Balanced fluids were no better than saline for children in septic shock

For years, intensive-care doctors have argued over which bag of fluid to hang first for a child crashing with sepsis: a "balanced" crystalloid that roughly matches the body's own chemistry, or plain 0.9% saline, which carries far more chloride. In adults, balanced fluids have edged ahead in some large trials, and many units switched on that basis. The PRoMPT BOLUS trial set out to test whether the choice actually changes outcomes in children — and the answer, in the largest paediatric trial of its kind, is that it does not [s1].

What the trial did

PRoMPT BOLUS was a pragmatic randomised trial run at 47 emergency departments in five countries [s1]. It enrolled children from 2 months to under 18 years of age who arrived with suspected septic shock and abnormal perfusion, and assigned them to fluid resuscitation with either balanced fluid or 0.9% saline for up to 48 hours [s1]. "Pragmatic" is the operative word: rather than dictate every step of care, the trial simply fixed which fluid was used and otherwise let clinicians treat as usual, which makes the result more likely to hold up in a real emergency department [s1].

The primary outcome was a major adverse kidney event — a composite of death, new renal-replacement therapy (dialysis or its equivalent), or persistent kidney dysfunction — measured at 30 days after enrollment or at hospital discharge, whichever came first [s1]. That endpoint was chosen because the main theoretical harm of chloride-rich saline is to the kidneys, so if balanced fluid helps anywhere, this is where it should show.

What it found

Of 9041 children enrolled, 277 (6.1%) in the balanced-fluid group and 282 (6.2%) in the saline group withdrew, leaving 4235 and 4247 for the analysis [s1]. A primary-outcome event occurred in 137 children (3.4%) on balanced fluid and 124 (3.0%) on saline [s1]. The difference was 0.4 percentage points (95% confidence interval −0.5 to 1.3), a risk ratio of 1.10 (95% CI 0.88 to 1.40), and a P value of 0.85 — about as flat a null as trials produce [s1]. The median number of hospital-free days over the 28 days after enrollment was 23 in both groups (interquartile range 19 to 25) [s1].

Where the two fluids did differ was in blood chemistry, exactly as their compositions predict. Hyperchloraemia — an excess of chloride in the blood — occurred in 868 children (31.4%) on balanced fluid versus 1383 (49.0%) on saline [s1]. Hypernatraemia (high sodium) occurred in 52 (1.8%) versus 89 (3.1%), while hyperlactataemia was slightly more common on balanced fluid, in 260 (19.8%) versus 228 (16.7%) [s1]. No differences in other safety outcomes or adverse events were seen [s1].

How to read it

The clean interpretation is that, for a child in septic shock, which crystalloid the team reaches for first does not measurably change the odds of death, dialysis, or lasting kidney damage [s1]. The laboratory abnormalities that drove the whole hypothesis — chloride and sodium disturbances — were indeed more common with saline, but they did not translate into worse patient outcomes over 30 days [s1]. That is a useful reminder that a difference on a blood test is not automatically a difference that matters to a patient.

A few caveats keep this from being the last word. The overall event rate was low — around 3% — which means the trial had to be large to detect a difference and still cannot rule out a very small one at the edges of its confidence interval [s1]. The composite endpoint pools death with milder kidney dysfunction, and a pragmatic design leaves other aspects of care to vary. But the sheer size and the breadth of the null argue against a clinically important advantage for either fluid.

Funding here is a point in the result's favour rather than a red flag: the trial was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and other public sources, not by a maker of either fluid, so there was no commercial stake in the answer [s1]. The protocol was registered before enrolment began [s2].

For families, the practical takeaway is reassurance, not alarm: whichever standard fluid a paediatric team uses, the current evidence says a child's chances turn on speed and quality of sepsis care, not on the label on the bag. This article describes research and is not medical advice; fluid choice in a critically ill child is a decision for the treating team.

What to watch

The adult literature is not perfectly settled either, and some clinicians will still prefer balanced fluids on physiological grounds where they are equally available and no more costly [s1]. The more important frontier is upstream of the fluid question entirely — how fast sepsis is recognised and how much fluid, of any kind, is the right amount, since over-resuscitation carries its own harms. PRoMPT BOLUS narrows one long-running debate; it does not end the larger one about how best to resuscitate a child in shock.

Sources

• Balanced Fluid or 0.9% Saline in Children Treated for Septic Shock — New England Journal of Medicine, 24 April 2026
• PRoMPT BOLUS trial registration (NCT04102371) — ClinicalTrials.gov, first posted 25 September 2019