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Evaluation of electrocardiographic repolarization parameters after administration of trimethoprim-sulfadiazine, detomidine, or their combination in horses

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  • 1 Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 1870 Frederiksberg C, Denmark.
  • | 2 Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 2630 Taastrup, Denmark.
  • | 3 Laboratory of Experimental Cardiology, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen N, Denmark.
  • | 4 Department of Cardiology, Herlev and Gentofte University Hospital, 2900 Hellerup, Denmark.

Abstract

OBJECTIVE

To determine whether administration of trimethoprim-sulfadiazine (TMS), detomidine (DET), or TMS plus DET would be associated with changes in ECG repolarization parameters in horses.

ANIMALS

9 healthy adult horses.

PROCEDURES

Each horse received 4 treatments in a blinded, randomized, crossover study design as follows: TMS, 16 to 24 mg/kg, IV; DET, 0.015 to 0.02 mg/kg, IV; TMS plus DET; and saline (0.9% NaCl) solution. Surface ECG traces were obtained over 24 hours, and repolarization parameters were measured at predefined time points after each treatment and compared with a 2-way ANOVA for repeated measures.

RESULTS

Heart rate–corrected QT intervals (QTc) were significantly increased after administration of DET (mean ± SD difference in QTc, 36.57 ± 23.07 milliseconds; increase of 7%) and TMS plus DET (44.96 ± 29.16 milliseconds; increase of 9%), compared with baseline (before treatment) values and values after administration of saline solution. Saline solution and TMS alone did not affect QTc.

CONCLUSIONS AND CLINICAL RELEVANCE

Administration of DET or TMS plus DET was associated with a significant and possibly clinically relevant prolongation of QTc, with prolongation of 7% to 9%, a range that is considered as a risk factor for the development of cardiac arrhythmias in people. Results were unexpected because DET is considered to be a safe sedative for horses.

Abstract

OBJECTIVE

To determine whether administration of trimethoprim-sulfadiazine (TMS), detomidine (DET), or TMS plus DET would be associated with changes in ECG repolarization parameters in horses.

ANIMALS

9 healthy adult horses.

PROCEDURES

Each horse received 4 treatments in a blinded, randomized, crossover study design as follows: TMS, 16 to 24 mg/kg, IV; DET, 0.015 to 0.02 mg/kg, IV; TMS plus DET; and saline (0.9% NaCl) solution. Surface ECG traces were obtained over 24 hours, and repolarization parameters were measured at predefined time points after each treatment and compared with a 2-way ANOVA for repeated measures.

RESULTS

Heart rate–corrected QT intervals (QTc) were significantly increased after administration of DET (mean ± SD difference in QTc, 36.57 ± 23.07 milliseconds; increase of 7%) and TMS plus DET (44.96 ± 29.16 milliseconds; increase of 9%), compared with baseline (before treatment) values and values after administration of saline solution. Saline solution and TMS alone did not affect QTc.

CONCLUSIONS AND CLINICAL RELEVANCE

Administration of DET or TMS plus DET was associated with a significant and possibly clinically relevant prolongation of QTc, with prolongation of 7% to 9%, a range that is considered as a risk factor for the development of cardiac arrhythmias in people. Results were unexpected because DET is considered to be a safe sedative for horses.

Supplementary Materials

    • Supplementary Figure S1 (PDF 247 kb)
    • Supplementary Table S1 (PDF 30 kb)
    • Supplementary Table S2 (PDF 22 kb)
    • Supplementary Table S3 (PDF 56 kb)
    • Supplementary Table S4 (PDF 33 kb)
    • Supplementary Table S5 (PDF 29 kb)
    • Supplementary Table S6 (PDF 31 kb)
    • Supplementary Table S7 (PDF 32 kb)
    • Supplementary Table S8 (PDF 32 kb)
    • Supplementary Table S9 (PDF 31 kb)
    • Supplementary Table S10 (PDF 31 kb)
    • Supplementary Table S11 (PDF 31 kb)
    • Supplementary Table S12 (PDF 26 kb)
    • Supplementary Table S13 (PDF 47 kb)
    • Supplementary Table S14 (PDF 38 kb)

Contributor Notes

Dr. Trachsel's present address is Equine Clinic: Surgery and Radiology, Freie University Berlin, 14163 Berlin, Germany.

Dr. Pedersen's present address is Gubra, 2970 Hørsholm, Denmark.

Address correspondence to Dr. Trachsel (dagmarsenta.trachsel@fu-berlin.de).