Dr. Hammond

Clinical question: Is early, aggressive, fluid resuscitation in acute pancreatitis or moderate fluid resuscitation the best and safest way to prevent progression to moderately severe or severe pancreatitis?

Background: Early, aggressive, fluid resuscitation is widely recommended and used in the management of acute pancreatitis. However, subsequent studies have shown this strategy may result in increased adverse events without significantly improving morbidity and mortality.

Study design: Investigator-initiated, multicenter, open-label, randomized, clinical trial

Setting: 18 medical centers in four countries (Italy, India, Morocco, Spain)

Synopsis: 249 patients were enrolled and randomly assigned to receive either aggressive or moderate fluid resuscitation for acute pancreatitis. Aggressive fluid resuscitation was defined as a bolus of 20 mL/kg lactated Ringers followed by an infusion at 3 mL/kg/hr. Moderate fluid resuscitation was defined as a 1.5 mL/kg/hr lactated Ringers infusion for all patients, preceded by a 10 mL/kg bolus only if there were clinical signs of hypovolemia. Moderately severe or severe pancreatitis was defined per the Revised Atlanta Classification as the development of one or more of the following: creatinine >1.9; systolic blood pressure <90 despite fluid resuscitation; PaO2/FiO2 <300; exacerbation of a pre-existing condition; or local pancreatic complications on imaging. Exclusion criteria included a medical history of congestive heart failure, uncontrolled hypertension, hypernatremia, hyponatremia, hyperkalemia, hypercalcemia, chronic pancreatitis, chronic kidney disease, decompensated cirrhosis, or presenting with moderately severe to severe pancreatitis.

The trial was halted at its interim analysis due to significant between-group differences in the safety outcome with no significant difference in the primary outcome. Development of fluid overload (safety outcome) was 20.5% in the aggressive fluid resuscitation group versus 6.3% in the moderate group (adjusted relative risk, 2.85; 95% CI, 1.36 to 5.94). Progression to moderately severe or severe pancreatitis (primary outcome) was 22.1% in the aggressive fluid resuscitation group versus 17.3% in the moderate group (adjusted relative risk 1.30; 95% CI 0.78 to 2.18).

Bottom line: Moderate fluid resuscitation in patients with acute pancreatitis is preferred as it reduces the risk of fluid overload without increasing the risk of the development of moderately severe or severe pancreatitis.

Citation: de-Madaria E, et al. Aggressive or moderate fluid resuscitation in acute pancreatitis. N Engl J Med. 2022;15;387(11):989-1000.

Dr. Hammond is an associate physician at the University of California, San Diego.