Online Supplemental Material
Development and Validation of an Empiric Tool to Predict Favorable Neurologic Outcomes among Pediatric ICU Survivors
Authors: Punkaj Gupta, MBBS; Mallikarjuna Rettiganti, PhD; Jeffrey M. Gossett, MS; Jennifer
Daufeldt, RN; Tom B. Rice, MD; Randall C. Wetzel, MBBS
Supplemental Table 1. Definition of study variables Favorable Neurologic
Outcome (primary)
Favorable neurologic outcome is defined as either no change, or decline by only 1, or improvement in PCPC from ICU admission to ICU discharge. Using this definition, unfavorable neurologic outcome meant a decline in PCPC by at least 2 between ICU admission and ICU discharge.
Favorable Neurologic Outcome (secondary)
Favorable neurologic outcome as either no change, or improvement in PCPC from ICU admission to ICU discharge. Using this definition, unfavorable neurologic outcome meant a decline in PCPC by at only 1 between ICU admission and ICU discharge.
Shock/Hypotension Shock/hypotension was defined as mean blood pressure 2 SD below the age-appropriate normal at any time during the ICU stay. The VPS Star Codes used for this definition includes 458, 785.51, 785.52, 785.59B, 958.4, 995.0, 998.0.
Acute Respiratory Failure Acute respiratory failure was defined as the need for positive pressure ventilation in the form of non-invasive or invasive mechanical
ventilation. The VPS Star Codes used for this definition includes 518.5, 799.1, 786.0.
Renal Insufficiency Renal Insufficiency is defined as new onset oliguria with sustained urine output < 0.5 cc/kg/hr. for 24 hours and/or a rise in creatinine > 1.5 times upper limits of normal for age (or twice the most recent
preoperative/preprocedural values if these are available), with or without need for dialysis (including peritoneal dialysis and/or hemodialysis) or hemofiltration. The VPS Star Codes used for this definition includes 584, 588.9.
Seizure A seizure is defined as the clinical and/or electroencephalographic recognition of epileptiform activity. The VPS Star Codes used for this definition includes 345, 780.3.
Cardiac Arrest Cardiac arrest event is defined as any event characterized by either pulselessness or critically compromised perfusion treated with external chest compressions for ≥ 1 minute and/or defibrillation that elicited a unit-wide or hospital-wide emergency response. This definition is in consensus with AHA operational definition for cardiopulmonary resuscitation event. The VPS Star Codes used for this definition includes 427.5, 779.85.
Stroke Stroke of abrupt onset confirmed by radiologic exam and caused by a disturbance in blood flow in the brain either due to brain ischemia or brain hemorrhage, when the neurologic deficit does not resolve within 24 hours. The VPS Star Codes used for this definition includes 432.9, 431, 772, 432.1, 852.0, 852.2, 853, 432.0, 434, 436, 348.1, 768.7.
24/7 coverage ICUs staffed by around-the-clock mandatory attending level intensivist coverage are categorized in the 24/7 group in the VPS database. This coverage may or may not be associated with additional coverage such
as resident and/or fellow and/or advanced nurse practitioner. The VPS database collects patient- and center-level data for all sites on a quarterly basis for all variables including data for 24/7 in-house intensivist presence.
