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Reference: Sanchez-Pinto, L.N., et al. Development and Validation of the Phoenix Criteria for Pediatric Sepsis and Septic Shock. JAMA 2024.
Guest Skeptic: Prof. Damian Roland is a Consultant at the University of Leicester NHS Trust and Honorary Professor for the University of Leicester’s SAPPHIRE group. He specializes in Paediatric Emergency Medicine and is a passionate believer and advocate of FOAMed. Damian is also part of the Don’t Forget the Bubbles Team.
Dr. Damian Roland
Case: A 3-year-old boy arrives at the emergency department (ED) with a high fever, rapid breathing, and lethargy. His parents state that he has had a fever and cough for the past three days. He tested positive for influenza two days ago but seems to be getting worse. On exam, he has crackles in his right lung field. His pulse oximeter reads 88% on room air. His heart rate is elevated. He looks sleepy but is clinging to his parents. A medical trainee you are working with asks, “He looks really sick. Is this pneumonia or could this be sepsis?”
Background: Pediatric sepsis is a major global health concern, causing an estimated 3.3 million deaths annually. The 2005 International Pediatric Sepsis Consensus Conference (IPSCC) criteria were established based on expert consensus and used for diagnosis. However, they’ve been criticized for low specificity and not being adaptable across different resource settings.
The SGEM has covered sepsis multiple times:
- SGEM #448: More than a Feeling-Gestalt vs CDT for Predicting Sepsis
- SGEM #371: All of My Lovit, Vitamin C Won’t Work for You
- SGEM #346: Sepsis-You were Always on My Mind
- SGEM Xtra: Petition to Retire the Surviving Sepsis Campaign Guidelines
- SGEM #207: Ahh (Don’t) Push It- Pre-hospital IV Antibiotics for Sepsis
- SGEM #174: Don’t Believe the Hype – Vitamin C Cocktail for Sepsis
- SGEM #168: HYPRESS – Doesn’t got the Power
- SGEM #92: Arise Up, Arise Up (EGDT vs Usual Care for Sepsis)
- SGEM #90: Hunting High and Low (Best MAP for Sepsis Patients)
- SGEM #69: Cry Me a River (Early Goal-Directed Therapy) Process Trial
Today we’re covering the newest criteria, the Phoenix Criteria, for the diagnosis of pediatric sepsis and septic shock. It is more evidence-based and incorporates data from high and low-resource settings.
Clinical Question: How accurately can a new clinical decision rule (The Phoenix Sepsis Score) diagnose pediatric sepsis and septic shock in hospitalized children within the first 24 hours?
Reference: Sanchez-Pinto, L.N., et al. Development and Validation of the Phoenix Criteria for Pediatric Sepsis and Septic Shock. JAMA 2024.
- Population: Children less than 18 years of age with suspected sepsis and septic shock who were admitted to one of ten hospitals in five countries.
- Exclusions: Newborns and children with postconceptional age of <37 weeks
- Intervention: The Phoenix Criteria, which is a scoring system based on clinical signs, symptoms, and laboratory values.
- Comparison: International Pediatric Sepsis Consensus Conference (IPSCC) criteria
- Outcome:
- Primary Outcome: In-hospital mortality
- Secondary Outcomes: Composite of early death (within 72 hours of presentation) and requirement for extracorporeal membrane oxygenation (ECMO). For the Phoenix Scoring System, they used the area under the receiver operating characteristic curve (AUROC) and for binary criteria, positive predictive value (PPV) and sensitivity.
- Trial: Multicenter, retrospective cohort study
Dr. Elizabeth Alpern
Guest Authors: Dr. Elizabeth Alpern is a Professor of Emergency Medicine and Chief of Emergency Medicine at Lurie Children’s Hospital of Chicago and Vice Chair of Pediatrics at Northwestern University Feinberg School of Medicine. She’s also a clinical epidemiologist and expert in large databases including the PECARN registry.
