Evaluation of the physiological parameters, quality of sedation and reversal with the use of atipamezole in mules (Equus) sedated with dexmedetomidine

[Avaliação dos parâmetros fisiológicos, qualidade da sedação e da reversão com o uso do atipamezole em muares (Equus) sedados com dexmedetomidina]

ABSTRACT

The objective of this study was to evaluate the sedative, cardiorespiratory, and intestinal motility effects of dexmedetomidine administered intravenously in mules, before and after the use of the reversal agent. All animals were sedated with the recommended dose, with a significant decrease in HR until T30, returning to close to baseline values at T40. MINT reduced significantly between T10 and T50. Significant hyperglycemia was observed at T10. A significant reduction in head height was detected, with the highest values being observed at T20. In relation to tactile, auditory, and coordination stimuli, a significant reduction was noted, for the first two until T30 and for the latter until T10. After using the reversal agent, MINT returned to normal. It is concluded that the use of dexmedetomidine at a dose of 5mcg/kg in mules is safe and that it promotes a sedative effect for a period of 30 minutes. Furthermore, attention should be paid to the undesirable effect on intestinal motility, as this increases the predisposition to colic syndrome; the reversal agent atipamezole is effective for reversing intestinal motility.

Keywords:
alpha-2 agonist; antisedan(; dexdomitor(; mule; reverser

RESUMO

Objetivou-se, com o presente estudo, avaliar os efeitos sedativos, cardiorrespiratórios e a motilidade intestinal da dexmedetomidina, administrada pela via intravenosa, em muares, antes e após o uso de reversor. Todos os animais apresentaram-se sedados com a dose preconizada, com diminuição significativa da FC até o momento T30, com retorno próximo aos valores basais em T40. A MINT reduziu significativamente entre T10 e T50. Hiperglicemia significativa foi observada em T10. Redução significativa na altura da cabeça foi detectada, sendo até T20 os maiores valores alcançados. Em relação aos estímulos tátil, auditivo e à coordenação, notou-se redução significativa, sendo, para os dois primeiros, até T30 e, para o último, T10. Após o uso do reversor, a MINT retornou à normalidade. Conclui-se que o uso da dexmedetomidina na dose de 5mcg/kg em muares é segura e que promove efeito sedativo por um período de 30 minutos. Ainda, que se deve atentar ao efeito indesejável sobre a motilidade intestinal, uma vez que aumenta a predisposição à síndrome cólica, e que o reversor atipamezole é efetivo para a reversão da motilidade intestinal.

Palavras-chave:
alfa-2 agonista; antisedan⁽; dexdomitor⁽; mula; reversor

INTRODUCTION

Mules are hybrid animals, obtained by crossing the male Equus asinus with the female Equus caballus (Pereira Neto et al., 2014; Miranda and Palhares, 2017), which play an important role in society due to their hardiness, stamina, and adaptability to hot climates (Ramos and Lima, 2021) and prolonged exercise (Ribeiro et al., 2004; Pereira Neto et al., 2014).

Because they combine elements of horses and donkeys, mules present different sizes, temperaments, and body types. Physiologically, they are more similar to horses than to donkeys (Matthews and Van Loon, 2013), however, anatomical, behavioral, and physiological differences need to be taken into account when handling them or during treatment by a veterinarian.

Many clinical, surgical, or diagnostic procedures are performed on horses while they are under sedation. The protocol used is variable, however, it needs to provide sedation of a sufficient degree and duration for the procedure, good analgesia, no or little reaction to external stimuli, and minimal ataxia (Ringer et al., 2013). Alpha-2 adrenergic drugs (xylazine, romifidine, detomidine, and dexmedetomidine) have been used in mules for these purposes, with doses similar to those used in horses, obtaining sedation and analgesia with a reduced duration or similar to that in horses (Bidwell, 2010). In a study involving the use of xylazine in mules, Latzel (2008) reported that the half-life of this alpha-2 agonist is 15 minutes shorter than in horses and that the dose used in horses does not promote sufficient sedation, requiring a 50% higher dose. In general, when using alpha-2 agonists in mules, higher doses are required than in horses (Matthews et al., 1997; Latzel, 2008), probably due to their greater metabolization capacity (Henze et al., 2011). The doses used need to consider behavior, personality, and application route, with the dose of dexmedetomidine intravenously varying from 2.5 to 10(g/kg (Bidwell, 2010). This group stands out for its greater selectivity, specificity, and potency (Maze and Tranquilli, 1991).

