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. Author manuscript; available in PMC: 2015 Dec 1.
Published in final edited form as: Crit Care Med. 2014 Dec;42(12):2575–2581. doi: 10.1097/CCM.0000000000000547

Cerebral performance category at hospital discharge predicts long-term survival of cardiac arrest survivors receiving targeted temperature management

Cindy H Hsu 1, Jiaqi Li 1, Marisa J Cinousis 1, Kelsey R Sheak 1, David F Gaieski 1, Benjamin S Abella 1, Marion Leary 1
PMCID: PMC4236246  NIHMSID: NIHMS604325  PMID: 25072759

Abstract

Objective

Despite recent advancements in post-cardiac arrest resuscitation, the optimal measurement of post-arrest outcome remains unclear. We hypothesized that cerebral performance category (CPC) score can predict the long-term outcome of post- arrest survivors who received targeted temperature management (TTM) during their post-arrest hospital care.

Design

Retrospective chart review.

Setting

Two academic medical centers from May, 2005 to December, 2012.

Patients

The medical records of 2,417 out-of-hospital and in-hospital post-cardiac arrest patients were reviewed to identify 140 out of 582 survivors who received TTM.

Interventions

None.

Measurements and Main Results

The CPC scores at hospital discharge were determined by three independent abstractors. The 1-month, 6-month, and 12-month survival of these patients were determined by reviewing hospital records, querying the Social Security Death Index, and follow-up telephone calls. The unadjusted long-term survival and adjusted survival association with CPC were calculated. Of the 2,417 identified cardiac arrest patients, 24.1% (582/2417) were successfully resuscitated, of whom 24.1% (140/582) received post-arrest TTM. Overall, 42.9% (60/140) were discharged with CPC 1, 27.1% (38/140) with CPC 2, 18.6% (26/140) with CPC 3, and 11.4% (16/140) with CPC 4. CPC 1 survivors had the highest long-term survival followed by CPC 2 and 3, with CPC 4 having the lowest long-term survival (p < 0.001, log-rank test). We found that CPC 3 (hazard ratio = 3.62, p < 0.05) and CPC 4 (hazard ratio = 12.73, p <0.001) remained associated with worse survival after adjusting for age, gender, race, shockable rhythm, time to TTM initiation, total duration of resuscitation, withdrawal of care, and location of arrest.

Conclusion

Patients with different CPC scores at discharge have significantly different survival trajectories. Favorable CPC at hospital discharge predicts better long-term outcomes of cardiac arrest survivors who received TTM than those with less favorable CPC scores.

Keywords: Cerebral Performance Category, targeted temperature management, therapeutic hypothermia, cardiac arrest, survival, resuscitation

BACKGROUND

Cardiac arrest remains one of the leading causes of death in the United States, affecting approximately 350,000 individuals each year with about half of them occurring in-hospital (1). Despite recent advancements in cardiopulmonary resuscitation, post-arrest survival to hospital discharge remains low for both out-of-hospital cardiac arrest (OHCA) (2) and in-hospital cardiac arrest (IHCA) (3, 4). Moreover, previous studies have suggested that approximately two-thirds of the OHCA patients and a quarter of the IHCA patients died from neurological injury (5).

Post-cardiac arrest targeted temperature management (TTM) has been shown to improve survival and neurologic outcome of cardiac arrest patients (6–9) and is now a Class I and IIb recommendation for patients resuscitated from shockable and non-shockable rhythms, respectively (10). Recent data from the multicenter, international, randomized TTM trial found no difference in the survival and neurologic outcome of OHCA survivors who were maintained at 33°C compared to 36°C, but emphasized the importance of active post-arrest temperature management to prevent pyrexia (11, 12). Many measurement tools have been utilized in attempt to describe post-arrest neurologic functional outcome (13–25). However, little is known regarding the parameter that best predicts long-term survival of both OHCA and IHCA patients. Large retrospective cohort studies thus far have focused on in-hospital survival (2–4,26–28). A few smaller studies have examined predictors of long-term survival (29–32) and even fewer studies specifically evaluated the long-term prognosis of patients who received TTM (11, 15,20, 21, 25, 33, 34). As such, cardiac arrest survivors and their families are often faced with many uncertainties regarding their survival duration and neurologic outcome upon hospital discharge.

