EBM Review Series: Fluids in Pediatric Sepsis
VACEP Evidence-Based Medicine for General Emergency Physicians Series
Authors: Allison Savon, DO PGY-3, Danielle Nesbit, DO | VCU Health
Reviewers: Andrea Klein, MD PGY-3, Andrew Moore, MD | Virginia Tech Carilion
Editor: Winston Wu, MD | Virginia Tech Carilion
The VACEP Evidence-Based Medicine Review Series allows Virginia emergency medicine residents and attendings to share and analyze a recent peer-reviewed clinical study. Authors read and write a report, which is then reviewed by peers.
This case covers the April 2026 New England of Journal of Medicine article “Balanced Fluid or 0.9% Saline in Children Treated for Septic Shock.”
THE CASE
An otherwise healthy 7-year-old male presents to the emergency department with fever, cough and shortness of breath. His parents state that he had a fever for the past week with the highest temperature being 40 degrees Celsius. He has been increasingly fatigued. No vomiting, nausea or decreased urination noted. Up to date on vaccines. Parents deny any sick contacts that they know of, however; he does attend school. On physical exam, temp is 39.8 degrees Celsius, HR 168, BP 80/40, RR 38, O2 89% on RA. He is ill appearing, dry mucous membranes and delayed capillary refill. You notice that he has increased work of breathing with crackles in the right lower lobe with auscultation of the lungs. You immediately put him on a nasal cannula, establish IV access and order a sepsis workup. Lactate on a point of care lab comes back as 6.5.
The nurse asks you what fluids you would like to use for resuscitation. What is your response?
BACKGROUND
Balanced fluids such as lactated ringers, Hartman’s solution, or Plasma-Lyte were previously recommended over normal saline in the setting of septic shock in the Surviving Sepsis Campaign International Guidelines for the Management of Sepsis and Septic Shock in Children1, as they were shown to reduce the incidence of acute kidney injury and decrease the incidence of renal replacement therapy. This was previously based on the SMART trial2. However, there was not a decrease in overall mortality. The 2025 AHA/AAP guidelines state that either fluid is beneficial, however, they also note that maintenance fluids with normal saline can be associated with a hyperchloremic metabolic acidosis although most other studies did not demonstrate this in practice3.
STUDY SUMMARY
In the PRoMPT BOLUS trial6, Balamuth et al present a pragmatic clinical trial to address outcomes on balanced crystalloid fluids compared to normal saline in pediatric sepsis patients. This was a large scale trial conducted at 47 emergency departments across five different countries. Patients were age 2 months to <18 years with suspected septic shock and abnormal perfusion. Each patient was randomly assigned to receive either a balanced fluid or 0.9% saline for fluid resuscitation up to 48 hours. The primary outcome was major adverse kidney event (MAKE-30); a composite of death, new renal replacement therapy, or persistent kidney dysfunction, measured at 30 days after enrollment or at hospital discharge, whichever came first.
The authors found that there was no meaningful difference in outcome between the two groups. A major adverse kidney event occurred in 3.4% of children in the balanced fluid group and 3.0% of children in the saline group. That difference was not statistically significant (risk ratio 1.10; 95% CI, 0.88 to 1.40). This suggests that neither fluid led to more deaths, dialysis or lasting kidney damage than the other. In terms of secondary effects, there were some differences in lab values. Hyperchloremia occurred more often in the normal saline group, occurring in roughly half of the saline group (49%) as compared to 31% of the balanced fluid group. Hypernatremia was also slightly more common with saline and hyperlactatemia occurred more frequently in the balanced crystalloid fluids. The authors concluded that these laboratory differences did not translate into meaningful outcomes and determined that there was no benefit to balanced fluid over saline.
METHODS:
About the EBM Review Series
This is a literature review series started by the University of Virginia’s Josh Easter, MD, MSc, a VACEP board member working to connect the academic community in Virginia. We invite each residency in Virginia (and D.C.) to create a faculty/resident team to submit and review articles. Sign up to submit one.
