Esmolol (esmolol hydrochloride) is an intravenous cardioselective beta-1 adrenergic antagonist. Esmolol is FDA-approved for short-term duration use in control of supraventricular tachycardia, such as a rapid ventricular rate in patients with atrial fibrillation or atrial flutter. Esmolol is used in various settings including urgent care, perioperatively, and postoperatively. It is also indicated in sinus tachycardia, where a rapid rate requires intervention secondary to other comorbidities. Esmolol is further FDA-approved for tachycardia and hypertension induced by intubation. Off-label, it is used for rate and rhythm control in aortic dissection, acute coronary syndrome, non-ST elevation myocardial infarction, hypertensive emergencies, thyrotoxicosis, refractory ventricular tachycardia, refractory to defibrillation ventricular fibrillation, and to decrease catecholamine response during electroconvulsive therapy.[1][2][3][4]

Esmolol is a short-acting, cardio-selective, beta-blocker, which is a class II anti-arrhythmic agent that is a competitive antagonist on the beta-1-adrenergic receptors primarily in the myocytes. By blocking the action of adrenergic activity of epinephrine and norepinephrine, it decreases inotropic contractility, heart rate, and conduction. Esmolol increases atrioventricular refractory time, decreases oxygen demand of the myocardium, and decreases atrioventricular conduction. A minor beta-2-adrenergic blockade has been reported with high intravenous infusion doses. Esmolol is rapidly absorbed, the onset of action is within 60 seconds, and it maintains a steady state within 5 minutes of initiation of infusion. If a loading dose is administered, a steady state can be achieved by the 2-minute mark. The drug has a 9-minute half-life and rapid renal clearance. Rapid metabolism translates into the rapid decrease of pharmacological effect (within 10 to 30 minutes) once the infusion is discontinued, making esmolol safer when titrated appropriately. Hydrolysis of the ester linkage metabolizes Esmolol by the esterases in the cytosol of erythrocytes. The metabolite has a half-life of 3.7 hours and is excreted via urine. Of note, esmolol does not have any membrane stabilizing activity or alpha-adrenergic blockade.

Esmolol is administered intravenously, preferably through a central venous access, however, can also be infused peripherally. FDA approval was based on adult subjects; Pediatric dosages have been experimental and are not approved by the FDA.[5][6][7][8]

FDA-Approved

Perioperative and Postoperative Tachycardia and Hypertension

Two methods

• Bolus of 1000 mcg/kg over 30 seconds, followed by 150 mcg/kg per minute infusion, with a max dose of 300 mcg/kg per minute.
• A bolus of 500 mcg/kg over 1 minute, followed by 50 mcg/kg per minute infusion for 4 minutes. If the desired effect is not reached, may increase in 50 mcg/kg per minute increments until the max dose of 300 mcg/kg per minute.

Supraventricular Tachycardia and Sinus Tachycardia

• Bolus loading dose of 500 mcg/kg over 1 minute, followed by 50 mcg/kg/min infusion for 4 minutes. If the desired effect is not reached, may increase in 50 mcg/kg per minute increments until the max dose of 200 mcg/kg per minute.
• For rapid efficacy, may follow the initial loading dose and infusion of 50 mcg/kg per minute by a second 500 mcg/kg bolus over 1 minute and increase drip to 100 mcg/kg per minute for 4 minutes.

Off-Label Use

Hypertensive Emergency

• Loading dose of 500 to 1000 mcg/kg over 1 minute (can be repeated once), followed by infusion of 50 mcg/kg per minute until the max dose of 200 mcg/kg per minute is achieved.

Aortic Dissection

• Loading dose of 500 mcg/kg over 2 to 5 minutes, followed by infusion of 10 to 20 mcg/kg per minute.

Acute Coronary Syndrome

• Loading dose of 500 mcg/kg over 1 minute, followed by 50 mcg/kg per minute infusion titrated every 5 to 15 minutes until the max dose of 300 mcg/kg per minute.

Electroconvulsive Therapy

• Loading dose of 1000 mcg/kg over 1 minute prior to administration of anesthesia.

