Between January 2005 and July 2010, we treated 680 subjects with in-hospital or out-of-hospital cardiac arrest (). We identified 151 subjects who were awake on presentation and thus did not receive a CT scan (GCS motor score=6). We excluded subjects with surgical or traumatic causes of arrest (N=11), withdrawal of care or failure to sustain pulses long enough to receive CT scan (N=20), and current incarceration (N=3). If a patient had two cardiac arrests within 6 months, we excluded the second cardiac arrest (N=4). A cranial CT was not performed at this hospital within 24 hours of cardiac arrest for 233 comatose patients. This latter group included patients with CT scan performed at another hospital, CT scan performed >24 hours after arrest, and in-hospital cardiac arrests for whom CT scanning was less common practice. Finally, we did not analyze CT scans for subjects with intracranial hemorrhage (N=10), intravenous contrast from prior studies (N=3), and large scanning artifacts (N=5). A total of 240 CT scans remained for analysis. Out-of-hospital cardiac arrest and therapeutic hypothermia were more common in the study cohort than in the entire cardiac arrest population ().
Patient demographics for study cohort, comatose patients without CT, all excluded patients, and entire database.
Attenuation measurements for all regions of interest were not normally distributed (). Gray matter attenuation in the basal ganglia level (CN, PU, THL) tended to be higher than in the high convexity levels (MC1, MC2). White matter attenuation also tended to be higher in the basal ganglia level (CC, PIC) than in the centrum semiovale and high convexity levels (MWM1, MWM2). Gray matter attenuation in all regions (CN, PU, THL, MC1, MC2) was significantly different between survivors and non-survivors (p<0.005). White matter attenuation (CC, PIC, MWM1, MWM2) did not differ between survivors and non-survivors. Gray matter attenuation values were associated with survival (p<0.02), whereas white matter values were not associated with survival. In ROC curves, gray matter attenuation in each region was a weak predictor of survival (AUC for CN=0.62, PU=0.63, THL=0.65, MC1=0.63, and MC2=0.61).
A. Median (IQR) attenuation values for survivors and non-survivors. (CN=caudate nucleus, PU=putamen, THL=thalamus, PIC=posterior limb of internal capsule, MC=medial cortex, MWM=medial white matter) B. Median (IQR) GWR for survivors and non-survivors.
GWR ranged from 0.98 to 1.77 in cerebrum, 0.79 to 1.57 in basal ganglia and 0.95 to 1.58 for average (). In the 29 subjects who were awake on presentation (GCS-motor=6), median GWR was 1.24 (IQR 1.20-1.32) for cerebrum, 1.30 (IQR 1.28-1.35) for basal ganglia, and 1.27 (IQR 1.24-1.33) for average. GWR measured in cerebrum and basal ganglia were correlated (Pearson’s r=0.448; p<0.01). Cerebrum GWR tended to be lower, with the majority of data points falling below the identity line.
Association of GWR with Initial GCS Motor Score
Average, basal ganglia, and cerebral GWR were associated with initial GCS Motor Score (p<0.001, ). The majority of patients with GWR<1.20 had initial GCS motor scores of 1.
Average GWR decreases with initial GCS-motor score. Subjects with the lowest GWR had GCS-motor scores = 1.
To measure inter-rater reliability of GWR estimates, a second investigator measured GWR from a randomly generated sample of 5% of the study cohort. Ratios between investigators had a Pearson’s correlation coefficient of 0.642, indicating good agreement. Test-retest reliability was measured from a randomly generated sample of 10% of the study cohort and also was extremely consistent, with a Pearson’s correlation coefficient of 0.931.
Influence of Arrest-to-CT Time Interval
The time elapsed between the cardiac arrest and cranial CT (arrest-to-CT Interval) varied from 9 minutes to 23.8 hours (median 4.2 hours, IQR 2.7-6.9). Arrest-to-CT interval was 6 hours or less in the majority of cases (67%) (). There was no association between arrest-to-CT interval and gray matter attenuation in any measured region. Likewise, arrest-to-CT interval was not associated with basal ganglia GWR (p=0.24), cerebrum GWR (p=0.08), or average GWR (p=0.09).
Association of GWR with Survival and Outcome
Average, basal ganglia, and cerebral GWR were significantly higher in survivors than in non-survivors (p<0.005), and all were positively associated with survival (p<0.005). Average GWR was the strongest predictor of mortality as assessed using ROC curves (basal ganglia AUC=0.69; cerebrum AUC=0.67; average AUC = 0.72). Average GWR < 1.20 predicted death with a sensitivity of 36% (CI 29-45%), a specificity of 98% (CI 91-100%), a positive predictive value of 97% (CI 87-99%), and a negative predictive value of 46% (CI 39-54%). The false positive rate for predicting death with this cutoff was 2/58, or 3% (CI 1-13%).
Average, basal ganglia, and cerebral GWR were statistically associated with CPC and MRS (p≤0.001, Kruskal-Wallis) (). However, inspection of the data reveals that this association merely reflected the low GWR in patients who died (MRS=6; CPC=5).
Figure 3 Average GWR on initial CT scan is related to functional outcome at hospital discharge measured by a) Cerebral Performance Category and b) Modified Rankin Scale. Lower GWR was associated with CPC and mRS, but this association results from the fact that (more ...)
shows mortality as a function of average GWR for patients receiving hypothermia (N=167) and patients not receiving hypothermia (N=72). Average and basal ganglia GWR were associated with survival in both groups (p<0.05, binary logistic regression), but cerebral GWR was only associated with survival in the hypothermia group (hypothermia p<0.001; no-hypothermia p=0.12). Both groups show near 100% mortality with average GWR< 1.2, although 2 patients with GWR=1.17 and GWR =1.15 who were treated with hypothermia did survive to hospital discharge.
Mortality increases in subjects with lower average GWR receiving hypothermia (top) and patients not receiving hypothermia (bottom).