For Doctors in a Hurry
- Clinicians debate whether balanced crystalloids improve outcomes compared to 0.9% saline in children requiring resuscitation for septic shock.
- This pragmatic trial at 47 emergency departments randomized 9,041 pediatric patients to receive either balanced fluids or 0.9% saline.
- Primary outcome events occurred in 3.4% of the balanced group and 3.0% of the saline group (P=0.85; risk ratio 1.10).
- The researchers concluded that balanced crystalloids did not significantly reduce the incidence of death or persistent kidney dysfunction in children.
- These findings suggest that saline remains a viable resuscitation fluid for pediatric septic shock without increasing major adverse kidney events.
Crystalloid Selection in Pediatric Septic Shock
Septic shock remains a critical emergency in pediatric medicine, requiring immediate fluid resuscitation to reverse hypoperfusion and prevent multi-organ failure [1]. While isotonic crystalloids are the standard of care, the optimal choice between 0.9% saline and balanced solutions, such as lactated Ringer's or multiple electrolyte solutions, remains a subject of significant clinical debate [2]. Concerns persist that the high chloride concentration in 0.9% saline may trigger hyperchloremic acidosis and activate tubuloglomerular feedback, potentially leading to renal vasoconstriction and acute kidney injury [3]. Although some smaller studies in children have suggested that balanced fluids might reduce the risk of new or progressive kidney dysfunction, the evidence regarding definitive clinical outcomes has been inconsistent [4, 5]. A large-scale international trial now provides clarity, demonstrating that the biochemical differences between these fluids do not translate into meaningful differences in patient survival or renal recovery, allowing physicians to confidently use either fluid for initial stabilization.
Trial Design and Patient Population
The PRoMPT BOLUS trial was designed as a pragmatic clinical trial, a study format integrated into routine clinical practice to evaluate interventions under real-world conditions rather than highly controlled, artificial environments. Conducted across 47 emergency departments in five countries, this large-scale investigation provides a broad international perspective on pediatric resuscitation. The study (ClinicalTrials.gov number NCT04102371) received primary funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. By involving a diverse range of clinical sites, the researchers sought to determine if the choice of crystalloid fluid impacts outcomes in the heterogeneous population of children presenting with life-threatening infections. The study population consisted of children aged 2 months to less than 18 years who presented with suspected septic shock and clinical evidence of abnormal perfusion, such as delayed capillary refill or altered mental status. A total of 9,041 patients were initially enrolled and randomly assigned to receive fluid resuscitation with either balanced fluid or 0.9% saline for up to 48 hours. After the withdrawal of 277 patients (6.1%) in the balanced-fluid group and 282 patients (6.2%) in the 0.9% saline group, the final analysis included 4,235 patients in the balanced-fluid group and 4,247 patients in the 0.9% saline group. This 48-hour intervention window focused on the acute phase of stabilization, the critical period when the biochemical properties of the resuscitation fluid are most likely to influence renal function and systemic recovery.
Primary Renal and Survival Outcomes
To evaluate the comparative efficacy of the two resuscitation strategies, the researchers focused on a primary outcome defined as a major adverse kidney event. This composite metric included death from any cause, the initiation of new renal-replacement therapy (such as dialysis or continuous hemofiltration), or persistent kidney dysfunction, assessed at 30 days after enrollment or at the time of hospital discharge. The analysis revealed that a primary-outcome event occurred in 137 patients (3.4%) in the balanced-fluid group compared to 124 patients (3.0%) in the 0.9% saline group. Statistical analysis demonstrated no significant difference between the two treatment arms. The absolute difference in primary outcome events was 0.4 percentage points (95% confidence interval [CI], -0.5 to 1.3). Furthermore, the risk ratio for the primary outcome was 1.10 (95% CI, 0.88 to 1.40; P = 0.85), indicating that the choice of fluid did not meaningfully alter the risk of mortality or severe renal complications. For the practicing clinician, these findings provide reassurance that 0.9% saline remains a safe and viable option for pediatric septic shock, without an increased risk of driving patients toward dialysis or long-term renal failure.
Secondary Metrics and Electrolyte Variations
Beyond the primary renal and survival endpoints, the researchers evaluated the speed of recovery by measuring hospital-free days, a metric that quantifies the number of days a patient is alive and out of the hospital during a fixed 28-day period. The median number of hospital-free days was 23 in both the balanced-fluid and 0.9% saline groups, with an identical interquartile range of 19 to 25 days. This suggests that the choice of resuscitation fluid did not influence the duration of hospitalization or the speed at which patients achieved clinical stability. While hard clinical outcomes remained similar, the biochemical profiles of the patients showed distinct variations based on the fluid administered. Hyperchloremia (excessive chloride levels in the blood) occurred in 1,383 patients (49.0%) in the 0.9% saline group, compared to 868 patients (31.4%) in the balanced-fluid group. Similarly, the incidence of hypernatremia (elevated serum sodium) was higher in the saline group, affecting 89 patients (3.1%) versus 52 patients (1.8%) in the balanced-fluid group. The study also monitored for hyperlactatemia, a marker of tissue hypoperfusion or metabolic stress, which was observed in 260 patients (19.8%) in the balanced-fluid group and 228 patients (16.7%) in the 0.9% saline group. No differences in other safety outcomes or adverse events were seen between the two treatment arms. Ultimately, these data indicate that while 0.9% saline is more likely to induce transient hyperchloremia and hypernatremia, these laboratory abnormalities do not compromise the overall safety profile or recovery trajectory of children treated for septic shock.
References
1. Evans L, Rhodes A, Alhazzani W, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. Critical Care Medicine. 2021. doi:10.1097/ccm.0000000000005337
2. Lehr AR, Rached-d’Astous S, Parker M, et al. Impact of balanced versus unbalanced fluid resuscitation on clinical outcomes in critically ill children: protocol for a systematic review and meta-analysis. Systematic Reviews. 2019. doi:10.1186/s13643-019-1109-2
3. Redant S, Legrand M, Langman Y, et al. Urgent need for a randomized controlled trial with only septic patients!. Annals of Intensive Care. 2019. doi:10.1186/s13613-019-0596-6
4. Vijendra B, Bertol AB, Almeida MMGD, Freitas PHAGD, Simão ÁMS, Faria BLD. Balanced crystalloid versus saline for resuscitation in pediatric septic shock: a systematic review and meta-analysis. BMC Pediatrics. 2025. doi:10.1186/s12887-025-05442-w
5. Sankar MJ, Muralidharan MJ, Lalitha MAV, et al. Multiple Electrolytes Solution Versus Saline as Bolus Fluid for Resuscitation in Pediatric Septic Shock: A Multicenter Randomized Clinical Trial*. Critical Care Medicine. 2023. doi:10.1097/CCM.0000000000005952
