Hydration, Indomethacin to Prevent Pancreatitis Following ERCP

Investigators performed a meta-analysis to determine which clinical strategy is most effective for the prevention of PEP in patients with ERCP.

Aggressive hydration (AH) plus rectal indomethacin appears to be the most efficient strategy for preventing postendoscopic retrograde cholangiopancreatography pancreatitis (PEP) in average-risk to high-risk patients with endoscopic retrograde cholangiopancreatography pancreatitis (ERCP), according to a study in the Journal of Clinical Gastroenterology.

Researchers conducted a systematic literature review of PubMed, EMBASE, and Cochrane CENTRAL databases from inception to January 14, 2020.They identified studies that investigated the efficacy of American Society of Gastrointestinal Endoscopy-recommended and European Society of Gastrointestinal Endoscopy-recommended endoscopic (ie, pancreatic duct stent) and pharmacologic interventions (ie, AH, rectal diclofenac, or indomethacin, sublingual nitrate) and their combinations. They identified 38 studies with 8980 patients and 10 different interventions for PEP prevention.

After performing direct comparisons for pharmacologic and endoscopic interventions relative to a control group, the study authors found that all interventions were better when compared with controls.

Pancreatic stents (PS) reduced the odds of PEP by 64% compared with controls (odds ratio [OR], 0.36; 95% CI, 0.26-0.50; P <.01). Rectal nonsteroidal anti-inflammatory drugs (NSAIDs) reduced PEP events by 52% (OR, 0.48; 95% CI, 0.31-0.74; P <.01), compared with placebo. PEP reduction with rectal diclofenac was 52% (OR, 0.48; 95% CI, 0.31-0.74), and PEP reduction with rectal indomethacin was 44% (OR, 0.56; 95% CI, 0.35-0.89). The difference between the groups was not significant.

After calculating the network effect estimate as a weighted average of both direct and indirect comparisons in the network, the investigators found that all treatments were better than placebo or no intervention for preventing PEP. AH+indomethacin appeared to achieve the most effective response (OR, 0.028; 95% credible intervals [CrI], 0.00094-0.20).

AH+indomethacin had the highest probability of being ranked best (95%) for the primary outcome of PEP prevention, followed by AH with rectal diclofenac (78%) and sublingual glyceryl nitrate with rectal diclofenac (68%).

To rank interventions among high-risk patients, the investigators identified studies evaluating only these patients and conducted a network meta-analysis. The network estimate was significant only for PS (OR, 0.25; 95% CrI, 0.12-0.42) and rectal indomethacin (OR, 0.36; 95% CrI, 0.11-0.99), compared with controls.

Among several study limitations, the researchers noted the risk of publication bias, as new treatments may have been selectively published. In addition, a limited number of studies evaluating combinations of rectal NSAIDs with AH or sublingual nitrate and reporting positive outcomes may have overestimated efficacy.

“Our findings should encourage future research to explore the role of pharmacologic combinations to decrease PEP incidence further and to assess if this approach can be an alternative to PS, even in high-risk patients,” the investigators stated.


Radadiya D, Brahmbhatt B, Reddy C, Devani K. Efficacy of combining aggressive hydration with rectal indomethacin in preventing post-ERCP pancreatitis: a systematic review and network meta-analysis. J Clin Gastroenterol. Published online March 25, 2021. doi: 10.1097/MCG.0000000000001523