Intraoperative Complication, Malignant Female Reproductive System Neoplasm, Pain
Conditions
Brief summary
This randomized clinical trial studies epidural anesthesia within an enhanced recovery pathway (ERP) in reducing pain in patients undergoing gynecologic surgery. An epidural analgesia (pain relief) is a small tube placed in the lower back that numbs the nerves and stops the feeling of pain. It stays in place for several days after surgery and may be helpful for pain control in patients with gynecologic cancer after surgery. ERP is a set of specific steps used before, during, and after surgery by health care providers to care for patients after surgery. ERPs include patient education, not using laxatives before surgery, increasing activity after surgery, and scheduled use of medications for pain and nausea. Giving epidural anesthesia as part of an ERP may improve pain control in patients undergoing gynecologic surgery.
Detailed description
PRIMARY OBJECTIVES: I. Mean postoperative pain score for the first 24 hours post-operatively, (measured by the Numeric Rating Scale \[NRS\], which rates pain on a 1-10 scale, collected routinely on the post-operative floor) will be compared between the epidural and no-epidural groups. SECONDARY OBJECTIVES: I. Total opioid use measured in oral morphine equivalents for the first two days post-surgery. II. Length of hospital stay (measured in hours from admission to time of discharge order placement). III. Post-operative antiemetic use and number of recorded episodes of emesis. IV. Return of bowel function (measured in hours from completion of surgery to passage of flatus). V. Subject satisfaction at the 4 week post-operative visit (as measured by two pain satisfaction questions taken from the Hospital Consumer Assessment of Healthcare Providers and Systems \[HCAHPS\] survey). VI. Post-operative complications (urinary tract infections \[UTIs\], thromboembolic events, pneumonia, blood transfusion, myocardial infarction, falls). VII. Readmission rate. VIII. Epidural discontinuation rates prior to planned removal (in epidural group only). IX. Stress and inflammation serum and saliva markers at baseline and the first day after surgery, as well as at their postoperative visit. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients undergo epidural placement in the First Day Surgery pre-operative area or similar areas suitable for insertion of epidural catheters. In the post-operative anesthesia care unit, patients may receive medication via the epidural on an as needed basis, as determined by the anesthesia team. Dosing and rate of standardized medication will be managed by the anesthesia team until the epidural is removed. Patients complete the ERP comprising increased activity, dietary restrictions, fluid balance, as well as anti-nausea, anti-inflammatory and pain medications at specific times. Patients will have access to additional pain medications as needed to control their pain. ARM II: Patients complete the ERP comprising increased activity, dietary restrictions, fluid balance, as well as anti-nausea, anti-inflammatory and pain medications at specific times. Patients will have access to additional pain medications as needed to control their pain.
Interventions
DRUGEpidural analgesia
Receive epidural placement. Standard epidural medications and dosage are as follows: * 0.1% ropivicaine + 10 mcg/mL hydromorphone at 6 mL/hr continuous rate * 3 mL/hr RN bolus, to be used as needed based on pain ratings * 3 mL/30 minutes patient bolus, which is available on patient demand.
