In horses as well as in other mammalian species, the α2-adrenoceptor agonist drugs cause dose-dependent sedation, analgesia, and myorelaxation as a result of their interaction with α2-adrenoceptors, which are widely distributed throughout body systems.1,2 The cardiovascular, sedative, and analgesic effects of the most commonly used α2-adrenoceptor agonists (xylazine hydrochloride, detomidine hydrochloride, and romifidine hydrochloride) in horses have been described.1,3–6 One of the most undesirable effects of α2-adrenoceptor agonists is ataxia and alteration in general locomotory patterns.7,8 In horses, the degree of sedation-induced ataxia has been estimated on the basis of qualitative and subjective criteria.2,9–11 Recently, accelerometry has been used to determine the effects of sedation on the movement patterns of horses.12 Accelerometers are assessment devices that measure acceleration of the surface to which they are attached13; they measure the instantaneous change of velocity of a body during a given interval, which corresponds to the acceleration applied to that body.14 The efficiency of accelerometry in detecting velocity changes after sedation with xylazine hydrochloride has been evaluated; researchers concluded that this kinetic assessment technique offers a practical, accurate, easy to use, portable, and low-cost method of objectively monitoring gait abnormalities in horses after sedation with xylazine.12
Because differences in the duration of the altered locomotor patterns following administration of various α2-adrenoceptor agonist drugs have been described4,7,11,15 and because accelerometry can detect and quantify these effects,12 our hypothesis was that accelerometry should be able to detect differences in the effects of α2-adrenoceptor agonist drugs on locomotion in horses. The aim of the study reported here was to compare the duration of the effects on movement patterns of adult horses sedated with equipotent doses of xylazine hydrochloride, detomidine hydrochloride, and romifidine hydrochloride and to determine whether accelerometry is able to quantify differences among drug treatments.
Materials and Methods
Animals—Six mature horses (3 mares, 2 geldings, and 1 stallion), with a median body mass of 469 kg (range, 434 to 535 kg) and median age of 15 years (range, 2 to 20 years), were used. A full clinical examination was performed on all horses to ensure they were healthy and not lame. All assessments were undertaken in a quiet environment. The horses were familiar with the movement protocol and the track where all the measurement sessions were performed. The study was approved by the Complutense University Animal Care and Use Committee.
Treatments—Each horse was used as its own control, and 4 treatments were administered to each horse: saline (0.9% NaCl) solution (10 mL [control treatment]); xylazine hydrochloridea (0.5 mg/kg) diluted in saline solution to a volume of 10 mL; detomidine hydrochlorideb (0.01 mg/kg) diluted in saline solution to a volume of 10 mL; and romifidine hydrochloridec (0.04 mg/kg) diluted in saline solution to a volume of 10 mL. Each treatment was administered via an IV 16-gauge catheterd inserted into the left jugular vein; the catheter was immediately removed after the drug administration. Treatments were administered in a blinded fashion at a minimum interval of 7 days and with random order of injections.
Data acquisition—The portable gait analyzere used consisted of 3 orthogonal accelerometers that measure accelerations at the sacrum and along the dorsoventral, longitudinal, and lateral axes of the horse; the device included a 3-D accelerometric acceleration sensor, a data logger, and a scientific software programf for processing the acceleration signals. This recorder collected data continuously while each horse was walking at a sampling rate of 100 Hz; positive values were obtained when accelerations were in the dorsal, cranial, and left directions. The same researcher (RHP) positioned the accelerometer transducer on all occasions, and the data logger was inserted into a leather pocket fixed on the left side of an elastic girth fastened around the thorax. Data were transferred to a computer after the tests were finished.
Gait analysis—Twelve walking trials were performed, and each trial involved an accelerometric gait assessment. Each horse, with the accelerometer transducer in position, was walked at its own comfortable speed along a 50-m concrete track covered by a 2-cm thick rubber mat. Data were collected only when horses walked away from the stables because they always walked faster toward the stables.
On the day of the test, the 3-D accelerometric sensor was attached to the skin over the midline of the sacrum region with double adhesive tape. Fifteen minutes before administration of the test injection, the horse was walked 3 times over a distance of 50 m across the runway. Baseline accelerometric recordings were registered. Each horse was then injected with 1 of the 4 solutions (0 minutes), and accelerometric recordings were repeated 5 and 15 minutes after the injection and then every 15 minutes thereafter for 2 hours. The walking test was performed once at the 5-minute evaluation and twice at the other evaluation time points (ie, at 15, 30, 45, 60, 75, 90, 105, and 120 minutes after injection).
