Materials and Methods

Animals—This study was approved by the Purdue University Animal Care and Use Committee. Thirty client-owned healthy sexually intact male cats of various breeds (domestic shorthair, Siamese, Persian, and Abyssinian) were enrolled in this study. Owner consent was obtained for each animal. The mean ± SEM age of the cats was 8.57 ± 1.2 months (range, 2 to 24 months) with a median age of 6 months. The mean body weight of the cats was 2.74 ± 0.27 kg (6.03 ± 0.59 lb) with a range of 0.9 to 4.98 kg (1.98 to 10.96 lb); median body weight was 2.7 kg (5.94 lb). Cats were considered to be healthy on the basis of physical examination findings, history, and basic blood test results (PCV and total protein, blood glucose, and BUN concentrations). Food was withheld from cats between 4 and 12 hours (for cats < 3 months of age, food was withheld for 4 hours to avoid hypoglycemia). All cats had free access to water prior to anesthesia and surgery. Cats were acclimated to their cages for 2 hours prior to anesthesia.

Experimental protocols—This study had a blinded, randomized, split-plot design with 30 cats assigned to 1 of 3 main treatment groups. Each treatment group consisted of 10 cats. The 3 main treatment groups were DKBut (dexmedetomidine^a [25 μg/kg], ketamine^b [3 mg/kg {1.36 mg/lb}], and butorphanol^c [0.2 mg/kg]), DKH (dexmedetomidine [25 μg/kg], ketamine [3 mg/kg], and hydromorphone^d [0.05 mg/kg {0.02 mg/lb}]), and DKBup (dexmedetomidine [25 μg/kg], ketamine [3 mg/kg], and buprenorphine^e [30 μg/kg {13.64 μg/lb}]). Within each main treatment group, cats were then further assigned to receive either saline (0.9% NaCl) solution (n = 5) or atipamezole^f (250 μg/kg [113.64 μg/lb]; 5) as a means to reverse the anesthetic effects of dexmedetomidine at the completion of the surgery. With saline solution or atipamezole as treatment factors with each of the 3 main treatment groups, there were 6 groups. The reversal agent (atipamezole or saline solution) was given after the termination of surgery. The drug doses used in this study were derived from our clinical experience and literature comparison.

All drugs were drawn up separately and mixed in the same syringe immediately prior to administration. All drugs were administered IM in either the right or left quadriceps femoris muscles. An injection of meloxicam^g (0.2 mg/kg, SC) was administered to each cat immediately prior to the conclusion of surgery. All surgeries were performed by an experienced surgeon (BRA). The surgeon and anesthetists were blinded to the treatment protocols.

Surgical procedures—A small incision was made through the scrotum over each testis, and the testis was exteriorized. The spermatic cord was tied onto itself for hemostasis, and the testis was removed. The scrotal incisions were left open to heal by second intention.

Cardiorespiratory monitoring—Heart rate, respiratory rate, indirect blood pressure (measured by the same oscillometric device consistently throughout the study), and body temperature were continuously monitored. These recordings started at 5 minutes prior to the drug administration at 0 minutes. Six minutes after drug administration, heart rate and respiratory rate were determined by auscultation, Spo₂ was determined,^h noninvasive blood pressure was measured by the oscillometric device,ⁱ and body temperature was recorded. The same variables were measured and recorded 10 minutes after drug administration and then every 5 minutes thereafter until anesthesia was reversed (approx 20 minutes after drug injection) or the animal recovered spontaneously to sternal recumbency. End-tidal partial pressure of CO₂ was measured with a main stream capnograph^j if the cat was able to be intubated. An ECG^k was continuously monitored until surgery was completed. To assess the respiratory effect of the injectable combinations, the cats were maintained on room air. If the Spo₂ was < 90% during anesthesia, 100% oxygen was administered until the Spo₂ was > 95%.

Monitoring of anesthesia and analgesia—Time from injection of the anesthetics to the onset of sedation, lateral recumbency, and completion of endotracheal intubation were recorded. Ten minutes were allotted from drug administration to complete endotracheal intubation. During these 10 minutes, based on the cat's clinical signs in response to intubation, 3 attempts were permitted for endotracheal intubation. The ease of endotracheal intubation was scored according to preset criteria (Appendix 1). Once intubated, the endotracheal tube was left in place until the cat began to swallow and cough against the tube. At that time, the endotracheal tube was removed and the total time of intubation was recorded. If the cat could not be intubated, this was recorded and the surgery performed without endotracheal intubation. An additional 10 minutes was allowed for surgical preparation and completion of surgery.

