Large International Trial Shows No Difference Between Fluid Types for Pediatric Septic Shock Treatment
Key Insights
A landmark clinical trial involving over 8,000 children across five countries found no significant difference in kidney complications between balanced crystalloid fluid (search) and 0.9% saline (search) for treating pediatric septic shock (search).
The study, published in The New England Journal of Medicine, showed major adverse kidney events occurred in 3.4% of children receiving balanced fluid versus 3% receiving saline, with no difference in mortality or hospital length of stay.
Results provide definitive evidence that emergency physicians can confidently use either fluid type as standard care for children with septic shock (search), ending decades of clinical debate.
A comprehensive international clinical trial has resolved a longstanding debate in pediatric emergency medicine by demonstrating that two commonly used intravenous fluid treatments for children with septic shock (search) produce equivalent clinical outcomes. The study, involving over 8,000 participants across 47 emergency departments in five countries, found no significant difference in kidney complications between balanced crystalloid fluid (search) and 0.9% saline (search) solution.
Study Design and Scope
The PRoMPT BOLUS trial, conducted from August 2020 through October 2025, represents the largest clinical trial ever undertaken for pediatric septic shock (search) treatment. Researchers enrolled 8,482 children aged 2 months through 17 years (50.8% boys; median age 6.8 years) who presented to emergency departments with suspected septic shock across Australia, Canada, Costa Rica, New Zealand, and the United States.
The pragmatic trial design assigned 4,235 children to receive balanced crystalloid fluid (search) and 4,247 children to receive 0.9% saline (search). Each participant required at least two fluid boluses to be included in the analysis. The primary outcome measured was major adverse kidney events within 30 days of treatment, including renal replacement therapy, persistent kidney dysfunction (search), and death.
Key Clinical Findings
The trial's primary endpoint showed no statistically significant difference between treatment groups. Major adverse kidney events occurred in 3.4% of children who received balanced fluid compared to 3% of children who received saline (risk ratio = 1.1; 95% CI, 0.88-1.4). Secondary outcomes also showed no meaningful differences, including length of hospitalization, hospital-free days following treatment, death before discharge, or death within 90 days of treatment.
Participants in both groups achieved a median of 23 hospital-free days during the 28 days following enrollment, demonstrating comparable recovery trajectories regardless of fluid type administered.
Biochemical Differences Without Clinical Impact
While the study detected expected biochemical differences between the two fluid types, these variations did not translate into clinically meaningful outcomes. Children receiving 0.9% saline (search) had significantly higher incidences of hypernatremia (search) and hyperchloremia (search), while those receiving balanced fluid showed slightly higher incidence of hyperlactatemia (search).
"I think we were reassured — or gained confidence — by the fact that we saw all of the biochemical differences that were expected," said Frances Balamuth, MD, PhD, MSCE, professor of pediatrics at Perelman School of Medicine at the University of Pennsylvania. "But those didn't translate to clinical changes."
Clinical Practice Implications
The findings provide immediate clinical guidance for emergency physicians treating pediatric septic shock (search), a life-threatening condition requiring rapid intervention. For decades, pediatricians have debated which intravenous resuscitation treatment was superior for children with severe infections.
"Saline has the advantage of a long record — 150 years of use," explained Scott L. Weiss, MD, MSCE, FCCM, chief of critical care medicine at Nemours Children's Hospital (search). "It's inexpensive, it's compatible with pretty much all other medications, which makes it a practical choice when you are giving multiple things to a patient in short periods of time through similar IVs."
Previous studies from Vanderbilt University Medical Center had suggested that balanced fluid might reduce complications compared to saline, leading some physicians to switch their practice patterns. However, surveys of emergency physicians showed that the vast majority continued using saline, while intensive care unit physicians showed more balanced preferences between the two options.
Study Limitations and Future Research
Researchers acknowledge several limitations that may affect broader application of their findings. The study focused on children with community-acquired sepsis presenting to emergency departments in high-resource settings, making generalization to low-resource environments or hospital-acquired sepsis uncertain.
Additionally, because treatment was initiated based on immediate clinical observations of suspected septic shock (search) rather than waiting for laboratory confirmation, the authors cannot exclude the possibility that one fluid type might be preferred for the sickest subset of children or those requiring very high fluid volumes.
The research team continues investigating potential subtle differences through ongoing ancillary studies. They collected blood and urine samples at three sites to examine kidney injury biomarkers and are conducting electronic health record analysis to track long-term outcomes. Another study is investigating endothelial and glycocalyx biomarkers to better understand the mechanistic effects of each fluid type.
Research Support and Collaboration
This research was supported by NIH grants R01HD101528 and P50DK114786 and led by the Pediatric Emergency Care Applied Research Network (search) (PECARN), funded through the Emergency Medical Services for Children program of the Health Resources and Services Administration in collaboration with international institutions.
"Our findings are very clear that any fluid you have on hand is safe and effective to use, and most kids will do great with that," Balamuth concluded. The results, published April 24 in The New England Journal of Medicine and presented at the Pediatric Academic Societies annual meeting, provide definitive evidence that emergency physicians can confidently choose either intervention as standard care for pediatric septic shock (search).