Table 1.
Baseline Characteristics and Hospital Course of Patients with Postdischarge Follow-up according to Treatment Group
| Characteristics | Sedation Protocol (n = 576) | Usual Care (n = 497) | P Value* |
|---|---|---|---|
| Baseline characteristics | |||
| Age at PICU admission | |||
| Median (IQR), yr | 1.4 (0.3–6.8) | 3.4 (0.8–8.9) | <0.001 |
| n (%) | <0.001 | ||
| 2 wk to <2 yr | 336 (58) | 210 (42) | |
| 2 to <6 yr | 87 (15) | 106 (21) | |
| 6 to <18 yr | 153 (27) | 181 (36) | |
| Female, n (%) | 270 (47) | 226 (45) | 0.63 |
| Non-Hispanic white, n/total (%) | 304/571 (53) | 259/492 (53) | 0.86 |
| Parent education | 0.68 | ||
| Some high school, n (%) | 58 (13) | 38 (12) | |
| High school graduate/GED, n (%) | 105 (24) | 92 (28) | |
| Some college or technical school, n (%) | 151 (35) | 85 (26) | |
| College graduate/postgraduate, n (%) | 122 (28) | 108 (33) | |
| Unknown, n | 140 | 174 | |
| Median household income of zip code of residence | 0.41 | ||
| <$40,000, n (%)† | 98 (17) | 123 (25) | |
| $40,000–$79,999, n (%)† | 375 (65) | 279 (56) | |
| ≥$80,000, n (%)† | 102 (18) | 95 (19) | |
| Missing, n | 1 | 0 | |
| Normal functional status at baseline, n (%)‡ | 425 (74) | 346 (70) | 0.34 |
| PRISM III-12 score, median (IQR)§ | 6 (3–11) | 8 (5–13) | 0.002 |
| Risk of mortality based on PRISM III-12 score, %, median (IQR) | 2.2 (1.0–7.7) | 4.8 (1.7–14.2) | 0.004 |
| Any medical history, n (%) | |||
| Prematurity (<36 wk postmenstrual age) | 90 (16) | 64 (13) | 0.38 |
| Asthma (prescribed bronchodilators or steroids) | 64 (11) | 96 (19) | 0.01 |
| Cancer (current or previous diagnosis) | 32 (6) | 37 (7) | 0.29 |
| Primary diagnosis category, n (%) | <0.001 | ||
| Bronchiolitis or asthma (or reactive airway disease) | 242 (42) | 133 (27) | |
| Pneumonia or aspiration pneumonia | 218 (38) | 234 (47) | |
| Acute respiratory failure related to sepsis | 56 (10) | 80 (16) | |
| Other acute diagnoses|| | 46 (8) | 35 (7) | |
| Other chronic diagnoses¶ | 14 (2) | 15 (3) | |
| Hospital course | |||
| Duration of mechanical ventilation, d, median (IQR)** | 6.1 (3.9–9.9) | 6.1 (3.9–10.9) | 0.39 |
| Length of stay, d, median (IQR) | |||
| PICU | 9.1 (6.0–14.8) | 10.1 (6.3–18.1) | 0.19 |
| Hospital | 14 (9–24) | 17 (10–30) | 0.09 |
| Rescue therapy (ECMO and/or HFOV), n (%) | 86 (15) | 67 (13) | 0.78 |
| Moderate/severe PARDS based on worst OI or OSI during hospitalization, n (%)†† | 414 (72) | 368 (74) | 0.51 |
| MODS, n (%)‡‡ | <0.001 | ||
| Respiratory dysfunction only | 183 (32) | 108 (22) | |
| Concurrent MODS (Day 0 or 1) | 329 (57) | 346 (70) | |
| New MODS (Day 2 or later) | 64 (11) | 43 (9) | |
| Sedatives administered | |||
| Fentanyl as primary opioid agent, n (%) | 206 (36) | 415 (84) | <0.001 |
| Opioid exposure | |||
| Mean daily dose, mg/kg, median (IQR) | 1.4 (0.7–2.5) | 1.8 (0.9–2.8) | 0.23 |
| Peak daily dose, mg/kg, median (IQR) | 3.4 (1.7–6.2) | 4.2 (2.4–7.0) | 0.20 |
| Benzodiazepine exposure | |||
| Mean daily dose, mg/kg, median (IQR) | 1.4 (0.7–2.7) | 1.4 (0.6–2.6) | 0.21 |
| Peak daily dose, mg/kg, median (IQR) | 3.2 (1.6–6.2) | 3.6 (1.7–7.0) | 0.79 |
| Secondary sedatives, n (%) | |||
| Dexmedetomidine | <0.001 | ||
| None or used as a peri-extubation agent | 464 (81) | 322 (65) | |
| Used as a primary agent | 41 (7) | 69 (14) | |
| Used as a secondary agent | 71 (12) | 106 (21) | |
| Ketamine | 132 (23) | 163 (33) | 0.10 |
| Propofol | 85 (15) | 61 (12) | 0.73 |
| Barbiturates | 63 (11) | 98 (20) | 0.29 |
| Clonidine | 69 (12) | 67 (13) | 0.77 |
| Methadone | 72 (13) | 160 (32) | <0.001 |
| No. of sedative classes received ≥ 3, n (%) | 279 (48) | 376 (76) | <0.001 |