Accelerometric variables—The validation and reproducibility of the accelerometric measurements with the triaxial accelerometric devicee have been described.12,16–18 The kinematic, coordination, and energetic variables studied have also been described.16,19–23
The stride kinematic variables included speed (m/s), stride frequency (cycles/s or Hz), and stride length (m). The coordination variable regularity (a coefficient of correlation corresponding to a peak of the autocorrelation function of the dorsoventral acceleration measured at a time equal to the half stride and stride duration) was determined to assess the acceleration pattern similarity of successive strides over the course of time. The energetic variables included dorsoventral power or activity (W/kg [power absorbed/unit mass of tissue]); propulsive power, craniocaudal activity, or longitudinal activity (propulsive power; W/kg); mediolateral power, lateral activity, or side-to-side activity (mediolateral power; W/kg); and total power (W/kg), defined as the sum of the 3 powers calculated in each axis. The values obtained reflect body kinesia.24 The force of acceleration (N/kg) was calculated by dividing the total power of accelerations by speed. Use of this variable avoids potential bias in the calculation of the total power due to different speeds. Finally, the mediolateral, dorsoventral, and propulsive power as a percentage of total power were calculated by dividing the different power components by the total power (ie, mediolateral power/total power, dorsoventral power/total power, and propulsive power/total power, respectively).
Each accelerometric variable was calculated at each walking test (21 times at different time points during stabilized walking) starting in the fifth second after the beginning of the test and then every second for 25 seconds. By use of this method, the initial and final non-stable strides were discarded and the walking distance was still sufficient for analysis. The final value for each variable at each time point was calculated as the mean of the 21 measurements, 3 times (63 measurements) for the baseline (−15 minutes), once (21 measurements) 5 minutes after drug administration, and twice (42 measurements) at 15, 30, 45, 60, 75, 90, 105, and 120 minutes after drug administration.
Statistical analysis—Statistical analysesg were performed, and data were grouped and summarized as percentage ± SD values relative to baseline recordings. Power components were also expressed by percentage of total power. Data were tested for normality of distribution via the Kolmogorov-Smirnov test. Data were contrasted by a 2-way ANOVA. If interaction was detected, a single-factor repeated-measures ANOVA was then conducted to find differences over time, and significance was set at a value of P < 0.05, with Bonferroni correction when indicated.
Results
All horses completed the study, and no data were excluded from the statistical analysis. Even though some variability in the susceptibility of the horses to the drugs' sedative effects was observed, no significant differences among control values were observed at any time. Administration of α2-adrenoceptor agonist drugs decreased many of the variables investigated. Values of the stride kinematic, coordination, and energetic variables, along with significant differences, at baseline (−15 minutes) and at 5, 15, and every 15 minutes thereafter over a period of 2 hours following administration of the test injection were summarized (Tables 1 and 2).
Values of stride kinematic and coordination variables before (baseline [-15 minutes]) and at 5, 15, and then every 15 minutes (total period of 2 hours) after an IV injection (at 0 minutes) of saline (0.9% NaCl) solution (10 mL [SS]), xylazine hydrochloride (0.5 mg/kg) diluted in saline solution to a volume of 10 mL, detomidine hydrochloride (0.01 mg/kg) diluted in saline solution to a volume of 10 mL, or romifidine hydrochloride (0.04 mg/kg) diluted in saline solution to a volume of 10 mL in 6 healthy horses.
