Background
Methods
Design
Participants at follow-up
Procedure
Health-related quality of life outcomes
Statistical analyses
Results
Tested populations | Total PICU population | Tested post-PICU populationa | ||||
---|---|---|---|---|---|---|
Healthy control children, N = 405 | Post-PICU patients, N = 786 | Early-PN, N = 723 | Late-PN, N = 717 | Early-PN, N = 391 | Late-PN, N = 395 | |
Demographics | ||||||
Age at 2-year follow-up (mean ± SEM), years | 6.0 ± 0.2 | 5.7 ± 0.2 | NA | NA | 5.7 ± 0.2 | 5.6 ± 0.2 |
Male gender, no. (%) | 219 (54.1) | 455 (57.9) | 415 (57.4) | 412 (57.5) | 230 (58.8) | 225 (57.0) |
Known non-Caucasian race, no. (%)b | 33 (8.1) | 63 (8.0) | 50 (6.9) | 33 (4.6) | 38 (9.7) | 25 (6.3) |
Known non-European origin, no. (%)b | 54 (13.3) | 152 (19.3) | 161 (22.3) | 128 (17.9) | 88 (22.5) | 64 (16.2) |
Known not exclusive Dutch or English language, no. (%) | 76 (18.8) | 184 (23.4) | 122 (16.9) | 106 (14.8) | 95 (24.3) | 89 (22.5) |
Socio-economic status, no. (%) | ||||||
Educational level parentsc,d | ||||||
Educational level 1 | 13 (3.2) | 37 (4.7) | NA | NA | 12 (3.1) | 25 (6.3) |
Educational level 1.5 | 23 (5.7) | 54 (6.9) | NA | NA | 28 (7.2) | 26 (6.6) |
Educational level 2 | 55 (13.6) | 184 (23.4) | NA | NA | 96 (24.6) | 88 (22.3) |
Educational level 2.5 | 76 (18.8) | 131 (16.7) | NA | NA | 60 (15.3) | 71 (18.0) |
Educational level 3 | 215 (53.1) | 200 (25.4) | NA | NA | 100 (25.6) | 100 (25.3) |
Educational level unknown | 23 (5.7) | 180 (22.9) | NA | NA | 95 (24.3) | 85 (21.5) |
Patient characteristics upon PICU admission | ||||||
Infant (age < 1 year) at randomization, no. (%) | NA | 363 (46.2) | 328 (45.4) | 325 (45.3) | 177 (45.3) | 186 (47.1) |
STRONGkids risk level, no. (%)e | ||||||
Medium | NA | 707 (89.9) | 644 (89.1) | 644 (89.8) | 351 (89.8) | 356 (90.1) |
High | NA | 79 (10.1) | 79 (10.9) | 73 (10.2) | 40 (10.2) | 39 (9.9) |
PeLOD score, first 24 h in PICU (mean ± SEM)f | NA | 20 ± 0.4 | 19.7 ± 0.4 | 20.1 ± 0.5 | 20 ± 0.6 | 20 ± 0.6 |
PIM3 score (mean ± SEM)g | NA | −3.5 ± 0.0 | −3.2 ± 0.1 | −3.2 ± 0.1 | −3.4 ± 0.1 | −3.5 ± 0.1 |
Diagnostic category, no. (%)h | ||||||
Surgical | ||||||
Cardiac | NA | 339 (43.1) | 279 (38.6) | 268 (37.4) | 173 (44.2) | 166 (42.0) |
Other | NA | 249 (31.7) | 211 (29.2) | 215 (30.0) | 125 (32.0) | 124 (31.4) |
Medical | ||||||
Respiratory | NA | 83 (10.6) | 99 (13.7) | 96 (13.4) | 39 (9.7) | 45 (11.4) |
Other | NA | 115 (14.6) | 134 (18.5) | 138 (19.2) | 55 (14.1) | 60 (15.2) |
Malignancy, no. (%) | 0 (0.0) | 42 (5.3) | 51 (7.1) | 33 (4.6) | 26 (6.6) | 16 (4.1) |
Diabetes, no. (%) | 0 (0.0) | 1 (0.1) | 3 (0.4) | 0 (0.0) | 1 (0.3) | 0 (0.0) |
Syndrome, no. (%)i | 5 (1.2) | 79 (10.1) | 123 (17.0) | 118 (16.5) | 34 (8.7) | 45 (11.4) |