Supplemental Table 2. Patient Characteristics
Variable N All Patients
N=160,570
Unfavorable Neurological
N=1,675
Favorable Neurological**
N=158,899
P
Male gender 160,559 88,800 (55.3%) 975 (58.2%) 87,825 (55.3%) 0.02
Weight (kg) 160,570 16 (8 to 38) 16 (8, 41) 16 (8, 38)
Chromosomal anomaly 160,570 6,027 (3.8%) 21 (1.3%) 6,006 (3.8%) < 0.001
Age (Months) 160,570 47.7
(10.0 to 139.4)
47.2 (6.8, 136.2)
47.7 (10.0, 139.4)
Race/Ethnicity 153,049 < 0.001
White 77,729 (50.8%) 708 (44.6%) 77021 (50.9%)
African American 23,864 (15.6%) 298 (18.8%) 23,566 (15.6%)
Hispanic 32,737 (21.4%) 365 (23.0%) 32,376 (21.4%)
Other race 18,719 (12.2%) 218 (13.7%) 18,501 (12.2%)
Clinical Data
PIM-2 score at ICU admission 160,570 -4.7 (-5.8 to -4.1)
-3.2 (-4.3, -2.0)
-4.7
(-5.9, -4.1) < 0.001 Acute respiratory failure 160,570 48,944 (30.5%) 966 (57.7%) 47,978 (30.2%) < 0.001 Shock/Hypotension 160,570 9,091 (5.7%) 213 (12.7%) 8,878 (5.6%) < 0.001 Cardiac Arrest 160,570 2,757 (1.7%) 290 (17.3%) 2,467 (1.6%) < 0.001 Renal insufficiency 160,570 3,845 (2.4%) 96 (5.7%) 3,749 (2.4%) < 0.001
Stroke 160,570 11,733 (7.3%) 888 (53.0%) 10845 (6.8%) < 0.001
Seizures 160,570 22,715 (14.1%) 418 (25.0%) 22,297 (14.0%) < 0.001
Head trauma 156,336 7,973 (5.1%) 653 (39.2%) 7,320 (4.7%) < 0.001
Non-head trauma 156,335 5,317 (3.4%) 373 (22.4%) 4,944 (3.2%) < 0.001 Congenital heart disease 160,565 34,079 (21.2%) 163 (9.7%) 33,920 (21.3%) < 0.001 Acquired heart disease 160,565 2,678 (1.7%) 43 (2.6%) 2,637 (1.7%) 0.004 Cardiac surgery 160,570 18,023 (11.2%) 109 (6.5%) 17,918 (11.3%) < 0.001 Cardiopulmonary bypass 18,023 11,924 (66.2%) 34 (31.2%) 11,894 (66.4%) < 0.0001 Resource Utilization data
ECMO 160,570 751 (0.5%) 69 (4.1%) 682 (0.4%) < 0.001
Nitric Oxide 160,570 3,071 (1.9%) 83 (5.0%) 2,988 (1.9%) < 0.001
Dialysis 160,570 2,099 (1.3%) 53 (3.2%) 2,046 (1.3%) < 0.001
Mechanical Ventilation 160,570 < 0.001
No Ventilation 113,261 (70.5%) 279 (16.7%) 112,982 (71.1%)
Conventional ventilation 46,346 (28.9%) 1,344 (80.2%) 45,006 (28.3%)
HFOV 963 (0.6%) 52 (3.1%) 911 (0.6%)
Days of MV 47,309 2 (1, 5) 4 (0, 10) 1 (0, 3) < 0.001
ICU length of stay 160,570 1.7 (0.9, 3.9) 10.6 (5.0, 19.7) 1.5 (0.8, 3.6) < 0.001 24/7 physician coverage 159,628 123,059 (77.1%) 1,268 (76.2%) 121,795 (77.1%) 0.39
Continuous variables are summarized by interquartile range, IQR as Median (25th percentile, 75th percentile). Categorical variables are summarized as N (percent). ** Favorable neurologic outcome was defined as either no change, or decline by only 1, or improvement in PCPC from ICU admission to ICU discharge. Abbreviations: PIM-2: Pediatric Index of Mortality; ECMO: Extracorporeal Membrane Oxygenation; MV: Mechanical Ventilation; HFOV: High Frequency Oscillatory Ventilation; ICU:
Intensive Care Unit.