Thyrotoxicosis

• 50 to 100 mcg/kg per minute

Intubation Cholinergic Response

• Loading dose of 1000 to 2000 mcg/kg administered 1.5 to 3 min prior to endotracheal intubation.

Ventricular Tachycardia/Ventricular Fibrillation

• Loading dose of 500 mcg/kg bolus, followed by 50 mcg/kg per minute

Esmolol should be used short-term, with a maintenance dose infusion not exceeding 48 hours. Most patients who are on esmolol infusions will be transitioned to other long-term agents. Once the effects of esmolol are no longer needed, it should not be discontinued suddenly. New medication should be initiated, followed by titrated esmolol down by 50% and reassessing hemodynamic stability. If the patient is stable, continue to slowly titrate the esmolol down, while titrating the new agent up until the desired goal heart rate and/or blood pressure. Esmolol does not require dosage adjustment for renal or hepatic impairment. Peripheral extravasations can cause thrombophlebitis. If the extravasation occurs, the infusion should be stopped, the line should be gently aspirated, and the limb should be elevated.

The most common adverse reaction with esmolol is a hemodynamic compromise, which happens to over 10% of all patients. The risk of asymptomatic (25%) and symptomatic (12%) hypotension occurs at all doses, but the risk is dose-dependent. Hypotension in Esmolol patients often appears once doses reach 150 mcg/kg per minute. In clinical trials, Esmolol-induced hypotension was usually corrected by titrating down or discontinuing the infusion. Patients also experienced dizziness (3%), peripheral ischemia (1%), and infusion site reaction (8%) such as blistering/necrosis/thrombophlebitis.

Rare side effects (less than 1% of patients without comorbidities) included bradycardia, decompensated heart failure, asystolic cardiac arrest, and heart block.

Esmolol did not show any significant laboratory abnormalities, and patients tolerated the drug well while being infused for up to 24 hours. However, some cases of hyperkalemia with esmolol use have been reported. Electrolyte levels should be monitored for hyperkalemia in patients who have renal disease. Hypoglycemic induced tachycardia is often not present with the use of Esmolol, like other beta-blockers. Patients who are on Esmolol and are known diabetics should be closely monitored. Esmolol has also been reported to exacerbate coronary vasospasms, such as Prinzmetal’s Angina.

In a setting of a patient with pheochromocytoma, esmolol should be given with an alpha-blocker not to have beta-blockage without opposed alpha. Patients with a history of hyperthyroidism should be closely monitored after discontinuation of esmolol may exacerbate hyperthyroidism. Esmolol may also aggravate arterial insufficiency in patients with a history of the significant peripheral vascular disease.

Esmolol is contraindicated in patients with sinus bradycardia, sick sinus syndrome, atrioventricular heart block, heart failure, cardiogenic shock, pulmonary hypertension, and history of hypersensitivity reactions to esmolol. Esmolol and calcium channel blockers should not be given together, as this may exacerbate hypotension and bradycardia.

Patients with first-degree heart block and nodal dysfunctions are at an increased risk of progressive heart block, bradycardia, and AV dissociation. Patients with preexisting heart failure are at greater risk of complete heart failure and cardiogenic shock. Patients with airway disease, such as asthma and chronic obstructive pulmonary disease should be cautious when using any beta-blocker, such as Esmolol. Even though effects on beta-2 is minimal, some risk may exist.

Esmolol is a category C drug in pregnancy. During trials in third-trimester pregnancy and labor, Esmolol has been shown to cause fetal bradycardia, which persisted after the drug infusion was discontinued. There is no conclusive data regarding milk excretion; however, due to the serious potential for adverse effects, it should not be used in breastfeeding mothers.

Drug-Drug Interactions

Numerous drug-drug interactions exist with esmolol, most significant being:

• Digitalis: 10% to 20% increase of digoxin levels, with may aggravate slow AV conduction and heart rate
• Anticholinesterases: Prolonged neuromuscular junction blockage and recovery time
• Calcium channel blockers: Decreases myocardial contractility, may trigger a cardiac arrest
• Vasoconstrictor and inotropic agents: Esmolol should not be used to control heart rate elevation in patients who receive peripheral vascular constrictive agents such as epinephrine, norepinephrine, and dopamine.