OTHERIntraoperative Complication Management and Prevention
Undergo ERP
PROCEDUREPain Therapy
Undergo ERP
Sponsors
University of Wisconsin, Madison
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients undergoing gynecologic surgery via midline vertical laparotomy at University of Wisconsin Hospital and Clinics (UWHC) * Patients must be English speaking * Patients must have the ability to understand visual and verbal pain scales * Patients must be eligible for epidural placement
Exclusion criteria
* Known allergy to local anesthetics * Known history of chronic pain disorders and/or chronic opioid use defined as \> 10 mg of oral (PO) morphine or equivalent used daily for at least 30 days prior to enrollment * Patient is a prisoner or incarcerated * Significant liver disease that would inhibit prescription of opioids * Significant kidney disease that would inhibit administration of gabapentin * Patient has a history of opioid dependence requiring rehabilitation or the use of opioid antagonists * Patient is pregnant * Patients with a planned exploration with biopsies (no organs removed) will be excluded from the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Relative Pain Scores, as Measured by the Pain Numeric Rating Scale (NRS) | Up to 24 hours post-surgery | Relative pain scores between the epidural and non-epidural group will be analyzed by calculating a two-sided 95% confidence interval on the difference in mean scores between the two groups and concluding non-inferiority if this lies entirely below 2 points (mean non-epidural pain score proven, within a 95% confidence limit, to be at most 2 points worse than mean pain score in the epidural group). NRS rates pain on a 1-10 scale, with 1 being no pain, and 10 being the worst pain imaginable. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Difference in IL-2 Levels Between Pre-operative and Post-operative Values | Baseline to up to day 1 post-surgery | Will be compared using two-sided 95% confidence intervals for their mean differences. Superiority tests at the two-sided .05 level will be conducted by determining whether these confidence intervals overlap. |
| Epidural Discontinuation Rates Prior to Planned Removal (in Epidural Group Only) | Up to post-operative day 14 | Will be tabulated and presented for each group (where applicable). |
| Length of Hospital Stay (Hours) | From admission to time of discharge order placement | Will be compared using two-sided 95% confidence intervals for their mean differences. Superiority tests at the two-sided .05 level will be conducted by determining whether these confidence intervals overlap. |
| Length of Time Until Return of Bowel Function | From completion of surgery to passage of flatus (report in days) | Will be compared using two-sided 95% confidence intervals for their mean differences. Superiority tests at the two-sided .05 level will be conducted by determining whether these confidence intervals overlap. |
| Number of Recorded Episodes of Emesis | Up to 5 days post-surgery | Will be compared using two-sided 95% confidence intervals for their mean differences. Superiority tests at the two-sided .05 level will be conducted by determining whether these confidence intervals overlap. |
| Average Daily Pain Score as Measured by Pain NRS Scores | Up to 2 days following surgery | Will be compared using two-sided 95% confidence intervals for their mean differences. Superiority tests at the two-sided .05 level will be conducted by determining whether these confidence intervals overlap. |
| Post-operative Antiemetic Use (Measured in mg of Ondanestron Used in the First 24 Hours After Surgery) | Up to 4 weeks post-surgery | Will be compared using two-sided 95% confidence intervals for their mean differences. Superiority tests at the two-sided .05 level will be conducted by determining whether these confidence intervals overlap. |
| Post-operative Complications (UTIs, Thromboembolic Events, Pneumonia, Blood Transfusion, Myocardial Infarction, Falls) | Up to 6 weeks post-surgery | \# of events in each group will be reported |
| Readmission Rate | Up to 6 weeks post-surgery | Will be compared using two-sided 95% confidence intervals for their mean differences. Superiority tests at the two-sided .05 level will be conducted by determining whether these confidence intervals overlap. |
| Total Opioid Use Measured in Oral Morphine Equivalents (mg) | Up to first 2 days post-surgery | Will be compared using two-sided 95% confidence intervals for their mean differences. Superiority tests at the two-sided .05 level will be conducted by determining whether these confidence intervals overlap. |
| Patient Satisfaction Scores Related to Pain Metrics, as Measured by the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) Survey | At 4 weeks post-operative visit | Will be compared using two-sided 95% confidence intervals for their mean differences. Superiority tests at the two-sided .05 level will be conducted by determining whether these confidence intervals overlap. Scores range from 1 to 4, with higher scores indicating higher satisfaction. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm I (Epidural Placement, ERP) Patients undergo epidural placement in the First Day Surgery pre-operative area or similar areas suitable for insertion of epidural catheters. In the post-operative anesthesia care unit, patients may receive medication via the epidural on an as needed basis, as determined by the anesthesia team. Dosing and rate of standardized medication will be managed by the anesthesia team until the epidural is removed. Patients complete the ERP comprising increased activity, dietary restrictions, fluid balance, as well as anti-nausea, anti-inflammatory and pain medications at specific times. Patients will have access to additional pain medications as needed to control their pain.
Epidural analgesia: Receive epidural placement. Standard epidural medications and dosage are as follows:
* 0.1% ropivicaine + 10 mcg/mL hydromorphone at 6 mL/hr continuous rate
* 3 mL/hr RN bolus, to be used as needed based on pain ratings
* 3 mL/30 minutes patient bolus, which is available on patient demand.
Intraoperative Complication Management and Prevention: Undergo ERP
Pain Therapy: Undergo ERP | 52 |
| Arm II (ERP) Patients complete the ERP comprising increased activity, dietary restrictions, fluid balance, as well as anti-nausea, anti-inflammatory and pain medications at specific times. Patients will have access to additional pain medications as needed to control their pain.
