It’s 11 pm, and you’re working in the paediatric Emergency Department (ED). A 7-year-old checks in, appearing unwell. She is febrile and tachycardic, with low blood pressure. You start worrying. Could this be sepsis?
After evaluating the patient, you determine she needs fluids and antibiotics urgently. The nurse brings you two bags of fluid: normal saline and lactated Ringer’s. Which do you choose? And does it even matter?
Background
Crystalloid fluid resuscitation is a key part of managing septic shock in children. Normal saline is widely available, relatively inexpensive, and, above all, familiar. But there is nothing especially “normal” about normal saline.
Normal saline is not very physiological. It has a higher chloride content than human plasma, and high-volume administration has been associated with hyperchloremia, metabolic acidosis, and decreased renal blood flow.
Balanced crystalloids, such as lactated Ringer’s, Plasma-Lyte, and Hartmann’s solution, are closer in composition to human plasma. Clinicians have theorised that balanced fluids might be less harmful to the kidneys when they are already under stress in a septic state.
Adult trials (SMART and SALT-ED) and smaller paediatric studies (Sankar et al) hinted at a benefit from balanced fluids in treating septic shock in children. Other trials, including BaSICS and a 2023 Cochrane review, found little difference between normal saline and balanced solutions.
Enter PRoMPT BOLUS.
Balamuth F, Weiss SL, Long E, et al, for the PRoMPT BOLUS Investigators of the PECARN, PERC, and PREDICT Networks. Balanced Fluid or 0.9% Saline in Children Treated for Septic Shock. N Engl J Med. 2026 Apr 24:10.1056/NEJMoa2601969. doi: 10.1056/NEJMoa2601969. Epub ahead of print. PMID: 42028918; PMCID: PMC13134814. Read it on PubMed
The Research Question
In children treated for suspected septic shock in the emergency department, does fluid resuscitation with balanced crystalloids, compared with 0.9% saline, reduce major adverse kidney events within 30 days?
Population: Children aged 2 months to 18 years with suspected septic shock, recruited from 47 emergency departments across multiple international research networks.
Intervention: Balanced fluid (lactated Ringers, Plasma-Lyte, or Hartmann’s solution).
Comparison: Normal saline.
Outcomes: The primary outcome was a composite of death, renal-replacement therapy, or persistent kidney dysfunction, defined as a final serum creatinine at least 200% of baseline with a minimum increase of 0.3 mg/dL. Secondary outcomes included length of hospital stay, hospital-free days during the 28 days after enrolment, and death from any cause before hospital discharge and within 90 days of randomisation. Safety outcomes included electrolyte abnormalities within four days of enrolment, arterial or venous thrombosis, and cerebral oedema diagnosed during clinical care.
Trial design: Multicentre, pragmatic, open-label, randomised controlled trial.
Across the two treatment groups, the median age was 6.8 years, and 50.8% of patients were male. The respiratory tract was the most common site of infection (46.6% of patients). At presentation, 13.8% of patients had stage 1 acute kidney injury, 4.9% had stage 2, and 5.1% had stage 3. Around 14.2% of patients received vasoactive medications, and 9.7% underwent invasive mechanical ventilation.
What Did They Find?
There was no significant difference in death, new renal-replacement therapy, or kidney dysfunction between children treated with balanced fluids and those treated with normal saline.
The incidence of primary-outcome events was similar between balanced fluids (3.4%) and saline (3.0%): a difference of 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. A post hoc analysis found no effect modification when saline was administered before randomisation.
How about mortality?
In-hospital mortality was 1.1% in both groups. At 90 days, mortality was 2.3% in the balanced-fluid group and 2.1% in the saline group, a difference too small to be clinically meaningful.
What about length of stay and hospital-free days?
These were nearly identical between groups.
Were there any notable differences?
Balanced fluids led to less hyperchloremia (31% versus 49%) and less hypernatremia, but slightly more hyperlactatemia. Despite the rise in hyperlactatemia, the incidence of thrombosis and cerebral oedema did not differ between groups, and there was no significant difference in adverse events overall.
In other words, your labs may look more appealing, but your patient will likely have the same outcome.
It’s worth revisiting the difference between Lab-Oriented Outcomes (LOOs) and Patient-Oriented Outcomes (POOs) in this DFTB blog post.
