Highlights
– In a prospective cohort from 22 international centers presented at ACG 2025, higher early intravenous fluid rates were associated with lower odds of BUN elevation but higher odds of new-onset or persistent SIRS at 6 and 24 hours after presentation.
– Each 1 mL/kg/h increase in fluid rate was linked to about 29–33% higher odds of new/persistent SIRS, while being associated with 12–17% lower odds of a BUN rise.
– The observed relationships are likely confounded by illness severity (sicker patients receive more fluids), underscoring the need for individualized, frequently reassessed fluid strategies and randomized trial data to guide practice.
Background: Why early fluids and BUN/SIRS matter in acute pancreatitis
Acute pancreatitis is a common, potentially life-threatening inflammatory condition of the pancreas with a highly variable clinical course. Early risk stratification is critical because a subset of patients will progress to organ failure, infected necrosis, and death. Two early, bedside-evaluable markers that clinicians commonly use to identify patients at risk for severe disease are blood urea nitrogen (BUN) and systemic inflammatory response syndrome (SIRS).
BUN is a frequently used surrogate for intravascular depletion and renal perfusion; rising BUN in the first 24 hours has been repeatedly associated with worse outcomes in acute pancreatitis. SIRS—defined by abnormalities in temperature, heart rate, respiratory rate and white blood cell count—provides a simple measure of systemic inflammation and has prognostic value when present early or when it persists.
Intravenous fluid resuscitation is a central early therapy for most patients with acute pancreatitis. Traditional guidance from major societies has recommended prompt fluid administration to correct hypovolemia and maintain end-organ perfusion; however, the optimal rate, volume, and target remain debated. Excessive fluid resuscitation may cause edema of the lungs and other organs and contribute to complications, while inadequate fluid therapy may predispose to renal impairment and worsening pancreatic ischemia.
Study design and methods (presented data)
Investigators prospectively enrolled adult patients admitted with acute pancreatitis at 22 international sites across four continents between 2015 and 2018. They examined IV fluid administration rates and volumes at 6 and 24 hours after presentation and related these to BUN levels and SIRS status at baseline and 24 hours, and to later clinical outcomes (disease severity, pancreatic necrosis, and organ failure).
For the purposes of this analysis a “moderately aggressive” fluid resuscitation rate was defined as >1.5 mL/kg/h, reflecting commonly referenced guidance (the American College of Gastroenterology recommendations were used as a contextual benchmark).
Key outcome measures included change in BUN from presentation to 24 hours, presence of new-onset or persistent SIRS between admission and 24 hours, and downstream clinical endpoints including severe disease, necrosis, and organ failure. The investigators used multivariable analyses to evaluate associations of fluid rate with SIRS and BUN changes; reported results were expressed as odds ratios (ORs) per 1 mL/kg/h increase in IV fluid rate.
Key findings
Patient-level fluid exposure
– At 6 hours after presentation, 950 patients had received a mean of 1173 mL of IV fluids, corresponding to an average rate of 2.59 mL/kg/h.
– At 24 hours, 957 patients had received a mean of 3251 mL of IV fluids, corresponding to an average rate of 1.81 mL/kg/h.
Early changes in SIRS and BUN
– Between admission and 24 hours, approximately 31% of patients experienced either new-onset or persistent SIRS (9% new SIRS and 22% persistent SIRS).
– Around 32% of patients had an elevation in BUN over the first 24 hours.
Associations of fluid rate with SIRS and BUN
– Each 1 mL/kg/h increase in fluid rate at 6 hours was associated with higher odds of new or persistent SIRS (OR 1.33).
– Each 1 mL/kg/h increase in fluid rate at 24 hours was similarly associated with higher odds of new or persistent SIRS (OR 1.29).
– Conversely, each 1 mL/kg/h increase in fluid rate was associated with lower odds of BUN elevation (OR 0.88 at 6 hours; OR 0.83 at 24 hours).
– Mean change in BUN stratified by SIRS behavior: patients without SIRS had a mean BUN decline of 1.5 mg/dL, whereas those with new or persistent SIRS had a mean BUN increase of 0.7 mg/dL (P = .005).
Clinical outcomes
– The presented analysis focused on early physiologic markers (BUN and SIRS) and their associations with fluid rates; the investigators emphasized that SIRS and clinical severity appear to be associated and likely to drive both treatment decisions (more fluids) and downstream adverse outcomes.
Interpretation and mechanistic considerations
The dataset shows a consistent pattern: higher early fluid rates are associated with less BUN rise but more SIRS. Several non–mutually exclusive mechanisms and explanations are plausible.
1. Confounding by indication: The most important explanation is confounding by severity. Clinicians typically administer more aggressive fluids to patients who appear sicker (tachycardia, hypotension, oliguria, laboratory derangements, or established SIRS). Thus, higher fluid rates may be a marker of severity rather than the cause of subsequent inflammation.
2. Hemodilution and renal perfusion: Higher fluid rates would be expected to blunt rises in BUN by improving renal perfusion and by simple dilutional effects. Therefore, a lower observed BUN rise in patients receiving greater fluids is physiologically plausible and may not imply reduced disease severity.
