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Risk Factors for Post-ERCP Pancreatitis in High-Risk Patients Receiving Post-procedure Rectal Indomethacin

Journal of Gastrointestinal Surgery volume 22, pages 1903–1910 (2018)Cite this article

Abstract

Background

Post-ERCP pancreatitis (PEP) is the most common adverse event of ERCP. Rectal indomethacin has been widely administered to decrease the incidence of PEP in high-risk patients. However, it cannot completely prevent the occurrence of PEP. The purpose of the study was to evaluate the risk factors for PEP in high-risk patients receiving post-ERCP indomethacin.

Methods

From June 2012 to July 2015, patients undergoing ERCP and at high risk for PEP in three tertiary hospitals in China were enrolled. All patients received indomethacin after the procedure. Patient-related and procedure-related risk factors for PEP were collected. Logistic regression analysis was used to investigate the risk factors.

Results

Seven hundred ninety patients at high risk for PEP received post-ERCP indomethacin. The incidence of overall PEP and moderate-to-severe PEP was 8.0 and 1.5%, respectively. In multivariate analysis, suspected sphincter of Oddi dysfunction (SOD) (OR 2.73; 95%CI 1.38–5.43; p = 0.004), the presence of hilar obstruction (OR 4.53; 95%CI 1.60–12.81; p = 0.004), number of cannulation attempts ≥ 13 (OR 2.00; 95%CI 1.07–3.77; p = 0.030), inadvertent pancreatic duct (PD) cannulation ≥ 1 (OR 2.26; 95%CI 1.04–4.90; p = 0.040), and pancreatic contrast injections ≥ 1 (OR 2.30; 95%CI 1.02–5.23; p = 0.046) were high risk factors for overall PEP. For moderate-to-severe PEP, suspected SOD (OR 4.67; 1.19–18.35; p = 0.027), the presence of hilar obstruction (OR 7.95; 1.39–44.97; p = 0.010), and more cannulation attempts (OR 3.71; 1.09–12.65; p = 0.036) were three independent risk factors.

Conclusions

A substantial number of high-risk patients had PEP even receiving post-ERCP rectal indomethacin. The independent risk factors included suspected SOD, hilar stricture, more cannulation attempts, inadvertent PD cannulation, and PD contrast injections.

Trial Registration

NCT02709421

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Fig. 1
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Abbreviations

ERCP:

Endoscopic retrograde cholangiopancreatography

PEP:

post-ERCP pancreatitis

SOD:

Suspected sphincter of Oddi dysfunction

PD:

Pancreatic duct

NSAIDs:

Nonsteroidal anti-inflammatory drugs

WGC:

Wire-guide cannulation

BMI:

Body mass index

IQR:

Interquartile range

SD:

Standard deviation

ROC:

Receiver operating characteristic

RCT:

Randomized controlled study

OR:

Odds ratio

CI:

Confidence interval

TBIL:

Total bilirubin

ALT:

Alaninetransaminase

GOT:

Glutamic-oxaloacetic transaminase

References

  1. Kochar B, Akshintala VS, Afghani E, et al. Incidence, severity, and mortality of post-ERCP pancreatitis: a systematic review by using randomized, controlled trials. Gastrointest Endosc 2015;81:143–149.

    Article  Google Scholar 

  2. Committee ASoP, Anderson MA, Fisher L, et al. Complications of ERCP. Gastrointest Endosc 2012;75:467–73.

    Article  Google Scholar 

  3. Cennamo V, Fuccio L, Zagari RM, et al. Can a wire-guided cannulation technique increase bile duct cannulation rate and prevent post-ERCP pancreatitis?: A meta-analysis of randomized controlled trials. Am J Gastroenterol 2009;104:2343–50.

    Article  Google Scholar 

  4. Singh P, Das A, Isenberg G, et al. Does prophylactic pancreatic stent placement reduce the risk of post-ERCP acute pancreatitis? A meta-analysis of controlled trials. Gastrointest Endosc 2004;60:544–50.

    Article  Google Scholar 

  5. Elmunzer BJ, Waljee AK, Elta GH, et al. A meta-analysis of rectal NSAIDs in the prevention of post-ERCP pancreatitis. Gut 2008;57:1262–7.

    CAS  Article  Google Scholar 

  6. Dumonceau JM, Andriulli A, Elmunzer BJ, et al. Prophylaxis of post-ERCP pancreatitis: European Society of Gastrointestinal Endoscopy (ESGE) Guideline - updated June 2014. Endoscopy 2014;46:799–815.

    Article  Google Scholar 

  7. Yokoe M, Takada T, Mayumi T, et al. Japanese guidelines for the management of acute pancreatitis: Japanese Guidelines 2015. J Hepatobiliary Pancreat Sci 2015;22:405–32.

