Pragmatic Pediatric Trial of Balanced Versus Normal Saline Fluid in Sepsis: A Pilot Feasibility Study
Condition: Shock, Septic
MeSH terms: Sepsis; Shock, Septic
Intervention: Lactated Ringer; Normal saline
Intervention description: LR is a sterile, nonpyrogenic "balanced" solution used for fluid and electrolyte replenishment via intravenous or intraosseous administration. Each 100 mL of LR contains 600 mg sodium chloride (NaCl), 310 mg of sodium lactate (C3H5NaO3), 30 mg of potassium chloride (KCl), and 20 mg of calcium chloride (CaCl2 · 2H20) with an approximate potential of hydrogen (pH) of 6.5 (6.0 to 7.5).; Normal saline solution is an "unbalanced" crystalloid solution containing 154 mEq/L of sodium and 154 milliequivalent (mEq/L) of chloride.
Phase: Phase 1
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Single-center, open-label, randomized pragmatic clinical trial
Masking: None (Open Label)
Masking description: Study participants, care provider, investigator, and outcomes assessor will not be masked to intervention allocation.
Enrollment: 50.0
Sex: All
Minimum age: 6 Months
Maximum age: 17 Years
Healthy volunteers: No
Keywords: Sepsis; Septic shock; Pediatric; Fluid resuscitation; Saline; Lactated Ringer's; Crystalloid; Mortality; Pragmatic trial; Feasibility

Summary:

      The objective of this pilot study is to assess overall feasibility prior to embarking on a
      larger randomized pragmatic trial comparing the clinical effectiveness of fluid resuscitation
      with NS versus LR for pediatric patients with suspected septic shock. Necessary feasibility
      assessments include ensuring appropriate compliance with study fluid in each of the two arms,
      effectiveness of study enrollment using a pragmatic study design embedded within routine
      clinical practice, and acceptability of using Exception from Informed Consent (EFIC).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Males or females age >6 months to <18 years

          2. Clinician concern for septic shock, operationalized as:

               1. a "positive" ED sepsis alert confirmed at the physician-led "sepsis huddle" OR

               2. a physician diagnosis of suspected septic shock requiring parenteral antibiotics
                  and fluid resuscitation as per the ED sepsis management pathway

          3. administration of at least 20 mL/kg IV/ intraosseous (IO) fluid resuscitation

          4. Receipt of ≤40 mL/kg IV/IO crystalloid fluid prior to randomization

          5. Additional fluid deemed likely to be necessary to treat poor perfusion, defined as
             either hypotension or abnormal (either "flash" or >2 second) capillary refill (as
             determined by clinician's judgment)10

          6. Parental/guardian permission (informed consent) if time permits; otherwise, EFIC
             criteria met

        Exclusion Criteria:

          1. Clinician judgement that patient's condition deems it unsafe to administer either NS
             or LR (since patients will be equally likely to receive NS or LR at time of study
             enrollment), including (but not limited to):

               1. Clinical suspicion for impending brain herniation based on data available at or
                  before patient meets criteria for study enrollment

               2. Known hyperkalemia, defined as non-hemolyzed whole blood or plasma/serum
                  potassium > 6 mEq/L, based on data available at or before patient meets criteria
                  for study enrollment

               3. Known hypercalcemia, defined as plasma/serum total calcium >12 mg/dL or whole
                  blood ionized calcium > 1.35 mmol/L, based on data available at or before patient
                  meets criteria for study enrollment

               4. Known acute fulminant hepatic failure, defined as plasma/serum alanine
                  aminotransferase (ALT) >10,000 U/L or total bilirubin >12.0 mg/dL, based on data
                  available at or before patient meets criteria for study enrollment

               5. Known history of severe hepatic impairment, defined as diagnosis of cirrhosis,
                  "liver failure", or active listing for liver transplant

               6. Known history of severe renal impairment, defined as current dependency on
                  peritoneal dialysis or hemodialysis

               7. Known metabolic disorder, inborn error of metabolism, or primary mineralcorticoid
                  deficiency (e.g., mitochondrial disorder, urea cycle disorder, amino acidemia,
                  fatty acid oxidation disorder, glycogen storage disorder, congenital adrenal
                  hypoplasia, Addison's disease) as reported by subject, LAR or accompanying
                  caregiver, or as listed in the medical record

          2. Known pregnancy determined by routine clinical history disclosed by patient and/or
             legally authorized representative (LAR) (or other accompanying acquaintance)

          3. Known prisoner as determined by routine social history disclosed by patient and/or LAR
             (or other accompanying acquaintance)

          4. Known allergy to either normal saline or lactated Ringer's as determined by routine
             allergy history disclosed by patient and/or LAR (or other accompanying acquaintance)
             or as indicated in the medical record

          5. Indication of prior declined consent to participate based on presence of "PRoMPT BOLUS
             Opt-Out" bracelet