Cardiovascular response to epinephrine varies with increasing duration of cardiac arrest

Epinephrine (adrenaline) is widely used as a primary adjuvant for improving perfusion pressure and resuscitation rates during cardiopulmonary resuscitation (CPR). Epinephrine is also associated with significant myocardial dysfunction in the post-resuscitation period. We tested the hypothesis that the cardiac effects of epinephrine vary according to the duration of cardiac arrest.

Cardiac arrest (CA) was induced in Sprague-Dawley rats with an IV bolus of KCl (40 microg/g). Three series of experiments were performed with CPR begun after 2, 4, or 6 min of cardiac arrest. Epinephrine (0.01 mg/kg) IV or placebo was given immediately in the 2 and 4 min CA groups. In the 6 min group, CPR was started after 6 min CA and epinephrine was given at 15 min if no return of spontaneous circulation (ROSC) occurred. Time to ROSC was recorded in all groups. Cardiac function was determined with trans-thoracic echocardiography at baseline, 5, 30 and 60 min after ROSC.

After 2 min CA, 8/8 (100%) placebo animals and 8/8 (100%) epinephrine animals attained ROSC. Cardiac index was significantly increased during the first 60 min in the epinephrine group compared with the placebo group (p<0.01). After 4 min of cardiac arrest, 14/29 (48%) placebo animals and 14/16 (88%) epinephrine animals attained ROSC (p<0.01). Cardiac index after ROSC returned to baseline in both groups, although tended to be lower in the epinephrine group. After 6 min CA, 10/31 (32%) animals attained ROSC without epinephrine and 17/21 (81%) animals with epinephrine (p<0.01). Post-ROSC depression of cardiac index was greatest in the epinephrine group (p<0.05).

As the duration of cardiac arrest increases, a paradoxical myocardial epinephrine response develops, in which epinephrine becomes increasingly more important to attain ROSC, but is increasingly associated with post-ROSC myocardial depression.