In children with septic shock, does the choice between balanced crystalloids and 0.9% saline actually matter? This episode reviews the composition and physiologic differences between commonly used crystalloids, summarizes the 2026 PRoMPT BOLUS trial, and discusses how its findings fit with the updated Surviving Sepsis Campaign pediatric guidelines. We also consider the trial’s limitations and what the results mean for fluid selection at the bedside.

Learning Objectives

By the end of this episode, listeners should be able to:

1. Compare the composition and physiologic effects of 0.9% saline and balanced crystalloids used for pediatric fluid resuscitation.
2. Summarize the design and major findings of the PRoMPT BOLUS trial.
3. Describe important limitations of PRoMPT BOLUS when applying its results to children with septic shock.
4. Apply current evidence and 2026 Surviving Sepsis Campaign recommendations when selecting crystalloid fluids for pediatric septic shock.

References

1. Weiss SL, Peters MJ, Oczkowski SJW, et al. Surviving Sepsis Campaign International Guidelines for the Management of Sepsis and Septic Shock in Children 2026. Pediatr Crit Care Med. 2026. Published April 1, 2026.
   Jointly issued by the Society of Critical Care Medicine and Infectious Diseases Society of America. Recommendation 24 suggests balanced/buffered crystalloids over 0.9% saline for children with septic shock requiring fluid boluses (conditional recommendation, very low certainty), while recognizing 0.9% saline as a suitable alternative and preferred in selected situations such as hyponatremia or concern for increased intracranial pressure.
2. 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.
   Published April 24, 2026. PRoMPT BOLUS was a large pragmatic randomized trial comparing balanced crystalloids with 0.9% saline in children treated for suspected septic shock and found no reduction in major adverse kidney events within 30 days with balanced fluids.

Transcript

This transcript was generated using Descript and subsequently reviewed and lightly edited for spelling, grammar, and clarity. Minor inaccuracies may remain, and the audio recording should be considered the definitive version of this content.

Welcome to PEM Currents: The Pediatric Emergency Medicine Podcast. As always, I’m your host, Brad Sobolewski, and today we’re gonna talk about which fluid we should use when managing a septic pediatric patient. So when we resuscitate a child with septic shock, the major decision is usually not whether to give crystalloid, but which crystalloid to give.

And for a long time, there’s been a gradual shift towards balanced fluids such as Lactated Ringer’s or Plasma-Lyte, largely because they are more physiologic and produce less hyperchloremia than normal saline. The question’s always been whether those biochemical differences actually translate into better clinical outcomes.

That is the question that a study called PRoMPT BOLUS was designed to answer. So before getting into the trial, it’s worth briefly reviewing what these fluids actually contain. So normal saline is 0.9% sodium chloride. It contains one hundred and fifty-four milliequivalents per liter of sodium and a hundred and fifty-four milliequivalents per liter of chloride.

The chloride concentration is substantially higher than plasma. Balanced crystalloids contain less chloride and have some other electrolytes and a buffer. Lactated Ringer’s contains approximately a hundred and thirty milliequivalents per liter of sodium, one hundred and nine of chloride, four of potassium, a small amount of calcium, and lactate as a buffer.

Plasma-Lyte contains approximately one hundred and forty of sodium, ninety-eight of chloride, five of potassium, magnesium, and acetate and gluconate as buffers. The concern with normal saline is that the large chloride loads can produce hyperchloremic metabolic acidosis. There’s also been concern about adverse effects on renal blood flow and kidney function.

Balanced fluids are designed to more closely approximate plasma composition, so the hypothesis has been that they might reduce kidney injury. That hypothesis has been supported by physiologic data and by some adult studies, although pediatric evidence before PRoMPT BOLUS was limited and inconsistent. The 2026 Surviving Sepsis Campaign Pediatric Guidelines recommend crystalloids over albumin for initial resuscitation and conditionally suggest balanced or buffered crystalloids over 0.9% saline in children with septic shock who require fluid boluses.

Importantly, that recommendation is based on very low-certainty evidence. Balanced options again include Lactated Ringer’s, Hartmann’s solution, or Plasma-Lyte. If balanced fluids are not readily available, saline remains an acceptable alternative. Saline may also be preferable in some specific situations like significant hyponatremia or concern for increased intracranial pressure.

For children in resource-abundant settings, the general approach is still ten to twenty mLs per kilo per bolus with reassessment after each bolus, potentially up to forty to sixty mLs per kilo in the first hour if perfusion remains abnormal and there are no signs of fluid overload. Now, PRoMPT BOLUS, the full name of which is the Pragmatic Pediatric Trial of Balanced versus Normal Saline Fluid in Sepsis, was an international randomized pragmatic trial designed to specifically compare the two fluid strategies in children with suspected septic shock.

The final trial enrolled nine thousand and forty-one children from two months to younger than eighteen years across forty-seven emergency departments in five countries. Children were randomized to predominantly balanced crystalloid or predominantly 0.9% saline, and the assigned fluid strategy was used for bolus and maintenance crystalloid during the initial treatment period.

The balanced fluid arm was not a single product. Depending on the site, children could get Lactated Ringer’s, Hartmann’s solution, or Plasma-Lyte. That’s important when interpreting the study. PRoMPT BOLUS was really testing a strategy of predominantly balanced crystalloid versus a strategy of predominantly saline use rather than comparing LR versus saline alone, though LR was the most commonly used one.