To reverse the cardiovascular, sedative and analgesic effects promoted by alpha-2 adrenergic agents, alpha-2 adrenergic antagonists are available, which contribute to the great popularity of this pharmacological class. Among the available antagonists, yohimbine and atipamezole stand out, the second being the most specific (Schwartz and Clark, 1998; Hubbell and Muir, 2006). It is worth highlighting that for reversal, one must consider the loss of analgesia and possible side effects, and the dosage based on body weight, since high doses can promote excitability, muscle tremors, severe hypotension, tachycardia, ptyalism, and diarrhea (Rankin, 2017).

Although the sedative effects of alpha-2 adrenergic drugs are well known in horses, few reports on donkeys and mules are found in the literature. Furthermore, in relation to dexmedetomidine and its reversal agent atipamezole, no studies were found in the literature involving mules, which are widely used in the North and Northeast regions of the country. Therefore, the objective of the current study was to evaluate the quality of sedation with dexmedetomidine in mules and the reversal with atipamezole administered intramuscularly.

MATERIAL AND METHODS

This study was approved by the Ethics Committee on the Use of Animals of the Faculty of Sciences of Tocantins (CEUA/FACIT.TO), under number 05.2021/02.

Seven healthy, adult female mules were used, with an average weight of 376kg, which received 5(g/kg of dexmedetomidine intravenously. The animals were evaluated on the property to which they belonged, in a quiet place, without external sound stimuli or vehicle traffic, and had contact only with the people involved in the research. To avoid interference of fasting on gastrointestinal motility, it was decided not to fast the animals before the evaluation. Before (T0) and every 10 minutes after drug administration (Dexdomitor, Dexmedetomidine Hydrochloride, Zoetis, Brazil) (T10 to T60) the following measurements were made: sedation variables (degree of ataxia, head height in relation to the ground - ACRS, response to external tactile, visual, and auditory stimuli), cardiorespiratory variables (heart rate - HR and respiratory rate - RR, systolic blood pressure - SBP and diastolic blood pressure - DBP), intestinal motility (MINT), and blood glucose concentration (GLUC), which was measured at T0, T10, and T60. For each variable, the same evaluator always performed the evaluation in all animals studied.

Immediately after measuring the T60 moment, atipamezole (Antisedan, Atipamezole Hydrochloride, Zoetis, Brazil) was administered intramuscularly at a dose of 25(g/kg. New measurements were carried out at 10 (T+10) and 60 (T+60) minutes after application of the reversal agent, at which time the variables HR, RR, and MINT were analyzed.

Sedative effects were assessed by the ACRS (Bryant et al., 1991 with modifications), measured in centimeters (cm), using a tape measure graduated in one-centimeter intervals. The tape was positioned in front of the animal and the distance between the lower lip and the ground was measured by visualization. The basal height (M0) was considered as the height of the animal's head before application of the product (100%) and the values ​​obtained in each evaluation were converted into percentages relative to those initially recorded. In addition, the degree of ataxia was evaluated by observing the position assumed by the animal while standing (postural instability), assigning scores from 0 to 3, where 0 = no ataxia, maintaining balance; 1 = postural stability, but with rhythmic and discreet lateral body movements; 2 = more intense body movements with a tendency to lean to one side; and 3 = severe ataxia, crossed pelvic limbs and frequent and sudden flexions of the carpal joints (Table 1).

Regarding responses to stimuli, the recommendations of Ringer et al. (2013), with modifications. To assess the response to tactile stimulation (thoracic and pelvic limbs and ear), the pastern region of the thoracic and pelvic limbs near the coronary line and the internal part of the ear were pressed with the tip of a pen. The response was classified as a score, where 0 = absence of response even after strong pressure and 3 = severe response, with movement of raising the stimulated limb or shaking the head. For auditory stimulation, the evaluator, who was positioned one meter behind the animal, clapped their hands loudly and then classified the response, where 0 = no response and 3 = severe response, with the animal moving its head vigorously or vocalizing. For visual stimulation, a white cloth was waved in front of the animal, without producing sound or air movement, and the reaction was graded in scores, where 0 = no response, with no signal after viewing the object, and 3 = severe response, with vigorous movement of the animal. The evaluation and classification methods are demonstrated in Table 1.

