Balanced fluid did not beat 0.9% saline in paediatric septic shock, in a trial big enough to settle it

Design

pragmatic randomised clinical trial at 47 emergency departments in five countries (PRoMPT BOLUS)

Population

9,041 children aged 2 months to under 18 years with suspected septic shock and abnormal perfusion; 8,482 analysed

Primary outcome

major adverse kidney event (death, new renal-replacement therapy or persistent kidney dysfunction) at 30 days or discharge

Effect

3.4% with balanced fluid vs 3.0% with 0.9% saline (difference 0.4 percentage points, 95% CI -0.5 to 1.3; RR 1.10, 0.88-1.40); hyperchloraemia 31.4% vs 49.0%

PRoMPT BOLUS enrolled 9,041 children aged 2 months to under 18 years with suspected septic shock and abnormal perfusion, across 47 emergency departments in five countries, randomised to balanced crystalloid or 0.9% saline for up to 48 hours. Major adverse kidney events at 30 days — death, new renal-replacement therapy or persistent kidney dysfunction — occurred in 3.4% of the balanced-fluid group and 3.0% of the saline group. Hospital-free days were identical at a median of 23.

The biochemistry moved exactly as predicted and the outcomes did not. Hyperchloraemia occurred in 31.4% of the balanced-fluid group and 49.0% of the saline group, and hypernatraemia in 1.8% against 3.1%. Saline does what saline has always been said to do to the electrolytes. It just does not appear to hurt these children.

That is the assumption this challenges. The case for balanced fluid in paediatric sepsis has rested largely on the plausibility of the chloride mechanism and on extrapolation from adult data, and this is the first trial with the size to test it directly in children.

For Indian emergency practice the practical reading is permissive. Balanced solutions cost more and are not stocked everywhere; on this evidence a unit that has only normal saline is not resuscitating children worse because of it. Give the fluid you have, promptly.

• Do not delay fluid resuscitation in a shocked child to source a balanced solution
• Where both are stocked, either is defensible; timeliness and volume matter more than the choice
• Expect hyperchloraemia in about half of children given saline, and interpret the chloride accordingly rather than switching for it
• Reassess perfusion after each bolus; this trial tested the fluid, not the strategy for how much to give
• Keep monitoring for the composite that matters — new renal-replacement therapy and persistent dysfunction, not the electrolyte panel

The statistics, in plain English

The risk ratio of 1.10 with a 95% confidence interval of 0.88 to 1.40 crosses 1.0, and the absolute difference of 0.4 percentage points has an interval of -0.5 to 1.3 — with over 8,000 children analysed, that narrowness is what allows a confident null rather than an underpowered one. A trial this size can exclude a benefit larger than about half a percentage point in absolute terms. The electrolyte differences are large and statistically unambiguous, which is the point worth understanding: a real and reproducible biochemical effect need not translate into a clinical one, and the assumption that it does is what this trial tested.

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