Supplemental Table 3. Final model predicting favorable neurological outcome using alternative definition**
Label Comparison Coefficient S.E. OR (95% CI) P
Age 12 months increase 0.0312 0.0058 1.03 (1.02, 1.04) < 0.001
Weight 5 kg increase -0.0558 0.0067 0.95 (0.93, 0.96) < 0.001
Weight 10 kg increase -0.1116 0.0134 0.89 (0.87, 0.92) < 0.001
Race Black vs. White -0.0656 0.0468 0.94 (0.85, 1.03) 0.1608
Race Hispanic vs. White 0.0184 0.0475 1.02 (0.93, 1.12) 0.6992
Race Other vs. White -0.1118 0.0525 0.89 (0.81, 0.99) 0.0331
Chromosomal Anomaly Yes vs. No 0.9923 0.1168 2.70 (2.15, 3.39) < 0.001 PIM-2 Score at ICU admission 1 unit increase -0.2751 0.0146 0.76 (0.74, 0.78) < 0.001 Acute respiratory Failure Yes vs. No 0.1567 0.0413 1.17 (1.08, 1.27) 0.0001
Shock/Hypotension Yes vs. No -0.1696 0.0584 0.84 (0.75, 0.95) 0.0037
Cardiac Arrest Yes vs. No -0.7489 0.0688 0.47 (0.41, 0.54) < 0.001
Renal Insufficiency Yes vs. No -0.1948 0.0846 0.82 (0.70, 0.97) 0.0213
Stroke Yes vs. No -1.3143 0.0401 0.27 (0.25, 0.29) < 0.001
Seizures Yes vs. No -0.3051 0.0415 0.74 (0.68, 0.80) < 0.001
Head trauma Yes vs. No -1.4148 0.0491 0.24 (0.22, 0.27) < 0.001
Non-Head trauma Yes vs. No -0.6621 0.0589 0.52 (0.46, 0.58) < 0.001
Acquired Heart Disease Yes vs. No 0.1639 0.1194 1.18 (0.93, 1.49) 0.1696
Cardiac Surgery Yes vs. No 0.6729 0.0713 1.96 (1.70, 2.25) < 0.001
ECMO Yes vs. No -0.6718 0.1296 0.51 (0.40, 0.66) < 0.001
Nitric oxide Yes vs. No 0.2632 0.0931 1.30 (1.08, 1.56) 0.0047
CMV CMV vs. None -1.0261 0.045 0.36 (0.33, 0.39) < 0.001
HFOV HFOV vs. None -1.1546 0.1312 0.32 (0.24, 0.41) < 0.001
ICU length of stay 3 day increase -0.0506 0.0031 0.95 (0.95, 0.96) < 0.001 Days of Mechanical Ventilation 3 day increase -0.0932 0.0081 0.91 (0.90, 0.93) < 0.001
** Favorable neurologic outcome was defined as either no change, or improvement in PCPC from ICU admission to ICU discharge. Abbreviations: PIM-2: Pediatric Index of Mortality; ECMO: Extracorporeal Membrane Oxygenation; CMV: Conventional Mechanical Ventilation; HFOV: High Frequency Oscillatory Ventilation; ICU: Intensive Care Unit; LOS: Length of stay, MV: Mechanical Ventilation. An online calculator for the tool can be accessed at https://soipredictiontool.shinyapps.io/GNOScore/.