Cerebral Performance Category (CPC) is one of the more widely used assessments of the functional status of cardiac arrest patients. Its score ranges from 1 (good cerebral performance) to 5 (brain death), with CPC 1 and 2 generally categorized in prior investigations as good neurological outcome and 3 to 5 as poor outcome (35–37). Recent studies have demonstrated that CPC at hospital discharge can predict the long-term survival outcome of OHCA (38) and elderly survivors of IHCA (39). However, little is known regarding the correlation between CPC scores and long-term survival of patients who received TTM following cardiac arrest resuscitation. We hypothesize that CPC score could be a useful predictor of long-term survival of both OHCA and IHCA patients who received post-arrest TTM.

MATERIALS AND METHODS

We performed a retrospective analysis of 2,417 cardiac arrest patients cared for at two academic medical centers between May, 2005 and December, 2012. We identified the patients who received post-arrest care after return of spontaneous circulation (ROSC) and survived to hospital discharge and the subset of them who received TTM. All TTM was performed with an external cooling device to achieve a targeted temperature of 33 to 34°C. The CPC scores at hospital discharge were determined by one of three independent abstractors. The 1-month, 6-month, and 12-month survival of these patients were determined by reviewing hospital records, querying the Social Security Death Index, and follow-up telephone calls. Study cohort characteristics were analyzed using ANOVA to test the equivalence in means of continuous variables between CPC groups. Chi-square tests and Fisher's exact tests were used to test for equivalence in proportions for the categorical variables. This study was approved by the University of Pennsylvania Institutional Review Board with waiver of informed consent.

Survival time was calculated as the difference between date of death and discharge date or between May 4, 2013 and discharge date for those still alive. Non-parametric Kaplan-Meier survival analysis was used to compare survival among four CPC categories of the overall cohort then within the OHCA and IHCA subgroups. Log-rank test was used to determine whether differences in survival were statistically significant. Cox proportional hazards regression models were used to estimate survival associated with CPC, with and without adjusting for relevant covariates. For the adjusted model, we adjusted for age, gender, race, shockable rhythm, time to TTM initiation, total duration of resuscitation, withdrawal of care, and location of arrest. Both hazard ratios from unadjusted and adjusted Cox proportional hazard model were determined. Patients for whom adjusted variables were not available were removed from the hazard ratio analysis. ANOVA was used to determine whether there were significant differences between the missing data from the different CPC groups. All analyses were conducted using R Version 2.15.

RESULTS

Of the 2,417 identified patients with cardiac arrest, 24.1% (582/2417) survived to hospital discharge, and 24.1% (140/582) of them received post-arrest TTM (Figure 1). The mean age was 54.4±15.7 years; 65% (91/140) were male, 49.6% (64/140) had initial shockable rhythms, and 64.8% (83/140) were OHCA events (Table 1). Overall, 42.9% (60/140) were discharged with CPC 1, 27.1% (38/140) with CPC 2, 18.6% (26/140) with CPC 3, and 11.4% (16/140) with CPC 4 (Figure 1). There were significant differences between the mean age, percentage of shockable initial rhythm, withdrawal of care, and location of arrest between the CPC groups (Table 1). CPC 1 had the most patients with shockable rhythm (66.7%) and OHCA (82.4%), while CPC 4 had the most withdrawal of care (37.5%).

Figure 1.

Figure 1

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Flow Diagram of Study Population. Of the 2,417 identified patients with cardiac arrest, 582 survived to hospital discharge and 140 received post-arrest TTM. Of the TTM survivors, 42.9% (60/140) was discharged with CPC 1, 27.1% (38/140) with CPC 2, 18.6% (26/140) with CPC 3, and 11.4% (16/140) with CPC 4. CPC = Cerebral Performance Category; TTM = Targeted Temperature Management

Table 1.

Patient Characteristics According to CPC Scores. CPC = Cerebral Performance Category; TTM = targeted temperature management; OHCA = out-ofhospital cardiac arrest; IHCA = in-hospital cardiac arrest; sd = standard deviation

