bowel resection during surgery as it may adversely effect return of bowel function * Patients that have required regular opioid intake for the 7 days preceding surgery. * NSAIDs within 8 hours of surgery. * Chronic steroid use with the exception of low-dose inhaled steroid formulations. * Chronic alcohol or drug abuse. * Patients currently pregnant. * Patients unable to provide informed consent. * Age \>85 * Any physical, medical, and mental condition that would make participation in the study inadvisable.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Opioid Rescue - 48 Hours | First 48 hours including pre-operative and intra-operative medications | Mean number opioid rescue in the first 48 hours calculated by converting all opiates to intravenous morphine |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patient Satisfaction - Pain Control at 24 Hours, 48 Hours, and Discharge | At 24 hours 48 hours, and discharge (up to 7 days) | Subjects will rate their overall satisfaction with pain control on a 5-point Likert scale: 1=Strongly disagree; 2=Disagree; 3=Neutral; 4=Agree; 5=Strongly Agree |
| Patient Satisfaction - Nausea Control at 24 Hours, 48 Hours, and Discharge | At 24 hours, 48 Hours, and Discharge (up to 7 days) | Subjects will rate their overall satisfaction with nausea control on a 5-point Likert scale 1=Strongly disagree; 2=Disagree; 3=Neutral; 4=Agree; 5=Strongly Agree |
| Return of Bowel Function | Duration of hospital stay (up to 7 days). | Time to return of bowel function (passage of flatus) in hours |
| Patient Satisfaction - Pruritis at 24 Hours, 48 Hours, and Discharge | At 24 hours, 48 Hours, and Discharge (up to 7 days) | Subjects will rate their overall satisfaction with pruritis control on a 5-point likert scale 1=Strongly disagree; 2=Disagree; 3=Neutral; 4=Agree; 5=Strongly Agree |
| Length of Stay | Surgery to discharge | Mean length of post-operative stay in days |
| Patient Satisfaction - Bloating at 24 Hours, 48 Hours, and Discharge | At 24 hours, 48 Hours, and Discharge (up to 7 days) | Subjects will rate their overall satisfaction with bloating on a 5-point likert scale 1=Strongly disagree; 2=Disagree; 3=Neutral; 4=Agree; 5=Strongly Agree |
Countries
United States
Participant flow
Recruitment details
68 participants were enrolled between December 2013 and May 2014 at local institution
Participants by arm
| Arm | Count |
|---|---|
| Experimental (Normal Saline) Placebo: Normal saline (100cc) will be given IV as the placebo medication every six hours for a total of eight doses with the first dose being given at time of anesthesia induction.
Morphine patient-controlled-anesthesia (PCA) for the initial 24 hours post-operation with a low-dose basal rate (0.5mg/hr) and patient administered boluses prn. Oral oxycodone from 24-48 hours post-operation will be used prn for pain and then patients will be transitioned to oral combined oxycodone/acetaminophen for the remainder of their hospital stay. | 29 |
| Experimental (IV Acetaminophen) IV acetaminophen: IV acetaminophen (1,000mg) will be given every six hours for a total of eight doses with the first dose being given at time of anesthesia induction.
