Randomized Study Comparing the Use of Epidural Analgesia to Intravenous Narcotics for Laparoscopic Colorectal Resection.

Sponsor

University of California, Irvine (Other)

Overall Status

Completed

CT.gov ID

NCT02086123

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

2.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Laparoscopic colorectal surgery (LCS) has gained wide acceptance in the treatment of various pathology from diverticular disease to colon cancer. In comparison to conventional open surgery LCS has the benefits of shorter hospital stay, reduced postoperative pain, lower wound-related complication rates, better cosmetic results and earlier return to normal activities.

Despite the fact that laparoscopic colorectal surgery is done through smaller incisions, there is still a considerable amount of abdominal wall trauma with these procedures. This still can cause a significant amount of postoperative discomfort, which can add to patients' stress, decreased satisfaction, and prolong length of hospital stay. Postoperative pain can be difficult to control and has been mainly managed pharmacologically with the use of narcotics and non-narcotic medications delivered through different routes. The effectiveness of pain control depends on the medication, its dosage, frequency and route of administration. The latter is mainly achieved through the intravenous route in the immediate postoperative period in laparoscopic colorectal surgery patient, as patients are restricted from having anything by mouth until return of bowel function.

Another route of delivery is the use of local anesthetics as well as opioids via an epidural catheter. Epidural analgesia (EA) has the potential to offer excellent pain control and decrease the rate of postoperative ileus. Despite the extensive use of epidural anesthesia in obstetrics, to date there has been very few studies looking at the effectiveness of epidural analgesia in laparoscopic colorectal surgery.

The primary purpose of this study is to evaluate the impact of epidural analgesia as compared to conventional analgesia on the length of hospital stay in patients undergoing laparoscopic colorectal procedures. The secondary objectives of the study will be to evaluate patient satisfaction, quality of life, pain control and return of bowel function in patients treated with either epidural analgesia or intravenous narcotics.

Condition or Disease	Intervention/Treatment	Phase
Pain, Postoperative	Procedure: Epidural Analgesia Procedure: Parenteral Analgesia (Intravenous)	N/A

Detailed Description

Laparoscopic colorectal surgery has now become the standard of care in the treatment of many colorectal pathologies. In comparison to open or conventional surgery it has the benefit of decreased length of hospital stay (1), reduced postoperative pain, earlier return of bowel function (2,3) , earlier return to normal activities and improved cosmetic results.

Several criteria must be met before patients are discharged from the hospital. These discharge criteria are the same objective criteria we use to discharge our surgical patients:

Return of bowel function (as manifested by passage of flatus or bowel movement)
Ability to tolerate a regular diet
Stable vital signs for 24 hrs
Good pain control on oral medications
Ability to void freely
Return to a similar level of preoperative functioning

All attending surgeons will strictly adhere to the above 6 criteria when discharging patients.

Poor pain control is known to increase the length of hospital stay after surgery. Good pain control thus becomes essential in order to decrease the length of hospital stay and make patients more comfortable.

Pain control has been traditionally achieved through the intravenous route with the use of narcotic and non-narcotic medications. Postoperative pain is mainly incisional in nature and is due to enhanced responses to mechanical and thermal stimuli in the area of incision (6). Despite the fact that laparoscopic surgery is done through smaller incisions, several of these incisions are required to place the different trocars needed to safely perform the procedure. These incisions still cause a significant amount of pain and discomfort.

Opioid narcotics delivered systemically through the intravenous route are well known for their side effects, which range from mild nausea to opioid-induced bowel dysfunction (6). They are also known to prolong postoperative ileus by blocking coordinated bowel motility after surgery. The pathophysiology of ileus is multifactorial and incompletely understood. Major mechanisms contributing to ileus include surgical stress from physical manipulation of the bowel, secretion of inflammatory mediators, changes in fluid balance, hormones and electrolyte concentrations (7). Postoperative ileus can take several days to resolve and every effort should be made to help the bowel regain its function. This includes judicious use of IV fluids, correcting electrolyte abnormalities and finding the right balance between adequate pain control and delivering the right amount of intravenous pain medications. Controlling postoperative pain in an adequate manner without substantial systemic side effects becomes of primary importance. One way would be through the use of epidural analgesia where local anesthetics are injected through a catheter placed into the epidural space. The injection can cause both a loss of sensation and a loss of pain, by blocking the transmission of signals through nerves in or near the spinal cord while preserving motor function. The epidural space is the space inside the bony spinal canal but outside the membrane called the Dura mater. Thus there is no contact with the cerebrospinal fluid and the spinal cord itself.

Several trials of epidural analgesia in colorectal surgery patients have demonstrated the potential benefits of this technique such as decreased postoperative pain (8-10,12,14-18), faster return of bowel function with faster resolution of ileus (8,9,12, 14, 16,17) as well as a decreased incidence of nausea (17). These trials also showed that patients using epidural analgesia required less pain medications (10,11). A retrospective review from Sweden demonstrated a reduction in mortality after epidural anesthesia in patients undergoing rectal resection (19).

