Lactated Ringer's Versus Normal Saline for Acute Pancreatitis
Lactated Ringer's Versus Normal Saline for Acute Pancreatitis
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.

 The objective of this study is to assess the comparative efficacy of normal saline versus
 lactated ringer's solution in the management of acute pancreatitis.

 Patients presenting to the Los Angeles County Hospital with acute pancreatitis will be
 randomized to fluid resuscitation with NS or LR with volumes of fluid administered according
 to a pre-determined algorithm that will be the same for both treatment arms.

 The primary outcome of the study will be the change in SIRS prevalence from enrollment to 24
 hours. Secondary outcomes will include the change in SIRS prevalence from enrollment to 48
 hours and 72 hours, development of moderately severe or severe pancreatitis, change in PASS
 score, ICU admission, length of hospitalization, persistent pain or disability after
 discharge, and time of advancement to oral diet and discharge.
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.