Comparación de los efectos sedantes y fisiológicos de la xilazina y acepromazina en alpacas (Vicugna pacos)

Resumen

La evaluación de diferentes principios activos en camélidos sudamericanos es escasa en comparación con otras especies domésticas. El objetivo de este estudio fue evaluar el efecto de dos sedantes sobre los parámetros fisiológicos y los niveles de sedación en alpacas huacaya. Se formaron dos grupos de 15 alpacas macho adultas: G_X y G_A, a los que se les administró xilazina 0.5 mg/kg de peso corporal por inyección intramuscular y acepromazina 0.5 mg/kg de peso corporal por inyección intramuscular, respectivamente. En el G_A, la frecuencia cardíaca aumentó con mayor variabilidad y fue significativa al minuto 15. La frecuencia respiratoria disminuyó con menos variación que en G_X. La saturación periférica de oxígeno no se alteró en ningún grupo. Aunque la temperatura difirió al inicio, fue similar al minuto 15 (p>0.05). Ningún sedante mostró diferencias significativas entre control y post-sedación (p>0.05). En G_X, el 86,67% de las alpacas no evidenciaron sedación (escala: sin sedación, leve, buena y profunda), una alpaca mostró sedación leve y otra buena sedación. En G_A, el 66,67% tuvo una sedación buena y el 33,33% una sedación profunda. En conclusión, a las dosis empleadas, la xilazina y la acepromazina no causaron alteraciones fisiológicas relevantes en alpacas macho huacaya, aunque la acepromazina incrementó la frecuencia cardíaca y redujo la frecuencia respiratoria.

Introduction

The alpaca (Vicugna pacos) is a native species distributed across the Altiplano of South America at altitudes ranging from 4,000 to 5,000 meters (Hunter, 2020). This species has adapted to extreme environmental conditions where other animals would not thrive, making it an attractive livestock option in the context of climate change, water scarcity, and the reduction of agricultural land (Zarrin et al., 2020). While most research on alpacas focuses on the characteristics of their fiber (Hunter, 2020), studies on the species’ response to central nervous system depressant drugs remain limited.

Sedation is an advanced state of tranquilization characterized by reduced nervous excitation, leading to slower reactions (Bahn y Holt, 2005). Sedatives are widely used in veterinary medicine to immobilize patients chemically for minor surgical procedures. These drugs are also routinely administered as preanesthetic medications, as they facilitate the induction and maintenance of general anesthesia in domestic animals (Costea et al., 2023). However, little is known about their effects on physiological parameters in camelids.

The most used sedatives in veterinary medicine include phenothiazines (e.g., acepromazine) and α2-adrenergic agonists (e.g., xylazine), both of which have been incorporated into protocols for specific surgical procedures in alpacas (Abrahamsen, 2009; Espezua et al., 2015), as well as in other South American camelids (DuBois et al., 2004). Nevertheless, their effects on physiological parameters in less-studied species, such as alpacas, remain poorly understood.

In animal models, sedation is evaluated based on reduced motor activity and excitability (Rudolph y Antkowiak, 2004). In this context, physiological parameters serve as practical indicators for assessment. Given the limited information available on the effects of sedatives on different physiological systems in alpacas, this study aimed to evaluate the effects of two sedatives at pharmacological doses on physiological parameters in alpacas and to assess the quality of sedation. The findings are expected to contribute to the development of safer intervention protocols for this species.

Materials and methods

The study was conducted at the alpaca breeding facility of the Fondo de Crédito para el Desarrollo Agroforestal (FONCREAGRO), located at an altitude of 3,897 m in the highlands of the Cajamarca mountain range (Cajamarca, Peru). The alpacas were raised in a semi-extensive grazing system, feeding on natural pastures and drinking water from local highland lagoons.

Two groups of 15 adult male alpacas (over two years of age and clinically healthy) were formed using simple randomization. A large group of male alpacas was gathered in a single pen. The capture of animals was performed by an alpaca herder (caretaker of the animals) previously trained in proper alpaca handling techniques. Captures were carried out one by one without any predetermined order, avoiding any selection based on physical traits or behavior, thereby ensuring a random capture process. Animals not meeting the inclusion criteria (i.e., younger than two years) were immediately released. Each eligible alpaca, as it was captured, was alternately allocated to one of the two experimental groups until both groups reached the required sample size (Figure 1 and Figure 2).

