한국학술정보. Key Words: Seizures, Prognosis, Out-of-hospital Cardiac Arrest

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1 Relevance of Seizure with Mortality and Neurologic Prognosis of Out of Hospital Cardiopulmonary Arrest (OHCA) Patients Who had Treated with Therapeutic Hypothermia after Return of Spontaneous Circulation Hong Sup Lee, M.D., Gun Lee, M.D., Jin Joo Kim, M.D., Hyun Mi Park, M.D. 1, Jae Ho Jang, M.D., Sung Youn Hwang, M.D. 2, Sung Youl Hyun, M.D., Hyuk Jun Yang, M.D. Purpose: The purpose of this study is to evaluate relevance of postanoxic seizure with prognosis in cases of outof hospital cardiac arrest (OHCA) patients treated with TH and to research the prognostic role of portable electroencephalography (EEG). Methods: A total of 180 OHCA patients arrived during July of 2008 and June of 2011, and 144 patients who had been treated with therapeutic hypothermia were included in this study. Portable EEG was taken 24 hours after induction of TH and classified by the attending neurologist. As an outcome variable, overall mortality and neurological outcome after six months from discharge were evaluated (Good neurological outcome; Cerebral performance category (CPC) scale 1, 2, Poor neurological outcome; CPC scale 3~5). Results: Among 144 patients, 93 patients (63.9%) were male, and mean age was 51. Eighty two patients (56.9%) survived and almost 30% (43/144) of patients had a good neurological outcome. Sixty five patients (45.1%) had seizures, and, among this group, 19 patients (29.2%) were discharged with a good neurological outcome. No statistical difference was observed between the seizure group and the non-seizure group. Initial rhythm, APACHI II score, and time from basic life support to return of spontaneous circulation (OR, 2.169; 95% CI, 1.158~4.063, OR 1.107; 95% CI 1.064~1.152, OR 1.014; 95% CI 1.006~1.022, respectively) showed statistical importance, however, the seizure group (OR, 0.67, 95% CI, 0.356~1.032, p=0.065) had no statistical relevance with mortality. Grading of EEG by the neurologist showed a positive association with neurological outcomes (p<0.001). Factors associated with good neurological outcome were VF/VT initial rhythm (p=0.005), cardiac cause of arrest (p=0.001), high initial body temperature (p<0.001), low APACHI II score (p=0.010), and shorter time interval between arrest from basic life support (p=0.005). Conclusion: In our study, the seizure group showed no relevance with mortality and prognosis. In hope of achieving a better outcome, careful treatment should be provided in cases of OHCA patients with seizure. Conduct of larger, prospective studies is needed. Key Words: Seizures, Prognosis, Out-of-hospital Cardiac Arrest Department of Emergency Medicine, Gachon University Gil Medical Center, Incheon, Korea, Department of Neurology, Gachon University Gil Medical Center, Incheon, Korea 1, Department of Emergency Medicine, Sungkyunkwan University, School of Medicine, Samsung Changwon Hospital, Changwon, Korea 2 14

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3 16 / Table 1. Classification of EEG records (Hockaday, et al. 1965) Grade I Within Normal limits Alpha rhythm Predominant alpha with rare theta Grade II Mildly abnormal Predominant theta, with rare alpha Predominant theta, with some delta Grade III Moderately abnormal Delta, mixed with theta and rare alpha Predominant theta, with no other activity Grade IV Severely abnormal Diffuse delta, with brief isoelectric intervals Scattered delta in some leads only with absence of activity in other leads Grade V Extremely abnormal A nearly flat record No EEG at all EEG: electroencephalography Fig. 1. This diagram shows distribution of enrolled patients. OHCA: out-of hospital cardiac arrest, ROSC: return of spontaneous circulation, TH: therapeutic hypothermia, CPC: cerebral performance category

4 17 Table 2. Basal characteristics of the patients (N=144, N (%)) Gender, M 93 (64.6) Age, yr, mean ( SD) ( 15.4) Other hospital CPR 43 (29.9) Initial Rhythm, shockable 45 (31.3) Cause of Arrest, Cardiac 67 (46.5) TH methods COOL GUARD (52.1) ARCTIC SUN 54 (37.5) BLANKETROL II 15 (10.4) BT(i), C, mean ( SD) 35.5 ( 1.3) AR_BLS, min, mean ( SD) 07.6 ( 7.1) BLS_ACLS, min, mean ( SD) 93 (64.6) Seizure 65 (45.1) APACHE II, mean ( SD) 25.2 ( 5.4) Lactate, mmol/l, mean ( SD) 08.4 ( 3.7) Survived 82 (56.9) CPC, good 43 (29.9) SD: standard deviation, BT (i): initial body temperature, AR_BLS: duration from arrest to start the basic life support, BLS_ACLS: duration from starting the basic life support to start the advanced cardiac life support, APACHE: acute physiology and chronic health evaluation, CPC: cerebral performance category (good CPC: 1-2, poor CPC: 3-5), CPR: cardiopulmonary resuscitation. *, p<0.05 Table 3. Variables by Seizure (N=144, n (%)) Yes (n=65) Seizure No (n=79) p-value Gender, Male 42 (64.6) 51 (64.6) Age, yr, mean ( SD) 48.7 (16.4) 53.1 (14.4) Initial Rhythm, Shockable 17 (26.2) 28 (35.4) Cause of Arrest, Cardiac 25 (38.5) 42 (53.2) Other hospital CPR 14 (21.5) 30 (38.0) TH methods, COOL GUARD (55.4) 39 (49.4) ARCTIC SUN 24 (36.9) 30 (38.0) BLANKETROL II 05 (07.7) 10 (12.7) BT(i), C, mean ( SD) 35.7 (1.2) 35.6 (01.3) AR_BLS, min, mean ( SD) 07.4 (07.4) 07.8 (06.8) BLS_ACLS, min, mean ( SD) 18.5 (09.2) 19.2 (09.2) APACHE II, mean ( SD) 24.9 (05.7) 25.5 (05.2) Lactate, mmol/l, mean ( SD) 08.2 (03.3) 8.5 (04.0) Survived 42 (64.6) 41 (50.6) CPC, good (6 M) 19 (29.2) 24 (30.4) SD: standard deviation, BT (i): initial body temperature, AR_BLS: duration from arrest to start the basic life support, BLS_ACLS: duration from starting the basic life support to start the advanced cardiac life support, APACHE: acute physiology and chronic health evaluation, CPC: cerebral performance category (good CPC: 1-2, poor CPC: 3-5), CPR: cardiopulmonary resuscitation. * p<0.05

