Early, aggressive fluid resuscitation in acute pancreatitis led to a higher incidence of fluid overload without improving clinical outcomes in the landmark WATERFALL trial.
Early aggressive hydration is widely recommended for the management of acute pancreatitis, but evidence for this practice is limited.
“The WATERFALL trial demonstrates that aggressive fluid resuscitation in acute pancreatitis is not safe, it is not associated with improved outcomes, and it should be abandoned,” Enrique de-Madaria, MD, PhD, with Hospital General Universitario Dr. Balmis, Alicante, Spain, told this news organization.
The trial settles a “new and clear reference for fluid resuscitation in this frequent disease: lactated Ringer’s solution 1.5 mL/kg per hour (preceded by a 10 mL/kg bolus over 2 hours only in case of hypovolemia),” added Dr. de-Madaria, president of the Spanish Association of Gastroenterology.
“This moderate fluid resuscitation strategy is associated with a much lower frequency of fluid overload and a trend toward improved outcomes. For such reasons, it should be considered as a new standard of care in the early management of acute pancreatitis,” Dr. de-Madaria said.
The WATERFALL trial results were published in the New England Journal of Medicine.
The results are “stunning and, given the carefully crafted trial methods, irrefutable,” Timothy Gardner, MD, with the section of gastroenterology and hepatology, Dartmouth–Hitchcock Medical Center, Lebanon, N.H., wrote in a linked editorial.
The trial was conducted at 18 centers across India, Italy, Mexico, and Spain. Patients who presented with acute pancreatitis were randomly allocated to aggressive or moderate resuscitation with lactated Ringer’s solution.
Aggressive fluid resuscitation consisted of a bolus of 20 mL/kg of body weight, followed by 3 mL/kg per hour. Moderate fluid resuscitation consisted of a bolus of 10 mL/kg in patients with hypovolemia or no bolus in patients with normovolemia, followed by 1.5 mL/kg per hour in all patients in this group.
Patients were assessed at 12, 24, 48, and 72 hours, and fluid resuscitation was adjusted according to clinical status.
A total of 249 patients were included in the interim analysis – 122 in the aggressive-resuscitation group and 127 in the moderate-resuscitation group.
The data and safety monitoring board terminated the trial at the first interim safety analysis as a result of the development of fluid overload in 20.5% of the patients in the aggressive-resuscitation group versus 6.3% of those in the moderate-resuscitation group (adjusted relative risk, 2.85; 95% confidence interval, 1.36-5.94; P = .004).
“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 at baseline, patients with SIRS at baseline (thus, with a higher risk of development of severe pancreatitis), and patients with hypovolemia,” the investigators reported.
This clear signal of harm was coupled with no significant difference in the incidence of moderately severe or severe pancreatitis (22.1% in the aggressive-resuscitation group and 17.3% in the moderate-resuscitation group; aRR, 1.30; 95% CI, 0.78-2.18; P = .32).
Patients in the aggressive-resuscitation group spent a median of 6 days in the hospital, compared with 5 days for patients in the moderate-resuscitation group.
“These findings do not support current management guidelines, which recommend early aggressive resuscitation for the treatment of acute pancreatitis,” the study team wrote.