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Long B, Gottlieb M. Aggressive intravenous fluid resuscitation for acute pancreatitis. Academic Emergency Medicine. Published online April 20, 2023:acem.14741.

Study Population: 953 patients with acute pancreatitis enrolled in 9 randomized controlled trials

Efficacy Endpoints

Survival rate

Harm Endpoints

Primary: mortality
Secondary: clinical improvement, fluid-related-complications, sepsis, acute respiratory failure, and total hospital days

Narrative

Acute pancreatitis (AP) has an incidence of 34 cases per 100,000 person-years and mortality of 1.6 deaths per 100,000 person-years.1^, 2^, 3^, 4 International guidelines recommend early fluid resuscitation with isotonic crystalloids to treat hypovolemia and prevent organ hypoperfusion.5^, 6^, 7^, 8^, 9 Several meta-analyses, however, have demonstrated inconsistent findings with aggressive intravenous (IV) fluid therapy in AP.10^, 11^, 12 Moreover, the recent WATERFALL trial reported a three-fold increased risk of fluid overload in those who received aggressive IV fluid hydration.13 Therefore it is important to assess the evidence for aggressive IV fluid resuscitation in patients with AP.

The systematic review summarized here included randomized controlled trials (RCTs) of adult patients diagnosed with AP based on the revised Atlanta classification.14 This classification requires at least two of the following to be present for diagnosis: abdominal pain consistent with AP, serum lipase or amylase at least three times greater than the upper limit of normal, or classic imaging findings of AP.14^, 15^, 16 The systematic review classified the severity of AP based on the Atlanta international symposium and revised Atlanta classification.15^, 16 Patients with mild(absence of organ failure and local or systemic complications) and moderately severe (transient organ failure or local or systemic complications) AP were classified into the non-severe AP group. Aggressive fluid resuscitation was defined as fluid resuscitation greater than 10 mL/kg/hour for initial management, a fluid bolus of 10 mL/kg/hour for 2 hours followed by 2-3 mL/kg/hour in the first 24 hours, or isotonic fluids >500 mL/hour for the first 12-24 hours. The comparison group received non-aggressive resuscitation, defined as fluid administration less than the thresholds defined above. The primary outcome was all-cause mortality. Secondary outcomes included rate of clinical improvement, fluid-related-complications (abdominal compartment syndrome, pulmonary or peripheral edema, and any sign of volume overload), sepsis, acute respiratory failure, and total hospital days.

The systematic review included 9 RCTs (n=953 patients).14 Two trials evaluated patients with severe AP, while 6 trials evaluated those with non-severe AP. Five studies were conducted in China, while the remainder included the United States (one study), Mexico (one study), and Thailand (one study). One study involved multiple countries (India, Italy, Mexico, and Spain). The majority of studies compared a 20 ml/kg bolus then 3 mL/kg/hour infusion (aggressive) with 10 ml/kg bolus then 1.5 mL/kg/hour infusion (non-aggressive).

Aggressive IV hydration was associated with increased risk of mortality compared to non-aggressive fluid hydration when data for patients with severe and non-severe AP were pooled together (9 RCTs, risk ratio [RR]: 2.4, 95% confidence interval [CI]: 1.4 to 4.2, absolute risk difference [ARD]: 4.7%, number needed to harm [NNH]: 21). Aggressive fluid hydration was associated with increased risk of mortality in those with severe AP (2 RCTs, pooled RR: 2.5, 95% CI: 1.4 to 4.4, ARD: 19.5%, NNH: 5) but not in patients with non-severe AP (3 RCTs). Regarding secondary outcomes, the authors found increased risk of fluid-related complications (5 RCTs, pooled RR: 2.5, 95% CI: 1.7 to 3.8, ARD: 12.5%, NNH: 7) when patients with severe and non-severe AP were pooled.

Caveats

This systematic review has several limitations. While it included only RCTs there were small numbers of patients in each trial, reducing statistical power to detect potential differences. This was particularly notable for severe AP, which comprised only 211 total patients. Second, while the review did include trials from multiple countries, 5 trials were conducted in China, limiting the applicability to other countries or settings. Third, the included RCTs did not report the total hydration volumes in hospitalized patients, so the true volumes patients in the aggressive hydration and non-aggressive hydration groups received are unclear. Fourth, there were a variety of etiologies for AP in the included patients, adding clinical heterogeneity. Fifth, the certainty of evidence for all study outcomes was determined to be low to very low, primarily due to methodological issues and small sample sizes of the included RCTs.

Based on the available evidence, aggressive fluid hydration seems to increase the risk of mortality and complications in patients with AP. Further data, more carefully documented, and from larger studies and across multiple countries are necessary to improve the certainty and reliability of these findings. Despite the limitations and low certainty, however, this evidence base appears far stronger than the largely observational evidence underlying longstanding recommendations for aggressive hydration in AP. Thus, we have assigned an NNT color recommendation of Black (Harms > Benefits) for aggressive IV hydration in those with AP and look forward to future trials that we hope will bring further clarity.

The original manuscript was published in Academic Emergency Medicine as part of the partnership between TheNNT.com and AEM.

Author

Brit Long, MD; Michael Gottlieb, MD
Supervising Editors: Shahriar Zehtabchi, MD

Published/Updated

May 9, 2023