Characteristics Overall CPC1 CPC2 CPC3 CPC4 p-value
N=140 N=60 N=38 N=26 N=16
Mean age, yr (sd) 54.4 (15.7) 50.2 (14.5) 58.1 (16.9) 59.7 (14.6) 53.1 (15.1) <0.05
Female, % (n) 35.0 (49) 40.0 (24) 28.9 (11) 30.8 (8) 37.5 (6) 0.677
Race White, % (n) 46.4 (65) 46.7 (28) 52.6 (20) 42.3 (11) 37.5 (6) 0.309
Black, % (n) 40 (56) 40 (24) 34.2 (13) 34.6 (9) 62.5 (10)
Other, % (n) 13.6 (19) 13.3 (8) 13.2 (5) 23.1 (6) 0 (0)
Shockable initial rhythm, % (n) 49.6 (64) 66.7 (36) 52.9 (18) 28.0 (7) 18.8 (3) <0.001
Mean time to TTM initiation, hours 3.3 (4.6) 2.3 (3.4) 3.2 (4.0) 5.3 (7.1) 4.4 (4.1) 0.084
Mean total duration of resuscitation in minutes (sd) 42.3 (113.0) 46.9 (119.4) 21.8 (44.5) 73.0 (184.6) 27.1 (18.1) 0.360
Withdrawal of care, % (n) 5.8 (8) 0 (0) 0 (0) 7.7 (2) 37.5 (6) <0.001
Location of arrest OHCA, % (n) 64.8 (83) 82.4 (42) 54.1 (20) 42.3 (11) 71.4 (10) <0.05
IHCA, % (n) 32.1 (45) 15 (9) 44.7 (17) 57.7 (15) 25 (4)
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When non-parametric Kaplan-Meier survival analysis was used to compare survival among four CPC categories (Figure 2A), the estimated survival rates of each CPC group and of the overall cohort showed variability. CPC 1 survivors had the highest long-term survival followed by CPC 2 and 3, with CPC 4 having the lowest long-term survival (p < 0.001, log-rank test). The one-year survival estimate was 0.915 for CPC 1, 0.736 for CPC 2, 0.536 for CPC 3, and 0.125 for CPC 4 (Table 2A). We also performed separate Kaplan-Meier survival analysis for the OHCA and IHCA subgroups. We found that the CPC 1 and CPC 2 OHCA survivors had similar unadjusted survival trajectories (Figure and Table 2B), while IHCA CPC 2 survivors had worse unadjusted survival and no IHCA CPC 4 patients survived to 6 months (Figure and Table 2C).

Figure 2.

Figure 2

Figure 2

Figure 2

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Kaplan-Meier Survival Plot By CPC of the A) Overall Cohort, B) OHCA Subgroup, and C) IHCA Subgroup. CPC = Cerebral Performance Category; OHCA = out-of-hospital cardiac arrest; IHCA = in-hospital cardiac arrest

Table 2.

Survival Estimates by CPC of the A) Overall Cohort, B) OHCA Subgroup, and C) IHCA Subgroup. The 6-month to 3-year survival estimates are presented with 95% confidence intervals. CPC = Cerebral Performance Category; OHCA = out-of-hospital cardiac arrest; IHCA = in-hospital cardiac arrest

2A) Overall
CPC1 CPC2 CPC3 CPC4
6 month 0.933 (0.872 – 0.999) 0.763 (0.639 – 0.911) 0.577 (0.415 – 0.802) 0.438 (0.251– 0.763)
1 year 0.915 (0.846 – 0.989) 0.736 (0.608 – 0.891) 0.536 (0.374 – 0.768) 0.125 (0.034 – 0.457)
2 year 0.845 (0.750 – 0.953) 0.669 (0.512 – 0.874) 0.536 (0.374 – 0.768) NA
3 year 0.845 (0.750 – 0.953) 0.535 (0.355 – 0.806) NA NA
2B) OHCA
CPC1 CPC2 CPC3 CPC4
6 month 0.929 (0.854 – 1.000) 0.850 (0.707 – 1.000) 0.545 (0.318 – 0.936) 0.700 (0.467 – 1.000)
1 year 0.903 (0.817 – 0.998) 0.850 (0.707 – 1.000) 0.455 (0.238 – 0.868) 0.200 (0.058 – 0.691)
2 year 0.832 (0.715 – 0.968) 0.850 (0.707 – 1.000) 0.455 (0.238 – 0.868) 0.100 (0.016 – 0.642)
3 year 0.832 (0.715 – 0.968) 0.850 (0.707 – 1.000) NA NA
2C) IHCA
CPC1 CPC2 CPC3 CPC4
6 month 0.889 (0.706 – 1.000) 0.647 (0.456 – 0.919) 0.600 (0.397 – 0.907) NA
1 year 0.762 (0.521 – 1.000) 0.588 (0.395 – 0.876) 0.600 (0.397 – 0.907) NA
2 year 0.762 (0.521 – 1.000) 0.471 (0.260 – 0.850) 0.600 (0.397 – 0.907) NA
3 year 0.762 (0.521 – 1.000) 0.235 (0.075 – 0.739) NA NA
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Table 3 provides estimated hazard ratios from both unadjusted and adjusted Cox Proportional Hazards Models. For the adjusted model, we adjusted for age, gender, race, shockable rhythm, time to TTM initiation, total duration of resuscitation, withdrawal of care, and location of arrest. We found that worse CPC scores were associated with higher hazards of death (p<0.001). Compared to CPC 1, CPC 3 (hazard ratio = 3.62, p < 0.05) and CPC 4 (hazard ratio = 12.73, p <0.001) remained associated with worse survival after adjusting for all the aforementioned variables (Table 3). In the adjusted model, 49 out of 140 (35%) observations were eliminated from the hazard ratio analysis due to unavailable data. The distribution and percentage of missing data were similar across all CPC groups (Table 4).