| Time after administration of treatment (min) | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Variable | Treatment | Baseline | 5 | 15 | 30 | 45 | 60 | 75 | 90 | 105 | 120 |
| Speed (m/s) | SS | 100 ± 0.00 | 99.61 ± 2.47†‡§ | 100.67 ± 3.78†‡§ | 100.77 ± 2.13†‡§ | 97.87 ± 4.87‡§ | 98.65 ± 3.19§ | 98.48 ± 3.42 | 100.09 ± 4.15 | 100.58 ± 2.97§ | 97.15 ± 3.36 |
| Xylazine | 100 ± 0.00 | 68.22 ± 8.25* | 76.39 ± 8.51* | 82.60 ± 6.07* | 88.98 ± 6.64‡ | 93.48 ± 10.55 | 96.07 ± 8.06 | 97.27 ± 6.41 | 99.04 ± 5.92 | 99.02 ± 5.39 | |
| Detomidine | 100 ± 0.00 | 65.57 ± 7.17* | 72.19 ± 7.84* | 76.19 ± 8.36* | 80.60 ± 8.20*† | 85.02 ± 7.90 | 89.29 ± 8.57 | 90.99 ± 8.32 | 94.01 ± 8.29 | 94.60 ± 5.51 | |
| Romifidine | 100 ± 0.00 | 76.65 ± 5.91* | 78.81 ± 6.24* | 80.82 ± 3.91* | 83.20 ± 3.98* | 86.12 ± 3.85* | 89.50 ± 4.20 | 90.31 ± 5.42 | 93.42 ± 4.16* | 93.66 ± 3.74 | |
| Stride frequency (cycles/s) | SS | 100 ± 0.00 | 98.74 ± 2.65†‡§ | 99.06 ± 3.53†‡§ | 99.28 ± 3.08†‡§ | 97.94 ± 3.73§ | 98.87 ± 2.81§ | 98.85 ± 1.78§ | 98.68 ± 4.24§ | 98.68 ± 3.74 | 99.05 ± 3.49 |
| Xylazine | 100 ± 0.00 | 71.86 ± 4.08* | 77.68 ± 5.57* | 84.70 ± 3.59* | 90.21 ± 4.38§ | 96.97 ± 7.34 | 97.06 ± 5.60 | 96.41 ± 4.56 | 98.15 ± 5.04 | 98.66 ± 3.91 | |
| Detomidine | 100 ± 0.00 | 70.89 ± 7.52* | 77.09 ± 3.07* | 79.04 ± 7.90* | 83.35 ± 7.76 | 87.73 ± 7.51 | 89.96 ± 7.71 | 91.77 ± 8.23 | 94.08 ± 7.07 | 96.07 ± 6.22 | |
| Romifidine | 100 ± 0.00 | 78.21 ± 6.828 | 79.58 ± 6.12* | 81.44 ± 6.20* | 83.55 ± 3.83*† | 88.77 ± 3.75* | 90.18 ± 4.10* | 90.93 ± 4.05* | 92.06 ± 4.90 | 93.55 ± 3.53 | |
| Stride length (m) | SS | 100 ± 0.00 | 101.06 ± 1.79 | 101.46 ± 2.75 | 101.48 ± 3.90 | 101.15 ± 3.55 | 99.82 ± 3.21 | 99.59 ± 3.20 | 101.20 ± 4.27 | 101.94 ± 3.28 | 97.80 ± 2.86 |
| Xylazine | 100 ± 0.00 | 94.69 ± 7.54 | 97.61 ± 6.45 | 99.35 ± 4.74 | 98.43 ± 3.93 | 96.60 ± 3.48 | 98.72 ± 2.41 | 100.70 ± 2.27 | 100.97 ± 1.05 | 100.28 ± 1.57 | |
| Detomidine | 100 ± 0.00 | 92.88 ± 4.50 | 94.74 ± 4.73 | 96.30 ± 3.07 | 96.92 ± 1.44 | 97.26 ± 1.95 | 99.22 ± 2.12 | 99.25 ± 2.03 | 99.65 ± 2.98 | 100.03 ± 3.06 | |
| Romifidine | 100 ± 0.00 | 98.15 ± 5.12 | 98.71 ± 4.88 | 99.57 ± 4.86 | 99.30 ± 4.11 | 97.19 ± 4.08 | 99.10 ± 3.22 | 98.96 ± 1.92 | 101.37 ± 1.64 | 100.52 ± 1.51 | |
| Regularity (%) | SS | 100 ± 0.00 | 98.61 ± 5.45†‡§ | 103.85 ± 10.33†‡§ | 108.12 ± 7.04†‡§ | 106.71 ± 15.47§ | 103.70 ± 11.62 | 104.44 ± 5.62§ | 99.88 ± 7.67† | 99.49 ± 5.67† | 102.33 ± 8.58‡ |
| Xylazine | 100 ± 0.00 | 50.42 ± 13.97* | 60.85 ± 15.28* | 73.52 ± 12.58* | 81.88 ± 6.89 | 90.68 ± 7.47 | 87.66 ± 7.79 | 84.99 ± 4.37* | 90.30 ± 3.80* | 91.73 ± 4.51* | |
| Detomidine | 100 ± 0.00 | 41.73 ± 10.90* | 59.49 ± 15.60* | 70.29 ± 13.62* | 78.36 ± 12.93 | 85.41 ± 9.94 | 86.47 ± 13.19 | 86.69 ± 14.67 | 92.95 ± 12.52 | 90.72 ± 6.62* | |
| Romifidine | 100 ± 0.00 | 59.61 ± 19.93* | 68.57 ± 11.20* | 70.92 ± 11.49* | 80.15 ± 6.85* | 84.57 ± 7.52 | 86.99 ± 6.20* | 86.68 ± 4.98 | 90.90 ± 2.48 | 88.35 ± 6.81 | |
All variables are expressed as a mean percentage ± SD, relative to baseline values. For each test, the horse was fitted with a portable gait analyzer consisting of 3 orthogonal accelerometers that measured accelerations at the sacrum and along the dorsoventral, longitudinal, and lateral axes of the horse. Accelerometric variables were calculated at each of 12 walking tests (mean value of 21 measurements obtained 3 times [63 measurements] for the baseline, once [21 measurements] at 5 minutes after drug administration, and twice [42 measurements] at 15, 30, 45, 60, 75, 90, 105, and 120 minutes after drug administration).
For a given variable, value is significantly (P < 0.05) different from the saline solution value at that time point.
For a given variable, value is significantly (P < 0.05) different from the xylazine value at that time point.
For a given variable, value is significantly (P < 0.05) different from the detomidine value at that time point.
For a given variable, value is significantly (P < 0.05) different from the romifidine value at that time point.