Known parental smoking between birth and PICU admission, no. (%) | NA | 354 (45.0) | NA | NA | 184 (47.1) | 170 (43.0) |
Acute effects of randomization and post-randomization treatments in PICU | ||||||
Duration of stay in the PICU (mean ± SEM), days | NA | 7.4 ± 0.5 | 9.2 ± 0.8 | 6.5 ± 0.4 | 8.4 ± 0.9 | 6.4 ± 0.5 |
Patients who acquired a new infection in PICU, no. (%) | NA | 105 (13.4) | 134 (18.5) | 77 (10.7) | 66 (16.9) | 39 (9.9) |
Duration of mechanical ventilatory support (mean ± SEM), days | NA | 4.7 ± 0.4 | 6.4 ± 0.7 | 4.4 ± 0.3 | 5.5 ± 0.7 | 3.9 ± 0.4 |
Number of days with hypoglycemia < 40 mg/dl (mean ± SEM), days | NA | 0.1 ± 0.0 | 0.1 ± 0.0 | 0.2 ± 0.0 | 0.1 ± 0.0 | 0.2 ± 0.0 |
Duration of antibiotic treatment (mean ± SEM), days | NA | 5.1 ± 0.5 | 6.7 ± 0.7 | 4.6 ± 0.3 | 5.8 ± 0.8 | 4.3 ± 0.5 |
Duration of hemodynamic support (mean ± SEM), days | NA | 2.5 ± 0.3 | 3.0 ± 0.3 | 2.4 ± 0.2 | 2.6 ± 0.4 | 2.3 ± 0.3 |
Duration of treatment with opioids (mean ± SEM), days | NA | 4.7 ± 0.3 | 6.1 ± 0.6 | 4.1 ± 0.2 | 5.4 ± 0.5 | 4.1 ± 0.3 |
Duration of treatment with benzodiazepines (mean ± SEM), days | NA | 4.2 ± 0.3 | 5.4 ± 0.6 | 4.0 ± 0.3 | 4.5 ± 0.5 | 3.9 ± 0.5 |
Duration of treatment with hypnotics (mean ± SEM), days | NA | 1.4 ± 0.2 | 1.8 ± 0.2 | 1.3 ± 0.1 | 1.6 ± 0.4 | 1.2 ± 0.1 |
Duration of treatment with alpha-2-agonists (mean ± SEM), days | NA | 1.0 ± 0.2 | 1.1 ± 0.3 | 1.0 ± 0.2 | 0.9 ± 0.3 | 1.1 ± 0.3 |
Duration of treatment with corticosteroids (mean ± SEM), days | NA | 1.2 ± 0.1 | 1.6 ± 0.2 | 1.3 ± 0.1 | 1.3 ± 0.2 | 1.0 ± 0.2 |
HRQoL outcomes assessed at 2 years’ follow-up | No. (%) available data per outcome (N = 1191) | Beta-estimate (95% CI) for the comparison of patients vs. controls, adjusted for risk factorsa | p value | Beta-estimate (95% CI) for the comparison late-PN vs. early-PN, adjusted for risk factorsb | p value |
---|---|---|---|---|---|
Parent-reported HRQoL in children (ITQOL & CHQ-PF50) | |||||
Physical functioning | 960 (81) | − 6.34 (− 8.59 to − 4.10) | < 0.001 | 1.32 (− 1.54 to 4.17) | 0.36 |
Bodily pain | 967 (81) | − 6.81 (− 9.54 to − 4.07) | < 0.001 | 1.20 (− 2.32 to 4.73) | 0.50 |
General behavior | 967 (81) | − 1.87 (− 3.88 to 0.14) | 0.07 | 2.28 (− 0.01 to 4.57) | 0.05 |
General health | 961 (81) | − 27.20 (− 29.91 to − 24.49) | < 0.001 | 2.92 (− 0.47 to 6.31) | 0.09 |
Change in health | 965 (81) | 12.94 (9.93–15.95) | < 0.001 | − 0.88 (− 4.37 to 2.61) | 0.62 |
Parental impact—emotional | 964 (81) | − 7.92 (− 10.50 to − 5.33) | < 0.001 | 2.40 (− 0.80 to 5.60) | 0.14 |
Parental impact—time | 965 (81) | − 5.41 (− 8.07 to − 2.76) | < 0.001 | 3.05 (− 0.37 to 6.47) | 0.08 |
Family activity | 960 (81) | − 6.18 (− 8.78 to − 3.58) | < 0.001 | 3.58 (0.32–6.84) | 0.03 |
