The Modified Clinical Progression Scale for Pediatric Patients: Evaluation as a Severity Metric and Outcome Measure in Severe Acute Viral Respiratory Illness

Shannon B Leland; Steven J Staffa; Margaret M Newhams; Robinder G Khemani; John C Marshall; Cameron C Young; Aline B Maddux; Mark W Hall; Scott L Weiss; Adam J Schwarz; Bria M Coates; Ronald C Sanders Jr; Michele Kong; Neal J Thomas; Ryan A Nofziger; Melissa L Cullimore; Natasha B Halasa; Laura L Loftis; Natalie Z Cvijanovich; Jennifer E Schuster; Heidi Flori; Shira J Gertz; Janet R Hume; Samantha M Olson; Manish M Patel; David Zurakowski; Adrienne G Randolph; Pediatric Acute Lung and Sepsis Investigator’s Network Pediatric Intensive Care Influenza Study Group (PALISI PICFLU) Investigators and Overcoming COVID-19 Investigators

doi:10.1097/PCC.0000000000003331

The Modified Clinical Progression Scale for Pediatric Patients: Evaluation as a Severity Metric and Outcome Measure in Severe Acute Viral Respiratory Illness

Pediatr Crit Care Med. 2023 Dec 1;24(12):998-1009. doi: 10.1097/PCC.0000000000003331. Epub 2023 Aug 4.

Authors

Shannon B Leland^{1

2}, Steven J Staffa¹, Margaret M Newhams¹, Robinder G Khemani^{3

4}, John C Marshall⁵, Cameron C Young¹, Aline B Maddux⁶, Mark W Hall⁷, Scott L Weiss⁸, Adam J Schwarz⁹, Bria M Coates¹⁰, Ronald C Sanders Jr¹¹, Michele Kong¹², Neal J Thomas¹³, Ryan A Nofziger¹⁴, Melissa L Cullimore¹⁵, Natasha B Halasa¹⁶, Laura L Loftis¹⁷, Natalie Z Cvijanovich¹⁸, Jennifer E Schuster¹⁹, Heidi Flori²⁰, Shira J Gertz²¹, Janet R Hume²², Samantha M Olson²³, Manish M Patel²³, David Zurakowski^{1

2}, Adrienne G Randolph^{1

2}; Pediatric Acute Lung and Sepsis Investigator’s Network Pediatric Intensive Care Influenza Study Group (PALISI PICFLU) Investigators and Overcoming COVID-19 Investigators

Affiliations

¹ Department of Anesthesiology, Critical Care, and Pain Medicine, Boston Children's Hospital, Boston, MA.
² Department of Anaesthesia, Harvard Medical School, Boston, MA.
³ Department of Anesthesiology and Critical Care Medicine, Children's Hospital Los Angeles, Los Angeles, CA.
⁴ Department of Pediatrics, University of Southern California, Keck School of Medicine, Los Angeles, CA.
⁵ Department of Surgery, Li Ka Shing Knowledge Institute, St Michael's Hospital, University of Toronto, Toronto, ON, Canada.
⁶ Department of Pediatrics, Section of Critical Care Medicine, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO.
⁷ Division of Critical Care Medicine, Department of Pediatrics, Nationwide Children's Hospital, Columbus, OH.
⁸ Division of Critical Care, Department of Anesthesiology and Critical Care, The University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
⁹ Division of Critical Care Medicine, Children's Hospital Orange County (CHOC), Orange, CA.
¹⁰ Division of Critical Care Medicine, Department of Pediatrics, Northwestern University Feinberg School of Medicine, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL.
¹¹ Section of Pediatric Critical Care, Department of Pediatrics, Arkansas Children's Hospital, Little Rock, AR.
¹² Division of Pediatric Critical Care Medicine, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL.
¹³ Department of Pediatrics, Penn State Hershey Children's Hospital, Penn State University College of Medicine, Hershey, PA.
¹⁴ Division of Critical Care Medicine, Department of Pediatrics, Akron Children's Hospital, Akron, OH.
¹⁵ Division of Pediatric Critical Care, Department of Pediatrics, Children's Hospital and Medical Center, Omaha, NE.
¹⁶ Division of Pediatric Infectious Diseases, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN.
¹⁷ Section of Critical Care Medicine, Department of Pediatrics, Texas Children's Hospital, Houston, TX.
¹⁸ Division of Critical Care Medicine, UCSF Benioff Children's Hospital Oakland, Oakland, CA.
¹⁹ Division of Pediatric Infectious Disease, Department of Pediatrics, Children's Mercy Kansas City, Kansas City, MO.
²⁰ Division of Pediatric Critical Care Medicine, Department of Pediatrics, Mott Children's Hospital and University of Michigan, Ann Arbor, MI.
²¹ Division of Pediatric Critical Care, Department of Pediatrics, Cooperman Barnabas Medical Center, Livingston, NJ.
²² Division of Pediatric Critical Care, University of Minnesota Masonic Children's Hospital, Minneapolis, MN.
²³ Influenza Division and CDC COVID-19 Response Team, Centers for Disease Control of Prevention, National Center for Immunization and Respiratory Diseases (NCIRD), Atlanta, GA.