Energetic variable values before (baseline [-15 minutes]) and at 5, 15, and then every 15 minutes (total period of 2 hours) after an IV injection (at 0 minutes) of saline solution, xylazine, detomidine, or romifidine in the 6 healthy horses in Table 1.
| Time after administration of treatment (min) | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Variable | Treatment | Baseline | 5 | 15 | 30 | 45 | 60 | 75 | 90 | 105 | 120 |
| Dorsoventral power (W/kg) | SS | 100 ± 0.00 | 94.44 ± 14.16†‡§ | 105.38 ± 23.70†‡§ | 102.01 ± 14.41†‡§ | 95.67 ± 17.94‡§ | 101.25 ± 20.95§ | 99.24 ± 15.31 | 104.67 ± 26.25 | 110.29 ± 23.39 | 108.51 ± 27.11 |
| Xylazine | 100 ± 0.00 | 21.09 ± 10.95* | 28.78 ± 13.75* | 36.04 ± 12.38* | 52.33 ± 15.95 | 76.95 ± 30.81 | 85.95 ± 28.03 | 81.12 ± 17.91 | 86.16 ± 13.44 | 88.72 ± 14.76 | |
| Detomidine | 100 ± 0.00 | 22.04 ± 8.11* | 26.35 ± 10.39* | 33.14 ± 10.19* | 39.61 ± 11.08* | 53.98 ± 16.15 | 65.49 ± 20.33 | 68.62 ± 20.39 | 79.73 ± 24.06 | 88.13 ± 24.37 | |
| Romifidine | 100 ± 0.00 | 34.39 ± 10.07* | 36.64 ± 9.97* | 39.42 ± 10.98* | 42.51 ± 7.55* | 58.45 ± 9.91* | 63.42 ± 14.96 | 69.68 ± 13.30 | 74.65 ± 16.99 | 78.39 ± 17.87 | |
| Propulsive power (W/kg) | SS | 100 ± 0.00 | 92.43 ± 10.04†‡§ | 100.62 ± 13.27†‡§ | 98.95 ± 10.61†‡§ | 92.57 ± 12.97‡§ | 94.74 ± 10.13§ | 94.63 ± 7.56§ | 94.23 ± 10.52 | 97.19 ± 8.25 | 97.00 ± 12.78 |
| Xylazine | 100 ± 0.00 | 40.47 ± 13.05* | 49.36 ± 17.61* | 56.62 ± 15.35* | 65.66 ± 12.71 | 84.82 ± 23.35 | 88.95 ± 19.83 | 85.5 ± 10.66 | 87.87 ± 8.92 | 92.89 ± 13.35 | |
| Detomidine | 100 ± 0.00 | 40.38 ± 14.54* | 46.65 ± 15.98* | 50.35 ± 12.69* | 55.72 ± 15.15* | 64.38 ± 15.03 | 69.23 ± 18.16 | 72.16 ± 15.99 | 82.43 ± 17.77 | 85.64 ± 11.69 | |
| Romifidine | 100 ± 0.00 | 57.26 ± 14.09* | 56.83 ± 13.55* | 57.35 ± 8.56* | 59.69 ± 7.79* | 68.97 ± 9.88* | 70.88 ± 10.61* | 74.34 ± 12.58 | 74.59 ± 13.24 | 77.78 ± 13.42 | |
| Mediolateral power (W/kg) | SS | 100 ± 0.00 | 99.86 ± 6.08 | 105.75 ± 11.39 | 108.48 ± 14.61 | 116.65 ± 26.24 | 117.94 ± 24.21 | 117.84 ± 37.96 | 114.86 ± 21.92 | 121.5 ± 33.98 | 122.26 ± 38.94 |
| Xylazine | 100 ± 0.00 | 62.94 ± 20.50 | 64.75 ± 20.29 | 71.55 ± 17.86 | 79.31 ± 17.24 | 95.42 ± 31.47 | 93.53 ± 29.60 | 91.19 ± 22.38 | 98.27 ± 20.57 | 102.57 ± 15.50 | |
| Detomidine | 100 ± 0.00 | 57.53 ± 34.26 | 73.05 ± 25.92 | 73.21 ± 25.62 | 71.28 ± 24.30 | 77.26 ± 24.04 | 83.14 ± 23.89 | 80.49 ± 18.73 | 83.38 ± 14.11 | 96.10 ± 12.56 | |
| Romifidine | 100 ± 0.00 | 84.71 ± 21.93 | 83.26 ± 23.77 | 86.87 ± 20.05 | 85.00 ± 20.72 | 88.46 ± 19.48 | 88.88 ± 18.50 | 87.46 ± 18.65 | 95.79 ± 5.04 | 98.03 ± 7.75 | |
| Total power (W/kg) | SS | 100 ± 0.00 | 96.11 ± 9.61†‡§ | 102.56 ± 14.19†‡§ | 102.21 ± 9.72†‡§ | 98.78 ± 13.33‡§ | 104.65 ± 12.03‡§ | 100.25 ± 8.40§ | 103.15 ± 11.91§ | 106.94 ± 10.91 | 106.76 ± 17.28 |
| Xylazine | 100 ± 0.00 | 38.80 ± 13.69* | 48.26 ± 16.87* | 54.61 ± 15.51* | 66.97 ± 14.80‡ | 87.43 ± 26.14 | 90.27 ± 21.19 | 85.93 ± 13.70 | 91.20 ± 9.66 | 92.68 ± 12.00 | |
| Detomidine | 100 ± 0.00 | 37.93 ± 10.65* | 44.36 ± 12.73* | 47.09 ± 8.97* | 52.39 ± 10.69*t | 62.90 ± 14.10* | 71.71 ± 17.75 | 73.86 ± 16.18 | 82.86 ± 17.55 | 88.21 ± 12.81 | |