Supplemental Table 4. Sample calculation for predicting favorable neurological outcome using alternative definition**
Example Patient Formula for calculation Sample calculation
Intercept 3.633 3.633
Age = 1 month -0.002598 × (age in months) -0.002598 × (1)= -0.002598
Weight = 10 kg -0.01116 × (weight in kg) -0.01116 × (10) = -0.1116
White race= no +0 (white race) +0 (0) = 0
African American race= yes -0.0656 (African American race) -0.0656 (1) = -0.0656
Hispanic race = no -0.0184 (Hispanic ethnicity) -0.0184 (0) = 0
Other race = no -0.1118 (other race) -0.1118 (0) = 0
Chromosomal anomaly= no +0.9923 (chromosomal anomaly) +0.9923 (0) = 0 PIM-2 score at ICU admission= -2 -0.2751 × (PIM-2 score) -0.2751 × (-2) = +0.5502 Acute respiratory failure= yes +0.1567 (acute respiratory failure) +0.1567 (1) = +0.1567 Shock/hypotension= yes -0.1696 (shock/hypotension) -0.1696 (1) = -0.1696
Cardiac arrest= yes -0.7489 (cardiac arrest) -0.7489 (1) = -0.7489
Renal insufficiency= yes -0.1948 (renal insufficiency) - 0.1948 (1) = -0.1948 Stroke= yes -1.314 (brain hemorrhage/ischemia) -1.314 (1) = -1.314
Seizures= yes -0.3051 (seizures) -0.3051 (1) = -0.3051
Head trauma= no -1.4148 (head trauma) -1.4148 (0) = 0
Non-head trauma= no -0.6621 (non-head trauma) -0.6621 (0) = 0
Acquired heart disease= no + 0.1639 (acquired heart disease) +0.1639 (0) = 0
Cardiac surgery= no + 0.6729 (cardiac surgery) +0.6729 (0) = 0
ECMO= yes - 0.6718 (ECMO) -0.6718 (1) = -0.6718
Nitric oxide= no + 0.2632 (nitric oxide) +0.2632 (0) = 0
HFOV= yes - 1.1546 (HFOV) -1.1546 (1) = -1.1546
Conventional ventilation= no -1.0261 (conventional ventilation) -1.0261 (0) = 0 ICU length of stay = 30 days -0.01687 × (ICU length of stay) -0.01687 × (30) = -0.5061 Mechanical ventilation duration= 10 days -0.03106 × (days of MV) -0.03106 × (10) = -0.3106
Total logit -1.2154
Probability favorable neurological outcome (%)
exp (logit)/ (1+exp(logit)) exp-1.2154/(1+ exp-1.2154) = 0.229 or 22.9%
Note: If the variable is YES, multiply by 1; if the variable is NO, multiply by 0. ** Favorable neurologic outcome was defined as either no change, or improvement in PCPC from ICU admission to ICU discharge. Abbreviations: PIM-2:
Pediatric Index of Mortality; ECMO: Extracorporeal Membrane Oxygenation; HFOV: High Frequency Oscillatory Ventilation; ICU: Intensive Care Unit; MV: Mechanical Ventilation. An online calculator for the tool can be accessed at https://soipredictiontool.shinyapps.io/GNOScore/.
Supplemental Table 5. Comparison of predicted with observed outcomes by quintile of predictive index**
New tool Probability Favorable Neurologic Outcome
Incidence Ratio Quintile N Minimum Maximum Average Observed
(O)
Expected
(E) O/E (95% CI)
1 28,240 0.0001 0.9955 0.9439 26,340 26,654.74 0.988 (0.976, 1.000)
2 28,240 0.7871 0.9958 0.9711 27,254 27,423.81 0.994 (0.982, 1.006)
3 28,240 0.8764 0.9964 0.9769 27,493 27,588.81 0.997 (0.985, 1.009)
4 28,240 0.9054 0.9971 0.9811 27,534 27,706.5 0.994 (0.982, 1.006)
5 28,156 0.9359 0.9993 0.9839 27,577 27,701.43 0.996 (0.984, 1.008)
Overall 141,116 0.0001 0.9993 0.9713 136,198 137,075.29 0.994 (0.989, 0.999)
Favorable neurologic outcome was defined as either no change, or improvement in PCPC from ICU admission to ICU discharge.
Supplemental Table 6. Intra-cluster correlation coefficient (ICC) as a ratio of between cluster variation to the sum of between cluster and within cluster variation.
Variable ICC
Favorable Neurological Outcome (PCPC change by 2) 0.035 Favorable Neurological Outcome (PCPC change by 1) 0.094
Age 0.048
Weight 0.047
Race 0.183
Chromosomal anomaly 0.013
PIM-2 Score 0.097
Acute respiratory failure 0.093
Shock/hypotension 0.013
Cardiac Arrest 0.003
Renal failure 0.017
Stroke 0.057
Seizures 0.025
Head trauma 0.020
Non-head trauma 0.035
Acquired heart disease 0.022
Cardiac surgery 0.078
ECMO 0.009
Nitric Oxide 0.037
Mechanical Ventilation 0.103
Length of Mechanical Ventilation 0.024
Length of ICU stay 0.041
