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Ephedrine in Veterinary Medicine

Alicia M Skelding, BSc Agr, DVM, MSc, DVSc, DACVAA

Assistant Professor, Veterinary Anesthesiologist

Michigan State University, College of Veterinary Medicine





Sympathomimetic drugs are agents that mimic the effect of the sympathetic nervous system in the body. They exert their effects by interacting with adrenergic receptors that exist throughout the body. The adrenergic receptors are of two main types, α adrenergic receptors (α1, α2 subtypes) and β adrenergic receptors (β1, β2, β3 subtypes). In veterinary species, sympathomimetic drugs are commonly used to provide cardiovascular support. Specific to veterinary patients under general anesthesia, they are very often used to combat hypotension -arguably the most common anesthetic complication. 


There are a number of sympathomimetics that are frequently used in veterinary patients, chosen often for their specific effects on the adrenergic receptors and consideration for the species in question. The most common sympathomimetics are epinephrine, norepinephrine, dopamine, dobutamine, ephedrine, phenylephrine, and isoproterenol.  


Ephedrine is a synthetic, mixed-acting, non-catecholamine that differs from most sympathomimetics in administration in that it can be administered as a single intravenous bolus, as well as a constant rate infusion. Ephedrine elicits sympathomimetic effects two ways; directly by stimulating adrenergic receptors and indirectly by increasing the norepinephrine concentration at sympathetic nerve terminals by competing for its reuptake. Studies suggest that ephedrine at clinical doses has more activity at β adrenergic receptors, more often increasing contractility, heart rate and decreasing systemic vascular resistance. As previously mentioned, ephedrine can be administered as a bolus dose because its duration of action can last for 15–20 minutes. One of the negative aspects of using ephedrine is that repeated doses can result in a diminished response to successive doses (tachyphylaxis) due to catecholamine depletion and/or replacement of the endogenous norepinephrine with ephedrine at the presynaptic nerve terminal, especially with high doses. 


There are a small number of studies evaluating the use of ephedrine in veterinary species; namely dogs, cats and horses. In clinical cases of hypotension in isoflurane-anesthetized dogs, ephedrine administered as a single intravenous bolus resulted in increases in mean arterial pressure and heart rate that lasted approximately five minutes. A repeat dose ten minutes later was ineffective at further improving heart rate or blood pressure. In cats, intramuscular ephedrine has been found to be successful at maintaining systolic arterial pressure close to baseline following premedication as well as delaying the onset of hypotension following inhalant anesthesia. In horses, a constant rate infusion of ephedrine has been found to be effective in treating hypotension by improving cardiac output and not affecting heart rate.


The clinical dose range for ephedrine when administered as an intravenous bolus is 0.06-0.2 mg/kg in dogs and cats, and 0.03-0.06 mg/kg in horses. When used at a constant rate infusion, 10-20 μg/kg/minute is a reasonable dose range, although only studied in horses.


Unfortunately, the use of ephedrine across other veterinary species has not been well studied. Perhaps this is attributed to more interest in other agents that are commonly administered as constant rate infusions. Ephedrine is a reasonable choice of sympathomimetic for an initial improvement in mean arterial pressure or where constant rate infusion administration is not possible. It should be kept in mind that the improvement in mean arterial pressure, specifically in dogs and cats, seems to be very transient and further cardiovascular support may need to be added.



References:

Chen et al. (2007) Use of ephedrine and dopamine in dogs for the management of hypotension in routine clinical cases under isoflurane anesthesia. VAA 34, 301–311.


Ebert. (2013) Autonomic nervous system pharmacology, Pharmacology and Physiology for Anesthesia Foundations and Clinical Application. 1st Edn. Elsevier Saunders, Philadelphia, PA, USA, pp. 218–233. 


Egger et al. (2009) Efficacy of preanesthetic intramuscular administration of ephedrine for prevention of anesthesia-induced hypotension in cats and dogs. CVJ 50, 179–184. 


Skelding and Valverde (2020) Sympathomimetics in Veterinary Species. The Vet J 258, 105455


Takasaki et al. (1972) Tachyphylaxis of indirectly acting sympathomimetic amines. The Kurume Medical Journal 19, 1–10. 


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1 Comment


Dr Skelding, Thanks for this nice summary of the use of ephedrine to treat hypotension during anesthesia. I would like to add one detail of clinical importance. Different than catecholamine-sympathomimetics, ephedrine crosses the blood brain barrier and excites the central nervous system. It increases MAC of inhalant anesthetics (Steffey et al. 1975) and can facilitate movement in patients at a light plane of anesthesia. This is particularly concerning in horses.

Steffey EP, Eger EI. The effect of seven vasopressors of halothane MAC in dogs. Br J Anaesth. 1975 Apr;47(4):435-8. doi: 10.1093/bja/47.4.435. PMID: 237518.

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