• Do NSAIDs Prevent PEP?

Do NSAIDs Prevent PEP?

Rectal indomethacin does not prevent pancreatitis following endoscopic retrograde cholangiopancreatography (ERCP), researchers report from a randomized controlled study published in the April issue of Gastroenterology. These findings contradict more than a decade of evidence that nonsteroidal anti-inflammatory drugs (NSAIDs) decrease the risk of post-ERCP pancreatitis (PEP).

Acute pancreatitis is the most common gastrointestinal indication for admission to the hospital in the US. It frequently occurs after ERCP, and extensive research has been devoted to reduce this outcome. Rectal administration of NSAIDs has been reported to reduce the incidence of acute pancreatitis after ERCP.

One NSAID in particular, rectal indomethacin, has been used extensively, because a controlled trial reported that a single (100 mg) dose of rectal indomethacin significantly reduced the risk of PEP from ERCP. As a result of this study and others, the European Society for Gastrointestinal Endoscopy in 2014 recommended routine rectal administration indomethacin or diclofenac during ERCP in all patients without contraindication.

However, it is not clear whether rectal NSAIDs prevent PEP in patients not at high risk for PEP (average-risk patients).

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John M. Levenick et al investigated the ability of rectal indomethacin to prevent PEP in all patients undergoing ERCP in a prospective, randomized, double-blind, placebo-controlled trial of 449 consecutive patients. Approximately 70% of the cohort were at average risk for PEP. The subjects were assigned to groups given either a single (100 mg) dose of rectal indomethacin (n=223) or a placebo suppository (n=226) during the procedure.

Levenick et al found that 16 patients in the indomethacin group (7.2%) and 11 in the placebo group (4.9%) developed PEP—a nonsignificant difference. Complications and the severity of PEP were similar between groups. The trial was stopped due to its futility.

Neither the severity of pancreatitis, risk of gastrointestinal bleeding, rate of readmission to the hospital within 30 days, or mortality differed significantly between the groups (see figure).

In a subgroup analysis, among patients with only biliary manipulation, 3 of 124 (2.4%) in the placebo group and 2 of 125 (1.6%) in the indomethacin group had PEP. In patients with pancreatic ductal instrumentation only, 3 of 28 (10.7%) in the placebo group and 6 of 32 (18.8%) in the indomethacin group developed PEP. Manipulation of both ducts (including wire access only) resulted in PEP in 5 of 70 (7.1%) patients in the placebo group and in 8 of 70 (11.4%) in the indomethacin group. None of these differences were significant.

Levenick et al state that although rectal NSAIDs prevent PEP in high-risk individuals, these drugs do not reduce the incidence or severity of PEP in consecutive patients undergoing ERCP.

In an editorial that accompanies the article, Martin L. Freeman and Richard A. Kozarek state that previous studies of NSAIDs for prevention of PEP did not include a cross-section of ERCPS typically performed in the US.

Nonetheless, many institutions began using rectal indomethacin in all patients undergoing ERCP. Levenick et al state that universal prophylaxis using rectal indomethacin for PEP is not beneficial and should not be recommended.

Because rectal NSAIDs are inexpensive and have little chance of causing serious side effects, some say that a slight increase in chance of preventing PEP outweighs the minimal risk. Levenick et al state, however, than guidelines that promulgate universal prophylaxis based on presumptive application to groups not fully studied are not justified—not only can assumptions lead to unnecessary medication use and charges, but also to liabilities.

Freeman and Kozarek say that the keys to preventing PEP include selection of appropriate patients for ERCP, avoiding pancreatic manipulations whenever possible for average-risk biliary indications, and placement of pancreatic stents.

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