Supplemental Digital Content for:
“A Simple and Robust Bedside Model for Mortality Risk in Pediatric Patients with ARDS”
Aaron C Spicer MD, MAS1; Carolyn S Calfee MD, MAS2; Matt S Zinter, MD3,8; Robinder G Khemani MD, MsCI4; Victoria P Lo BS5; Mustafa F Alkhouli BA3; Benjamin Orwoll MD3,8; Ana L Graciano MD6; Juan P Boriosi MD7; James P Howard MD, PhD8; Heidi R Flori MD8; Michael A Matthay MD2; Anil Sapru MD, MAS3
Supplemental Methods
Calculated variables evaluated for associations with mortality included the modified lung injury score1, exhaled tidal volume, 24 Hour Pediatric Risk of Mortality (PRISM) III2, Pediatric Logistic Organ Dysfunction score (PELOD)3,4, daily PELOD5, cumulative fluid balance since meeting ARDS criteria, PaO2/FiO2 (P/F) ratio, oxygenation index [mean airway pressure/(P/F ratio) x 100], and dynamic compliance of the respiratory system (tidal volume/(Peak Inspiratory Pressure – PEEP)6.
Tidal volume was standardized to body weight in intubated, conventionally mechanically ventilated subjects, using end-tidal returned volumes. If returned tidal volumes were not available, delivered volumes were utilized.
PRISM III utilizes the worst values of 17 physiologically-based parameters from the first 24 hours of intensive care to quantify severity of illness. Probability of death can be estimated from raw PRISM III through a proprietary formula which includes other risk factors such as cancer-related admission2. We evaluated the raw PRISM III score specifically to enable evaluation of cancer/HSCT history separately.
PELOD quantifies the worst organ dysfunction accumulated over the duration of intensive care and was designed as a surrogate outcome measure3,4. We used a daily PELOD as a surrogate for organ failure on the day of interest5. In order to evaluate the prognostic value of extrapulmonary organ dysfunction independent of lung disease, we removed the respiratory parameters from the PELOD score7,8.
Fluid balance since meeting ARDS criteria was standardized to body surface area to account for the differing sizes of critically ill children9.
For patients receiving nasal cannula, fraction of inspired oxygen was calculated according to the American Association of Respiratory Care guidelines10. For those subjects without arterial blood gas data, predicted P/F was calculated using the saturation/FiO2 ratio11. Tidal volume and dynamic compliance of the respiratory system were evaluated only in intubated, conventionally mechanically ventilated subjects. Oxygenation index was evaluated only in intubated patients.
Past medical history was grouped by involved organ system or etiology as recorded from the medical record by site investigators. Each noted involved organ system was included, as was the etiology if noted; for example, a patient with Trisomy 21, congenital heart disease and scoliosis would be categorized as having genetic, cardiovascular and muscular/neuromuscular conditions.
