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.

Atkinson TP, Kaliner MA: Anaphylaxis. Med Clin North Am 1992;76:841–855.
Lieberman P: Anaphylaxis and anaphylactoid reactions; in Middleton E, Ellis EF, Yunger JW, Reed CE, Adkinson NF, Buse WW (eds): Allergy: Principles and Practice, ed 5. St. Louis, Mosby, 1998, pp 1079–1092.
Burke JA, Levi R, Guo ZG, Corey EJ: Leukotrienes C4, D4 and E4: Effects on human and guinea-pig cardiac preparations in vitro. J Pharmacol Exp Ther 1982;221:235–241.
Felix S, Baumann G, Helmus S, Sattelberger U: The role of histamine in cardiac anaphylaxis: Characterization of histaminergic H1- and H2-receptor effects. Basic Res Cardiol 1988;83:531–539.
Roizen ME, Levy J, Moss J: Anaphylactic and anaphylactoid reactions; in Hall JB, Schmidt GA, Wood LDH (eds): Principles of Critical Care, ed 2. New York, McGraw-Hill, 1998, pp 1595–1604.
Miller R, Ghatek A, Rothman P, Neugut A: Anaphylaxis in the United States: An investigation into its epidemiology. J Allergy Clin Immunol 2000;105:S349.
Slater JE, Mostello LA, Shaer C: Rubber-specific IgE in children with spina bifida. J Urol 1991;146:578–579.
Niclas RA, Bernstein IL, Li JT, Lee FE, Spector SL, Dykewics MS, Fineman S, Berger WE, Blessing-Moore J, Schuller DE: Diagnosis and management of anaphylaxis. J Allergy Clin Immunol 1998;101:S465–S498.
Barach EM, Nowak RM, Lee TG, Tomalanovich MC: Epinephrine for treatment of anaphylactic shock. JAMA 1984;251:2118–2122.
Simons FER, Chad Z, Dean JM, Watson WTA: Position statement: Fatal anaphylactic reactions to food in children. Can Med Assoc J 1994;150:337–339.
Black CD, Peterson S, Simons FER: Epinephrine for outpatient treatment of anaphylaxis: A population based study. J Allergy Clin Immunol 2001;107:S58.
Orange RP, Kaliner MA, Laria PJ, Austen KF: Immunological release of histamine and slow reacting substance of anaphylaxis from human lung. 2. Influence of cellular levels of cyclic AMP. Fed Proc 1971;30:1725–1728.
Smith PL, Kagey-Sobotka A, Bleecker ER, Traystman R, Kaplan AP, Gralnick H, Valentine MD, Permutt S, Lichtenstein LM: Physiologic manifestations of human anaphylaxis. J Clin Invest 1980;66:1072–1080.
Muelleman RI, Pribble JP, Salomone JA 3rd: Blood pressure effects of thyrotropin-releasing hormone and epinephrine in anaphylactic shock. Ann Emerg Med 1988;17:309–313.
Mink SN, Bands C, Becker A, Elkin J, Sharma S, Unruh H, Kepron W: Effect of bolus epinephrine on systemic hemodynamics in canine anaphylactic shock. Cardiovasc Res 1998;40:546–556.
Simons FER, Roberts JR, Gu X, Simons KJ: Epinephrine absorption in children with a history of anaphylaxis. J Allergy Clin Immunol 1998;101:33–37.
Simons FER, Gu X, Simons KJ: Epinephrine absorption in adults. J Allergy Clin Immunol 2001:108:871–873.
Kepron W, Jackson C, Sehon A: A canine model for the study of hapten-specific suppression of IgE-mediated bronchoconstriction in anaphylaxis. Int Arch Allergy Appl Immunol 1987;82:468–470.
Kepron W, James J, Kirk B, Sehon A, Tse K: A canine model for reaginic hypersensitivity and allergic bronchoconstriction. J Allergy Clin Immunol 1977;59:64–69.
Correa E, Mink S, Unruh H, Kepron W: Left ventricular contractility is depressed in IgE-mediated anaphylactic shock in dogs. Am J Physiol 1991;260:H744–H751.
Hjemdahl P: Plasma catecholamines – analytical challenges and physiological limitations. Baillieres Clin Endocrinol Metab 1993;7:307–353.
Frederiksen M, Henthorn T, Ruo T, Atkinson A: Pharmacokinetics of pentobarbital in dogs. J Pharmacol Exp Ther 1983;225:355–360.
Unruh H, Wang R, Bose D, Mink S: Does pentobarbital anesthesia depress left ventricular contractility in dogs? Am J Physiol 1991;261:H700–H706.
Snedecor GW, Cochran WG: Statistical Methods, ed 6. Ames, Iowa State University Press, 1967, pp 271–275.
Scholtzhauer SD, Littell RC: SAS System for Elementary Statistical Analysis. Cary, SAS Institute, 1987, pp 113–125.
Horowitz BZ, Panacek EA: Cardiopulmonary resuscitation; in Hall JB, Schmidt GA, Wood LDH (eds): Principles of Critical Care, ed 2. New York, McGraw-Hill, 1998, pp 71–78.
Austen KR: Systemic anaphylaxis in the human lung. N Engl J Med 1974;291:661–664.
Kaliner M, Orange RP, Austen KF: Immunological release of histamine and slow reacting substance of anaphylaxis from human lung. 4. Enhancement by cholinergic and alpha adrenergic stimulation. J Exp Med 1972;136:556–567.
Mink S, Becker A, Sharma S, Unruh H, Duke K, Kepron W: Role of autacoids in cardiovascular collapse in anaphylactic shock in anaesthetized dogs. Cardiovasc Res 1999;43:173–182.
Simons FER, Gu X, Silver NA, Simons KJ: EpiPen Jr versus EpiPen in young children weighing 15 to 30 kg at risk for anaphylaxis. J Allergy Clin Immunol 2002;109:171–175.
Bailey PL, Stanley TH: Intravenous opioid anesthetics; in Miller RD (ed): Anesthesia. New York, Churchill Livingstone, 1994, pp 291–387.
Pisko E, Weniger F, DeGroat WC: The effect of halothane on preganglionic and postganglionic sympathetic activity in the cat. Brain Res 1970;20:330–334.
Wagner EM, Mitzner WA, Blecker ER: Peripheral circulatory alterations in canine anaphylactic shock. Am J Physiol 1986;251:H934–H940.
Sampson HA, Mendelson L, Rosen JP: Fatal and near-fatal anaphylactic reactions to food in children and adolescents. N Engl J Med 1992;327:380–384.
Pumphrey RSH: Lessons for management of anaphylaxis from a study of fatal reactions. Clin Exp Allergy 2000;30:1144–1150.
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