Figure 1. Huacaya male alpacas led into a corral within the breeding facility for subsequent evaluation and selection as participants in the experimental groups.

Figure 2. Huacaya male alpacas housed in a corral, where random selection of individuals was performed for assignment to each experimental group.

Each group received a different sedative drug. The first group (G_X) was administered xylazine hydrochloride at a dose of 0.5 mg/kg, body weight (BW) (Halatal®-X, Marethfarm S.A., Peru) by intramuscular (IM) injection. The second group (G_A) received 0.5 mg/kg BW, acepromazine maleate (Promazil®, Marethfarm S.A., Peru) by IM injection. These sedatives were selected based on their commercial availability in the study region.

The dose of xylazine was selected based on the literature on alpacas and llamas (Abrahamsen, 2009). For acepromazine, no specific dosing guidelines were available for alpacas; therefore, the same dose on a mg/kg basis was used to allow a direct comparative evaluation of sedative effect between both drugs under equivalent exposure conditions. This approach aimed to detect any species-specific sensitivity or tolerance to acepromazine, while ensuring the dose remained within a range reported as safe in other camelids, such as llamas (Hashem y Keller, 1993).

We acknowledge that the acepromazine dose used may have been relatively high compared with empirical doses in other large animal species, and that comparing drugs with different pharmacological mechanisms at the same mg/kg dose does not allow a strict equivalence of potency. However, the decision was methodological, seeking to standardize one experimental variable (dose) to facilitate the detection of qualitative differences in physiological response rather than to establish equipotent dosing between the two sedatives. Although xylazine and acepromazine belong to different pharmacological classes and have distinct mechanisms of action, the comparative dose selection was intended to standardize the experimental conditions and isolate the effect of the drug class rather than confound it with differing dose levels.

The alpacas were weighed using a suspension harness and a hanging scale to determine the required volume of each sedative. The calculated volume (therapeutic dose [mg/kg] × BW [kg] / drug concentration) was administered intramuscularly in the caudal third of the neck using a 5-mL syringe and a 23-gauge × 25-mm hypodermic needle. All procedures were carried out within the breeding facility. Under normal farm management conditions, alpacas are kept in pens overnight without access to food. Therefore, the procedure was performed the following morning without requiring a specific fasting period. The animals are brought into the pens at 5:00 p.m. and taken out to pasture at 7:30 a.m. the following day.

Following sedative administration, each alpaca was released within the facility and observed for behavioral responses. Physiological parameters were recorded every five minutes for three consecutive measurements to evaluate changes in response to the drug. Respiratory rate (RR) was determined by counting respiratory cycles, rectal temperature (T°) was measured using a digital thermometer, and heart rate (HR) and peripheral oxygen saturation (SpO₂) were assessed using a veterinary pulse oximeter (CONTEC^TM, Contec Medical Systems Co., Ltd., China), which was placed in the ear.

Sedation quality was assessed using a modified scale ranging from 0 to 3, adapted from scoring systems applied to horses (Casoni et al., 2015; Schauvliege et al., 2019; Thakur et al., 2011). A score of 0 indicated the absence of sedation, 1 represented mild sedation, 2 showed good sedation, and 3 corresponded to marked sedation (Table 1). However, it should be noted that the evaluation of sedation was not performed in a blinded manner, which may have introduced observer bias in the assessment. Future studies should consider implementing blinded assessments to improve objectivity and reduce potential bias.

Table 1. Scoring scale for assessing the level of sedation induced by tranquilizers in alpacas. ↑

Score (grade)	Indicators
0 (no sedation)	The alpaca is attentive, maintains an upright posture, and engages with its environment and interaction with the evaluator. Its ears respond to stimuli in the surroundings, such as movement.
1 (mild sedation)	Reduced response to environmental stimuli. Ears partially react to their surroundings, exhibiting minimal or no ptosis.
2 (good sedation)	The alpaca is in a sternal recumbent position, showing no response to environmental stimuli. There is noticeable ear ptosis.
3 (deep sedation)	The alpaca maintains stable support on its limbs in a sternal recumbency position, showing no response to background activity. The lower lip droops, and there is notable ear ptosis, with minimal or no movement of the ears.

