title: Adverse effects of high-dose epinephrine on cerebral blood flow during experimental cardiopulmonary resuscitation.
abstract: OBJECTIVE
  To study the effects of high-dose epinephrine, compared with standard-dose epinephrine, on the dynamics of superficial cortical cerebral blood flow as well as global cerebral oxygenation during experimental cardiopulmonary resuscitation. We hypothesized that high-dose epinephrine might be unable to improve cerebral blood flow during cardiopulmonary resuscitation as compared with standard-dose epinephrine.
  
  
  METHODS
  Randomized controlled study.
  
  
  METHODS
  University hospital research laboratory.
  
  
  METHODS
  A total of 20 male anesthetized piglets.
  
  
  METHODS
  Ventricular fibrillation was induced. A nonintervention interval of 8 mins was followed by open-chest cardiopulmonary resuscitation. The animals were randomized to receive repeated bolus injections of either 20 microg/kg (standard-dose group, n = 10) or 200 microg/kg (high-dose group, n = 10) of epinephrine.
  
  
  RESULTS
  Focal cortical cerebral blood flow was measured continuously by using laser Doppler flowmetry. The duration of blood flow increase was significantly shorter in the high-dose group after the second dose of epinephrine. In the high-dose group there was also a consistent tendency for lower peak levels and shorter duration of flow increase in response to repeated bolus doses of epinephrine. Cerebral oxygen extraction ratio was significantly lower in the high-dose group after administration of epinephrine.
  
  
  CONCLUSIONS
  Repeated bolus doses of epinephrine 200 microg/kg, as compared with 20 microg/kg, do not improve superficial cortical cerebral blood flow during experimental open-chest cardiopulmonary resuscitation. High-dose epinephrine appears to induce vasoconstriction of cortical cerebral blood vessels resulting in redistribution of blood flow from superficial cortex. This might be one explanation for the failure of high-dose epinephrine to improve overall outcome in clinical trials.
authors.affiliation: Department of Surgical Sciences, Anesthesiology & Intensive Care, Uppsala University Hospital, Sweden. rolf.gedeborg@anestesi.uu.se
authors.forename: R
authors.initials: R
authors.lastname: Gedeborg
authors.forename: H C
authors.initials: HC
authors.lastname: Silander
authors.forename: E
authors.initials: E
authors.lastname: Ronne-Engström
authors.forename: S
authors.initials: S
authors.lastname: Rubertsson
authors.forename: L
authors.initials: L
authors.lastname: Wiklund
mesh_terms: D000818:Animals; D016887:Cardiopulmonary Resuscitation; D002540:Cerebral Cortex / Q000098:blood supply*; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000633:toxicity*; D017078:Laser-Doppler Flowmetry; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D013552:Swine; D014693:Ventricular Fibrillation / Q000503:physiopathology
chemical_list: D004837:Epinephrine