Esmolol is a cardioselective short-acting beta-1 receptor blocker with no significant sympathomimetic effects, available by the brand name of Brevibloc (among others).

Esmolol Uses:

• Intraoperative and postoperative tachycardia and/or hypertension:

  • Use for treating intraoperative and postoperative tachycardia and/or hypertension

• Sinus tachycardia:

  • Used for treating non-compensatory sinus tachycardia

• Supraventricular tachycardia and atrial fibrillation/flutter:

  • Control of ventricular rate in patients with supraventricular tachycardia or atrial fibrillation/flutter

• Off Label Use of Esmolol in Adults:

  • Used in electroconvulsive therapy (attenuation of adrenergic response)
  • Used in  hypertensive emergencies
  • Used in  intubation (attenuation of adrenergic response)
  • Used in thyroid storm
  • Used in thyrotoxicosis
  • Used in ventricular tachycardia

Esmolol Dose in Adults

Esmolol Dose in the treatment of Intraoperative and postoperative tachycardia and/or hypertension: IV:

• Immediate control:

  • If necessary, a 150 mcg per kg per minute infusion is given after the initial bolus of 1,000 mcg per kg over 30 seconds.
  • To maintain the desired heart rate and/or blood pressure, alter the infusion rate as necessary (up to 300 mcg per kg per minute).

• Gradual control:

  • A 50 mcg per kg per minute infusion is given after the initial bolus of 500 mcg per kg over 1 minute.
  • If the reaction is insufficient, the infusion may be increased by 50 mcg per kg per minute increments (no more frequently than every 4 minutes) up to a maximum of 300 mcg per kg per minute;
  • Prior to each increase in the infusion rate, a loading dosage that is equal to the original bolus (500 mcg per kg over 60 seconds) may be given.
• Doses more than 200 mcg per kg per minute have the least extra influence on the regulation of tachycardia.
• One-third of patients may need greater doses (250 to 300 mcg per kg per minute) to control postoperative hypertension; the safety of doses longer than 300 mcg per kg per minute has not been researched.

Esmolol Dose in the treatment of Hypertensive emergencies (off-label):

• IV: 500 to 1,000 mcg per kg over 1 minute as a loading dose, then 50 mcg per kg per minute as an infusion.
• Repeat the loading dosage and adjust the infusion rate by 50 mcg each time you need more blood pressure management.

Esmolol Dose in the treatment of Supraventricular tachycardia and atrial fibrillation/flutter or non-compensatory sinus tachycardia:

• 50 mcg per kg per minute infusion for 4 minutes after a 500 mcg per kg loading dosage (optional); the response to this initial infusion rate may be a rough indicator of the responsiveness of the ventricular rate.
• If the reaction is insufficient, the infusion may be continued at 50 mcg per kg per minute or titrated upward to a maximum of 200 mcg per kg per minute in increments of 50 mcg per kg per minute (raised no more frequently than every 4 minutes).
• Re-bolus with a second 500 mcg per kg loading dosage over 1 minute in order to get a quicker response after the original loading dose and 50 mcg per kg per minute infusion.
• Before raising the infusion rate to 150 mcg per kg per minute, a third (and final) 500 mcg per kg loading dosage may be given, if necessary.
• The infusion rate may be increased to a maximum rate of 200 mcg per kg per minute after 4 minutes of the 150 mcg per kg per minute infusion (without a bolus dose).
• The recommended maximum dose for supraventricular tachycardia is 300 mcg/kg/minute, according to the ACC/AHA/HRS recommendations.
   

Note:

• A continuous infusion at a constant dose reaches a steady-state in around 30 minutes if no loading dose is given.
• In general, doses as little as 25 mcg per kg per minute may be sufficient. The typical effective dose ranges from 50 to 200 mcg per kg per minute.
• For up to 48 hours, maintenance infusions can be continued.

Esmolol Dose in the treatment of Electroconvulsive therapy (off-label):

• IV: Delivered one minute before the onset of anaesthesia at 1,000 mcg per kilogramme.

Esmolol Dose for Intubation (off-label):

• IV: Administered 1.5 to 3 minutes prior to intubation, 1,000–2,000 mcg per kilogramme.

Esmolol Dose in the treatment of Thyrotoxicosis or thyroid storm (off-label):

• IV: Between 50 and 100 mcg per kilogramme each minute.

Esmolol Dose in the treatment of Ventricular tachycardia (off-label):

• IV: 50 mcg per kg per minute after a 500 mcg per kg bolus.