Other recorded variables included the time from injection of anesthetics to the beginning of surgery and the total time of the surgical procedure. To compare anesthesia quality among the injectable anesthetic combinations, every attempt was made to standardize the procedures. The overall quality of anesthesia and recovery were graded according to preset criteria (Appendices 2 and 3).

During the surgery, based on the clinical judgment of the anesthetists or if an animal had signs of inadequate anesthesia such as increased heart rate or respiratory rate or purposeful movements related to surgical stimulation, isoflurane^l with 100% oxygen was titrated to effect via endotracheal tube or face mask connected to a nonrebreathing anesthetic circuit (modified Jackson-Rees anesthetic circuit) until an adequate plane of anesthesia was achieved. When isoflurane use was required, administration was started at 2% and titrated to effect. When the animal reached a stable plane of anesthesia, the end-tidal isoflurane concentration was recorded from either the endotracheal tube or through the well-fitted face mask and administration of isoflurane was discontinued. If the animal continued to have signs of a light plane of anesthesia, isoflurane supplementation was reinstituted. The total duration of isoflurane supplementation was recorded. The number of cats that received isoflurane supplementation in each group was recorded and compared.

Once castration was completed, either atipamezole or the same volume of saline solution was administered IM to the cat according to the treatment group. Time required for cats to achieve sternal recumbency after atipamezole or saline solution administration and time required for cats to maintain standing position after atipamezole or saline solution administration were also recorded. The cat was observed for any signs of pain during recovery. Pain behavior was scored and recorded according to set criteria (Appendix 4). An additional dose of the same opioid was given to cats that had signs of pain during the recovery period (within the first 3 hours after surgery). The number of cats that required an additional dose of an opioid as rescue analgesia was also recorded. Cats were placed on circulating heating blankets during surgery, and forced-air warmers were used during recovery to maintain a body temperature ≥ 36.7°C (98°F).

Statistical analysis—All data were analyzed with a commercially available software program.^m Analysis of variance procedures⁹ were used to determine the significance of the differences attributable to treatment groups. Factorial models were fit and repeated-measures models used when data were considered over time. Effects of treatments with saline solution alone and atipamezole were assessed over time, and when significant, pairwise t tests were performed to further ascertain differences in treatment groups. All data are presented as mean ± SEM. Values of P ≤ 0.05 were considered significant.

Results

Anesthesia quality—The onset of sedation occurred from 1.2 ± 0.2 minutes to 2.0 ± 0.3 minutes after injection and was followed by a smooth induction of anesthesia. Lateral recumbency occurred from 2.6 ± 0.2 minutes to 4.6 ± 1.0 minutes after the single IM injection for each anesthetic combination. The time from anesthetic administration to the beginning of surgery was from 10.8 ± 1.2 minutes to 14.0 ± 1.8 minutes. The duration of surgery was from 2.8 ± 0.8 minutes to 6.0 ± 1.8 minutes. None of the cats had vomiting, salivation, or any other adverse effects immediately following administration of these combinations of anesthetics. By 20 minutes after drug administration, surgery was completed in all treatment groups. There were no significant differences among groups in time from injection of the anesthetic combinations to onset of sedation, assumption of lateral recumbency, or start of surgery. The duration of endotracheal intubation was from 5.6 ± 3.4 minutes to 6.4 ± 4.2 minutes for the atipamezole-treated cats and was from 10.0 ± 6.2 minutes to 15.2 ± 8.5 minutes for the saline solution–treated cats. There were also no significant differences among groups in duration of endotracheal intubation or surgery. All cats completed the study and recovered uneventfully from anesthesia and surgery.

Endotracheal intubation could only be achieved in 43% (13/30) of the cats at 10 minutes after the drug administration (Table 1). A significantly (P < 0.01) higher number (n = 7) of cats that received DKBup had signs of an insufficient plane of anesthesia during surgical stimulation and required isoflurane supplementation to attain and maintain a surgical plane of anesthesia, compared with cats in the DKBut (1) and DKH (2) treatment groups. Mean duration of isoflurane supplementation was short (between 2 and 4.3 minutes), and the isoflurane percentage used was 1.5% for maintenance of anesthesia in all cases. Overall, there were no significant differences in intubation, anesthesia, recovery, and postoperative pain scores (Table 2) among treatment groups.