Morphine PCA for the initial 24 hours post-operation with low-dose basal rate (0.5mg/hr) with patient administered boluses prn. Oral oxycodone from 24-48 hours post-operation will be used prn and then patients will be transitioned to oral combined oxycodone/acetaminophen for the remainder of their hospital stay. | 30 |
| Total | 59 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 2 |
| Overall Study | Did not complete satisfaction surveys | 2 | 2 |
| Overall Study | Physician Decision | 1 | 0 |
Baseline characteristics
| Characteristic | Experimental (IV Acetaminophen) | Total | Experimental (Normal Saline) |
|---|---|---|---|
| Age, Continuous | 51.73 years STANDARD_DEVIATION 12.69 | 51.05 years STANDARD_DEVIATION 14.358 | 50.34 years STANDARD_DEVIATION 16.101 |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment United States | 30 Participants | 59 Participants | 29 Participants |
| Sex: Female, Male Female | 30 Participants | 59 Participants | 29 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 34 | 0 / 34 |
| other Total, other adverse events | 0 / 34 | 0 / 34 |
| serious Total, serious adverse events | 2 / 34 | 1 / 34 |
Outcome results
Primary
Opioid Rescue - 48 Hours
Mean number opioid rescue in the first 48 hours calculated by converting all opiates to intravenous morphine
Time frame: First 48 hours including pre-operative and intra-operative medications
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental (Normal Saline) | Opioid Rescue - 48 Hours | 54.4803 Milligrams of intravenous morphine equiv | Standard Deviation 22.86841 |
| Experimental (IV Acetaminophen) | Opioid Rescue - 48 Hours | 48.9253 Milligrams of intravenous morphine equiv | Standard Deviation 22.94435 |
p-value: 0.35695% CI: [-6.3904, 17.50042]t-test for Equality of Means
Secondary
Length of Stay
Mean length of post-operative stay in days
Time frame: Surgery to discharge
Population: Participants experiencing adverse event leading to increased length of stay were not analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental (Normal Saline) | Length of Stay | 3.62 Days | Standard Deviation 1.147 |
| Experimental (IV Acetaminophen) | Length of Stay | 3.57 Days | Standard Deviation 1.305 |
95% CI: [-0.587, 0.695]
Secondary
Patient Satisfaction - Bloating at 24 Hours, 48 Hours, and Discharge
Subjects will rate their overall satisfaction with bloating on a 5-point likert scale 1=Strongly disagree; 2=Disagree; 3=Neutral; 4=Agree; 5=Strongly Agree
Time frame: At 24 hours, 48 Hours, and Discharge (up to 7 days)
Population: Participants who completed the bloating satisfaction survey
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Experimental (Normal Saline) | Patient Satisfaction - Bloating at 24 Hours, 48 Hours, and Discharge | At 24 hours | 3.58 score on a scale | Standard Deviation 1.472 |
| Experimental (Normal Saline) | Patient Satisfaction - Bloating at 24 Hours, 48 Hours, and Discharge | At 48 hours | 3.75 score on a scale | Standard Deviation 1.152 |
| Experimental (Normal Saline) | Patient Satisfaction - Bloating at 24 Hours, 48 Hours, and Discharge | At Discharge | 3.79 score on a scale | Standard Deviation 1.141 |
| Experimental (IV Acetaminophen) | Patient Satisfaction - Bloating at 24 Hours, 48 Hours, and Discharge | At 24 hours | 4.23 score on a scale | Standard Deviation 0.951 |
| Experimental (IV Acetaminophen) | Patient Satisfaction - Bloating at 24 Hours, 48 Hours, and Discharge | At 48 hours | 3.69 score on a scale | Standard Deviation 1.05 |
| Experimental (IV Acetaminophen) | Patient Satisfaction - Bloating at 24 Hours, 48 Hours, and Discharge | At Discharge | 3.35 score on a scale | Standard Deviation 1.093 |
p-value: 0.217ANOVA
Secondary
Patient Satisfaction - Nausea Control at 24 Hours, 48 Hours, and Discharge
Subjects will rate their overall satisfaction with nausea control on a 5-point Likert scale 1=Strongly disagree; 2=Disagree; 3=Neutral; 4=Agree; 5=Strongly Agree
Time frame: At 24 hours, 48 Hours, and Discharge (up to 7 days)
Population: Participants who completed the nausea control survey.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Experimental (Normal Saline) | Patient Satisfaction - Nausea Control at 24 Hours, 48 Hours, and Discharge | At 24 hours | 3.88 score on a scale | Standard Deviation 0.9 |
