Recent research indicates that Lactated Ringer's (LR) solution is a more effective choice than normal saline (NS) for early fluid resuscitation in patients with pancreatitis. The findings suggest that LR can reduce disease severity and prevent complications by modulating the systemic inflammatory response. This shift challenges the long-standing practice of using NS as the primary resuscitation fluid.
Lactated Ringer's vs. Normal Saline
Pancreatitis, affecting approximately 34 out of every 100,000 adults annually, is characterized by inflammation of the pancreas, potentially leading to multiorgan failure. Traditionally, aggressive fluid resuscitation with NS has been the cornerstone of early management. However, emerging evidence suggests that the type of fluid used may significantly impact patient outcomes.
LR's electrolyte composition, closely mirroring human plasma, has garnered attention for its potential to mitigate the inflammatory response associated with severe pancreatitis. Unlike NS, LR minimizes the risk of hyperchloremic acidosis and electrolyte imbalances, which can exacerbate the condition. Studies have demonstrated that LR reduces levels of inflammatory markers such as CRP and IL-6, key drivers of the inflammatory cascade in acute pancreatitis.
A pivotal retrospective analysis across 22 international sites revealed that patients receiving LR within the first 24 hours of hospitalization experienced lower rates of disease progression and fewer severe complications compared to those receiving NS. This study affirmed LR's anti-inflammatory effects and its ability to reduce the risk of fluid overload.
Impact on Clinical Outcomes
Data from the APPRENTICE registry, tracking treatment patterns and outcomes in pancreatitis patients across multiple continents, have highlighted the association between LR use and improved outcomes. Patients treated with LR demonstrated a lower incidence of severe pancreatitis and fewer local and systemic complications. These benefits are linked to the reduction of inflammatory markers like CRP and IL-6.
Specifically, the retrospective analysis of APPRENTICE registry patients showed that early LR administration was associated with a significant reduction in systemic inflammatory response syndrome (SIRS), a major predictor of severe outcomes. Additionally, fewer patients progressed to necrotizing pancreatitis, a severe complication associated with increased morbidity and mortality.
Furthermore, the analysis revealed a reduction in ICU admissions and overall length of hospital stay among patients treated with LR. These outcomes are critical for emergency physicians, as they reduce the strain on critical care resources and minimize the risk of iatrogenic complications associated with prolonged critical care stays. A large analysis of over 20,000 admissions in the VA system found that resuscitation with LR was associated with lower one-year mortality compared with NS (adjusted odds ratio, 0.61 [95% confidence interval, 0.50-0.76]).
The WATERLAND Trial
While retrospective studies provide valuable insights, they are limited by their design. The ongoing WATERLAND trial, an international multicenter study, aims to provide definitive evidence on the superiority of LR compared to NS in treating pancreatitis. The trial will randomize over 700 patients to receive either LR or NS, focusing on primary endpoints such as the development of moderately severe or severe pancreatitis and safety outcomes like fluid overload.
Notably, the WATERLAND trial will also monitor cytokines like IL-6 and CRP to determine whether LR can better control the inflammatory response driving disease progression. Subgroup analyses will explore specific subpopulations that may benefit most from LR, particularly those with higher inflammatory burdens.
Implications for Clinical Practice
The growing consensus supports LR as a safe and effective choice for early resuscitation in pancreatitis, with evidence suggesting it may be superior to NS in reducing disease severity and preventing complications. Incorporating these data into everyday practice requires a shift away from the automatic use of normal saline, considering the patient's disease severity, inflammatory status, and risk factors.
As more data from the WATERLAND trial and other studies emerge, a continued shift in how pancreatitis is managed in emergency departments is anticipated. The potential benefits for patients, particularly those at high risk of severe disease, are significant, underscoring the importance of making informed choices about fluid resuscitation.
