et al. [82] reported a longer‐lasting hypertension was observed following IV administration of detomidine (0.03 mg/kg). Interestingly, in that study, mean arterial blood pressure showed the characteristic biphasic patterns for all four α2 agonists (xylazine, detomidine, medetomidine, and romifidine), but all the values were within or above normal values. In other words, hypotension, defined as below‐normal arterial blood pressure values, was not observed with any of the α2 agonists in this study [82]. Unlike xylazine, detomidine at IV doses less than 0.04 mg/kg did not produce an oxytocin‐like effect on the uterus in gravid cattle. Doses higher than 0.04 mg/kg may increase the electrical activity of the uterine muscles, but it did not induce the synchronization of the bursts of potentials that is characteristic of parturition. Therefore, detomidine at the therapeutic dose is unlikely to induce premature parturition in pregnant ruminants [56, 57].
The sedative effects of detomidine gel applied intravaginally (0.2 mg/kg) has been studied in alpacas. The onset, the time to maximal sedation, and the duration of sedation were 13.0 ± 2.5, 25 ± 4, and 65 ± 12 minutes, respectively. Four of six alpacas assumed sternal recumbency position during sedation. The result of this study showed that intravaginal detomidine produced moderate sedation which was not as profound as that of IV detomidine [92].
2.3.2.3 Medetomidine
Medetomidine induced dose‐dependent sedation and analgesia in sheep at doses of 0.001–0.007 mg/kg IV, with the level of analgesia produced by 0.005 mg/kg comparable to that of 0.015 mg/kg of fentanyl [93]. At 0.04 mg/kg IM, medetomidine induced 30–45 minutes of good analgesia and marked muscle relaxation and 58 minutes of recumbency. Full recovery usually occurred within 1½–2 hours after regaining the righting reflex [94]. When used as a preanesthetic administered 30 minutes prior to induction with propofol and maintenance with isoflurane, medetomidine (0.005 or 0.01 mg/kg IM) decreased heart rate and respiratory rate. Mean arterial blood pressure values were significantly higher following a high dose (0.01 mg/kg IM) as compared to those without preanesthetic medetomidine or those administered at a lower dose (0.005 mg/kg IM). In general, the administration of medetomidine reduced the dose requirement of propofol for induction and isoflurane for maintenance of anesthesia during surgery [95]. In sheep breathing room air that are anesthetized with medetomidine (0.02 mg/kg IV) and ketamine (2 mg/kg IV), PaO2, arterial pH, and arterial O2 saturation (SaO2) decreased and PaCO2 increased significantly. Supplementation of 100% O2 improved PaO2 and SaO2 [96]. Similar to all other α2 agonist drugs, medetomidine (0.01 mg/kg IV) caused characteristic hypoxemia in sheep breathing room air during sedation [82].
When given to produce lumbosacral analgesia in goats, medetomidine at doses of 0.01, 0.02, and 0.03 mg/kg diluted in sterile water to a total volume of 5 ml produced satisfactory analgesia in the perineum and flank regions, and the analgesia extended to the thorax, forelimbs, neck, and head for a period of at least 3 hours. Ten goats receiving 0.02 mg/kg underwent laparotomy surgery; adequate analgesia was apparent in all tissue layers (from skin to external and internal oblique muscles and transverse muscles). All 10 goats recovered uneventfully from surgery. Lateral recumbency and characteristic side effects of other α2 agonists were observed during the study, particularly with higher doses (0.02 and 0.03 mg/kg). One goat receiving 0.01 mg/kg was paralyzed following lumbosacral injection and was humanely euthanized. Because of the caudal extension of the spinal cord into the cauda equina in goats, it was speculated that the trauma to the conus medullaris and/or cauda equina resulting from struggling of the animal at the time of spinal needle insertion was responsible for the paralysis observed in this goat [97].
