Discussion
We found that combined hydroxychloroquine/azithromycin results in significant QTc prolongation in approximately one in four hospitalized patients. The degree of QTc prolongation is severe, exceeding 500 ms in 14% of patients, and resulting in a case of TdP. Thus combined hydroxychloroquine/azithromycin should not be administered without continuous telemetry monitoring, even in the setting of a clinical trial. Determinants of QTc prolongation include older age, impaired renal function, baseline QTc >460 ms, and concurrent use of other high-risk QTc-prolonging drugs. Care is required to minimize the concurrent administration of these medications. Vigilance in QTc and arrhythmia monitoring is required for patients in whom the concurrent use of high-risk QTc drugs is necessary, with particular attention to intravenous propofol given the frequency of its use in severe infection. Propofol, which is often used as a sole agent without clinical sequalae, may increase pro-arrhythmic risk when administered with hydroxychloroquine/azithromycin in patients with severe COVID-19 infection.