Saline Revisited: Are Balanced Fluids Better in Pediatric Patients? PRoMPT BOLUS Study Insights

It’s a question nearly as old as time — or at least as old as Lactated Ringer’s solution: which fluids serve our critically ill children best? Plenty of studies have taken a swing at this, with a variety of results but never quite settling the debate.  Concerns about normal saline largely stem from its supraphysiologic chlorine content, which has been thought to cause hyperchloremic metabolic acidosis, kidney injury, coagulation abnormalities, and potentially worsened systemic inflammatory response (Weiss 2017). Prior studies have explored clinical differences between fluids with some showing increased rates of acute kidney injury and small increased need for renal replacement therapy with normal saline as compared to balanced fluids (Sankar 2023, Long 2025). Still, many of these studies were hampered by small sample sizes and the lingering sense that we were all waiting for another trial to settle the debate. Despite these prior papers, there is still uncertainty. Enter the PRoMPT BOLUS trial — fashionably late, but hopefully worth the wait (Balamuth 2026).  Let’s take a minute to review the insights generated from the PRoMPT BOLUS study:

PRoMPT BOLUS: Methods

• The authors of this study used a pragmatic, open-label, randomized trial to compare balanced crystalloid vs 0.9% saline.
• This study put the MULTI in multicenter with 47 sites throughout the US, Canada, Australia/New Zealand, and Costa Rica – basically a world tour! 
• 9,041 patients, ages 2 months to <18 years with suspected sepsis requiring more than one fluid bolus were enrolled and continued on the same fluids for at least 24 hours
• The primary outcome was Major Adverse Kidney Events within 30 days (MAKE30)
  • Mortality
  • Need for renal replacement therapy
  • Persistent kidney dysfunction up to 30 days

PRoMPT BOLUS: Results

• The primary outcome evaluating for major adverse kidney events within 30 days found no clinically significant difference in these events between balanced fluids and saline.
  • Balanced fluids: 3.4%
  • Saline: 3.0% 
• Secondary outcomes showed no meaningful differences between: 
  • Hospital length of stay
  • Hospital-free days
  • Safety events including thrombosis or cerebral edema
• Where the fluids did part ways was in the laboratory values: 
  • Normal saline was associated with hyperchloremia and hypernatremia
  • Balanced fluids was associated with hyperlactemia

The labs noticed. Clinically, not so much.

PRoMPT BOLUS: Discussion

• This was a large study that showed there was no notable benefit with the use of balanced fluid over 0.9% saline when looking at effects on renal function.
• Electrolyte differences (notably hypernatremia and hyperchloremia) were observed but did not translate into differences in clinical outcomes. 
• The authors acknowledge that a key limitation is the early definition of septic shock, which may have overcaptured patients based on vital signs rather than laboratory data — casting a slightly wider net in the name of early enrollment.
• This early enrollment may have also contributed to the low incidence of adverse events, suggesting the study population may have been somewhat less sick than anticipated
• While subgroup analysis of the more severely ill patients suggested a possible benefit of the balanced fluids, the study was not powered to make definitive claims

Will this change practice? 

This was a well-designed study that prioritized large-scale enrollment while minimizing disruption to usual care. The lack of clinically significant differences suggests that fluid choice can reasonably be individualized. If I’m faced with a patient who is already hypernatremic or hyperchloremic, I’ll still lean toward a balanced solution such as Lactated Ringer’s solution.

That said, real-world decision-making is as much about logistics as it is about physiology. One of the main practical limitations of balanced fluids is medication compatibility. We love Ceftriaxone (“Cef-kill-it-all”) in pediatrics, but it’s a classic example of an incompatibility that often necessitates a second IV if using LR for fluid resuscitation. When IV real estate is at a premium in small patients, thinking about compatibility becomes less of a pharmacologic detail and more of a daily survival strategy. For me, this translates to a simple cognitive shortcut during resuscitation: fewer line-management decisions, less mental bandwidth consumed, and a quicker reach for 0.9% normal saline for my initial bolus solution in most pediatric patients.

Moral of the Morsel

• The Nephrons Stayed Neutral! Balanced fluids compared to normal saline did not meaningfully reduce mortality, renal replacement therapy, persistent kidney dysfunction, hospital length of stay, or hospital-free days compared with normal saline.
• The Labs Had Drama, the Patients Did Not! Normal saline was associated with more hyperchloremia and hypernatremia, while balanced fluids were associated with more hyperlactemia — but these lab differences did not translate into meaningful clinical outcome differences.
• Fluids are Easy! Lines are Hard. Fluid choice can be individualized: balanced fluids may make sense in patients who are already hypernatremic or hyperchloremic, but in real-world pediatric resuscitation, medication compatibility and limited IV access may make normal saline the simpler first-bolus choice.

References: 

1. Weiss SL, Keele L, Balamuth F, et al. Crystalloid Fluid Choice and Clinical Outcomes in Pediatric Sepsis: A Matched Retrospective Cohort Study. J Pediatr. 2017;182:304-310.e10. doi:10.1016/j.jpeds.2016.11.075
2. 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
3. Long B, Gottlieb M. Balanced Crystalloids for Pediatric Sepsis and Septic Shock. Acad Emerg Med. 2026;33(1):e70115. doi:10.1111/acem.70115
4. Balamuth F, Weiss SL, Long E, et al. Balanced Fluid or 0.9% Saline in Children Treated for Septic Shock. N Engl J Med. Published online April 24, 2026. doi:10.1056/NEJMoa2601969