Clinical Pharmacokinetics and Therapeutic Efficacy of Esmolol

Abstract

Esmolol is a unique cardioselective β(1)-receptor blocking agent with a rapid onset and short duration of action. Since our previous review in 1995, the pharmacokinetics and efficacy of esmolol have been investigated in a number of acute care settings. Three studies investigated the pharmacokinetics and safety of esmolol in the paediatric population. The disposition of esmolol in children was found to be linear with plasma concentrations increasing in proportion to dose over the ranges studied. The pharmacokinetic estimates for esmolol showed a shorter elimination half-life (t(½)) [2.7-4.8 minutes] and a higher clearance (281 mL/kg/min) in newborns and infants than that found in children (>2 years old) and adults. Dosing requirements to achieve targeted blood pressure in post-coarctectomy patients were substantially higher (mean 700 μg/kg/min) than that used in adults. Esmolol was effective in controlling hypertension following cardiac surgery and terminating supraventricular arrhythmias in children. The efficacy of esmolol has been established in a variety of patients, including those with unstable angina, myocardial ischaemia, supraventricular arrhythmias, peri- and postoperative tachycardia and hypertension, and electroconvulsive therapy. With careful titration and monitoring, esmolol can be used effectively in patients with congestive heart failure and chronic obstructive lung disease because of its unique short t(½) and β(1)-selectivity. Different dosage schedules have been developed depending on clinical setting and diagnosis. Generally, a loading dose of ≤500 μg/kg/min over 1 minute is administered followed by a continuous infusion of 25-300 μg/kg/min. Hypotension, being the primary adverse effect, can be minimized by careful dosage titration and patient monitoring. In the perioperative setting involving tracheal intubation and extubation, a number of recent studies have suggested that titration of esmolol to a haemodynamic endpoint can be safe and effective, resulting in a decreased incidence of myocardial ischaemia. The most effective regimen in attenuating the response to heart rate and blood pressure after laryngeal tracheal intubation was a loading dose of 500 μg/kg/min for 4 minutes followed by a continuous infusion of 200-300 μg/kg/min. In cardiac and non-cardiac surgical patients esmolol has been shown to decrease episodes of myocardial ischaemia and arrhythmias. In the perioperative period for non-cardiac surgery routine use of β-blockers (β-adrenoceptor antagonists) is no longer recommended. However, in patients at high risk for myocardial ischaemia or undergoing high-risk surgery where a β-blocker is indicated, esmolol is the ideal perioperative agent to minimize the risk of hypotension and bradycardia based on its pharmacodynamic and pharmacokinetic characteristics. For postoperative patients in atrial fibrillation, esmolol achieves rapid ventricular rate control. However, for the prevention of postoperative atrial fibrillation esmolol provides no advantage over oral β-blockers. I...

Autonomic modulation of repolarization instability in patients with heart failure prone to ventricular tachycardia

“…The lack of response to esmolol due to an insufficient dosage is possible. Esmolol bolus and high-dose infusion, however, frequently produce hypotension (53), which can smudge the effects on QTV and were suitably avoided. A drug-specific ineffectiveness of esmolol to reduce QTV is unlikely as the efficacy of ␤-blockers was shown to be a class effect than that of a generic drug (15).…”

Esmolol is noninferior to metoprolol in achieving a target heart rate of 65 beats/min in patients referred to coronary CT angiography: A randomized controlled clinical trial

“…11,12 The rapid onset and offset of effects of esmolol provide an element of safety not previously available with longer-acting b-adrenoceptor antagonists. 13 During coronary CTA, short and effective HR control is desirable; therefore, esmolol might be a good alternative to the standard of care metoprolol. Currently, esmolol is routinely administered in the intensive care unit for the treatment of acute supraventricular arrhythmias; however, administration before coronary CTA for HR reduction is an "off-label" indication.…”

Esmolol for the treatment of recurrent ventricular tachycardia

“…Esmolol is a cardio-selective beta1-receptor blocking agent with a rapid onset and a short duration of action (t1/2=9 minutes). 6 The efficacy of esmolol has been successfully tested both during CA due to refractory VF 7-11 increasing ROSC and survival and during pulseless ES 12 overcoming ACLS drugs. However the efficacy of esmolol in treating hemodynamically tolerated ventricular arrhythmias has never been described and so we reported these two cases.…”