Anesthesia induction to conclusion of surgery—In the first 19 minutes after drug administration, heart rate decreased significantly to 26% to 33%, 16% to 25%, and 28% to 33% of the baseline values beginning at 6 minutes after DKBut, DKH, and DKBup injection, respectively (Figure 1). There was no significant difference in the decrease in heart rate among treatment groups. Thereafter, heart rates were well maintained (range, 98 to 158 beats/min) in all treatment groups. The lowest heart rates were in saline solution–treated cats, compared with atipamezole-treated cats, with 111.6 ± 14.6 beats/min at 40 minutes in the DKBup–saline solution group, 98.7 ± 3.7 beats/min at 60 minutes in the DKBut–saline solution group, and 105.7 ± 8.5 beats/min at 65 minutes in the DKH–saline solution group. Bradycardia was defined as a heart rate < 80 beats/min and was not observed during the study. No cardiac arrhythmias were noted at any time.

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Mean ± SEM heart rate for 30 cats (n = 5 cats/group) after a single IM injection of various combinations of anesthetic drugs for castration (DKBut, DKBup, or DKH), which was followed by IM administration of atipamezole (A) or saline (0.9% NaCl) solution (S) at the conclusion of surgery (arrow). Time of administration of the anesthetic combination was designated as time 0. Baseline heart rate was obtained at −5 minutes. Duration of anesthesia induction, surgery, and recovery from anesthesia are indicated at the bottom of the figure. ^*Within a time point, value differs significantly (P < 0.05) from the values for the other treatment groups.

Citation: Journal of the American Veterinary Medical Association 239, 11; 10.2460/javma.239.11.1453

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Arterial blood pressures had a biphasic pattern (Figures 2–4). There was a significant increase in mean arterial blood pressure to 20% to 28%, 14% to 30%, and 24% to 25% from the baseline values during the first 20 minutes for DKBut, DKH, and DKBup groups, respectively. Mean arterial blood pressures were significantly higher in the DKBut-atipamezole–treated cats at 10 and 15 minutes after drug administration than for cats in other treatment groups. Thereafter, the mean arterial blood pressure decreased but remained > 75 mm Hg, except in 1 cat in the DKBup-atipamezole group for which mean arterial blood pressure was 67 mm Hg at 20 minutes.

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Mean ± SEM values for systolic arterial blood pressure in the same cats as in Figure 1. See Figure 1 for remainder of key.

Citation: Journal of the American Veterinary Medical Association 239, 11; 10.2460/javma.239.11.1453

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Mean ± SEM values for mean arterial blood pressure in the same cats as in Figure 1. See Figure 1 for remainder of key.

Citation: Journal of the American Veterinary Medical Association 239, 11; 10.2460/javma.239.11.1453

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Mean ± SEM values for diastolic arterial blood pressure in the same cats as in Figure 1. See Figure 1 for remainder of key.

Citation: Journal of the American Veterinary Medical Association 239, 11; 10.2460/javma.239.11.1453

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The baseline respiratory rates were significantly higher in the DKBup–saline solution (72.0 ± 13.7 breaths/min) and DKBut–saline solution (77.6 ± 17.3 breaths/min) groups than all the other treatment groups. The respiratory rates decreased from the baseline recorded rate (animal awake) and subsequently remained within the reference range for anesthetized cats (25 to 41 breaths/min; Figure 5). The DKBup–saline solution group had significantly higher respiratory rates (49.8 ± 12.4 breaths/min) at 6 minutes after drug administration than all the other treatment groups. Thereafter, there were no significant differences in respiratory rates among treatment groups. End-tidal partial pressure of CO₂ (recorded only in cats that were intubated) were mildly increased (range, 38 to 57 mm Hg; data not shown) indicating some mild respiratory depression in all the treatment groups. Hypoxemia with Spo₂ < 90% (range, 85% and 89%) was detected in 2 cats in the DKBut group, 1 cat in the DKH group, and 1 cat in the DKBup group. The hypoxemia occurred within the first 5 minutes after drug administration, and oxygen was supplemented until these cats maintained their Spo₂ > 95%. The duration of 100% oxygen supplementation, either via face mask or via endotracheal tube, was between 5 and 10 minutes. All cats responded to 100% oxygen supplementation with an increase and maintenance of Spo₂ > 95%.

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Mean ± SEM values for respiratory rate in the same cats as in Figure 1. See Figure 1 for remainder of key.

