UMEM Educational Pearls

Enter the WATERFALL trial into the present flood of fluid strategy trials, a multi-country (primarily Spain) open-label RCT of “Aggressive” versus “Moderate” fluid resuscitation with lactated ringers for early mild acute pancreatitis.

Population: 249 adults (1/3 of the planned enrollment) presenting to the ED within 24hrs hours of abdominal pain onset diagnosed with mild acute pancreatitis. Numerous exclusions for local pancreatic complications, acute or chronic organ dysfunction (including CHF and CKD), among many others. Average age of 57, 51% female, 61% due to gallstones, median Charleson index of 2, median BISAP of 1, and 52% clinically judged hypovolemic on enrollment.

Interventions: 1:1 randomization to two complex protocols, both with time points every 48 hours and same criteria for initiating oral diet.

  • “Aggressive”: Immediate 20ml/kg bolus of LR hours with repeat 20ml/kg boluses for hypoperfusion followed by 3ml/kg/hr infusion for 12hrs, then 1.5-3ml/kg/hr for at least 36hrs
  • “Moderate”: 10ml/kg bolus only if hypovolemic with repeat 10ml/kg boluses for hypoperfusion followed 1.5 ml/kg/hr infusion for 20hrs

Outcomes/Results: Primary outcome was development of moderate of severe pancreatitis with no difference found between the two strategies. Median fluid at 72 hours was 8.3L (IQR 7.1- 10.8) in the aggressive arm and 6.6L (IQR 4.1 - 8.0) in the moderate arm.  Several point estimates favor the moderate group, but none statistically significant and there was not a difference in symptom or SIRS improvement at 72 hours.  The trial was stopped after 1/3 enrollment when the monitoring board noted a significantly increased rate of fluid overload in the aggressive arm (20.5%) versus the moderate arm (6.6%). 


-Aggressive fluids for mild acute pancreatitis didn’t show benefit over a moderate strategy and showed some harms in contrast to previous smaller studies and some guideline recommendations in mild disease

-Only reached 1/3 of target enrollment significantly limiting analysis

-This was by design not a trial of severe or critical disease

-The open label nature may have affected some endpoints, including safetly endpoints

-Another trial to shift our thinking a bit about how to use and safely limit fluid resuscitation


Aggressive or Moderate Fluid Resuscitation in Acute Pancreatitis. De-Madaria et al. N Engl J Med 2022;387:989-1000
DOI: 10.1056/NEJMoa2202884