The Waterfall Trial
The American College of Gastroenterology(1) recommends early aggressive fluid resuscitation in the first 12 – 24 hours of 250-500ml per hour of Lactate Ringer’s solution. In patients with volume depletion (hypotension and tachycardia), a further bolus is recommended. It is possible with this approach and I have often seen it, where patients can receive 10-15 litres of fluid in the first 24 hours.
Fluid therapy is important in acute pancreatitis as is correlates with correcting necrosis that occurs in areas of hypoperfusion in the pancreas. (Read a summary of fluid resuscitation in acute pancreatitis here)
These guidelines are based mostly consensus opinion, as there is not much robust research in this area. More recent work suggests that aggressive fluid resuscitation does not improve outcomes and may be associated with decreased survival (2).
The Waterfall Trial (3)(Early Weight-Based Aggressive vs Nonaggressive Goal-Directed Fluid Resuscitation in the Early Phase of Acute Pancreatitis) looked at the safety and efficacy of aggressive fluid resuscitation compared to moderate fluid resuscitation.
What they did
Multicenter, open-label, parallel-group, randomised, controlled superiority trial, conducted in 18 centres.
Patients with acute pancreatitis as per the revised Atlanta Classification and who had presented within 24 hours of pain onset were randomised to aggressive vs moderate fluid resuscitation.
N= 249, with 122 receiving aggressive therapy and 127 receiving moderate resuscitation.
Fluid volumes used
Lactated Ringer’s was used
- Aggressive fluid resuscitation was a 20ml/kg bolus then 3ml/kg/hr infusion
- Moderate fluid resuscitation was 1.5ml/kg/hr with no bolus, unless hypovolaemic; then a 10ml/kg bolus was given.
The Protocol is shown below
The patients were examined at 3, 12, 24, 48 and 72 hours to assess for fluid overload.
Primary Outcome: The development of moderate or severe acute pancreatitis.
Secondary Outcomes: These included organ failure and hospital, including ICU, length of stay.
- The aggressive therapy group received a median of 7.8 litres in 48 hours as compared to the moderate resuscitation group who received 5.5 litres.
- There was no difference between the two groups in terms of developing moderately severe or severe pancreatitis (primary outcome)
- The aggressive fluid resuscitation group was associated with a significantly higher rate of fluid overload and a longer hospital stay.
- The trial was stopped as it was showing increased harm without improvement in the aggressive resuscitation group.
The authors concluded:
“…the use of aggressive fluid resuscitation led to a higher risk of volume overload and did not show the hypothesized benefit in disease-specific outcomes. “
Limitations of the study as per the authors?
- The trial was terminated prior to adequate power being achieved
- It was an open labelled trial that may lead to bias.
- The aggressive fluid resuscitation group may have received therapy that was too aggressive.
My take on this
My view is that the aggressive group probably did not receive treatment as aggressive as we sometimes see. In most cases patients receive a 1-2 litre bolus followed by 250-500mL per hour ie
I think this study adds to the evidence and supports the less aggressive use of fluids in pancreatitis. Unless the patient is significantly dehydrated, no bolus is needed. Even if there is some dehydration, a smaller bolus of 10/ml/kg should be used and care should be taken to not use actual patient weight. For example, a 150kg patient will mean a very large bolus has been given.
The evidence is becoming more compelling for a less aggressive and tailored approach to fluid resuscitation in acute pancreatitis.
- Tenner S, Baillie J, DeWitt J, Vege SS; American College of Gastroenterology. American College of Gastroenterology guideline: management of acute pancreatitis. Am J Gastroenterol 2013;108:1400-16.
- Singh VK, Gardner TB, Papachristou GI, et al. An international multicenter study of early intravenous f luid adminis- tration and outcome in acute pancreatitis. United European Gastroenterol J 2017;5: 491-8.
- de-Madaria E. et al. Aggressive or Moderate Fluid Resuscitation in Acute Pancreatitis. NEJM September 2022. 387;11:989-1000