Table 1
Descriptive numerical scale used to evaluate sedation scores in mules. Adapted from Ringer et al. (2013) and Bryant et al. (1991)

Score/Variable	Ataxia	Haptic response	Auditory Response	Visual Response
	Visual assessment of the animal' stability/instability	Touch the ear, thoracic and pelvic limbs with a pen	Clap behind the animal	Wave a white cloth in front of the animal
0	Shows no signs of instability	No response even with strong pressure	No response, no audible acknowledgment signal	No response, no visual response signal
1	Stable, but with light balance	Light response, slightly decreased reflex, with normal or strong pressure	Light response, minimal ear movement or slight head elevation	Light response, minimal ear movement or slight head elevation
2	Unstable, animal visibly sways	Intermediate response, animal withdraws the limb after normal pressure	Intermediate response, moderate reactions and slow movements	Intermediate response, moderate reactions and slow movements
3	Severe ataxia	Rapid response, animal withdraws the limb after gentle pressure	Rapid response, animal turns and/or moves vigorously	Rapid response, animal turns and/or moves vigorously

HR was measured through indirect cardiac auscultation on the left side of the chest, performed for one minute, using a stethoscope. RR was recorded by visually observing chest movements for one minute. GLUC was measured with a portable digital glucometer (G-Tech, Free model) and SBP and DBP were measured using a portable digital non-invasive pressure device (G-Tech, Accumed model), with the cuff positioned on the pastern and fixed with adhesive tape.

MINT was assessed by auscultation of intestinal borborygmi in the four abdominal quadrants with a conventional stethoscope. Auscultation was performed for one minute in each quadrant, always by the same evaluator. The motility was classified according to Boscan et al. (2006), with scores as follows: 0 (absence of heard bowel movement, frequency ≥ 1/min); 1 (no heard bowel movement, frequency > 1/min); 2 (no heard bowel movement, frequency ≥ 1/min); 3 (long and loud borborygmi, frequency 1/min); 4 (long and loud borborygmi, frequency 2 to 4/min); 5 (long and loud borborygmi, frequency > 4/min). After classification at each assessment time, the scores obtained in each quadrant were added and the final score was obtained.

The data obtained were analyzed by Analysis of Variance (ANOVA), using the F test, with a 95% confidence interval considering the value of P<0.05. To verify a significant difference between the times measured for each parameter, the Tukey HSD test was applied with a 95% confidence interval, considering a value of P<0.05.

RESULTS

Signs of sedation were observed in all animals after administration of dexmedetomidine, at a dose of 5μg/kg intravenously. The signs included ataxia, reduced frequency and speed of movement, lowering of the head and neck, lip and eyelid ptosis, and sialorrhea and were observed on average four minutes after application, this being the latency period. The effects observed are among those listed when using alpha-2 adrenergic agonists (Freeman and England, 2000). Abass et al. (2022) obtained sedation classified as deep in donkeys, manifested by reduced consciousness, lowering of the head, lip ptosis, and decreased response to external stimuli, using doses of 5 and 7 μg/kg of dexmedetomidine. Sedation in the study began after five minutes and was maintained for 90 minutes.

The peak sedative effect of alpha-2 adrenergic agonists described in the literature occurs after between two and five minutes via the intravenous route in horses (Grimsrud et al., 2009; Valverde, 2010), due to one of their pharmacological properties, which is rapid distribution (Bettschart-Wolfensberger et al., 2005; Gozalo-Marcilla et al., 2013; Medeiros et al., 2017). The intravenous route was used in the study in question with the aim of reducing individual variations related to the speed of drug absorption, which occurs more frequently via the intramuscular route (Ambrisko and Hikasa, 2003).

The onset of the sedative effect obtained in the present study corroborates what was found in the literature in horses and donkeys using alpha-2 adrenergic agonists (Spyridaki et al., 2004; Hubbell and Muir, 2006; Abass et al., 2022). However, the maintenance of the effect differs, since, considering the height of the head in relation to the ground, HR, RR, and the response to stimuli, the sedation lasted 30 minutes and not 60 minutes or 90 minutes as stated by Lizarra and Janovyak (2013), Lizarra et al. (2017a) and Abass et al. (2022). This finding corroborates the study with ponies, where after intravenous bolus of dexmedetomidine at a dose of 3.5(g /kg, the elimination half-life of the drug was 20 minutes (Bettschart-Wolfensberger et al., 2005). Lizarra et al. (2017b) confirmed that when the dose of dexmedetomidine is increased, the sedation time increases. These authors, by increasing the dose from 4 to 5μg/kg, extended the sedation time from 30 to 60 minutes. This significant increase did not occur when compared with the dose used in the ponies in the study cited above. Other studies using alpha-2 agonists in donkeys and horses also reported an increase in the duration of sedation because of an increase in the dose used (Jochle and Hamm, 1986; Mostafa et al., 1995; El-Maghraby and Atta, 1997, El-Maghraby et al., 2005).