Table 3.

Hazard Ratios from Unadjusted and Adjusted Cox Proportional Hazard Model. HR = hazard ratio compared to CPC 1; Unadjusted and adjusted hazard ratio with 95% confidence interval and p-value

Unadjusted Adjusted
HR CI p-value HR CI p-value
CPC1 1 - - 1 - -
CPC2 3.24 (1.34, 7.84) <0.01 0.87 (0.24, 3.12) 0.834
CPC3 5.12 (2.09, 12.57) <0.001 3.62 (1.06, 12.35) <0.05
CPC4 18.56 (7.61, 45.25) <0.001 11.99 (2.98, 48.22) <0.001
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Table 4.

Distribution and Percentage of Missing Data by CPC. CPC = Cerebral Performance Category

% Missing (n) p-value
Variables Overall CPC1 CPC2 CPC3 CPC4
Shockable initial rhythm 7.9 (11) 10.0 (6) 10.5 (4) 3.8 (1) 0.0 (0) 0.448
Time to TTM initiation 20.7 (29) 18.3 (11) 23.7 (9) 26.9 (7) 12.5 (2) 0.649
Total duration of resuscitation 7.9 (11) 8.3 (5) 7.9 (3) 11.5 (3) 0.0 (0) 0.607
Location of arrest 8.6 (12) 0.15 (9) 3.6 (1) 0.0 (0) 12.5 (2) 0.054
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DISCUSSION

In this study, we found evidence that CPC scores at hospital discharge are associated with long-term survival of cardiac arrest patients who received TTM. Specifically, CPC scores of 3 and 4 at hospital discharge were associated with worse long-term survival after adjusting for age, gender, race, shockable initial rhythm, time to TTM initiation, total duration of resuscitation, withdrawal of care, and location of arrest. In addition, patients with worse CPC at discharge had larger decrement in their unadjusted long-term survival over time. The data from our study may help to determine the duration of resources such as medical assessment, home-care assistance, and physical and occupational therapy required for post-arrest survivors after their hospital discharge.

Our findings are consistent with recent studies on the association between CPC at hospital discharge and long-term survival of cardiac arrest patients. Phelps et al (38) found that 62% of OHCA patients over a 9-year period in King County, WA, had CPC 1 at discharge, 23% had CPC 2, 10% had CPC 3, and 5% had CPC 4. They found that a more favorable CPC was associated with better long-term prognosis, with 5 year survival of 74% for CPC 1, 55% for CPC 2, 44% for CPC 3, and 22% for CPC 4. Our study showed a similar survival distribution of CPC groups but differed from Phelps et al. in that we focused on patients who received TTM but included both OHCA and IHCA patients. Our study cohort had higher percentages of patients with CPC 3 and CPC 4 at discharge compared to that of Phelps et al, and we did not see a difference between the adjusted hazard ratio for the CPC 1 and CPC 2 groups. Interestingly, our subgroup Kaplan-Meier survival analysis of the OHCA TTM survivors also showed that CPC 1 and CPC 2 groups had similar unadjusted survival trajectories (Table and Figure 2B), although this finding was from much smaller sample sizes compared to that of Phelps et al.

