Balanced fluids, saline show comparable outcomes in pediatric septic shock, with Scott Weiss, MD

A large, multinational clinical trial involving more than 9,000 pediatric patients with suspected septic shock found no meaningful difference in clinical outcomes between balanced crystalloids and 0.9% saline for initial resuscitation. These data were presented at the 2026 Pediatric Academic Societies (PAS) Meeting and published in The New England Journal of Medicine.^1,2

Sepsis remains a leading cause of pediatric morbidity and mortality, with more than 18,000 children hospitalized annually in the United States and approximately 1 in 10 at risk of death. The study evaluated major adverse kidney events within 30 days (MAKE30) and found similar rates between fluid groups.

Although biochemical differences were observed—such as higher chloride levels with saline—these did not translate into differences in mortality, kidney outcomes, or hospital-free days.

In a recent video interview, Scott Weiss, MD, a pediatric intensivist at Nemours Children’s Hospital and co-lead investigator, contextualized these findings for practicing clinicians, emphasizing practical implications for emergency and critical care settings.

No clear superiority between balanced fluids and saline

Weiss underscored that the trial addresses a long-standing clinical question regarding fluid selection in pediatric septic shock.

“I think pediatricians can take from this trial that either saline or balanced fluids are both safe and effective for treatment of children who present to an emergency department with suspicion of septic shock,” Weiss said.

Prior observational and adult studies had raised concerns about chloride load associated with saline and potential adverse outcomes. However, this large pediatric trial did not demonstrate superiority of balanced fluids despite those theoretical concerns.

The findings are particularly relevant because most children with suspected sepsis are initially managed in emergency departments, where rapid decision-making and fluid availability are critical.

Findings reinforce current clinical practice guidelines

The results largely support existing flexible approaches to fluid resuscitation rather than prompting a shift in practice.

“I think our findings really reinforce current practice, which basically allows for a variety of different crystalloid fluids to be used, and do not demonstrate that there’s a clear preference for 1 fluid type or the other,” Weiss explained.

This is notable given that the Surviving Sepsis Campaign has issued conditional recommendations favoring balanced fluids based on lower-quality evidence. The current trial provides more definitive pediatric-specific data, suggesting that either option is appropriate.

Weiss also highlighted practical considerations, including cost and availability, particularly in diverse clinical settings.

Biochemical differences do not translate to clinical outcomes

One of the study’s key findings was the disconnect between laboratory changes and patient-centered outcomes.

“It was more likely to develop for children who are resuscitated with saline to develop a hyperchloremia…[but] that did not translate into important patient-centered outcomes,” Weiss said.

While hyperchloremia has been associated with worse outcomes in observational studies, the randomized data suggest that these biochemical differences alone should not drive fluid selection.

However, Weiss noted that electrolyte optimization may still be relevant in specific scenarios, particularly in patients requiring large-volume resuscitation or those with significant acid-base disturbances.

Potential considerations for severely ill subgroups

Although no statistically significant subgroup differences were identified, Weiss acknowledged that uncertainty remains for the most critically ill patients.

“It’s not possible for us to definitively exclude the possibility of benefit of balanced fluid in the sickest subset of children with sepsis,” he said.

He added that in cases involving high fluid volumes or severe illness, clinicians may reasonably consider balanced fluids, even though definitive benefit has not been proven.

This nuanced interpretation supports individualized decision-making in complex cases.

Implications for global and resource-limited settings

The findings may have particular relevance for global pediatric care, where resource constraints often influence treatment decisions.

“It is very reasonable for sites to use the fluid that is most accessible to them…either should be sufficient,” Weiss stated.

Although the trial primarily included well-resourced centers, the absence of a superior fluid suggests that institutions do not need to prioritize one type over another when availability is limited.

This reinforces a pragmatic approach to pediatric sepsis care worldwide.

Weiss reports no relevant disclosures.

References

1. Balamuth F, Weiss SL, Long E, et al. Balanced fluid or 0.9% saline in children treated for septic shock.” N Engl J Med. Published online April 24, 2026. doi:10.1056/NEJMoa2601969
2. Large international study confirms similar efficacy and safety of common fluid treatments for pediatric sepsis. News release. Children’s Hospital of Philadelphia. April 24, 2026. Accessed April 24, 2026. https://www.eurekalert.org/news-releases/1125374?