| Romifidine | 100 ± 0.00 | 54.75 ± 10.91* | 55.81 ± 12.42* | 57.06 ± 12.06* | 58.13 ± 5.65* | 70.3 ± 6.62* | 73.53 ± 8.52* | 78.47 ± 10.63* | 81.14 ± 10.77 | 84.60 ± 12.63 | |
| Force of acceleration (N/kg) | SS | 100 ± 0.00 | 96.47 ± 8.07†‡§ | 101.58 ± 10.90†‡§ | 101.63 ± 9.36†‡§ | 100.75 ± 11.23†‡§ | 105.97 ± 10.35‡§ | 101.77 ± 7.62‡ | 102.95 ± 10.25‡ | 106.21 ± 9.72‡§ | 109.64 ± 15.73 |
| Xylazine | 100 ± 0.00 | 56.05 ± 14.59* | 67.79 ± 13.16* | 65.87 ± 16.48* | 74.96 ± 13.79* | 92.39 ± 19.55 | 93.18 ± 15.82 | 89.16 ± 10.84 | 92.00 ± 7.52 | 93.45 ± 9.85 | |
| Detomidine | 100 ± 0.00 | 57.28 ± 11.99* | 60.67 ± 11.74* | 61.67 ± 7.28* | 64.62 ± 8.72* | 73.34 ± 11.50* | 79.29 ± 13.63* | 80.52 ± 11.95* | 87.46 ± 13.19* | 92.95 ± 9.18 | |
| Romifidine | 100 ± 0.00 | 71.07 ± 9.13* | 70.38 ± 11.21* | 70.56 ± 13.09* | 69.91 ± 6.22* | 81.66 ± 6.74* | 82.2 ± 8.67 | 87.03 ± 10.63 | 86.88 ± 9.92* | 90.24 ± 12.11 | |
| Dorsoventral component of power (%) | SS | 33.79 ± 7.03 | 33.03 ± 7.25†‡§ | 33.66 ± 7.46†‡§ | 33.04 ± 6.52†‡§ | 31.01 ± 6.75‡§ | 32.08 ± 8.02 | 32.01 ± 8.43 | 33.50 ± 9.44 | 34.00 ± 9.53 | 32.95 ± 8.75 |
| Xylazine | 33.89 ± 5.89 | 14.85 ± 3.33* | 19.79 ± 3.71* | 21.98 ± 3.89* | 26.52 ± 4.31 | 30.27 ± 6.26 | 32.32 ± 4.66 | 32.40 ± 4.63 | 32.13 ± 4.85 | 31.79 ± 4.56 | |
| Detomidine | 28.41 ± 5.82 | 10.53 ± 3.54* | 12.30 ± 3.02* | 15.93 ± 5.09* | 19.42 ± 5.19* | 22.88 ± 5.20 | 24.95 ± 5.41 | 25.84 ± 4.39 | 27.02 ± 5.09 | 27.18 ± 6.22 | |
| Romifidine | 29.10 ± 4.48 | 15.10 ± 5.30* | 16.64 ± 4.84* | 16.50 ± 5.09* | 18.44 ± 5.37* | 23.23 ± 5.65 | 24.30 ± 6.44 | 26.27 ± 6.04 | 25.05 ± 5.93 | 26.10 ± 5.50 | |
| Propulsive component of power (%) | SS | 26.08 ± 3.48 | 24.88 ± 2.66 | 24.87 ± 2.91 | 24.74 ± 3.24 | 22.96 ± 3.36 | 23.18 ± 3.09 | 23.11 ± 3.36 | 23.33 ± 3.09 | 22.73 ± 2.53 | 22.53 ± 2.86 |
| Xylazine | 25.53 ± 2.01 | 23.55 ± 3.43 | 25.75 ± 3.04 | 25.97 ± 1.23 | 25.34 ± 1.91 | 25.70 ± 1.81 | 25.90 ± 0.93 | 25.73 ± 1.73 | 24.95 ± 2.64 | 24.98 ± 1.75 | |
| Detomidine | 28.22 ± 5.11 | 23.13 ± 5.66 | 24.81 ± 6.18 | 25.55 ± 5.38 | 27.25 ± 4.73 | 27.41 ± 3.36 | 26.43 ± 3.47 | 27.47 ± 4.14 | 28.23 ± 4.29 | 26.64 ± 4.43 | |
| Romifidine | 29.49 ± 2.09 | 27.04 ± 4.98 | 27.18 ± 4.92 | 26.20 ± 4.79 | 27.13 ± 4.54 | 27.76 ± 4.25 | 27.64 ± 3.90 | 28.38 ± 4.75 | 25.64 ± 4.16 | 26.57 ± 3.93 | |
| Mediolateral component of power (%) | SS | 40.12 ± 8.84 | 42.07 ± 11.13†‡§ | 41.45 ± 11.66‡§ | 42.22 ± 10.25‡§ | 46.03 ± 13.24 | 44.73 ± 11.50 | 44.87 ± 13.15 | 43.07 ± 11.77 | 43.26 ± 13.57 | 44.50 ± 12.74 |
| Xylazine | 40.58 ± 8.10 | 61.60 ± 12.09* | 54.46 ± 7.37 | 52.05 ± 5.83 | 48.14 ± 10.69 | 44.03 ± 6.76 | 41.78 ± 7.94 | 41.87 ± 6.67 | 42.92 ± 8.55 | 43.23 ± 7.08 | |
| Detomidine | 43.35 ± 8.72 | 66.34 ± 3.58* | 62.87 ± 7.53* | 58.51 ± 4.68* | 53.32 ± 7.12 | 49.71 ± 5.98 | 48.62 ± 8.34 | 46.67 ± 8.42 | 44.74 ± 12.20 | 46.18 ± 8.06 | |
| Romifidine | 41.39 ± 9.87 | 57.85 ± 9.28* | 56.17 ± 8.23* | 57.29 ± 11.00* | 54.42 ± 8.85 | 49.01 ± 10.27 | 48.06 ± 11.65 | 45.34 ± 10.15 | 49.31 ± 10.90 | 47.31 ± 9.70 | |
Values of dorsoventral, propulsive, mediolateral, and total power and force of acceleration are expressed as a mean percentage ± SD, relative to baseline values (in units indicated). Components of power are expressed as the power value divided by total power × 100 (%).
