Abstract

Introduction: Creatine kinase BB isoenzyme (CK-BB) levels in CSF after cardiac arrest (CA) have been shown to predict never awakening though have not been evaluated in patients treated with therapeutic hypothermia (TH). Clinically, CSF CK-BB is tested in those who have not already awakened and are suspected of having a poor prognosis. We aimed to evaluate CSF CK-BB as a prognostic biomarker in the era of TH. Methods: We performed a retrospective cohort study at a single institution of CA patients admitted between 2010 and 2020 and with CSF CK-BB assayed between 36 and 84 hours after CA. We examined the proportion of patients who awakened at hospital discharge and latest follow up in the electronic health record for various CSF CK-BB thresholds. We examined concordance and additive value somatosensory evoked potentials (SSEP). Awakening was defined as following commands or having comprehensible speech. Results: Among 214 eligible patients, mean age was 55 ± 15 years, 72% were male, 33% were non-white, 17% had initial ventricular fibrillation or tachycardia, 90% were out-of-hospital CA, and 83% had TH. A total of 19 (9%) awoke at a mean of 22 ± 28 days. Two patients in a vegetative state at discharge later awoke at 73 (CSF CK-BB 163 U/L) and 101 days (228 U/L). A CSF CK-BB cut-off of ≥ 230 U/L predicted never awakening with a specificity of 100% (binomial 95% CI 82-100%) and a sensitivity of 69% (95% CI 62-76%). When combined with bilaterally absent SSEP, the specificity remained 100% while the sensitivity increased to 80% (95% CI 73-85%). Results were similar after excluding 165 (77%) who had withdrawal of life-sustaining treatment. Discordant findings among 149 patients who had both studies were seen in 13 (9%) with intact SSEP bilaterally but CSF CK-BB ≥ 230 U/L and in 20 (13%) with absent SSEP bilaterally but CSF CK-BB < 230, none of whom awoke. Conclusion: CSF CK-BB levels accurately predict never awakening among CA survivors treated with TH. As part of multimodal prognostic testing with SSEP, the CSF CK-BB cutoff of 230 can optimize sensitivity while maintaining a specificity of 100%. These results are susceptible to a self-fulfilling prophecy, and specificity has a large confidence interval because only a small number of eligible patients awakened.

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