Two Resuscitation Fluids Led to Similar Outcomes in Kids With Septic Shock

Among children treated for septic shock, use of balanced crystalloid fluid for resuscitation did not improve outcomes compared with 0.9% saline, a pragmatic trial showed.

Across 47 emergency departments in five countries, a major adverse kidney event (a composite of death, new renal-replacement therapy, or persistent kidney dysfunction) occurred in 3.4% of patients in the balanced-fluid group compared with 3% of those in the saline group (risk ratio 1.10, 95% CI 0.88-1.40, P=0.85), reported Scott Weiss, MD, of Nemours Children’s Hospital in Wilmington, Delaware, and colleagues in the New England Journal of Medicine.

The study was also presented at the Pediatric Academic Societies annual meeting in Boston.

Co-author Fran Balamuth, MD, PhD, of Children’s Hospital of Philadelphia, told MedPage Today that the study “showed that both fluids are equally safe and effective for children in their initial resuscitation, which I think is good news, meaning that people can use whatever fluid they have available.”

“Both fluids are cheap, they don’t have storage challenges, [and] they are immediately available in almost every emergency department around the world,” she said.

Steven Kernie, MD, of Children’s Hospital at Montefiore Einstein in New York City, noted that the question of which kind of isotonic fluid is better for someone with sepsis or septic shock “has been an ongoing debate for decades.”

Even though there were kids included in the study who ultimately did not have septic shock, the findings offer “reassurance” that “isotonic fluids of any kind are totally fine,” he told MedPage Today.

The authors noted that despite widespread use of 0.9% saline, it contains a “supraphysiologic concentration of chloride associated with hyperchloremia, metabolic acidosis, and decreased renal blood flow.”

Balanced fluid, on the other hand, has an “electrolyte composition that more closely resembles that of human plasma,” they wrote, and has been shown to be “associated with lower frequencies of acute kidney injury, receipt of renal-replacement therapy, and death than 0.9% saline in some studies involving adults and in some involving children.”

However, other studies have suggested that balanced fluid does not provide benefit and is associated with harm. Even so, in 2020, the Surviving Sepsis Campaign put forth a conditional recommendation for balanced fluid over 0.9% saline in kids with septic shock.

With the current study, “we confirmed the biochemical differences that we’re seeing in adult studies and also in prior studies in children,” Balamuth said, but “those biochemical differences didn’t translate into clinical outcomes.”

Weiss told MedPage Today that his team “undertook this study to address the knowledge gap about whether switching to balanced fluid as a primary resuscitation and maintenance fluid would improve outcomes for children who presented with a suspicion of septic shock and required initial fluid treatment in an emergency department setting.”

They enrolled children ages 2 months to 17 years with suspected septic shock and abnormal perfusion who were randomly assigned to receive fluid resuscitation with either balanced fluid or saline for up to 48 hours. Ultimately, they ended up with 277 kids in the balanced-fluid group and 282 in the saline group. Median age was 6.8 years, and about 50% were boys.

For kids with follow-up laboratory values measured within 4 days of enrollment, hyperchloremia and hypernatremia occurred less often, and hyperlactatemia more often, with balanced fluid than with saline.

As for secondary outcomes, the median number of hospital-free days within 28 days of enrollment was 23 in both groups. The incidence of death before hospital discharge was 1.1% in both groups, and the incidence of death within 90 days was 2.3% in the balanced-fluid group and 2.1% in the saline group.

There were no differences in other safety outcomes or adverse events.

Limitations of the study included that its results may not be generalizable to low-resource contexts or hospital-acquired sepsis, Weiss and colleagues noted.

Furthermore, septic shock was defined “using immediately accessible clinical signs of abnormal perfusion to capture patient data near the onset of fluid therapy rather than waiting for abnormal laboratory results,” they added. “Although this approach aligns with clinical practice and the trial population was representative of children treated for septic shock in an emergency department, the low incidence of a primary outcome event diminished statistical power to detect planned differences between groups.”