Citation: Journal of the American Veterinary Medical Association 239, 11; 10.2460/javma.239.11.1453

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Recovery period with and without atipamezole treatment—Overall, heart rates did not change significantly among treatment groups and were maintained between 99 and 126 beats/min during the recovery period. Although atipamezole-treated cats had higher heart rates than the saline solution–treated cats during the first 3 to 5 minutes after atipamezole administration (Table 3), the only significantly higher heart rates among groups were recorded at 20 minutes in the DKBup-atipamezole–treated cats (Figure 1). Mean arterial blood pressure did not change significantly over time during recovery and was maintained between 80 and 122 mm Hg (Figure 3) in all groups, except in the DKBut-atipamezole–treated cats. This group of cats had significantly higher systolic, diastolic, and mean arterial blood pressures than all other treatment groups (Figures 2–4). Body temperatures were maintained between 37.67° and 38.61°C (99.8° and 101.5°F) for all cats throughout the study. There was no significant difference among groups with regard to body temperature.

Speed of recovery and recovery quality—Atipamezole administration significantly shortened the duration of recovery time in all the treated cats (Table 4), compared with that of saline solution–treated cats. All the atipamezole-treated cats were able to recover to sternal recumbency between 5.6 ± 1.1 minutes and 12.0 ± 1.0 minutes and maintained a standing position between 6.0 ± 1.3 minutes and 13.4 ± 0.9 minutes after IM injection of atipamezole. In contrast, saline solution–treated cats did not recover to standing until between 70.0 ± 5.8 minutes and 101.0 ± 32.1 minutes after saline solution administration. There was no significant difference in recovery duration (time from reversal injection to standing) in saline solution–treated cats among treatment groups. Recovery was uneventful for all animals. Despite the reversal of dexmedetomidine with atipamezole, no dissociative adverse effects such as muscle trembling, salivation, head shaking, vocalization, or defecation were observed after atipamezole administration. None of the cats had signs of pain or required rescue analgesia during the 3 hours of postoperative monitoring.

Discussion

The results of this study showed that the 3 dexmedetomidine-ketamine–opioid anesthetic combinations rapidly induced lateral recumbency within 5 minutes following a single IM injection in cats. This result is similar to the report by Selmi et al⁴ in which cats treated with dexmedetomidine (10 μg/kg) alone or in combination with either ketamine (5 mg/kg) or butorphanol (0.2 mg/kg) assumed lateral recumbency within 5 minutes following drug administration. Based on the results of these studies, the duration from injection to onset of lateral recumbency is likely to be dependent on the dexmedetomidine dose and is not altered with the addition of butorphanol or ketamine. In addition, the lack of a significant time difference among treatment groups in inducing lateral recumbency suggests that the receptor class (μ-κ–receptor agonist [hydromorphone], μ-opioid receptor antagonist and κ-receptor agonist [butorphanol], or partial μ-receptor agonist [buprenorphine]) of the opioids did not matter.

The dexmedetomidine dose used in this study (25 μg/kg, IM) was lower than the manufacturer-labeled dose (40 μg/kg) for dexmedetomidine used alone in cats. Slingsby and Taylor⁷ reported that to induce analgesia in cats with dexmedetomidine alone, a dose of 40 μg/kg is necessary. These authors also suggested that if a lower dose of dexmedetomidine is used, an additional analgesic is required.⁷ In the present study, we combined dexmedetomidine (25 μg/kg) with ketamine and an opioid for castration in cats.

Although these combinations were able to rapidly induce lateral recumbency uniformly in the cats, only 13 of 30 (43%) could be orotracheally intubated. This indicated that the depth of anesthesia was not profound enough to permit acceptance of the endotracheal tube with these anesthetic combinations within 10 minutes after IM administration. Because the number of cats that could not be intubated was nearly identical among treatment groups, it was concluded that there was no difference in terms of opioid receptor class in enhancing endotracheal intubation. A previous study⁴ in cats demonstrated that dexmedetomidine (10 μg/kg) induced sedation and that muscle relaxation was enhanced when combined with either ketamine or butorphanol. However, no endotracheal intubation was attempted in that study.

