Prospective Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Feb 6, 2019; 7(3): 300-310
Published online Feb 6, 2019. doi: 10.12998/wjcc.v7.i3.300
Split-dose or hybrid nonsteroidal anti-inflammatory drugs and N-acetylcysteine therapy for prevention of post-retrograde cholangiopancreatography pancreatitis
Laura Pavel, Gheorghe Gh Bălan, Alexandra Nicorescu, Georgiana Emmanuela Gîlcă-Blanariu, Cătălin Sfarti, Ștefan Chiriac, Smaranda Diaconescu, Vasile Liviu Drug, Gheorghe Bălan, Gabriela Ștefănescu
Laura Pavel, Gheorghe Gh Bălan, Georgiana Emmanuela Gîlcă-Blanariu, Cătălin Sfarti, Ștefan Chiriac, Vasile Liviu Drug, Gheorghe Bălan, Gabriela Ștefănescu, Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, Iași 700115, România
Alexandra Nicorescu, Endocrinology, “Grigore T. Popa” University of Medicine and Pharmacy, Iași 700115, România
Smaranda Diaconescu, Department of Mother and Child Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Iași 700115, România
Author contributions: Pavel L, Bălan GG, Gîlcă-Blanariu GE, Bălan G and Ștefănescu G, participated in the protocol design, identification and inclusion of candidates, collection of clinical information, and patient follow-up; Bălan GG, Sfarti C, Drug VL, Chiriac Ș band Bălan G performed the endoscopic interventions; Pavel L, Diaconescu S, Nicorescu A and Ștefănescu G participated in the protocol design and statistical analysis; all authors were involved in critical review of the results and approved the final manuscript.
Institutional review board statement: The Institutional Review Board of “Gr. T. Popa” University of Medicine and Pharmacy - Iași provided approval for this study (IRB No. 27/03/2017).
Clinical trial registration statement: This study is registered at ClinicalTrials.gov, registration number NCT03708458.
Informed consent statement: Consent was obtained from all the patients that were included in the study.
Conflict-of-interest statement: The authors declare that they have no competing interests.
CONSORT 2010 statement: The CONSORT 2010 Statement was uploaded.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Smaranda Diaconescu, MD, PhD, Associate Professor, Department of Mother and Child Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 16 Universității str, Iași 700115, România. turti23@yahoo.com
Telephone: +40-74492216 Fax: +40-232222453
Received: October 30, 2018
Peer-review started: October 31, 2018
First decision: November 15, 2018
Revised: December 18, 2018
Accepted: December 21, 2018
Article in press: December 24, 2018
Published online: February 6, 2019
Processing time: 92 Days and 11.9 Hours
Abstract
BACKGROUND

Despite significant technical and training improvements, the incidence of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) has not significantly dropped. Although many studies have evaluated the efficacy of various agents, e.g. nonsteroidal anti-inflammatory drugs, octreotide, antioxidants, administered via various dosages, routes (oral, intrarectal or parenteral), and schedules (before or after the procedure), the results have been conflicting.

AIM

To evaluate efficacy of three pharmacologic prophylactic methods for prevention of PEP.

METHODS

In this prospective, single-center randomized trial, patients who underwent first-time ERCP for choledocholithiasis were randomly assigned to three groups. The first group received 600 mg N-acetylcysteine 15 min prior to ERCP, and per-rectum administration of 50 mg indomethacin both prior to and after completion of the ERCP. The second group was administered only the 50 mg indomethacin per-rectum both prior to and after the ERCP. The third group was administered per-rectum 100 mg indomethacin only after the ERCP, representing the control group given the guideline-recommended regimen. The primary end-point was PEP prevention.

RESULTS

Among the total 211 patients evaluated during the study, 186 fulfilled the inclusion criteria and completed the protocol. The percentages of patients who developed PEP in each of the three groups were not significantly different (χ2 = 2.793, P = 0.247). Among the acute PEP cases, for all groups, 14 patients developed mild pancreatitis (77.77%) and 4 moderate. No severe cases of PEP occurred, and in all PEP cases the resolution was favorable. No adverse events related to the medications (digestive hemorrhage, rectal irritation, or allergies) occurred.

CONCLUSION

The efficacies of split-dose indomethacin and combined administration (N-acetylcysteine with indomethacin) for preventing PEP were similar to that of the standard regimen.

Keywords: Endoscopic retrograde cholangiopancreatography; Prophylaxis; Post-endoscopic retrograde cholangiopancreatography pancreatitis; Nonsteroidal anti-inflammatory drugs; N-acetylcysteine

Core tip: Despite significant technical and training improvements, the incidence of post-endoscopic retrograde-cholangiopancreatography (ERCP) pancreatitis has not dropped significantly. The present prospective, single-center randomized trial aimed to evaluate the efficacy of three prophylactic approaches for preventing post-ERCP pancreatitis. The results obtained demonstrate that the efficacies for preventing post-ERCP pancreatitis for both split-dose administration of indomethacin and combined administration of N-acetylcysteine before the procedure with administration of indomethacin post-ERCP are similar to that of the guideline-recommended regimen; although, a slightly more rapid improvement in the biological response was observed for the study group receiving the combination therapy (nonsteroidal anti-inflammatory drugs associated with N-acetylcysteine).