Philadelphia and Boston, April 24, 2025 – A major study, led by researchers at Children's Hospital of Philadelphia, Nemours Children's Health, and Children's National Hospital and involving an extensive network of medical centers across the United States and abroad, found that different types of crystalloid fluid resuscitation were equally effective for staving off the most serious adverse kidney events after the treatment of pediatric patients with suspected septic shock. The findings of this large clinical trial are detailed today in a study published by The New England Journal of Medicine and are being presented at the Pediatric Academic Societies (PAS) Meeting in Boston.
Sepsis is a life-threatening response to infection that causes organ failure. The combination of the body's immune system and the infection together cause an abnormal response, which can prevent different organ systems from working normally. The disease is estimated to send more than 18,000 children across the country to hospitals each year. While many decades of research and improvements in clinical care have significantly improved outcomes for pediatric sepsis patients, about 1 in 10 children nationally with sepsis or septic shock are still at risk of dying.
In some previous multi-center studies, researchers found that critically ill adults who received balanced crystalloid fluid – an intravenous (IV) treatment meant to exhibit similar properties to human plasma – resulted in lower risk of complications and death compared with a standard 0.9% saline IV solution. This prompted researchers to explore whether a similar study could determine whether one fluid treatment was superior for pediatric sepsis patients.
"We knew we were going to need thousands of patients to answer this question, which we knew would be a challenge," said co-lead author Fran Balamuth, MD, PhD , an attending physician and Division Chief of Emergency Medicine at CHOP. "Yet we were excited to proceed because these fluids are inexpensive and universally available around the world, meaning that we wouldn't have decades of waiting to take action once the study was complete; we could be pragmatic and take immediate action based on the results that we found."
Because suspected cases of sepsis are uncommon among the general population, Balamuth, co-lead author Scott L. Weiss, MD , attending physician and Division Chief of Critical Care at Nemours Children's Hospital, Delaware, and their colleagues required the collaboration of many hospitals to achieve the data standards needed for meaningful conclusions. For this, they collaborated with Nathan Kuppermann, MD , Executive Vice President and Chief Academic Officer of Children's National Hospital and Director of the Children's National Research Institute, who has a history of running successful clinical trials in acutely ill children, and served as the senior author.
"This trial demonstrates the power of large collaborative research networks to answer important clinical questions for children," Kuppermann said. "By enrolling thousands of patients across multiple countries, we were able to provide the kind of evidence clinicians need to guide care for children with suspected septic shock."
In the United States, the team utilized the Pediatric Emergency Care Applied Research Network (PECARN) , a group of 18 hospitals across the country that make up a multi-institutional network for research in pediatric emergency medicine as part of the federal Emergency Medical Services for Children Program. Collaborative institutions in Canada, Australia, New Zealand, and Costa Rica also contributed to the data. In the end, a total of 47 emergency departments across five countries were represented in the study, with more than 9,000 patients enrolled who received either balanced fluid or 0.9% saline.
The primary outcome of the study was Major Adverse Kidney Events by 30 days (MAKE30), an important outcome for kidney injury that accounts for death, new renal replacement therapy or persistent renal dysfunction. The researchers found that MAKE30 occurred in 3.4% of patients enrolled in the balanced fluid group and 3.0% in the 0.9% saline ground. The study found biochemical differences in children treated with the two fluids, including a higher frequency of elevated blood chloride levels in the 0.9% saline group, and higher lactate levels in the balanced fluid group. Both groups had 23 median hospital-free days of 28, and there were no differences in mortality or other safety outcomes or adverse events.
"This trial confirms that either balanced fluid or 0.9% saline are effective and safe for the initial resuscitation of children with suspected septic shock, and that a fluid strategy that reduces hyperchloremia does not necessarily translate to improved patient outcomes," said Weiss, an attending physician and Division Chief of Critical Care at Nemours Children's Hospital, Delaware. "We also did not identify differences across subgroups. However, despite the large number of participants, it is important to note that we cannot exclude the possibility of benefit of one fluid or the other in a subset of children with the most severe illness."
"A large trial like this definitively answers a question we've had in our field for many, many years," Balamuth said. "In an emergency department with a child with suspected sepsis, you can treat the child with whichever fluid is readily available. And we think that's great news for children around the world."
This study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development grant R01HD101528, the National Institute of Diabetes and Digestive and Kidney Diseases grant P50DK114786, the National Institute of General Medical Sciences grant R01GM145698, Commonwealth of Pennsylvania Department of Health SAP #4100085749, The Medical Research Future Fund International Clinical Trial Collaboration grant GNT1190814, Canberra, Australia and the Canadian Institutes of Health Research grant 173498. Additional support was provided by the Children's Hospital of Philadelphia Research Institute and Alberta Children's Hospital Research Institute. The Pediatric Emergency Care Applied Research Network (PECARN) is funded through the Emergency Medical Services for Children Network Development Demonstration Program of the Maternal and Child Health Bureau, Health Resources and Services Administration, under cooperative agreement awards U03MC00008, U03MC00001, U03MC00003, U03MC00006, U03MC00007, U03MC22684, and U03MC22685. The Paediatric Research in Emergency departments International Collaborative (PREDICT) network was part funded by a National Health and Medical Research Council (NHMRC) Centre of Research Excellence grant GNT2024601, Canberra, Australia, the Murdoch Children's Research Institute, Parkville, Australia, and the Victorian Government's Operational Infrastructure Support program, Melbourne, Australia.
Balamuth et al, "Balanced Fluid versus 0.9% Saline in Children Treated for Septic Shock." N Engl J Med. Online April 24, 2026. DOI: 10.1056/NEJMoa2504747.
About Children's Hospital of Philadelphia:
A non-profit, charitable organization, Children's Hospital of Philadelphia was founded in 1855 as the nation's first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals, and pioneering major research initiatives, the hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country. The institution has a well-established history of providing advanced pediatric care close to home through its CHOP Care Network , which includes more than 50 primary care practices, specialty care and surgical centers, urgent care centers, and community hospital alliances throughout Pennsylvania and New Jersey, as well as the Middleman Family Pavilion