See Table 1 for remainder of key.
Stride kinematic variables—Significant differences in speed and stride frequency were detected between saline solution treatment and each α2-adrenoceptor agonist drug treatment. Nevertheless, there was no significant difference in stride length among the 4 treatments. Speed was significantly reduced following detomidine (P = 0.029) and romifidine (P = 0.002) treatments, compared with findings following saline solution treatment. With regard to calculated percentages, speed was decreased (relative to baseline values) at 5 minutes after treatment with detomidine, xylazine, or romifidine by 34.43%, 31.78%, and 23.35%, respectively. Compared with the effect of saline solution, significant differences in speed were evident for 30 and 45 minutes following administration of xylazine and detomidine, respectively; significant differences in speed were consistently evident for 60 minutes and again at 105 minutes following administration of romifidine. Stride frequency was also significantly reduced following treatment with xylazine (P = 0.015), detomidine (P = 0.029), or romifidine (P = 0.002), compared with the effect of saline solution; the duration of these differences was 30 minutes for the xylazine and detomidine treatments and 90 minutes for the romifidine treatment. At 5 minutes after administration of detomidine, xylazine, or romifidine, stride frequency decreased by 29.11%, 28.14%, and 21.79% relative to baseline values, respectively.
Coordination variable—Regularity was significantly reduced after treatment with xylazine (P = 0.002), detomidine (P = 0.012), or romifidine (P = 0.005), compared with the effect of saline solution treatment. Following xylazine administration, such significant differences were evident for 30 minutes and again at 90 through 120 minutes. Following detomidine administration, such significant differences were evident for 30 minutes and again at 120 minutes. Following romifidine administration, such significant differences were evident for 45 minutes and again at 75 minutes. At 5 minutes after administration of detomidine, xylazine, or romifidine, regularity decreased by 58.27%, 49.58%, and 40.39% relative to baseline values, respectively.
Energetic variables—Significant differences in dorsoventral power, propulsive power, mediolateral power, and total power were detected between saline solution treatment and each α2-adrenoceptor agonist drug treatment (Table 2). Dorsoventral power was significantly reduced following administration of detomidine (P = 0.014) or romifidine (P = 0.009), compared with the effect of saline solution treatment. At 5 minutes after treatment with xylazine, detomidine, or romifidine, dorsoventral power decreased by 78.91%, 77.96%, and 65.61% relative to baseline values, respectively. Compared with the effects of saline solution treatment, propulsive power was significantly reduced following administration of detomidine (P = 0.044) or romifidine (P = 0.004) treatments, whereas mediolateral power was significantly (P = 0.029) reduced following administration of detomidine only. Total power was significantly reduced following administration of detomidine (P = 0.008) or romifidine (P = 0.002), compared with the effect of saline solution treatment. The significant differences (compared with the effect of saline solution) in total power were evident for 30, 60, and 90 minutes following administration of xylazine, detomidine, and romifidine, respectively. At 5 minutes after treatment with detomidine, xylazine, or romifidine, total power decreased by 62.07%, 61.2%, and 42.25% relative to baseline values, respectively.
Force of acceleration was also significantly decreased following detomidine (P = 0.007) and romifidine (P = 0.009) treatments, compared with the effect of saline solution treatment. Following xylazine administration, such significant differences were evident for 45 minutes. Following detomidine administration, such significant differences were evident for 105 minutes. Following romifidine administration, such significant differences were evident for 60 minutes and again at 105 minutes. At 5 minutes after treatment with xylazine, detomidine, or romifidine, force of acceleration decreased by 42.72%, 43.95%, and 28.93% relative to baseline values, respectively.
