In Response Hoffman et al.1 provide an elegant alternative hypothesis for the presumed lidocaine-induced neurotoxicity described by us.2 They suggest that the neurotoxicity could better be explained by the inhibition of ATP-binding cassette transporters, especially P-glycoprotein by phenytoin, leading to an intracellular accumulation of lidocaine in the brain. The authors had clearly noticed that the patient’s deterioration in neurological status was temporally related to the dosing of phenytoin. It was our interpretation that altered pharmacokinetics resulted in neurotoxicity despite nontoxic lidocaine concentrations by conventional assays, probably due to immaturity of the brain. However, this alternative hypothesis might provide a better explanation for lidocaine neurotoxicity in the clinical setting reported. We had raised the possibility of an interaction between phenytoin and lidocaine but could not generate the unifying hypothesis that Hoffman et al. have. We would argue that the contribution of phenytoin to the generation of refractory ventricular arrhythmia, however, was minimal, because phenytoin therapy was commenced at the end of the medical treatment phase. The emphasis of our paper was to highlight the occurrence of a possible reversible neurotoxicity after lidocaine exposure in a neonate with life-threatening arrhythmias. Our intent was not to elucidate the cause of the malignant arrhythmia or describe the antiarrhythmic therapy. This issue has been dealt with by several reviews describing the anesthetic management of patients with long QT syndrome.3,4 Although there is evidence that amiodarone in the acute phase may provoke torsades de pointes (TdP), there is also evidence to the contrary, especially in patients with chronic heart failure. In a case series of 6 consecutive patients chronic amiodarone therapy admitted due to syncope and TdP, the potential for TdP was increased in those with female gender, hypokalemia, concomitant use of other drugs adversely affecting transmural dispersion of repolarization (e.g., trazadone, loratadine), and bradycardia.5 Rapid phase III repolarization6 and a reduction of transmural dispersion of repolarization7 by amiodarone have been suggested as mechanisms that might reduce the incidence of TdP with amiodarone therapy. However, we do advocate careful choice and dosing of antiarrhythmic agents that adversely affect ventricular repolarization in children with long QT syndrome undergoing general anesthesia for noncardiac surgery. Aruna T. Nathan, MBBS, FRCA Maryam Y. Naim, MD Department of Anesthesiology and Critical Care Medicine Children’s Hospital of Philadelphia Philadelphia, PA Victoria L. Vetter, MD, MPH Division of Cardiology Department of Cardiology Children’s Hospital of Philadelphia Philadelphia, PA