Researchers at the University of Washington School of Medicine have performed the first randomized controlled clinical trial showing that a painful and even life-threatening bowel condition called acute colonic pseudo-obstruction can be effectively treated with intravenous neostigmine.
Results of the study will be published in the July 15 issue of the New England Journal of Medicine. However, the journal is releasing the study seven weeks early on its Web site, http://www.nejm.org, to ensure that doctors who treat the condition are notified as quickly as possible. The article is entitled "Neostigmine for the Treatment of Acute Colonic Pseudo-Obstruction."
Acute colonic pseudo-obstruction occurs in some hospitalized patients following surgery or severe medical illness. The condition is caused by a loss of normal motility or spontaneous bowel action. Also called Ogilvie's syndrome, it causes a severely distended colon (large intestine).
If conservative treatments to restore normal bowel function are not successful, some patients require colonic decompression by emergency colonoscopy or surgery, to prevent ischemia (cutoff of blood supply to the bowel) or perforation of the bowel. Some 3 percent of patients with the condition suffer a perforated bowel and half of those patients die.
In this prospective, double-blind, placebo-controlled trial, Drs. Robert J. Ponec, Michael D. Sanders and Michael B. Kimmey of the Division of Gastroenterology at University of Washington Medical Center confirm earlier uncontrolled studies showing that treatment with intravenous neostigmine is effective in relieving the condition.
The UW study involved 21 patients with a wide range of medical and surgical diagnoses, who had marked abdominal distention and dilated colon and who had failed to improve after 24 hours of conservative treatment. (Conservative treatment included nothing by mouth, nasogastric suction, intravenous fluids, electrolyte replacement and, where possible, withdrawal of drugs that adversely affect the colon's motility, such as narcotic pain relievers.)
They were randomly assigned to treatment with either intravenous neostigmine or saline solution as a placebo (inactive substance). A physician who was unaware of which treatment the patient had received recorded clinical response, abdominal circumference, and X-ray measurements of the colon. Patients who did not respond to the initial injection were eligible to receive neostigmine three hours later.
The study showed that colonic decompression was achieved in 10 of 11 patients who received neostigmine, compared to none of the 10 patients who received placebo, as determined by clinical response, and reductions in abdominal girth and colonic diameters.
The median time to clinical response, in the form of passing stool or gas, was four minutes. Seven of the patients who had received placebo later received neostigmine, with successful results. One patient who originally received the drug required a second open-label dose, with successful results. The most frequent side effects of the drug were mild abdominal pain and excessive salivation. Slowing of the heart beat in two patients required treatment with atropine.
"Our study confirms earlier studies showing that neostigmine is an effective, safe and inexpensive way to decompress the colon in patients with acute colonic pseudo-obstruction," said Kimmey, who is professor of medicine/gastroenterology at UW School of Medicine and director of GI endoscopy at UW Medical Center. "It should be considered prior to colonoscopy in patients with acute colonic pseudo-obstruction who have not responded to conservative management."
Journal
New England Journal of Medicine