Guidelines for transfer to oral therapy (beta-blocker, calcium channel blocker):

• Thirty minutes after the initial dose of the substitute medication, the infusion should be cut in half.
• The manufacturer advises monitoring the patient's response after the second dose of the substitute medication and ceasing esmolol if control is satisfactory for the first hour.

Esmolol Dose in Children

Note: The dose must be adjusted based on each person's response and tolerance.

Esmolol Dose in the treatment of Hypertensive emergency/urgency:

• Infants, Children, and Adolescents:

  • Continuous IV infusion:
    • 100 to 500 mcg per kg per minute infusion; an alternative strategy is to start treatment with a bolus of 100 to 500 mcg/kg over 1 minute, followed by an infusion of 25 to 100 mcg per kg per minute; gradually increase the dose up to
    • 500 mcg per kg per minute as necessary.

Esmolol Dose in the treatment of Postoperative hypertension: 

• Infants and Children:

  • Initial IV bolus:
    • Titrate to effect after an initial dose of 100 to 500 mcg per kg, followed by a continuous IV infusion at a rate of 100 to 500 mcg per kg per minute.
    • Effective dosages might range from 125 to 1,000 mcg per kilogramme per minute.

Esmolol Dose in the treatment of Supraventricular tachycardia (SVT): 

• Children and Adolescents:

  • The average maintenance dose is 50 to 500 mcg per kg per minute; doses up to 1,000 mcg per kg per minute have been observed.
  • The initial IV bolus is 100 to 500 mcg per kg over 1 minute, followed by a continuous IV infusion at an initial rate of 25 to 100 mcg per kg per minute.

Esmolol Pregnancy Risk Category: C

• In some studies on animal reproduction, adverse events were reported.
• Supraventricular Tachycardia (SVT) is treated with Esmolol. However, pregnant women may prefer other agents.
• Fetal bradycardia has been linked to Esmolol.
• Chronic use of beta-blockers during pregnancy can also lead to adverse fetal/neonatal outcomes.
• However, esmolol has a short-acting beta blocker and is not recommended for long-term use.

Esmolol use during breastfeeding:

• It is unknown if breast milk contains esmolol.
• The manufacturer suggests that the mother decide whether to stop breastfeeding or discontinue the drug. This is in consideration of the risk of serious adverse reactions in breastfed babies.
• Its short half-life and inability to be used for prolonged periods should limit exposure to breastfeeding infants.

Esmolol Dose in Kidney Disease:

No dosage adjustment required. Not removed by hemo- or peritoneal dialysis. A supplemental dose is not necessary.

Esmolol Dose in Liver disease:

No dosage adjustment required.

Common Side Effects of Esmolol:

• Cardiovascular:

  • Asymptomatic hypotension
  • Symptomatic hypotension

Less Common Side Effects of Esmolol:

• Cardiovascular:

  • Peripheral Ischemia

• Central Nervous System:

  • Dizziness
  • Drowsiness
  • Headache
  • Agitation
  • Confusion

• Gastrointestinal:

  • Nausea
  • Vomiting

• Local:

  • Infusion site reaction

Contraindications to Esmolol:

• Hypersensitivity to esmolol and any component of the formulation
• Grave sinus bradycardia
• Heart block of greater than the first degree is not possible (except for patients who have a working artificial ventricular pacemaker);
• sick sinus syndrome;
• Decompensated Heart Failure
• Cardiogenic shock
• IV administration of calcium channel blocking agents (eg verapamil), in close proximity of esmolol (ie while cardiac effects from other drugs are still present).
• Pulmonary hypertension

Canadian labeling: Additional contraindications not in US labeling

• Patients who require inotropic drugs and/or vasopressors for maintaining cardiac output and systolic pressure;
• Hypotension
• Right ventricular failure secondary pulmonary hypertension
• Untreated pheochromocytoma

Warnings and precautions

• Anaphylactic reactions

  • Patients who have had severe allergic reactions to allergens in the past should be cautious. Beta-blockers can make it more difficult for patients to react to repeated challenges.
  • Treatment of anaphylaxis (eg, epinephrine) in patients taking beta-blockers may be ineffective or promote undesirable effects.

• Extravasation:

  • A vesicant, indeed. Before and during infusion, make sure the catheter or needle is positioned correctly.
  • Avoid extravasation.

