Hassieb Din, MD

Aggressive fluid resuscitation has long been the cornerstone of treatment for 

While initial observational studies suggesting hypovolemia is associated with pancreatic necrosis fueled this practice, subsequent work has signaled that increased volume resuscitation may not improve outcomes. 

Randomized controlled trials comparing different volumes of fluid resuscitation, though, have had heterogeneous results and were limited by their small sample sizes and inclusion criteria.

E. de-Madaria et al. conducted an open-label, parallel-group, multicenter randomized controlled trial comparing moderate versus aggressive fluid resuscitation in patients with acute pancreatitis of multiple disease severities.

Adult patients with a diagnosis of acute pancreatitis according to the Revised Atlanta Classification who presented to the emergency department within 24 hours of pain onset were recruited from 18 centers. 

Patients meeting criteria for moderately severe or severe disease at baseline were excluded. Enrolled patients were randomly assigned to either receive aggressive or moderate fluid resuscitation per the trial protocol (Figure 1). 

Randomization was stratified according to trial center, systemic inflammatory response syndrome (SIRS), and hypovolemia. 

Enrolled patients underwent an initial physical assessment at 3 hours and then both biochemical and physical assessments at periodic intervals up to 72 hours, with adjustment of volume resuscitation based on the protocol and presence of hypovolemia, normovolemia, or hypervolemia. 

Oral feeding was initiated at 12 hours if abdominal pain was significantly improved. The sample size included all patients who underwent randomization and the data were analyzed according to an intention-to-treat principle.

A total of 249 patients were enrolled in the study and randomly assigned to the aggressive resuscitation group (n = 122) or the moderate resuscitation group (n = 127). Patients in the aggressive resuscitation group received a median of 7.8 L (interquartile range [IQR], 6.5 - 9.8) of fluid while patients in the moderate fluid resuscitation group received a median of 5.5 liters (IQR, 4.0 - 6.8). 

There was no significant difference between the aggressive and moderate fluid resuscitation groups in the primary outcome of rates of development of moderately severe (22.1%) or severe acute pancreatitis (17.3%; adjusted relative risk [aRR], 1.30; 95% confidence interval [CI], 0.78 - 2.18; 

However, aggressive fluid resuscitation was associated with a significantly higher incidence of fluid overload (20.5% vs 6.3%; aRR, 2.85; 95% CI, 1.36 - 5.94) with 1 patient in the aggressive fluid group requiring orotracheal intubation, and 6 patients classified as having moderate-to-severe fluid overload.

While not statistically significant, there was also a notable trend toward worse symptom intensity, longer hospital stay duration, and increased incidence of necrotizing pancreatitis among patients in the aggressive fluid resuscitation group. 

These safety results were reviewed by the data and safety monitoring board who halted the trial early due to the worse safety outcomes in the aggressive resuscitation group that were not balanced by improved outcomes. Subgroup analysis to assess the effect of baseline hypovolemia and SIRs did not find any major differences compared to the main analysis. 

While patients with acute pancreatitis have traditionally been treated with early aggressive fluid resuscitation, E. de-Madaria et al. demonstrated that this practice does not significantly improve the prevention of moderately severe or severe acute pancreatitis. Furthermore, when accounting for the risk of volume overload, these data lend support towards a more conservative fluid resuscitation approach.

This study is limited by its early termination and is thus underpowered to definitively evaluated efficacy.

While the study’s fluid resuscitation protocol is one method for managing patients with acute pancreatitis, there remains debate over the best practice for managing these patients during the first 24 hours. Still, this trial is the best evidence to date supporting the practice for less aggressive fluid resuscitation in patients with acute pancreatitis.

1. de-Madaria E, Buxbaum JL, Maisonneuve P, et al. Aggressive or Moderate Fluid Resuscitation in Acute Pancreatitis. N Engl J Med. 2022;387(11):989-1000. doi:10.1056/NEJMoa2202884

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A recent randomized controlled trial showed the limitations of either option, despite being a cornerstone of care.