Data were organized in Excel spreadsheets and analyzed using descriptive statistics. The normality of the data was assessed with the Shapiro-Wilks test, and statistical comparisons were made accordingly. For normally distributed independent data, means were compared using Student's t-test; for non-normally distributed data, the Mann-Whitney U test was used for analysis. Changes in physiological parameters over time were examined using repeated-measures ANOVA for parametric data (verified with Mauchly’s test) and the Friedman test for non-parametric data, given their dependent nature. A significance level of p<0.05 was considered for all analyses.

Results

The HR, RR, and SpO₂ did not differ significantly between groups at baseline (time 0, before drug administration) (p>0.05), unlike body temperature. At minute 15, the most notable effects were an increase in HR and a decrease in RR in the G_A group (Table 2). The HR and RR exhibited the most significant variation in response to both sedatives, with a higher coefficient of variation (CV) (Table 2) (Figure 3).

Table 2. Pairwise comparisons of physiological parameters under the effect of xylazine and acepromazine sedation in male huacaya alpacas in Sorochuco, Celendín (Cajamarca, Peru). ↑

Parameter	Measure	Min 0		Min 5		Min 10		Min 15
		GX	GA	GX	GA	GX	GA	GX	GA
HR (Beats/min)	Mean±SD	68.60±15.69	64.33±11.16	70±12.26	79.40±26.97	71.60±16.27	74.13±27.77	64.67±9.06	74.93±16.36
	Median (IQR)	72 (53-79)	67 (54-76)	72 (60-79)	76 (55-92)	71 (59-80)	75 (50-87)	64 (58-69)	74 (59-89)
	Min-Max	36-90	49-80	47-90	45-143	46-112	43-150	51-86	45-98
	CV (%)	22.87	17.35	17.52	33.97	22.73	37.46	14.01	21.83
	Normality	0.50	0.06	0.76	0.38	0.79	0.09	0.48	0.46
	p-value	0.455		0.233		0.950		0.045
RR (Breaths/min)	Mean±SD	34.07±8.30	34.27±6.27	36.27±8.75	32.13±5.15	35.20±8.97	32.93±5.60	35.20±7.88	29.47±5.53
	Median (IQR)	36 (24-40)	36 (32-38)	36 (32-44)	32 (28-36)	36 (28-44)	32 (28-38)	36 (28-40)	28 (26-34)
	Min-Max	22-48	24-48	20-48	24-40	20-48	24-40	20-48	20-38
	CV (%)	24.37	18.31	24.12	16.04	25.48	17	22.4	18.76
	Normality	0.25	0.64	0.22	0.06	0.24	0.70	0.62	0.36
	p-value	0.941		0.118		0.413		0.029*
T (°C)	Mean±SD	38.26±0.36	37.89±0.38	38.41±0.36	37.21±3.68	38.35±0.34	38.03±0.68	38.27±0.53	37.77±0.81
	Median (IQR)	38.40 (37.90-38.50)	38 (37.50-38.10)	38.40 (38.20-38.60)	38.10 (37.70-38.50)	38.30 (38.20-38.40)	38 (37.60-38.20)	38.50 (38.10-38.60)	38 (37.40-38.30)
	Min-Max	37.60-38.70	37.20-38.50	37.70-39.10	24-38.80	37.70-39.30	37.20-40	37.10-39.10	36-38.70
	CV (%)	0.94	1.01	0.93	9.88	0.89	1.8	1.39	2.15
	Normality	0.05	0.18	0.57	0.00	0.14	0.04	0.06	0.16
	p-value	0.012*		0.118		0.010*		0.084
SpO2 (%)	Mean±SD	93±5.08	93.33±4.76	93.27±5.35	93.93±5.92	94.13±4.84	93.60±5.14	90.27±7.43	94.67±3.42
	Median (IQR)	92 (90-98)	95 (88-97)	93 (90-97)	95 (92-98)	96 (91-98)	94 (89-98)	93 (86-96)	94 (92-99)
	Min-Max	83-99	86-99	78-99	78-99	84-99	83-99	77-99	88-99
	CV (%)	5.47	5.1	5.74	6.3	5.14	5.49	8.23	3.61
	Normality	0.15	0.02	0.23	0.00	0.04	0.05	0.02	0.22
	p-value	0.835		0.392		0.818		0.117

*Statistical difference (p<0.05). When the normality of both groups was greater than 0.05, means were compared using Student's t-test. When at least one group had a normality value below 0.05, medians were compared using the Mann-Whitney U test. SD: standard deviation; IQR: interquartile range; CV: coefficient of variation; Min: minimum; Max: maximum. HR: heart rate; RR: respiratory rate; T: temperature [°C: Celsius degrees]; %SpO₂: blood oxygen saturation percentage.