A redistribution of the various components of power was observed after administration of the α2-adrenoceptor agonist treatments to the horses. A significant decrease in the dorsoventral aspect was observed after detomidine (P = 0.012) and romifidine (P = 0.921) treatments, compared with findings for the saline solution treatment, mainly at the expense of an increase in the mediolateral component; no significant changes among treatments were observed for the propulsive component. However, significant differences were observed in the duration of the effects of all 3 drugs (Table 2).
Discussion
In horses, the cardiovascular, sedative, and analgesic effects of the most commonly used α2-adrenoceptor agonists have been widely described, but the different doses and methods used to evaluate those effects on sedation are likely responsible for the different reported effects and durations of effect.2–5,7 In the present study, in which horses were evaluated with the acceleration sensor attached over the sacral region during walking, administration of the α2-adrenoceptor agonist drugs resulted in important alterations in locomotor patterns, with significant differences in duration of effect among the drugs, which were demonstrated via accelerometry. In fact, significant drug-related changes were evident in almost all accelerometric variables, with some variables being more greatly affected than others. The 3 α2-adrenoceptor agonist drugs had the same effects but to variable degrees, along with different durations of effect depending on the administered drug.
Speed is known to be the critical variable influencing the kinematics and kinetics of a gait.25 In the present study, an interesting pattern was the significant decrease in speed observed in all horses following treatment with any 1 of the 3 α2-adrenoceptor agonist drugs, compared with the effect of saline solution treatment. The significant decrease in speed following xylazine administration lasted only 30 minutes, whereas the injection of romifidine resulted in a significant decrease for a 60-minute period, and this difference was again evident at 105 minutes after drug administration. The stride length is deduced from the relationship between the velocity and the stride frequency, with velocity being the product of stride length and stride frequency.18 In another study25 involving horses, which used an instrumented treadmill, the stride frequency and stride length changed in a linear fashion with velocity. In addition, in an overground situation, stride length was the primary contributor to changes in speed of walking.26 In the present study, stride length did not change from control values after administration of any of the drugs; the slower stride frequency associated with drug administration was likely the major contributor to the loss in speed probably because of the inhibition of the locomotor activity produced by α2-adrenoceptor agonist drugs.12,27,28 The duration of slower stride frequency (compared with the effect of saline solution treatment) was significantly longer (90 minutes) after administration of romifidine than it was after administration of either xylazine or detomidine (30 minutes each).
Regularity is an accelerometry-specific variable. Each of the 3 α2-adrenoceptor agonist drugs used in the present study was associated with a significant decrease in the regularity values (ie, an increased stride-to-stride variability).h In the present study, regularity was the most sensitive and discriminate variable in the locomotor pattern analysis of sedated horses. Considering the results obtained, it seems that some residual effect associated with α2-adrenoceptor agonist drug administration remained in the horses (even after a ≥ 7-days interval between successive treatments) and that the effects on regularity were shorter for romifidine than for xylazine and detomidine. In another report,7 the maximal effect of xylazine in horses was detected within 5 minutes and lasted for 15 to 60 minutes after IV administration, depending on the dose used; the degree of ataxia induced by xylazine was more severe but of shorter duration than that induced by detomidine.
Regularity has been measured in humans and dogs and is a pertinent variable in various muscular and neurologic diseases23,24; also, variability is increased in humans who are prone to falling.29 On the basis of our clinical experience, falling during locomotion is uncommon among horses sedated with the drug doses used in the present study. However, because some of the horses appeared more susceptible to the drugs' sedative effects than were others, the most sedated horses were likely to stumble during locomotion. The results of the present study confirmed that the accelerometric autocorrelation regularity could potentially be a sensitive variable with which to detect and quantify incoordinated movements during walking.12
Although the movement pattern of sedated horses differs from that of ataxic horses,15 accelerometry and, more specifically, regularity determination could potentially be used to provide diagnostic and prognostic information when assessing ataxia.12 In the present study, we could not compare or correlate accelerometric and subjective ataxia assessment data. Such data would have contributed to identification of the most reliable accelerometric variable with which to quantify altered gait and to confirmation of the usefulness of regularity as an indicator of incoordination. In the study horses, the decrease in regularity was greatest after detomidine administration, with the least effect occurring after romifidine injection. Although treatment with romifidine resulted in a smaller decrease in regularity values, compared with those achieved following treatment with xylazine or detomidine, the effect lasted significantly longer. These findings support previous descriptions of the degree and duration of sedation induced via administration of these drugs in horses; significant drug treatment effects relative to placebo effects but not between the 3 evaluated α2-adrenoceptor agonist drugs have also been described.3 In another study4 in horses, the scores for the sedative effects of romifidine were, in general, lower than those of detomidine, but the effect of romifidine lasted as long. In the present study, the effects of romifidine lasted significantly longer than those of detomidine.
Previous studies2,4,10 in horses have also revealed that romifidine induces less severe ataxia than detomidine and that the reported qualitative differences between those drugs are related to dose differences.5 Also, the duration of the altered gait is longer after the administration of romifidine.2 Similar differences between xylazine and detomidine have been described.7 The results of the present study have confirmed that the doses of the different α2-adrenoceptor agonist drugs should be assessed separately due to the degree and duration of their effects.5
In addition, significant drug-related decreases in power values were detected in the present study. Of the 3 α2-adrenoceptor agonists administered to the study horses, romifidine treatment resulted in smaller decreases in power values, but again, the duration of the drug's effects was significantly longer. In another study,30 IV administration of romifidine at a dose of 40 μg/kg induced apparent sedation within 5 minutes and the maximal effect persisted for 45 and 60 minutes in all horses.
