Adrenaline (Epinephrine)

Overview

Adrenaline (epinephrine) is a potent endogenous catecholamine and sympathomimetic agent widely used in emergency and critical care settings in dogs and cats. It acts as both a vasopressor and bronchodilator, making it essential in life-threatening conditions such as cardiopulmonary arrest and anaphylaxis.

The clinical effects of adrenaline are dose-dependent. At lower doses, beta-adrenergic effects predominate, leading to increased cardiac output, bronchodilation, and peripheral vasodilation. At higher doses, alpha-1 effects become more prominent, resulting in vasoconstriction and increased systemic vascular resistance to support blood pressure.

Mechanism of Action (MOA): Adrenaline stimulates alpha-1, alpha-2, beta-1, and beta-2 adrenergic receptors. Beta-1 stimulation increases heart rate and myocardial contractility, while beta-2 activation causes bronchodilation. Alpha-1 receptor stimulation leads to peripheral vasoconstriction, increasing blood pressure and redistributing blood flow to vital organs. Its overall effect is a rapid enhancement of cardiovascular and respiratory function, although its duration of action is short (approximately 2–5 minutes).

Indications

Adrenaline (epinephrine) is primarily used in dogs and cats in emergency and critical care situations where rapid cardiovascular or respiratory support is required. Its use is centered around life-threatening conditions requiring immediate intervention.

• Cardiopulmonary arrest (CPA): First-line drug used during cardiopulmonary resuscitation to restore circulation by increasing coronary and cerebral perfusion pressure. Current guidelines recommend it for non-shockable rhythms such as asystole and pulseless electrical activity, and advise against giving it in a shockable rhythm before the first defibrillation attempt.
• Anaphylaxis and severe allergic reactions: Used to counteract the effects of histamine release, including hypotension, bronchoconstriction, and vascular collapse.
• Bronchoconstriction (e.g., status asthmaticus): Given at the anaphylaxis dose, it provides rapid bronchodilation and improves airflow in acute, severe respiratory distress. It is reserved for emergency treatment of life-threatening bronchoconstriction; its non-selective receptor effects and very short duration make it unsuitable for routine or longer-term management of airway disease.
• Refractory hypotension under anesthesia: Adrenaline given as a continuous rate infusion may be considered for hypotension under anesthesia that has not responded to other inotropic support. Because it increases tissue oxygen demand and causes severe splanchnic vasoconstriction, it is used only when other interventions have failed.

Dosage (Reference)

Dog

In dogs, adrenaline is used in emergency situations such as cardiopulmonary arrest and anaphylaxis. Rapid administration and correct dosing are critical due to its potent effects and short duration of action.

Cat

In cats, the references publish the same regimens as for dogs, although the doses are based primarily on experimental studies in dogs and clinical studies are not available.

Warnings & Precautions

Adrenaline is a potent sympathomimetic agent with significant cardiovascular effects. Its use requires careful dosing, appropriate patient selection, and close monitoring, particularly in critical or compromised patients.

• Pre-existing conditions: Use with caution in patients with diabetes mellitus, hypertension, or hyperthyroidism, as adrenergic stimulation may worsen these conditions.
• Hypovolemia: Use cautiously in hypovolemic patients; adrenaline is not a substitute for appropriate fluid therapy and underlying volume deficits should be corrected.
• Dose accuracy: Overdosage can be fatal, especially in small patients; always verify dose and concentration before administration.
• Route of administration: Intracardiac injection is not recommended, because of the risk of arrhythmias, and it offers no advantage over the intravenous route. The one exception is during open-chest CPR, where injection into the left ventricle may be used.
• Monitoring after administration: If an owner-administered pen has been used, monitor the patient for at least 6 hours. After systemic anaphylaxis, monitoring for 24 to 48 hours is advised: shock can recur within about 12 hours of the initial presentation.
• Product handling: Do not confuse different vial concentrations (e.g., 1:1000 vs other dilutions), as this may lead to serious dosing errors.
• Drug stability: Adrenaline is sensitive to light and air; do not use solutions that appear pink, brown, or contain precipitate.
• Compatibility: For IV infusion, dilute epinephrine in a compatible infusion solution and protect from light and air; avoid alkaline solutions, and discard if discolored or if a precipitate develops.
• Contraindications in an emergency: In a life-threatening situation there are no absolute contraindications to adrenaline. The relative contraindications that apply outside an emergency include closed-angle glaucoma, known hypersensitivity, shock from a cause other than anaphylaxis, general anesthesia with an inhalant agent, parturition, dilated cardiomyopathy or coronary insufficiency, thyrotoxicosis, uncontrolled diabetes or hypertension, and toxemia of pregnancy.
• Prefibrillatory cardiac rhythm: Use with extreme caution in a patient whose rhythm is already close to fibrillating, because of the drug’s excitatory effect on the heart.
• Pulmonary and renal perfusion: Adrenaline increases pulmonary vascular resistance and moderately decreases renal blood flow.
• Small appendages: Do not inject into a small appendage such as a toe or an ear, either directly or combined with a local anesthetic: the vasoconstriction may cause tissue necrosis and sloughing.
• Extravasation: Give through a central line where possible; extravasation from a peripheral vein can cause local tissue necrosis, which is treated with phentolamine infiltrated locally.
• Human adrenaline pens: Human adrenaline pen injectors are not recommended for treating suspected anaphylaxis in animals: the fixed dose is usually too small to be effective, and by the time an animal has collapsed it is unlikely to change the outcome.
• After an owner-given dose: Adrenaline given by an owner is not a substitute for immediate veterinary care; the animal should be seen as soon as possible after it is used.
• Accidental human injection: Accidental self-injection is a real risk when an auto-injector is used on a struggling animal; anyone who injects themselves should seek emergency medical care immediately.
• Look-alike, sound-alike: Do not confuse adrenaline (epinephrine) with ephedrine; the two names are similar, the drugs are not interchangeable, and both are stocked as injections.
• Pregnancy and lactation: Adrenaline crosses the placenta and may delay the second stage of labor, but it should not be withheld from a pregnant animal in a life-threatening situation. Small amounts appear in milk and are unlikely to affect a nursing offspring, because the drug is destroyed in the gastrointestinal tract.

