Balanced Fluid or 0.9% Saline in Children Treated for Septic Shock

Published April 23, 2026
N Engl J Med 2026;395:870-881
DOI: 10.1056/NEJMoa2601969
Abstract
Background
Whether treatment with balanced crystalloid fluid leads to better outcomes than 0.9% saline in children treated for septic shock is debated.
Methods
In this pragmatic clinical trial conducted at 47 emergency departments in five countries, patients (2 months to <18 years of age) with suspected septic shock and abnormal perfusion were randomly assigned to receive fluid resuscitation with either balanced fluid or 0.9% saline for up to 48 hours. The primary outcome was a major adverse kidney event (a composite of death, new renal-replacement therapy, or persistent kidney dysfunction) at 30 days after enrollment or hospital discharge, whichever occurred first.
Results
Of 9041 enrolled patients, 277 (6.1%) in the balanced-fluid group and 282 (6.2%) in the 0.9%-saline group withdrew from the trial, leaving 4235 and 4247 patients, respectively, for analysis. A primary-outcome event occurred in 137 patients (3.4%) in the balanced-fluid group and in 124 (3.0%) in the 0.9%-saline group (difference, 0.4 percentage points; 95% confidence interval [CI], −0.5 to 1.3; risk ratio, 1.10; 95% CI, 0.88 to 1.40; P=0.85). The median number of hospital-free days during 28 days after enrollment was 23 (interquartile range, 19 to 25) in both groups. Hyperchloremia occurred in 868 patients (31.4%) in the balanced-fluid group and in 1383 (49.0%) in the 0.9%-saline group; hypernatremia in 52 (1.8%) and 89 (3.1%), respectively; and hyperlactatemia in 260 (19.8%) and 228 (16.7%). No differences in other safety outcomes or adverse events were seen.
Conclusions
Among children treated for septic shock, no significant difference was seen in the incidence of death, new renal-replacement therapy, or persistent kidney dysfunction when fluid resuscitation was administered with balanced fluid as compared with 0.9% saline. (Funded by Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; PRoMPT BOLUS ClinicalTrials.gov number, NCT04102371.)
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Notes
This article was published on April 24, 2026, at NEJM.org.
A data sharing statement provided by the authors is available with the full text of this article at NEJM.org.
Supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD101528); the National Institute of Diabetes and Digestive and Kidney Diseases (P50DK114786); the Commonwealth of Pennsylvania Department of Health (SAP #4100085749); the Medical Research Future Fund International Clinical Trial Collaboration, Canberra, Australia (GNT1190814); and the Canadian Institutes of Health Research (173498). Additional support was provided by the Children’s Hospital of Philadelphia Research Institute and Alberta Children’s Hospital Research Institute. The Pediatric Emergency Care Applied Research Network (PECARN) is funded by awards (U03MC00008, U03MC00001, U03MC00003, U03MC00006, U03MC00007, U03MC22684, and U03MC22685) from the Emergency Medical Services for Children Network Development Demonstration Program of the Maternal and Child Health Bureau, Health Resources and Services Administration, under a cooperative agreement. The Pediatric Research in Emergency Departments International Collaborative (PREDICT) network is funded in part by a grant (GNT2024601) from the National Health and Medical Research Council Center of Research Excellence, Canberra, Australia; the Murdoch Children’s Research Institute, Parkville, Australia; and the Victorian Government’s Operational Infrastructure Support program, Melbourne, Australia.
Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.
We thank the staff at the global Pediatric Emergency Research Network for endorsement of this trial; the staff at the National Center for Advancing Translational Sciences Trial Innovation Network for consultation of the trial design and methods and for providing financial support of the PRoMPT BOLUS pilot and feasibility trial; J. Michael Dean, M.D., Charlie Casper, Ph.D., SallyJo Zuspan, and Melissa Metheney from the PECARN Emergency Medical Services for Children Data Center and Rick Watts from the Pediatric Emergency Research Canada (PERC) Data Coordinating Center for their insightful comments and advice regarding data collection efforts across sites in the PERC network; Jill Baren, M.D., M.B.E., for ethics consultation of the design phase of this trial; Nadir Yehya, M.D., M.S.C.E., and Ed Oakley, M.B.B.S., F.A.C.E.M., for their contributions to the trial methods; members of the Pediatric Acute Lung Injury and Sepsis Investigators Network, the Society of Critical Care Medicine Discovery Network, the Australian and New Zealand Intensive Care Society Pediatric Study Group, the Australasian College for Emergency Medicine Clinical Trials Network, and the Children’s Inpatient Research Collaboration of Australia and New Zealand for review and endorsement of the trial; and Andrew Costarino, M.D., for serving as the independent medical monitor for this trial.
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Copyright © 2026 Massachusetts Medical Society. All rights reserved.
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History
Published online: April 23, 2026
Published in issue: September 3, 2026
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Cited by
- Fluid Resuscitation in Patients with Sepsis — For Whom the Balance Tolls, New England Journal of Medicine, 395, 9, (921-922), (2026)./doi/full/10.1056/NEJMe2609856
- Balanced crystalloid versus saline for resuscitation in adult sepsis: a systematic review and meta-analysis, Frontiers in Medicine, 13, (2026).https://doi.org/10.3389/fmed.2026.1906761
- Acute Bronchiolitis, Pediatric Acute Respiratory Distress Syndrome, and Sepsis: Leading Journal Reads and What This Means, Pediatric Critical Care Medicine, 27, 7, (891-895), (2026).https://doi.org/10.1097/PCC.0000000000003995
- IV bolus, maintenance and medication carrier fluid in children with community-acquired sepsis: a multicentre cohort study, Archives of Disease in Childhood, (archdischild-2025-330189), (2026).https://doi.org/10.1136/archdischild-2025-330189
- Sepsis pediátrica en la era de la Surviving Sepsis Campaign 2026: de la reanimación, a la medicina de precisión y el seguimiento a largo plazo, Revista Mexicana de Pediatría, 93, 2, (87-93), (2026).https://doi.org/10.35366/123614
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* The study involved 9041 enrolled patients (2 months to <18 years old) with suspected septic shock and abnormal perfusion.
* Patients were randomly assigned to receive either balanced fluid or 0.9% saline for up to 48 hours of fluid resuscitation.
* The primary outcome was a major adverse kidney event at 30 days after enrollment or hospital discharge, whichever occurred first.
* In the balanced-fluid group, 137 patients (3.4%) experienced the primary outcome; in the 0.9%-saline group, 124 patients (3.0%) experienced the primary outcome.
* The difference in the incidence of the primary outcome was 0.4 percentage points; the risk ratio was 1.10 (95% CI, 0.88 to 1.40; P=0.85).
* The median number of hospital-free days during 28 days post-enrollment was 23 in both groups (interquartile range, 19 to 25).
* Hyperchloremia occurred in 868 patients (31.4%) in the balanced-fluid group and 1383 patients (49.0%) in the 0.9%-saline group.
* Hypernatremia occurred in 52 patients (1.8%) in the balanced-fluid group and 89 patients (3.1%) in the 0.9%-saline group.
* Hyperlactatemia occurred in 260 patients (19.8%) in the balanced-fluid group and 228 patients (16.7%) in the 0.9%-saline group.
* No significant differences were seen in other safety outcomes or adverse events.

