Accuracy of Uncorrected versus Corrected QT Interval for Prediction of Torsade de Pointes Associated with Intravenous Haloperidol

Authors


James E. Tisdale, Pharm.D., Department of Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, Purdue University, W7555 Myers Building, WHS, 1001 West 10th Street, Indianapolis, IN 46202; e-mail: jtisdale@iupui.edu.

Abstract

Study Objective. To determine if the uncorrected QT interval (QTu) more accurately predicts drug-induced torsade de pointes than QT intervals corrected using the Bazett's (QTB), Fridericia (QTFrid), or Framingham (QTFram) methods.

Design. Retrospective analysis of a previously reported case-control study of risk factors for haloperidol-induced torsade de pointes.

Setting. Large tertiary care teaching hospital.

Patients. Forty-six critically ill patients who received intravenous haloperidol for sedation; seven developed torsade de pointes.

Measurements and Main Results. The QT intervals were measured manually by one investigator from electrocardiograms performed before and during haloperidol therapy. Logistic regression analysis for prediction of torsade de pointes was performed, incorporating QTu, QTB, QTFrid, QTFram, and RR intervals measured during treatment. Receiver operating characteristics (ROC) curves were constructed. Primary outcome measures were proportion of explained variation (maximum-rescaled R2); area under the ROC curves for QTu, QTB, QTFrid, QTFram, and RR interval; and sensitivity and specificity for prediction of haloperidol-induced torsade de pointes. The QTu was associated with the highest R2 compared with QTFram, QTFrid, QTB, and RR interval (0.77, 0.73, 0.68, 0.53, and 0.30, respectively). No significant differences in areas under the ROC curves were found between any of the QT-interval methods. Areas under the ROC curves for QTu and QTFram trended toward being greater than that associated with the RR interval. All QT-interval methods were highly sensitive (100% for each), whereas the RR interval was less sensitive (86%); QTu and QTFram were most specific (82%) compared with the QTFrid (72%), QTB (64%), and RR interval (36%).

Conclusion. Compared with QTB and QTFrid, the QTu and QTFram best predicted haloperidol-induced torsade de pointes in critically ill patients; the QTFram offered no advantage over the QTu.

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