Family cohesion | 962 (81) | − 2.25 (− 4.97 to 0.47) | 0.10 | 0.70 (− 2.41 to 3.81) | 0.66 |
Parent-reported HRQoL in children 2.5 to 3 years only (ITQOL) | |||||
Temperament and moods | 548 (83) | − 1.14 (− 3.46 to 1.17) | 0.33 | − 0.33 (− 2.87 to 2.20) | 0.80 |
Growth and development | 547 (83) | − 3.09 (− 6.02 to − 0.15) | 0.04 | 1.56 (− 1.52 to 4.65) | 0.32 |
Getting along | 543 (82) | − 0.25 (− 2.53 to 2.03) | 0.83 | 1.56 (− 0.82 to 3.94) | 0.20 |
Parent-reported HRQoL in children aged 4–18 years only (CHQ-PF50) | |||||
Role functioning emotional/behavior | 425 (80) | − 6.73 (− 12.86 to − 0.60) | 0.03 | − 1.26 (− 7.30 to 4.79) | 0.68 |
Role functioning due to physical problems | 424 (80) | − 7.87 (− 14.35 to − 1.39) | 0.02 | 0.71 (− 5.00 to 6.43) | 0.81 |
Mental health | 425 (80) | − 5.28 (− 8.45 to − 2.11) | 0.001 | 0.01 (− 3.62 to 3.65) | 0.99 |
Self-esteem | 426 (80) | − 2.34 (− 6.20 to 1.51) | 0.23 | 1.08 (− 2.28 to 4.45) | 0.53 |
Parent-reported HRQoL in children (HUI2; single utility scores) | |||||
Sensation | 959 (80) | − 0.03 (− 0.06 to 0.00) | 0.03 | 0.02 (− 0.02 to 0.06) | 0.30 |
Mobility | 959 (80) | − 0.02 (− 0.04 to 0.01) | 0.007 | 0.01 (− 0.02 to 0.023) | 0.62 |
Emotions | 962 (81) | − 0.01 (− 0.02 to 0.00) | 0.06 | 0.00 (− 0.02 to 0.01) | 0.43 |
Cognition | 958 (80) | − 0.01 (− 0.02 to 0.00) | 0.13 | 0.01 (− 0.01 to 0.03) | 0.26 |
Self-care | 960 (81) | − 0.04 (− 0.08 to 0.00) | 0.03 | 0.01 (− 0.04 to 0.05) | 0.83 |
Pain | 961 (81) | 0.00 (− 0.02 to 0.01) | 0.56 | 0.00 (− 0.02 to 0.02) | 0.66 |
Multi-attribute utility function on dead-healthy scale | 944 (79) | − 0.04 (− 0.06 to − 0.02) | < 0.001 | 0.01 (− 0.01 to 0.03) | 0.40 |
Parent-reported HRQoL in children (HUI3; single utility scores) | |||||
Vision | 958 (80) | 0.00 (− 0.01 to 0.01) | 0.96 | 0.00 (− 0.02 to 0.01) | 0.77 |
Hearing | 961 (81) | 0.00 (− 0.02 to 0.02) | 0.80 | 0.01 ( − 0.02 to 0.03) | 0.57 |
Speech | 960 (81) | − 0.04 (− 0.07 to 0.01) | 0.01 | 0.02 (− 0.01 to 0.06) | 0.21 |
Ambulation | 959 (80) | − 0.04 (− 0.06 to − 0.01) | 0.002 | 0.01 (− 0.02 to 0.04) | 0.45 |
Dexterity | 962 (81) | − 0.01 (− 0.04 to 0.01) | 0.24 | 0.01 (− 0.03 to 0.04) | 0.71 |
Emotions | 962 (81) | − 0.007 (− 0.01 to 0.00) | 0.05 | 0.00 (− 0.01 to 0.00) | 0.41 |
Cognition | 944 (79) | − 0.01 (− 0.03 to 0.00) | 0.15 | 0.01 (− 0.02 to 0.04) | 0.52 |
Pain | 961 (81) | − 0.01 (− 0.03 to 0.01) | 0.25 | 0.00 (− 0.02 to 0.03) | 0.71 |
Multi-attribute utility function on dead-healthy scale | 931 (78) | − 0.06 (− 0.09 to − 0.03) | < 0.001 | 0.02 (− 0.02 to 0.05) | 0.33 |
HRQoL of parents (SF-12) | |||||
Physical component score | 938 (79) | − 0.38 (− 1.57 to 0.82) | 0.53 | 0.66 (− 0.75 to 2.08) | 0.36 |
Mental component score | 938 (79) | − 0.88 (− 2.22 to 0.45) | 0.19 | 1.12 (− 0.47 to 2.71) | 0.17 |