Reexamining Hypotonic Intravenous Fluid Use

This study will be a randomized patient-blinded 0.45 NS-controlled clinical trial evaluating
children ages 6 months to 16 years presenting to the Emergency Department (ED) at Ann &
Robert H. Lurie Children's Hospital of Chicago (Lurie Children's) with vomiting and/or
diarrhea requiring intravenous fluid therapy. Children will be treated with fluid boluses
per ED physician's discretion as is standard of care. After this initial intravenous
therapy, children will be admitted to the medical observation unit or general medicine floor
for additional fluid therapy. Per standard of care, they will be evaluated clinically by the
treating physician who will determine if any additional 0.9 NS boluses are required and
administer them at that time. Per standard of care, the treating physician will obtain the
information needed to complete the admission history and physical documentation and based on
this information will be able to determine if the patient is eligible for the study. The
treating physician will complete the Initial Screening Form to document whether the patient
is eligible. If a patient is eligible, the treating physician will obtain consent or inform
investigators of the patient so that they may obtain consent (depending on whether the
treating hospitalist has been trained to obtain consent). For patients who consent to
participate, information from the admission History and Physical exam will be extracted on
Study Form A. Recruitment will occur only at Lurie Children's. The consent form will provide
written information for the family; there are no other recruitment materials. A sign with a
reminder about the study will be posted in physician areas.

Those who are eligible and consent to participate in the study will be randomized to receive
either 5% dextrose containing 0.45 NS or 5% dextrose with 0.9 NS for their maintenance
fluids (see table below). If the treating physician would like to include potassium in the
IVF, the potassium concentration will be the standard potassium concentration in both groups
(20 mEq/liter). The use of potassium at this concentration is part of standard of care
unless patients have a contraindication to its inclusion; this decision made by the treating
physician will not alter inclusion in the study and the use of potassium will not impact the
results. Block randomization will be utilized using sequential envelopes which will contain
the preselected fluid type. This sealed envelope will be opened by the attending hospitalist
who will put in the fluid orders. Fluids will be covered by opaque bags so that patients and
parents will be blinded to study fluid type. Attending hospitalist physicians and nursing
staff will not be blinded to study fluids as all data for this study are objective
measurements and our primary outcome is an objective laboratory measurement. The standard
fluid administration rate determined by patient weight will be used and this same formula
will be applied for both groups. Baseline electrolytes and blood pressure will be checked
upon acceptance in the study (prior to maintenance fluid administration) and at 8 hours.
Patients in the study will have a basic electrolyte panel drawn through their IV catheter at
the beginning of the study prior to the start of their IVF. We will follow standardized
protocol for obtaining labs from the IV catheter. If sample cannot be obtained this way, we
will obtain them through via a blood draw from the vein if the family agrees. These
laboratory studies will be ordered by the physician and completed by trained nursing and/or
laboratory staff. This study requires 0.5ml of blood and will provide baseline blood levels
of sodium, chloride, bicarbonate, potassium, and glucose. Complete medical and family
historical data and socio-demographic information is obtained on all patients as part of the
routine admission to the hospital and this information will be extracted from the patient
chart for comparison of the two groups.

A majority of patients who are admitted for IVF are either unable to take fluids by mouth or
take insufficient amounts of fluids, especially during their first 8 hours of their
hospitalization. We anticipate most patients being NPO (nothing by mouth) or on clear fluid
diets in the first 8 hours of the hospital stay, reducing oral salt intake. Information
regarding oral fluid intake during the first 8 hours will also be extracted from patient
chart (intake and output charting). Patients will be otherwise treated per the discretion of
their physician for all other aspects of their care, including decision to stop maintenance
IVF therapy. After 8 hours, the study IVF will be removed and a second basic electrolyte
panel will be obtained. This will provide information about the change in blood sodium
levels as well as other electrolytes. After study fluids have been removed and blood samples
have been obtained, the treating physician may choose to continue IVF with either type of
fluid or discontinue fluids. If the patient does not require IVF for the full 8 hours, the
second blood sample will be obtained only if the patient was on the study IVF for >5 hours.
In this circumstance, the second blood draw will be obtained whenever the treating physician
decides to stop the study IVF. If the IVF are stopped earlier than 5 hours, the primary
outcome of a change in sodium of >3 is less relevant. Thus, the patient will be removed from
the study and a second blood sample will not be obtained.

This study will be conducted entirely during the hospitalization period. Based on a
preliminary study we conducted evaluating 103 patients admitted with nausea, diarrhea, and
dehydration, the average length of stay for intravenous fluids was 63 hours with greater
than 99% of patients needing more than 8 hours of intravenous fluids. Thus, this study would
be conducted within the first 8 hours of therapy and will not extend either length of stay
or IVF administration. No additional clinic visitations, hospitalizations, or outpatient
resources will be utilized. This study will involve laboratory studies but does not involve
radiographic studies or other invasive procedures.

Inclusion Criteria:

- Children 6 months to 16 years of age

- Symptoms of acute gastroenteritis (acute vomiting and/or diarrhea; symptoms of the
"stomach flu")

- Admission to the hospital

- Requiring maintenance IVF as determined by the inpatient attending clinical judgment.

Exclusion Criteria:

- Age <6 months or age >16 years

- Weight >60 kg

- Admission to the PICU

- Chronic kidney disease

- Endocrine disorders

- Liver or heart disease

- Malignancies

- Human immunodeficiency virus

- Cystic fibrosis

- Epilepsy

- Guillan Barre Syndrome

- Multiple sclerosis.

- Any diuretic medications or medication known to affect ADH secretion

- Abnormal baseline sodium concentration (<133 mEq/L or > 147 mEq/L)

- Abnormal baseline systolic blood pressure (>95% based on age and height normative
values)

- Hypotonic or isotonic fluids is deemed contraindicated

- Receives any additional intravenous fluids (NS or lactated ringer boluses) after
study fluids have been initiated

- Taking a full diet at the time of admission

- Parents or legal guardians cannot be reached for consent

- Parents and children do not speak English or Spanish as their primary language

- High volume diarrhea (>3 loose stools per day) for a >1 week duration