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.
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.
Perioperative and Postoperative Tachycardia and Hypertension
Supraventricular Tachycardia and Sinus Tachycardia
Acute Coronary Syndrome
Intubation Cholinergic Response
Ventricular Tachycardia/Ventricular Fibrillation
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.
Numerous drug-drug interactions exist with esmolol, most significant being:
Esmolol is an ultra-fast-acting medication, which can alter heart rate and pressure very quickly. While the patient is on esmolol, it is recommended that they have continuous blood pressure monitoring, heart rate, mean arterial pressure, and if possible ECG. An arterial line will provide the best method of continuous blood pressure monitoring, which is beneficial in use with esmolol. When given peripherally, the intravenous (IV) site should be checked regularly to ensure that it did not infiltrate and extravasate. As mentioned above, in patients with comorbidities, appropriate blood levels should be monitored, such as glucose (diabetes), thyroid levels (hyperthyroid), potassium (renal insufficiency), and peripheral pulses (peripheral vascular disease).
An overdose of esmolol can result in a myriad of symptoms and effects. Cardiac signs of toxicity include, but not limited to bradycardia, AV block of any degree, complete AV dissociation, decrease contractility, cardiogenic shock, asystole, and PEA. Neurologic signs of toxicity include but not limited to respiratory irregularities, seizures, coma, and psychiatric symptomatology. Other signs of toxicity may manifest as bronchospasms, gastrointestinal mesenteric ischemia, peripheral cyanosis and pulselessness.
Since Esmolol has a very short half-life (9 minutes), toxicity should be treated by discontinuation of the esmolol infusion. Acute toxicity is often self-limited and is treated supportively. Toxicity which results in bradycardia should be treated by atropine, pacing, and other anticholinergic agents. Cardiogenic shock can be treated with inotropic agents likes dobutamine, dopamine, and isoproterenol. Bronchospasms, even though rare, should be treated with a beta-2 agonist, such as albuterol. The Advanced Cardiac Life Support protocols should treat PEA and asystolic cardiac arrest. As with other beta-blocker overdoses, intravenous glucagon and calcium chloride can be given to mitigating the effects of eEsmolol while it is being metabolized.