Epidural Anesthesia Within an Enhanced Recovery Pathway in Reducing Pain in Patients Undergoing Gynecologic Surgery

Study Overview
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Brief Summary
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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
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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.

Official Title
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UW14030: Epidural Anesthesia as Part of an Enhanced Recovery Pathway in Gynecologic Surgery

Conditions
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Intraoperative Complication, Malignant Female Reproductive System Neoplasm, Pain

Intervention / Treatment
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* Drug: Epidural analgesia
* Other: Intraoperative Complication Management and Prevention
* Procedure: Pain Therapy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (epidural placement, ERP)<br>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. | Drug: Epidural analgesia<br>* 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.<br>* Other names: Exalgo;Other: Intraoperative Complication Management and Prevention<br>* Undergo ERP<br>* Other names: Intraoperative Complication Management/Prevention;Procedure: Pain Therapy<br>* Undergo ERP<br>* Other names: Pain, Pain Management;|
| Active Comparator: Arm II (ERP)<br>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. | Other: Intraoperative Complication Management and Prevention<br>* Undergo ERP<br>* Other names: Intraoperative Complication Management/Prevention;Procedure: Pain Therapy<br>* Undergo ERP<br>* Other names: Pain, Pain Management;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Up to 24 hours post-surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Up to 2 days following surgery | 
| 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. | Baseline to up to day 1 post-surgery | 
| Epidural Discontinuation Rates Prior to Planned Removal (in Epidural Group Only) | Will be tabulated and presented for each group (where applicable). | Up to post-operative day 14 | 
| 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. | From admission to time of discharge order placement | 
| 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. | From completion of surgery to passage of flatus (report in days) | 
| 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. | Up to 5 days post-surgery | 
| 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. | At 4 weeks post-operative visit | 
| 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. | Up to 4 weeks post-surgery | 
| Post-operative Complications (UTIs, Thromboembolic Events, Pneumonia, Blood Transfusion, Myocardial Infarction, Falls) | # of events in each group will be reported | Up to 6 weeks post-surgery | 
| 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. | Up to 6 weeks post-surgery | 
| 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. | Up to first 2 days post-surgery |