IM administration of medetomidine (0.01–0.03 mg/kg IM) has also been used in llamas. Sternal recumbency (5.3 ± 4.7 minutes) and mild to moderate sedation (37.3 ± 9.5 minutes) without analgesia were observed in two of three llamas receiving 0.01 mg/kg of the drug. All llamas receiving 0.02 mg/kg assumed sternal recumbency but with only slightly more profound sedation (58 ± 12.1 minutes) and analgesia (30 minutes) than that of 0.01 mg/kg. When the dose was increased to 0.03 mg/kg, medetomidine induced immobilization (91.5 ± 24.7 minutes) with profound analgesia (61.7 ± 2.9 minutes) and muscle relaxation. The only side effect observed during the period of immobilization was a significant decrease in heart rate. Atipamezole (0.125 mg/kg IM) effectively reversed the effect of medetomidine (0.03 mg/kg IM), and standing recovery occurred within 5.8 ± 3.3 minutes [98].
2.3.2.4 Romifidine
In foals, romifidine was reported to produce sedation and analgesia with greater intensity and longer duration than xylazine [99]. Celly et al. [82] reported that romifidine at 0.05 mg/kg IV produced a similar degree of hypoxemia but a significantly longer duration of initial hypertension than other α2 agonists. When xylazine (0.15 mg/kg IV), detomidine (0.03 mg/kg IV), romifidine (0.05 mg/kg IV), and medetomidine (0.01 mg/kg IV) were administered to sheep at quasiequipotent doses, similar decreases in PaO2 and increases in respiratory rate and maximum changes in transpulmonary pressure (ΔP pl) were observed with all four drugs except the duration of increase in respiratory rate, and ΔP pl were longest with romifidine [82].
When romifidine (0.05 mg/kg) was administered by lumbosacral epidural injection, it produced moderate to complete analgesia of the perineum, flank, and abdominal regions. Increasing the dose to 0.075 mg/kg did not enhance the degree of analgesia but only prolonged the duration. Khattri et al. [100] indicated that higher doses of romifidine (0.075 mg/kg) produced a wider region of analgesia from the tail regions to the thorax. This may be the result of a higher concentration of the injected drug solution with 0.075 mg/kg than 0.05 mg/kg since the total volume of the injected solution was maintained at the same 4 ml for both dosages in this study. Side effects resulting from spinally administered romifidine included dose‐dependent ataxia and decreased heart rate, respiratory rate, and mean arterial blood pressures [100].
In camels, the sedative and analgesic effects of romifidine were assessed at three different doses (0.04, 0.08, and 0.12 mg/kg IV). Both the sedative and analgesic effects were dose dependent with the duration of sedation (37, 51, and 65 minutes, respectively) lasting longer than the analgesic effect (21, 34, and 46 minutes, respectively). Bradycardia, ruminal tympany, increased urine output, and hyperglycemia are commonly observed side effects during romifidine sedation. Camels may not represent domestic camelids like llamas and alpacas, and they have been reported to require higher doses of xylazine to produce a similar degree of sedation. Thus, llamas and alpacas may require a lower dose of romifidine to produce desirable sedation and analgesia [101].
2.3.3 Swine
2.3.3.1 Xylazine
Compared to other domestic species, pigs are the least sensitive to xylazine. A higher dose (1.65 mg/kg IV, 2.2 mg/kg IM) is required to produce mild to moderate sedation, but still the pigs are easily aroused and able to flee when approached [8, 14]. Vomiting and bloating have been observed in pigs that were not fasted prior to anesthesia [16, 21]. When tested at doses of 1, 2, 4, 8, and 16 mg/kg IV in young pigs, xylazine alone did not produce effective sedation and analgesia. Xylazine induced a significant decrease in mean arterial blood pressure, but it gradually returned to baseline values 10 minutes after administration [102].
2.3.3.2 Detomidine
In pigs, doses of detomidine at 0.04 mg/kg IV or 0.08 mg/kg IM have been used in combination with ketamine to produce short‐term anesthesia [103]. Analgesia following lumbosacral epidural administration of detomidine was not as profound as xylazine in pigs [104]. In addition, detomidine‐ or xylazine‐induced epidural analgesia may be mediated through a different mechanism of action in that IV administration of an antagonist was capable of antagonizing epidural detomidine‐induced sedation, analgesia, and immobilization but was only able to antagonize the sedation induced by epidural xylazine but not the analgesia and immobilization [104]. This observation is supported by reports in horses and cattle [105–107]. Perhaps the difference of response to the IV administration of an antagonist lies in the fact that xylazine itself has local anesthetic