Lactated Ringer's Versus Normal Saline for Acute Pancreatitis

December 6, 2021 updated by: James Buxbaum, University of Southern California

Lactated Ringer's Versus Normal Saline in the Management of 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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

121

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90033
        • LAC+USC Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Lactated Ringer
Patients will receive fluid administration of Lactated Ringer's solution at a pre-determined volume algorithm that is the same for both arms
Other: Fluid administration
Fluid administration of bolus and maintenance fluids
Other Names:
  • Fluid
Experimental: Normal Saline
Patients will receive fluid administration of Normal Saline solution at a pre-determined volume algorithm that is the same for both arms
Other: Fluid administration
Fluid administration of bolus and maintenance fluids
Other Names:
  • Fluid

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
SIRS at 24 hours
Time Frame: 24 hours
Change in SIRS prevalence from enrollment to 24 hours
24 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
SIRS at 48 hours
Time Frame: 48 hours
Proportion of patients with change in SIRS from enrollment to 48 hours
48 hours
SIRS at 72 hours
Time Frame: 72 hours
Change in SIRS prevalence from enrollment to 72 hours
72 hours
Moderately severe acute pancreatitis
Time Frame: 48 hours
Development of moderately severe acute pancreatitis
48 hours
Severe acute pancreatitis
Time Frame: >48 hours
Development of severe acute pancreatitis
>48 hours
PASS score
Time Frame: 24 hours
Change in PASS score from enrollment to 24 hours
24 hours
PASS score
Time Frame: 48 hours
Change in PASS score from enrollment to 48 hours
48 hours
PASS score
Time Frame: 72 hours
Change in PASS score from enrollment to 72 hours
72 hours
ICU admission
Time Frame: >72 hours
ICU admission and ICU intervention including intubation, respiratory distress with out intubation defined as RR>20 AND O2 Sat<90% on room air, death, development of extrapancreatic fluid collection (EPFS)
>72 hours
Length of hospitalization
Time Frame: >72 hours
Length of hospitalization
>72 hours
Pain after discharge based on a 0-10 intensity scale (10 most severe, 0 none)
Time Frame: 2 weeks
Report of persistent pain or disability after discharge based on telephone follow-up based on a 0-10 intensity scale (10 most severe, 0 none)
2 weeks
Advance diet
Time Frame: >48 hours
Time to advancement of oral diet
>48 hours
Time to work
Time Frame: 2 weeks
Time to work after hospitalization based on post-discharge telephone follow-up
2 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Southern California

Investigators

  • Principal Investigator: James Buxbaum, MD, University of Southern California

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 18, 2018

Primary Completion (Actual)

August 16, 2021

Study Completion (Actual)

August 16, 2021

Study Registration Dates

First Submitted

February 12, 2018

First Submitted That Met QC Criteria

August 20, 2018

First Posted (Actual)

August 22, 2018

Study Record Updates

Last Update Posted (Actual)

December 8, 2021

Last Update Submitted That Met QC Criteria

December 6, 2021

Last Verified

December 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • APP-17-06494

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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