April 11, 2012 — A single indomethacin suppository administered to patients immediately after endoscopic retrograde cholangiopancreatography (ERCP) appears to significantly reduce the risk for pancreatitis compared with placebo in high-risk patients, according to the findings of a large randomized trial.
B. Joseph Elmunzer, MD, assistant professor of internal medicine, Division of Gastroenterology, University of Michigan Medical Center, Ann Arbor, and colleagues reported their findings in the April 12 issue of the New England Journal of Medicine.
According to the researchers, rectal nonsteroidal anti-inflammatory drugs (NSAIDs) are seldom used in post-ERCP pancreatitis in clinical practice because there is no conclusive evidence from randomized controlled trials.
"Moreover, it remains unclear whether NSAIDs provide incremental benefit over temporary pancreatic stents, the only proven prophylactic intervention for post-ERCP pancreatitis," Dr. Elmunzer and colleagues write.
The current study included 602 patients at elevated risk for post-ERCP pancreatitis who were randomly assigned to receive a single dose of rectal indomethacin or placebo immediately after ERCP.
Most patients (82.3%) were at high risk for post-ERCP pancreatitis because of a clinical suspicion of sphincter of Oddi dysfunction, and more than half had sphincter hypertension, as documented on manometry. Other reasons included a history of post-ERCP pancreatitis, pancreatic sphincterotomy, more than 8 cannulation attempts, or ampullectomy.
Post-ERCP pancreatitis was defined as new upper abdominal pain, an increase in pancreatic enzymes to at least 3 times the upper limit of the normal range 24 hours after ERCP, and hospitalization for at least 2 nights.
Post-ERCP pancreatitis was observed in 9.2% of patients receiving indomethacin compared with 16.9% receiving placebo (P = .005), representing a 46% relative risk reduction with prophylactic indomethacin.
In addition, moderate-to-severe pancreatitis was noted in 4.4% in the indomethacin group and 8.8% in the placebo group (P = .03). The authors also found that prophylactic indomethacin was associated with a shorter hospital stay (3.5 days vs 4.0 days; P < .001).
Indomethacin was well tolerated: There was no significant difference in the frequency or severity of bleeding events between groups.
"[P]rophylactic rectal indomethacin significantly reduced the incidence and severity of post-ERCP pancreatitis in patients at elevated risk for this complication, particularly in those with a clinical suspicion of sphincter of Oddi dysfunction," the authors conclude.
"The results of the study were very impressive," Dr. Elmunzer noted in a university news release. "We found that indomethacin was highly protective."
The Data Have Immediate Clinical Relevance
"These recent finding have great clinical relevance," said Ulrich Christian Bang, MD, PhD, from the Department of Gastroenterology at Hvidovre Hospital in Denmark, who was not involved in the work.
"In light of the potential severe morbidity related to post-ERCP acute pancreatitis, the benefit of this easily applied prophylactic measure should be interesting news for all clinicians performing ERCPs," Dr. Bang told Medscape Medical News.
According to Dr. Bang, these findings together with earlier supportive results indicate that NSAIDs administered either orally or rectally are effective.
"In light of the minimal side effects associated with 1-dose NSAID (especially no increased prevalence of [gastrointestinal] bleeding), this approach may be valid for immediate introduction into clinical practice," he said.
Dr. Bang added that a difficult task before ERCP is to appropriately identify high-risk patients, and that further studies on certain subgroups are needed. "Nonetheless, indomethacin seems to be the most promising approach to reduce the incidence of post-ERCP for the time being."
The study was supported by the National Institutes of Health. Several authors have received honoraria, grant support, speakers fees, and other financial reimbursement from companies including, but not limited to, Olympus Inc, Xlumena, US Endoscopy, Eli Lilly and Company, Sandhill Scientific, Up To Date, Abbott, JBR Pharma, Boston Scientific, Salix, Pfizer, Novartis, Astra Zeneca, and Medscape. Dr. Bang has disclosed no relevant financial relationships.
N Engl J Med. 2012;366:1414-1422. Abstract
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Cite this: Indomethacin Reduces Post-ERCP Pancreatitis Risk - Medscape - Apr 11, 2012.