Higher incidence of volume overload with aggressive fluid resuscitation for acute pancreatitis (WATERFALL)

Reference

De-Madaria E, Buxbaum JL, Maisonneuve P, et al, for the ERICA Consortium. Aggressive or moderate fluid resuscitation in acute pancreatitis. N Engl J Med 2022;387(11):989-1000.

Synopsis

For this international, multicenter trial, the investigators randomized adult patients admitted to the hospital with acute pancreatitis to receive aggressive (n = 122) or moderate (n = 127) fluid resuscitation. Patients with evidence of organ failure or chronic pancreatitis were excluded, among others. In the aggressive resuscitation group, patients received a bolus of lactated Ringer’s solution at 20 mL/kg of body weight over 2 hours, followed by a continuous infusion at 3 mL/kg per hour. In the moderate resuscitation group, patients received either a 10 mg/kg bolus (if hypovolemic) or no bolus, followed by a continuous infusion at 1.5 mL/kg per hour. Patients’ volume statuses were evaluated at 3, 12, 24, 48, and 72 hours using physical and biochemical assessments. Rate of fluid administration was adjusted as needed. Oral feeding was started at 12 hours if patients reported a pain score of 5 or less on a scale of 0 to 10. Fluid administration continued for at least 48 hours in the aggressive group and 20 hours in the moderate group. The 2 groups were similar at baseline and analysis was by intention to treat. After 48 hours, patients in the aggressive resuscitation group had received a median of 7.8L of fluid compared with 5.5L in the moderate resuscitation group. For the primary outcome — the development of moderate to severe pancreatitis — there was no significant difference detected between the 2 groups (22.1% in the aggressive group vs 17.3% in the moderate group; P = .32). However, with regard to the safety outcome, patients in the aggressive resuscitation group had a significantly higher rate of volume overload (20.5% vs 6.3%; adjusted relative risk 2.85; 95% CI 1.36 - 5.94; P = .004). The trial was stopped early, after the first interim analysis, because of evidence of increased harm without evidence of benefit.