Multiple subgroup analyses found no convincing difference when treating sicker patients, using higher fluid volumes, or in those with acute kidney injury. There is a small possibility that the sickest patients, those with extreme acidosis and hyperlactatemia, may have had some benefit from balanced fluids, but not enough to justify a change in practice.
What Did PRoMPT BOLUS Do Well?
The trial enrolled a large sample of around 9,000 patients and recruited them early, before large volumes of fluid had already been given. It drew on international collaboration across multiple research networks, and it kept its focus squarely on patient-oriented outcomes rather than biochemical markers alone.
Limitations of the Study
Event rates were lower than expected, which narrows the statistical power to detect smaller differences between groups. Clinicians should be careful generalising these findings to low-resource contexts, where fluid choice and availability differ. Although all patients required fluid for abnormal perfusion, only 14% of patients in both groups required vasoactive medications, meaning the study population was broader than the patients typically treated in an intensive care unit. Finally, the investigators could not distinguish patients who may have been enrolled more than once.
CASP Checklist: How Good Was the Paper?
Did the study address a clearly focused issue?
Yes.
Was the assignment of participants to interventions randomised?
Yes. All participants who entered the study were accounted for at its conclusion. An intention-to-treat analysis was used, and there was no significant unexplained loss to follow-up that would have affected the conclusions.
Were participants, investigators, and outcome assessors masked to the intervention?
No. This was an open-label RCT, so clinicians knew which fluid the patient received. However, the study investigators and statistical team were blinded to outcomes throughout the study, and the study groups were similar at baseline across age, illness severity, comorbidities, and renal function.
Were the groups treated equally apart from the intervention?
Not entirely clear. Aside from fluid type, other aspects of care were left to the treating clinician. Concurrent therapies such as vasoactive medications, corticosteroids, mechanical ventilation, and ECMO were used equally across groups. Bicarbonate was used slightly more often in the saline group (5.8% versus 4.6%), and there was no difference in bolus or total fluid volume administered between groups.
Were the effects of the intervention reported comprehensively?
Yes. The authors reported primary and secondary outcomes, mortality, renal outcomes, biochemical markers, length of stay, hospital-free days, and subgroup analyses.
How precise are the results?
Reasonably precise. The confidence interval was relatively narrow given the large sample size.
Do the benefits of the intervention outweigh the harms and costs?
Not in a patient-oriented way. Biochemical markers such as hyperchloremia improved with balanced fluids, but mortality, kidney injury, hospital-free days, and length of stay were all comparable. Balanced fluids may also carry a higher cost. Importantly, no major harms were identified with either fluid type.
Can the results be applied to the local population?
Yes, with the caveat that lower-resource healthcare systems may face challenges applying this study to their own practice.
Would the intervention provide greater value to the people in your care than existing interventions?
Likely not for most patients. The study suggests that in children with suspected septic shock, balanced fluids don’t provide greater clinical benefit than normal saline. This trial does not support a major shift in practice away from normal saline.
So What Do I Do With My Patient?
Based on PRoMPT BOLUS, fluid choice for paediatric septic shock probably matters less than we once thought. Balanced fluids do not improve patient-centred outcomes, and normal saline remains a reasonable choice, at least for the initial 24 to 48 hours of resuscitation.
The Bottom Line
Recognise and treat sepsis early. Use whatever fluid you have available.
References
Semler, M.W., Self, W.H., Wanderer, J.P., Ehrenfeld, J.M., Wang, L., Byrne, D.W., Stollings, J.L., Kumar, A.B., Hughes, C.G., Hernandez, A. and Guillamondegui, O.D., 2018. Balanced crystalloids versus saline in critically ill adults. New England Journal of Medicine, 378(9), pp.829-839.
Self, W.H., Semler, M.W., Wanderer, J.P., Wang, L., Byrne, D.W., Collins, S.P., Slovis, C.M., Lindsell, C.J., Ehrenfeld, J.M., Siew, E.D. and Shaw, A.D., 2018. Balanced crystalloids versus saline in noncritically ill adults. New England Journal of Medicine, 378(9), pp.819-828.
Sankar, J., Ismail, J., Sankar, M.J., CP, S. and Meena, R.S., 2017. Fluid bolus over 15–20 versus 5–10 minutes each in the first hour of resuscitation in children with septic shock: a randomized controlled trial. Pediatric Critical Care Medicine, 18(10), pp.e435-e445.
Surviving Sepsis Campaign. International guidelines for the management of septic shock and sepsis-associated organ dysfunction in children.
