Tag Archives: indomethacin

Ketorolac After ERCP -Pediatric Study

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JA Mark, RE Kramer. JPGN 2021; 73: 542-547. Ketorolac Is Safe and Associated With Lower Rate of Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis in Children With Pancreatic Duct Manipulation

Methods: This retrospective chart review (n=298) examined the outcomes of pediatric patients who receivied ketorolac during ERCP compared to those who did not; ketorolac, was dosed using weight-based dosing (0.5 mg/kg/dose max 30 mg).

Key findings:

  • Most common indications for ERCP were choledocholithiasis, biliary stricture, and chronic/recurrent pancreatitis
  • Therapeutic ERCP: 91% of ketorolac group and 89% of non-ketorolac group; sphincterotomy was performed in 55% of both groups
  • Post-ERCP bleeding rates were not significantly different between ketorolac and non-ketorolac groups (0.6% vs 0%, P = 1)
  • PEP (post-ERCP pancreatitis) rates were not significantly different between the ketorolac and no ketorolac group 15/166 vs 17/132 (9% vs 13%, P = 0.29)
  • Patients who had cannulation and/or injection of the PD had significantly higher rates of PEP (23/140 (16%) vs 9/158 (6%), P < 0.003)
  • For high-risk pediatric patients with injection of contrast into and/or cannulation of the pancreatic duct, the rates of PEP were significantly lower for patients who received ketorolac (11% vs 25%, P = 0.035). In Table 2, the authors indicate that PEP in this high risk group occurred in 11/88 (12.5%) [mild discrepancy from abstract of 11%] of ketorolac group and 13/52 (25%)

It is possible that ketorolac (or other NSAIDs) in all patients may be beneficial but difficult to demonstrate without a larger cohort. In adults, “indomethacin reduces risk and severity of PEP in both high and average risk adults…and there is some evidence that NSAIDS given before ERCP may be more effective than those given later.” Thus, the authors state that use of ketorolac could be administered to all ERCP patients beforehand (w/o contraindication) or limited to the higher risk patients.

My take: In pediatric patients needing an ERCP, those with high-risk features (eg. injection of contrast into and/or cannulation of the pancreatic duct), use of ketorolac is likely to reduce the frequency of post-ERCP pancreatitis.

Related blog posts:

Why an ERCP Study Matters to Pediatric Care

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While there are pediatric patients who undergo endoscopic retrograde cholangiopancreatography (ERCP), this is a relatively infrequent occurrence. Nevertheless, a recent study has a couple useful clinical pearls that may have broader application.

  1. Clin Gastroenterol Hepatol 2014; 12: 303-07.
  2. Clin Gastroenterol Hepatol 2014; 12: 308-10 Associated editorial
  3. Gastroenterol 2014; 146: 581-82. Associated summary

Key points/Implications:

  • Aggressive hydration may prevent post-ERCP pancreatitis. In the study, the treatment group received an average of 3290 mL over the 9-hour period compared with 945 mL in the standard infusion group.
  • Implication: The speculation from the study and the editorials is that improved pancreatic perfusion will result in better oxygenation and reduce the likelihood of  pancreatitis. In the 2nd reference, the author states that his practice is to administer “at least 3 L of crystalloid in recovery to young, healthy patients who have undergone high-risk ERCP and an additional 3 to 5 L within the first 12 hospital hours to those admitted with postprocedure pain”
  • The best fluid (for post-ERCP and acute pancreatitis) may be lactated Ringer’s (LR).
  • Implication: The lactate in LR may help reduce pancreatitis by avoiding acidosis which could promote zymogen activation and pancreatic inflammation. A previous small trial (n=40) of acute pancreatitits from any cause showed lesser degrees of systemic inflammatory response with LR in compared with normal saline (Clin Gastroenterol Hepatol 2011; 9: 710-17e1).
  • This study adds aggressive IVFs as another intervention to prevent ERCP.  Rectal indomethacin and prophylactic stent placement (in high-risk patients) are other accepted treatments.

Study details:

This pilot study randomly assigned 39 patients to aggressive hydration and 23 to standard hydration; all patients were inpatients who were not at risk for fluid overload. The aggressive group received 3 mL/kg/h during the procedure, a 20 mL/kg bolus after the procedure, and then continued on 3 mL/kg/hr for 8 hours.  In contrast, the standard group received LR at 1.5 mL/kg/h during and for 8 hours afterwards.

Demographics: The average age was 43 years in the aggressive hydration group and 45 years in the standard group. 78% were hispanic.  The ERCP procedures were mostly “average risk.”  74% had ERCP for choledocholithiasis.  Only 2 subjects needed precut sphinterotomy (3%).

Results:

  • No patients in the aggressive hydration group developed acute pancreatitis compared with 4 (17%) in the standard hydration group
  • Elevated amylase (23% vs. 39%) and epigastric pain (8% vs 22%) were also less frequent in the aggressive hydration group.

Numerous Limitations: This was a small pilot study with an atypical population; thus, the findings are difficult to generalize.  A false-positive (type 1 error) can easily occur due to the small numbers, especially as the standard hydration group had a rate of acute pancreatitis that was about double from previous studies. In addition, this study was not blinded and could have been susceptible to bias.  Furthermore, the authors defined acute pancreatitis differently than in previous studies.  In this study, the authors required enzyme increases 2 or 8 hours after ERCP with new abdominal pain; in previous studies, the definition of acute pancreatitis relied on enzyme increases for at least 24 hours after the ERCP.

Take-home message for those not doing ERCPs: Think about using lactated ringer’s and aggressive hydration in otherwise-well patients who present with acute pancreatitis.

Related blog entries:

Indomethacin to prevent post-ERCP pancreatitis

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“Take two and call me in the morning” may now apply to the use of indomethacin in preventing post-ERCP pancreatitis.  A multicenter, randomized, placebo-controlled, double-blind clinical trial has shown that rectal indomethacin (two 50 mg suppositories) can reduce the rate of post-ERCP pancreatitis (NEJM 2012; 366: 1414-22).

A total of 602 adult patients were enrolled.  Patient selection favored those at increased risk for post-ERCP pancreatitis (eg. suspicion of sphincter of Oddi dysfunction) and excluded those at low risk for this complication (eg. routine biliary stent exchange, chronic calcific pancreatitis, or a pancreatic head mass).  Other exclusion criteria included active pancreatitis, elevated creatinine (>1.4 mg/dL), active peptic ulcer disease, and those already receiving a NSAID.

The suppositories (or placebo) were administered immediately after ERCP while the patient remained in the procedure room.

Post-ERCP pancreatitis developed in 27 of 295 patients (9.2%) in indomethacin group and in 52 of 307 patients (16.9%) in placebo group.  In addition, moderate-to-severe pancreatitis was reduced as well 4.4% compared with 8.8% respectively.  In addition, there were no increased adverse events in the treatment arm; there was no increased risk of bleeding in particular.

While the mechanism of improvement is unclear, NSAIDs are potent inhibitors of phospholipase A2, cyclooxygenase, and neutrophil-endothelial interactions, all of which are known to play a role in the pathogenesis of acute pancreatitis.

Additional references:

  • -Am J Gastroenterol 2007; 102: 978-83.  Use of indomethacin to reduce pancreatitis after ERCP
  • -Gut 2008; 57: 1262-7.  Meta-analysis of rectal NSAIDs to prevent post-ERCP pancreatitis