Table 1.
Demographic and day 1 clinical characteristics of the four phenotypes
| Characteristic1 | Total | PedSep-A | PedSep-B | PedSep-C | PedSep-D |
|---|---|---|---|---|---|
| No. of patients, N (%) | 404 (100) | 136 (34) | 102 (25) | 110 (27) | 56 (14) |
| Demographic | |||||
| Age years* mean (SD) | 7 (6) | 3 (4) | 8 (6)a | 10 (5)a,b | 8 (6)a |
| Male* N (%) | 224 (55.4) | 63 (46.3) | 68 (66.7)a | 59 (53.6) | 34 (60.7) |
| Female* N (%) | 180 (44.6) | 73 (53.7) | 34 (33.3) | 51 (46.4) | 22 (39.3) |
| Hispanic* N (%) | 67 (16.6) | 28 (20.6) | 12 (11.8) | 23 (20.9) | 4 (7.1) |
| Non-Hispanic* N (%) | 323 (80.0) | 100 (73.5) | 86 (84.3) | 86 (78.2) | 51 (91.1) |
| Previous healthy* N (%) | 180 (44.6) | 96 (70.6)b,c,d | 28 (27.5) | 37 (33.6) | 19 (33.9) |
| Surgery* N (%) | 49 (12.1) | 6 (4.4) | 19 (18.6)a | 12 (10.9) | 12 (21.4)a |
| Organ dysfunction | |||||
| SIRS criteria, mean (SD)2 | 2.9 (0.8) | 2.9 (0.8) | 3.0 (0.8) | 2.8 (0.8) | 3 (0.8) |
| OFI* mean (SD)3 | 1.8 (0.9) | 1.4 (0.5) | 2.1 (0.6)a,c | 1.4 (0.6) | 3.1 (1.0)a,b,c |
| Inflammation | |||||
| CRP mg/dL* mean (SD) | 11.7 (10.4) | 7.3 (7.3) | 13.2 (11.5)a | 15.2 (10.4)a | 13.1 (11.2)a |
| Low temperature °C* mean | 36.6 (1.2) | 36.7 (0.9)b | 36.0 (1.6) | 37.1 (0.9)a,b,d | 36.3 (1.0) |
| High temperature °C* mean | 37.8 (1.3) | 37.8 (1.1) | 37.4 (1.3) | 38.3 (1.2)a,b,d | 37.8 (1.4) |
| ALC/mm3* median (IQR) | 1.2 (0.6–2.1) | 1.9(1.3–3.2)b,c,d | 1.1(0.6–1.9)c | 0.6 (0.2–1.0) | 1.1(0.6–2.1)c |
| Ferritin ng/mL* median (IQR) | 218 (98.0–625.3) | 125(69.8–207.8) | 223(116.5–544.2)a | 405(176.2–1485.7)a,b | 610 (221.1–2482.0)a,b |
| Pulmonary | |||||
| Pulmonary OFI* N (%) | 270 (66.8) | 108 (79.4)c | 87 (85.3)c | 37 (33.6) | 38 (67.9)c |
| Intubation* N (%) | 211 (52.2) | 72 (52.9)c | 94 (92.2)a,c,d | 15 (13.6) | 30 (53.6)c |
| Cardiovascular or hemodynamic | |||||
| Heart rate bpm* mean (SD) | 155.4 (31.3) | 168.1 (30.8)b,c,d | 146.5 (27.9) | 150.4 (27.6) | 150.6 (35.8) |
| Systolic blood pressure*, mean (SD) mmHg | 81.9 (19.3) | 85.0 (15.7)b | 74.8 (22.0) | 86.3 (17.2)b | 78.9 (21.9) |
| Cardiovascular OFI* N (%) | 284 (70.3) | 63 (46.3) | 92 (90.2)a | 85 (77.3)a | 44 (78.6)a |
| Renal | |||||
| Creatinine mg/dL* median (IQR) | 0.5 (0.3–0.8) | 0.3 (0.2–0.4) | 0.6 (0.4–1.0)a | 0.6 (0.4–0.7)a | 1.4 (0.6–2.6)a,b,c |
| Renal OFI* N (%) | 30 (7.4) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 30 (53.6)a,b,c |
| Hepatic | |||||
| Hepatic OFI* N (%) | 40 (9.9) | 3 (2.2) | 9 (8.8) | 11 (10.0)a | 17 (30.4)a,b,c |
| Hematologic | |||||
| Hemoglobin g/dL* mean (SD) | 9.8 (2.0) | 10.1 (1.8)b,d | 9.4 (2.1) | 10.2 (2.1)b,d | 9.1 (1.8) |
| Platelets K/mm3* mean (SD) | 171.1 (123.2) | 260.1 (122.0)b,c,d | 154.3 (95.1)c,d | 118.8 (83.5)d | 88.2 (108.0) |
