Assessment of the risk of QT-interval prolongation associated with potential drug-drug interactions in patients admitted to Intensive Care Units.

OBJECTIVES

To evaluate the relationship between drug interactions and QT-interval prolongation in patients admitted to a general intensive care unit (ICU).

METHODS

This study was approved by the Institutional Review Board and written informed consent was obtained from all patients. From May 2015 to July 2016, all patients over 18 years-old admitted to the ICU for more than 24 h and in whom the QT-interval on the ECG could be read were prospectively included in this observational, cross-sectional study. All medications administered in the 24 h prior to admission were recorded and the QT-interval was measured upon ICU admission and corrected with Bazzet's formula (QTc). Drug-drug interactions involving drugs potentially associated with QTc prolongation (DDIQT) were searched and QTc increase associated with pharmacokinetic (PK-DDIQT) and pharmacodynamic (PD-DDIQT) interactions was assessed with multiple regression adjusted by patient varibles.

RESULTS

The study population consisted of 283 patients, 54.4% males, mean age 57.6 ± 16.7 years-old. Forty five (15.9%) patients presented 65 DDIQT with predominance of pharmacodynamic (66.1%). The risk of DDIQT prescription increased with lower systolic blood pressure, in hypokalemia, in non-diabetics and with the number of medications. PK-DDIQT alone did not affect the QTc interval (7.75 ms, 95%CI: -22.4 to 37.9 ms, p = 0.61), but PD-DDIQT increased QTc by 28.4 ms (95%CI: 9.67 to 47.4 ms, p = 0.003). Most PD-DDIQT involved metoclopramide with ondansetron or amiodarone, and ondansetron with ciprofloxacin.

CONCLUSIONS

In patients exposed to drugs associated with prolonged QTc in the 24 h prior to ICU admission, pharmacodynamic DDIQT are associated with increased risk of QTc prolongation.