3. Tissue edema and inflammatory signaling: Excessive fluid administration has the potential to exacerbate interstitial and pulmonary edema, increase intra-abdominal pressures, and theoretically worsen organ dysfunction or inflammatory signaling. Whether this contributes to persistent SIRS on a biologic level cannot be determined from the present observational data, but the possibility merits attention.
Expert commentary: clinical implications and limits of the evidence
Comment from the presenting authors: “Patients who are more ill receive more fluids, making it appear that fluids caused worse outcomes; however, SIRS likely drove the poor outcomes,” the investigators noted. This succinctly highlights the central challenge in interpreting the associations.
Practical implications for clinicians
– Individualize fluid therapy. Early resuscitation remains important in hypovolemic or hemodynamically compromised patients, but a one-size-fits-all aggressive approach is not supported by this observational analysis.
– Reassess frequently. Frequent bedside reassessment (vital signs, urine output, repeated labs including BUN and hematocrit, and careful clinical exam for signs of volume overload) is essential in the first 24 hours.
– Use validated risk tools as adjuncts. Scores such as BISAP (which includes BUN and SIRS elements) can help predict severe disease and may orient clinicians toward more intensive monitoring or interventions.
Limitations to emphasize
– Observational design and confounding: Associations cannot be interpreted as causal. Sicker patients preferentially received higher fluid rates, which may account for the link with SIRS and worse outcomes.
– Unmeasured variables: The analysis as presented did not detail fluid type (crystalloid composition), exact timing of boluses versus maintenance infusions, use of vasopressors, or the degree of hemodynamic compromise at baseline—factors that could importantly modify outcomes.
– Endpoints and timing: SIRS is a nonspecific inflammatory metric; using it as a principal outcome is informative but limited. The relationship to longer-term clinically meaningful endpoints (infected necrosis, persistent organ failure, mortality) requires careful adjustment and/or randomized data.
Where this fits with guideline-based practice and prior literature
Current major guidelines, including the American College of Gastroenterology, recommend early fluid resuscitation for patients with hypovolemia or evidence of systemic compromise but emphasize reassessment with the goal of avoiding both under-resuscitation and fluid overload. Bedside markers such as BUN and SIRS are established prognostic tools; the BISAP score (including BUN and SIRS items) is an example of an early risk tool that correlates with outcomes and is simple to apply at presentation.
The findings presented here reinforce that fluid administration affects physiologic markers—reducing BUN rise—but that the relationship to systemic inflammation is complex and influenced by illness severity and likely by the balance between restoring perfusion and avoiding excess interstitial edema.
Practical recommendations
– Assess volume status and hemodynamics at presentation; reserve aggressive resuscitation for those with clear hypovolemia or shock physiology, and tailor rates to body weight and comorbidities.
– Start with judicious initial boluses where indicated, then reassess frequently (every 1–4 hours in higher-risk patients) using vitals, urine output, BUN, hematocrit, lung exam/oxygenation, and bedside ultrasound where available.
– Watch for signs of fluid overload (rising oxygen requirements, new crackles, increasing peripheral edema, or evidence of elevated central venous pressure) and de-escalate or restrict fluids accordingly.
– Use BUN trends and SIRS presence as complementary, not interchangeable, signals—BUN can reflect intravascular status and renal perfusion while SIRS captures systemic inflammation.
Research gaps and future directions
Randomized controlled trials that compare prespecified, protocolized fluid strategies (including different rates, targets, and fluid types) with careful monitoring of both short-term physiologic markers and hard clinical endpoints remain the gold standard to determine causation. Such trials should address stratification by baseline severity, include standardized criteria for fluid titration and de-escalation, and systematically capture fluid-related complications (pulmonary edema, abdominal compartment syndrome).
Conclusion
This international prospective cohort presented at ACG 2025 found that higher early IV fluid rates were associated with lower odds of BUN elevation but higher odds of new or persistent SIRS at 6 and 24 hours. The most plausible interpretation is that sicker patients received more fluids (confounding by indication), and that fluids reduce BUN by improving renal perfusion or dilution, while persistent SIRS reflects underlying disease severity. Clinicians should individualize fluid therapy in acute pancreatitis, reassess frequently, and be mindful of both under-resuscitation and fluid overload. Well-designed randomized trials remain necessary to define optimal early fluid strategies across the spectrum of disease severity.
Funding and clinicaltrials.gov
The analysis was presented by Daniel Marino, MD, MBA (NYU Langone Health) at the American College of Gastroenterology Annual Scientific Meeting on October 27, 2025. No specific funding source or clinicaltrials.gov identifier was reported in the presented abstract information supplied with this summary.
References
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2. Banks PA, Bollen TL, Dervenis C, et al. Classification of acute pancreatitis—2012: revision of the Atlanta classification and definitions. Gut. 2013;62(1):102–111.
3. Wu BU, Johannes RS, Sun X, Tabak Y, Conwell DL, Banks PA. The early prediction of mortality in acute pancreatitis: development of a simple bedside index (BISAP). Clin Gastroenterol Hepatol. 2008;6(10):1090–1096.
4. Marino D. High fluid rates may raise inflammation risk in pancreatitis. Presentation, American College of Gastroenterology Annual Scientific Meeting, Phoenix, Arizona. October 27, 2025.
