Combined use of indomethacin and hydration is the best conservative approach for post-ERCP pancreatitis prevention: A network meta-analysis

Post-ERCP pancreatitis (PEP) is a life-threatening complication. Given the lack of a causative treatment for pancreatitis, it is of vital importance to minimize this risk of PEP. Multi-target preventive therapy may be the best choice for PEP prevention as disease development is multifactorial. We aimed to assess the efficacy of a combination of indomethacin and hydration – type and amount – for PEP prevention via a network meta-analysis. Through a systematic search in three databases, we searched all randomized controlled trials involving hydration and indomethacin and ranked the PEP preventive efficacy with a Bayesian network meta-analysis using the PRISMA for Network Meta-Analyses (PRISMA-NMA) guideline. The RoB2 tool was used for risk of bias assessment, surface under the cumulative ranking curve (SUCRA) for ranking and PROSPERO for the study protocol [reg. no. CRD42018112698]. We used risk ratios (RR) for dichotomous data with 95% credible intervals (95% CrI). The quantitative analysis included 7559 patients from 24 randomized controlled trials. Based on the SUCRA values, a combination of lactated Ringer's and indomethacin is more effective than single therapy with a 94% certainty. The percent relative risk ratios estimate preventive efficacy 70–99% higher for combinations than single therapies. Aggressive hydration with indomethacin (SUCRA 100%) is also significantly more effective than all other interventions (percent relative effect 94.3–98.1%). A one-hit-on-each-target therapeutic approach is recommended in PEP prevention with an easily accessible combination of indomethacin and aggressive hydration for all average and high-risk patients without contraindication. Graphical abstract. The pancreatic cellular damage is a consequence of (i) the manipulation of the papilla and (ii) the ionic concentration and osmolarity of the contrast agent. The mechanical insult leads to an elevated pressure and local oedema, which can block the outflow of the pancreatic juice from the main duct. Whereas experimental data suggest that low pH level can worsen the outcome of the disease via neurogenic pathways [79] and also via acceleration of trypsinogen auto activation [80]. [Display omitted] •Acute pancreatitis prevention has an enormous societal and clinical relevance.•ESGE 2020 prioritizes NSAID and suggests hydration only in NSAID contraindication.•Combination has significant additive effect with 70–99% efficacy (85–94% certainty).•Aggressive hydration in the comb