Goals
Provide a brief monthly synopsis of a high yield article germane to the practice of emergency medicine for distribution to all VACEP members
Provide an opportunity for a peer reviewed publication and invited presentation for faculty and trainees
Foster an academic community focused on evidenced based medicine for emergency medicine residency programs in the region
This trial was a phase 3, double-blind, double-dummy, parallel-group randomized controlled trial. It compared intravenous TNK with an oral placebo versus 300 mg oral aspirin with an intravenous placebo for treatment of CRAO within a 4.5 hour window from onset of symptoms. It was coordinated by Oslo University Hospital and involved sites across six European countries. Adult patients diagnosed with CRAO within the 4.5 hour treatment window and who had a best corrected visual acuity (BCVA) of 20/200 or worse were included in the study. Patients were assessed initially by ophthalmology, then by an acute stroke team and had neuroimaging in accordance with hospital stroke guidelines. They were admitted to a stroke unit and managed according to institutional stroke guidelines after thrombolytic administration. Following discharge patients had outpatient follow-up with both ophthalmology and neurology. The groups were block randomized with a 1:1 ratio to tenecteplase + placebo vs aspirin + placebo group.
STRENGTHS, LIMITATIONS, IMPLICATIONS
The authors acknowledged several limitations. First, it is unclear whether the results are generalizable to low-resource settings where access to fluids, monitoring and intensive care may differ substantially. Additionally, the trial diagnosed septic shock using immediately available clinical signs rather than laboratory values. This differs from the Phoenix criteria which relies on the use of lactate and other labs as part of the criteria, so the enrolled population may not be able to be generalized perfectly when compared to a strictly lab-defined sepsis cohort.
Third, the primary outcome of the study counted all-cause death rather than death specifically from kidney injury. This is an incredibly broad endpoint, granted isolating kidney-specific mortality would be difficult in practice. Lastly, the authors were unable to study specific subgroups, such as patients with severe sepsis who would receive larger amounts of fluids. If given a larger quantity of fluids, would the chance of adverse renal event occur? Would the effects occur proportionally to the quantity of fluids? This could be further studied in the future.
A major strength of this study was its size and diversity. It enrolled over 9,000 patients across 47 emergency departments in five different countries. In addition, this was a randomized trial. This study not only looked at just fluid boluses, but also maintenance fluids. This is particularly important as starting maintenance fluids after bolusing is a strong recommendation in the Surviving Sepsis Campaign International Guidelines for the Management of Sepsis and Septic Shock in Children 20261.
CASE CONCLUSION
In the emergency department, we are often asked to make quick decisions based on the patient in front of us. Typically, a balanced crystalloid is given as a bolus in the ED. This study challenges that notion as it shows either fluid could be used without major kidney effects in the pediatric population. It likely will not change maintenance fluids practices given the chance of secondary effects. Treating sepsis is a familiar task in the pediatric ED. Knowing that either fluid can be used equally can help with resource utilization and cost reduction.
Your nurse is waiting for your reply. You respond with a lactated ringer’s bolus- only because she has the bag spiked and ready to hang. The patient’s blood pressure normalizes and tachycardia improves.
SOURCES
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;27(4):379-434. doi:10.1097/PCC.0000000000003927
Semler MW, Self WH, Wanderer JP, et al. Balanced crystalloids versus saline in critically ill adults. N Engl J Med. 2018;378(9):829-839. doi:10.1056/NEJMoa1711584
Lasa JJ, Dhillon GS, Duff JP, et al. Part 8: Pediatric Advanced Life Support: 2025 American Heart Association and American Academy of Pediatrics guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Pediatrics. 2026;157(1). doi:10.1542/peds.2025-074351
Maitland K, Kiguli S, Opoka RO, et al. Mortality after fluid bolus in African children with severe infection. N Engl J Med. 2011;364(26):2483-2495. doi:10.1056/NEJMoa1101549
Schlapbach LJ, Watson RS, Sorce LR, et al; Society of Critical Care Medicine Pediatric Sepsis Definition Task Force. International Consensus Criteria for Pediatric Sepsis and Septic Shock. JAMA. 2024;331(8):665-674. doi:10.1001/jama.2024.0179
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
