Table 1.
Factors Present at Admission and Hospital Course Variables according to Change in Functional Status from Baseline to Follow-up
| Variable | Unchanged or Improved Functional Status (n = 757) | Decline in Functional Status (n = 192) | Unadjusted P Value* | Adjusted P Value† |
|---|---|---|---|---|
| Factors present at hospital admission | ||||
| Sociodemographic factors and preexisting health status | ||||
| Age at PICU admission, n (%) | 0.06 | |||
| 2 wk to <2 yr | 400 (53) | 89 (46) | ||
| 2 to <6 yr | 142 (19) | 31 (16) | ||
| 6 to <18 yr | 215 (28) | 72 (38) | ||
| Female, n (%) | 357 (47) | 81 (42) | 0.23 | |
| Non-Hispanic white, n/total (%) | 395/755 (52) | 109/190 (57) | 0.20 | |
| Parent education, n (%) | 0.08 | |||
| Some high school | 72 (13) | 8 (6) | ||
| High school graduate/GED | 137 (25) | 33 (26) | ||
| Some college or technical school | 158 (29) | 47 (38) | ||
| College graduate/postgraduate | 177 (33) | 37 (30) | ||
| Unknown, n | 213 | 67 | ||
| Median household income of ZIP code of residence, n (%)‡ | 0.09 | |||
| <$40,000 | 156 (21) | 35 (18) | ||
| $40,000–$79,999 | 446 (59) | 128 (67) | ||
| ≥$80,000 | 155 (20) | 29 (15) | ||
| Normal functional status at baseline, n (%)§ | 561 (74) | 119 (62) | 0.0002 | |
| Any medical history, n (%) | ||||
| Prematurity (<36 wk postmenstrual age) | 99 (13) | 38 (20) | 0.004 | |
| Asthma (prescribed bronchodilators or steroids) | 114 (15) | 17 (9) | 0.006 | |
| Cancer (current or previous diagnosis) | 29 (4) | 22 (11) | 0.0002 | |
| Features of the presenting acute illness | ||||
| PRISM III-12 score, median (IQR)‖ | 7 (3–11) | 8 (3–14.5) | 0.003 | |
| Risk of mortality based on PRISM III-12 score, median (IQR), % | 2.9 (1.0–8.9) | 4.2 (1.3–20.1) | 0.0002 | |
| Primary diagnosis category, n (%) | <0.0001 | |||
| Bronchiolitis or asthma (or reactive airway disease) | 287 (38) | 42 (22) | ||
| Pneumonia or aspiration pneumonia | 319 (42) | 87 (45) | ||
| Acute respiratory failure related to sepsis | 80 (11) | 35 (18) | ||
| Other acute diagnoses¶ | 60 (8) | 17 (9) | ||
| Other chronic diagnoses¶ | 11 (1) | 11 (6) | ||
| Hospital course variables | ||||
| Moderate/severe PARDS based on worst OI or OSI during hospitalization, n (%)** | 535 (71) | 154 (80) | 0.03 | 0.04 |
| Early NMB (for the entire duration of Days 1 and 2), n (%) | 107 (14) | 33 (17) | 0.35 | 0.64 |
| HFOV, n (%) | 94 (12) | 33 (17) | 0.21 | 0.47 |
| ECMO, n (%) | 14 (2) | 7 (4) | 0.17 | 0.30 |
| Noninvasive ventilation before intubation, n (%) | 318 (42) | 77 (40) | 0.77 | 0.77 |
| Noninvasive ventilation after extubation, n (%) | 326 (43) | 96 (50) | 0.07 | 0.07 |
| Duration of mechanical ventilation, median (IQR), d | 5.9 (3.8–9.2) | 9.3 (5.0–15.5) | <0.0001 | <0.0001 |
| Duration of mechanical ventilation, n (%) | ||||
| <7 d | 455 (60) | 70 (36) | <0.0001 | <0.0001 |
| 7 to <14 d | 211 (28) | 65 (34) | ||
| 14 to <28 d | 64 (8) | 38 (20) | ||
| ≥28 d (including transfers by Day 28) | 27 (4) | 19 (10) | ||
| MODS (concurrent or new), n (%)†† | 534 (71) | 154 (80) | 0.02 | 0.16 |
| Extrapulmonary organ dysfunction during hospitalization, n (%) | ||||
| Cardiovascular | 326 (43) | 100 (52) | 0.06 | 0.46 |
| Neurologic | 358 (47) | 102 (53) | 0.26 | 0.57 |
| Hematologic | 112 (15) | 60 (31) | <0.0001 | 0.0001 |
| Renal | 40 (5) | 22 (11) | 0.002 | 0.02 |
| Hepatic | 146 (19) | 53 (28) | 0.02 | 0.17 |
| Number of organ dysfunctions, median (IQR) | 2 (1–3) | 3 (2–4) | 0.0003 | 0.02 |
| Mean daily opioid dose, median (IQR), mg/kg | 1.5 (0.7–2.5) | 2.0 (0.9–3.5) | 0.05 | 0.04 |
| Mean daily benzodiazepine dose, median (IQR), mg/kg | 1.3 (0.7–2.4) | 1.6 (0.7–3.5) | 0.0006 | 0.0002 |
| Synthetic primary opioid agent, n (%)‡‡ | 438 (58) | 106 (55) | 0.48 | 0.22 |
| Dexmedetomidine, n (%) | 269 (36) | 84 (44) | 0.009 | 0.008 |
| Clonidine, n (%) | 76 (10) | 46 (24) | <0.0001 | <0.0001 |
| Ketamine, n (%) | 193 (26) | 59 (31) | 0.26 | 0.35 |
| Barbiturates, n (%) | 110 (15) | 32 (17) | 0.43 | 0.35 |
| Methadone, n (%) | 147 (19) | 57 (30) | 0.02 | 0.01 |