| Measures of wakefulness, pain, and agitation, %, median (IQR)§§ | |||
| Study days awake and calm | 86 (67–100) | 75 (50–100) | 0.004 |
| Study days with an episode of pain | 50 (29–67) | 22 (5–43) | <0.001 |
| Study days with an episode of agitation | 60 (33–80) | 45 (14–67) | 0.01 |
| Sedation-related adverse events, n (%)|||| | |||
| Inadequate pain management | 93 (16) | 71 (14) | 0.68 |
| Inadequate sedation management | 146 (25) | 107 (22) | 0.69 |
| Iatrogenic withdrawal syndrome, n/total at risk for withdrawal (%)¶¶ | 217/332 (65) | 169/239 (71) | 0.40 |
Definition of abbreviations: ECMO = extracorporeal membrane oxygenation; GED = General Educational Development; HFOV = high-frequency oscillatory ventilation; IQR = interquartile range; MODS = multiple organ dysfunction syndrome; OI = oxygenation index; OSI = oxygen saturation index; PARDS = pediatric acute respiratory distress syndrome; PCPC = Pediatric Cerebral Performance Category; PICU = pediatric ICU; POPC = Pediatric Overall Performance Category; PRISM III-12 = Pediatric Risk of Mortality III score from first 12 hours in the PICU; SBS = State Behavioral Scale; WAT-1 = Withdrawal Assessment Tool-Version 1.
P values for comparison between treatment groups were calculated using linear, cumulative logit, logistic, multinomial logistic, and proportional hazards regression for log-transformed continuous, ordinal, binary, nominal, and time-to-event variables, respectively. All regression analyses except for those using multinomial logistic regression accounted for PICU as a cluster variable using generalized estimating equations.
Median household income of zip code of residence in 2011 (16).
Normal functional status at baseline was defined as PCPC = 1 and POPC = 1. POPC must be greater than or equal to PCPC (10).
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 (17).
Other acute primary diagnoses include pulmonary edema, thoracic trauma, laryngotracheobronchitis, pulmonary hemorrhage, pertussis, pneumothorax (nontrauma), acute respiratory failure related to multiple blood transfusions, pulmonary embolus, and chemical pneumonitis.
Other chronic primary diagnoses include acute respiratory failure after bone marrow transplantation, acute chest syndrome/sickle cell disease, acute exacerbation lung disease (cystic fibrosis or bronchopulmonary dysplasia), pulmonary hypertension (not primary), and pulmonary leukostasis.
Patients were assigned 28 days if they remained intubated or were transferred or died before Day 28 without remaining extubated for more than 24 hours, therefore making this outcome the inverse equivalent of ventilator-free days.
PARDS severity was defined using the 2015 Pediatric Acute Lung Injury Consensus Conference criteria (42).
MODS was defined as respiratory dysfunction plus one or more extrapulmonary organ dysfunction(s), with concurrent MODS defined by onset on Day 0 or 1 and new MODS by onset on Day 2 or later (43).
Study days awake and calm was defined as modal SBS score −1 or 0, episode of pain as highest pain score greater than or equal to 4, and episode of agitation as highest SBS score +1 or +2.
Inadequate pain management was defined as pain score greater than 4 (or pain assumed present if receiving neuromuscular blockade) for 2 consecutive hours and inadequate sedation management as SBS score greater than 0 (or agitation assumed present if receiving neuromuscular blockade) for 2 consecutive hours.
Iatrogenic withdrawal syndrome was defined as WAT-1 score ever greater than or equal to 3 in survivors who completed weaning from 5 or more days of opioids and had at least one WAT-1 assessment.