Figure 3. Physiological parameters in alpacas sedated with xylazine (X) and acepromazine (A). ↑

When comparing physiological parameter values between control measurements (time 0, pre-medication) and the three post-administration measurements for each group, HR increased with acepromazine and remained nearly unchanged with xylazine. The RR increased with xylazine and decreased with acepromazine. Body temperature showed the least variation in both groups, while SpO₂ increased slightly with xylazine and remained relatively stable with acepromazine. However, no statistically significant differences were observed for any of the sedatives (p>0.05) (Table 3).

Table 3. Comparison of the effects of both sedatives on physiological parameters in male huacaya alpacas in Sorochuco, Celendín (Cajamarca, Peru). ↑

Parameter	Measure	Xylazine					Acepromazine
		Min 0	Min 5	Min 10	Min 15	p-value	Min 0	Min 5	Min 10	Min 15	p-value
HR	Mean	68.60	70	71.60	64.676	0.550a	64.33	79.40	74.13	74.93	0.290a
RR	Mean	34.07	36.27	35.20	35.20	0.918a	34.27	32.13	32.93	29.47	0.136a
T	Mean/Median	38.26	38.41	38.35	38.27	0.871a	38	38.10	38	38	0.246f
%SpO2	Median	92	93	96	93	0.399f	95	95	94	94	0.952f

Level of significance p<0.05. Parametric data that met the sphericity assumption were compared using repeated measures ANOVA (a). Groups with at least one non-parametric data point were compared using the Friedman test (f). HR: heart rate (beats/min); RR: respiratory rate (breaths/min); T: temperature [°C: degrees Celsius]; %SpO₂: oxygen saturation percentage.

Regarding the quality of sedation, 13 out of 15 alpacas (86.67%) treated with xylazine were classified as exhibiting minimal or no signs of sedation (score 0). In contrast, 10 out of 15 alpacas (66.67%) treated with acepromazine evidenced a good grade of sedation (score 2) (Figure 4).

Figure 4. Sedation quality of xylazine and acepromazine in huacaya alpacas based on sedation grade. ↑

Discussion

Acepromazine tended to increase HR and decrease RR in the evaluated alpacas, with a statistically significant difference noted at minute 15 (p<0.05). However, SpO₂ remained unchanged between groups (p>0.05). HR and RR were the physiological parameters that showed the most variation in response to both sedatives. Additionally, the physiological values recorded after sedation did not differ significantly from those of the control group (pre-medication). The observed increase in HR and decrease in RR following acepromazine administration may be attributed to its peripheral vasodilatory effect, which leads to hypotension (Pypendop y Ilkiw, 2012). In response, the body initiates a compensatory mechanism, reflex tachycardia, to maintain cardiac output and tissue perfusion, thereby explaining the increased HR despite the overall sedative effect (Sarkar et al., 2017).

Similarly, acepromazine lowered body temperature, but these values did not differ significantly from those of the controls. Because it causes vasodilation and hypotension, this change interferes with thermoregulation and can therefore cause hypothermia (Pypendop y Ilkiw, 2012). These properties could explain the observed results, which may become more pronounced at higher doses. It is essential to note that alpacas are typically raised at high altitudes, where extreme cold is a common occurrence. Therefore, special attention should be paid to body temperature management to prevent hypothermia and potentially fatal outcomes.

Moreover, a significant temperature difference was observed between groups at minutes 0 and 10 (p=0.012 and p=0.010, respectively) (Table 2). However, as these groups were independent, the difference cannot be attributed to a pre-anesthetic effect. In contrast, when temperature was analyzed within each group over time (i.e., dependent measures), no significant changes were found (G_X: p=0.871; G_A: p=0.246). In this context, the lack of intra-group variation suggests that the sedatives did not significantly influence body temperature.

