HPB SO45 - Level 1 evidence comparing aggressive versus non-aggressive intravenous fluid therapy in acute pancreatitis

Abstract Background Fluid balance in the management of acute pancreatitis (AP) is challenging and has been described as a “double-edged sword” whereby adequate fluids are required to counteract systemic hypovolaemia whilst excessive fluids may exacerbate systemic oedema. Given that data generated from randomised studies are conflicting, the optimal rate and type of fluid resuscitation for AP are yet to be determined. We aimed to perform a comprehensive meta-analysis of all existing randomized controlled trials (RCTs) to evaluate comparative outcomes of aggressive versus non-aggressive intravenous fluid (IVF) therapy in patients with AP. Method A systematic search of electronic data sources and bibliographic reference lists were conducted. All RCTs reporting outcomes of aggressive versus non-aggressive IVF therapy in AP were included and their risk of bias were assessed. Effect sizes were determined for overall mortality, systemic inflammatory response syndrome (SIRS), sepsis, respiratory failure, pancreatic necrosis, severe pancreatitis, clinical improvement, AKI, and length of stay using random-effects modelling. Trial sequential analysis was conducted to determine risk of types 1 or 2 errors. Results Ten RCTs enrolling 993 patients with AP who received aggressive (n = 475) or non-aggressive (n = 518) IVF therapy were included. Aggressive IVF therapy was associated with significantly higher rate of sepsis (OR:2.68, P=0.0005) and longer length of stay (MD:0.94, P<0.00001). There was no statistically significant difference in mortality (RD:0.02, P=0.31), SIRS (OR:0.93, P=0.89), respiratory failure (OR:2.81, P=0.07), pancreatic necrosis (OR:1.98, P = 0.06), clinical improvement (OR:1.12, P=0.83), severe pancreatitis (OR:1.31, P=0.38) or AKI (OR:1.06, P=0.91). Subgroup analysis demonstrated higher morbidity and mortality with aggressive fluids in severe AP. Trial sequential analysis detected risk of type 2 error. Conclusion Aggressive IVF therapy may be associated with higher morbidity in patients with acute pancreatitis compared with the non-aggressive approach, particularly in patients with more severe disease. It may also prolong length of hospital stay. The available evidence is subject to type 2 error indicating the need for adequately powered RCTs.