Intra-op Lidocaine and Ketamine Effect on Postoperative Bowel Function

Colorectal Cancer Clinical Trial

Official title:

A Randomised Controlled Trial of Lidocaine Infusion Plus Ketamine Injection Versus Placebo to Decrease Postoperative Ileus

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00229567
• Other study ID #: Bio-REB 03-1316
• Status: Terminated
• Phase: N/A
• First received: September 27, 2005
• Last updated: April 18, 2007
• Start date: September 2005
• Est. completion date: November 2006

Study information

• Verified date: April 2007
• Source: University of Saskatchewan
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial Summary

Bowel function after bowel surgery is delayed (postoperative ileus)by both opiates and the surgery itself. We hypothesized that decreasing opiate use by other analgesics will speed the return of bowel function after surgery. Lidocaine and Ketamine are drugs that appear to be synergistic and do not slow peristalsis. This study is a Randomised Controlled Trial of Lidocaine Infusion Plus Ketamine Injection versus Placebo to to determine whether they will decrease opiate use and then whether decreased opiate use will speed the return of bowel function.

Description:

Introduction: Postoperative ileus is a normal response to the surgical handling of bowel that causes transient impairment of bowel motility after abdominal surgery. It is characterized by distension, absence of bowel sounds, and lack of passage of flatus and stool. The duration of postoperative ileus is related to the degree of surgical manipulation and the location of surgery. Colonic surgery is associated with the longest duration of ileus. Morphine patient-controlled intravenous analgesia (PCIA) is commonly used to provide pain control after bowel surgery. The bowel wall contains opiate receptors that decrease bowel peristalsis in the presence of morphine. Thus, both surgery and PCIA slow return of normal bowel function.

Lidocaine and ketamine are non-opioid analgesics that have been shown to be safe and efficacious in low doses when combined with morphine for post-operative pain control. Since the addition of lidocaine or ketamine to a morphine PCIA regimen results in lower total use of morphine, and since lidocaine or ketamine does not slow peristalsis, , it is reasonable to expect that low-dose lidocaine or ketamine plus PCIA morphine will result in faster return of bowel function than PCIA morphine alone.

Intravenous lidocaine was first shown to relieve cancer pain in the 1950s. Since then, intravenous lidocaine has been shown also to relieve pain after a wide variety of surgeries. Ketamine is a non-opioid analgesic that has been shown to be safe and efficacious in very low doses when combined with morphine for post-operative pain control . A review of ketamine for postoperative pain control recently completed by Dr McKay has shown that ketamine is most efficacious when given after a painful surgical insult, and that preoperative bezodiazepines prevent ketamine-induced hallucinations (submitted for publication). Groudine, in patients undergoing radical retropubic prostatectomy, determined that intravenous lidocaine infusion intraoperatively decreased the duration of postoperative ileus, decreased the pain scores postoperatively, and resulted in a 50% reduction in morphine use, and a 20% reduction in hospitalization time. This was felt to be due to early ambulation, earlier times to passing gas and having a bowel movement, and faster advancement to a full diet and oral analgesics. Lidocaine plasma levels were well below toxic range.

We propose a double-blind placebo-controlled study of patients undergoing elective or urgent colon surgery with an anastomotic procedure. All patients will receive normal PCA morphine in addition to study drugs or placebo. Research will be conducted at Saskatoon teaching hospitals. This procedure was chosen as it is associated with a longer duration of ileus compared to other abdominal surgeries and more likely to show a significant treatment effect.

If previous data is applicable to colonic surgery then we can expect a decrease in postoperative analgesic requirements, earlier return of bowel function, earlier progression to full diet and earlier discharge dates.

The dose of lidocaine we propose has been shown to be safe in thousands of patients for whom it was used to treat arrhythmias; that of ketamine in more than twenty studies of postoperative pain control.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 60
• Est. completion date: November 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 79 Years

Eligibility

Inclusion Criteria:

• age 18 to 79

• booked for urgent or elective colon surgery undergoing a left, right, or transverse hemicolectomy via laparotomy

Exclusion Criteria:

• patients requiring emergency surgery

• pregnant subjects or those who might be pregnant

• subjects allergic to lidocaine, ketamine, morphine, naproxen, or acetaminophen

• subjects with epidural analgesia

• subjects unable to understand and implement a Patient-Controlled Intravenous Analgesia system

• subjects who do not know English well enough to understand the consent form and assessments

• subjects with known hepatic or renal failure or cardiac dysrhythmias or atrioventricular block

• patients with pre-existing functional bowel motility disorders including Crohn's disease and ulcerative colitis

• daily use of laxatives, inability to have a bowel movement without laxatives, use of suppositories or enemas on a daily basis, or use of antimotility agents

• patients with Parkinson’s disease

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Colorectal Cancer

Intervention

Drug:
• Lidocaine infusion plus ketamine injection

Locations

Country	Name	City	State
Canada	Saskatoon Health Region, 410 22nd Street East	Saskatoon	Saskatchewan

Sponsors (2)

Lead Sponsor	Collaborator
University of Saskatchewan	Saskatoon Health Region

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean time after surgery to completion of the following postoperative markers:
Primary	drinking and retaining 500ml clear fluids,
Primary	presence of bowel sounds
Primary	passage of flatus, and
Primary	passage of stool.
Secondary	pain after cough by VAS
Secondary	narcotic usage
Secondary	nausea
Secondary	vomiting
Secondary	infection, dehiscence and other surgical complications
Secondary	time to readiness for discharge from hospital