Epinephrine CRI

Endogenous catecholamine with α₁, α₂, β₁, and β₂ agonist activity. Low-dose IV (≈0.01 mg/kg) directly stimulates cardiac β₁ receptors for increased heart rate and contractility, increasing cardiac output along with myocardial work and oxygen consumption. β₂ activity in the periphery decreases peripheral vascular resistance (lowering diastolic BP). At higher dosages (≈0.1 mg/kg), peripheral vasoconstriction predominates via α₁ effects. Metabolized by MAO and COMT to inactive metabolites; does not cross the blood-brain barrier.

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Clinical background

Epinephrine is the highest-impact, highest-risk drug in the catecholamine family. It is the indispensable drug for cardiopulmonary resuscitation and anaphylaxis, but as a CRI it is reserved for hypotension that has not responded to other inotropes or vasopressors. Its non-selective receptor activity makes it powerful but unpredictable across the dose range, which is why most clinicians reach for norepinephrine first when a CRI is the goal.

Pharmacology

Endogenous catecholamine with α₁, α₂, β₁, and β₂ agonist activity. The dose-response is biphasic in a clinically meaningful way:

• Lower doses (~0.01–0.1 µg/kg/min): β₁ effects predominate. Heart rate and contractility rise; cardiac output increases. β₂-mediated peripheral vasodilation lowers diastolic blood pressure modestly. Net effect: improved cardiac output without large changes in mean blood pressure.
• Higher doses (≳0.3 µg/kg/min): α₁ vasoconstriction overtakes β₂ vasodilation. Systemic vascular resistance rises sharply. The drug now resembles norepinephrine in its blood-pressure effect, but with substantially more β-driven tachycardia and arrhythmogenicity.

Epinephrine is metabolized rapidly by COMT and MAO; onset is within 1–2 minutes IV and the duration after stopping the infusion is short. The drug does not cross the blood–brain barrier.

Indications

Primary use cases:

• Cardiopulmonary resuscitation (bolus dosing, not a CRI indication)
• Anaphylaxis (initial bolus; CRI follows if shock persists)
• Anesthesia-induced or septic hypotension that has not responded to fluid resuscitation, lightening of anesthetic plane, and a first-line vasopressor (norepinephrine or dopamine)
• Refractory bradycardia where atropine has failed

Per Plumb’s, epinephrine for hypotension should be considered only when other interventions have failed, because of increased tissue oxygen demand and severe splanchnic vasoconstriction at higher infusion rates. The Surviving Sepsis Campaign positions epinephrine as the first alternative or addition to norepinephrine when MAP targets are not being met. In small-animal practice, that translates to: try norepinephrine first, then add or substitute epinephrine if MAP remains inadequate.

Dosing

• Anaphylaxis with established shock: 0.05 µg/kg/min slow IV infusion, titrated to clinical response
• Anesthesia-induced hypotension nonresponsive to other inotropes: 0.125–2 µg/kg/min CRI

Start at the bottom of the published range and titrate. Most patients responding to epinephrine will respond at <0.5 µg/kg/min. Doses approaching or exceeding 1 µg/kg/min should prompt reassessment of indication and contributing causes.

CPR doses are bolus, not CRI, and use a separate calculator.

Administration

Two commercial epinephrine concentrations exist and are easily confused:

• 1 mg/mL (formerly labeled 1:1000), the strength used to prepare CRIs
• 0.1 mg/mL (formerly labeled 1:10 000), the cardiac-arrest bolus formulation

Read the vial twice. Mixing these up has caused both under- and over-doses, including fatalities in human medicine. Plumb’s flags epinephrine as a high-alert medication.

Epinephrine is stable in 5% dextrose, dextrose-saline combinations, lactated Ringer’s, Ringer’s, and 0.9% sodium chloride. It becomes unstable in 5% dextrose at pH > 5.5, check solution color before and during the infusion and discard if it turns pink, brown, or develops a precipitate. Do not mix with sodium bicarbonate.

A central line is preferred for any sustained infusion. Peripheral administration is acceptable in emergencies, but the infusion site must be visible and checked frequently for extravasation.

Drug interactions

• Halogenated inhalant anesthetics (isoflurane, sevoflurane) sensitize the myocardium. Arrhythmia risk is substantially increased when epinephrine is given under inhalational anesthesia, the most common veterinary CRI scenario. If arrhythmias develop, propranolol may be used to manage them.
• Acepromazine and other phenothiazines can produce “epinephrine reversal.” α₁ blockade by acepromazine unmasks unopposed β₂ vasodilation, and an epinephrine bolus or infusion can paradoxically worsen hypotension. Use norepinephrine or phenylephrine instead in acepromazine-premedicated patients.
• Beta-blockers can produce unopposed α-mediated vasoconstriction with severe hypertension when epinephrine is given.
• Tricyclic antidepressants and MAO inhibitors potentiate epinephrine’s effects.

Adverse effects

• Tachyarrhythmias, sinus tachycardia, premature ventricular complexes, ventricular tachycardia, atrial fibrillation. Risk rises with dose, with concurrent inhalant anesthesia, and with electrolyte derangements (especially hypokalemia).
• Hypertension at higher doses
• Splanchnic ischemia and hyperlactatemia at sustained higher doses
• Pulmonary edema (rare; usually in patients with pre-existing left heart disease)
• Extravasation injury, tissue necrosis from local α₁ vasoconstriction
• Restlessness and tremors (lower-dose CRIs are usually well tolerated in this respect)

Monitoring

• Continuous ECG, arrhythmias are common and appear before clinical signs
• Continuous or frequent blood pressure
• Lactate trend if shock is the indication
• Urine output as a perfusion marker
• Mucous membrane color, CRT, extremity temperature
• Serum potassium and magnesium, derangements amplify arrhythmia risk

Extravasation

Epinephrine extravasation can cause severe local tissue necrosis. If it occurs, stop the infusion immediately, aspirate what you can through the catheter before removing it, and consider local infiltration with phentolamine. The same management applies as for norepinephrine extravasation.

Weaning

Wean by reducing the rate in 0.05 µg/kg/min increments every 10–15 minutes while watching MAP. As with norepinephrine, do not stop abruptly unless transitioning to another vasopressor.

Sources

• Plumb’s Veterinary Drugs, epinephrine monograph (current edition).
• Hart S, Silverstein DC. Catecholamines. In: Silverstein DC, Hopper K, eds. Small Animal Critical Care Medicine. 3rd ed. Elsevier; 2023:855–859. Chapter 147; Table 147.1.