A clinical trial involving children aged 2 months to under 18 years with suspected septic shock and abnormal perfusion compared fluid resuscitation with either balanced crystalloid fluid or 0.9% saline was conducted across 47 emergency departments in five countries. The primary outcome assessed was a major adverse kidney event at 30 days post-enrollment or discharge. Of the enrolled patients, a similar number withdrew from the study between the two groups. There was no statistically significant difference observed in the incidence of the primary outcome—major adverse kidney event—between the two fluid groups, with differences noted as zero (0.4 percentage points) and a high P-value (P=0.85). The median number of hospital-free days during 28 days post-enrollment was similar across both groups. Furthermore, hyperchloremia rates differed between the groups, with a higher rate observed in the 0.9%-saline group. Other safety outcomes and adverse events did not show significant differences between the fluid administration strategies.

The trial demonstrates a finding of equipoise regarding fluid choice for septic shock in children, as the difference in major adverse kidney events between balanced fluid and 0.9% saline was statistically non-significant (P=0.85). This lack of statistical differentiation in the primary outcome suggests that from a hard endpoint perspective, either resuscitation strategy appears equally effective or ineffective across these specific outcomes. However, the significant divergence in electrolyte profiles—specifically hyperchloremia and changes in sodium levels—between the groups warrants deeper examination. The fact that the 0.9%-saline group exhibited a substantially higher rate of hyperchloremia (49.0%) compared to the balanced fluid group (31.4%), despite the lack of a statistically significant adverse outcome, suggests a context-dependent effect where electrolyte management influences patient status even when organ failure endpoints are not significantly separated by the intervention. This highlights the tension between purely outcome-based metrics and physiological realities; balancing resuscitation might involve managing systemic physiology separately from just tracking severe events. The implication is that while both fluids achieve similar acute outcomes, their impact on specific electrolyte homeostasis must be considered in clinical practice for vulnerable pediatric populations.

Balanced Fluid or 0.9% Saline in Children Treated for Septic Shock

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Balanced Fluid or 0.9% Saline in Children Treated for Septic Shock

Facts Only

Executive Summary

Full Take

Sentinel — Human