A large study led by researchers at Children’s Hospital of Philadelphia, Nemours Children’s Health Hospital, and Children’s National Hospital, and involving a broad network of medical centers across the United States and abroad, found that different types of crystalloid resuscitation were equally effective in preventing the most serious kidney adverse events after treatment of pediatric patients with suspected septic shock. The results of this large-scale clinical trial are detailed in a study published today. New England Medical Journal and presented at the Pediatric Society of America (PAS) conference in Boston.
Sepsis is a life-threatening reaction to infection that causes organ failure. The combination of the body’s immune system and infection can cause an abnormal response that interferes with the normal functioning of various organ systems. It is estimated that the disease sends more than 18,000 children to the hospital each year nationwide. Decades of research and improved clinical care have significantly improved outcomes for pediatric sepsis patients, but nationally, approximately 1 in 10 children with sepsis or septic shock remains at risk of death.
In several previous multicenter studies, researchers found that critically ill adults who received balanced crystalloids, an intravenous (IV) treatment intended to exhibit properties similar to human plasma, had a lower risk of complications and death than those given standard 0.9% saline IV. This led researchers to consider whether similar studies could determine whether certain fluid treatments are better for pediatric sepsis patients.
We knew we would need thousands of patients to answer this question, and we knew it would be difficult. Still, these fluids are cheap and universally available around the world, so we were excited to move forward with our research. That meant we didn’t have to wait decades to take action once our research was complete. We are realistic and can take immediate action based on the results we find. ”
Fran Balamuth, MD, PhD, Co-author, Principal Investigator, CHOP Emergency Medicine Director
Because cases of suspected sepsis are rare in the general population, Balamus, co-lead author Scott L. Weiss, MD, attending physician and chief of critical care at Nemours Children’s Hospital in Delaware, and colleagues required the collaboration of many hospitals to achieve the data standards needed for meaningful conclusions. To this end, they collaborated with senior author Nathan Kupperman, M.D., executive vice president and chief academic officer at Children’s National Hospital and director of the Children’s National Institute, who has a history of conducting successful clinical trials in acutely ill children.
“This trial demonstrates the power of large collaborative research networks to answer important clinical questions for children,” Kupperman said. “By enrolling thousands of patients in multiple countries, we were able to provide clinicians with the evidence they need to guide the treatment of children with suspected septic shock.”
In the United States, the team utilized the Pediatric Emergency Care Applied Research Network (PECARN). PECARN is a group of 18 hospitals nationwide that make up a multicenter network for research in pediatric emergency medicine as part of the federal government’s Pediatric Emergency Medical Services Program. Collaborating institutions in Canada, Australia, New Zealand, and Costa Rica also contributed data. Ultimately, a total of 47 emergency departments in five countries participated in the study, enrolling more than 9,000 patients who received balanced fluids or 0.9% saline.
The primary outcome of this study was major adverse renal events up to 30 days (MAKE30), with the key outcome being renal damage resulting in death, new renal replacement therapy, or persistent renal impairment. The researchers found that MAKE30 occurred in 3.4% of patients enrolled in the balanced fluid group, and in 3.0% of patients in the 0.9% salt intake group. The study found biochemical differences in children treated with the two infusions, including more frequently elevated blood chloride levels in the 0.9% saline group and higher lactate levels in the balanced infusion group. Median hospital-free days between the two groups were 23 and 28 days, and there were no differences in mortality, other safety outcomes, or adverse events.
“This study confirms that either balanced fluids or 0.9% saline are effective and safe for the initial resuscitation of children with suspected septic shock,” said Weiss, attending physician and director of critical care at Nemours Children’s Hospital in Delaware. “It also confirms that fluid strategies that reduce hyperchloremia do not necessarily lead to improved patient outcomes.” “We also did not identify differences between subgroups. However, it is important to note that despite the large number of participants, we cannot rule out the possibility that one or the other fluid may be beneficial in the subset of children with the most severe disease.”
“Large trials like this definitively answer questions that we have had in this field for many years,” Balamus said. “If a child presents to the emergency department with suspected sepsis, they can be treated with any readily available fluid. We think this is great news for children around the world.”
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Children’s Hospital of Philadelphia
Reference magazines:
Musunuru, K. Others. (2025). Patient-specific in vivo gene editing to treat rare genetic diseases. New England Medical Journal. DOI: 10.1056/NEJMoa2504747. https://www.nejm.org/doi/10.1056/NEJMoa2504747
