Critical Kids: PRoMPT Bolus

Authors: Kyle Smiley (EM Resident, BAMC, San Antonio, TX), Jason Woods (PEM Attending, CHCO, Aurora, CO)// Reviewed by: Alex Koyfman, MD (@EMHighAK); Brit Long, MD (@long_brit)

Welcome to Critical Kids, an emDOCs series focused on pediatric emergency medicine. Pediatric emergencies are challenging. We’ll provide summaries of hot-off-the-press guidelines and evidence to support your decisions at the bedside.

Background

• From 2026 Surviving Sepsis Campaign Guidelines:
  • “Sepsis is a life-threatening acute organ dysfunction due to infection, and septic shock is a subset of these patients with circulatory dysfunction that confers a higher risk of mortality”¹
• Roughly 25 million annual cases of pediatric sepsis globally²
  • Approximately 3.3 million (13%) result in fatality
    • Rates highest in developing world
  • Even in the United States, pediatric sepsis carries a 10.1% mortality rate³
    • Mortality has not improved from 2016-2022
•  Fluid resuscitation is an inexpensive, first-line therapy
• Adult trials comparing various crystalloid types for resuscitation have shown mixed results
  • Positive trials
    • SALT-ED: compared lactated Ringer’s (LR) or Plasma-Lyte (PL) vs normal saline (NS) in non-critically ill emergency department patients⁴
      • No mortality benefit but decreased negative kidney outcomes (AKI, new renal replacement therapy) in non-critical patients receiving balanced crystalloid compared to NS
    • SMART: compared LR or PL to NS in critically ill ICU patients⁵
      • Reduced rates of AKI, new renal replacement therapy (RRT), or death within 30 days when receiving balanced crystalloid compared to NS
  •  Negative trials
    • BaSICS: compared PL vs NS in critically ill ICU patients⁶
    • PLUS: compared PL vs NS in critically ill ICU patients⁷
      • Both showed no difference in morality, AKI, or new RRT
•  Only one large trial has evaluated fluid resuscitation by crystalloid type in pediatric patients with sepsis
  • FEAST: 3,141 children with severe sepsis or septic shock in sub-Saharan Africa comparing 20 mL/kg boluses of NS, 20 mL/kg boluses of 5% albumin, and no fluid bolus⁸
    • Both IV fluid bolus groups had increased mortality compared to no fluid bolus
    • 57% of children had malaria and received fluids instead of blood transfusion, likely skewing results

Study Design

• The Balanced Fluid or 0.9% Saline in Children Treated for Septic Shock is a pragmatic, open-label, randomized clinical trial that enrolled 9041 patients across 47 domestic and international emergency departments
  • Randomized 4512 in balanced fluid cohort and 4529 in 0.9% saline control (NS)
    • 277 (6.1%) and 282 (6.2%) withdrew from the trial respectively
    • Balanced fluids utilized were lactated Ringer’s (LR), Plasma-Lyte, or Hartmann’s solution
  • Inclusion criteria: all children at participating centers aged 2 months to <18 years with presumed or confirmed septic shock necessitating fluid resuscitation
    • Received maximum of 40 ml/kg prior to enrollment
    • Enrolled at index visit prior to discharge or admission
  • Exclusion criteria: children who had received >40 ml/kg prior to randomization and patients who the treating physician felt would could be harmed by one of the treatment fluid types
  • Intervention fluid was continued until 11:59 p.m. of the day after enrollment
• Primary outcome was a composite outcome of major adverse kidney events within 30 days (MAKE30) from enrollment or hospital discharge
  • Death from any cause, any renal replacement therapy, or persistent kidney dysfunction (serum creatinine >200% of baseline and at least > 0.3 mg/dL)
• Secondary outcomes were length of hospitalization, hospital-free days, death during hospitalization or within 90 days of enrollment, and the individual components of primary outcome
• Safety outcomes were electrolyte abnormalities occurring within first 4 days in the trial, any thrombotic event, development of cerebral edema

