QTc Prolongation and Arrhythmia Development in the Treatment of ICU Delirium: An Investigation of Medication-Related Risk Factors
Anli Francis
Department of Pharmacy, The Ohio State University Wexner Medical Center, Ohio, USA.
Daniel S. Eiferman
Department of Surgery, The Ohio State University Wexner Medical Center, Ohio, USA.
J. Michael Boyd
Department of Pharmacy, The Ohio State University Wexner Medical Center, Ohio, USA.
Gary Phillips
Center for Biostatistics, The Ohio State University, Ohio, USA.
Claire V. Murphy *
Department of Pharmacy, The Ohio State University Wexner Medical Center, Ohio, USA.
*Author to whom correspondence should be addressed.
Abstract
Aims: Antipsychotics are commonly used for ICU delirium, although there is limited data describing the risk of QTc prolongation with these therapies. This study aimed to evaluate the prevalence of and risk factors for QTc prolongation associated with antipsychotic agents for ICU delirium.
Study Design: A retrospective cohort study of patients with ICU delirium who received an antipsychotic agent.
Place and Duration of Study: The Ohio State University Wexner Medical Center Surgical and Medical ICUs, between January 1st, 2012 and January 1st, 2015.
Methodology: QTc prolongation was defined as QTc >500 ms or >20% increase from baseline. The primary outcome was the prevalence of QTc prolongation. Secondary outcomes included risk factors for QTc prolongation, prevalence of Torsades de Pointes (TdP) or ventricular arrhythmias, ICU length of stay, length of delirium treatment, and all-cause ICU mortality.
Results: Two hundred and nine patients were included, with 27 (13%) patients developing QTc prolongation. In univariate analysis, patients with QTc prolongation had higher baseline QTc (median 453 vs. 442.5 ms) and increased use of concomitant antiarrhythmic (22.2 vs 8.2%) and antidepressant (11.1 vs 5.5%) agents. In multivariable logistic regression, medium [AOR 0.2; 95% CI 0.06-0.74; P=.02] and high [AOR 0.10; 95% CI 0.01-0.80; P=.03] antipsychotic agent dose intensity were associated with decreased risk of QTc prolongation. Three patients in the no QTc prolongation group developed a ventricular arrhythmia, but no episodes of TdP were observed in either group.
Conclusions: The rate of QTc prolongation in patients receiving antipsychotics for ICU delirium was relatively low and may not correlate with arrhythmia risk. While no clinically relevant risk factors were identified to predict risk of QTc prolongation in this population, the low rate of QTc prolongation and ventricular arrhythmias indicate that further research is needed to determine if frequent ECG monitoring is truly indicated in this population.
Keywords: Torsades de pointes, QT prolongation, drug-related side effects and adverse reactions, delirium, critical illness.