Dr. Halden Scott is an Associate Professor of Pediatrics at the University of Colorado School of Medicine and an attending physician at Children’s Hospital Colorado
where she also serves as Director of Research. Her research interest includes the diagnosis and treatment of sepsis across the emergency care continuum.
Authors’ Conclusions: “The novel Phoenix sepsis criteria, which were derived and validated using data from higher- and lower-resource settings, had improved performance for the diagnosis of pediatric sepsis and septic shock compared with the existing IPSCC criteria.”
Quality Checklist for Clinical Decision Tools:
- The study population included or focused on those in the ED. Yes and No
- The patients were representative of those with the problem. Yes
- All important predictor variables and outcomes were explicitly specified. Yes
- This is a prospective, multicenter study including a broad spectrum of patients and clinicians (level II). No and Yes
- Clinicians interpret individual predictor variables and score the clinical decision rule reliably and accurately. No.
- This is an impact analysis of a previously validated CDR (level I). No
For Level I studies, the impact on clinician behavior and patient-centric outcomes is reported. No - The follow-up was sufficiently long and complete. Yes
- The effect was large enough and precise enough to be clinically significant. Yes
- Study Funding: “This work was supported by Eunice Kennedy Shriver National Institute of Child Health and Human Development grant R01HD105939 to Drs Sanchez-Pinto and Bennett. Dr Schlapbach received support from the NOMIS Foundation. The Society of Critical Care Medicine provided support to the Pediatric Sepsis Definition Task Force for travel of members, coordination of meetings, and other logistical support.”
- Conflicts of Interest: Many authors received funding from government entities and some from industry
Results: They collected data from over three million emergency departments, inpatient, and intensive care unit encounters from ten health systems in the United States, Colombia, Bangladesh, China, and Kenya.
Dr. Halden Scott
Five sites in the United States (higher-resource settings) and two sites in Bangladesh and Colombia (low-resource settings) were included in the derivation.
One site from the United States, China, and Kenya were included in the validation.
There are four main systems included in the Phoenix Sepsis Score: respiratory, cardiovascular, coagulation, and neurologic. They recommended that sepsis should be considered for any child with suspected infection and score of at least 2 points.
“Septic shock” was identified by at least 1 point in the cardiovascular component.
Key Results: The Phoenix Criteria demonstrated strong diagnostic performance, with high sensitivity and improved precision over previous sepsis criteria.
Children with suspected infection in the first 24 hours of presentation had in-hospital mortality of 0.7% in higher-resource settings and 3.6% in lower-resource settings.
Children with sepsis had a mortality of 7.1% in higher resource settings and 28.5% in lower resource settings.
Children with septic shock had a mortality of 10.8% in higher resource settings and 33.5% in lower resource settings.
The Phoenix score had a higher positive predictive value (PPV) and higher or comparable sensitivity for in-hospital mortality and early death or ECMO compared to the IPSCC definition.
Tune into the podcast to hear the authors’ responses to our questions.
Scoring Tool Development
This was a huge effort amongst a multidisciplinary group. The team reviewed many organ dysfunction scoring systems. They were run through multiple models (stacked regression, LASSO, logistic regression). The team voted through a modified Delphi process on thresholds for the score.
With such a large team and so many processes, were there any big areas of agreement or disagreement?
Chosen Criteria
The final Phoenix score focuses on four organ systems: respiratory, cardiovascular, coagulation, and neurologic. Some criteria are lab criteria which certain centers may not have or may not be able to get results in a timely fashion. We’re probably not calculating PaO2/SpO2: FiO2 ratios in the emergency department. Data on the use of lactate seems mixed. Inter-rater reliability of GCS scores can be quite variable.
How did you choose which components under each organ system to include? Some may also argue that the thresholds for lactate or GCS are also pretty lenient.
“Suspected Infection”
The inclusion of patients based on “suspicion” of sepsis might lead to selection bias, affecting generalizability.
