Early electrophysiologic markers predict functional outcome associated with temperature manipulation after cardiac arrest in rats.

Approximately 164,600 cardiac arrests (CAs) occur in the United States each year (1). Among initial survivors, 80% remain comatose after resuscitation (2) and neurological complications represent the leading cause of disability (3, 4). The ischemic brain is sensitive to temperature, such that small differences can critically influence neuropathological outcomes (5). Hyperthermia has been demonstrated to worsen ischemic outcome and is associated with increased brain injury in animal models (5, 6) and clinical studies (7-9). On the other hand, induced hypothermia to 32-34°C is recommended for comatose survivors of CA (10, 11) and was recently shown to significantly mitigate brain injury in animal models (12-14) and clinical trials (15-18). Neurological monitoring of comatose CA survivors is complicated by the requirement for sedative and paralytic agents, particularly in patients who are treated with hypothermia. Comatose CA survivors are typically cared for by nurses and physicians in general or cardiac intensive care units with little specialized training in neurological examination. In addition, the ability to detect even major changes in brain function in comatose patients is limited. Electroencephalography (EEG) is frequently employed for neuromonitoring and prognostication (19-21). A recent publication from our group demonstrated that physicians were more likely to withdraw supportive measures in patients with negative neurologic predictors (22). As a diagnostic tool, however, waveform-based EEG analysis is subjective and laborious, with results depending on the interpreter’s expertise(23). Previous attempts to use early quantitative EEG (qEEG) as a measure of neurological recovery after CA have utilized power spectral analysis (24). A readily translatable tool for tracking the effect of temperature on recovery of cortical electrical function has not been thoroughly elucidated. We have previously established and validated a rodent model for global ischemic brain injury after CA (25, 26) using a standardized Neurological Deficit Scale (NDS) that was adapted from human and animal scales (12, 14, 17, 27-29). We developed the theoretical measure information quantity (IQ) to provide an objective measure of entropy in EEG amplitude (30). Our subsequent work showed that greater injury was associated with lower entropy and reduced IQ values. This methodology tracked functional outcome (23, 25, 26, 31-36) and accurately differentiated EEG recovery between rats treated with hypothermia and normothermia after cardiac arrest (23, 33). To expand on these findings, we evaluated the impact of qEEG-IQ marker for monitoring the effect of temperature on neurological recovery.