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

Phase 3

Completed

Conditions: Intraoperative Complication
Pain
Malignant Female Reproductive System Neoplasm

Interventions: Drug: Epidural analgesia
Other: Intraoperative Complication Management and Prevention
Procedure: Pain Therapy

Registration Number: NCT02423876

Lead Sponsor: University of Wisconsin, Madison

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 104

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I (epidural placement, ERP)	Epidural analgesia	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 I (epidural placement, ERP)	Intraoperative Complication Management and Prevention	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 I (epidural placement, ERP)	Pain Therapy	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 (ERP)	Pain Therapy	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 (ERP)	Intraoperative Complication Management and Prevention	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.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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).
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.
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.
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
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.
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.
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.
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.
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.