Because an obvious relationship exists between power and speed23 and a positive correlation between propulsive power and velocity has been described,20 we obtained force of acceleration by dividing the total power of accelerations by speed as a mean to avoid potential bias due to different velocities in the calculation of total power.23 Decreases in force of acceleration (compared with findings for the saline solution treatment) lasted much longer after detomidine and romifidine administration, compared with decreases detected after the injection of xylazine, but again there were no significant differences among drug treatments. Again, these results supported previous reports that romifidine induces less severe ataxia than does detomidine in horses.4 Nevertheless, these qualitative differences between the 2 drugs have been related to dose differences.5 In the present study, we did not find significant differences in force of acceleration among drug treatments, but it appeared that romifidine induced less severe locomotor pattern alterations than did detomidine after the administration of equipotent doses of those drugs. The durations of the decreases in total power and force of acceleration were significantly longer for romifidine than for xylazine and detomidine.
For force of acceleration and power values, the decreases detected after the administration of α2-adrenoceptor agonist drugs could be attributed to a myorelaxation effect.2,12 This excellent muscle relaxation appeared to be greater after the administration of detomidine (albeit nonsignificantly), compared with findings for romifidine.
In the present study, we found that in clinically normal horses that had an accelerometer positioned over the sacral region and were walking, the 3-axial distribution of power was dominated by the mediolateral direction. The contributions of the other 2 components were similar to one another. In dogs that had an accelerometer positioned over the sternum, the distribution was dominated by the dorsoventral and the craniocaudal directions, with only slight involvement of the mediolateral axis.23 Another interesting finding in sedated horses is the redistribution of the 3-axial power, in which there is a significant increase in the mediolateral component of power mainly at the expense of the dorsoventral component, with the propulsive component globally maintained.12 All 3 drugs caused this redistribution in the horses of the present study, with no significant differences among treatments. In this study, detomidine administration resulted in a greater increase in the mediolateral component, compared with the effects of either xylazine or romifidine. This change reflected the obvious incoordinated waddling and rolling gait of sedated horses, which lasted significantly longer for detomidine and romifidine than for xylazine. The horses had a disorganized movement but always, as for other conditions, increased the step width to provide a wider base of support.23 With sedation, similar to ataxia, horses may exaggerate sideways movement of the center of gravity and amplify the amount of forces occurring in the lateral direction.31 The results of the present study were similar to those of another investigation32 performed to establish the reliability of postural sway analysis for measuring balance in horses. Trembling, locking and unlocking of joints, weight shifts, and obvious swaying were signs that appeared during the first 10 to 15 minutes after detomidine administration; in general, the effects were inapparent after 45 to 60 minutes. We agree with the recommendation of those researchers to allow a period of 15 minutes after administration of the equipotent doses described in the present study before performing procedures that rely on a balanced stance, such as farriery or trailering.32
Given the fact that the administration of romifidine resulted in a smaller decrease in power values but a longer duration of action, compared with findings for the other 2 α2-adrenoceptor agonist drugs, we suggest that romifidine may be the first choice for situations in which a horse's balance and coordination are important but prolonged drug effect would be desirable, such as traveling in a trailer. Also, the short and slight alteration in regularity observed after the administration of this drug could be ideal for procedures such as farriery, loading in a trailer, or certain short-duration diagnostic procedures (radiography, ultrasonography, or standing CT and MRI examinations), considering that ataxia may compromise safety during procedures that require horses to maintain balance.32
In the present study, accelerometric evaluation of horses sedated with α2-adrenoceptor agonist drugs revealed that romifidine had a comparatively weaker effect on accelerometric variables than did detomidine or xylazine, although the difference was not significant. The duration of the romifidine-associated effects was significantly longer, confirming that romifidine has more prolonged sedative properties, compared with those of detomidine and xylazine. Quantification of gait abnormalities via accelerometry could potentially be useful for detection and evaluation of the effects of newly developed α2-adrenoceptor agonist drugs or other sedative and analgesic molecules and provide a means of comparison of drug-induced effects on locomotion in horses.
Xilagesic 20%, Laboratorios Calier SA, Barcelona, Spain.
Detogesic, Laboratorio Fort Dodge Veterinaria SA, Girona, Spain.
Sedivet, Laboratorio Boehringer Ingelheim SA, Barcelona, Spain.
Surflo, Terumo Europe NV, Leuven, Belgium.
Equimetrix, Centaure Metrix, Evry, France.
Equimetrix-Centaure 3D, Centaure Metrix, Evry, France.
SPSS, version 19.0 for Windows, SPSS Inc, Chicago, Ill.
Auvinet B, Alix AS, Chaleil D, et al. Gait regularity: measurement and significance (abstr). Gait Posture 2005;21:S143.
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