Pediatrics · Medical Literature
Balanced Fluid or 0.9% Saline in Children Treated for Septic Shock
Abstract
New England Journal of Medicine, Ahead of Print.
Clinical relevance
In children aged 2 months to under 18 years treated for suspected septic shock in the emergency department, does resuscitation with balanced crystalloid fluid reduce Major Adverse Kidney Events within 30 days (MAKE30) compared with 0.9% saline? __SNAPSHOT__ {"studyDesign":"Pragmatic, multicenter, randomized controlled trial (PRoMPT BOLUS)","setting":"47 emergency departments across five countries: United States, Canada, Australia, New Zealand, and Costa Rica; conducted through the PECARN, PERC, and PREDICT pediatric research networks; August 26, 2020 through October 31, 2025","sampleSize":"n=8,482 (balanced fluid: n=4,235; 0.9% saline: n=4,247)","population":"Children aged 2 months to <18 years (median age 6.8 years; 50.8% male) presenting to the emergency department with clinician-suspected sepsis and planned treatment with more than one fluid bolus for abnormal perfusion consistent with septic shock","intervention":"Balanced crystalloid fluid (e.g., lactated Ringer's, Plasma-Lyte, Hartmann's solution) for both bolus resuscitation and maintenance hydration for up to 48 hours","comparator":"0.9% normal saline for both bolus resuscitation and maintenance hydration for up to 48 hours","primaryOutcome":"MAKE30: Major Adverse Kidney Events within 30 days — a composite of death from any cause, new renal replacement therapy, or persistent kidney dysfunction at hospital discharge or 30 days, whichever came first","followUp":"30 days (primary outcome); 90-day mortality reported as secondary outcome","fundingSource":"Government: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NIH/NICHD); additional funding from Medical Research Future Fund (Australia) and Canadian Institutes of Health Research (CIHR); not industry-sponsored"}
Key findings
The primary composite outcome of MAKE30 occurred in 3.4% of children in the balanced fluid group and 3.0% of children in the 0.9% saline group (risk ratio = 1.1; 95% CI, 0.88–1.40; p not reported in abstract). This difference was neither statistically nor clinically significant. The absolute risk difference was +0.4 percentage points favoring saline numerically, though the confidence interval crosses 1.0, indicating no meaningful difference (NNH if harm were real: approximately 250 [calculated]). All prespecified secondary outcomes — including length of hospitalization, hospital-free days, death before discharge, and death within 90 days — were also similar between groups. Biochemical differences were observed: the saline group had higher serum chloride levels and the balanced fluid group had higher lactate levels; however, neither difference translated into differential patient-centered outcomes. No clinically important differential safety signals were reported between groups.
Practice implications
IMPORTANT CAVEAT: Only the abstract and secondary reporting sources are available; the full manuscript, pre-specified statistical analysis plan, subgroup analyses, and detailed adverse event tables have not been independently reviewed. This limitation must be acknowledged when applying these findings clinically. Within that constraint: PRoMPT BOLUS is the largest pediatric sepsis resuscitation trial conducted to date and provides high-quality pragmatic evidence that balanced crystalloid fluids and 0.9% saline are clinically equivalent for the primary endpoint of MAKE30 in children treated for suspected septic shock in the emergency department. The trial directly challenges the biological plausibility argument that hyperchloremia from saline would translate to measurable kidney harm in this population: it did not, at least at the event rates observed. The findings are broadly generalizable given enrollment across 47 EDs in five countries and a wide pediatric age range (2 months to <18 years). However, important gaps remain: (1) the trial was conducted in emergency department settings — applicability to PICU-initiated resuscitation or ongoing inpatient fluid management beyond the initial resuscitation period is uncertain; (2) patients requiring only a single bolus were excluded, limiting generalizability to milder presentations; (3) subgroup-level data (e.g., by age, pathogen type, pre-existing renal disease, cancer status) are not available from the abstract; (4) the prior 2026 Surviving Sepsis Campaign guideline conditionally favored balanced fluids over saline in children with very low certainty — PRoMPT BOLUS now substantially upgrades the evidence base and supports equipoise between the two fluids. The trial does not establish superiority of either fluid and supports clinical discretion in fluid selection based on institutional availability, cost, and individual patient factors. __LIMITATIONS__ 1. Abstract-only availability: Full statistical methods, pre-specified subgroup analyses, and detailed safety data cannot be independently verified. 2. Pragmatic design: While enhancing generalizability, the open-label pragmatic design precluded blinding of clinicians and may have introduced co-intervention differences beyond the randomized fluid. 3. Composite endpoint: MAKE30 combines outcomes of differing clinical severity (death, renal replacement therapy, persistent kidney dysfunction); component-level data are not available from the abstract. 4. ED-specific enrollment: Results may not generalize to patients resuscitated exclusively in the ICU or those with resuscitation begun prior to ED arrival. 5. Exclusion of single-bolus patients: Children requiring only one bolus were excluded, potentially enriching the sample for more severely ill patients and limiting applicability to the full spectrum of pediatric septic shock. 6. Event rate: The overall MAKE30 event rate of approximately 3–3.4% is low, raising the question of whether the trial was powered to detect small but potentially meaningful absolute differences if they exist. 7. Heterogeneity across five countries: Differences in standard of care, concurrent therapies, and ICU resources across participating countries may influence effect estimates. 8. Biochemical outcomes not linked to clinical outcomes: Higher chloride (saline) and higher lactate (balanced) were observed but not adjudicated for mechanistic contribution to outcomes. 9. Follow-up limited to 30–90 days: Long-term renal outcomes beyond 90 days were not assessed. __BOTTOM_LINE_CATEGORY__ practice_changing __BOTTOM_LINE__ PRoMPT BOLUS, the largest pediatric septic shock resuscitation trial to date (n=8,482 across 47 international EDs), found no statistically or clinically significant difference in MAKE30, mortality, or other secondary outcomes between balanced crystalloid and 0.9% saline. Clinicians may use either fluid for resuscitation of children with suspected septic shock without expectation of differential kidney or survival outcomes. These results support revising the prior conditional Surviving Sepsis Campaign preference for balanced fluids in children to one of equipoise, allowing fluid selection based on availability, cost, and clinical context.