None of the animals in the current work presented complications during or after the study, however, all showed a significant reduction in MINT after the application of dexmedetomidine, with a return close to the basal value after 60 minutes (Table 2). Rezende et al. (2015) using the same dose and route recommended in this study but in horses, also identified a reduction in gastrointestinal motility for 60 minutes after administration of the drug. Abass et al. (2022), using intravenous dexmedetomidine at different doses in donkeys, identified a significant reduction in intestinal contractility after application. At a dose of 5μg/kg, the authors evidenced a significant reduction in the motility of the duodenum, jejunum, right colon, and cecum for up to 90 minutes post-injection when compared to the placebo group and for 60 minutes in the left colon, concluding that an intravenous injection of dexmedetomidine at doses of 3, 5, and 7μg/kg significantly inhibits the peristaltic movement of the different intestinal segments. This antiperistalsis effect is due to inhibition of excitatory cholinergic pathways in the enteric nervous system via β2-adrenergic receptors, or activation of inhibitory neural pathways (Freeman and England, 2001; Herbert et al., 2002; James et al., 2004; Rezende et al., 2015). Although this parameter was evaluated for only 120 minutes, the animals were monitored on subsequent days and no complications linked to this fact were noted.

The use of abdominal auscultation in horses is common in research that seeks to evaluate pain and the influence of diets and drugs on intestinal motility and in the clinical routine of veterinarians (Singh et al., 1996; Teixeira Neto et al., 2004; Boscan et al., 2006; Ribeiro Filho et al., 2012; Donnellan et al., 2013; Carregaro et al., 2014; Taffarel et al., 2015; Salciccia et al., 2019). This technique was also chosen due to its simple execution, low cost, short execution time, and the lack of need for expensive equipment and an evaluator with previous experience, when compared to abdominal ultrasound. In the clinical routine in the field, it is common to use only abdominal auscultation, with ultrasound being used by some veterinarians or veterinary hospitals in cases of colic.

Regarding the assessment of vital parameters (Tab. 2), HR decreased significantly from T10 to T30, with a return to close to the baseline value from T40 onwards. Furthermore, it was possible to detect a statistical difference between the T60 moment from T10 and T20, with the first being significantly higher. Regarding RR, there was a decrease from T10 to T60, however, without statistical difference. In the same sense, DBP and SBP also demonstrated no statistical differences over time, although with different behavior between them at T10, where the former presented a slight increase and the latter a slight reduction.

Table 2
Mean±standard deviation of heart rate (HR), respiratory rate (RR), diastolic blood pressure (DBP), systolic blood pressure (SBP), intestinal motility (MINT), and blood glucose (GLUC) in mules before and every 10 minutes after intravenous administration of dexmedetomidine

Variable	Evaluation Moments
	T0	T10	T20	T30	T40	T50	T60
HR (bpm)	41.29± 3.90A	32.43± 5.53Ba	31.57± 5.41Ba	34.57± 5.71Bab	37.14± 7.90Aab	35.57± 6.50Aab	39.29± 6.47Ab
RR (mpm)	28.71± 8.42A	25.14± 14.87Aa	20.86± 11.05Aa	20.29± 12.35Aa	19.57± 9.80Aa	19.71± 12.31Aa	24.29± 13.77Aa
DBP (mmHg)	89.86± 26.75A	100.29± 28.53Aa	99.17± 31.71Aa	103.00± 9.20Aa	105.20± 24.04Aa	109.83± 23.90Aa	120.83± 13.91Aa
SBP (mmHg)	160.71± 45.01A	132.86± 20.55Aa	150.00± 47.44Aa	161.00± 36.26Aa	177.20± 29.09Aa	164.33± 39.11Aa	170.00± 23.53Aa
MINT	15.42± 1.51A	5.28± 6.12Bab	3.14± 3.48Ba	4.71± 4.85Bab	8.14± 6.17Bab	8.57± 5.02Bab	10.57± 5.02Ab
GLUC	79.86± 8.43A	110.29± 27.90B	-	-	-	-	104.57± 19.04A

• ^A
  Different uppercase letters on the same line indicate a significant difference (p<0.05) compared to the baseline value (T0). ^abDifferent lowercase letters on the same line indicate a significant difference (p<0.05) between moments (T10 to T60).