Drug Interactions

Most clinically relevant interactions with adrenaline are related to additive sympathomimetic effects, altered cardiovascular responses, or increased risk of arrhythmias. Careful monitoring is required when used with the following medications.

• Other sympathomimetic agents: Concurrent use may lead to excessive cardiovascular stimulation and increased risk of toxicity due to additive effects.
• Antihistamines and thyroxine: May potentiate the effects of adrenaline, increasing the risk of exaggerated cardiovascular responses.
• Beta-blockers (e.g., propranolol): May block beta effects, leading to unopposed alpha stimulation and a marked increase in blood pressure.
• Alpha-blockers and diuretics: May reduce or antagonize the pressor effects of adrenaline.
• Myocardial-sensitizing agents (e.g., halothane, high doses of digoxin): Increase the risk of cardiac arrhythmias when used concurrently.
• Oxytocic agents: Concurrent use may result in significant hypertension.
• Halogenated inhalant anesthetics: An increased risk of arrhythmias when adrenaline is given to a patient under inhalant anesthesia. Propranolol may be used if arrhythmias develop.
• Phenothiazines (e.g., acepromazine): May reverse the pressor effect of adrenaline through alpha-1 blockade, so that blood pressure falls instead of rising. This is known as adrenaline reversal.
• Alpha-2 agonists: Adrenaline possesses alpha-agonist effects of its own and must NOT be used to treat the cardiac effects that dexmedetomidine, medetomidine and xylazine cause.
• MAOIs, reserpine and tricyclic antidepressants: Monoamine oxidase inhibitors (amitraz, selegiline) and reserpine may potentiate the pressor effect of adrenaline; tricyclic antidepressants (amitriptyline, clomipramine) may potentiate the effects of adrenaline.
• Alkaline solutions and sodium bicarbonate: Adrenaline is destroyed by alkalis and oxidizing agents and must not be mixed with sodium bicarbonate or run through the same line.
• Lidocaine in methylxanthine toxicosis: When treating methylxanthine (chocolate or caffeine) toxicosis, adrenaline should not be used at the same time as lidocaine.

Side Effects & Overdose

Side Effects

Adverse effects of adrenaline are primarily related to its potent cardiovascular stimulation and are dose-dependent. These effects are more likely with higher doses or repeated administration.

• Increased myocardial oxygen demand: Adrenaline increases myocardial work and myocardial oxygen consumption.
• Arrhythmias: Including serious disturbances such as ventricular fibrillation.
• Tachycardia: Compared with norepinephrine, adrenaline is more likely to increase heart rate and cause tachyarrhythmias.
• Peripheral effects: Cold extremities due to vasoconstriction.
• Dry mouth: May occur as a result of sympathetic stimulation.
• Injection site reactions: Repeated injections may cause local tissue necrosis.
• Other reported effects: Pulmonary edema, hyperglycemia, tremors and excitability, vomiting, hypertension, and lactic acidosis with prolonged use.
• How much of this is extrapolated: Most of what is known about the adverse effects of this drug is taken from the human label and assumed to apply to animals.

Overdose

Overdose of adrenaline can be life-threatening and results in severe exaggerated sympathomimetic effects, primarily affecting the cardiovascular system.

• Severe arrhythmias: Including ventricular fibrillation and potentially fatal cardiac disturbances.
• Marked hypertension: Excessive vasoconstriction leading to dangerously high blood pressure.
• Other severe toxicity: Cerebral hemorrhage may follow the rise in blood pressure, and renal failure, metabolic acidosis and cold skin may also occur.
• Management: Immediate supportive care is required, including oxygen therapy and control of heart rate. Because the drug is short-acting, treatment is mainly supportive; where it is not enough, an alpha-blocker such as phentolamine or a beta-blocker such as propranolol may be used for severe hypertension or arrhythmias. A prolonged period of hypotension may follow, which may itself need treating with noradrenaline.
• Critical importance of dosing: Even small dosing errors can result in severe or fatal outcomes, particularly in small animals.
• Other signs, and the commonest route error: Pulmonary edema with dyspnea, and vomiting, are also part of the overdose picture. The same picture follows an intravenous dose that was intended to be given under the skin or into muscle.

