Epinephrine Fails to Hasten Hemodynamic Recovery in Fully Developed Canine Anaphylactic Shock

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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.

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