Clinical Drug Experience Knowledgebase

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

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.