A large clinical trial supported by the National Institutes of Health (NIH) compared two commonly used treatments for pediatric patients treated for septic shock and found no difference in meaningful outcomes. The trial, which enrolled over 9,000 participants across five countries, sought to answer a longstanding question about which intravenous crystalloid fluid type was the superior option for children who were in septic shock, a life-threatening condition triggered by severe infection which requires immediate medical treatment.
"For decades, pediatricians have debated which is the best intravenous resuscitation treatment for children with severe infections who have suspected septic shock," said Rohan Hazra, M.D., acting director of NIH's Eunice Kennedy Shriver National Institute of Child Health and Human Development, which funded the study. "This largest-ever clinical trial for children treated for septic shock has immediate clinical application and allows physicians caring for these vulnerable patients to know they can confidently choose either intervention as a standard of care."
For the study, scientists sought to compare balanced crystalloid fluid, an IV solution designed to closely mimic the electrolyte composition of human plasma, to a 0.9% saline IV solution. They assigned over 4,200 participants between the ages of 2 months and 17 years into each arm of the trial and found no significant differences between the groups for incidences of death, persistent kidney disfunction, or new renal-replacement therapy (a type of dialysis treatment to temporarily replace kidney function).
Participants in both groups received their assigned IV fluid type for 24-48 hours and achieved a median of 23 hospital-free days during the 28 days following enrollment. Children receiving the 0.9% saline solution had significantly higher incidences of abnormally high levels of chloride and sodium in their blood, while those receiving the balanced fluid had slightly higher incidence of abnormally high lactate in their blood. These were expected biochemical differences caused by the different fluid types, but, notably, this study found that these fluid-induced differences in blood profiles did not translate into meaningful differences in patient outcomes. There were also no other differences in safety outcomes between the treatments.
Researchers acknowledge that while their trial's large sample size allowed them to identify small differences in patient outcomes, there were still some limitations for broader application of treatments. Because the study targeted children with community-acquired sepsis who presented to an emergency department in high-resource locations, the authors are uncertain if these results can be generalized to low-resource settings or when a patient has hospital-acquired sepsis. Additionally, because treatment was initiated when septic shock was suspected using immediate clinical observations rather than waiting for abnormal laboratory results, which are often not available when symptoms appear, the authors cannot exclude the possibility that a specific fluid type could be preferred among the sickest subset of children or those who require treatment with very high fluid volumes. Despite these limitations, these results now confirm that emergency physicians can be reassured that either balanced fluid or 0.9% saline are safe and effective for children treated for septic shock.
This research was supported by NIH grants R01HD101528 and P50DK114786 and led by the Pediatric Emergency Care Applied Research Network (PECARN), a network for research in pediatric emergency medicine funded through Emergency Medical Services for Children (EMSC) program of the Health Resources and Services Administration (HRSA) in collaboration with institutions in Canada, Australia, New Zealand, and Costa Rica.
