Antipsychotics and the QTc Interval During Delirium in the Intensive Care Unit

Abstract

ImportanceAntipsychotic medications, often prescribed for delirium in intensive care units (ICUs), may contribute to QTc interval prolongation.ObjectiveTo determine whether antipsychotics increase the QTc interval in patients with delirium in the ICU.Design, Setting, and ParticipantsAn a priori analysis of a randomized clinical trial in medical/surgical ICUs within 16 centers across the US was conducted. Participants included adults with delirium in the ICU with baseline QTc interval less than 550 ms. The study was conducted from December 2011 to August 2017. Data analysis was performed from April 25 to August 18, 2021.InterventionsPatients were randomized 1:1:1 to intravenous haloperidol, ziprasidone, or saline placebo administered twice daily until resolution of delirium, ICU discharge, or 14 days.Main Outcomes and MeasuresTwelve-lead electrocardiograms were used to measure baseline QTc before study drug initiation and telemetry was used to measure QTc before each subsequent dose of study drug. Unadjusted day-to-day changes in QTc were calculated and multivariable proportional odds regression was used to estimate the effects of antipsychotics vs placebo on next-day maximum QTc interval, adjusting for prespecified baseline covariates and potential interactions with sex. Safety end points, including the occurrence of torsade de pointes, were evaluated. All analyses were conducted based on the intention to treat principle.ResultsA total of 566 patients were randomized to haloperidol (n = 192), ziprasidone (n = 190), or placebo (n = 184). Median age was 60.1 (IQR, 51.4-68.7) years; 323 were men (57%). Baseline median QTc intervals across the groups were similar: haloperidol, 458.0 (IQR, 432.0-479.0) ms; ziprasidone, 451.0 (IQR, 424.0-472.0) ms; and placebo, 452.0 (IQR, 432.0-472.0) ms. From day 1 to day 2, median QTc changed minimally: haloperidol, −1.0 (IQR, −28.0 to 15.0) ms; ziprasidone, 0 (IQR, −23.0 to 20.0) ms; and placebo, −3.5 (IQR, −24.8 to 17.0) ms. Compared with placebo, neither haloperidol (odds ratio [OR], 0.95; 95% CI, 0.66-1.37; P = .78) nor ziprasidone (OR, 1.09; 95% CI, 0.75-1.57; P = .78) was associated with next-day QTc intervals. Effects were not significantly modified by sex (P = .41 for interaction). There were 2 occurrences of nonfatal torsade de pointes, both in the haloperidol group. Neither was associated with study drug administration.Conclusions and RelevanceThe findings of this trial suggest that daily QTc interval monitoring during antipsychotic use may have limited value in patients in the ICU with normal baseline QTc and few risk factors for QTc prolongation.Trial RegistrationClinicalTrials.gov Identifier: NCT01211522