The correlation between necrosis and acute pancreatitis, as well as the possible benefits of fluid resuscitation, has been investigated in a small number of studies. It is known that severe disease develops in about 35% of patients with acute pancreatitis, and this can lead to worse outcomes. However, there is some disagreement over the best way to administer fluids during the early stages of the disease. Two trials involving patients with severe pancreatitis showed that rapid fluid expansion was associated with decreased survival [1-2], while a trial involving patients without SIRS showed that those who were not originally at high risk for moderate-to-severe disease improved more quickly when given vigorous hydration rather than moderate hydration [3]. A systematic review showed a lower incidence of adverse events and lower mortality with moderate hydration than with aggressive hydration, but it was limited by the heterogeneity and quality of the source studies [4].
WATERFALL (an Open-Label Multicenter Randomized Controlled Trial of Early Weight-Based Aggressive vs. Nonaggressive Goal-Directed Fluid Resuscitation in the Early Phase of Acute Pancreatitis: an Outcome Assessment) was designed to assess the safety and effectiveness of aggressive fluid resuscitation as contrasted with moderate fluid resuscitation in a varied population of people with acute pancreatitis at varying degrees of severity [5].
The study was conducted in India, Italy, Mexico, and Spain and 249 patients with various degrees of acute pancreatitis were assigned to receive aggressive fluid resuscitation with 20 ml/kg over 2 hours followed by 3 ml/kg/hour (n = 122), or moderate fluid resuscitation using 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 (n = 127). Fluid administration amounts were adjusted thereafter depending on the medical condition of the patient.
The study found that there was no significant difference in the development of moderately severe or severe pancreatitis during hospitalization between the aggressive-resuscitation group and the moderate-resuscitation group (22.1% vs 17.3, RR, 1.30; 95% confidence interval [CI], 0.78 to 2.18; P = 0.32). Additionally, fluid overload was significantly higher in the aggressive-resuscitation group compared to those who received moderate resuscitation (20.5% vs 6.3%, RR, 2.85; 95% CI, 1.36 to 5.94, P = 0.004).
The study was cut short because of early safety concerns and lack of effectiveness, leaving only a smaller number of patients randomized out of the 744 originally intended. In order to get an accurate measure of efficacy, we would need more patients to go through the trial; however, this exposes them to an increased risk of fluid overloading. Another limitation of the study is the possibility of bias due to the open-label nature of the trial.
The study concluded that when compared to moderate fluid resuscitation, aggressive fluid resuscitation in the treatment of acute pancreatitis was found to be linked with a higher risk of volume overload as well as a lack of the anticipated benefit in disease-specific outcomes. Based on this, I would feel comfortable changing my practice to be more conservative in fluid resuscitation in patient with acute pancreatitis, what about you?
Based on the WATERFALL trial results, will you change your practice in resuscitating patients with acute pancreatitis?
- Yes
- No
- Never heard of the study!
REFERENCES
Mao EQ, Tang Y-Q, Fei J, et al. Fluid therapy for severe acute pancreatitis in acute response stage. Chin Med J (Engl) 2009;122:169-73.
Mao E-Q, Fei J, Peng Y-B, Huang J, Tang Y-Q, Zhang S-D. Rapid hemodilution is associated with increased sepsis and mortality among patients with severe acute pancreatitis. Chin Med J (Engl) 2010;123:1639-44.
Buxbaum JL, Quezada M, Da B, et al. Early aggressive hydration hastens clinical improvement in mild acute pancreatitis. Am J Gastroenterol 2017;112:797-803.
Di Martino M, Van Laarhoven S, Ielpo B, et al. Systematic review and meta-analysis of fluid therapy protocols in acute pancreatitis: type, rate, and route. HPB (Oxford) 2021;23:1629-38.
De-Madaria E et al. Aggressive or Moderate Fluid Resuscitation in Acute Pancreatitis. N Engl J Med 2022; 387:989-1000. DOI: 10.1056/NEJMoa2202884