Aggressive fluid therapy in Acute Pancreatitis is harmful

Enrique de-Madaria, M.D., Ph.D., James L. Buxbaum, M.D., Patrick Maisonneuve, Dipl.Eng., Ana García García de Paredes, M.D et el published study in NEJM comparing aggressive versus moderate fluid therapy in Acute pancreatitis. 


Early aggressive hydration is widely recommended for the management of acute pancreatitis.  This is based on animal model observation of regional hypoperfusion of the pancreas, leading to more necrosis. Initial observational studies indicated that hemoconcentration, which is a surrogate for systemic hypovolemia, was associated with pancreatic necrosis. Randomized, controlled trials comparing different volumes of intravenous fluid, which were limited by small size and overly specific inclusion criteria, have provided conflicting results.


Patients with acute pancreatitis were randomly assigned patients  to receive goal-directed aggressive or moderate resuscitation with lactated Ringer’s solution. Aggressive fluid resuscitation consisted of a bolus of 20 ml per kilogram of body weight, followed by 3 ml per kilogram per hour. Moderate fluid resuscitation consisted of a bolus of 10 ml per kilogram in patients with hypovolemia or no bolus in patients with normovolemia, followed by 1.5 ml per kilogram per hour.


18 yrs or older patients with Acute pancreatitis, diagnosed according to the Revised Atlanta Classification (which requires meeting two of the following three criteria: typical abdominal pain, serum amylase or lipase level higher than 3 times the upper limit of the normal range, or signs of acute pancreatitis on imaging). 

Patients who met the criteria for moderately severe or severe disease at baseline (shock, respiratory failure, and renal failure) or who had baseline heart failure (New York Heart Association functional class II, III, or IV), uncontrolled arterial hypertension, hypernatremia, hyponatremia, hyperkalemia, hypercalcemia, an estimated life expectancy of less than 1 year, chronic pancreatitis, chronic renal failure, or decompensated cirrhosis were excluded.


18 centers across four countries (India, Italy, Mexico, and Spain)


Development of moderately severe or severe acute pancreatitis (according to the Revised Atlanta Classification) during the hospitalization. Moderately severe or severe acute pancreatitis was defined as the meeting of at least one of the following criteria on the Revised Atlanta Classification: local complications, exacerbation of a preexisting coexisting condition, a creatinine level of at least 1.9 mg per deciliter (170 μmol per liter), a systolic blood pressure of less than 90 mm Hg despite fluid resuscitation, and a ratio of the partial pressure of arterial oxygen (Pao2) to the fraction of inspired oxygen (Fio2) of no more than 300. 


Fluid overload. Two of the following three criteria: symptoms, physical signs, and imaging evidence of hypervolemia. Auscultation for S3 or S4, orthostatic variables, and effusions on chest radiography (which are frequently exudative in acute pancreatitis) were not used.


Duration of hospital stay; intensive care unit (ICU) admission; the number of days in the ICU; the use of nutritional support or invasive treatment after randomization and during the hospitalization; the presence of SIRS ; persistent SIRS (lasting >48 hours within the first 72 hours after randomization); C-reactive protein levels in blood at 48 hours and 72 hours; death; a composite outcome of death, persistent organ failure (lasting >48 hours), or infected necrotizing pancreatitis. 


The trial was halted owing to between-group differences in the safety outcomes without a significant difference in the incidence of moderately severe or severe pancreatitis (22.1% in the aggressive-resuscitation group and 17.3% in the moderate-resuscitation group; adjusted relative risk, 1.30; 95% confidence interval [CI], 0.78 to 2.18; P=0.32). Fluid overload developed in 20.5% of the patients who received aggressive resuscitation and in 6.3% of those who received moderate resuscitation (adjusted relative risk, 2.85; 95% CI, 1.36 to 5.94, P=0.004). Total of 249 patients were included in study prior to halt.


Early aggressive fluid resuscitation in acute pancreatitis resulted in a higher incidence of fluid overload without improvement in clinical outcomes.

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