Abstract
BACKGROUND: The role and timing of endoscopic retrograde cholangiopancreatography (ERCP) in acute gallstone pancreatitis remains controversial. A number of clinical trials and meta-analyses have provided conflicting evidence. OBJECTIVES: To systematically review evidence from randomized controlled trials (RCTs) assessing the clinical effectiveness and safety of the early routine ERCP strategy compared to the early conservative management with or without selective use of ERCP strategy, based on all important, clinically relevant and standardized outcomes including mortality, local and systemic complications as defined by the Atlanta Classification (Bradley 1993) and by authors of the primary study, and ERCP-related complications in unselected patients with acute gallstone pancreatitis. SEARCH METHODS: We searched the CENTRAL (The Cochrane Library), MEDLINE, EMBASE, and LILACS databases and major conference proceedings up to January 2012, using the Cochrane Upper Gastrointestinal and Pancreatic Diseases model with no language restrictions. SELECTION CRITERIA: RCTs comparing the early routine ERCP strategy versus the early conservative management with or without selective use of ERCP strategy in patients with suspected acute gallstone pancreatitis. We included studies in which the population with acute gallstone pancreatitis was a subgroup within a larger group of patients. We only included studies involving only a selected subgroup of patients with acute gallstone pancreatitis (actual severe pancreatitis) in subgroup analyses. DATA COLLECTION AND ANALYSIS: Two review authors conducted study selection, data extraction, and methodological quality assessment independently. Using intention-to-treat analysis with random-effects models, we combined dichotomous data to obtain risk ratios (RR) with 95% confidence intervals (CI). We assessed heterogeneity using the Chi² test and I² statistic. To explore sources of heterogeneity, we conducted a priori subgroup analyses according to predicted severity of pancreatitis, cholangitis, biliary obstruction, time to ERCP in routine ERCP strategy, use of selective ERCP in conservative management strategy, and risk of bias. To assess the robustness of our results, we carried out sensitivity analyses using different summary statistics (RR versus odds ratio (OR)) and meta-analytic models (fixed versus random-effects), and per-protocol analysis. We performed influence analysis by exclusion of each study. MAIN RESULTS: Five RCTs comprising 644 participants were included in the main analyses. Two additional RCTs, comprising only patients with actual severe acute gallstone pancreatitis, were included only in subgroup analyses. There was statistical heterogeneity among trials for mortality, but not for other outcomes. In unselected patients with acute gallstone pancreatitis, there were no statistically significant differences between the two strategies in mortality (RR 0.74, 95% CI 0.18 to 3.03), local and systemic complications as defined by the Atlanta Classification (RR 0.86, 95% CI 0.52 to 1.43; and RR 0.59, 95% CI 0.31 to 1.11 respectively) and by authors of the primary study (RR 0.80, 95% CI 0.51 to 1.26; and RR 0.76, 95% CI 0.53 to 1.09 respectively). The results were robust to sensitivity and influence analyses except for systemic complications as defined by the Atlanta Classification. There was no evidence to suggest that the results were dependent on predicted severity of pancreatitis. Among trials that included patients with cholangitis, the early routine ERCP strategy significantly reduced mortality (RR 0.20, 95% CI 0.06 to 0.68), local and systemic complications as defined by the Atlanta Classification (RR 0.45, 95% CI 0.20 to 0.99; and RR 0.37, 95% CI 0.18 to 0.78 respectively) and by authors of the primary study (RR 0.50, 95% CI 0.29 to 0.87; and RR 0.41, 95% CI 0.21 to 0.82 respectively). Among trials that included patients with biliary obstruction, the early routine ERCP strategy was associated with a significant reduction in local complications as defined by authors of the primary study (RR 0.54, 95% CI 0.32 to 0.91), and a non-significant trend towards reduction of local and systemic complications as defined by the Atlanta Classification (RR 0.53, 95% CI 0.26 to 1.07; and RR 0.56, 95% CI 0.30 to 1.02 respectively) and systemic complications as defined by authors of the primary study (RR 0.59, 95% CI 0.35 to 1.01). ERCP complications were infrequent. AUTHORS' CONCLUSIONS: In patients with acute gallstone pancreatitis, there is no evidence that early routine ERCP significantly affects mortality, and local or systemic complications of pancreatitis, regardless of predicted severity. Our results, however, provide support for current recommendations that early ERCP should be considered in patients with co-existing cholangitis or biliary obstruction.