Lessons on Aggressive Intravenous Hydration in Acute Pancreatitis: A Meta-Analysis of Clinical Trials

Abstract

Purpose: Largely based on animal studies and indirect evidence in humans, experts have put forth the notion that aggressive intravenous hydration (AIH), early in the course, would attenuate the severity of the disease in patients with acute pancreatitis (AP). Recent clinical studies in human subjects evaluating the efficacy of AIH have demonstrated conflicting results. The purpose of our study was to systematically review, analyze and combine the different studies in a meta-analysis to determine patterns of efficacy that may exist in order to promote appropriate fluid management in patients with AP. Methods: In order to be included in the analysis, the published study needed to include patients with AP were enrolled in a consecutive, prospective or retrospective fashion. The study needed to provide information regarding the amount of fluid for each group, and outcome, such as organ failure, necrosis and mortality. The amount of fluid over the first 24-48 hours needed to be provided. When combining the various studies, the weighted mean of power (sample size) was used to determine the relative value of significance. Sensitivity analysis evaluated sample sizes, timing, type of fluids and severity of patients included. Results: Ten published studies fulfilled the criteria to be included in the analysis, which included 1,495 patients. There were six retrospective, four prospective studies. While three studies concluded that AIH was beneficial, seven studies showed no benefit and/or harm. Using a weighted mean analysis, when evaluating the effectiveness of AIH beyond 24 hours, there was no significant difference in the development of organ failure, pancreatic necrosis or mortality (OR 1.2, CI 0.4 -1.9). However, in a subgroup analysis excluding patients presenting with severe disease, there was a significant benefit to AIH in preventing organ failure and/or pancreatic necrosis (OR 1.8, CI 1.5 -2.8, p = 0.02). Additionally, there was a significant decrease in organ failure and/or pancreatic necrosis if the AIH was given early, within the first 24 hours (OR 2.1, CI 1.6 - 2.9, p= 0.03) and 6-12 hours (p = 0.02). Conclusion: Based on this meta-analysis, AIH appears to be most beneficial when applied to patients with AP early in the course of the disease, within the first 6-24 hours, before severe disease develops. In general, there does not appear to be a benefit to AIH in patients with AP beyond the first 24 hours. Clinicians should recognize the importance of applying the principles of AIH as early as possible, especially to patients who have mild disease. The benefit of early aggressive hydration appears to be preventing severe disease, organ failure and/or pancreatic necrosis.