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Transitioning From SIRS to Phoenix With the Updated Pediatric Sepsis

Criteria:The Difficult Task of Simplifying the Complex

Article in Journal of the American Medical Association · January 2024

DOI: 10.1001/jama.2023.27988

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EDITORIAL
Transitioning From SIRS to Phoenix With the Updated
Pediatric Sepsis Criteria
The Difficult Task of Simplifying the Complex
Roberto Jabornisky, MD, PhD; Nathan Kuppermann, MD, MPH; Sebastián González-Dambrauskas, MD
Everyone must acknowledge the difficulty of distinguishing
diseases…whoever denies this may as well deny that there is such
a thing as medical art.
William Cullen1
Diagnosis as a Social Construct in Medicine
The art of making a diagnosis is essential to high-quality
medical practice and is arguably the most valuable skill of a
health care practitioner. Diagnosis serves as the articulation
of the language of medical
science, guiding medical
Editorial practice at every clinical en-
counter and through health
Related articles
policy.1 Developing medical
knowledge entails a social
construct rooted in the prevailing medical framework, ethi-
cal perspectives, and the socialization of these ideas among
physicians. For medical knowledge to evolve, there must be
an interaction between a condition’s definition and its scien-
tific identification. This framework is shaped by how these
elements interact and how the definition of a condition is
configured.2
Medical science has been driven to establish boundaries
defining the start of illnesses, although this frequently sim-
plifies complex biological phenomena. The trade-off
between sensitivity and specificity unfolds in the face of this
complexity and is particularly acute for syndromes such as
sepsis. In the face of these challenges, we discuss the new
diagnostic paradigm for pediatric sepsis published in this
issue of JAMA.3
The Transition From SIRS to the Phoenix Criteria
Pediatricians commonly rely on sepsis definitions estab-
lished in 2005. 4 These definitions were based on expert
opinions from physicians in high-resource settings and
depend on the identification of an infection-induced sys-
temic inflammatory response syndrome (SIRS).4 Introduction
of adult Sepsis-3 definitions in 2016 marked a shift in the
conceptual framework from infection-associated SIRS to
infection-associated organ dysfunction. 5 In response to
emerging data indicating that SIRS criteria in children lacked
specificity for identifying those at higher risk of mortality,6
the pediatric sepsis research community took action. In 2019,
a task force of 35 pediatric sepsis experts from 12 countries
on 6 continents to develop updated operational definitions
was convened.3
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Opinion
Unlike the creation of previous criteria, these investiga-
tors developed a 3-pronged data-driven approach, which
included a global survey,7 a meta-analysis,8 and the devel-
opment of a new organ dysfunction scoring system. Consis-
tent with adult Sepsis-3,5 the task force considered that the
existing sepsis definitions did not meet clinicians’ needs
and suggested that definitions focusing on organ dysfunc-
tion would be more pertinent.3 The subsequent research
phase led to the creation of the Phoenix Sepsis Score.9 This
score was developed using robust multivariable regression
techniques to derive and validate a composite model using
organ dysfunction measures from electronic health data in
10 health systems across 5 countries, including high- and
low-resource settings.9 This involved complex data harmo-
nization across many different large electronic databases
encompassing more than 3.6 million pediatric encounters.
The primary objective was to identify and validate factors
associated with in-hospital mortality in children with sep-
sis, with the positive predictive value and sensitivity serv-
ing as the primary performance measures. The task force
then established novel pediatric sepsis definitions following
a modified Delphi process.
The Phoenix Pediatric Sepsis Criteria
The updated pediatric sepsis definition is now operational-
ized by 2 or more points in the Phoenix Sepsis Score (indicat-
ing life-threatening organ dysfunction of the respiratory,
cardiovascular, coagulation, and/or neurologic systems) in a
child with suspected or confirmed infection.3 Septic shock is
operationalized by the presence of sepsis in addition to 1 or
more points in the cardiovascular component of the Phoenix
Sepsis Score (ie, severe hypotension, blood lactate >5 mmol/L,
or vasoactive medication infusion). 3 These criteria per-
formed better than previous criteria across differently re-
sourced settings. A substantial change in the newly proposed
criteria is the removal of SIRS as a diagnostic factor. This adds
clarity and minimizes confusion, particularly in the emer-
gency department setting, where many febrile children who
do not have sepsis meet SIRS criteria (eg, febrile infants with
bronchiolitis who have tachycardia and tachypnea). Addition-
ally, the distinction of severe sepsis as a separate condition has
been eliminated, as the term is redundant with sepsis. Con-
sidering the worldwide implications of this change, it is im-
portant to acknowledge the challenges that will be encoun-
tered in adoption by the global pediatric community, especially
in low-resource settings.
(Reprinted) JAMA Published online January 21, 2024 E1
 Opinion Editorial