Chan et al (39) linked the IHCA database of Get with the Guidelines-Resuscitation (GWTG-R) with Medicare claim files to identify elderly patients greater than 65 years of age who survived to hospital discharge after IHCA from 2000 to 2008. They found that 59% survived for at least 1 year and 50% survived to 2 years. Their study cohort consisted of 48.1% with CPC 1 at discharge, 34.3% with CPC 2, 14.4% with CPC 3, and 3.2% with CPC 4. Our 1-year survival distribution was similar to that of Chan et al where the risk adjusted 1-year survival of CPC 1 was 72.8%, of CPC 2 was 61.1%, of CPC 3 was 42.2%, and of CPC 4 was 10.2%. They also found 1-year survival to be lower for older patients, men, and black patients. Although Chan et al examined a much larger cohort of elderly IHCA patients than included in our study, it was not clear how many patients in that study received TTM. However, Mikkelsen et al recently reported that TTM was underutilized in the GWTG-R cohort, with TTM applied to only 2% of patients from 2003 to 2009 (40). Our subgroup Kaplan-Meier survival analysis of the IHCA TTM survivors suggested that IHCA CPC 2 survivors might have worse unadjusted survival and no IHCA CPC 4 TTM patients survived to 6 months, although the individual sample sizes of the IHCA CPC groups were small.

Our study has several limitations. First, this study was conducted at two tertiary centers that shared the same TTM protocol, which may limit the applicability of our findings to other settings. Both Phelps et al (38) and Chan et al (39) saw differences between the long-term survival of CPC 1 and CPC 2, whereas we did not see any differences in hazard ratio after adjusting for age, gender, race, shockable rhythm, time to TTM, total duration of resuscitation, withdrawal of care, and OHCA. This could be explained by several factors. Our smaller sample size of the post-arrest TTM patients and the higher percentage of missing data (35%) for the adjusted variables might have contributed to the insufficient power seen in the adjusted hazard ratio for CPC 1–3. However, we found that the distribution and percentage of missing data were consistent in all variables between the different CPC groups. We also did not adjust for other comorbidities or the cause of death. The CPC score at discharge was determined either by reviewing medical records for explicitly stated CPC scores or extrapolated from clinical notes by one of three different abstractors. Thus, it is possible that inter-rater reliability may vary for the study cohort (41–43). Finally, as we focused only on the patients who received TTM, it is possible that the baseline differences between the TTM and non-TTM groups could affect the prognosticative accuracy of the discharge CPC score.

There are inherent limitations associated with the use of CPC as the sole prognosticative tool. Although we obtained valuable information regarding the long-term survival rate of cardiac arrest patients based on their CPC at discharge, we did not study their long-term neurologic or functional status after discharge. Thus, it is possible that differences exist between the functional status of CPC1 and 2 patients after hospital discharge despite no significant differences in their long-term survival. CPC has been criticized as a fairly crude measurement of neurological recovery and functional status due to its assessment of multiple functional domains with variable reliability and subjectivity. Prior studies have suggested that CPC can underestimate the level of neuropsychologic and cognitive impairments (43–50) as well as societal participation in cardiac arrest survivors (46). In addition to CPC, other global assessment tools such as the Glasgow Coma Scale, Glasgow Outcome Scale, Glasgow Outcome Scale–Extended, and modified Rankin scores as well as predictive models that specifically addresses the outcome TTM patients such as the 5-R score (34) have been proposed as alternative classification schemata and may have greater predicative value (36, 42, 50). To address the aforementioned limitations, we hope to examine the differences in the functional status between the CPC groups in the future by utilizing neurocognitive tests.

CONCLUSIONS

Post-arrest TTM patients with different CPC score at discharge have significantly different survival trajectories. Favorable CPC at hospital discharge predicts better long-term outcomes of cardiac arrest survivors who received TTM than those with less favorable CPC scores. Specifically, CPC 3 and CPC 4 scores are associated with worse long-term outcome in post-arrest patients. As TTM becomes more widely utilized in post-arrest care, CPC at discharge could serve as a useful prognostic assessment for providers and survivors. Further studies and neurocognitive testing of post-arrest survivors may help to predict the duration and types of outpatient resources necessary after their hospital discharge.

Acknowledgments

Copyright form disclosures: Dr. Leary consulted for Stryker Medical and disclosed ownership (Resuscor, LLC - no financial income currently). Dr. Abella consulted for Velomedix Corp and Heartsine Corp, has stock options with Resuscor, and received support from Medivance and Stryker (Honorarium). His institution received grant support from NIH NHLBI, Philips Healthcare, Medtronic, and Stryker.

Footnotes

The remaining authors have disclosed that they do not have any potential conflicts of interest.

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