Severe Pediatric Sepsis Remains Highly Prevalent Public Health Problem

Severe pediatric sepsis is a formidable challenge for critical care specialists who unfortunately see children in pediatric intensive care units (PICUs) die from body-wide inflammation and subsequent organ damage that can occur when the immune system responds to infection. Until recently, researchers had not defined the true scope of severe pediatric sepsis worldwide.

Julie Fitzgerald, MD, PhD, a pediatric intensivist, and Scott Weiss, MD, MSCE, an attending physician in Pediatric Critical Care at The Children’s Hospital of Philadelphia, led an international, multicenter prospective point prevalence study called Sepsis, Prevalence, Outcomes, and Therapies (SPROUT) to identify patients admitted to PICUs for severe sepsis and characterize the therapies that they received and their outcomes.

Previous studies that attempted to look at the epidemiology of severe pediatric sepsis used administrative databases based on billing codes or were conducted at single centers. Dr. Fitzgerald and Dr. Weiss received an overwhelmingly positive response three years ago when they approached fellow members of the broad, international Pediatric Acute Lung Injury and Sepsis Investigators Network (PALISI) with their study design. They were eager to get a clearer and bigger picture of severe sepsis that they could rely on to provide baseline data for future interventional trials to improve survival for their patients.

“When we look at our own ICUs, while mortality has gone down, it is still a lot higher than what was being reported in these administrative studies,” said Dr. Fitzgerald, who also is an assistant professor at the Perelman School of Medicine at the University of Pennsylvania. “So, in our minds, we were trying to resolve that discrepancy. We wanted to see what other ICUs’ experiences were in terms of how much sepsis they had and what their mortality rates were. We thought it was a bigger problem than maybe was being appreciated based on those administrative studies.”

They conducted SPROUT in 128 sites from 26 countries and screened a total of 6,925 patients on five days throughout 2013 and 2014. Using consensus criteria for severe pediatric sepsis, the researchers identified 569 patients. Their average age was 3, and 25 percent did not survive, which was much higher than previous administrative studies that reported mortality rates in the 5 percent to 8 percent range.

“Another key feature was the burden of pediatric severe sepsis in ICUs worldwide,” said Dr. Weiss, who also is an assistant professor of Anesthesiology, Critical Care, and Pediatrics at the Perelman School of Medicine at the University of Pennsylvania. “We found an overall prevalence of 8.2 percent, which means that your average PICU is treating at least one child with severe sepsis at any one time. So it is an incredibly common cause of pediatric critical illness, and it highlights the ongoing problem of severe sepsis.”

With these new estimates, researchers now have a better idea of how many centers and patients would be available for future interventional studies of severe pediatric sepsis. SPROUT also provided data on other outcomes measures such as multiorgan dysfunction syndrome, ventilator days, and the need for vasoactive medications. This information will facilitate better study planning, Dr. Fitzgerald said.

“SPROUT highlights the incredible collaborative spirit of the pediatric critical care community worldwide and the willingness and desire of investigators, even from relatively small sites from across the world, to participate in efforts to better understand the burden of the disease that we’re caring for and to ultimately put into place efforts to improve the care that we provide,” Dr. Weiss said.

The SPROUT study investigators’ work is especially noteworthy because they received no financial compensation for their participation. Dr. Weiss and Dr. Fitzgerald gratefully acknowledged the funding and divisional support from CHOP’s Robert Berg, MD, division chief Critical Care Medicine, and Vinay Nadkarni, MD, endowed chair of Critical Care Medicine. CHOP’s Clinical Futures also provided grant support to help develop the research database to launch the study. They also thanked Jenny Bush, clinical research study coordinator.

The senior author on the study, Neal Thomas, MD, is a leader in the PALISI network and an established clinical scientist in pediatric critical care at Hershey-Penn State. He has been supported by the CHOP Division of Critical Care Medicine to mentor junior faculty at CHOP, including Drs. Weiss and Fitzgerald.

Results from the SPROUT study appeared online in the American Journal of Respiratory and Critical Care Medicine.