The primary outcome was something called MAKE30, M-A-K-E thirty, or major adverse kidney events within thirty days. This was a composite outcome that included death, new renal replacement therapy, or persistent kidney dysfunction. That choice of outcome is useful because the biologic rationale for balanced fluids has always centered largely on kidney protection.

The investigators were therefore asking whether the lower chloride exposure associated with balanced fluids translated into clinically meaningful renal benefit. So what was the result? Well, the spoiler is that the answer was no. So MAKE30 occurred in three point four percent of children receiving balanced fluids and three percent receiving saline.

The relative risk was one point one with a ninety-five percent confidence interval from point eight eight to one point four. There were also no significant differences in death, new renal replacement therapy, persistent kidney dysfunction, or hospital-free days. In practical terms, balanced crystalloids did not improve the major patient-centered outcomes the trial was designed to measure.

There were clear biochemical differences between the groups. Hyperchloremia occurred in thirty-one point four percent of children receiving balanced fluids compared with forty-nine percent with saline. Hypernatremia was also less common with balanced fluids, one point eight versus three point one percent.

Hyperlactatemia was slightly more common in the balanced fluid group, nineteen point eight compared with sixteen point seven percent. So the fluids behaved differently in the ways that you would expect physiologically. Balanced crystalloids clearly reduced hyperchloremia, but that difference did not translate into fewer major kidney events, less dialysis, shorter hospitalization, or lower mortality.

There are several limitations to this study worth keeping in mind. The first is that this was a broad emergency department population with suspected septic shock, not a study limited to children with the most severe forms of shock. Only a minority of patients required vasoactive medications, and overall mortality was low.

The results are therefore most applicable to the typical child with suspected septic shock receiving early ED resuscitation. They do not completely answer whether fluid composition might matter more in a smaller subgroup of children receiving very large fluid volumes or prolonged resuscitation. The second limitation is that the event rate for MAKE30 was lower than expected.

When the trial was designed, investigators anticipated an event rate of about six percent in the saline group. The observed rate was closer to three percent. That means there were fewer outcome events than anticipated, which reduced the ability to detect a very small treatment effect. So the trial makes a large benefit from balanced fluids unlikely, but it can’t exclude a small or subtle difference.

A third limitation is that the balanced fluid group included several different solutions. Lactated Ringer’s, Plasma-Lyte, and Hartmann’s are all considered under the umbrella of balanced crystalloids, but they’re not chemically identical. The study therefore supports the broader conclusion that a balanced fluid strategy is not superior to saline for most children in this setting, rather than providing equivalence between any single specific balanced solution and saline, even though Lactated Ringer’s is used far and away most often.

The trial was also intentionally pragmatic, which means that there was some crossover between fluid types. Adherence was defined as receiving at least seventy-five percent of crystalloid as the assigned fluid rather than requiring exclusive use of one fluid. That could reduce the ability to detect a small treatment effect, but it also makes the study more reflective of real clinical practice.

The investigators themselves described the trial as a comparison of predominant rather than exclusive use of balanced crystalloids versus saline. Finally, the trial was open label, so clinicians knew which fluid the child was receiving. That introduces the possibility of treatment bias, though the primary outcome relied on relatively objective measures.

A substantial proportion of children also did not have a measured baseline creatinine, so baseline kidney function sometimes had to be imputed using age- and sex-based values. That’s worth remembering because persistent kidney dysfunction was part of the primary composite outcome. Taken together, I think PRoMPT BOLUS makes the bedside decision simpler.

Balanced fluids remain a completely reasonable and defensible choice. They cause less hyperchloremia, and there’s no reason to abandon them if they’re already part of your usual resuscitation fluid strategy or your order sets. At the same time, the largest pediatric randomized trial now shows no improvement in major kidney or mortality outcomes compared with normal saline.

So if you use saline at your local hospital, that’s okay too. The 2026 Surviving Sepsis Campaign still conditionally favors balanced crystalloids, but that recommendation is based on very low-certainty evidence. So PRoMPT BOLUS adds important randomized data suggesting that for most children with septic shock, either crystalloid strategy is reasonable.

The practical takeaway is that the choice of crystalloid is probably less important than getting the resuscitation itself right. Give 10 to 20 mLs per kilo when a fluid bolus is indicated, reassess frequently, watch for improvement in perfusion and for signs of fluid overload, and move to vasoactive support when fluid alone is not correcting the shock.

Balanced crystalloids will produce less hyperchloremia. Normal saline will produce more. In PRoMPT BOLUS, that biochemical difference did not translate into a difference in kidney injury, dialysis, or mortality. For most children with septic shock, balanced fluids are fine, normal saline is fine, and timely, thoughtful resuscitation matters much more than which bag is hanging.

I hope you found this episode on fluids for sepsis in children helpful and that you’ll be able to take this knowledge back to the bedside the next time you work in the emergency department. If you’ve got other topics you want me to cover, especially as they relate to practice-changing research in pediatrics, like the PRoMPT BOLUS trial from the Pediatric Emergency Care Applied Research Network, PECARN as we call it, let me know.

Send it my way. If you have time to leave a review on your favorite podcast site, please do so. It helps other people find the show, and definitely share this with your colleagues. I think this study and perhaps this podcast episode could be a great combo for an upcoming journal club. For PEM Currents, the Pediatric Emergency Medicine Podcast, this has been Brad Sobolewski.

See you next time.