Proton pump inhibitor has no effect in the prevention of post-endoscopic sphincterotomy delayed bleeding: a prospective randomized controlled trial

Zhengping Yu, Jinli He, Ronglai Cao, Zhenzhen Yang, Baolian Li, Junbo Hong, Youxiang Chen, Liang Zhu, Zhengping Yu, Jinli He, Ronglai Cao, Zhenzhen Yang, Baolian Li, Junbo Hong, Youxiang Chen, Liang Zhu

Abstract

Background and aims: Bleeding is one of the common adverse events of endoscopic retrograde cholangiopancreatography (ERCP), which is mainly caused by endoscopic sphincterotomy (EST). At present, it remains unclear whether proton pump inhibitor (PPI) should be used to prevent post-EST bleeding. Therefore, we performed a randomized controlled trial to investigate whether PPI is effective in the prevention of post-EST delayed bleeding.

Methods: Consecutive eligible patients were randomly assigned (1:1) to experimental group (PPI group) or control group (normal saline, NS group). The patients in PPI group received intravenous esomeprazole 40 mg and normal saline 100 mL every 12 h for 2 days after ERCP immediately, and followed by oral esomeprazole (Nexium) 20 mg once a day for 7 days. Correspondingly, patients in the control group received intravenous normal saline 100 mL and did not take PPIs or any acid-suppressing drugs during hospitalization and after discharge. All patients were followed up for 30 days after ERCP. The primary endpoint was the incidence and severity of post-EST delayed bleeding.

Results: Between July 2020 and July 2022, 290 patients were randomly assigned to PPI group (n = 146) or NS group (n = 144). 5 patients from each group were excluded from the final analysis. There were 6 patients with post-EST delayed bleeding, with an incidence rate of 2.14%. The median time of delayed bleeding was 2.5 days after ERCP. 3 cases (2.12%, 3/141) occurred in the PPI group, with 1 case of mild and 2 cases of moderate bleeding. 3 cases (2.16%, 3/139) occurred in the NS group, with 2 cases of mild and 1 case of moderate bleeding. There was no significant difference in the incidence and the severity of post-EST delayed bleeding between the two groups (p = 1.000).

Conclusion: Prophylactic use of PPI after EST does not reduce the incidence and severity of post-EST delayed bleeding in patients.

Clinical trial registration: https://www.chictr.org.cn/searchproj.aspx, identifier ChiCTR2000034697.

Keywords: delayed bleeding; endoscopic papillary sphincterotomy; endoscopic retrograde cholangiopancreatography; proton pump inhibitor; randomized controlled trials.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2023 Yu, He, Cao, Yang, Li, Hong, Chen and Zhu.

Figures

Figure 1
Figure 1
Trial flow diagram.