Intraoperative Complication Management and Prevention: Undergo ERP
Pain Therapy: Undergo ERP | 52 |
| Total | 104 |
Baseline characteristics
| Characteristic | Arm I (Epidural Placement, ERP) | Arm II (ERP) | Total |
|---|---|---|---|
| Age, Customized 20-29 years | 2 Participants | 1 Participants | 3 Participants |
| Age, Customized 30-39 years | 1 Participants | 1 Participants | 2 Participants |
| Age, Customized 40-49 years | 8 Participants | 11 Participants | 19 Participants |
| Age, Customized 50-59 years | 19 Participants | 16 Participants | 35 Participants |
| Age, Customized 60-69 years | 16 Participants | 18 Participants | 34 Participants |
| Age, Customized 70-79 years | 5 Participants | 3 Participants | 8 Participants |
| Age, Customized 80-89 years | 1 Participants | 2 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 3 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 51 Participants | 49 Participants | 100 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 3 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 48 Participants | 48 Participants | 96 Participants |
| Region of Enrollment United States | 52 participants | 52 participants | 104 participants |
| Sex: Female, Male Female | 52 Participants | 52 Participants | 104 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 / 52 | 0 / 52 |
| other Total, other adverse events | 35 / 52 | 28 / 52 |
| serious Total, serious adverse events | 1 / 52 | 1 / 52 |
Outcome results
Primary
Relative Pain Scores, as Measured by the Pain Numeric Rating Scale (NRS)
Relative pain scores between the epidural and non-epidural group will be analyzed by calculating a two-sided 95% confidence interval on the difference in mean scores between the two groups and concluding non-inferiority if this lies entirely below 2 points (mean non-epidural pain score proven, within a 95% confidence limit, to be at most 2 points worse than mean pain score in the epidural group). NRS rates pain on a 1-10 scale, with 1 being no pain, and 10 being the worst pain imaginable.
Time frame: Up to 24 hours post-surgery
Population: Modified intent to treat analysis
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Arm I (Epidural Placement, ERP) | Relative Pain Scores, as Measured by the Pain Numeric Rating Scale (NRS) | 3.87 score on a scale |
| Arm II (ERP) | Relative Pain Scores, as Measured by the Pain Numeric Rating Scale (NRS) | 4.95 score on a scale |
Secondary
Average Daily Pain Score as Measured by Pain NRS Scores
Will be compared using two-sided 95% confidence intervals for their mean differences. Superiority tests at the two-sided .05 level will be conducted by determining whether these confidence intervals overlap.
Time frame: Up to 2 days following surgery
Population: modified intent to treat
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Arm I (Epidural Placement, ERP) | Average Daily Pain Score as Measured by Pain NRS Scores | 3.98 score on a scale |
| Arm II (ERP) | Average Daily Pain Score as Measured by Pain NRS Scores | 5.12 score on a scale |
Secondary
Difference in IL-2 Levels Between Pre-operative and Post-operative Values
Will be compared using two-sided 95% confidence intervals for their mean differences. Superiority tests at the two-sided .05 level will be conducted by determining whether these confidence intervals overlap.
Time frame: Baseline to up to day 1 post-surgery
Population: Modified intent to treat analysis
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Arm I (Epidural Placement, ERP) | Difference in IL-2 Levels Between Pre-operative and Post-operative Values | 9.6 nmol/L |
| Arm II (ERP) | Difference in IL-2 Levels Between Pre-operative and Post-operative Values | 15.5 nmol/L |
Secondary
Epidural Discontinuation Rates Prior to Planned Removal (in Epidural Group Only)
Will be tabulated and presented for each group (where applicable).
Time frame: Up to post-operative day 14
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm I (Epidural Placement, ERP) | Epidural Discontinuation Rates Prior to Planned Removal (in Epidural Group Only) | 4 Participants |
Secondary
Length of Hospital Stay (Hours)
Will be compared using two-sided 95% confidence intervals for their mean differences. Superiority tests at the two-sided .05 level will be conducted by determining whether these confidence intervals overlap.
