title: Constant infusion of epinephrine, but not bolus treatment, improves haemodynamic recovery in anaphylactic shock in dogs.
abstract: OBJECTIVE
  Epinephrine (Epi) is the treatment of choice for reversing cardiovascular collapse in anaphylactic shock (AS). In this condition, most treatment guidelines have been anecdotally derived and no randomized clinical trials have been conducted. In the present study, we examined the time course of haemodynamic recovery in a canine model of AS when Epi was administered at the initiation of allergen challenge before fully developed shock had occurred.
  
  
  METHODS
  Randomized, controlled, crossover studies were performed approximately 3-5 weeks apart in ragweed-sensitized dogs while the animals were ventilated and anaesthetized. Epi was administered by bolus intravenous (i.v.), subcutaneous (s.c.), intramuscular (i.m.) routes and by continuous i.v. infusion (CI). The findings obtained in the Epi treatment (T) studies were compared with those found in a no treatment (NT) study. In the bolus studies, Epi was administered at 0.01 mg/kg, while in the CI study, the dose of Epi was titrated to maintain mean arterial pressure (MAP) at 70% of preshock levels. MAP, cardiac output (CO), stroke volume (SV), and pulmonary wedge pressure (Pwp) were determined over a 3 h period.
  
  
  RESULTS
  In the CI study, haemodynamics (CO, MAP, and SV) were significantly higher than those measured in the NT study and the bolus studies over approximately the first hour of the study. In the CI study, the amount of Epi infused was significantly less than in the bolus studies.
  
  
  CONCLUSIONS
  When administered at the initiation of allergen challenge, bolus treatment of Epi by i.m., i.v., or s.c. routes caused limited haemodynamic improvement in AS. In contrast, constant infusion of Epi at a lower total dose produced significant haemodynamic improvement. Within the limits of this anaesthetized canine model, the results suggest that CI should be the preferred route in the treatment of AS when this treatment option is available.
authors.affiliation: Department of Medicine and Pharmacology and Therapeutics, University of Manitoba, Winnipeg, MB, Canada. minksn@cc.umanitoba.ca
authors.forename: S N
authors.initials: SN
authors.lastname: Mink
authors.forename: F E R
authors.initials: FE
authors.lastname: Simons
authors.forename: K J
authors.initials: KJ
authors.lastname: Simons
authors.forename: A B
authors.initials: AB
authors.lastname: Becker
authors.forename: K
authors.initials: K
authors.lastname: Duke
mesh_terms: D000485:Allergens / Q000276:immunology; D031164:Ambrosia / Q000276:immunology; D000707:Anaphylaxis / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D000818:Animals; D018592:Cross-Over Studies; D004195:Disease Models, Animal; D004285:Dogs; D004334:Drug Administration Schedule; D004837:Epinephrine / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use; D006439:Hemodynamics / Q000187:drug effects; D007262:Infusions, Intravenous; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D014662:Vasoconstrictor Agents / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use
chemical_list: D000485:Allergens; D014662:Vasoconstrictor Agents; D004837:Epinephrine