Treatment of Ventricular Tachyarrhythmias Refractory To Shock With Beta Blockers: The SHOCK and BLOCK Trial

Sudden cardiac death (SCD) is a catastrophic event and most commonly results from acute ventricular tachyarrhythmias (abnormal and lethal heart rhythms). It is often triggered by acute coronary events, which may occur in persons without known cardiac disease or in association with structural heart disease. Advanced therapies such as thrombolytic agents, percutaneous coronary intervention, and implantable cardioverter defibrillators are of no value to thousands of victims who do not survive. Many instances of SCD cannot be predicted and any intervention directed toward the general population would have to be applied to an estimated 1000 persons for every 1 person in whom SCD might be prevented. Thus, it would be reasonable to develop new treatment strategies to improve response to resuscitative efforts.

Prompt electrical defibrillation (electrical shocks) is the treatment of choice in persons who develop SCD due to ventricular fibrillation (VF) or pulseless ventricular tachycardia (pVT). However, in up to 25% of all cardiac arrests, patients develop shock resistant VF, defined as VF persisting beyond three defibrillation attempts, and 87-97% of these patients die. Medical therapy, including antiarrhythmic agents, sympathomimetic agents (i.e. stimulants), and buffers have been relegated to a secondary role since there is little evidence that they are of benefit and there use is considered indeterminate or class IIB. Furthermore, the "Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care" of the American Heart Association and the International Liaison Committee on Resuscitation recommend antiarrhythmic drugs as "acceptable" and "probably helpful" in the treatment of VF that persists after three or more external defibrillation shocks. It has been previously reported that the survival rate of hospital patients suffering a cardiac arrest in which epinephrine was required was only 6%. Furthermore, Dorian et al reported a survival to hospital admission of 22.8% in patients suffering an out of hospital cardiac arrest and receiving amiodarone. It is believed that the acute effects of amiodarone are due to the class II or beta blocking effects of the drug.

Resuscitation can only be considered successful if the survivor has no disabling cognitive function. The American Heart Association/International Liaison Committee on Resuscitation guidelines state that with a duration of cardiac arrest of > 8 to 10 minutes, the frequency of significant, permanent neurologic damage becomes unacceptably high. Newer treatment modalities are needed to improve patient outcomes.

Epinephrine has been used during cardiopulmonary resuscitation for more than 100 years yet its use has become controversial because it is associated with increased myocardial oxygen consumption, ventricular tachyarrhythmias, and myocardial dysfunction during the period after resuscitation. The current International Guidelines on Emergency Cardiac Care cite both epinephrine and vasopressin as acceptable vasopressor drugs for treatment of refractory VF but neither drug is acknowledged to be of proven benefit.

Beta blockers might improve patient outcomes by blunting the adverse affects of a hyperadrenergic state that occurs during a cardiac arrest and by improving the balance between myocardial oxygen supply and demand. Ditchey et al showed in an animal model that pretreatment with a beta blocker prior to cardiac arrest followed by standard epinephrine therapy results in reduced myocardial injury during CPR without compromising successful defibrillation or post resuscitation left ventricular function.