Epinephrine reduces cerebral perfusion during cardiopulmonary resuscitation.
OBJECTIVE
Epinephrine has been the primary drug for cardiopulmonary resuscitation (CPR) for more than a century. The therapeutic rationale was to restore threshold levels of myocardial and cerebral blood flows by its alpha1 (alpha1) and alpha2 (alpha2)-adrenergic agonist vasopressor actions. On the basis of coincidental observations on changes in microvascular flow in the cerebral cortex, we hypothesized that epinephrine selectively decreases microvascular flow.


METHODS
Randomized prospective animal study.


METHODS
University-affiliated research laboratory.


METHODS
Domestic pigs.


METHODS
Four groups of five male domestic pigs weighing 40 +/- 3 kg were investigated. After induction of anesthesia, endotracheal intubation was followed by mechanical ventilation. A frontoparietal bilateral craniotomy was created. Ventricular fibrillation was induced and untreated for 3 minutes before the start of precordial compression, mechanical ventilation, and attempted defibrillation. Animals were randomized to receive central venous injections during CPR of 1) placebo, 2) epinephrine, 3) epinephrine in which both alpha1- and beta (beta)-adrenergic effects were blocked by previous administration of prazosin and propranolol, and 4) epinephrine in which both alpha2- and beta-adrenergic effects were blocked by previous administration of yohimbine and propranolol.


RESULTS
Cerebral cortical microcirculatory blood flow (MBF) was measured with orthogonal polarization spectral imaging. Cerebral cortical carbon dioxide and oxygen tensions (Pbco2 and Pbo2) were concurrently measured using miniature tissue optical sensors. Each animal was resuscitated. No differences in the number of electrical shocks for defibrillation or in the duration of CPR preceding return of spontaneous circulation were observed. Yet when epinephrine induced increases in arterial pressure, it significantly decreased Pbo2 tension and increased Pbco2 tension. Epinephrine therefore significantly decreased MBF and increased indicators of cerebral ischemia. Reduced MBF and magnified brain tissue ischemia during and after cardiopulmonary resuscitation were traced to the alpha1-adrenergic agonist action of epinephrine. When the alpha2 effects of epinephrine were blocked, reduced MBF and tissue ischemia persisted. No differences in cardiac output, end tidal Pco2, arterial Po2 and Pco2, and brain temperature were observed before inducing cardiac arrest and following return of spontaneous circulation.


CONCLUSIONS
In this model, epinephrine through its alpha1-agonist action had adverse effects on cerebral microvascular blood flow such as to increase the severity of cerebral ischemia during CPR.
Ristagno
Giuseppe
G
Weil Institute of Critical Care Medicine, Rancho Mirage, CA, USA.
Tang
Wanchun
W
Huang
Lei
L
Fymat
Alain
A
Chang
Yun-Te
YT
Sun
Shijie
S
Castillo
Carlos
C
Weil
Max Harry
MH
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D016887:Cardiopulmonary Resuscitation; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004837:Epinephrine / Q000494:pharmacology*; D008297:Male; D012039:Regional Blood Flow / Q000187:drug effects; D013552:Swine
D000316:Adrenergic alpha-Agonists; D004837:Epinephrine