title: Response to repeated equal doses of epinephrine during cardiopulmonary resuscitation in dogs.
abstract: OBJECTIVE
  Advanced cardiac life support (ACLS) guidelines recommend a 3- to 5-minute interval between repeated doses of epinephrine. This recommendation does not take into account the dose of epinephrine used, and only very limited data exist regarding the hemodynamic responses to repeated "high" doses of epinephrine. The objective of this study was to analyze the hemodynamic responses to repeated, equal, high doses of epinephrine administered during cardiopulmonary resuscitation (CPR) in a canine model of ventricular fibrillation (VF).
  
  
  METHODS
  This study used a secondary analysis of data collected in a prospective, randomized study, primarily designed to assess the effects of acid buffers in a canine model of cardiac arrest. VF was electrically induced. After 10 minutes, CPR was initiated, including ventilation with FIO(2)=1.0, external chest compressions, administration of epinephrine (0.1 mg/kg repeated every 5 minutes) and defibrillation. Animals were randomized to receive either NaHCO(3), Carbicarb, tromethamine (THAM), or NaCl. The hemodynamic variables were sampled from each experiment's paper chart at 1-minute intervals, and the responses to the first 4 doses of epinephrine were compared.
  
  
  RESULTS
  Thirty-six animals (9 in each buffer group) were included in this analysis. Systolic, diastolic, and coronary perfusion pressures increased steeply (by 100%, 130%, and 190%, respectively) only after the first epinephrine dose. These pressures peaked at 2 to 3 minutes and decreased only slightly and insignificantly during the rest of the 5-minute interval, until the next epinephrine dose. No further significant increases in arterial pressures were observed in response to the next 3 doses of epinephrine, administered 5 minutes apart.
  
  
  CONCLUSIONS
  The hemodynamic effects of high-dose epinephrine (0.1 mg/kg) during CPR appear to last longer than 5 minutes. Therefore, longer intervals between doses may be justified with high doses of epinephrine.
authors.affiliation: Pediatric Intensive Care Unit, Rambam Medical Center, and the Department of Physiology, the Bruce Rappaport Faculty of Medicine and the Rappaport Institute for Research in the Medical Sciences, Haifa, Israel. g_barjoseph@rambam.health.gov.il
authors.forename: G
authors.initials: G
authors.lastname: Bar-Joseph
authors.forename: T
authors.initials: T
authors.lastname: Weinberger
authors.forename: S
authors.initials: S
authors.lastname: Ben-Haim
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002021:Buffers; D002254:Carbonates / Q000008:administration & dosage / Q000494:pharmacology; D016887:Cardiopulmonary Resuscitation / Q000379:methods*; D004195:Disease Models, Animal; D004285:Dogs; D004334:Drug Administration Schedule; D004338:Drug Combinations; D004353:Drug Evaluation, Preclinical; D004359:Drug Therapy, Combination; D004837:Epinephrine / Q000008:administration & dosage* / Q000494:pharmacology; D017410:Practice Guidelines as Topic; D011897:Random Allocation; D017693:Sodium Bicarbonate / Q000008:administration & dosage / Q000494:pharmacology; D012965:Sodium Chloride / Q000008:administration & dosage / Q000494:pharmacology; D013997:Time Factors; D014325:Tromethamine / Q000008:administration & dosage / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000008:administration & dosage* / Q000494:pharmacology; D014693:Ventricular Fibrillation / Q000188:drug therapy* / Q000503:physiopathology*
chemical_list: D000316:Adrenergic alpha-Agonists; D002021:Buffers; D002254:Carbonates; D004338:Drug Combinations; D014662:Vasoconstrictor Agents; C046283:sodium bicarbonate, sodium carbonate drug combination; D014325:Tromethamine; D012965:Sodium Chloride; D017693:Sodium Bicarbonate; D004837:Epinephrine