Esmolol. A review of its therapeutic efficacy and pharmacokinetic characteristics

Esmolol is an ultra short-acting intravenous cardioselective beta-antagonist. It has an extremely short elimination half-life (mean: 9 minutes; range: 4 to 16 minutes) and a total body clearance [285 ml/min/kg (17.1 L/h/kg)] approaching 3 times cardiac output and 14 times hepatic blood flow. The alpha-distribution half-life is approximately 2 minutes. When esmolol is administered as a bolus followed by a continuous infusion, onset of activity occurs within 2 minutes, with 90% of steady-state beta-blockade occurring within 5 minutes. Full recovery from beta-blockade is observed 18 to 30 minutes after terminating the infusion. Esmolol blood concentrations are undetectable 20 to 30 minutes postinfusion. The elimination of esmolol is independent of renal or hepatic function as it is metabolised by red blood cell cytosol esterases to an acid metabolite and methanol. The acid metabolite, which is renally eliminated, has 1500-fold less activity than esmolol. Methanol concentrations remain within the range of normal endogenous levels. Clinically, esmolol is used for the following: (i) situations where a brief duration of adrenergic blockade is required, such as tracheal intubation and stressful surgical stimuli; and (ii) critically ill or unstable patients in whom the dosage of esmolol is easily titrated to response and adverse effects are rapidly managed by termination of the infusion. In adults, bolus doses of 100 to 200mg are effective in attenuating the adrenergic responses associated with tracheal intubation and surgical stimuli. For the control of supraventricular arrhythmias, acute postoperative hypertension and acute ischaemic heart disease, doses of < 300 micrograms/kg/min, administered by continuous intravenous infusion, are used. The principal adverse effect of esmolol is hypotension (incidence of 0 to 50%), which is frequently accompanied with diaphoresis. The incidence of hypotension appears to increase with doses exceeding 150 micrograms/kg/min and in patients with low baseline blood pressure. Hypotension infrequently requires any intervention other than decreasing the dose or discontinuing the infusion. Symptoms generally resolve within 30 minutes after discontinuing the drug. In surgical and critical care settings where clinical conditions are rapidly changing, the pharmacokinetic profile of esmolol allows the drug to provide rapid pharmacological control and minimises the potential for serious adverse effects.