5 18 / Table 4. Variables by Neurologic outcome (N=144, n (%)) Good (n=43) Neurologic Outcome Poor (n=101) p-value Gender, Male 34 (79.1) 59 (58.4) <0.180 Age, yr, mean ( SD) 45.2 (12.7) 53.7 (15.9) <0.020 Initial Rhythm, Shockable 26 (60.5) 19 (18.8) <0.001 Cause of Arrest, Cardiac 35 (81.4) 32 (31.7) <0.001 other hospital CPR 15 (34.9) 29 (28.7) <0.399 TH methods, COOL GUARD (53.5) 52 (51.5) ARCTIC SUN 19 (44.2) 35 (34.7) <0.100 BLANKETROL II 01 (02.3) 14 (13.9) BT(i), C, mean ( SD) 36.1 (01.0) 35.2 (01.3) <0.000 AR_BLS, min, mean ( SD) 05.5 (04.3) 08.6 (07.8) <0.016 BLS_ACLS, min, mean ( SD) 15.7 (07.6) 20.3 (09.5) <0.005 APACHE II, mean ( SD) 22.3 (04.0) 26.5 (05.5) <0.045 Lactate, mmol/l, mean ( SD) 07.4 (03.4) 08.8 (03.7) <0.005 Seizure, yes 19 (44.2) 46 (45.5) <0.881 SD: standard deviation, BT (i): initial body temperature, AR_BLS: duration from arrest to start the basic life support, BLS_ACLS: duration from starting the basic life support to start the advanced cardiac life support, APACHE: acute physiology and chronic health evaluation, CPC: cerebral performance category (good CPC: 1-2, poor CPC: 3-5), CPR: cardiopulmonary resuscitation. * p<0.05 Table 5. Multivariate Cox Regression analysis for Mortality (after 90 Days) Factors p-value Hazard ratio 95% CI of odds ratio Lower Upper Initial rhythm < Seizure < APACHI II < BLS_ROSC < CPC: Cerebral performance category, CI: confidence interval, APACHE: acute physiology and chronic health evaluation BLS_ROSC: duration from starting the basic life support to return of spontaneous circulation. Table 6. Multiple logistic regression analysis for good CPC (at 6 month after discharge) Factors p-value Odds ratio 95% CI of odds ratio Lower Upper Initial rhythm < Cause of arrest < Age < BT (i). < APACHI II < AR_BLS < CPC: Cerebral performance category, CI: confidence interval, BT (i): initial body temperature, APACHE: acute physiology and chronic health evaluation, AR_BLS: duration from arrest to start the basic life support.

6 19 Table 7. Variables by Neurologic outcome with seizure (N=65, n (%)) Good (n=19) Neurologic Outcome Poor (n=46) p-value Gender, Male 16 (84.2) 16 (56.5) <0.034 Age, yr, mean ( SD) 44.52(10.8) (17.5)00. <0.213 Initial Rhythm, Shockable 09 (47.4) 08 (17.4) <0.012 Cause of Arrest, Cardiac 13 (68.4) 12 (26.1) <0.001 Other hospital CPR 06 (31.6) 08 (17.4) <0.206 APACHE II, mean ( SD) (03.3) (06.2)00. <0.032 Lactate, mmol/l, mean ( SD) (03.1) (03.4)00. <0.352 Portable EEG grade 1 03 (15.8) 08 (17.4) < (52.6) 03 (06.5) 3 04 (21.0) 06 (13.0) 4 02 (10.5) 26 (56.5) 5 0 (0) 03 (06.5) SD: standard deviation, APACHE: acute physiology and chronic health evaluation, CPC: cerebral performance category (good CPC: 1-2, poor CPC: 3-5), EEG: electroencephalography. * p<0.05 Fig. 2. This graph is Kaplan Meyer curve showing negative relevance with seizure and mortality. Patients with seizure group (dotted line) are showing higher cumulative probability of survival than non-seizure group (full line).

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