Abstract
Treatment options are limited for acute pancreatitis (AP). Early aggressive fluid resuscitation (AFR) has been widely considered beneficial because of theoretical improvement in end-organ perfusion, including the pancreas and gut, with pancreatic necrosis and bacterial translocation as consequences of ischemia. There is scarce direct evidence for its association to improved outcomes. Furthermore, it has been described that AFR may be associated with poor outcomes in severe AP. WATERFALL is an investigator-initiated international multicenter open-label randomized controlled trial comparing AFR vs. moderate fluid resuscitation (MFR) in AP. The main outcome variable will be the incidence of moderate to severe AP (a clinically relevant outcome that has been validated). Aggressive fluid resuscitation will consist in lactated Ringer solution (LR) 20-mL/kg bolus (administered over 2 h) followed by LR 3 mL/kg per hour. Patients randomized to MFR will receive an LR bolus 10 mL/kg in case of hypovolemia or no bolus in patients with normal volemia, followed by LR 1.5 mL/kg per hour. The patients will be assessed at 3 (±1), 12 (±4), 24 (±4), 48 (±4), and 72 (±4) h from recruitment, and fluid resuscitation will be adjusted to the patient's clinical and analytical status according to a protocol. Based on a prospective multicenter study, the incidence of moderate to severe AP is 35%. Sample sizes of 372 patients per group (overall 744) achieve 80% power to detect a difference in the incidence of moderate to severe AP of 10%, at a significance level (α) of 0.05 using a two-sided z-test, assuming a 10% dropout rate. These results assume that three sequential tests are made using the O'Brien–Fleming spending function to determine the test boundaries.
Highlights
Acute pancreatitis (AP) is the third leading cause of hospital admission for gastrointestinal disease (1)
ML/min per 1.73 m2) (8) Clinical signs or symptoms of volume overload or heart failure at recruitment (9) Shock or respiratory failure according to the revised Atlanta classification at recruitment (10) Time from pain onset to arrival to emergency room >24 h (11) Time from confirmation of pancreatitis to randomization >8 h (12) Severe comorbidity associated with an estimated life expectancy
Observational studies showed a close relationship between hemoconcentration and necrosis and hypothesized that aggressive fluid resuscitation (AFR) may prevent pancreatic necrosis by increasing pancreatic blood flow (5)
Summary
Acute pancreatitis (AP) is the third leading cause of hospital admission for gastrointestinal disease (1). While the majority of patients with AP have a mild course, 35% develop moderate to severe disease, which is associated with high morbidity and an increased risk of mortality (2). Another study by Buxbaum et al (11) in the United States suggested that AFR hastens clinical improvement among patients with predicted mild AP, but was not powered to address clinically important outcomes, such as the development of organ failure (12). Moderate to severe AP as defined by the revised Atlanta classification (13) has been validated as a clinically relevant outcome variable in several studies, including our nationwide Spanish multicenter prospective cohort study involving more than 1,600 patients (2). An adequately powered RCT focused on clinically relevant outcome variables and taking into account the patients’ perspective is needed to define the appropriate fluid strategy in AP
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
