Prolonged recovery of renal function after prostatectomy for prostatic outflow obstruction.

Comment Ventricular arrhythmia associated with prolongation of the Q-Tc interval is a well known side effect of several drugs. In our patient the close temporal relation of prolongation of the Q-Tc interval and infusion of erythromycin with the maximum interval occurring at the end of the infusion and a gradual return to normal over the next few hours strongly suggested a direct dependence of the Q-Tc interval on the plasma concentrations of erythromycin. That we recorded this phenomenon during two separate drug infusions lends support to this suggestion. A possible association of erythromycin with ventricular arrhythmias has been reported.' 2 Prolongation of the Q-T interval was the common feature in all cases. Nevertheless, given the widespread use of erythromycin, the low rate of drug associated arrhythmias recognised is remarkable. In our patient ventricular extrasystoles and torsades de pointes occurred only at the time when peak plasma concentrations would be expected and when the longest Q-Tc interval was seen. How erythromycin alters cardiac repolarisation is not clear, but a recent electrophysiological study has shown that erythromycin exerts a concentration dependent quinidine-like effect.3 Aside from the mode of administration leading to different peak plasma concentrations other factors must be considered. In patients with pre-existing prolongation of the Q-T interval-for example, in idiopathic long Q-T syndrome4-erythromycin may worsen the repolarisation abnormality and induce arrhythmias. As in other published cases' our patient had a normal Q-T interval before being given the drug. Other factors such as alterations of erythromycin pharmacokinetics resulting in different individual susceptibility may be important. Both structural damage of liver tissue and cotreatment with other drugs competing for the same hepatic cytochrome (P450IIIA4) may impair hepatic drug clearance and lead to critically raised plasma concentrations of erythromycin. The hepatic dysfunction present in our patient may have been a main factor contributing to the erythromycin toxicity. To minimise the danger of toxic plasma concentrations rapid injections of erythromycin should be avoided as recommended by the manufacturers. In patients at risk close Q-Tc and rhythm monitoring may be advisable. In a patient with impaired hepatic drug metabolism or pre-existing cardiac disease a smaller dose or an alternative antibiotic should be considered.