Small doses of droperidol do not present relevant torsadogenic actions: a double-blind, ondansetron-controlled study

Abstract

Aim: Drugs used for postoperative nausea and vomiting prophylaxis are believed to provoke torsadogenic changes in cardiac repolarization. The aim of this study was to assess the effect of small doses of droperidol on the parameters of cardiac repolarization, including the QTc interval and transmural dispersion of repolarization.

Methods: A total of 75 patients were randomly allocated to receive 0.625 or 1.25 mg droperidol or 8 mg ondansetron. The QTc interval was calculated using Bazett's formula and the Framingham correction. The transmural dispersion of repolarization was determined as Tpeak -Tend time.

Results: Transient QT prolongation, corrected with both formulae, followed 1.25 mg of droperidol 10 min after administration. No change in the QTc value was observed in the other groups. When corrected with Bazett's formula, QTc was prolonged above 480 ms in two patients receiving 1.25 mg droperidol (at the 10(th) and 20(th) minute of the study) and in one receiving ondansetron. No patients developed a QTc B prolongation over 500 ms. No increase above 480 ms was observed relative to the Framingham correction method. There were no significant differences in the Tpeak -Tend time either between or within the groups.

Conclusion: In men without cardiovascular disorders small doses (1.25 mg) of droperidol prophylaxis induced transient QTc prolongation without changes in transmural dispersion of repolarization. The apparently low risk of the drug applies only in low risk male patients with a low pro-QTc score.

Keywords: corrected QT interval; droperidol; ondansetron; postoperative nausea and vomiting; torsadogenic action; transmural dispersion of repolarization.

Figure 1

QT interval measurement using the tangent method (the end of the T wave is the intercept between the isoelectric line with the tangent drawn through the maximum down slope of the T wave). X represents T_peak − T_end time (modified from http://en.ecgpedia.org/wiki)

Figure 2

Mean and 95% confidence intervals of uncorrected QT intervals during different time points. +5, +10, +15, and +20 refer to the time in minutes from the study's beginning. , group D 0.625; , group D 1.25; , group O

Figure 3

Mean and 95% confidence intervals of the QT intervals corrected using Bazett's formula (QT_cB) across different time points. *P = 0.033 compared with initial values in the same group and P = 0.019 compared with subsequent measurements. , group D 0.625; , group D 1.25; , group O

Figure 4

Mean and 95% confidence intervals of QT interval corrected using Framingham formula (QT_cF) across different time points. *P = 0.0009 compared with initial values in the same group and P = 0.036 compared with subsequent measurements. , group D 0.625; , group D 1.25; , group O

Figure 5

Changes in the T_peak – T_{end time} during the study. , group D 0.625; , group D 1.25; , group O

Figure 6

Mean and 95% confidence limits of the heart rate (HR) during the study. *P < 0.01 compared with the value at the 20^th min in the same group; †P < 0.05 compared with initial value in the same group; ‡P < 0.00005 compared with values at 15^th and 20^th minute of the study; §P < 0.005 compared with values at 15^th and 20^th min of the study. , group D 0.625; , group D 1.25; , group O

Figure 7

Mean and 95% confidence limits of the mean arterial pressure (MAP) during the study. *P < 0.05 compared with initial value in the same group; †P = 0.02, ‡P = 0.0005, §P = 0.002 compared with initial value in the same group. , group D 0.625; , group D 1.25; , group O