Clinical Pearls & Morning Reports

Posted by Carla Rothaus

Published September 14, 2022


How did aggressive hydration compare with moderate hydration regarding the primary outcome of the WATERFALL trial?

The WATERFALL trial investigated the safety and efficacy of aggressive fluid resuscitation as compared with moderate fluid resuscitation in patients with acute pancreatitis. Read the NEJM Original Article here.

Clinical Pearls

Q: How often does moderately severe or severe disease develop in patients with acute pancreatitis?

A: Moderately severe or severe disease develops in approximately 35% of patients with acute pancreatitis, a situation that is associated with worse outcomes. In animal models, regional hypoperfusion of the pancreas is spatially correlated with necrosis and may be corrected by fluid resuscitation. Initial observational studies indicated that hemoconcentration, which is a surrogate for systemic hypovolemia, was associated with pancreatic necrosis. Nevertheless, subsequent work indicated that the administration of a greater volume of fluid resuscitation during the first 24 hours may not improve outcomes.

Q: How did aggressive hydration compare with moderate hydration regarding the primary outcome of the WATERFALL trial?

A: There was no significant between-group difference in the development of moderately severe or severe acute pancreatitis (the primary outcome), which occurred in 22.1% of the patients in the aggressive-resuscitation group and in 17.3% of those in the moderate-resuscitation group (adjusted relative risk, 1.30; 95% confidence interval [CI], 0.78 to 2.18; P=0.32).

Morning Report Questions 

Q: Do the findings of the WATERFALL trial support current management guidelines for acute pancreatitis?

A: In the trial, aggressive fluid resuscitation was associated with a significantly higher incidence of fluid overload than moderate fluid resuscitation (20.5% vs. 6.3%; adjusted relative risk, 2.85; 95% CI, 1.36 to 5.94). Together with the primary end point results, these findings do not support current management guidelines, which recommend early aggressive resuscitation for the treatment of acute pancreatitis. An increased risk of fluid overload was detected in the overall population of patients and also in subgroups of patients without systemic inflammatory response syndrome (SIRS) at baseline, patients with SIRS at baseline (thus, with a higher risk of development of severe pancreatitis), and patients with hypovolemia. Although most episodes of fluid overload with aggressive hydration were nonsevere (the trial was designed to allow early detection and treatment), this situation was not balanced by an improvement in outcomes. Given the data showing increased harm without improvement with regard to the primary outcome, the data and safety monitoring board unanimously recommended that the trial be stopped.

Q: What were some of the limitations of the WATERFALL trial?

A: This trial was terminated at the first interim analysis; thus, it was underpowered to evaluate efficacy outcomes definitively. Another limitation is that the trial was open-label, which may have introduced bias. The exclusion of patients at high risk for volume overload could have meant the selection of patients with less severe disease.

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