    Article  Google Scholar 

  8. Elmunzer BJ, Higgins PD, Saini SD, et al. Does rectal indomethacin eliminate the need for prophylactic pancreatic stent placement in patients undergoing high-risk ERCP? Post hoc efficacy and cost-benefit analyses using prospective clinical trial data. Am J Gastroenterol 2013;108:410–5.

    CAS  Article  Google Scholar 

  9. Akbar A, Abu Dayyeh BK, Baron TH, et al. Rectal nonsteroidal anti-inflammatory drugs are superior to pancreatic duct stents in preventing pancreatitis after endoscopic retrograde cholangiopancreatography: a network meta-analysis. Clin Gastroenterol Hepatol 2013;11:778–83.

    CAS  Article  Google Scholar 

  10. Elmunzer BJ, Scheiman JM, Lehman GA, et al. A randomized trial of rectal indomethacin to prevent post-ERCP pancreatitis. N Engl J Med 2012;366:1414–22.

    CAS  Article  Google Scholar 

  11. Andrade-Davila VF, Chavez-Tostado M, Davalos-Cobian C, et al. Rectal indomethacin versus placebo to reduce the incidence of pancreatitis after endoscopic retrograde cholangiopancreatography: results of a controlled clinical trial. BMC Gastroenterol 2015;15:85.

    Article  Google Scholar 

  12. Thiruvengadam NR, Forde KA, Ma GK, et al. Rectal Indomethacin Reduces Pancreatitis in High- and Low-Risk Patients Undergoing Endoscopic Retrograde Cholangiopancreatography. Gastroenterology 2016;151:288–297.

    CAS  Article  Google Scholar 

  13. Inamdar S, Han D, Passi M et al. Rectal indomethacin is protective against post-ERCP pancreatitis in high-risk patients but not average-risk patients: a systematic review and meta-analysis. Gastrointest Endosc. 2017: 85:67–75

    Article  Google Scholar 

  14. Makela A, Kuusi T, Schroder T. Inhibition of serum phospholipase-A2 in acute pancreatitis by pharmacological agents in vitro. Scand J Clin Lab Invest 1997;57:401–7.

    CAS  Article  Google Scholar 

  15. Patai A, Solymosi N, Patai AV. Effect of rectal indomethacin for preventing post-ERCP pancreatitis depends on difficulties of cannulation: results from a randomized study with sequential biliary intubation. J Clin Gastroenterol 2015;49:429–37.

    CAS  Article  Google Scholar 

  16. Sotoudehmanesh R, Khatibian M, Kolahdoozan S, et al. Indomethacin may reduce the incidence and severity of acute pancreatitis after ERCP. Am J Gastroenterol 2007;102:978–83.

    CAS  Article  Google Scholar 

  17. Luo H, Zhao L, Leung J, et al. Routine pre-procedural rectal indometacin versus selective post-procedural rectal indometacin to prevent pancreatitis in patients undergoing endoscopic retrograde cholangiopancreatography: a multicentre, single-blinded, randomised controlled trial. Lancet 2016;387:2293–301.

    CAS  Article  Google Scholar 

  18. Freeman ML. Pancreatic stents for prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis. Clin Gastroenterol Hepatol 2007;5:1354–65.

    Article  Google Scholar 

  19. Cotton PB, Lehman G, Vennes J, et al. Endoscopic sphincterotomy complications and their management: an attempt at consensus. Gastrointest Endosc 1991;37:383–93.

    CAS  Article  Google Scholar 

  20. Cotton PB, Eisen GM, Aabakken L, et al. A lexicon for endoscopic adverse events: report of an ASGE workshop. Gastrointest Endosc 2010;71:446–54.

    Article  Google Scholar 

  21. Testoni PA, Mariani A, Giussani A, et al. Risk factors for post-ERCP pancreatitis in high- and low-volume centers and among expert and non-expert operators: a prospective multicenter study. Am J Gastroenterol 2010;105:1753–61.

    Article  Google Scholar 

  22. Freeman ML, DiSario JA, Nelson DB, et al. Risk factors for post-ERCP pancreatitis: a prospective, multicenter study, Gastrointest Endosc 2001;54:425–34.

    CAS  Article  Google Scholar 

  23. Testoni PA, Mariani A, Aabakken L, et al. Papillary cannulation and sphincterotomy techniques at ERCP: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline. Endoscopy 2016;48:657–83.

    Article  Google Scholar 

  24. Swahn F, Nilsson M, Arnelo U, et al. Rendezvous cannulation technique reduces post-ERCP pancreatitis: a prospective nationwide study of 12,718 ERCP procedures. Am J Gastroenterol 2013;108:552–9.

