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PHOENIX -- The novel Phoenix sepsis criteria, created by the Society of Critical Care Medicine (SCCM) Pediatric Sepsis Definition Task Force, improved diagnosis of pediatric sepsis and septic shock compared with existing criteria from 2005, a retrospective cohort study showed.

Among nearly 173,000 kids with suspected infection in the first 24 hours of an emergency and inpatient encounter, the integer version of the four-organ model Phoenix Sepsis Score had area under the precision recall curves of 0.23 to 0.38 (95% CI range 0.20-0.39) and area under the receiver operating characteristic curves of 0.71 to 0.92 (95% CI range 0.70-0.92) to predict mortality in the validation sets, reported Mark Hall, MD, of Nationwide Children's Hospital in Columbus, Ohio.

Hall and several other members of the task force presented the findings at the SCCM Critical Care Congress, and the new criteria were simultaneously published in .

The four-organ system model includes criteria for respiratory (mechanical ventilation, Pa0₂:Fi0₂, and Sp0₂:Fi0₂ ratios), cardiovascular (mean arterial pressure, lactate level, and vasoactive medications), coagulation (platelet count, international normalized ratio, D-dimer, and fibrinogen), and neurologic (Glasgow Coma Scale and pupillary reaction) dysfunction.

The task force ultimately adopted "an infection with life-threatening organ dysfunction" as a conceptual definition for sepsis.

During the presentation, Hall explained that previous sepsis criteria were simply not enough for providers on several levels.

"The currently used sepsis definitions that we've heard about ... were largely developed by consensus, were not data driven, were not developed with a broad resource availability in mind," he said. "We think about sepsis as defined by these definitions, and it applies to many, many patients on the regular ward who do not have life-threatening disease."

In their study, the task force members wrote that "new pediatric sepsis criteria should maximize identification of true-positive cases so that infected children with life-threatening organ dysfunction receive best-practice sepsis care, are appropriately enrolled in clinical studies, and are correctly represented in epidemiological surveillance."

"Simultaneously, new criteria must minimize false-positive cases so that children are not misdiagnosed with sepsis," they added. "This is important to reduce unnecessary use of antimicrobials and other treatments, optimize the efficiency of clinical studies, and avoid overcounting in surveillance."

Using a Phoenix Sepsis Score of 2 points or higher for children with suspected infection as criteria for sepsis and sepsis plus 1 or more cardiovascular points as criteria for septic shock resulted in a higher positive predictive value and better or similar sensitivity compared with the 2005 International Pediatric Sepsis Consensus Conference (IPSCC) criteria across 10 health systems in five differently resourced countries.

For example, for the primary outcome of death at the higher-resource sites, the Phoenix sepsis criteria had a positive predictive value of 5.3% to 7.1% (with a baseline mortality of 0.6% to 0.7%) and a sensitivity of 69.2% to 84.4% compared with the IPSCC severe sepsis criteria, which had a positive predictive value of 3.6% to 4.8% and a sensitivity of 58.7% to 70.7%, in the development and external validation sets, respectively.

For those curious, the criteria were symbolically named in reference to the mythological phoenix, but also for the location of this year's SCCM Congress where the criteria were unveiled.

indicated that patients with a Phoenix score of 2 or higher had an in-hospital mortality rate of 7.1% in higher-resource settings and 28.5% in lower-resource settings, more than eight times that of those with suspected infection not meeting these criteria.

Patients experiencing organ dysfunction in at least one of the four organ systems had higher mortality.

Patients who were in septic shock as defined by the Phoenix criteria had in-hospital mortality rates of 10.8% in higher-resource settings and 33.5% in lower-resource settings.

However, in an , Roberto Jabornisky, MD, PhD, of the National University of the Northeast in Corrientes, Argentina, and co-authors urged caution before taking up more widespread adoption of the Phoenix criteria.

"This important work introduces novel challenges for implementation, requiring substantial further investigation to ascertain whether these revised definitions result in improved patient care," the editorialists wrote. "These criteria must be further validated in a prospective manner, in differently resourced and varied settings, particularly those with the highest disease burden."

"Until then, it is essential to refrain from considering these criteria as an inflexible directive governing medical interventions for pediatric sepsis," they continued. "No definition can fully substitute for the clinical judgment of an experienced, vigilant clinician caring for an unwell child."

But presenter Enitan Carrol, MBChB, MD, of the University of Liverpool in England, noted that the Phoenix criteria can be somewhat malleable based on where they are applied, adding that "context is everything."

"These criteria must be applicable across all global settings," she said. "So they need to be sensitive enough -- and we see that in the data presented -- but also specific enough. It needs to be flexible enough, and we see the pragmatic approach that was taken with the development of the score, including the redundancy that's built into the score, as well as a parsimonious approach, which allows for that flexibility and adaptability across global settings."

Task force member Halden Scott, MD, of the University of Colorado School of Medicine in Aurora, echoed this sentiment during a Q&A session, noting that "these criteria are sufficient, but not necessary to require and benefit from sepsis treatment. There are many children outside of these criteria who should be treated ... for early sepsis. We've never had a good name for that."

In a second , Hallie Prescott, MD, MSc, of the University of Michigan in Ann Arbor, and co-authors described the organ dysfunction criteria as "both data driven and pragmatic." While they said that there are still important factors to consider in the diagnosis of sepsis, such as further research using a full 8-organ system, the impacts of the new criteria will be felt globally.

"This sepsis definition is supported by a robust body of research, inclusive of diverse geographic and resource settings. These new definitions and shared conceptual understanding of pediatric sepsis will support improvements in the management, research, and outcomes of children with sepsis worldwide," wrote Prescott and her fellow co-editorialists.

The multicenter retrospective cohort study included more than 3.6 million pediatric emergency and inpatient encounters from 2010 to 2019 across 10 health systems in the U.S., Colombia, Bangladesh, China, and Kenya, three of which were used as external validation sites. About 6% of patients experienced suspected infection within the first 24 hours. Of the patients suspected to have infection, 1.2% died.

Analysis showed that IPSCC criteria had area under the precision recall curves of 0.13 to 0.27 (95% CI range 0.13-0.28) and area under the receiver operating characteristic curves of 0.76 to 0.91 (95% CI range 0.74-0.92) to predict mortality in the validation sets.

The researchers acknowledged that "some of the organ dysfunction measures used in the modeling process may not have reflected actual organ dysfunction, but rather were due to iatrogenic effects or clinician therapeutic choices, such as a lower Glasgow Coma Scale score in a patient receiving sedation or initiation of vasoactive medications in a patient with minimal cardiovascular dysfunction."

"Future work to determine the effects of these variables and clinician choices on the performance of the criteria is needed," they wrote.