Balanced fluid does not protect the kidney in paediatric septic shock

Design

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

Population

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

Primary outcome

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

Effect

137/4,235 (3.4%) vs 124/4,247 (3.0%); difference 0.4 percentage points (95% CI -0.5 to 1.3), risk ratio 1.10 (95% CI 0.88-1.40), P=0.85

The case for balanced crystalloid over 0.9% saline has rested on chloride: hyperchloraemic acidosis reduces renal blood flow in animal models, and adult trials have suggested small benefits on kidney endpoints. PRoMPT BOLUS tested it in children at the scale needed to settle it, enrolling 9,041 patients aged 2 months to under 18 years with suspected septic shock and abnormal perfusion at 47 emergency departments across five countries, randomised to balanced fluid or 0.9% saline for up to 48 hours. The primary outcome was a major adverse kidney event at 30 days or discharge: a composite of death, new renal replacement therapy or persistent kidney dysfunction.

After withdrawals, 4,235 and 4,247 patients were analysed. The primary event occurred in 137 (3.4%) with balanced fluid and 124 (3.0%) with saline: difference 0.4 percentage points (95% CI -0.5 to 1.3), risk ratio 1.10 (95% CI 0.88 to 1.40), P=0.85. Median hospital-free days over 28 days were 23 in both groups.

The biochemistry behaved exactly as predicted while the outcome did not. Hyperchloraemia occurred in 31.4% with balanced fluid against 49.0% with saline, and hypernatraemia in 1.8% against 3.1%; hyperlactataemia was slightly commoner with balanced fluid, 19.8% against 16.7%. Other safety outcomes did not differ.

The change in practice is to stop treating fluid choice as a kidney-protective intervention in this population, and to stop delaying resuscitation to obtain a particular bag. Balanced fluid remains reasonable and produces less hyperchloraemia, which matters for its own reasons; it is not a reason to withhold or postpone volume in a shocked child. In Indian emergency departments, where 0.9% saline is the fluid most reliably to hand, this is a straightforwardly reassuring result: give what is available, promptly.

• Do not delay fluid resuscitation in a shocked child to obtain balanced fluid rather than saline
• Stop describing balanced crystalloid as kidney-protective in paediatric septic shock
• Continue to prefer balanced fluid where both are equally available, on the strength of less hyperchloraemia and hypernatraemia
• Keep measuring chloride and sodium during prolonged resuscitation; the biochemical differences were large even though outcomes were not
• Direct attention to the things that do change outcome: recognition, timely antibiotics and reassessment after each bolus

The statistics, in plain English

The absolute difference of 0.4 percentage points has a confidence interval from -0.5 to 1.3, which excludes any benefit large enough to matter in either direction, so this is a definitive null rather than an inconclusive one. With over 8,000 children analysed and 261 primary events, the trial was large enough that a real effect of the size adult trials suggested would have shown. The biochemical differences were substantial and highly consistent, hyperchloraemia in 31.4% against 49.0%, which confirms the fluids did what they should have; the outcome simply did not follow the biochemistry. That is a useful reminder that a mechanism that is real is not therefore clinically consequential.

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