Xylazine has been shown to decrease HR due to its agonistic effect on α2-adrenergic receptors. It reduces sympathetic activity and slows HR, decreasing RR, body temperature, and SpO₂. However, this effect is dose-dependent (Pypendop y Ilkiw, 2012; Ruiz-Colón et al., 2014). Therefore, it can be inferred that at a dose of 0.5 mg/kg, xylazine does not induce significant effects in alpacas, which supports the absence of variation observed in control measurements.

This limited response may be explained by interspecies variability in sensitivity to α2-agonists, which is influenced by receptor density, affinity, distribution, and the drug’s pharmacokinetics (absorption, distribution, metabolism, and elimination). It is possible that alpacas possess a lower α2-receptor density or metabolize xylazine more rapidly than species such as cattle, requiring higher doses to achieve marked sedative effects. Notably, ruminants are approximately 10-20 times more sensitive to xylazine than other species, such as horses and dogs, as they require only about one-tenth of the dose needed in those species to achieve a comparable sedative or analgesic effect (García‐Villar et al., 1981). These interspecies differences underscore the importance of species-specific evaluations when determining sedative protocols and dosages.

Most alpacas administered xylazine showed no signs of sedation, except for two individuals. In contrast, acepromazine produced effective sedation in most subjects, with one-fifth displaying signs of significant sedation. The more substantial sedative effect observed in the acepromazine group may be due to its mechanism of action, as alpacas appear to be more sensitive to the effects of dopamine antagonists, which produce profound sedation, while they seem less sensitive to α2-adrenergic antagonists (Pypendop y Ilkiw, 2012). Therefore, if xylazine is to be used as a sedative in alpacas, higher doses should be assessed to determine the optimal dosage for this species.

Although xylazine and acepromazine belong to different pharmacological classes and their equipotent doses are not well established in alpacas, the use of an identical dose (0.5 mg/kg) for both agents allowed for a standardized comparison of their physiological effects. While this limits direct pharmacodynamic equivalence, the findings suggest that alpacas were more susceptible to acepromazine at this dose, as evidenced by more pronounced changes in specific physiological parameters. This heightened sensitivity may reflect species-specific pharmacokinetics or pharmacodynamics, highlighting the need for further dose-response studies to determine optimal and comparable sedative protocols in this species.

This study had certain limitations, notably the short evaluation period, which may have limited the detection of more prolonged effects. Although the alpacas were observed freely for two hours after the final measurement and showed normal behavior, such as walking and grazing, physiological parameters were not recorded during this time due to constraints related to distance, feeding requirements, and scheduling. Therefore, the total duration of the sedative effect was not assessed. Further studies are needed to evaluate the duration of action of each sedative and their effects at different doses. In alpacas, xylazine administered at 0.1-0.5 mg/kg (IV, IM, or SC) has been reported to have a duration of less than 40 minutes (Anderson, 2013), although this may vary with dosage. In llamas, acepromazine maleate at 0.01-0.05 mg/kg IM induced sternal recumbency within 2.9±1.7 minutes, with recovery to standing occurring at 97±11 minutes (Prado et al., 2008).

Conclusion

In conclusion, both xylazine and acepromazine, at the administered doses, did not induce significant alterations in physiological parameters compared to normal values in huacaya male alpacas. However, alpacas were more susceptible to acepromazine, which increased HR and decreased RR. Furthermore, acepromazine, administered IM at a dose of 0.5 mg/kg body weight, provided effective sedation in alpacas.

Acknowledgements

The authors are grateful to Veterinarians Gerardo Briones and Wilder Briones for their support in providing facilities and access to the alpacas.

Author contributions

VRL: conceptualization, methodology, investigation, writing - original draft, writing - review & editing. MALR: investigation, data curation, visualization, writing - review & editing. MEJE: validation, formal analysis, project administration, funding acquisition, writing - review & editing.

Declaration of interests

The authors have no conflict of interest to declare.

Ethics Committee Approval: The study was approved by the Graduate School of the National University of Cajamarca (Directorate Resolution No. 006-2024). Additionally, the authors adhered to the Animal Protection and Welfare Law of the Peruvian State (Law No. 30407).

Funding

The authors declare that this study received financial support from the Asociación Fondo de Crédito para el Desarrollo Agroforestal–FONCREAGRO (FDG2001/035-24/FONC).

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