Comparing the Effects of Lactated Ringers and Normal Saline in Acute Pancreatitis

Acute pancreatitis represents inflammation of the pancreas that has been well identified in
the literature for several centuries. However, the phenomenon has only relatively recently
gained prominence in the pediatric literature. The incidence can be as high as 13 per 100,000
per year, a level which approaches that seen in adults, and the diagnosis has been
increasingly common over the last two decades. It affects all ages of children (including
infants) evidenced by well-established age appropriate diagnostic criteria. The precise
pathophysiological basis of the inflammation is not always as clear. Currently, the
prevailing theory is that there is an insult to the acinar cells of the pancreas likely via
an atypical calcium signal that releases a cascade of cellular activity and that ultimately
results in a disseminated cytokine storm. While there is certainly debate as to the inciting
event to this cascade, one thing that is clear is that extensive end-organ damage can occur
if this cytokine storm reaches systemic circulation. Therefore, the mainstay of management is
bowel (and specifically pancreatic) rest with significant fluid support to minimize or
mitigate the effect of the cytokines on the pancreas and other systemic organs such as the
lungs, heart, and kidneys. The remainder of therapy consists of appropriate analgesia and
antiemetics.

Unfortunately, most of the guidelines related to the details of management of acute
pancreatitis are extrapolated from the adult literature. There is only limited data regarding
management of acute pancreatitis in children. Recently, Wu et al. have shown compelling data
that suggest the choice of fluid for management of acute pancreatitis in adults should be
Lactated Ringers (LR). Their group demonstrated in a small randomized controlled trial
involving 40 adult patients with acute pancreatitis, that the patients randomized to the LR
arm of the study had significantly lower levels of C-reactive protein and Systemic
Inflammatory Response Syndrome (SIRS) markers compared with controls in the normal saline
(NS) group. They proposed that the mechanism for this difference may be related to the more
balanced pH of LR which might prevent, or at least further buffer, the systemic inflammation
that is triggered by the release of the offending cytokines from the pancreas. Currently,
both LR and NS are used at both Children's Hospital of The King's Daughters (CHKD) and
Children's National Health System (CNHS) at the discretion of the attending physician as the
standard of care for acute pancreatitis. The investigators hope to examine the question of
ideal fluid choice for fluid resuscitation in children with acute pancreatitis by assessing
recovery time in the context of measured inflammatory markers and SIRS status at 24 and 48
hours after admission.

This is a prospective randomized trial of pediatric patients in the emergency department (ED)
or inpatient ward diagnosed with acute pancreatitis. Patients meeting the study inclusion
criteria will be identified by an ED or inpatient physician. The ED or inpatient physician
will ask the eligible patient/parent if they are interested in hearing about the study. If
the eligible patient/parent is interested in hearing information about the study, the ED or
inpatient ward will notify the PI via telephone or page. The PI will come to the eligible
patient's room to explain the study and answer any questions, or the PI will page a research
team member to do so. If the patient/parent agrees to participate in the study, the research
team member will consent the parents of the patients aged 0-17 years or consent patients aged
18 years. Assent will be obtained from patients aged 8-17 years. Non-English speaking
patients/parents will be consented using an in-person translator or the blue phone
translating service. These consent and assent forms will be signed by a witness. At the time
of enrollment, the subject identification (ID) number and medical record number will be
entered into the electronic Subject ID Key. Once the patient is enrolled in the study, their
treatment will be randomized to either the LR or the NS group. Both treatments are current
standard of care for acute pancreatitis. Patients who choose not to participate in the study
will receive the standard of care treatment at the discretion of the attending physician,
which may involve either fluid, and will likely include most (if not all) of the lab studies
as outlined in this protocol.

The goal is to screen and enroll the subjects in either the ED or inpatient ward within 6
hours of diagnosis, as this is within the theoretical window prior to the development of
systemic inflammation. At the discretion of the attending physician, however, treatment can
begin in the ED or inpatient ward before enrollment in the study; patients will not have to
wait for necessary treatments. Patients will still be eligible to participate in the study if
treatment was begun in the ED or inpatient ward. The randomized treatment may end up being
the same or different than what was originally ordered by the attending physician. If any
such changes in treatment plan are noted, this will be considered for the data analysis.

The randomization plan will include constrained randomization using the permuted blocks
method. The research team member will open the envelope that contains the randomized
treatment and the Admission Order Sheet that details the orders that need to be placed on
admission. The research team member will communicate this information to the ED or inpatient
attending physician or staff member overseeing the patient's care at the time of enrollment.
All clinical treatments described in this protocol, including labs orders, are the current
standard of care for acute pancreatitis diagnosis. The purpose of the Admission Order Sheet
is to standardize the timeline of the lab work at admission, at 24 hours and 48 hours after
admission, not to request any additional lab work for the purposes of the study.

The subject will be placed on 1.5x maintenance IVF with the fluids to which they are
randomized. The patient will remain nil per os (NPO) for at least the first 24 hours, and the
time of initiating feeds after 24 hours will be at the discretion of the admitting team. As
the standard of care, the following studies will be obtained at the time of admission if not
previously obtained in the ED: Complete Metabolic Panel (CMP), gamma-glutamyltransferase
(GGT), Amylase, Lipase, Triglycerides, Complete Blood Count (CBC), and CRP, along with an
abdominal ultrasound. CBC, CRP, amylase and lipase levels will be obtained at 24 and 48 hours
(+/- 2 hours) as listed in the Admission Order Sheet. Similarly, a Basic Metabolic Panel
(BMP) will be collected at 24 and 48 hours (+/- 2 hours), with the addition of liver function
tests if liver enzyme levels are elevated at admission (as defined by transaminases greater
than 2 times the age appropriate upper limit of normal). SIRS status will be evaluated with
vital sign checks every 4 hours and the leukocyte counts every 24 hours.

The patients will be observed for additional known signs and complications of acute
pancreatitis such as persistent inflammation, shock, sepsis, electrolyte abnormalities, renal
failure or other end organ damage. Any adverse reactions during the trial will be treated
independent of the trial, and the attending physician will continue to manage the care of the
patient at their discretion. Any serious adverse reactions will be documented clinically and
reported to the CHKD or CNHS incident reporter systems, Eastern Virginia Medical School
(EVMS) Institutional Review Board (IRB), CNHS IRB and CHKD Human Research Coordination (HRC)
Committee .

The de-identified information will be collected from the patient's electronic medical record
by a research team member and entered directly into an Excel database. Patients transferred
from an outside ED should already have charts scanned into the Electronic Health Record (EHR)
as standard of care. If only a paper chart is available for any transferred patient, a
research team member will enter information directly from the paper chart into the Excel
database.

Inclusion Criteria:

- Patients aged 0-18 years diagnosed with acute pancreatitis in the emergency department
or inpatient ward at Children's Hospital of The King's Daughters or one of the
affiliated institutions participating in the study.

Exclusion Criteria:

- Patients greater than 18 years of age

- Patients who are not diagnosed with acute pancreatitis

- Patients who have any previous history of acute pancreatitis, past medical history of
underlying illness including congenital heart disease, chronic lung disease, or renal
failure

- Patients who have any of the following: hyperkalemia, systemic acidosis, acute
dehydration, extensive tissue breakdown, adrenal insufficiency, concomitant use of
potassium-sparing diuretics, use of extended-release preparations in patients with
esophageal compression caused by an enlarged left atrium, hypersensitivity to sodium
chloride, hypernatremia, or fluid retention

- Patients who are pregnant females

- Patients who have additional comorbidities at time of admission that would prevent
adequate treatment with the methods described above will be excluded