Balanced Fluid or Saline in Septic Shock? The Answer from PRoMPT BOLUS

Subtitle: A large, pragmatic randomised trial in more than nine thousand children found no meaningful difference in kidney outcomes between balanced crystalloid and 0.9% saline.

The clinical question

When fluid resuscitation is started for septic shock, should we choose a balanced crystalloid or 0.9% saline? This question has been debated in the adult critical care literature for years. The PRoMPT BOLUS trial addresses the same question with a much larger sample, this time in paediatric septic shock. The result is an important data point on how much fluid choice really matters in sepsis management.

The study in brief

PRoMPT BOLUS¹ is a multicentre, pragmatic, open-label randomised controlled trial conducted in 47 emergency departments in five countries (USA, Canada, Australia, New Zealand and Costa Rica). Patients aged 2 months to under 18 years with suspected septic shock and abnormal perfusion, who had received no more than 40 mL/kg of crystalloid before enrolment, were included. They were randomised to receive balanced fluid (lactated Ringer’s, Plasma-Lyte or Hartmann’s solution) or 0.9% saline for resuscitation and maintenance for up to 48 hours.

The primary outcome was MAKE30 (major adverse kidney event), a composite of death, new renal replacement therapy or persistent kidney dysfunction within 30 days of enrolment or by hospital discharge, whichever came first. In total, 9041 patients were enrolled; after withdrawals of data-use consent, 4235 patients in the balanced-fluid group and 4247 in the saline group were analysed.

Primary outcome (MAKE30): 3.4% with balanced fluid vs 3.0% with saline (risk ratio 1.10; 95% CI 0.88–1.40; P=0.85) — no statistically significant difference.

Hospital-free days: median 23 in both groups.

Biochemistry: hyperchloraemia (49.0% vs 31.4%) and hypernatraemia (3.1% vs 1.8%) were more frequent with saline; hyperlactataemia was more frequent with balanced fluid (19.8% vs 16.7%).

Interpreting the findings

This result is consistent with the PLUS trial,² one of the largest randomised trials in adults: in PLUS (n=5037), no difference in 90-day mortality was found between a balanced multi-electrolyte solution and saline. By extending this null result to children with septic shock, PRoMPT BOLUS strengthens the view that fluid type — at least across this broad population — is not a decisive factor for hard clinical outcomes.

An earlier, smaller paediatric trial by Sankar and colleagues³ (n=708, India) had reported a 38% relative reduction in new or progressive acute kidney injury with balanced fluid. However, the two trials used different outcome definitions: Sankar’s trial counted any 0.3 mg/dL rise in creatinine within the first 7 days, whereas MAKE30 in PRoMPT BOLUS required at least a doubling of creatinine from baseline — a stricter and more clinically meaningful threshold. Importantly, neither trial found a difference in mortality or length of stay. This suggests that the corrective effect of balanced fluid on biochemical parameters (chloride, sodium) does not always translate into hard clinical outcomes. The conditional recommendation for balanced fluids in the 2020 Surviving Sepsis Campaign paediatric guideline may need to be revisited in light of this large trial.

What does it mean at the bedside?

• In a child with septic shock, whether the initial resuscitation fluid is a balanced crystalloid or saline does not appear to meaningfully change kidney outcomes, mortality or length of stay. Both options can be considered reasonable.
• Large-volume saline resuscitation continues to cause hyperchloraemia and hypernatraemia; these deviations warrant monitoring but should not, on their own, be regarded as markers of clinical harm.
• The more frequent hyperlactataemia with balanced fluid may mislead clinicians who track lactate as a marker of shock severity; interpret the lactate trend together with the clinical picture, not in isolation.
• In many ICUs, including those in Turkey, fluid choice is largely driven by availability, cost and local protocol; at least in paediatric septic shock, this trial supports that pragmatic approach.
• In the sickest patients (high volume requirement, severe acidosis or hyperlactataemia at presentation), point estimates leaned slightly towards balanced fluid; a possible benefit in this subgroup could not be ruled out, so room for individual clinical judgement remains.

Limitations and caveats

The population was entirely paediatric (2 months to 18 years) and consisted of patients starting treatment in the emergency department for suspected septic shock; generalisability to adult ICU patients, hospital-acquired sepsis or resource-limited settings remains uncertain. The septic shock definition relied on perfusion abnormalities detectable at presentation rather than classic severe criteria; this pragmatic approach fits clinical practice but may have lowered the event rate and limited statistical power. Withdrawal of data-use consent (6.1–6.2%) was higher than planned, although sensitivity analyses indicated the results were not substantially affected. The open-label design could have indirectly influenced decisions on fluid volume or rate, although total fluid volumes were similar between groups. The trial also offers no clear explanation for the hyperlactataemia signal. Funding was public (Eunice Kennedy Shriver National Institute of Child Health and Human Development, among others).

Conclusion

This large, pragmatic and well-designed trial showed no meaningful difference between balanced fluid and 0.9% saline in kidney outcomes, mortality or length of stay in children with septic shock. Consistent with the adult PLUS trial, it reminds us once again that fluid type alone is not decisive in sepsis management; the emphasis should remain on early recognition, source control and appropriate volume titration.

References

1. Balamuth F, Weiss SL, Long E, et al. Balanced Fluid or 0.9% Saline in Children Treated for Septic Shock. N Engl J Med. 2026;395(9):870-881. doi:10.1056/NEJMoa2601969
2. Finfer S, Micallef S, Hammond N, et al. Balanced Multielectrolyte Solution versus Saline in Critically Ill Adults. N Engl J Med. 2022;386(9):815-826. doi:10.1056/NEJMoa2114464
3. Sankar J, Muralidharan J, Lalitha AV, et al. Multiple Electrolytes Solution Versus Saline as Bolus Fluid for Resuscitation in Pediatric Septic Shock: A Multicenter Randomized Clinical Trial. Crit Care Med. 2023;51(11):1449-1460. doi:10.1097/CCM.0000000000005952

Doç. Dr. Serdar Efe — Intensive Care Quality Platform