Time frame: From admission to time of discharge order placement
Population: Modified intent to treat
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Arm I (Epidural Placement, ERP) | Length of Hospital Stay (Hours) | 99.83 hours |
| Arm II (ERP) | Length of Hospital Stay (Hours) | 87.25 hours |
Secondary
Length of Time Until Return of Bowel Function
Will be compared using two-sided 95% confidence intervals for their mean differences. Superiority tests at the two-sided .05 level will be conducted by determining whether these confidence intervals overlap.
Time frame: From completion of surgery to passage of flatus (report in days)
Population: modified intent to treat analysis
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Arm I (Epidural Placement, ERP) | Length of Time Until Return of Bowel Function | 2.22 days |
| Arm II (ERP) | Length of Time Until Return of Bowel Function | 2.20 days |
Secondary
Number of Recorded Episodes of Emesis
Will be compared using two-sided 95% confidence intervals for their mean differences. Superiority tests at the two-sided .05 level will be conducted by determining whether these confidence intervals overlap.
Time frame: Up to 5 days post-surgery
Population: modified intent to treat analysis
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Arm I (Epidural Placement, ERP) | Number of Recorded Episodes of Emesis | .192 number of episodes |
| Arm II (ERP) | Number of Recorded Episodes of Emesis | .1875 number of episodes |
Secondary
Patient Satisfaction Scores Related to Pain Metrics, as Measured by the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) Survey
Will be compared using two-sided 95% confidence intervals for their mean differences. Superiority tests at the two-sided .05 level will be conducted by determining whether these confidence intervals overlap. Scores range from 1 to 4, with higher scores indicating higher satisfaction.
Time frame: At 4 weeks post-operative visit
Population: Modified intent to treat
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Arm I (Epidural Placement, ERP) | Patient Satisfaction Scores Related to Pain Metrics, as Measured by the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) Survey | 3.78 score on a scale of 1-4 |
| Arm II (ERP) | Patient Satisfaction Scores Related to Pain Metrics, as Measured by the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) Survey | 3.87 score on a scale of 1-4 |
Secondary
Post-operative Antiemetic Use (Measured in mg of Ondanestron Used in the First 24 Hours After Surgery)
Will be compared using two-sided 95% confidence intervals for their mean differences. Superiority tests at the two-sided .05 level will be conducted by determining whether these confidence intervals overlap.
Time frame: Up to 4 weeks post-surgery
Population: modified intent to treat analysis
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Arm I (Epidural Placement, ERP) | Post-operative Antiemetic Use (Measured in mg of Ondanestron Used in the First 24 Hours After Surgery) | 4.46 mg |
| Arm II (ERP) | Post-operative Antiemetic Use (Measured in mg of Ondanestron Used in the First 24 Hours After Surgery) | 3.17 mg |
Secondary
Post-operative Complications (UTIs, Thromboembolic Events, Pneumonia, Blood Transfusion, Myocardial Infarction, Falls)
\# of events in each group will be reported
Time frame: Up to 6 weeks post-surgery
Population: modified intent to treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm I (Epidural Placement, ERP) | Post-operative Complications (UTIs, Thromboembolic Events, Pneumonia, Blood Transfusion, Myocardial Infarction, Falls) | 15 Participants |
| Arm II (ERP) | Post-operative Complications (UTIs, Thromboembolic Events, Pneumonia, Blood Transfusion, Myocardial Infarction, Falls) | 12 Participants |
Secondary
Readmission Rate
Will be compared using two-sided 95% confidence intervals for their mean differences. Superiority tests at the two-sided .05 level will be conducted by determining whether these confidence intervals overlap.
Time frame: Up to 6 weeks post-surgery
Population: modified intent to treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm I (Epidural Placement, ERP) | Readmission Rate | 2 Participants |
| Arm II (ERP) | Readmission Rate | 2 Participants |
Secondary
Total Opioid Use Measured in Oral Morphine Equivalents (mg)
Will be compared using two-sided 95% confidence intervals for their mean differences. Superiority tests at the two-sided .05 level will be conducted by determining whether these confidence intervals overlap.
Time frame: Up to first 2 days post-surgery
Population: Modified intent to treat analysis
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Arm I (Epidural Placement, ERP) | Total Opioid Use Measured in Oral Morphine Equivalents (mg) | 50.1 mg |
| Arm II (ERP) | Total Opioid Use Measured in Oral Morphine Equivalents (mg) | 82.56 mg |