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.