Pragmatic Pediatric Trial of Balanced Versus Normal Saline Fluid in Sepsis

Inclusion Criteria:

1. Males or females age >2 months to <18 years

2. Clinician concern for septic shock, operationalized as:

3. a "positive" ED sepsis alert confirmed by a physician OR

4. physician decision to treat for septic shock OR

5. a physician diagnosis of septic shock requiring parenteral antibiotics andfluid resuscitation

6. Administration of at least one IV/Intraosseous (IO) fluid bolus for resuscitationand additional fluid deemed likely to be necessary to treat poor perfusion, orclinician judgment that >1 fluid bolus is highly likely to be required. Poorperfusion is defined as physician's judgement of hypotension or abnormal (either "flash" or "prolonged") capillary refill.

7. Receipt of ≤40 mL/kg IV/IO total crystalloid fluid prior to randomization

8. Parental/guardian permission (informed consent) if time permits; otherwise,Exception from informed consent (EFIC) criteria met

Exclusion Criteria:

1. Treating physician judges that patient's condition deems it unsafe to administereither NS or BF (since patients will be equally likely to receive NS or BF at timeof study enrollment), including:

2. Clinical suspicion for impending brain herniation

3. Known hyperkalemia, defined as non-hemolyzed whole blood or plasma/serumpotassium > 6 mEq/L, based on data available at or before patient meetscriteria for study enrollment

4. Known hypercalcemia, defined as plasma/serum total calcium >12 mg/dL or wholeblood ionized calcium >1.35 mmol/L, based on data available at or beforepatient meets criteria for study enrollment

5. Known acute fulminant hepatic failure, defined as plasma/serum alanineaminotransferase (ALT) >10,000 U/L or total bilirubin >12.0 mg/dL, based ondata available at or before patient meets criteria for study enrollment

6. Known history of severe hepatic impairment, defined as cirrhosis, "liverfailure", or awaiting transplant

7. Known history of severe renal impairment, defined as peritoneal dialysis orhemodialysis

8. Known metabolic/mitochondrial disorder, inborn error of metabolism, or primarymineralocorticoid deficiency as reported by participant, legally authorizedrepresentative (LAR) or accompanying caregiver, or as listed in the medicalrecord

9. Other concern for which the treating clinician deems it unsafe to administereither NS or LR

10. Known pregnancy determined by routine history disclosed by patient and/oraccompanying acquaintance.

11. Known prisoner

12. Known allergy to a crystalloid fluid

13. Indication of declined consent to participate based on presence of an opt-outbracelet with appropriate messaging embossed into the bracelet, the presence of thepatient's name on an opt-out list that will be kept up-to-date and checked prior torandomization, or verbal "opt-out" prior to enrollment.