References

    1. Chandrasekhara V, Khashab MA, Muthusamy VR, Acosta RD, Agrawal D, Bruining DH, et al. . Adverse events associated with ERCP. Gastrointest Endosc. (2017) 85:32–47. doi: 10.1016/j.gie.2016.06.051
    1. Freeman ML. Adverse outcomes of ERCP. Gastrointest Endosc. (2002) 56:S273–82. doi: 10.1067/mge.2002.129028
    1. Freeman ML, Nelson DB, Sherman S, Haber GB, Herman ME, Dorsher PJ, et al. . Complications of endoscopic biliary sphincterotomy. N Engl J Med. (1996) 335:909–19. doi: 10.1056/NEJM199609263351301
    1. Ferreira LE, Baron TH. Post-sphincterotomy bleeding: who, what, when, and how. Am J Gastroenterol. (2007) 102:2850–8. doi: 10.1111/j.1572-0241.2007.01563.x
    1. Dumonceau JM, Kapral C, Aabakken L, Papanikolaou IS, Tringali A, Vanbiervliet G, et al. . ERCP-related adverse events: European Society of Gastrointestinal Endoscopy (ESGE) guideline. Endoscopy. (2020) 52:127–49. doi: 10.1055/a-1075-4080, PMID:
    1. Rustagi T, Jamidar PA. Endoscopic retrograde cholangiopancreatography-related adverse events: general overview. Gastrointest Endosc Clin N Am. (2015) 25:97–106. doi: 10.1016/j.giec.2014.09.005, PMID:
    1. Andriulli A, Loperfido S, Napolitano G, Niro G, Valvano MR, Spirito F, et al. . Incidence rates of post-ERCP complications: a systematic survey of prospective studies. Am J Gastroenterol. (2007) 102:1781–8. doi: 10.1111/j.1572-0241.2007.01279.x, PMID:
    1. Feng Y, Zhu H, Chen X, Xu S, Cheng W, Ni J, et al. . Comparison of endoscopic papillary largeballoon dilation and endoscopic sphincterotomy for retrieval of choledocholithiasis: a meta-analysis of randomized controlled trials. J Gastroenterol. (2012) 47:655–63. doi: 10.1007/s00535-012-0528-9, PMID:
    1. Morris ML, Tucker RD, Baron TH, Song LM. Electrosurgery in gastrointestinal endoscopy: principles to practice. Am J Gastroenterol. (2009) 104:1563–74. doi: 10.1038/ajg.2009.105, PMID:
    1. Matsushita M, Takakuwa H, Shimeno N, Uchida K, Nishio A, Okazaki K. Prophylactic injection of hypertonic saline-epinephrine oral to the papilla for prevention of postsphincterotomy bleeding. J Clin Gastroenterol. (2010) 44:e167–70. doi: 10.1097/MCG.0b013e3181e5ceca
    1. Elta GH, Barnett JL, Wille RT, Brown KA, Chey WD, Scheiman JM. Pure cut electrocautery current for sphincterotomy causes less post-procedure pancreatitis than blended current. Gastrointest Endosc. (1998) 47:149–53. doi: 10.1016/s0016-5107(98)70348-7, PMID:
    1. Baron TH, Harewood GC. Endoscopic balloon dilation of the biliary sphincter compared to endoscopic biliary sphincterotomy for removal of common bile duct stones during ERCP: a metaanalysis of randomized, controlled trials. Am J Gastroenterol. (2004) 99:1455–60. doi: 10.1111/j.1572-0241.2004.30151.x
    1. Leung WK, But DY, Wong SY, Tong TS, Liu KS, Cheung KS, et al. . Prevention of post-sphincterotomy bleeding by proton pump inhibitor: a randomized controlled trial. J Dig Dis. (2018) 19:369–76. doi: 10.1111/1751-2980.12604, PMID:
    1. Cotton PB, Lehman G, Vennes J, Geenen JE, Russell RC, Meyers WC, et al. . Endoscopic sphincterotomy complications and their management: an attempt at consensus. Gastrointest Endosc. (1991) 37:383–93. doi: 10.1016/s0016-5107(91)70740-2, PMID:
    1. Leontiadis GI, Sharma VK, Howden CW. WITHDRAWN: proton pump inhibitor treatment for acute peptic ulcer bleeding. Cochrane Database Syst Rev. (2010) 5:Cd002094. doi: 10.1002/14651858.CD002094.pub4, PMID:
