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WATERFALL Trial

WATERFALL Trial

NEJM

September 15, 2022

Aggressive or Moderate Fluid Resuscitation in Acute Pancreatitis

Mazen Kherallah

Summarized by: 

What was the research question?

  • ·In patients with acute pancreatitis, is aggressive fluid resuscitation safe and effective compared to moderatel-agressive fluid strategy?


How did they do it?

  • A multicenter, open-label, parallel-group, randomized, controlled, superiority trial was conducted at 18 centers in India, Italy, Mexico, and Spain.

  • A total of 249 patients with varying degree of acute pancreatitis were randomized to receive aggressive fluid resuscitation with 20 ml/kg in 2 hours followed by 3 ml/kg/hour (122 patients), or moderate fluid resuscitation with a bolus of 10 ml per kilogram in patients with hypovolemia or no bolus in patients with normovolemia, followed by 1.5 ml/kg/hour (127 patients). Fluid rates were adjusted based on the clinical status of the patients.

  • The primary outcome was moderately severe or severe pancreatitis developed during hospitalization, and the main safety outcome was fluid overload.


What did they find?

  • The trial was terminated for safety concerns in the treatment group.

  • The primary outcome was not significantly different in the aggressive-resuscitation group compared to the moderate-resuscitation group (22.1% vs 17.3, RR, 1.30; 95% confidence interval [CI], 0.78 to 2.18; P = 0.32).

  • Fluid overload was significantly higher in the aggressive-resuscitation group compared to the moderate-resuscitation group (20.5% vs 6.3%, RR, 2.85; 95% CI, 1.36 to 5.94, P = 0.004).

  • The median hospital length of stay in the aggressive-resuscitation group was 6 days (interquartile range, 4 to 8), whereas it was 5 days (interquartile range, 3 to 7) in the moderate-resuscitation group.


Are there any limitations?

  • The study was ended early due to safety concerns and inefficacy, and thus not enough patients were observed. To get an accurate measure of efficacy, a larger number of patients would be needed, though this exposes them to the risks associated with fluid overload.

  • Possibility of bias due to the open-label nature of the trial.


What does it mean?

  • The use of aggressive fluid resuscitation in the treatment of acute pancreatitis was found to be associated with a higher risk of volume overload, as well as an absence of the predicted benefit in disease-specific outcomes, when compared to moderate fluid resuscitation.

  • Moderate fluid resuscitation is advised in patients with acute pancreatitis

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