Effective Dose of Isoproterenol-Containing Test Dose in Anesthetized Children

To the Editor: We read with interest the article by Kozek-Langenecker et al. [1] in which they demonstrated that the effective dose of isoproterenol (ISO) in the test dose required to increase the heart rate (HR) >20 bpm (CD20) in sevoflurane-anesthetized children was significantly larger than that in halothane-anesthetized children. Although their conclusion regarding the comparison between the two anesthetics is still valid, the actual CD20 values determined under sevoflurane and halothane anesthesia regrettably seem to be underestimated by the incremental dosing regimen of the potent beta-adrenergic agonist over relatively short intervals based on the following two reasons. First, although the authors stated that the accumulation of ISO was minimal, the plasma half-life of ISO has been reported to be 1.5-4.2 min in children and showed substantial interindividual variations [2,3]. In addition, the pharmacokinetic profile after repeated IV injections of ISO has never been studied in either adult or pediatric population. Therefore, up to five IV doses of ISO, ranging from 20 to 100 ng/kg, separated by 5-10 min, given in a single patient does not rule out the accumulation of ISO in the extracellular space. Indeed, previous similar studies, in which a single dose of ISO was administered in one patient, demonstrated that 50-75 ng/kg ISO produced average increases in HR from 21 to 23 bpm in halothane-anesthetized children [4,5], whereas the CD20 reported in Kozek-Langenecker et al.'s study [1]-32 ng/kg-is remarkably small. Second, the repeated stimulation of beta-receptor by its ligand produces rapid biphasic modulation (initially up-, then down-regulation) of the receptor over 30-40 min of administrations [6]. Hence, considerably smaller CD20 values may be explained by the enhanced HR response associated with initial hypersensitivity of beta-receptors caused by repeated administrations of this potent beta-adrenergic agonist. Makoto Tanaka, MD Toshiaki Nishikawa, MD Department of Anesthesia; Akita University School of Medicine; Akita 010-8543, Japan