37: Antipsychotics and QTc Interval in the ICU: Analysis of a Randomized Clinical Trial

Saturday, January 21, 2023

3:45 PM – 4:00 PM PT

Location: George R. Moscone Convention Center, 4

First Author(s)

Joanna Stollings, PharmD, FCCM

MICU Clinical Pharmacy Specialist
Vanderbilt University Medical Center
Nashville, Tennessee

Disclosure information not submitted.

Co-Author(s)

Christina Boncyk, MD

n/a
Nashville, Tennessee

Disclosure information not submitted.
WC

Wencong Chen, PhD

PhD
Vanderbilt University Medical Center, United States

Disclosure information not submitted.
RR

Rameela Raman, PhD

PhD
Vanderbilt University Medical Center, United States

Disclosure information not submitted.
DG

Deepak Gupta, MD, MSCI

MD, MSCI
Vanderbilt University Medical Center, United States

Disclosure information not submitted.
ER

Erika Rivera, MD

MD
Vanderbilt University Medical Center, United States

Disclosure information not submitted.
AM

Amelia Maiga, MD, MPH

MD, MPH
Vanderbilt Hospital, United States

Disclosure information not submitted.
SR

Shayan Rakhit, MD

MD
Vanderbilt University, United States

Disclosure information not submitted.
PP

Pratik Pandharipande, MD, FCCM

Professor of Anesthesiology and Surgery
Vanderbilt University Medical Center
Brentwood, Tennessee

Disclosure information not submitted.
E. Wesley Ely, MD, MPH, MCCM

Professor of Medicine and Critical Care
Vanderbilt University
Nashville, Tennessee

Disclosure(s): Eli Lilly: Clinical Trial Investigator (Ongoing)
Timothy Girard, MD, MSCI

University of Pittsburgh School of Medicine
Pittsburgh, Pennsylvania

Disclosure information not submitted.
MP

Mayur Patel, MD, MPH, FACS, FCCM

MD
Vanderbilt University Medical Center, United States

Disclosure information not submitted.

Disclosure(s):

E. Wesley Ely, MD, MPH, MCCM: Eli Lilly: Clinical Trial Investigator (Ongoing)

INTRODUCTION: Antipsychotic medications, still often prescribed for delirium in intensive care units (ICUs), may contribute to QTc prolongation and torsades de pointes. Using data from the MIND-USA study (Girard, NEJM 2018), we determined if antipsychotics increase QTc interval in delirious ICU patients.

METHODS : This study was planned a priori with FDA oversight. During this 16 site investigation, we randomized 566 ICU patients with delirium to receive IV haloperidol (N=192), ziprasidone (N=190), or placebo (N=184). We monitored pre-randomization 12-lead electrocardiograms (ECGs) and followed the QTc during study drug administration as well after receiving FDA-approval to enroll and continue study drug administration in patients with QTc up to 550 ms rather than the standard cutoff of 500 ms. We calculated changes in QTc pre/post-dose and used multivariable proportional odds regression to estimate the effect of antipsychotics on next day QTc, adjusting for pre-specified baseline covariates: pre-randomization QTc, post-randomization maximum pre-dose QTc, treatment group, age, sex, body-mass index (BMI), and SOFA score.

RESULTS: At baseline, median [IQR] QTc intervals across haloperidol, ziprasidone, and placebo treatment groups were 458 [432-479] ms, 451 [424-472] ms, and 452 [432-472] ms, respectively. The median change from Day 1 to Day 2 QTc were-1 [-28-15] ms, 0 [-23-20] ms, and -3.5 [-24.8-17] ms, respectively by treatment groups. The median days of exposure to an antipsychotic study drug or placebo was 4 [3,7]. Compared with placebo, neither haloperidol (odds ratio [OR]= 0.95, 95% CI 0.66 - 1.37) nor ziprasidone (OR 1.09, 95% CI 0.75 - 1.57) significantly affected next day QTc intervals (p=0.78). This effect was not significantly modified by sex. Only 2 occurrences of torsades de pointes occurred which were both in the haloperidol group. Neither patient had received haloperidol in the 4 days prior to the event so these were not judged to be study drug-related serious adverse events.

CONCLUSIONS: These prospectively-collected, multicenter data advance our understanding of the use of antipsychotics during critical illness. Antipsychotics did not significantly increase QTc intervals beyond that of placebo and there were no occurrences of study drug-related lethal cardiac arrhythmias.