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 in the United States and abroad, found that different types of CSF resuscitation were equally effective in preventing the most serious adverse events after treatment of suspected renal shock. The findings of this large clinical trial are detailed today in a study published by The New England Journal of Medicine and 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 functioning normally. The disease is estimated to send more than 18,000 children across the country to hospitals each year. While decades of research and improvements in clinical care have greatly improved outcomes for pediatric patients with sepsis, about 1 in 10 children nationwide with sepsis or septic shock is still at risk of death.
In some previous multicenter studies, researchers found that critically ill adults who received balanced crystalloid fluid—an intravenous (IV) treatment intended to exhibit similar properties to human plasma—had a lower risk of complications and death compared to a standard IV solution of 0.9% saline. This prompted the researchers to investigate whether a similar study could determine whether a fluid therapy was superior for pediatric sepsis patients.
We knew we would need thousands of patients to answer this question, which we knew would be a challenge. However, we were excited to move forward because these fluids are cheap and universally available around the world, meaning we wouldn’t have to wait decades to take action once the study was complete. we could be realistic and take immediate action based on the results we found.”
Fran Balamuth, MD, PhD, co-lead author, attending physician and Director of Emergency Medicine at CHOP
Because suspected cases of sepsis are uncommon in the general population, Balamuth, co-lead author Scott L. Weiss, MD, an attending physician and director of critical care at Nemours Children’s Hospital, Delaware, and their colleagues sought a multi-hospital collaboration 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 track record of successful clinical trials in acutely ill children and served as 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 in many countries, we have been able to provide the evidence clinicians need to guide the care of children with suspected septic shock.”
In the United States, the team used the Pediatric Emergency Care Applied Research Network (PECARN), a group of 18 hospitals across the country that form a multi-institutional network for research in pediatric emergency medicine as part of the federal Emergency Medical Services for Children program. Collaborating institutions in Canada, Australia, New Zealand, and Costa Rica also contributed data. In the end, a total of 47 emergency departments in five countries were represented in the study, with more than 9,000 patients receiving either balanced fluid or 0.9% saline.
The primary outcome of the study was Major Adverse Renal Events at 30 days (MAKE30), an important outcome for kidney damage responsible for death, new renal replacement therapy or persistent renal dysfunction. The researchers found that MAKE30 appeared in 3.4% of patients in the balanced fluid group and in 3.0% in the 0.9% saline group. The study found biochemical differences in children treated with the two fluids, including a higher incidence of elevated blood chloride levels in the 0.9% saline group and higher lactate levels in the balanced fluid group. Both groups had an average of 23 hospital-free days out 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 is 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 into improved patient outcomes,” said Weiss, MD and Director of Critical Care at Nemours. “We also found no differences between subgroups. However, despite the large number of participants, it is important to note that we cannot rule out the possibility of benefit of one or the other fluid in a subset of children with more severe disease.”
“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 whatever fluid is readily available. And we think that’s great news for children around the world.”
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