• Hyperkalemia:

  • In patients with risk factors, esmolol has been associated with increased serum potassium levels and hyperkalemia (eg renal impairment). During treatment, it's critical to keep an eye on serum potassium levels.

• Hypotension

  • Hypotension is a common condition.
  • Patients require close monitoring of blood pressure.
  • Hypotension can be reversed if blood pressure drops beyond acceptable levels. Usually, this happens within 30 minutes.

• Bronchospastic Disease:

  • Patients with bronchospastic diseases should not be given beta-blockers. However, it is possible to use esmolol with B-1 selectivity with caution and close monitoring.

• Conductive abnormality

  • Bradycardia can include sinus pause, heart block and severe bradycardia.
  • Before you start, consider preexisting conditions like sick sinus syndrome or first degree AV blocking.
  • It is not advisable for individuals to use this drug if they have sick sinus syndrome, second- or third-degree AV block, or if they have an artificial ventricular pacemaker.

• Diabetes:

  • Patients with diabetes mellitus should be cautious.
  • It can increase hypoglycemia or mask symptoms.

• Heart failure (HF):

  • Patients with compensated cardiac failure should be cautious and monitored for signs of deterioration.
  • Patients with decompensated cardiac failure should not be used.

• Myasthenia gravis:

  • Patients with myasthenia gravis should be cautious.

• Raynaud and peripheral vascular disease (PVD).

  • Patients with Raynaud and PVD may experience symptoms that can either precipitate or aggrave arterial insufficiency.
  • Be cautious and watch for arterial obstruction.

• Untreated Pheochromocytoma

  • Patients with pheochromocytoma must have adequate alpha-blockade before any beta-blocker can be used.

• Renal impairment

  • Patients with impaired renal function should be cautious; active metabolite must be retained.

• Thyroid disease:

  • Hyperthyroidism should be suspected and treated accordingly.
  • Rapid withdrawal can worsen hyperthyroidism symptoms or cause a thyroid storm.
  • Hyperthyroidism may be disguised (eg, Tachycardia).

Esmolol: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters:

• MAP (mean arterial pressure),
• heart rate,
• continuous ECG,
• Blood pressure,
• respiratory rate,
• Monitor IV site for extravasation;
• serum potassium (especially with renal impairment).

How to administer Esmolol?

IV:

• Depending on how quickly the desired impact is to take effect, loading dosages may be given over a period of 30 to 1 minutes.
• Avoid administering medication with a butterfly catheter or into tiny veins (can cause thrombophlebitis).
• If necessary, the medication port on pre-mixed bags should only be used to remove the initial bolus (not to be used for withdrawal of additional bolus doses).
• It is a vesicant; Make sure the needle or catheter is properly positioned before and throughout the infusion; Prevent extravasation.

Extravasation management:

• In the event of extravasation, immediately stop the infusion, disconnect (leave the cannula or needle in situ), and gently aspirate the extravasated solution (DO NOT flush the line);
• remove needle/cannula;
• Elevate the extremity.

Mechanism of action of Esmolol:

Antiarrhythmic class II: Competitively blocks beta-adrenergic stimulation at high doses with little to no beta-2 receptor effect, no intrinsic synthomimetic activity and no membrane stabilizing activities.

The beginning of action:

• IV beta-blockade: 2–10 minutes (fastest when loading doses of beta-blockade are administered).
• Hemodynamic effects last between 10-30 minutes. They can be prolonged after higher cumulative doses or extended use.

Protein binding:

• Esmolol: 55 percent ;
• Acid metabolite: 10 percent

Metabolism:

• Red blood cell esterases break it down in the blood, creating methanol and an acid metabolite with low action and no clinically significant side effects (does not achieve concentrations associated with methanol toxicity)

Half-life elimination:

• Children ≥18 months and Adolescents ≤16 years: Variable; mean range: 2.7 to 4.8 minutes (reported full range: 0.2 to 9.9 minutes).
• Adults: Esmolol: 9 minutes; Acid metabolite: 3.7 hours; elimination of metabolite decreases with end-stage renal disease

Excretion:

• Urine (~73% to 88% as acid metabolite, <2% unchanged drug)

International Brand Names of Esmolol:

• Brevibloc
• Brevibloc
• Cardesmo
• Esbloc
• Escord
• Esmocard
• Brevibloc in NaCl
• Brevibloc Premixed
• Brevibloc Premixed DS
• Ai Luo
• Breviblo
• Nevopax HP

Esmolol Brand Names in Pakistan:

There is no brand available in Pakistan.