“Suspected infection” was defined as the receipt of systemic antimicrobials or antimicrobial testing. This still creates quite a degree of subjectivity and possible variation amongst providers. Any tips about dealing with this?
Generalizability
This study used data from many institutions across the world. They had an international sample that included both high and low-resource settings. They also included children with complex healthcare needs. All of these things make the results more generalizable.
There was some missing data from one of the lower-resourced sites, and the higher-resourced sites were all tertiary children’s hospitals. When you undertake the next iteration of this project, are there plans to recruit from an even wider array of sites including more community hospitals in higher-resourced settings?
NOT a Screening Tool
An accompanying paper states:
“The Phoenix criteria for sepsis and septic shock were intended to identify life-threatening organ dysfunction due to infection in children. They were NOT designed for screening children at risk for developing sepsis or early identification of children with suspected sepsis.”
Set the record straight for us:
- Does a patient who scores a zero on the Phoenix score exclude the possibility of sepsis?
- What role do you think this study will play in the development of early sepsis identification in the future?
Comment on Authors’ Conclusion Compared to SGEM Conclusion: We agree with the authors’ conclusion.
SGEM Bottom Line: The Phoenix Sepsis score offers a new and improved evidence-based method of defining sepsis and septic shock in children.
Case Resolution: You tell the trainee that the patient looks very ill. You suspect the possibility of a superimposed bacterial pneumonia in the setting of influenza, but his sleepiness is concerning for possible sepsis. He is initially placed on BiPAP and receives empiric antibiotics, but his mental status continues to decline. He is intubated and transferred to the intensive care unit for further care.
Clinical Application:
Tune in to hear how the Phoenix criteria can be applied in the emergency department setting.
What Do I Tell My Student: This patient looks very sick. It may be pneumonia, but his ill-appearance and sleepiness make me concerned that he may also be septic. There are new criteria for sepsis and septic shock in children based on the Phoenix Sepsis Score, but it should not be used for screening. He is sick enough that we should be aggressive and treat him for presumed sepsis.
Reference: Sanchez-Pinto, L.N., et al. Development and Validation of the Phoenix Criteria for Pediatric Sepsis and Septic Shock. JAMA 2024.
Guest Skeptic: Prof. Damian Roland is a Consultant at the University of Leicester NHS Trust and Honorary Professor for the University of Leicester’s SAPPHIRE group. He specializes in Paediatric Emergency Medicine and is a passionate believer and advocate of FOAMed. Damian is also part of the Don’t Forget the Bubbles Team.
Dr. Damian Roland
Case: A 3-year-old boy arrives at the emergency department (ED) with a high fever, rapid breathing, and lethargy. His parents state that he has had a fever and cough for the past three days. He tested positive for influenza two days ago but seems to be getting worse. On exam, he has crackles in his right lung field. His pulse oximeter reads 88% on room air. His heart rate is elevated. He looks sleepy but is clinging to his parents. A medical trainee you are working with asks, “He looks really sick. Is this pneumonia or could this be sepsis?”
Background: Pediatric sepsis is a major global health concern, causing an estimated 3.3 million deaths annually. The 2005 International Pediatric Sepsis Consensus Conference (IPSCC) criteria were established based on expert consensus and used for diagnosis. However, they’ve been criticized for low specificity and not being adaptable across different resource settings.
The SGEM has covered sepsis multiple times:
- SGEM #448: More than a Feeling-Gestalt vs CDT for Predicting Sepsis
- SGEM #371: All of My Lovit, Vitamin C Won’t Work for You
- SGEM #346: Sepsis-You were Always on My Mind
- SGEM Xtra: Petition to Retire the Surviving Sepsis Campaign Guidelines
- SGEM #207: Ahh (Don’t) Push It- Pre-hospital IV Antibiotics for Sepsis
- SGEM #174: Don’t Believe the Hype – Vitamin C Cocktail for Sepsis
- SGEM #168: HYPRESS – Doesn’t got the Power
- SGEM #92: Arise Up, Arise Up (EGDT vs Usual Care for Sepsis)
- SGEM #90: Hunting High and Low (Best MAP for Sepsis Patients)
- SGEM #69: Cry Me a River (Early Goal-Directed Therapy) Process Trial
Today we’re covering the newest criteria, the Phoenix Criteria, for the diagnosis of pediatric sepsis and septic shock. It is more evidence-based and incorporates data from high and low-resource settings.