Key Notes

Practical clinical points that help optimize the safe and effective use of adrenaline (epinephrine) in dogs and cats in emergency and critical care settings:

• Ultra-short duration: Effects last only a few minutes (≈2–5 min), so repeated dosing or continuous reassessment is essential during resuscitation.
• Dose-dependent receptor effects: Lower doses favor beta effects (cardiac stimulation and bronchodilation), while higher doses produce stronger vasoconstrictive (alpha) effects.
• Central circulation delivery: Drug effectiveness depends on reaching central circulation quickly; ensure proper IV access during emergencies.
• Essential emergency drug: Adrenaline has long been the mainstay of drug therapy in cardiopulmonary resuscitation.
• Bronchodilation benefit: Particularly useful in patients with concurrent respiratory compromise due to its rapid airway-relaxing effect, but reserved for emergency treatment of life-threatening bronchoconstriction rather than routine airway management. A duration of effect of 1 to 3 hours has been reported for its bronchodilator action.
• Not for routine hypotension: Typically reserved for severe or life-threatening situations rather than mild or routine blood pressure support.
• Perfusion vs vasoconstriction balance: While it supports vital organ perfusion, excessive vasoconstriction at high doses may reduce peripheral blood flow.
• Team communication: Clear communication during emergency use (dose, concentration, route) is critical to avoid errors in high-stress situations.
• Pharmacokinetics: Onset is immediate and intense after intravenous injection and within 5 to 10 minutes after subcutaneous injection. The drug is not effective by mouth, does not cross the blood-brain barrier, and is broken down in the liver and other tissues by monoamine oxidase and catechol-O-methyltransferase.
• Route order in an arrest: Route preference during resuscitation is intravenous, then intraosseous, then intratracheal. Intramuscular and subcutaneous injection are not used during cardiovascular resuscitation, due to poor peripheral perfusion.
• Monitoring: Monitor heart rate, ECG and blood pressure, and where possible central venous pressure, respiratory rate and thoracic auscultation, urine production, blood gases and neurological status. If the drug is given into a peripheral vein, watch the site for tissue necrosis.
• Storage and handling: Store injections at 15 to 30 degrees Celsius and protect them from light; discard any solution that is pink or brown or contains a precipitate, and keep it away from alkalis and oxidizing agents. The human-labelled injection additionally states not to refrigerate or freeze, and that the presence of sulfite in the product should not deter its use.
• Available forms: Injectable solutions range from 0.1 to 10 mg/mL (1:10,000 to 1:100). A veterinary-labelled 1 mg/mL injection exists for dogs and cats. Human-labelled products include 1 mg/mL and 0.1 mg/mL injections; auto-injector or prefilled presentations of 0.3 mg/0.3 mL, 0.15 mg/0.15 mL and 0.15 mg/0.3 mL; and inhalation, topical, nebulizer and ophthalmic preparations of epinephrine bitartrate, the ophthalmic preparation being used in open-angle glaucoma.
• Pre-drawn syringes: In one study, 1 mg/mL adrenaline containing sodium metabisulfite, drawn into 1 mL plastic syringes with the needles left attached and recapped, maintained potency for 2 months at 15% humidity and 4 months at 95% humidity when stored at 38 degrees Celsius.
• Prolonging a local anesthetic: Adrenaline is also added to local anesthetic solutions at about 5 micrograms per mL to slow systemic absorption and prolong the block: in practice, remove 0.1 mL from a 20 mL bottle of local anesthetic and replace it with 0.1 mL of the 1 mg/mL solution. Do not use an adrenaline-containing solution around an extremity.
• Neonatal resuscitation: For a newborn puppy or kitten in cardiac arrest, a dose of 0.2 mg/kg into the umbilical vein or by the intraosseous route is used. Atropine is contraindicated during neonatal resuscitation due to exacerbation of myocardial hypoxemia.
• Transfusion-reaction anaphylaxis: An anaphylactic transfusion reaction is treated the same way: stop the transfusion, give intravenous crystalloid, and give adrenaline at 0.01 mg/kg intravenously.
• Competition status: Adrenaline is classed as a class 2 substance by racing authorities and its use may not be permitted in certain animal competitions; check the rules before administering it to a competing animal.
• What changed in the 2024 guidelines: Resuscitation guidance has changed since these formularies were printed: the current guidelines retire the high-dose regimen and give one standard dose of 0.01 mg/kg intravenously or intraosseously every 3 to 5 minutes for non-shockable rhythms. For a shockable rhythm that persists beyond the first shock they suggest vasopressin as the first-line vasopressor, or adrenaline 0.01 mg/kg if vasopressin is not available.