| Experimental (Normal Saline) | Patient Satisfaction - Nausea Control at 24 Hours, 48 Hours, and Discharge | At 48 hours | 4.12 score on a scale | Standard Deviation 0.992 |
| Experimental (Normal Saline) | Patient Satisfaction - Nausea Control at 24 Hours, 48 Hours, and Discharge | At Discharge | 4.17 score on a scale | Standard Deviation 0.761 |
| Experimental (IV Acetaminophen) | Patient Satisfaction - Nausea Control at 24 Hours, 48 Hours, and Discharge | At 24 hours | 3.73 score on a scale | Standard Deviation 1.041 |
| Experimental (IV Acetaminophen) | Patient Satisfaction - Nausea Control at 24 Hours, 48 Hours, and Discharge | At 48 hours | 3.50 score on a scale | Standard Deviation 1.068 |
| Experimental (IV Acetaminophen) | Patient Satisfaction - Nausea Control at 24 Hours, 48 Hours, and Discharge | At Discharge | 3.65 score on a scale | Standard Deviation 0.797 |
p-value: 0.643ANOVA
Secondary
Patient Satisfaction - Pain Control at 24 Hours, 48 Hours, and Discharge
Subjects will rate their overall satisfaction with pain control on a 5-point Likert scale: 1=Strongly disagree; 2=Disagree; 3=Neutral; 4=Agree; 5=Strongly Agree
Time frame: At 24 hours 48 hours, and discharge (up to 7 days)
Population: Participants who completed the pain satisfaction survey at 24 hours
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Experimental (Normal Saline) | Patient Satisfaction - Pain Control at 24 Hours, 48 Hours, and Discharge | At 24 hours | 4.21 score on a scale | Standard Deviation 0.721 |
| Experimental (Normal Saline) | Patient Satisfaction - Pain Control at 24 Hours, 48 Hours, and Discharge | At 48 hours | 4.08 score on a scale | Standard Deviation 0.881 |
| Experimental (Normal Saline) | Patient Satisfaction - Pain Control at 24 Hours, 48 Hours, and Discharge | At Discharge | 4.58 score on a scale | Standard Deviation 0.654 |
| Experimental (IV Acetaminophen) | Patient Satisfaction - Pain Control at 24 Hours, 48 Hours, and Discharge | At 24 hours | 4.19 score on a scale | Standard Deviation 1.021 |
| Experimental (IV Acetaminophen) | Patient Satisfaction - Pain Control at 24 Hours, 48 Hours, and Discharge | At 48 hours | 4.04 score on a scale | Standard Deviation 0.824 |
| Experimental (IV Acetaminophen) | Patient Satisfaction - Pain Control at 24 Hours, 48 Hours, and Discharge | At Discharge | 4.23 score on a scale | Standard Deviation 0.951 |
p-value: 0.029ANOVA
Secondary
Patient Satisfaction - Pruritis at 24 Hours, 48 Hours, and Discharge
Subjects will rate their overall satisfaction with pruritis control on a 5-point likert scale 1=Strongly disagree; 2=Disagree; 3=Neutral; 4=Agree; 5=Strongly Agree
Time frame: At 24 hours, 48 Hours, and Discharge (up to 7 days)
Population: Participants who completed the pruritus satisfaction survey
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Experimental (Normal Saline) | Patient Satisfaction - Pruritis at 24 Hours, 48 Hours, and Discharge | At 24 hours | 3.71 score on a scale | Standard Deviation 1.459 |
| Experimental (Normal Saline) | Patient Satisfaction - Pruritis at 24 Hours, 48 Hours, and Discharge | At 48 hours | 3.67 score on a scale | Standard Deviation 1.404 |
| Experimental (Normal Saline) | Patient Satisfaction - Pruritis at 24 Hours, 48 Hours, and Discharge | At Discharge | 3.54 score on a scale | Standard Deviation 1.382 |
| Experimental (IV Acetaminophen) | Patient Satisfaction - Pruritis at 24 Hours, 48 Hours, and Discharge | At 24 hours | 3.58 score on a scale | Standard Deviation 1.391 |
| Experimental (IV Acetaminophen) | Patient Satisfaction - Pruritis at 24 Hours, 48 Hours, and Discharge | At 48 hours | 3.85 score on a scale | Standard Deviation 1.12 |
| Experimental (IV Acetaminophen) | Patient Satisfaction - Pruritis at 24 Hours, 48 Hours, and Discharge | At Discharge | 3.88 score on a scale | Standard Deviation 1.177 |
p-value: 0.647ANOVA
Secondary
Return of Bowel Function
Time to return of bowel function (passage of flatus) in hours
Time frame: Duration of hospital stay (up to 7 days).
Population: Only participants with documented return of bowel function prior to discharge were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental (Normal Saline) | Return of Bowel Function | 68.0878 Hours | Standard Deviation 22.99293 |
| Experimental (IV Acetaminophen) | Return of Bowel Function | 56.5696 Hours | Standard Deviation 27.88443 |
p-value: 0.10595% CI: [-2.49963, 25.53599]t-test for Equality of Means