Clinical Question: How accurately can a new clinical decision rule (The Phoenix Sepsis Score) diagnose pediatric sepsis and septic shock in hospitalized children within the first 24 hours?
Reference: Sanchez-Pinto, L.N., et al. Development and Validation of the Phoenix Criteria for Pediatric Sepsis and Septic Shock. JAMA 2024.
- Population: Children less than 18 years of age with suspected sepsis and septic shock who were admitted to one of ten hospitals in five countries.
- Exclusions: Newborns and children with postconceptional age of <37 weeks
- Intervention: The Phoenix Criteria, which is a scoring system based on clinical signs, symptoms, and laboratory values.
- Comparison: International Pediatric Sepsis Consensus Conference (IPSCC) criteria
- Outcome:
- Primary Outcome: In-hospital mortality
- Secondary Outcomes: Composite of early death (within 72 hours of presentation) and requirement for extracorporeal membrane oxygenation (ECMO). For the Phoenix Scoring System, they used the area under the receiver operating characteristic curve (AUROC) and for binary criteria, positive predictive value (PPV) and sensitivity.
- Trial: Multicenter, retrospective cohort study
Dr. Elizabeth Alpern
Guest Authors: Dr. Elizabeth Alpern is a Professor of Emergency Medicine and Chief of Emergency Medicine at Lurie Children’s Hospital of Chicago and Vice Chair of Pediatrics at Northwestern University Feinberg School of Medicine. She’s also a clinical epidemiologist and expert in large databases including the PECARN registry.
Dr. Halden Scott is an Associate Professor of Pediatrics at the University of Colorado School of Medicine and an attending physician at Children’s Hospital Colorado
where she also serves as Director of Research. Her research interest includes the diagnosis and treatment of sepsis across the emergency care continuum.
Authors’ Conclusions: “The novel Phoenix sepsis criteria, which were derived and validated using data from higher- and lower-resource settings, had improved performance for the diagnosis of pediatric sepsis and septic shock compared with the existing IPSCC criteria.”
Quality Checklist for Clinical Decision Tools:
- The study population included or focused on those in the ED. Yes and No
- The patients were representative of those with the problem. Yes
- All important predictor variables and outcomes were explicitly specified. Yes
- This is a prospective, multicenter study including a broad spectrum of patients and clinicians (level II). No and Yes
- Clinicians interpret individual predictor variables and score the clinical decision rule reliably and accurately. No.
- This is an impact analysis of a previously validated CDR (level I). No
For Level I studies, the impact on clinician behavior and patient-centric outcomes is reported. No - The follow-up was sufficiently long and complete. Yes
- The effect was large enough and precise enough to be clinically significant. Yes
- Study Funding: “This work was supported by Eunice Kennedy Shriver National Institute of Child Health and Human Development grant R01HD105939 to Drs Sanchez-Pinto and Bennett. Dr Schlapbach received support from the NOMIS Foundation. The Society of Critical Care Medicine provided support to the Pediatric Sepsis Definition Task Force for travel of members, coordination of meetings, and other logistical support.”
- Conflicts of Interest: Many authors received funding from government entities and some from industry
Results: They collected data from over three million emergency departments, inpatient, and intensive care unit encounters from ten health systems in the United States, Colombia, Bangladesh, China, and Kenya.
Dr. Halden Scott
Five sites in the United States (higher-resource settings) and two sites in Bangladesh and Colombia (low-resource settings) were included in the derivation.
One site from the United States, China, and Kenya were included in the validation.