Cardiovascular alterations are expected and linked to both the inhibition of sympathetic tone caused by the pre-synaptic reduction of noradrenaline, which favors the activity of the parasympathetic nervous system (Greene and Thurmon, 1988; Maze and Tranquilli, 1991), and through the activation of alpha-2 adrenergic receptors that modulate the activity of the central nervous system (Valverde, 2010). This bradycardia occurs even when the drug is administered in low doses (England and Clarke, 1996; Fonseca, 2018). Reduction in cardiac output, cardiac inotropic activity, and systemic vascular resistance are alterations detected after administration of dexmedetomidine in horses (Valverde, 2010). Hypertension followed by hypotension were described by Buhl et al., (2007) and Nyman et al., (2009), however, divergently, no significant differences were observed in DBP and SBP, as detected by Fonseca (2018).

Respiratory depression in response to depression of the respiratory center promoted by alpha-2 adrenergic drugs was cited by Wagner et al., (1991), Buhl et al., (2007), Nyman et al., (2009), Rosa (2014), Taylor et al., (2014) and Fonseca (2018). However, Bagatini et al. (2002) stated that dexmedetomidine does not cause considerable respiratory depression even at higher doses, and Fantoni et al., (1999), Nyman et al., (2009) and Wolfensberger (2017) reported that detomidine used alone does not cause a significant effect on the respiratory system, which was also observed in the present study, where there was a decrease in RR, but without statistical difference. An increase in arterial carbon dioxide pressure (PaCO₂) was observed with an insignificant clinical alteration in arterial oxygen pressure (PaO₂) (Fantoni et al., 1999; Nyman et al., 2009; Wolfensberger, 2017).

In the analysis of GLUC, a significant increase (hyperglycemia) was noted at T10 in relation to T0, while at T60 there was also an increase, although not significant (Table 2). Alpha-2 adrenergic drugs stimulate pancreatic adrenergic receptors, which inhibit the release of insulin, reducing the plasma concentration and, consequently, promoting transient hyperglycemia (Tranquilli et al., 1984; Saha et al., 2005; Ambrósio et al., 2012; Parentoni et al., 2020) and decrease the release of ACTH and cortisol (Taylor and Clarke, 2009). Due to its greater alpha-2 selectivity, dexmedetomidine promotes less hyperglycemic action than medetomidine, which also stimulates hepatic gluconeogenesis (Grimshund et al., 2015).

In horses and donkeys, the sedative effects of alpha-2 adrenergic drugs have already been described (Mostafa et al., 1995; El-Maghraby et al., 2005; Abdel-Wahed et al., 2008; Rosa, 2014; Fonseca, 2018), however, in mules there are no previous reports. To this end, the variables head height in relation to the ground, ataxia score, and response to stimuli are used (Mama et al., 2009; L’Ami et al., 2013; Fonseca, 2018). These sedative and cardiorespiratory effects are dose-dependent (Freeman and England, 2000), while the response to stimuli (tactile, auditory and visual) are normally maintained, even if in an attenuated form (England et al., 1992)

However, in the current study, the values measured and analyzed for HHRG (Table 3) showed a significant reduction in comparison to the baseline value from T10 to T30, with the lowest measurements being obtained in the first 20 minutes (T10 and T20), with HHRG close to 50% to the basal value. Lip ptosis and sialorrhea were symptoms that accompanied head lowering. Studies have reported a dose-dependent effect of detomidine in horses and donkeys, being that the higher the dose used, the greater the power of sedation, effects, and duration (Jochle and Hamm, 1986; Mostafa et al., 1995; El-Maghraby and Atta, 1997; Mama et al., 2009; Rosa, 2014, Fonseca, 2018). At an infusion rate of 5(g/kg/h od dexmedetomidine, Müller et al., (2012) produced a reduction in head height in horses of around 30 to 50%, while at a 7(g/kg/h of 70%. On the contrary, the use of dexmedetomidine in increasing doses did not promote a significant difference in the quality or duration of sedation, assessed by head height in donkeys (Lizarraga et al., 2017b).

The degree of ataxia varied over time, being significant only at T10, accompanying the reduction in head height, as occurred with the scores for visual, tactile, and auditory stimuli, which showed significant reductions from T10 to T30, in relation to T0. This finding does not corroborate the literature in relation to donkeys and horses, as although a decrease in responses to external stimuli can be verified, this is not statistically significant, since already in the basal collection some animals show exaggerated reactions while others do not respond to the same stimulus (Wagner et al., 1991; Castillo et al., 2018). Even after severe sedation with alpha-2 adrenergic drugs, the tactile stimulus was maintained (England and Clarke, 1996), this result being related to the fact that the animals became used to the stimulus (Castillo et al., 2018) and even reacted before the instrument (pen) touched their skin (Ringer et al., 2013).