During the surgery, there was a significantly higher number of cats (7/10) in the DKBup group that required isoflurane supplementation, compared with the DKBut and DKH groups. This fact indicates that dexmedetomidine-ketamine together with buprenorphine induces a less reliable depth of anesthesia than when dexmedetomidine-ketamine was combined with butorphanol or hydromorphone. There are several possible explanations for the insufficient surgical plane of anesthesia in the DKBup group. The most probable reason is the delayed onset of action of the buprenorphine following administration. Buprenorphine is known to have a slow onset of action. In a skin thermal antinociception test in cats,⁷ buprenorphine (20 μg/kg, IM) was found to have an onset of analgesia at 35 minutes that lasted for 7 to 8 hours. In the present study, it is likely that the onset of buprenorphine-induced analgesia was yet to be reached when the surgical incision started between 10 and 14 minutes after injection, resulting in inadequate analgesic contribution to the anesthetic combination. In contrast, the time to onset of analgesia of butorphanol and hydromorphone were shorter, and only 1 and 2 cats, respectively, required isoflurane supplementation for castration surgery with the same doses of dexmedetomidine and ketamine. Furthermore, buprenorphine has a less sedative and anesthetic-sparing effect in cats.¹⁰ In a study¹⁰ evaluating buprenorphine administration with or without dexmedetomidine in cats, it was found that buprenorphine (10 and 20 μg/kg, IM) did not produce sedation in cats, whereas dexmedetomidine (20 and 40 μg/kg, IM) induced profound sedation. In a study⁸ on dogs comparing dexmedetomidine-buprenorphine and dexmedetomidine-butorphanol for hip joint radiography, it was found that dexmedetomidine-buprenorphine induced poor sedation and was not recommended for such a procedure. The lack of contribution of sedation from buprenorphine in these cats likely weakened the total anesthetic effect of the DKBup combination, compared with the other 2 combinations. The analgesic effects of dexmedetomidine-ketamine and the less-than-peak analgesic effects of buprenorphine were not able to produce a surgical plane of anesthesia at 10 minutes.

Along the same line of reasoning, the more rapid onsets of butorphanol and hydromorphone contributed analgesic properties to the drug combination. Consequently, the combination provided sufficient anesthesia for surgical stimulation in the treated cats. It is possible that if surgery had been delayed for an additional 10 minutes in the DKBup group to allow buprenorphine to reach its peak effect, the depth of anesthesia could have been improved for the castration procedure. This result was observed in our previous study⁶ in dogs where surgery started 20 minutes after the administration of a dexmedetomidine-ketamine and buprenorphine combination and consistently allowed castration. Alternatively, had we increased the dose of dexmedetomidine from 25 to 40 μg/kg, IM, in combination with ketamine and an opioid, castration of the cats may have been completed without the aid of isoflurane. With the protocol used in the present study, practitioners would either have to allow more time for onset of adequate anesthesia or offer additional anesthesia by providing inhalant supplementation or injectable anesthetics to cats before completing the surgery. Further studies are needed to determine whether DKBup-treated cats require more time or additional analgesia to achieve a surgical plane of anesthesia.

In a previous study,⁷ the vomiting response was frequently observed in most cats when dexmedetomidine (2 to 40 μg/kg, IM) was administered. In the present study, none of the cats vomited when dexmedetomidine was combined with ketamine and an opioid. We hypothesize that these drug combinations induced anesthesia rapidly and suppressed the vomiting center of these cats.

Although there were significant decreases in heart rates at 5 minutes after the dexmedetomidine-ketamine-opioid administration from the awake baseline values, the heart rates were well maintained in all the cats throughout the study. In a previous study⁶ in dogs that received similar dexmedetomidine-ketamine-opioid combinations, some of the dogs' heart rates decreased to approximately 50% to 60% from the baseline to a low range between 45 and 55 beats/min. It is interesting to note that the heart rate of the cats did not become as bradycardic as that of dogs following dexmedetomidine-ketamine-opioid administration. This heart rate difference is likely the result of species differences in the response to dexmedetomidine anesthetic combinations. In another study⁷ on sedation in cats, the lowest heart rate observed with dexmedetomidine (10 μg/kg, IM) in combination with butorphanol (0.2 mg/kg) was 64 beats/min and occurred 54 minutes after drug administration, whereas the lowest heart rate observed in the dexmedetomidine and dexmedetomidine-ketamine group comparison was 92 and 88 beats/min, respectively.⁷ In the present study, the heart rates were better maintained despite the higher dose of dexmedetomidine. There are several possible reasons for this. Ketamine is known to increase heart rate, so the ketamine component of the combination treatment in this study may have influenced the maintenance of a high heart rate. Another important component of this study is the influence of surgical stimulation on heart rate. Also, it is possible that hydromorphone, as an opioid full μ-receptor agonist, may induce a higher vagal tone and therefore may be expected to cause a lower heart rate than either butorphanol or buprenorphine in these cats. However, this was not observed during the study. We concluded that a combination of ketamine and surgical stimulation most probably attenuated the vagal effect of these opioids.

