INCIDENCE OF CARDIAC-ARRHYTHMIAS DURING INTRAVENOUS PENTAMIDINE THERAPY IN HIV-INFECTED PATIENTS

Study objective: There have been 15 published cases of probable pentam idine-induced torsade de pointes (TdP). A prospective analysis of this complication of therapy is valuable considering the high frequency of Pneumocystis carinii pneumonia in the AIDS population, and the role o f pentamidine in its therapy. Design: Open, nonrandomized, prospective study of HIV-infected patients receiving intravenous pentamidine in a 12-month period. Setting: Walter Reed Army Medical Center, a tertiary care, referral-based facility in Washington, DC. Patients: Eighteen H IV-infected patients were enrolled with informed consent; four were wi thdrawn from statistical analysis after receiving only one or two dose s of empiric intravenously administered pentamidine. Measurements and results: Daily 12-lead electrocardiography, echocardiography, weekly s ignal-averaged electrocardiography, and weekly 24-h ambulatory electro cardiography were performed on each patient. Of the 14 subjects, 3 dev eloped TdP. These 3 patients and 2 others developed a prolonged rate c orrected, QT interval (QTc) to greater than 0.48 s (max QTc mean, 0.55 s, mean increase, 0.12 s). The QTc prolongation was noted in all five patients by the fourth daily dose (4 mg/kg/d) of pentamidine. The oth er 9 patients developed minimal change in QTc intervals throughout the rapy (max QTc mean, 0.45 s; mean increase, 0.03 s). The maximum QTc in crease was significantly different between these two cohorts (p < 0.03 ). The occurrence of TdP in the subgroup of patients developing prolon ged QTc intervals to greater than 0.48 s (3 of 5 patients), or a chang e in QTc of greater than 0.08 s (3 of 4 patients) over individual base line also was significant (p = 0.03 and p = 0.01, respectively). No ba seline clinical variables associated with TdP or QTc prolongation were identified. Conclusion: Intravenously administered pentamidine freque ntly results in QTc prolongation with a subsequent risk of TdP in HIV- infected patients. Ah patients treated with intravenously administered pentamidine should be evaluated with baseline and daily ECGs, at leas t during the first week of therapy, and should be closely monitored fo r a change in the QT interval. An increase in QTc to above 0.48 s or g reater than 0.08 s above baseline carries a significant risk for proar rhythmia, and in this instance, continuous electrocardiographic monito ring or an alternative antibiotic regimen should be considered.