    Article  Google Scholar 

  25. Leghari A, Ghazanfar S, Qureshi S, et al. Frequency and risk factors in the post-ERCP pancreatitis in a tertiary care centre. J Coll Physicians Surg Pak 2013;23:620–4.

    PubMed  Google Scholar 

  26. Wang P, Li ZS, Liu F, et al. Risk factors for ERCP-related complications: a prospective multicenter study. Am J Gastroenterol 2009;104:31–40.

    Article  Google Scholar 

  27. Cheng CL, Sherman S, Watkins JL, et al. Risk factors for post-ERCP pancreatitis: a prospective multicenter study. Am J Gastroenterol 2006;101:139–47.

    Article  Google Scholar 

  28. Ding X, Zhang F, Wang Y. Risk factors for post-ERCP pancreatitis: A systematic review and meta-analysis. Surgeon 2015;13:218–29.

    Article  Google Scholar 

  29. Rustagi T, Njei B. Factors Affecting the Efficacy of Nonsteroidal Anti-inflammatory Drugs in Preventing Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis: A Systematic Review and Meta-analysis. Pancreas 2015;44:859–67.

    CAS  Article  Google Scholar 

  30. Döbrönte Z, Toldy E, Márk L, et al. Effects of rectal indomethacin in the prevention of post-ERCP acute pancreatitis. Orv Hetil. 2012; 153: 990–996.

    Article  Google Scholar 

  31. Hashimoto S, Ito K, Koshida S, et al. Risk Factors for Post-Endoscopic Retrograde Cholangiopancreatography (ERCP) Pancreatitis and Stent Dysfunction after Preoperative Biliary Drainage in Patients with Malignant Biliary Stricture. Intern Med 2016;55:2529–36.

    Article  Google Scholar 

  32. Uchino R, Sasahira N, Isayama et al. Detection of painless pancreatitis by computed tomography in patients with post-endoscopic retrograde cholangiopancreatography hyperamylasemia. Pancreatology 2014;14:17–20

    CAS  Article  Google Scholar 

  33. Levenick JM, Gordon SR, Fadden et al. Rectal Indomethacin Does Not Prevent Post-ERCP Pancreatitis in Consecutive Patients. Gastroenterology. 2016;15:911–7

    Article  Google Scholar 

  34. ASGE Standards of Practice Committee Adverse events associated with ERCP. Gastrointest Endosc. 2017;85:32–47

    Article  Google Scholar 

Download references

Funding

This work was supported in part by the National Natural Science Foundation of China (81370585 and 81570482).

Author information

Author notes

  1. Xiaoyu Kang, Liyue Zheng, Wei Zeng and Shengye Yang contributed equally to this work.

Affiliations

  1. Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 127 Changle West Road, Xi’an, 710032, Shaanxi, China

    Xiaoyu Kang, Liyue Zheng, Shengye Yang, Rongchun Zhang, Xiangping Wang, Biaoluo Wang, Qin Tao, Shaowei Yao, Jie Chen, Yanglin Pan & Xuegang Guo

  2. Department of Gastroenterology, Chinese PLA 174 Hospital, Xiamen, Fujian, China

    Wei Zeng

  3. Department of Gastroenterology, Chenggong Hospital, Xiamen University, Xiamen, Fujian, China

    Wei Zeng

  4. The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China

    Hao Sun

Authors
  1. Xiaoyu Kang
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  2. Liyue Zheng
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  3. Wei Zeng
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  4. Shengye Yang
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  5. Hao Sun
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  7. Xiangping Wang
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  8. Biaoluo Wang
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  9. Qin Tao
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  10. Shaowei Yao
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  11. Jie Chen
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  12. Yanglin Pan
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Contributions

Yanglin Pan, XuegangGuo, Xiaoyu Kang, Wei Zeng, Hao Sun, Liyue Zheng, Shengye Yang, Rongchun Zhang, Xiangping Wang, Biaoluo Wang, Jie Chen, Qin Tao, Shaowei Yao: contribution meets all criteria.

Corresponding authors

Correspondence to Yanglin Pan or Xuegang Guo.

Ethics declarations

The study protocol was approved by the institutional review board of Xijing Hospital.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Kang, X., Zheng, L., Zeng, W. et al. Risk Factors for Post-ERCP Pancreatitis in High-Risk Patients Receiving Post-procedure Rectal Indomethacin. J Gastrointest Surg 22, 1903–1910 (2018). https://doi.org/10.1007/s11605-018-3864-0

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  • DOI: https://doi.org/10.1007/s11605-018-3864-0

Keywords

  • ERCP
  • Post-ERCP pancreatitis
  • Indomethacin
  • Risk factors