Game-changing results in fluid resuscitation

Early aggressive fluid resuscitation in acute pancreatitis It resulted in a higher rate of fluid overload without improving clinical outcomes in the landmark WATERFALL trial.

Early intensive hydration is widely recommended for the treatment of acute pancreatitis, but evidence for this practice is limited.

“The WATERFALL trial shows that aggressive fluid resuscitation in acute pancreatitis is not safe, is not associated with improved outcomes, and should be abandoned,” Enrique de Madaria, MD, PhD, with Dr. Palmis University General Hospital, Alicante, Spain, said. Medscape Medical News.

The trial settled on “a new and clear reference for fluid resuscitation in this recurrent disease: lactated Ringer’s solution 1.5 ml/kg per hour (preceded by a 10 ml/kg bolus over 2 hours only in case of hypovolemia), added de Madaria, president of the Spanish Society of Organ Diseases. digestive system;

“This moderate fluid resuscitation strategy is associated with a much lower frequency of fluid overload and a trend toward better outcomes. For these reasons, it should be considered a new standard of care in the early management of acute pancreatitis,” de Madaria said. .

WATERFALL EXPERIENCE RESULTS Posted today in New England Journal of Medicine.

The results are “amazing, and given our carefully designed experimental methods, are irrefutable,” Timothy Gardner, MD, M.D., Division of Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, wrote in Associated editorial.

Trial details

The trial was conducted at 18 centers across India, Italy, Mexico and Spain. Patients with acute pancreatitis were randomly assigned to aggressive or moderate resuscitation with lactated Ringer’s solution.

Aggressive fluid resuscitation consists of a dose of 20 ml/kg body weight, followed by 3 ml/kg per hour. Moderate fluid resuscitation consisted of a dose of 10 mL/kg in patients with hypovolemia or no bolus dose in patients with leukemia, followed by 1.5 mL/kg per hour in all patients in this group.

Patients were evaluated at 12, 24, 48 and 72 hours, and fluid resuscitation was adjusted according to clinical status.

A total of 249 patients were included in the interim analysis – 122 in the aggressive resuscitation group and 127 in the moderate resuscitation group.

The Data and Safety Monitoring Committee terminated the trial in the first interim safety analysis as a result of the development of fluid overload in 20.5% of patients in the aggressive resuscitation group versus 6.3% of the moderate (adjusted relative) resuscitation group. [RR], 2.85; 95% CI, 1.36 – 5.94; q = .004).

An increased risk of fluid overload has been detected in the general population as well as in subgroups of patients without systemic inflammatory response syndrome (SIRS) at baseline, patients with SIRS at baseline (and thus, with a higher risk of severe pancreatitis), and patients with hypovolemia,” the researchers report.

This clear indication of damage is coupled with no significant difference in the incidence of acute or severe pancreatitis (22.1% in the aggressive resuscitation group and 17.3% in the moderate resuscitation group; adjusted RR 1.30; 95% CI, 0.78–2.18; q = .32).

Patients in the aggressive resuscitation group spent an average of 6 days in the hospital, compared to 5 days for patients in the moderate resuscitation group.

“These findings do not support current management guidelines, which recommend early aggressive resuscitation for the treatment of acute pancreatitis,” the study team wrote.

The Landmark Experience

This is a “notable” and “clinically relevant trial given its selection of an aggressive and moderate-resuscitation treatment combination appropriate for the real world, its use of pancreatitis severity as the main clinical outcome, and its reliance on the carefully selected variable of excess fluid as a major safety outcome,” Gardner wrote in his editorial.

“Unlike most other randomized controlled trials of fluid resuscitation in acute pancreatitis, patients with varying primary pancreatitis severity were included, and changes in resuscitation rate were determined based on dynamic assessment of hemodynamic testing, imaging and clinical factors,” he adds.

Gardner says the results of the WATERFALL trial lead to several conclusions.

First, the need to focus on a constant rate of initial resuscitation – no more than 1.5 ml / kg body weight per hour. Physicians should administer a dose of 10 mL/kg only if there are signs of primary hypovolemia.

Second, careful clinical and hemodynamic monitoring is necessary during the first 72 hours after admission to ensure that patients remain at a euvolemic level and to avoid fluid overload.

Third, diuresis in patients with fluid excess in the first 72 hours is likely to be beneficial and certainly not detrimental to important clinical outcomes.

Gardner says the trial also highlights the need to focus research efforts on evaluating other drug treatments rather than crystal fluids.

“Conducting randomized controlled trials in acute pancreatitis is very difficult, and the limited human and financial resources available for appropriately powered trials in the field after a waterfall are much better spent on comparative efficacy and placebo-controlled trials to evaluate new therapeutic agents,” says Gardner. .

He concludes, “Now that we are past the waterfall, it is time to consider the final stages of new goals to tackle this challenging disease.”

Support for the trial was provided by the Carlos III Health Institute, the Spanish Society of Gastroenterology, and ISABIAL (Instituto Alicante Health and Biomedical Research). Author and Editor Disclosures It can be found here.

In Angel J Med. Posted on September 15, 2022. SummaryAnd the editorial

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