title: Epinephrine fails to hasten hemodynamic recovery in fully developed canine anaphylactic shock.
abstract: BACKGROUND
  Epinephrine (Epi) is the treatment of choice for reversing cardiovascular collapse in anaphylactic shock (AS). However, there are few data supporting its use in this condition, and most treatment guidelines have been anecdotally derived. In the present study, the time course of hemodynamic recovery from maximal hypotension was investigated in a canine model of AS in which Epi was administered by the intravenous (IV), subcutaneous (SQ) and intramuscular (IM) routes on different occasions. The findings obtained with Epi treatment were compared to those in a nontreatment study.
  
  
  METHODS
  Ragweed-sensitized dogs were examined in respective studies approximately 5 weeks apart in which Epi was administered by one of the above routes in a randomized design. Either Epi (0.01 mg/kg) or placebo was administered at maximal hypotension, and hemodynamics were followed for 3 h after shock. The animals were studied while ventilated and anesthetized. Mean arterial pressure (MAP), cardiac output, stroke volume (SV), pulmonary wedge pressure (Pwp) and plasma Epi concentrations were obtained at each measurement interval.
  
  
  RESULTS
  In the IV study, Epi produced a transient immediate increase in MAP, SV and Pwp as compared to the nontreatment study (144 vs. 52 mm Hg; 32 vs. 12 ml; 9 vs. 5 mm Hg; p < 0.01), but no differences were observed 15 min after shock. Hemodynamics were not different between Epi and no treatment at any intervals when Epi was given by the SQ and IM routes. AS compared with the placebo study, plasma Epi concentrations were higher in the IV and IM studies, but not in the SQ study.
  
  
  CONCLUSIONS
  Although higher Epi concentrations were observed in the IM and IV studies, a sustained benefit in hemodynamic recovery was not observed in this anesthetized, ventilated canine model. In AS, when administered during maximum shock after mediators have already been released, a single IM, IV or SQ dose of Epi may have limited utility in the treatment of cardiovascular collapse. Earlier administration of Epi, before maximal hypotension occurs, may produce a more beneficial effect.
authors.affiliation: Section of Respirology, University of Manitoba, Winnipeg, Man., Canada.
authors.forename: Edgar
authors.initials: E
authors.lastname: Bautista
authors.forename: F Estelle R
authors.initials: FE
authors.lastname: Simons
authors.forename: Keith J
authors.initials: KJ
authors.lastname: Simons
authors.forename: Allan B
authors.initials: AB
authors.lastname: Becker
authors.forename: Krika
authors.initials: K
authors.lastname: Duke
authors.forename: Michelle
authors.initials: M
authors.lastname: Tillett
authors.forename: Wayne
authors.initials: W
authors.lastname: Kepron
authors.forename: Steven N
authors.initials: SN
authors.lastname: Mink
mesh_terms: D000707:Anaphylaxis / Q000188:drug therapy* / Q000503:physiopathology*; D000818:Animals; D019540:Area Under Curve; D001794:Blood Pressure / Q000187:drug effects; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D002302:Cardiac Output / Q000187:drug effects; D004195:Disease Models, Animal; D004285:Dogs; D004837:Epinephrine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D011897:Random Allocation; D013318:Stroke Volume / Q000187:drug effects
chemical_list: D001993:Bronchodilator Agents; D004837:Epinephrine