Table 3
Mean±standard deviation, percentage (%) of reduction in relation to the baseline value to HHRG in mules before and every 10 minutes after intravenous administration of dexmedetomidine

Variable	Evaluation Moments
	T0	T10	T20	T30	T40	T50	T60
HHRG	110.14± 16.44A	57.71± 25.31 (52.40%)Ba	63.00± 28.57 (57.20%)Bab	78.14± 24.47 (70.95%)Bab	82.29± 26.27 (74.71%)Aab	89.57± 17.92 (81.32%)Ab	90.57± 23.01 (70.56%)Aab

• ^A
  Different uppercase letters on the same line indicate a significant difference (p<0.05) compared to the baseline value (T0). ^abDifferent lowercase letters on the same line indicate a significant difference (p<0.05) between moments (T10 to T60).

Pharmacological antagonism of alpha-2 agonists needs to be carried out with caution, respecting the dose, route of administration, and timing of the reversal (Hsu et al., 1987; Andrade and Sakate, 2003). In the present study, reversal was recommended 60 minutes after the application of dexmedetomidine, which eliminated the occurrence of undesirable effects, probably because it was performed after the period of initial vasoconstriction (Hsu et al., 1987).

The dose of the atipamezole reversal agent should be based on that used for the agonist, since recurrence of sedation may occur in the presence of a high dose of agonist and low dose of antagonist, as their period of action is short (Hubbell et al., 2013). The recommended dose in horses is 50 to 150(g/kg, however, the manufacturer recommends that the previously administered dose of dexmedetomidine should not be exceeded by more than eight times. Therefore, in the present study, a dose five times greater than that used for the agonist was established, that is, 25(g /kg, which may also have contributed to the non-occurrence of side effects, highlighting the excitation (Vigani and Garcia-Pereira, 2014).

The intramuscular route is recommended by the manufacturer and by Lemke (2007), as this route allows for excitability and side effects in the cardiovascular system. As the animals did not show excitability and HR and RR values did not change significantly after administration of the reversal agent, it can be inferred that the dose and route used are safe. A slight increase in RR was observed. Furthermore, a significant effect on MINT was observed (Table 4), which may justify its use in horses, as the reduction in intestinal motility promoted by alpha-2 adrenergic drugs is a pre-disposing factor for colic syndrome in horses. Finally, recovery of the ability to walk was also observed, demonstrating that the dose recommended via the IM route reverses the sedative effect of dexmedetomidine in mules.

Table 4
Mean±standard deviation of heart rate (HR), respiratory rate (RR), and intestinal motility (MINT) in mules ten (T+10) and 60 (T+60) minutes after intramuscular administration of atipamezole

Variable	Evaluation Moments
	T0	T60	T+10	T+60
HR (bpm)	41.29±3.90a	39.29±6.47a	40±7.50a	38.66±9.60a
RR (mpm)	28.71±8.42a	24.29±13.77a	25.71±9.48a	27.16±10.40a
MINT	15.42±1.51a	10.57±5.02a	12.28±1.25a	15.14±1.57b

• ^ab
  Different lowercase letters on the same line indicate a significant difference (p<0.05) between moments.

CONCLUSION

Considering the results found, it is possible to conclude that dexmedetomidine at a dose of 5µg/kg intravenously in mules promotes an intense sedative effect, with cardiac alterations similar to those of other alpha-2 adrenergic agents in horses, and a significant reduction in intestinal motility, which requires monitoring when using this drug. The drug takes up to 30 minutes to take effect and is recommended for quick procedures. Finally, atipamezole was effective in reversing the effects of dexmedetomidine on gastrointestinal motility, without relevant alterations in the variables evaluated.

ACKNOWLEDGEMENTS

To the National Academic Cooperation Program in the Amazon - PROCAD/Amazônia - from the Coordination for the Improvement of Higher Education Personnel - CAPES/Brazil and Programa de Pós-graduação em Sanidade Animal e Saúde Pública nos Trópicos (PPGSaspt) of the Universidade Federal do Norte do Tocantins (UFNT) by the support to develop this study (Notice number 016/2023 and 021/2024).

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Publication Dates

• Publication in this collection
  21 Feb 2025
• Date of issue
  Mar-Apr 2025

History

• Received
  15 Jan 2024
• Accepted
  15 Sept 2024