A 46-year-old woman presents to the intensive care unit with a diagnosis of acute pancreatitis. According to a recent study that compared aggressive fluid resuscitation with moderate fluid resuscitation, development of which of the following conditions was MOST likely increased with aggressive fluid resuscitation?
- □ (A) Moderately severe or severe pancreatitis
- □ (B) Volume overload
- □ (C) Kidney failure
Aggressive hydration has been promoted as the recommended treatment of acute pancreatitis, a condition that, although common, has not had advances in treatment other than early enteral feeding and lactated Ringer’s solution as the fluid of choice. Observational studies showed that hemoconcentration, a surrogate for hypovolemia, was associated with pancreatic necrosis. Evidence for the volume of fluid to administer and the rate of administration had been limited until a recent randomized controlled trial (the Early Weight-Based Aggressive vs. Nonaggressive Goal-Directed Fluid Resuscitation in the Early Phase of Acute Pancreatitis: an Open-Label Multicenter Randomized Controlled Trial [WATERFALL]).
In this multicenter trial, patients aged 18 years or older who received a diagnosis of acute pancreatitis no more than eight hours before enrollment and who presented to the emergency department no more than 24 hours after pain onset were randomized in a 1:1 ratio to aggressive or moderate resuscitation. Randomization considered the trial center, presence or absence of systemic inflammatory response syndrome, and the presence or absence of baseline hypovolemia. Patients with hypovolemia in the aggressive resuscitation group received a bolus of 20 mL/kg of lactated Ringer’s solution over two hours followed by infusion at a rate of 3 mL/kg/h. Patients with hypovolemia in the moderate resuscitation group received a bolus of 10 mL/kg lactated Ringer’s solution followed by infusion at a rate of 1.5 mL/kg/h. Additional boluses (20 mL/kg or 10 mL/kg) were administered in both groups if urine output was less than 0.5 mL/kg/h or systolic blood pressure was less than 90 mm Hg at timed checkpoints. In both groups, patients who were normovolemic received infusion at a rate of 1.5 mL/kg/h. At 12, 24, 48, and 72 hours, goal-directed resuscitation was assessed and adjusted as needed. Boluses were administered if hypovolemia was present; otherwise, infusions at 1.5 mL/kg/h continued for 20 hours in the moderate resuscitation group and 48 hours in the aggressive resuscitation group. If there was suspicion of fluid overload, infusion was decreased or stopped. The primary outcome was the development of moderately severe or severe acute pancreatitis.
A total of 249 patients were included in an interim analysis because the trial was terminated early by the safety monitoring board. The authors found no difference in the development of moderately severe or severe pancreatitis between the aggressive resuscitation group and the moderate resuscitation group (22.1% vs. 17.3%, respectively; adjusted relative risk [aRR], 1.30; 95% CI, 0.78-2.18). No notable difference was found in any of the clinical outcomes, including all complications, systemic inflammatory response syndrome, invasive or nutritional support, intensive care unit admission, organ failure, respiratory failure, or kidney failure. Both the study authors and the authors of an accompanying editorial inferred that statistical significance was not found because of the smaller-than-planned sample size and the early trial termination; however, both felt that the results would be unchanged even if the sample size had been larger.
Fluid overload occurred more often in the aggressive resuscitation group than in the moderate resuscitation group (20.5% vs. 6.3%; aRR, 2.85; 95% CI, 1.36-5.94), and diuretics, compared to decreased hydration alone, were overwhelmingly needed to manage fluid overload. As expected, the cumulative median volume of fluid over the 72-hour period was higher in the aggressive resuscitation group than in the moderate resuscitation group (8.3 L vs. 6.6 L).
In summary, this trial did not find any difference in the development of moderately severe or severe pancreatitis with aggressive versus moderate fluid resuscitation. However, the results do suggest that volume overload occurs more frequently with aggressive fluid resuscitation. The WATERFALL trial adds to the increasing literature that aggressive hydration may worsen some outcomes in critically ill patients.