Lactated Ringer's Versus Normal Saline for Acute Pancreatitis

Background: Acute pancreatitis is a common problem in the United States necessitating 275,000
hospital admissions per year, with resultant healthcare costs of approximately 2.5 billion
USD annually. As numerous trials have failed to show a benefit to specific pharmacologic
therapies in acute pancreatitis, the mainstay of treatment has been both supportive care and
early, aggressive fluid resuscitation. Small randomized studies have shown conflicting
results with regards to the influence of resuscitation fluid on outcomes in acute
pancreatitis, necessitating a large randomized trial to clarify if fluid choice matters or
not in the treatment of acute pancreatitis.

Objective: To assess the comparative efficacy of normal saline versus lactated ringer's
solution in the management of acute pancreatitis.

Study Design: Patients presenting to the Los Angeles County Hospital with acute pancreatitis
are the focus population of this study. Patients will be randomized to fluid resuscitation
with NS or LR within 8 hours of diagnosis of pancreatitis. The inclusion and exclusion
criterion will be assessed (see below). Randomization will be performed using a random
sequence algorithm with concealed allocation. The patients will be blinded to allocation by
covering the bag with an opaque covering. A study physician determining the outcomes will
also be blinded. Following randomization, the volumes of fluid administered for the
resuscitation will be determined by a pre-determined algorithm that will be the same for both
treatment arms. The hydration algorithm is as follows: all patients will receive a bolus of
the treatment fluid at a rate of 5 mL/kg/hour to be administered over the first two hours
(total 10 mL/kg) with an assessment for volume overload at 1 hour. They will then will
receive maintenance fluids at a rate of 3 mL/kg/hour. After 12 hours participants will have
blood urea nitrogen (BUN) assessed, which is part of the standard clinical procedure. Those
who do not have a fall in this parameter or who develop SIRS by this 12 hour checkpoint will
receive a second 5 mL/kg/hour bolus over two hours (as above) of their designated treatment
fluid followed by further treatment fluid at a rate of 3 mL/kg/hour. Those who do have a fall
in BUN will receive further treatment fluid at a rate of 3 mL/kg/hour for 12 additional
hours. Patients' volume status will be assessed in the following manner: study physicians
will perform a targeted physical exam which will include assessment of JVD, lung
auscultation, and monitoring for edema Q12 hours for the first 24 hours, then daily for the
remainder of the hospital admission. In elderly patients and those with co-morbidities, the
targeted physical exam will be performed Q12 hours for the entire hospital admission. Vitals
will also be obtained Q6-8 hours. If they develop signs of fluid overload including pitting
edema, ascites, anasacra, pulmonary edema, or dyspnea, or signs of renal failure including
oliguria, anuria, or hypotension, they will have their fluid rate managed at the discretion
of their treating physicians. However, it will be requested that if further fluid is given
that it be the assigned type (LR versus NS). At 24 hours patients will be assessed for SIRS
development (see outcomes). Beyond this point fluid rate will be per the primary team though
it still be encouraged that the assigned type of fluid (LR versus NS) is used for additional
resuscitation with the rate and volume beyond this point at the discretion of the treating
physician. However, if the treating physicians have a strong preference to change to a
different fluid type for clinical reasons this will be recorded (for post hoc analysis) and
the patient included in the intention to treat analysis.

Inclusion Criteria:

- Presentation with acute pancreatitis as defined by two of three criterion; amylase or
lipase > 3x the upper limit of normal, classical abdominal pain, or imaging suggestive
of pancreatitis. Such radiographic findings include swelling, edema, or heterogeneity
of the gland or peripancreatic fluid or stranding.

Exclusion Criteria:

- Patients with severe pancreatitis as defined by the Revised Atlanta Classification
will be excluded. Severe pancreatitis is defined by the Revised Atlanta Classification
as those with a Modified Marshall score of >2 for their cardiovascular renal, or
respiratory system will be excluded (Figure 2).13 Practically this includes patients
with systolic blood pressure <90, serum creatinine >1.9, and PaO2/FiO2 <300 (Figure
3). Since blood gases are unlikely to be drawn on those with mild pancreatitis we will
exclude patients with an oxygen saturation <92% on room air and certainly any patients
which require intubation for respiratory failure due to pancreatitis.

- Patients who cannot tolerate increased doses of fluids for other reasons will also be
excluded. This consists of those with cardiac insufficiency (CI, >NYHA Class II heart
failure), pulmonary edema, dialysis requirement, or severe liver dysfunction (albumin
< 3mg/dL, known cirrhosis).

- Pregnant women will also be excluded as they are prone to retain sodium and water,
which puts them at increased risk of pulmonary congestion, ascites or peripheral
edema.

- Patients who are incarcerated, younger than eighteen, or unable to give informed
consent will be excluded.

- Individuals who present with clinical signs of edema or anasacra, including pulmonary
congestion, peripheral swelling, and ascites, will also be ineligible for the study.

- Administration of fluids prior to the enrollment in the study will not be an exclusion
criterion as this reflects actual clinical practice (hydration during evaluation
period) however all fluids given prior to the study will be meticulously recorded.