However, the results of these reports concerning length of hospital stay, cost and quality of life have been inconclusive. Most of the trials conducted until now have been very small with no more than 39 patients in each arm in the largest trial (9-17). The only study that showed a decreased length of hospital stay consisted of a cohort of 22 patients compared to a "historic" standard group (12). This study was small and non-randomized (12). The remaining studies, despite being randomized, were again small and thus have failed to show a decreased length of hospital stay in patients receiving epidural analgesia as compared to intravenous analgesia (9-11, 13-15, 16). The hypothesis advocated by some was that if the epidural decreases postoperative pain and allows for a faster recovery of bowel function then it should decrease the length of hospital stay. On the other hand, epidurals are usually left in place for 2-3 days following surgery before patients are transitioned to different forms of pain medications. This transition might in fact take time and actually increase the length of hospital stay thus potentially adversely affecting hospital costs. In addition, all the studies conducted until now have failed to adequately assess quality of life in patients receiving EA after laparoscopic colectomy.

Other measures that have been shown to reduce length of hospital stay and opioid induced side effects are with the use of alvimopan which is a peripherally acting μ-opioid receptor antagonist, recently approved for the reduction of postoperative ileus after colectomy. Alvimopan was associated with reduced ileus-related morbidity compared with placebo, without compromising opioid-based analgesia in patients undergoing surgery (20-21). Thus the use of alvimopan may obviate advocating the use of EA solely to reduce opioid-induced ileus.

This is a large prospective randomized trial recruiting 160 patients in each arm: an epidural arm and a conventional analgesia one. The trial will be performed in adult patients undergoing elective laparoscopic colorectal surgery for both benign and malignant conditions at the University of California, Irvine (UCI). The primary end point of the study would be to show a difference in length of hospital stay of one day between the 2 groups, and the secondary end points would be to show a decreased incidence of pain, earlier return of bowel function, earlier ambulation, better quality of life, less incidence of complications and side effects in the epidural group. This will be the largest randomized trial looking at the use of epidural analgesia in laparoscopic colorectal surgery to be ever conducted. It will hopefully provide definitive answers regarding any difference in the length of hospital stay. It will also address issues related to cost-effectiveness as well as quality of life using validated questionnaires, points that were not addressed by previously published data.

Study Design

Study Type:

Interventional

Actual Enrollment :

87 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Supportive Care

Official Title:

Randomized Clinical Trial Comparing the Use of Perioperative Epidural Analgesia to Conventional Intravenous Narcotics and NSAIDS for Patients Undergoing Laparoscopic Colorectal Resection

Study Start Date :

May 1, 2012

Actual Primary Completion Date :

Mar 1, 2015

Actual Study Completion Date :

Apr 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Epidural Analgesia Subjects randomized to this arm will receive Bupivacaine + Fentanyl Epidural Analgesia. Subjects on this group could be allowed to receive Toradol Intravenously (IV) + Acetaminophen Orally (PO) if needed.	Procedure: Epidural Analgesia Bupivacaine + Fentanyl
Active Comparator: Parenteral Analgesia (Intravenous) Subjects randomized to this arm will receive Analgesia with Dilaudid 0.2 -0.4 mg Intravenously (IV) every 3 hours. Subjects on this group could be allowed to receive Toradol Intravenously (IV) + Acetaminophen Orally (PO) if needed.	Procedure: Parenteral Analgesia (Intravenous) Dilaudid 0.2 -0.4 mg IV every 3 hours

Arm

Intervention/Treatment

Active Comparator: Epidural Analgesia

Subjects randomized to this arm will receive Bupivacaine + Fentanyl Epidural Analgesia. Subjects on this group could be allowed to receive Toradol Intravenously (IV) + Acetaminophen Orally (PO) if needed.

Procedure: Epidural Analgesia

Bupivacaine + Fentanyl

Active Comparator: Parenteral Analgesia (Intravenous)

Subjects randomized to this arm will receive Analgesia with Dilaudid 0.2 -0.4 mg Intravenously (IV) every 3 hours. Subjects on this group could be allowed to receive Toradol Intravenously (IV) + Acetaminophen Orally (PO) if needed.

Procedure: Parenteral Analgesia (Intravenous)

Dilaudid 0.2 -0.4 mg IV every 3 hours

Outcome Measures

Primary Outcome Measures

Length of Hospital Stay [1-7 days]
The primary end point of the analyses is length of hospital stay from the date of admission for the surgical procedure to the day of hospital discharge.

Secondary Outcome Measures

Return of bowel function [1-7 days]
The secondary outcome is to measure the length of time in days from the day of the surgical procedure to the time of return of bowel function (passage of flatus and bowel movements).

Other Outcome Measures

Intensity of postoperative pain. [1-7 days]
Other secondary objective of the study is to evaluate the intensity of postoperative pain measured by the visual analog scale. This objective will be evaluated applying a daily questionnaire to the patients asking about their level of pain.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age ≥ 18 years
Subjects undergoing laparoscopic large bowel resection or rectal resection with anastomosis and/ or any type of ostomy (end, diverting)
University of California, Irvine Medical Center inpatients and outpatients scheduled for surgery
Elective surgery for benign and malignant conditions

Exclusion Criteria:

Emergency procedure including procedures done for bowel obstruction, constriction, fulminant inflammation
Infection
Patient participating in other trials that may affect the study outcome
Subjects with hypersensitivity to any of the anesthesia drugs used per Standard of Care at UCI Medical Center
Subjects with history of chronic pain
Pregnant patients or nursing females
Subjects with a history of severe cardiovascular, pulmonary, renal, hepatic, hematologic or systemic disease
Early Study Termination due to conversion to Open Surgery (subjects who were converted from laparoscopic to open surgery
Contraindication to epidural anesthesia (bleeding diathesis, severe hypovolemia, elevated intracranial pressure, infection at the site of injection, and severe stenotic valvular heart disease or ventricular outflow obstruction.