Supplemental Tables and Additional Outcomes
eTable1: Past Medical History and Associations with Mortality
Past Medical History / Survivors (n=257) / Non-Survivors (n=51) / p-valueNeurologic / 14% / 18% / 0.55
Respiratory / 14% / 14% / 0.9
Genetic / 11% / 16% / 0.33
Cancer / 7% / 31% / <0.001
Gastrointestinal/Nutritional / 10% / 16% / 0.25
Hematopoietic Stem Cell Transplant / 4% / 31% / <0.001
Benign Hematologic / 6% / 12% / 0.13
Cardiovascular / 6% / 6% / 0.93
Muscular/Neuromuscular / 6% / 2% / 0.26
Autoimmune/Inflammatory / 4% / 10% / 0.07
Renal / 4% / 6% / 0.42
Prematurity / 4% / 2% / 0.43
Primary Immunodeficiency / 3% / 4% / 0.64
Endocrine / 4% / 0% / 0.15
Malformation / 2% / 2% / 0.87
Chronic Infectious / 1% / 4% / 0.16
eTable2: Enrollment Site and Hospital Mortality
Site / Patients Enrolled / Hospital Mortality (%)*Benioff Children’s Hospital, San Francisco / 123 / 23 (19%)
Benioff Children’s Hospital, Oakland / 103 / 11 (11%)
Children’s Hospital of Central California / 18 / 4 (22%)
University of Wisconsin-Madison / 30 / 6 (20%)
Children’s Hospital Los Angeles / 34 / 7 (21%)
*p=0.398
Additional Outcomes
We examined ICU, 30-day and 60-day mortality as additional outcomes. ICU mortality was 14.6% (n=45), 30-day mortality was 12.3% (n=38), and 60-day mortality was 14.6% (n=45). In logistic models from Day 1 data, including age, sex, race, ethnicity, direct vs. indirect lung injury, cancer/HSCT, PRISM-3, and extrapulmonary PELOD as covariates, the odds ratio for OI and ICU mortality was 1.21 (95% CI 0.92, 1.61; p=0.17); for 30-day mortality, it was 1.27 (95% CI 0.95, 1.7; p=0.11); and for 60-day mortality, it was 1.42 (95% CI 1.06, 1.9; p=0.017). We repeated the analyses using Day 3 predictors. OI was associated with ICU mortality with OR 2.08 (95% CI 1.33, 3.26; p=0.001), 30-day mortality with OR 1.83 (95% CI 1.12, 3; p=0.016), and 60-day mortality with OR 1.93 (95% CI 1.22, 3.04; p=0.005). Again, these models were not significantly impacted by removal of PRISM-3 or extrapulmonary PELOD.
Supplemental References
1. Hammer J, Numa A, Newth CJ. Acute respiratory distress syndrome caused by respiratory syncytial virus. Pediatr Pulmonol. 1997;23(3):176-183.
2. Pollack MM, Patel KM, Ruttimann UE. PRISM III: an updated Pediatric Risk of Mortality score. Crit Care Med. 1996;24(5):743-752.
3. Leteurtre S, Duhamel A, Grandbastien B, Lacroix J, Leclerc F. Paediatric logistic organ dysfunction (PELOD) score. Lancet. 2006;367(9514):897; author reply 900-892.
4. Leteurtre S, Martinot A, Duhamel A, et al. Validation of the paediatric logistic organ dysfunction (PELOD) score: prospective, observational, multicentre study. Lancet. 2003;362(9379):192-197.
5. Leteurtre S, Duhamel A, Grandbastien B, et al. Daily estimation of the severity of multiple organ dysfunction syndrome in critically ill children. CMAJ. 2010;182(11):1181-1187.
6. Khemani RG, Conti D, Alonzo TA, Bart RD, 3rd, Newth CJ. Effect of tidal volume in children with acute hypoxemic respiratory failure. Intensive Care Med. 2009;35(8):1428-1437.
7. Leclerc F, Duhamel A, Deken V, et al. Nonrespiratory pediatric logistic organ dysfunction-2 score is a good predictor of mortality in children with acute respiratory failure. Pediatr Crit Care Med. 2014;15(7):590-593.
8. Lopez-Fernandez Y, Azagra AM, de la Oliva P, et al. Pediatric Acute Lung Injury Epidemiology and Natural History study: Incidence and outcome of the acute respiratory distress syndrome in children. Crit Care Med. 2012;40(12):3238-3245.
9. Willson DF, Thomas NJ, Tamburro R, et al: The relationship of fluid administration to outcome in the pediatric calfactant in acute respiratory distress syndrome trial. Pediatr Crit Care Med 2013;14:666-672
10. Shapiro BA, Peruzzi WT, Kozelowski-Templin R. Clinical application of blood gases. 5th ed. St. Louis, Mo.: Mosby; 1994.
11. Khemani RG, Patel NR, Bart RD, 3rd, Newth CJ. Comparison of the pulse oximetric saturation/fraction of inspired oxygen ratio and the PaO2/fraction of inspired oxygen ratio in children. Chest. 2009;135(3):662-668.
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