There are four main systems included in the Phoenix Sepsis Score: respiratory, cardiovascular, coagulation, and neurologic. They recommended that sepsis should be considered for any child with suspected infection and score of at least 2 points.
“Septic shock” was identified by at least 1 point in the cardiovascular component.
Key Results: The Phoenix Criteria demonstrated strong diagnostic performance, with high sensitivity and improved precision over previous sepsis criteria.
Children with suspected infection in the first 24 hours of presentation had in-hospital mortality of 0.7% in higher-resource settings and 3.6% in lower-resource settings.
Children with sepsis had a mortality of 7.1% in higher resource settings and 28.5% in lower resource settings.
Children with septic shock had a mortality of 10.8% in higher resource settings and 33.5% in lower resource settings.
The Phoenix score had a higher positive predictive value (PPV) and higher or comparable sensitivity for in-hospital mortality and early death or ECMO compared to the IPSCC definition.
Tune into the podcast to hear the authors’ responses to our questions.
Scoring Tool Development
This was a huge effort amongst a multidisciplinary group. The team reviewed many organ dysfunction scoring systems. They were run through multiple models (stacked regression, LASSO, logistic regression). The team voted through a modified Delphi process on thresholds for the score.
With such a large team and so many processes, were there any big areas of agreement or disagreement?
Chosen Criteria
The final Phoenix score focuses on four organ systems: respiratory, cardiovascular, coagulation, and neurologic. Some criteria are lab criteria which certain centers may not have or may not be able to get results in a timely fashion. We’re probably not calculating PaO2/SpO2: FiO2 ratios in the emergency department. Data on the use of lactate seems mixed. Inter-rater reliability of GCS scores can be quite variable.
How did you choose which components under each organ system to include? Some may also argue that the thresholds for lactate or GCS are also pretty lenient.
“Suspected Infection”
The inclusion of patients based on “suspicion” of sepsis might lead to selection bias, affecting generalizability.
“Suspected infection” was defined as the receipt of systemic antimicrobials or antimicrobial testing. This still creates quite a degree of subjectivity and possible variation amongst providers. Any tips about dealing with this?
Generalizability
This study used data from many institutions across the world. They had an international sample that included both high and low-resource settings. They also included children with complex healthcare needs. All of these things make the results more generalizable.
There was some missing data from one of the lower-resourced sites, and the higher-resourced sites were all tertiary children’s hospitals. When you undertake the next iteration of this project, are there plans to recruit from an even wider array of sites including more community hospitals in higher-resourced settings?
NOT a Screening Tool
An accompanying paper states:
“The Phoenix criteria for sepsis and septic shock were intended to identify life-threatening organ dysfunction due to infection in children. They were NOT designed for screening children at risk for developing sepsis or early identification of children with suspected sepsis.”
Set the record straight for us:
- Does a patient who scores a zero on the Phoenix score exclude the possibility of sepsis?
- What role do you think this study will play in the development of early sepsis identification in the future?
Comment on Authors’ Conclusion Compared to SGEM Conclusion: We agree with the authors’ conclusion.
SGEM Bottom Line: The Phoenix Sepsis score offers a new and improved evidence-based method of defining sepsis and septic shock in children.
Case Resolution: You tell the trainee that the patient looks very ill. You suspect the possibility of a superimposed bacterial pneumonia in the setting of influenza, but his sleepiness is concerning for possible sepsis. He is initially placed on BiPAP and receives empiric antibiotics, but his mental status continues to decline. He is intubated and transferred to the intensive care unit for further care.
Clinical Application:
Tune in to hear how the Phoenix criteria can be applied in the emergency department setting.
What Do I Tell My Student: This patient looks very sick. It may be pneumonia, but his ill-appearance and sleepiness make me concerned that he may also be septic. There are new criteria for sepsis and septic shock in children based on the Phoenix Sepsis Score, but it should not be used for screening. He is sick enough that we should be aggressive and treat him for presumed sepsis.