    1. Yang L, Qi J, Chen W, Guo Q, Xie R, Zhao Z, et al. . Low-dose PPI to prevent bleeding after ESD: a multicenter randomized controlled study. Biomed Pharmacother. (2021) 136:111251. doi: 10.1016/j.biopha.2021.111251, PMID:
    1. Schlenker C, Surawicz CM. Do we need our gastric acid? Risk of bacterial gastroenteritis with proton pump inhibitors. Gastroenterology. (2008) 135:1415–7. doi: 10.1053/j.gastro.2008.08.019, PMID:
    1. Yang YX, Metz DC. Safety of proton pump inhibitor exposure. Gastroenterology. (2010) 139:1115–27. doi: 10.1053/j.gastro.2010.08.023
    1. Deshpande A, Pant C, Pasupuleti V, Rolston DD, Jain A, Deshpande N, et al. . Association between proton pump inhibitor therapy and Clostridium difficile infection in a meta-analysis. Clin Gastroenterol Hepatol. (2012) 10:225–33. doi: 10.1016/j.cgh.2011.09.030, PMID:
    1. Fukuba N, Ishihara S, Sonoyama H, Yamashita N, Aimi M, Mishima Y, et al. . Proton pump inhibitor is a risk factor for recurrence of common bile duct stones after endoscopic sphincterotomy - propensity score matching analysis. Endosc Int Open. (2017) 5:E291–e296. doi: 10.1055/s-0043-102936, PMID:
    1. Kim KO, Kim TN, Kim SB, Lee JY. Characteristics of delayed hemorrhage after endoscopic sphincterotomy. J Gastroenterol Hepatol. (2010) 25:532–8. doi: 10.1111/j.1440-1746.2009.06123.x, PMID:
    1. Wilcox CM, Canakis J, Mönkemüller KE, Bondora AW, Geels W. Patterns of bleeding after endoscopic sphincterotomy, the subsequent risk of bleeding, and the role of epinephrine injection. Am J Gastroenterol. (2004) 99:244–8. doi: 10.1111/j.1572-0241.2004.04058.x, PMID:
    1. Sherman S, Hawes RH, Nisi R, Lehman GA. Endoscopic sphincterotomy-induced hemorrhage: treatment with multipolar electrocoagulation. Gastrointest Endosc. (1992) 38:123–6. doi: 10.1016/s0016-5107(92)70375-7, PMID:
    1. Kherad O, Restellini S, Martel M, Barkun A. Proton pump inhibitors for upper gastrointestinal bleeding. Best Pract Res Clin Gastroenterol. (2019) 42-43:101609. doi: 10.1016/j.bpg.2019.04.002
    1. Andersen J, Ström M, Naesdal J, Leire K, Walan A. Intravenous omeprazole: effect of a loading dose on 24-h intragastric pH. Aliment Pharmacol Ther. (1990) 4:65–72. doi: 10.1111/j.1365-2036.1990.tb00450.x, PMID:
    1. Green FW, Jr, Kaplan MM, Curtis LE, Levine PH. Effect of acid and pepsin on blood coagulation and platelet aggregation. A possible contributor prolonged gastroduodenal mucosal hemorrhage. Gastroenterology. (1978) 74:38–43. doi: 10.1016/0016-5085(78)90352-9, PMID:
    1. Chaimoff C, Creter D, Djaldetti M. The effect of pH on platelet and coagulation factor activities. Am J Surg. (1978) 136:257–9. doi: 10.1016/0002-9610(78)90241-6
    1. Dressman JB, Berardi RR, Dermentzoglou LC, Russell TL, Schmaltz SP, Barnett JL, et al. . Upper gastrointestinal (GI) pH in young, healthy men and women. Pharm Res. (1990) 7:756–61. doi: 10.1023/a:1015827908309, PMID:
    1. Yan J, Zhou CX, Wang C, Li YY, Yang LY, Chen YX, et al. . Risk factors for delayed hemorrhage after endoscopic sphincterotomy. Hepatobiliary Pancreat Dis Int. (2020) 19:467–72. doi: 10.1016/j.hbpd.2019.12.010, PMID:
    1. Ikarashi S, Katanuma A, Kin T, Takahashi K, Yane K, Sano I, et al. . Factors associated with delayed hemorrhage after endoscopic sphincterotomy: Japanese large single-center experience. J Gastroenterol. (2017) 52:1258–65. doi: 10.1007/s00535-017-1347-9, PMID:

Source: PubMed

Patrocinadores e Colaboradores

Condições médicas

Intervenções de drogas

3
Se inscrever