ECG Changes in Patients Treated with Mild Hypothermia after Cardio-pulmonary Resuscitation for Out-of-hospital Cardiac Arrest

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ECG Changes in Patients Treated with Mild Hypothermia after Cardio-pulmonary Resuscitation for Out-of-hospital Cardiac Arrest R. Schneider, S. Zimmermann, W.G. Daniel, S. Achenbach Department of Internal Medicine 2 (Cardiology), University of Erlangen Germany

Presenter Disclosure Information No Disclosures

Background I Annually, approximately 375.000 people in Europe experience sudden cardiac arrest Mild therapeutic hypothermia (MTH) has been shown to increase the rate of favourable neurological outcome and to reduce mortality in patients who have been successfully resuscitated* Class I recommendation for therapeutic hypothermia in comatose survivors of out-of-hospital cardiac arrest (OHCA), particularly if ventricular fibrillation was the initial rhythm** *The HACA Study group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest N Engl J Med 2002. 346(8):549-56; Bernard SA et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia NEJM 2002; 346:557-563 **Peberdy MA et al. AHA guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation 2010; 122: 768-786

Hypothermia Possible transient bradycardia under hypothermia Previous studies: Tiainen M et al., Crit Care Med 2009: 70 patients, increased occurence of premature ventricular beats under MTH, but no increased incidence of ventricular tachycardia or ventricular fibrillation Storm et al., Resuscitation 2011 34 patients, significant prolongation of the QTc interval during MTH No life-threatening arrhythmias, especially no Torsade de pointes

Aim of our Study Investigation of the effect of mild therapeutic hypothermia on parameters of the 12-lead ECG in patients admitted to hospital after cardio-pulmonary resuscitation for out-of-hospital cardiac arrest

Patients 68 consecutive patients Documented out-of hospital cardiac arrest due to ventricular fibrillation or asystole Successful CPR with return of a palpable pulse Restoration of spontaneous circulation (ROSC) within 60 min Comatose state after successful CPR

Cooling Procedure Endovascular cooling (Alsius CoolGard 3000, Icy Catheter) Target core temperature 33 C Maintenance phase: 24 hours Rewarming phase: returning the patient to temperature of 37 C by increasing the core temperature by 0.2 C/h; normothermia was maintained during the next 24 hours Sedation and analgesia by a combination of midazolam and fentanyl during hypothermia Muscle relaxation with administration of cisatracurium Serum potassium was measured throughout cooling and rewarming and substituted if necessary

ECG 12-lead-ECG: On admission During hypothermia: 12 h after achieving core temperature of 33 C After rewarming: 12 h after achieving core temperature of 37 C Determination of the following parameters: Heart rate PQ interval QRS duration Heart-rate-corrected QT interval: correction of the QT interval according to the Bazett formula (QTc = QT interval / RR interval) Continuous ECG telemetry for arrhythmias

Clinical Characteristics I n=68 Age, median 64.5 years (38-83 y.) Male gender 72.1% Cause of cardiac arrest - Acute coronary syndrome 36.7% (n = 25) - Primary arrhythmia 32.4% (n = 20) - Respiratory 23.5% (n = 18) - Other 7.4% (n = 5) Cardiac arrest initial rhythm - Ventricular fibrillation 58.8% (n = 40) - Asystole 30.9% (n = 21) - Pulseless Electrical Activity 2.9% (n = 2) - other/unknow 7.4% (n = 5)

Rhythm on admission Clinical Characteristics II n=68 - Sinus rhythm 75.0% (n=51) - Atrial fibrillation 16.2% (n=11) - AV-Block/Nodal rhythm/paced rhythm 8.8% (n=6) Treatment Amiodarone (300 mg bolus i.v.) - Pre-admission 22.1% (n=15) - ICU first 48 h 8.8% (n=6) Adrenalin - Pre-admission 79.4% (n=54) - total dose, median, range 2.0 mg 0-9.0 mg Noradrenalin - ICU first 72 h 92.6 (n=63) - total dose, median, range 7.4 mg 3.6-35.8 mg

Results parameters of the 12 lead ECG Admission MTH After MTH p-value p-value p-value ECG A ECG B ECG C A to B B to C A to C Heart rate (bpm) 87.1 ± 21 72.3 ± 20 90.4 ± 17 <0.001 <0.001 0.383 PR interval (ms) 167.2 ± 23 171.4 ± 39 156.9 ± 23 0.477 0.022 0.101 QRS duration (ms) 128.6 ± 31 119.2 ± 26 109.9 ± 27 0.025 0.045 <0.001 QT interval (ms) 414,3 ± 79 493.5 ± 87 390.3 ± 50 <0.001 <0.001 <0.001 QTc interval (ms) 480.3 ± 50 521.2 ± 47 473.7 ± 45 <0.001 <0.001 0.28

Heart rate (bpm) Hypothermia Heart rate 150 p<0.001 p<0.001 100 50 0 p=0.383 Admission MTH After MTH N=68

PR interval (ms) Hypothermia PR interval 400 p=0.477 p=0.022 300 200 100 0 p=0.101 Admission MTH After MTH N=68

QRS duration (ms) Hypothermia QRS duration 250 p=0.025 p=0.045 200 150 100 50 0 p<0.001 Admission MTH After MTH N=68

A.D., 73 y, m, OHCA, Admission HR 74 bpm, QTc 477 ms Hypothermia 33 C HR 63 bpm, QTc 510 ms

A.D., 73 y, m, OHCA, Admission HR 74 bpm, QTc 477 ms Hypothermia 33 C HR 63 bpm, QTc 510 ms

QTc interval (ms) Hypothermia QTc interval 700 p<0.001 p<0.001 600 500 400 p=0.284 300 Admission MTH After MTH N=68

Arrhythmias Arrhythmias during mild therapeutic hypothermia (MTH) Bradycardia < 50bpm/paced rhythm 8.8% (n=6) New atrial fibrillation 7.4% (n=5) Non-sustained ventriuclar tachycardia (nsvt) 20.6% (n=14) Sustained VT (svt) 1.5% (n=1) Ventricular fibrillation (VF) 2.9% (n=2) Torsade de pointes 0% (n=0) --> according to previous studies: no increased number of malignant arrythmias (sustained VT, VF) under MTH

Conclusion Mild therapeutic hypothermia ECG changes should be expected - decrease of heart rate - prolongation of the QTc interval - fully reversible after rewarming - not associated with life-threatening arrhythmias Effect of cooling on QTc interval must be considered to avoid misinterpretation of the ECG concerning the cause of out-of hospital cardiac arrest