Epinephrine reduces cerebral perfusion during cardiopulmonary resuscitation

Giuseppe Ristagno, Wanchun Tang, Lei Huang, Alain Fymat, Yun Te Chang, Shijie Sun, Carlos Castillo, Max Harry Weil

Research output: Contribution to journalArticlepeer-review

Abstract

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 (α1) and alpha2 (α2)-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. DESIGN: Randomized prospective animal study. SETTING: University-affiliated research laboratory. SUBJECTS: Domestic pigs. INTERVENTIONS: 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 α1- and beta (β)-adrenergic effects were blocked by previous administration of prazosin and propranolol, and 4) epinephrine in which both α2- and β-adrenergic effects were blocked by previous administration of yohimbine and propranolol. MEASUREMENTS AND MAIN 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 α1-adrenergic agonist action of epinephrine. When the α2 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 α1-agonist action had adverse effects on cerebral microvascular blood flow such as to increase the severity of cerebral ischemia during CPR.

Original languageEnglish
Pages (from-to)1408-1415
Number of pages8
JournalCritical Care Medicine
Volume37
Issue number4
DOIs
Publication statusPublished - Apr 2009

Keywords

  • Cardiopulmonary resuscitation
  • Cerebral microcirculation
  • Epinephrine
  • Tissue PCO
  • Tissue PO

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

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