| Antidelirium medication, n (%) | 12 (2) | 9 (5) | 0.01 | 0.07 |
| ≥4 sedative classes, n (%)§§ | 206 (27) | 79 (41) | 0.0007 | 0.0005 |
| Study days awake and calm (daily modal SBS score −1 or 0), median (IQR), % | 82 (60–100) | 78 (58–96) | 0.48 | 0.84 |
| Heavy sedation (daily modal SBS score ever −3), n (%) | 86 (11) | 26 (14) | 0.50 | 0.98 |
| Inadequate pain management, n (%)|||| | 101 (13) | 43 (22) | 0.004 | 0.008 |
| Inadequate sedation management, n (%)|||| | 160 (21) | 60 (31) | 0.0008 | 0.001 |
| Clinically significant iatrogenic withdrawal, n (%)¶¶ | 86 (11) | 31 (16) | 0.06 | 0.03 |
| Length of stay | ||||
| PICU, median (IQR), d | 8.9 (5.8–14.2) | 14.5 (7.9–25.0) | <0.0001 | <0.0001 |
| PICU, n (%) | ||||
| <7 d | 258 (34) | 34 (18) | <0.0001 | <0.0001 |
| 7 to <14 d | 300 (40) | 59 (31) | ||
| 14 to <28 d | 145 (19) | 60 (31) | ||
| ≥28 d | 54 (7) | 39 (20) | ||
| Hospital, median (IQR), d | 13 (9–22) | 24.5 (14–44) | <0.0001 | <0.0001 |
| Hospital, n (%) | ||||
| <7 d | 79 (10) | 9 (5) | <0.0001 | <0.0001 |
| 7 to <14 d | 316 (42) | 38 (20) | ||
| 14 to <28 d | 222 (29) | 60 (31) | ||
| ≥28 d | 140 (18) | 85 (44) | ||
| Opioids and/or benzodiazepines at hospital discharge, n (%) | 207 (27) | 76 (40) | 0.003 | 0.002 |
Definition of abbreviations: ECMO = extracorporeal membrane oxygenation; GED = Graduate Equivalency Degree; HFOV = high-frequency oscillatory ventilation; IQR = interquartile range; MODS = multiple organ dysfunction syndrome; NMB = neuromuscular blocking agent; OI = oxygenation index; OSI = oxygen saturation index; PARDS = pediatric acute respiratory distress syndrome; PICU = pediatric ICU; PRISM III-12 = Pediatric Risk of Mortality III score from first 12 hours in the PICU; SBS = State Behavioral Scale.
P values for comparison between groups were calculated using logistic regression accounting for PICU as a cluster variable using generalized estimating equations.
P values were calculated as above, adjusting for age group and PRISM III-12 score.
Median household income of ZIP code of residence in 2011 (16).
Normal functional status at baseline was defined as Pediatric Cerebral Performance Category (PCPC) = 1 and Pediatric Overall Performance Category (POPC) = 1. POPC must be greater than or equal to PCPC (13).
Severity of illness was defined by the PRISM III-12 score. The scale for the PRISM III-12 score ranges from 0 to 74, with higher scores indicating a higher risk of death (23).
Other acute primary diagnoses include pulmonary edema, thoracic trauma, laryngotracheobronchitis, pulmonary hemorrhage, pertussis, pneumothorax (nontrauma), pulmonary embolus, acute respiratory failure related to multiple blood transfusions, and chemical pneumonitis. Other chronic primary diagnoses include acute chest syndrome/sickle cell disease, acute respiratory failure after bone marrow transplantation, acute exacerbation lung disease (cystic fibrosis or bronchopulmonary dysplasia), and pulmonary hypertension (not primary).
PARDS severity was defined using the 2015 Pediatric Acute Lung Injury Consensus Conference criteria (18).
MODS was defined as respiratory dysfunction plus one or more extrapulmonary organ dysfunctions, with concurrent MODS defined by onset on Day 0/1 and new MODS by onset on Day 2 or later (19).
Synthetic primary opioid agent includes fentanyl, hydromorphone, and remifentanil.
§§Different sedative classes include opioids, benzodiazepines, α2-adrenergic agonists, propofol, barbiturates, ketamine, and chloral hydrate.
Inadequate pain management was defined as pain score >4 (or pain assumed present if receiving neuromuscular blockade) for 2 consecutive hours and inadequate sedation management as SBS score >0 (or agitation assumed present if receiving neuromuscular blockade) for 2 consecutive hours.
Clinically significant iatrogenic withdrawal was defined as rescue therapy (an opioid or benzodiazepine bolus or an increase in opioid or benzodiazepine infusion) to manage an increase in withdrawal symptoms for patients weaning from ≥5 days of opioids.