Quantitative EEG and neurological recovery with therapeutic hypothermia after asphyxial cardiac arrest in rats

Abstract

We test the hypothesis that quantitative electroencephalogram (qEEG) can be used to objectively assess functional electrophysiological recovery of brain after hypothermia in an asphyxial cardiac arrest rodent model. Twenty-eight rats were randomly subjected to 7-min (n = 14) and 9-min (n = 14) asphyxia times. One half of each group (n = 7) was randomly subjected to hypothermia (T = 33 degrees C for 12 h) and the other half (n = 7) to normothermia (T = 37 degrees C). Continuous physiologic monitoring of blood pressure, EEG, and core body temperature monitoring and intermittent arterial blood gas (ABG) analysis was undertaken. Neurological recovery after resuscitation was monitored using serial Neurological Deficit Score (NDS) calculation and qEEG analysis. Information Quantity (IQ), a previously validated measure of relative EEG entropy, was employed to monitor electrical recovery. The experiment demonstrated greater recovery of IQ in rats treated with hypothermia compared to normothermic controls in both injury groups (P < 0.05). The 72-h NDS of the hypothermia group was also significantly improved compared to the normothermia group (P < 0.05). IQ values measured at 4 h had a strong correlation with the primary neurological outcome measure, 72-h NDS score (Pearson correlation 0.746, 2-tailed significance <0.001). IQ is sensitive to the acceleration of neurological recovery as measured NDS after asphyxial cardiac arrest known to occur with induced hypothermia. These results demonstrate the potential utility of qEEG-IQ to track the response to neuroprotective hypothermia during the early phase of recovery from cardiac arrest.

Fig. 1

Temperature recording of normothermic and hypothermic rats with 7-min asphyxia (a) baseline 0–5 min, asphyxial CA period 10–17 min, CPR 17 min, hypothermia period 77–797 min, re-warming period 798–917 min; and 9-min asphyxia (b) baseline 0–5 min, asphyxial CA period 10–19 min, CPR 19 min, hypothermia period 79–799 min, re-warming period 800–919 min. The solid black line is mean temperature and gray field is SEM.

Fig. 2

NDS score by injury and temperature groups (Box-plot of median and interquartile range (25th and 75th percentile). Statistically significant differences existed between hypothermic and normothermic groups (z = −2.06, P = 0.039) and between 7-min and 9-min group (z = 3.05, P = 0.002).

Fig. 3

Raw EEG data of representative animals and IQ at various time points with 7 min asphyxia: (a) real-time raw EEG under hypothermia, (b) Real-time raw EEG under normothermia, (c) raw compressed EEG under hypothermia, (I) baseline prior to CA, 0 min, (II) early stage after CA, 20 min, (III) initiation of hypothermia, 60 min, (IV) hypothermia maintenance period, 4 h, (V) initiation of rewarming, 12 h, (VI) late recovery, 24 h, (VII) late recovery, 48 h, (VIII) late recovery, 72 h. (d) Raw compressed EEG under normothermia. (e) IQ plots for hypothermia and normothermia at the same time points, showing the return of the EEG to baseline (hatched line) in hypothermia treated animal.

Fig. 4

Comparison of IQ between hypothermic and normothermic rats subjected to 7-min (a) and 9-min (b) ischemia at different time periods: IQ1 baseline, IQ2 CA period, IQ3 hypothermia starting period, IQ4 hypothermia maintenance period, IQ5 re-warming period, IQ6 24 h after ROSC, IQ7 48 h after ROSC, IQ8 72 h after ROSC.