A large, international trial has found no significant difference in kidney-related or mortality outcomes between balanced crystalloids and 0.9% saline in children treated for septic shock, challenging assumptions about fluid selection in this population.1
The pragmatic, open-label, randomized trial, led by Fran Balamuth, MD, PhD, MSCE, and Scott L. Weiss, MD, MSCE, enrolled more than 9,000 pediatric patients across 47 emergency departments in five countries. Investigators compared a predominantly balanced crystalloid strategy—using solutions such as lactated Ringer’s or PlasmaLyte—with 0.9% saline for both resuscitation and maintenance fluids over a 24- to 48-hour period.
Eligible patients were between 2 months and under 18 years of age and were treated for suspected septic shock with evidence of abnormal perfusion. The primary end point was major adverse kidney events within 30 days (MAKE30), defined as a composite of death, new renal replacement therapy, or persistent kidney dysfunction. Of the 9,041 enrolled patients, 8,482 were included in the primary analysis after withdrawals, with balanced baseline characteristics across groups.1
Within 30 days, major adverse kidney events occurred in 3.4% of patients assigned to balanced fluids and 3.0% of those assigned to saline, a nonsignificant difference (RR, 1.10; 95% CI, 0.88 to 1.40; P = .85), according to the results.1
“Our results support the choice of either balanced fluids or 0.9% saline as crystalloid fluid for initial sepsis resuscitation in children,” said Dr. Balamuth, Division Chief of Emergency Medicine at Children’s Hospital of Philadelphia. “Both fluids are effective and safe.”
Rates of death, renal replacement therapy, and persistent kidney dysfunction were also similar between groups, as were hospital-free days and mortality at 90 days. Balanced fluids were associated with lower rates of hyperchloremia and hypernatremia than saline, whereas hyperlactatemia occurred more frequently in the balanced fluid group.1
“This trial highlights an important distinction between biochemical markers and clinical outcomes and that the two are not always connected,” said Dr. Weiss, who is in the Division of Critical Care, Department of Pediatrics, at Nemours Children’s Hospital in Wilmington, Delaware. “In aggregate, we did not see this translating into the clinical outcomes that we tracked, including mortality, persistent kidney injury, or hospital length of stay.”
Adverse events, including thrombosis and cerebral edema, were similar across both treatment arms.
Balanced crystalloids have been widely considered advantageous due to their more physiologic electrolyte composition and associations with improved outcomes in some prior studies. However, evidence across pediatric and adult populations has been inconsistent.
“The one other pediatric randomized trial showing benefit with balanced fluids was conducted in a population with a much higher prevalence of kidney injury,” Dr. Weiss said. “In contrast, larger aggregate analyses—including recent adult data—have not consistently demonstrated a difference.”
The results suggest that differences in patient populations, outcome definitions, and study designs may explain the variability in previous studies.1
According to the investigators, the findings do not support a clear advantage for either of the fluid strategies in most cases of pediatric septic shock.
Whether certain subgroups may benefit from balanced fluids is a key outstanding question, Dr. Balamuth noted.
“We cannot fully exclude a benefit in the sickest patients, particularly those with severe acidosis or markedly elevated lactate, but the numbers in those groups were small,” she said.
The authors also noted limitations, including relatively low event rates and uncertain generalizability to lower-resource settings. Yet when it comes to implications for practice, the findings may be particularly relevant in settings where access to balanced fluids is limited.
“I think our findings underscore that frontline providers can use whichever crystalloid fluid they have on hand to treat sepsis,” Dr. Weiss said. “There is no need to shift practice in order to obtain balanced fluids, as both options appear safe and effective.”
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
