Fluid resuscitation remains a cornerstone of sepsis management. Yet one of the most common interventions in emergency medicine has also been the subject of persistent debate: Which crystalloid should we use in the initial resuscitation of children with suspected sepsis?

Historically, normal saline (NS) has been the default fluid for pediatric septic shock. It is readily available, familiar to clinicians, inexpensive, and compatible with many medications. Over the last decade, however, adult studies have suggested that balanced crystalloids—including Lactated Ringer’s (LR) and Plasma-Lyte—may improve renal outcomes and possibly mortality. Whether those benefits extended to children remained uncertain, until now.

The PECARN PRoMPT BOLUS trial provides the strongest evidence to date addressing this question. Conducted across 47 sites in five countries and enrolling more than 9,000 children, this large pragmatic trial compared 0.9% saline with balanced crystalloids in suspected pediatric septic shock. The results demonstrate that both NS and balanced crystalloids are both safe and effective options for fluid resuscitation in suspected pediatric septic shock.

Why Did Fluid Choice Become Controversial?

The physiologic rationale favoring balanced crystalloids stems from the composition of normal saline.

Normal saline contains 154 mEq/L of both sodium and chloride and has a pH of approximately 5.0. Compared with plasma, NS is hypernatremic and hyperchloremic. Large-volume saline administration has been associated with hyperchloremic metabolic acidosis, raising concerns that excess chloride may contribute to renal vasoconstriction,  endothelial dysfunction, coagulopathy, and inflammation.

The Initial Case for Balanced Fluids

Balanced crystalloids more closely resemble human plasma. Lactated Ringer’s contains 130 mEq/L of sodium, 109 mEq/L of chloride, and has a pH of approximately 6.5. Although LR has limitations related to medication compatibility, its electrolyte composition is generally considered more physiologic.

Several adult studies suggested these biochemical differences translated into clinical benefit. In the SMART trial, 15,802 critically ill adults were randomized to receive saline or balanced crystalloids. Major adverse kidney events within 30 days (MAKE30)—a composite of death, new renal replacement therapy, or persistent renal dysfunction—occurred less frequently among patients receiving balanced fluids (14.3% versus 15.4%; OR 0.90; 95% CI, 0.82–0.99). Interestingly, multiple large studies since that time haven’t shown benefit, including a multisite crossover trial in Canada. A Cochrane review published just before PROMPT BOLUS found no benefit either in mortality or acute kidney injury after aggregating all available trials.

The pediatric story has proven more complicated. Studies failed to consistently demonstrate benefit, and some suggested potential harm. 

Enter PRoMPT BOLUS

PRoMPT BOLUS was designed to answer this question.

PRoMPT sought to determine whether balanced crystalloids, compared with NS, would improve outcomes in children with septic shock without increasing adverse events.

Several aspects of the trial deserve emphasis.

First, enrollment occurred in the emergency department. Although ICU-based enrollment was considered, investigators recognized that most children with sepsis first present to the ED. Early randomization minimized exposure to non-study fluids and ensured fluid choice reflected the realities of frontline emergency care.

Second, the study embraced a pragmatic design. The intervention altered only one aspect of routine care: the choice of fluids for initial resuscitation and maintenance during the first 48 hours. This approach enhanced generalizability while preserving the complexity and heterogeneity characteristic of pediatric sepsis practice.  All other elements of clinical care, including fluid volume and timing, were at the discretion of the treating clinical teams.

What Did PRoMPT BOLUS Find?

The primary outcome, MAKE30, occurred at nearly identical rates:

• Balanced fluids: 3.4 percent
• 0.9% saline: 3.0 percent

This difference was not statistically significant.

Similarly, investigators found no meaningful differences in mortality (1.1 percent before discharge in both groups), hospital length of stay, hospital-free days, or important adverse events including thrombosis and cerebral edema.

Biochemical differences did emerge. Hyperchloremia and hypernatremia, as expected, occurred more frequently among children receiving saline, while hyperlactatemia was more common among those receiving balanced fluids. These laboratory findings, however, did not translate into differences in patient-centered outcomes.

Subgroup analyses likewise demonstrated no significant heterogeneity of treatment effect across illness severity, baseline kidney function, or total crystalloid volume administered.

There were signals suggesting potential benefit of balanced fluids among children presenting with lactate concentrations greater than 5 mmol/L or bicarbonate concentrations below 15 mEq/L. However, confidence intervals crossed one, and the study was not powered to draw definitive conclusions regarding these subgroups. These findings should therefore be viewed as hypothesis-generating rather than practice-changing.

What This Means for Emergency Clinicians

Both normal saline and balanced crystalloids are safe and effective choices for the initial resuscitation of children with suspected septic shock. The choice of fluid does not influence mortality or kidney outcomes.

Rather than focusing on selecting the “perfect” crystalloid, clinicians should prioritize early recognition of sepsis, timely administration of antibiotics, appropriate fluid resuscitation, and ongoing reassessment of perfusion.

Fluid selection can be individualized based on medication compatibility, local availability, existing electrolyte abnormalities, and patient-specific considerations.

ACEP Declines to Endorse the Surviving Sepsis campaign guidelines

• In February 2026, ACEP refused to endorse the Surviving Sepsis treatment guidelines.
• This decision was based on concerns about conflicting guidelines for the treatment of adult and pediatric patients, and a belief that the guidelines developed do not fully reflect the most up-to-date and reality-based approach to care.
• ACEP is exploring the development of its own sepsis treatment guidelines, prioritizing current science and emergency physician expertise.

PRoMPT BOLUS offers the strongest evidence to date regarding fluid choice in children with suspected septic shock. For emergency clinicians, both 0.9 percent saline and balanced crystalloids are safe, effective, and appropriate choices for fluid resuscitation.  

Dr. VonHoltz is a pediatric emergency medicine physician at Children’s Hospital of Philadelphia and an Assistant Professor of Clinical Pediatrics at the Perelman School of Medicine at the University of Pennsylvania. She serves as Co-Chair of the Pediatric Emergency Care Applied Research Network (PECARN) Dissemination Committee, where her work focuses on developing strategies and systems to accelerate the dissemination of pediatric emergency care research and translate research findings into clinical practice. She founded and leads an emergency department–based program that connects families experiencing unmet health-related social needs with community and public resources through resource navigation, referral, and follow-up.