Pharmacoepidemiology of QT-interval prolonging drug administration in critically ill patients

Abstract

Purpose: Commonly prescribed medications produce QT-prolongation and are associated with torsades de pointes in non-acutely ill patients. We examined patterns of QT-prolonging drug use in critically ill individuals.

Methods: An administrative critical care database was utilized to identify patients receiving drugs associated with QT-interval prolongation or torsades de pointes for > or = 24 hours.

Results: Data from 212 016 individuals collected over a 63-month period was examined to identify 6125 patients (2.9%) receiving QT-interval prolonging drugs. These individuals had a mean (+/-SE) age of 63.0 (+/-0.2) years, were predominately male (55.4%) and Caucasian (84.4%), and were exposed to QT-interval prolonging agents for a mean (+/-SE) 53.1 (+/-0.4)% of their ICU length of stay. Respiratory and cardiovascular illnesses were the most common reasons for ICU admission (17.2, 12.0%, respectively). The most frequently administered agents were amiodarone (23.5%), haloperidol (19.8%), and levofloxacin (19.7%); no other single agent accounted for more than 10% of QT-interval prolonging drugs prescribed. Coadministration of QT-prolonging drugs occurred in 1139 patients (18.6%). These patients had higher ICU mortality rate and longer ICU lengths of stay, compared to patients not receiving coadministered drugs (p < 0.001 for both). For patients receiving coadministered drugs, overlap occurred for 71.4 (+/-0.8)% of the time that the drugs were given. Amiodarone coadministration with antibiotics, haloperidol coadministration with antibiotics, and haloperidol coadministration with amiodarone, comprised 15.2, 13.7, and 9.4%, of all coadministered agents, respectively.

Conclusions: QT-prolonging drugs were used in a minority of critically ill patients. Prospective evaluation in the ICU environment is necessary to determine whether administration of these agents is associated with adverse cardiac events comparable to those reported in ambulatory patients.

Figure 1. Administration of QT-interval prolonging drugs in critical illness

Frequency of QT-interval prolonging drug administration (as percentage of all QT-interval prolonging drugs administered) with associated mean (±SE) duration (days). Analysis was limited to drugs comprising at least 1% of all QT-interval prolonging drugs prescribed. Numbers in parentheses adjacent to drug names refer to the categorization with respect to risk of drug associated arrhythmia. As noted in Table 1, a designation of ‘1’ denotes generally accepted to have a risk of causing torsades de pointes while ‘2’ denotes reported association with torsades de pointes but for which substantial evidence is lacking(4). As this figure illustrates, with the exception of amiodarone, haloperidol, and erythromycin, most drugs administered to critically ill patients carry a designation of ‘2’.

Figure 2. Frequency of Coadministration of QT-interval prolonging drugs

Frequency of QT-interval prolonging drug coadministration is illustrated (as a percentage of all patients receiving the individual agent) with duration of coadministration (mean (±SE) days). Drug designations are as noted in Table 1 and Figure 1.