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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.Randomized prospective animal study.University-affiliated research laboratory.Domestic pigs.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.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.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.

Objective: To compare the rectilinear biphasic waveform with a biphasic truncated exponential waveform for pediatric defibrillation. Design: Prospective, randomized study. Setting: Experimental laboratory of a university-affiliated research institute. Subjects: Male domestic piglets (4-24 kg). Interventions: Eleven piglets (4-8 kg), which represented a patient

Objective: Direct observations of the microcirculation using orthogonal polarization spectral imaging have attracted attention and revealed that, especially in cardiogenic and distributive shock, there is discordance between the macrocirculation and the microcirculation. We evaluated serial changes and the effects of epinephrine on microcirculatory blood flow in the most severe form of circulatory failure, namely, cardiac arrest. Design and Setting: Controlled laboratory animal study. Subjects and Interventions: A total of 15 pigs were subjected to 5 mins of ventricular fibrillation and 5 mins of precordial compression before electrical defibrillation was attempted. In a subset, six animals received 1 mg of epinephrine after 1 min of precordial compression. Measurements and Main Results: Microcirculatory blood flow was visualized in the sublingual mucosa at baseline and 0.5, 1, and 5 mins of ventricular fibrillation, at 1 and 5 mins of precordial compression, and at 1 and 5 mins after return of spontaneous circulation. In addition, coronary perfusion pressure was re corded. Microcirculatory blood flow decreased dramatically in the 0.5 min after the onset of ventricular fibrillation. Precordial compression partially restored microcirculatory blood flow in each animal but to a significantly greater extent in animals that achieved return of spontaneous circulation. These changes were paralleled by similar changes in coronary perfusion pressure. Both variables were highly correlated. Administration of epinephrine resulted in a massive reduction of microcirculatory blood flow that lasted for ≥5 mins. Conclusions: In this model, microcirculatory blood flow was highly corretated with macrocirculatory hemodynamics, including coronary perfusion pressure in distinction with septic shock. Administration of epinephrine dramatically decreased microcirculatory blood flow. (Crit Care Med 2006; 34[Suppl.]:S454-S457)

Objective: Microcirculatory perfusion is disturbed in sepsis, and global hemodynamics does not necessarily reflect microcirculatory blood flow. In this study, we investigated the effect of the same level of mean arterial pressure (MAP) or cardiac index on the changes in buccal microcirculation between septic and hemorrhagic shock. Design: Prospective, controlled laboratory study. Setting: University-affiliated research laboratory. Interventions: A total of 20 Sprague-Dawley rats were divided into four groups : 1) septic shock induced by cecal ligation and perforation: when MAP decreased to 80 mm Hg, saline was infused at a rate of 25 mL.kg -1 .hr -1 for 2 hrs; 2) both time- and MAP-matched hemorrhagic shock : ?30% of total blood volume was withdrawn during the corresponding interval, followed by infusion aiming to restore MAP as required when MAP decreased to 80 mm Hg; 3) both time- and cardiac index-matched hemorrhagic shock : ?40% of total blood volume was withdrawn during the corresponding interval until MAP decreased to 50 mm Hg, which generally generated a cardiac index similar to those in septic animals, followed by infusion at the same rate for 2 hrsand 4) sham control : animals underwent the same procedure except no cecal ligation and perforation, bleeding, and infusion. Measurements and Main Results : Buccal microcirculation was visualized with the aid of an orthogonal polarization spectral image device. A semiquantitative score was calculated for vessels of