The task force deserves commendation for incorporating
the input of professionals from low-resource settings and for
validating the Phoenix Sepsis Score by creating an extensive
database that included hospitals in these settings, where the
greatest burden of sepsis occurs. 10 The disproportionate
impact was confirmed in the validation cohort, in which chil-
dren with sepsis had a 7.1% mortality rate in high-resource
settings and a 28.5% rate in low-resource settings.9 Those
with septic shock in the first 24 hours had a 10.8% mortality
rate at the former sites and a 33.5% mortality rate at the latter
sites.9 The new criteria demonstrated a higher positive pre-
dictive value and comparable or higher sensitivity to the
previous criteria for sepsis, severe sepsis, and septic shock.
However, only 3.1% of the cohort used to validate the score
came from low-resource settings, limiting its precision. 9
Notably, the Phoenix Sepsis Score demonstrated lower sensi-
tivity compared with previous criteria (23% vs 77%) at 1
lower-resource site,9 further underscoring the need for addi-
tional study before implementing the Phoenix Sepsis Score
broadly in lower-resource settings.
Furthermore, the global survey that served as the start-
ing point7 for developing this score reflected the perceptions
of physicians primarily working in hospital settings, particu-
larly in pediatric intensive care units (PICUs) (57%), with only
15% based in emergency departments. Moreover, all the low-
resource validation sites were institutions with electronic
health records and most had PICUs, which does not ad-
equately reflect conditions in most low-resource settings. These
factors introduce a distinct bias favoring a “PICU-based
consensus,” potentially limiting the generalizability and
adoption of the new criteria by health care practitioners in
non-PICU and nonhospital settings responsible for recogniz-
ing and managing children with sepsis. The authors also ac-
knowledge an additional barrier, the requirement for serum
lactate measurement and coagulation parameters in the score.
These laboratory tests are not readily available in many low-
resource settings,7 although it is noteworthy that the Phoenix
score performed well even in centers where lactate informa-
tion was not available.
It is important to recognize that the Phoenix Sepsis Score
was not designed as a screening tool for sepsis and should not
be misconstrued as an early warning tool or a sepsis test. The
purpose of the Phoenix Sepsis Score is to assist clinicians in
identifying children with both infection and life-threatening
organ dysfunction. The score was not designed to predict which
children are at risk of developing sepsis. As the authors have
stated, “The new pediatric sepsis criteria for sepsis and septic
shock are intended to operationalize the concept of life-
threatening organ dysfunction due to an infection in chil-
dren, not for screening or early identification of patients with
suspected sepsis.”3 Awareness of this more limited focus is criti-
cal for those who practice outside of the PICU setting.
Finally, the investigators did not eliminate the most sub-
jective part of the diagnostic pathway in sepsis which is the
“suspected infection” criteria. Clinicians seeking to imple-
ment these criteria must take this important aspect into con-
sideration when managing children with suspected sepsis.
Global Challenges of the Phoenix Sepsis Criteria
for Research and Clinical Practice
A clinically satisfactory definition of sepsis has been elusive
since the term was first coined by the ancient Greeks. 11
Reconceptualizing sepsis based on the enhanced compre-
hension of its nature and complexity and identifying it as
the pivotal juncture when an infection escalates into a life-
threatening condition was a bold, complex, and imperative
undertaking for which the authors should be praised. Iden-
tifying the moment when the immune system begins to
deregulate is a critical issue, along with whether clinicians
should wait for a patient to present with organ dysfunction
to diagnose sepsis. Given the higher mortality in lower-
resource settings, are other clinical criteria needed in these
settings for earlier detection?
This important work introduces novel challenges for imple-
mentation, requiring substantial further investigation to as-
certain whether these revised definitions result in improved
patient care. These criteria must be further validated in a pro-
spective manner, in differently resourced and varied set-
tings, particularly those with the highest disease burden.
Until then, it is essential to refrain from considering these
criteria as an inflexible directive governing medical interven-
tions for pediatric sepsis. No definition can fully substitute for
the clinical judgment of an experienced, vigilant clinician car-
ing for an unwell child. We commend the Pediatric Sepsis
Definition Task Force for their outstanding work, marking a
substantial advance in the approach to pediatric sepsis. Nev-
ertheless, recognizing that sepsis is a complex process, the jour-
ney ahead remains expansive. Dismissing the notion of
“simple” sepsis, we anticipate ongoing dialogues among cli-
nicians and researchers worldwide to further refine this up-
dated conceptual framework. The departure from the widely
adopted SIRS paradigm over the past 2 decades poses an im-
portant change yet a formidable challenge, as cultural shifts
in medicine are inherently arduous.

ARTICLE INFORMATION Unidad de Cuidados Intensivos de Niños del Centro REFERENCES

Author Affiliations: Department of Women,
Children, and Adolescents, Faculty of Medicine,
National University of the Northeast, Corrientes,
Argentina (Jabornisky); Red Colaborativa Pediátrica
de Latinoamérica (LARed Network), Montevideo,
Uruguay (Jabornisky, González-Dambrauskas);
Departments of Emergency Medicine and
Pediatrics, UC Davis School of Medicine and UC
Davis Health, Sacramento, California
(Kuppermann); Departamento de Pediatría y
Hospitalario Pereira Rossell, Facultad de Medicina,
Universidad de la República, Montevideo, Uruguay
(González-Dambrauskas).
Corresponding Author: Roberto Jabornisky, MD,
PhD, Universidad Nacional del Nordeste Facultad
de Medicina, 1240 Moreno, Corrientes 3400,
Argentina (rjabornisky@gmail.com).
Published Online: January 21, 2024.
doi:10.1001/jama.2023.27988
Conflict of Interest Disclosures: None reported.
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