Pharmacodynamics and pharmacokinetics of esmolol, a short-acting β-blocking agent, in children

Abstract

Esmolol, a short-acting intravenous cardioselective beta-blocking agent, was evaluated for age-dependent pharmacodynamic and pharmacokinetic features in 17 young patients (6 months to 14 years). A loading dose (500 micrograms/kg/min) alternating with a maintenance dose (25-200 micrograms/kg/min, titrating by 25 micrograms/kg/min every 4 min) was infused until the heart rate or mean arterial pressure decreased 10%. Cardiac index, left ventricular shortening fraction, and systemic vascular resistance were measured at baseline, peak esmolol effect, and recovery. Serum esmolol concentrations were obtained to determine the half-life and the elimination rate constant. Esmolol reduced the heart rate, blood pressure, shortening fraction, and cardiac index in all patients, but it did not change systemic vascular resistance. Maintenance esmolol dose was 118 +/- 49 micrograms/kg/min, and the half-life was 2.88 +/- 2.67 min. Blood pressure and heart rate returned to normal within 2-16 min, but cardiac index and shortening fraction took longer to recover. There were no statistically significant age-dependent pharmacodynamic effects, but blood pressure decreased prior to heart rate and cardiac index took longer to recovery in patients who weighed < or = 15 kg. The pharmacokinetic profile in young patients was similar to that of older patients, but the half-life was shorter. The only side effect was transient nausea and vomiting in one patient. Esmolol is a safe and efficacious beta-blocking agent in young patients.

Liquid chromatography–electrospray mass spectrometry (LC–MS) method for determination of esmolol concentration in human plasma

“…As anticipated, the LOQ with this LC-MS was lower than assays that utilized UV detection methods [3,4,6,7], or gas chromatography methods [8]. Most importantly, the sample volume required for this assay was significantly smaller than all previously reported methods, and will allow for multiple sampling in infants and children.…”

“…Quon and Stamfli initially reported that NaF was an effective inhibitor of esmolol esterase [2]. Numerous other investigators then used NaF as an inhibitor when studying the pharmacokinetics of esmolol [3,4,[9][10][11]. In 1991 Fan and Zhao reported that NaF concentrations as high as 30 mg/ml were unable to inhibit ex vivo metabolism, but detailed data were not presented [6].…”

“…Esmolol is inherently unstable in whole blood due to the ubiquitous presence of red cell esterases [2]. Most previous studies of esmolol pharmacokinetics have utilized sodium fluoride (NaF) to inactivate the red cell esterases [3][4][5]. However, a recent report suggested that NaF in concentrations as high as 30 mg/ml were not effective in stabilizing esmolol in whole blood specimens [6], raising significant concerns about the reliability of previously published results.…”

Drug Treatment of Hypertensive Crisis in Children

“…supraventricular tachycardia) and hypertension control after repair of coarctation. [42][43][44][45][46][47][48] Wiest and colleagues [48] utilized esmolol for acute postoperative hypertension in an open-label trial of pediatric patients after cardiac surgery. They included 20 cardiac surgery patients (10 with aortic coarctation repair, 10 with other congenital heart defect repairs) aged 1 month-12 years.…”

Advances in the pathogenesis and management of hypertensive crisis

“…They should not be used in patients with obstructive lung disease, such as asthma, and should be used with caution if the patient has congestive heart failure. Published experience on labetolol and esmolol therapy in pediatrics is limited [39,40].…”