| Hematologic OFI* N (%) | 39 (9.7) | 0 (0.0) | 0 (0.0) | 8 (7.3)a,b | 31 (85.7)a,b,c |
| Neurologic | |||||
| Glasgow Coma Scale Score* mean (SD)4,5 | 8.7 (5.3) | 8.5 (5.2)b | 4.7 (3.4) | 13.2 (3.1)a,b,d | 7.9 (5.5)b |
| CNS OFI N (%) | 54 (13.4) | 12 (8.8) | 24 (23.5)a,c | 6 (5.5) | 12 (21.4)c |
IQR interquartile range, SIRS systemic inflammatory response syndrome, OFI organ failure index, ALC absolute lymphocyte count, CNS central nervous system
SI conversion factors: to convert alanine transaminase and aspartate aminotransferase to μkat/L, multiply by 0.0167; bilirubin to μmol/L, multiply by 17.104; C-reactive protein to nmol/L, multiply by 9.524; creatinine to μmol/L, multiply by 88.4
*Comparisons across all 4 computable phenotypes were performed using the Kruskal–Wallis test, the χ2 test, or the Fisher’s exact test (Additional file 1: Table S3, p < 0.05 for all comparisons after adjustment)
1The variables in this table were log transformed for modeling (Additional file 1: Table S3). Comparisons across all 4 phenotypes were performed using the Kruskal–Wallis test, the χ2 test, or the Fisher’s exact test (Additional file 1: Table S3. p < 0.05 for all comparisons after adjustment)
2Indicates SIRS criteria ranging from 0 to 4 including abnormal heart rate, respiratory rate, temperature, and white blood cell count
3OFI is an integer score reflecting the number of organ failures. Scores are either 0 or 1 for cardiovascular, hepatic, hematologic, respiratory, neurological, and renal, and summed for total range of 0 to 6. Cardiovascular, need for cardiovascular agent infusion support; Pulmonary, need for mechanical ventilation support with the ratio of the arterial partial pressure of oxygen and the fraction of inspired oxygen (PaO2/FiO2) < 300 without this support; Hepatic, total bilirubin > 1.0 mg/dL and alanine aminotransferase (ALT) > 100 units/L; Renal, serum creatinine > 1.0 mg/dL and oliguria (urine output < 0.5 mL/kg/h); Hematologic, thrombocytopenia < 100,000/mm3 and prothrombin time INR > 1.5 × normal; Central Nervous System, Glasgow Coma Scale (GCS) Score < 12 in the absence of sedatives
4Corresponds to minimum or maximum value (as appropriate) within 6 h of hospital presentation
5GCS ranges from 3 to 15
aThe outcome characteristic of this computable phenotype is significantly higher than PedSep-A (p value < 0.05)
bThe outcome characteristic of this computable phenotype is significantly higher than PedSep-B (p value < 0.05)
cThe outcome characteristic of this computable phenotype is significantly higher than PedSep-C (p value < 0.05)
dThe outcome characteristic of this computable phenotype is significantly higher than PedSep-D (p value < 0.05)