Balanced Crystalloids Show No Clear Edge in Pediatric Sepsis

Key Takeaways

• MAKE30 was reported at similar rates with balanced fluids and saline.
• Death, renal replacement therapy, persistent kidney dysfunction, hospital-free days, and 90-day mortality were also similar between groups.
• Balanced fluids were associated with less hyperchloremia and hypernatremia, more hyperlactatemia, and similar adverse events.

In a large international pediatric septic shock trial, MAKE30 occurred in 3.4% of the balanced-fluid group and 3.0% of the saline group, with no significant kidney-related advantage for balanced fluids over saline. Laboratory differences were observed between strategies, but the clinical outcomes remained closely aligned. Overall, the findings showed no clear advantage for either fluid approach in the study population.

Fran Balamuth and Scott L. Weiss led the pragmatic, open-label, randomized trial, which enrolled more than 9,000 children across 47 emergency departments in five countries. The trial included 9,041 enrollees and 8,482 patients in the primary analysis. Eligible patients were 2 months to under 18 years old and were treated for suspected septic shock with abnormal perfusion. Investigators compared a predominantly balanced crystalloid strategy, including lactated Ringer’s or PlasmaLyte, with 0.9% saline for resuscitation and maintenance fluids over 24 to 48 hours. The primary endpoint was MAKE30, defined as death, new renal replacement therapy, or persistent kidney dysfunction within 30 days.

In the primary analysis, the relative risk for MAKE30 was 1.10, with a 95% confidence interval of 0.88 to 1.40 and P = .85. Death, new renal replacement therapy, persistent kidney dysfunction, hospital-free days, and 90-day mortality were also similar between groups. Kidney-related and mortality-related results were therefore closely aligned across the two fluid strategies. The findings did not show a measurable clinical advantage for the balanced-fluid strategy on the reported kidney, utilization, or mortality-related outcomes.

Balanced fluids were linked to lower rates of hyperchloremia and hypernatremia, while hyperlactatemia was more frequent in that group. Adverse events, including thrombosis and cerebral edema, were similar across both treatment arms. Earlier pediatric and adult studies have not pointed consistently in one direction, according to the report. Differences in patient populations, outcome definitions, and study design may help explain that variability. The biochemical differences did not coincide with between-group differences in the main clinical outcomes.

Investigators interpreted the findings as supporting either balanced fluids or 0.9% saline as acceptable options for initial pediatric sepsis resuscitation. They also noted relatively low event rates and uncertain generalizability to lower-resource settings in these emergency department-based populations. The results may be particularly relevant where access to balanced fluids is limited, but small subgroup numbers left the sickest patients less certain. Potential benefit in children with severe acidosis or markedly elevated lactate could not be fully excluded, although the numbers in these subgroups were small. The investigators said the findings did not indicate a need to change practice solely to obtain balanced fluids.