The significantly higher baseline respiratory rates observed in the DKBup–saline solution and DKBut–saline solution groups, compared with the other treatment groups, may have been the result of excitement or stress in these cats. This excitement or stress could have reduced the efficacy of the dexmedetomidine and, combined with a slower onset of the analgesic effect of buprenorphine, resulted in more DKBup-treated cats needing isoflurane supplementation. The findings that the cats in the DKBup–saline solution group had significantly higher respiratory rates even at 6 minutes after drug administration support the conclusion that this group was not well anesthetized at this time.

Hypoxemia was observed in a small percentage of the cats in each of the treatment groups during the first 5 minutes after drug administration. The hypoxemic cats responded well to 100% oxygen supplementation. The hypoxemic response was likely due to anesthesia-induced respiratory depression. Supplemental oxygen is strongly recommended for cats anesthetized with these injectable anesthetic protocols.

Most of the cats receiving buprenorphine required isoflurane (7/10) administration to attain adequate anesthesia and therefore also received oxygen supplementation. This makes the comparisons in hypoxemia between the groups less useful during the surgery. However, isoflurane supplementation was only necessary during surgery and further need of oxygen supplementation was not required > 20 minutes after administration of these drugs.

The blood pressure of the cats in this study increased initially following the administration of the dexmedetomidine-ketamine-opioid combinations. This increase was likely due to vasoconstriction induced by dexmedetomidine.

In private practice, it is common that the cat be sent home the same day of the castration. We chose to administer atipamezole to evaluate the speed and quality of recovery. The mean time from injection of atipamezole to standing position was between 6 and 14 minutes. It was a mean of 1 hour longer if the cat did not receive atipamezole as a reversal agent. This indicated that IM administration of atipamezole promptly and effectively reversed the effects of dexmedetomidine and significantly shortened the recovery time in atipamezole-treated cats, compared with saline solution–treated cats. Furthermore, in this study, we used only 3 mg of ketamine/kg as part of the combination. This low dose of ketamine allowed cats to receive atipamezole to antagonize the effects of dexmedetomidine without signs of a rough recovery (ie, ketamine hangover).

In the saline solution control cats, it is interesting to note that the duration of time from initial anesthetic injection to recovery to standing was shortest with the DKBup group (85.8 ± 6.5 minutes), compared with the DKBut (122.6 ± 21.5 minutes) and DKH (124.4 ± 31.7 minutes) groups. The lack of sedative effects of buprenorphine in cats has been previously demonstrated⁹ and could have accounted for the shorter recovery time in the DKBup-treated cats. Atipamezole reversed the effects of dexmedetomidine in the dexmedetomidine-ketamine-opioid combinations, which allowed the cats' heart rates to return to baseline values. Compared with those of the saline solution–treated cats, these heart rates were significantly higher. The blood pressures were significantly higher following atipamezole administration in the DKBut-atipamezole–treated cats than in cats that received atipamezole in the other main treatment groups. The reason for the higher blood pressure is unknown. There was no significant difference in heart rate, respiratory rate, and blood pressures among treatment groups for cats that received saline solution. This suggests that there was no significant difference between opioid types with regard to cardiorespiratory variables during the recovery period in these cats.

Regarding the buprenorphine-treated cats that received atipamezole immediately after surgery, some may argue that these cats did not have analgesia because the buprenorphine had not reached its full effect. Although buprenorphine did not reach its peak effect by 20 minutes, some analgesic property of buprenorphine would have been active as well as meloxicam and ketamine at the time of atipamezole administration.

In summary, all 3 opioids were suitable for combination use with dexmedetomidine-ketamine for anesthesia induction and immobilization of cats. However, the dexmedetomidine-ketamine in combination with butorphanol or hydromorphone tended to have immediate synergistic effects, compared with buprenorphine for castration. If the timing of surgery is to occur quickly (ie, within 10 to 14 minutes after drug administration) with DKBup, a backup plan of inhalant supplementation or injectable anesthesia is required to complete the surgery. Atipamezole administration for anesthetic reversal shortened the recovery time without inducing adverse effects. We recommend dexmedetomidine-ketamine combined with either butorphanol or hydromorphone as an injectable anesthetic combination for castration in cats commencing at 10 minutes after drug administration. Oxygen supplementation is strongly recommended when these injectable anesthetic protocols are used.