Balanced Fluids vs Normal Saline in Pediatric Septic Shock: New Evidence from a Large NEJM Trial

Introduction: Why Fluid Choice Matters in Sepsis Care

Septic shock in children is a life-threatening emergency that requires rapid fluid resuscitation to restore circulation and prevent organ failure. One of the most common treatments is intravenous crystalloid fluids, but there has long been debate about which type is best.

Two main options are widely used in hospitals:

• 0.9% sodium chloride solution (commonly called normal saline)
• Balanced crystalloid solutions such as lactated Ringer’s solution or Plasma-Lyte

A major question in critical care medicine is whether balanced fluids improve outcomes compared with normal saline, particularly in children who are vulnerable to kidney injury during severe infections.

A large international clinical trial published in The New England Journal of Medicine in April 2026 provides one of the most comprehensive answers to this question so far.

Overview of the NEJM Pediatric Sepsis Fluid Trial

The study, known as the PRoMPT BOLUS trial, was conducted across 47 emergency departments in five countries, including the United States, Canada, Australia, New Zealand, and Costa Rica. It enrolled children aged 2 months to under 18 years who were treated for suspected septic shock.

More than 9,000 children were randomly assigned to receive either:

• Balanced crystalloid fluids
• 0.9% saline

Fluids were used for both resuscitation boluses and maintenance therapy during the first 24 to 48 hours of treatment.

The study’s main goal was to determine whether balanced fluids reduce the risk of major kidney-related complications within 30 days compared with normal saline.

Primary Outcome: Kidney and Survival Results

The researchers focused on a combined outcome called “major adverse kidney events.” This included:

• Death from any cause
• Need for kidney replacement therapy such as dialysis
• Persistent kidney dysfunction at 30 days

The results showed no meaningful difference between the two groups.

• Balanced fluid group: 3.4% experienced a major kidney event
• Normal saline group: 3.0% experienced a major kidney event

Statistically, this difference was not significant. The risk ratio indicated no clear advantage for either fluid type.

Hospital recovery also looked similar in both groups. Children in each group had a median of 23 hospital-free days within the first 28 days after treatment began.

Safety and Electrolyte Differences

While overall clinical outcomes were similar, there were some differences in laboratory findings.

Children receiving balanced fluids had:

• Lower rates of hyperchloremia (high chloride levels in blood)
• Lower rates of hypernatremia (high sodium levels)

Children receiving normal saline had higher rates of these electrolyte imbalances, which is expected because saline contains a higher chloride concentration than human plasma.

However, an interesting finding was that hyperlactatemia occurred slightly more often in the balanced fluid group. The clinical significance of this is still unclear.

Importantly, there were no major differences in:

• Thrombosis (blood clots)
• Cerebral edema (brain swelling)
• Other serious adverse events

What Makes This Trial Important

This study is one of the largest pediatric emergency medicine trials ever conducted on fluid resuscitation in septic shock. It is also notable for its real-world design.

Key strengths include:

• Large sample size of over 9,000 children
• Multiple international hospital settings
• Inclusion of early-stage septic shock patients
• Use of both resuscitation and maintenance fluids

The trial was designed to reflect real clinical practice rather than highly controlled laboratory conditions, making its findings highly relevant for emergency departments.

How These Results Fit Into Previous Research

Earlier studies in both adults and children have suggested that balanced fluids might reduce kidney injury and improve survival. However, results have been inconsistent.

Some smaller pediatric studies showed possible benefits of balanced fluids, while other adult trials showed minimal or no difference.

The PRoMPT BOLUS trial helps clarify this uncertainty by providing high-quality evidence at scale. Its findings suggest that while balanced fluids may improve certain blood chemistry markers, they do not necessarily improve survival or kidney outcomes in a measurable way for most children with septic shock.

Clinical Implications for Pediatric Care

For clinicians, this study suggests that both balanced crystalloids and normal saline remain acceptable options for initial fluid resuscitation in pediatric septic shock.

Normal saline continues to be widely used due to availability, cost, and familiarity. Balanced fluids may still be preferred in some clinical scenarios, particularly where electrolyte balance is a concern, but the evidence does not strongly favor one over the other in terms of survival or kidney protection.

One important takeaway is that septic shock outcomes depend more on early recognition, timely antibiotic treatment, and appropriate overall resuscitation strategy rather than fluid type alone.

Limitations of the Study

Like all clinical trials, this study has limitations that should be considered when interpreting the results:

• The overall rate of severe kidney outcomes was relatively low, which reduces the ability to detect small differences
• Fluid treatment after the initial intervention period may have varied
• The study was conducted in emergency department settings, so results may not fully apply to hospital-acquired sepsis
• Some patients withdrew from the study or had missing data, although sensitivity analyses supported the main findings

Despite these limitations, the consistency of results across multiple analyses strengthens the reliability of the conclusions.

Conclusion

The NEJM PRoMPT BOLUS trial provides strong evidence that balanced crystalloid fluids do not significantly reduce the risk of death, dialysis, or long-term kidney dysfunction compared with normal saline in children treated for septic shock.

While balanced fluids reduce certain electrolyte abnormalities such as hyperchloremia, these biochemical differences do not appear to translate into improved clinical outcomes.

For now, both fluid types remain valid options in pediatric emergency care, and treatment decisions should be guided by clinical context, availability, and individual patient needs rather than expectations of major outcome differences.

Source

Balamuth F, Weiss SL, Long E, et al. Balanced Fluid or 0.9% Saline in Children Treated for Septic Shock. The New England Journal of Medicine. 2026; DOI: 10.1056/NEJMoa2601969. Published April 23, 2026.

Disclaimer

This article is a paraphrased educational summary of a peer-reviewed clinical trial and is intended for informational purposes only. It does not provide medical advice, diagnosis, or treatment recommendations. Clinical decisions should always be made by qualified healthcare professionals based on full clinical evaluation and up-to-date guidelines.