Abstract

Objectives: To develop, evaluate, and explore the use of a pediatric ordinal score as a potential clinical trial outcome metric in children hospitalized with acute hypoxic respiratory failure caused by viral respiratory infections.

Design: We modified the World Health Organization Clinical Progression Scale for pediatric patients (CPS-Ped) and assigned CPS-Ped at admission, days 2-4, 7, and 14. We identified predictors of clinical improvement (day 14 CPS-Ped ≤ 2 or a three-point decrease) using competing risks regression and compared clinical improvement to hospital length of stay (LOS) and ventilator-free days. We estimated sample sizes (80% power) to detect a 15% clinical improvement.

Setting: North American pediatric hospitals.

Patients: Three cohorts of pediatric patients with acute hypoxic respiratory failure receiving intensive care: two influenza (pediatric intensive care influenza [PICFLU], n = 263, 31 sites; PICFLU vaccine effectiveness [PICFLU-VE], n = 143, 17 sites) and one COVID-19 ( n = 237, 47 sites).

Interventions: None.

Measurements and main results: Invasive mechanical ventilation rates were 71.4%, 32.9%, and 37.1% for PICFLU, PICFLU-VE, and COVID-19 with less than 5% mortality for all three cohorts. Maximum CPS-Ped (0 = home at respiratory baseline to 8 = death) was positively associated with hospital LOS ( p < 0.001, all cohorts). Across the three cohorts, many patients' CPS-Ped worsened after admission (39%, 18%, and 49%), with some patients progressing to invasive mechanical ventilation or death (19%, 11%, and 17%). Despite this, greater than 76% of patients across cohorts clinically improved by day 14. Estimated sample sizes per group using CPS-Ped to detect a percentage increase in clinical improvement were feasible (influenza 15%, n = 142; 10%, n = 225; COVID-19, 15% n = 208) compared with mortality ( n > 21,000, all), and ventilator-free days (influenza 15%, n = 167).

Conclusions: The CPS-Ped can be used to describe the time course of illness and threshold for clinical improvement in hospitalized children and adolescents with acute respiratory failure from viral infections. This outcome measure could feasibly be used in clinical trials to evaluate in-hospital recovery.

MeSH terms

Adolescent
COVID-19* / therapy
Child
Disease Progression
Humans
Influenza, Human* / complications
Influenza, Human* / diagnosis
Influenza, Human* / therapy
Outcome Assessment, Health Care
Respiration, Artificial
Respiratory Distress Syndrome*
Respiratory Insufficiency* / etiology
Respiratory Insufficiency* / therapy
SARS-CoV-2

Abstract

MeSH terms

Grants and funding