Study Results

• MAKE30 occurred in 3.4% in balanced-fluid and 3.0% in the NS group, which was not statistically significant (4 percentage points [95% CI −0.5 to 1.3]; risk ratio 1.10 [95% CI 0.88 to 1.40])
  • Median total volume administered was 85 mL/kg in balanced fluids and 88 mL/kg in the NS group, which was not a significant difference
    • Patients received an average of 17-18 mL/kg of NS prior to enrollment in each group
      • Post-hoc analysis suggests no impact on primary outcome
    • Groups similar in median initial lactate, baseline serum creatinine, acute kidney injury
•  Death before hospital discharge, hospital-free days, death within 90 days were similar between groups
  • Rates of hyperchloremia and hypernatremia were decreased but hyperlactatemia was increased in balanced-fluid cohort
    • These differences were expected based on fluid composition but did not confer a difference in MAKE30
    • Serum creatinine, chloride, and bicarbonate differences increased proportionally with fluid volume received
•  No differences in thrombosis or cerebral edema between groups

Strengths

• Large, multicenter, international trial
• Robust inclusion of patients both healthy and with chronic disease
• Pragmatic design allowing physicians to determine amount of fluid, rate, and timing aligns with real-world practice
• Investigators blinded to outcomes

Limitations

• MAKE30 incidence lower than expected
  • Initial lactate <2 in both groups, raising questions about how sick patients were
  • MAKE30 is a composite outcome; its utility discerning patient centered outcomes is limited
• Significant treatment compliance issues regarding who received at least 75% of their assigned fluids
  • Only 80% in the balanced-fluid and 88% in the NS
  • However, results remained consistent in tipping-point analysis
• Physicians were aware of treatment assignment
  • Intentional to increase protocol compliance with possible electrolyte changes, though this may lead to bias
• Only included patients with presumed sepsis and hypoperfusion
  • Not generalizable to other causes/types of shock
• Study only performed in developed countries, so not generalizable to low-resource settings

Summary

• In developed countries, the type of crystalloid fluid for resuscitation does not appear to have a meaningful impact on patient-centered outcomes in pediatric patients with sepsis and hypoperfusion.
• However, we cannot apply these results to patients with other types of shock (e.g.-cardiogenic, neurogenic) or in other diseases with presumed requirement of large-volume fluid resuscitation (e.g.-diabetic ketoacidosis, severe burns).
  

References

1. Prescott HC, Antonelli M, Alhazzani W, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2026.Crit Care Med. 2026;54(4):725-812. doi:10.1097/CCM.0000000000007075
2. Rudd KE, Johnson SC, Agesa KM, et al. Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the Global Burden of Disease Study.Lancet. 2020;395(10219):200-211. doi:10.1016/S0140-6736(19)32989-7
3. Rhee C, Balamuth F, Dysart K, et al. National Estimates of Pediatric Sepsis in US Hospitals Using Clinical Data.JAMA. 2026;335(15):1321-1331. doi:10.1001/jama.2026.3100
4. Self WH, Semler MW, Wanderer JP, et al. Balanced Crystalloids versus Saline in Noncritically Ill Adults.N Engl J Med. 2018;378(9):819-828. doi:10.1056/NEJMoa1711586
5. Semler MW, Self WH, Wanderer JP, et al. Balanced Crystalloids versus Saline in Critically Ill Adults.N Engl J Med. 2018;378(9):829-839. doi:10.1056/NEJMoa1711584
6. Zampieri FG, Machado FR, Biondi RS, et al. Effect of Intravenous Fluid Treatment With a Balanced Solution vs 0.9% Saline Solution on Mortality in Critically Ill Patients: The BaSICS Randomized Clinical Trial.JAMA. Published online August 10, 2021. doi:10.1001/jama.2021.11684
7. Finfer S, Micallef S, Hammond N, et al. Balanced Multielectrolyte Solution versus Saline in Critically Ill Adults.N Engl J Med. 2022;386(9):815-826. doi:10.1056/NEJMoa2114464
8. Maitland K, Kiguli S, Opoka RO, et al. Mortality after fluid bolus in African children with severe infection.N Engl J Med. 2011;364(26):2483-2495. doi:10.1056/NEJMoa1101549
9. Balamuth F, Weiss SL, Long E, et al; PRoMPT BOLUS Investigators of the PECARN, PERC, and PREDICT Networks. Balanced Fluid or 0.9% Saline in Children Treated for Septic Shock. N Engl J Med. 2026 Apr 24:10.1056/NEJMoa2601969.