Balanced fluid is not better than saline in paediatric septic shock

Design

Pragmatic randomised controlled trial at 47 emergency departments across five countries

Population

8482 analysed children aged 2 months to under 18 years with suspected septic shock and abnormal perfusion

Primary outcome

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

Effect

3.4 per cent balanced fluid vs 3.0 per cent saline; difference 0.4 percentage points (95 per cent CI -0.5 to 1.3), risk ratio 1.10 (0.88 to 1.40), P = 0.85

PRoMPT BOLUS randomised children aged 2 months to under 18 years with suspected septic shock and abnormal perfusion, across 47 emergency departments in five countries, to fluid resuscitation with balanced crystalloid or 0.9 per cent saline for up to 48 hours. Of 9041 enrolled, 8482 remained for analysis.

The primary outcome, a major adverse kidney event at 30 days - death, new renal replacement therapy, or persistent kidney dysfunction - occurred in 137 children (3.4 per cent) on balanced fluid and 124 (3.0 per cent) on saline: difference 0.4 percentage points (95 per cent CI -0.5 to 1.3), risk ratio 1.10 (0.88 to 1.40), P = 0.85. Median hospital-free days over 28 days were 23 in both arms. The biochemical difference was real and large - hyperchloraemia in 31.4 per cent against 49.0 per cent, hypernatraemia 1.8 against 3.1 per cent - but it did not translate into the clinical outcome it was expected to drive.

That is the change. The presumption that balanced crystalloid must be better because saline causes hyperchloraemic acidosis has shaped guidelines and purchasing; a trial of 8,482 children says the biochemistry moves and the kidneys do not. In an Indian emergency department where balanced solutions cost more or are simply not on the shelf at 2 am, this removes a source of guilt and delay: give the fluid you have, promptly, in the right volume. Speed and volume were never the variables in question here, and they remain the ones that matter.

• Use whichever crystalloid is immediately available rather than delaying resuscitation to find a balanced solution.
• Do not treat hyperchloraemia after saline as a marker of kidney harm; it occurred far more often without worse outcomes.
• Keep the focus on time to first bolus and adequate volume, which this trial did not vary.
• Note the low event rate - about 3 per cent - which is what allows a null result to be believable here.
• Continue to monitor electrolytes; the biochemical differences were substantial even if not clinically expressed.

The statistics, in plain English

This is a null result with useful precision: a risk ratio of 1.10 with an interval from 0.88 to 1.40 excludes any large advantage for balanced fluid, and the absolute difference interval of -0.5 to 1.3 percentage points shows the outer bound is small in real terms. It does not prove exact equivalence - a difference of a fraction of a percentage point would not have been detected - but at a 3 per cent event rate that difference would not change practice. The dissociation between hyperchloraemia and kidney outcomes is the finding that overturns the prior assumption.

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