b Department of Statistics

A Comparison of Anesthetic and Cardiorespiratory Effects of Tiletamine Zolazepam Butorphanol and Tiletamine Zolazepam Butorphanol Medetomidine in Cats Jeff C. H. Ko, DVM, MS, DACVA a Lisa A. Abbo, DVM a Ann B. Weil, MS, DVM, DACVA a Brenda M. Johnson, BS, RVT a Mark Payton, PhD b a Department of Veterinary Clinical Sciences School of Veterinary Medicine Purdue University West Lafayette, IN 4797 b Department of Statistics College of Arts and Sciences Oklahoma State University Stillwater, OK 7478 CLI NI CA L RE L E VA N C E Using a randomized crossover design, this study compared the anesthetic and cardiorespiratory effects of three intramuscular anesthetic combinations in seven 2- year-old cats: tiletamine zolazepam (8 mg/kg) and butorphanol (.2 mg/kg) (TT); tiletamine zolazepam (3 mg/kg), butorphanol (.15 mg/kg), and medetomidine (15 µg/kg) (TTD); or the TTD protocol plus atipamezole (75 µg/kg IM) given 2 minutes later to reverse medetomidine. Analgesia was assessed using algometry and needle pricking. All three combinations effectively induced anesthesia suitable for orotracheal intubation within 5 minutes after injection. Hemoglobin oxygen saturation was lower than 9% at least once in all three groups between 5 and 15 minutes after drug administration. Blood pressure and heart and respiratory rates were within normal ranges. Both TT and TTD appeared to be effective injectable anesthetic combinations. TTD provided significantly better analgesia with a longer duration than did TT. Atipamezole administration shortened the duration of analgesia and decreased blood pressure but did not shorten total recovery time. INTRODUCTION Tiletamine zolazepam has been used alone or in combination with other anesthetic agents in cats. 1 8 One particular combination, tiletamine This project was funded by a research grant from Fort Dodge Animal Health, Overland Park, Kansas. zolazepam, ketamine, and xylazine, has been widely used in cats since its introduction in 1992. 6 8 With the advancement of α 2 agonist development, xylazine is less commonly used in small animals today and has gradually been replaced by medetomidine. In a study in cats, 9 the 16

J. C. H. Ko, L. A. Abbo, A. B. Weil, B. M. Johnson, and M. Payton MATERIALS AND METHODS This study was approved by the Purdue University Animal Care and Use Committee. Seven 2-year-old cats (three females and four males; mean body weight: 6.2 ± 1.1 kg) were used in this randomized, crossover study, with each cat receiving three IM drug combinations: TT: Tiletamine zolazepam (Telazol, Fort Dodge Animal Health; 8 mg/kg) and butorphanol (Torbugesic, Fort Dodge Animal Health;.2 mg/kg) TTD: Tiletamine zolazepam (3 mg/kg), butorphanol (.15 mg/kg), and medetomidine (Domitor, Pfizer Animal Health; 15 µg/kg) TTDA: Tiletamine zolazepam (3 mg/kg), butorphanol (.15 mg/kg), and medetomidine (15 µg/kg) followed by atipamezole (Antisedan, Pfizer Animal Health; 75 µg/kg IM) 2 minutes after TTD administration to reverse medetomidine All three anesthetic combinations rapidly induced sedation anesthesia and lateral recumbency within 3 minutes after administration. combination of medetomidine (8 µg/kg) and ketamine (5 mg/kg) was compared with either tiletamine zolazepam (15 mg/kg) or xylazine (1 mg/kg) and ketamine (1 mg/kg) for ovariohysterectomy; the authors concluded that the medetomidine ketamine combination provided better muscle relaxation and analgesia compared with the other two drug combinations. In another study in cats, 5 a combination of tiletamine zolazepam and butorphanol used for onychectomy was found to prevent epinephrine release for 2 hours and to provide adequate analgesia. The anesthetic and analgesic effects of tiletamine zolazepam in combination with butorphanol and medetomidine is currently unreported in cats. The objectives of this study were to evaluate and compare the anesthetic and cardiorespiratory effects of tiletamine zolazepam butorphanol (TT [Telazol Torbugesic]) and tiletamine zolazepam butorphanol medetomidine (TTD [Telazol Torbugesic Domitor]) in cats. It was hypothesized that TTD would have a longer duration of anesthesia and provide a better quality of analgesia than TT. It was further hypothesized that using atipamezole to reverse medetomidine in the TTD combination would decrease recovery time. Atipamezole was given 2 minutes after TTD administration to allow the residual effects of tiletamine and zolazepam during recovery to be assessed. It was hypothesized that the use of atipamezole 2 minutes after administration of TTD would shorten recovery time without affecting recovery quality; however, medetomidine reversal was expected to negatively affect the quality of analgesia in cats. Lower doses of tiletamine zolazepam and butorphanol were used in the TTD and TTDA groups because of the anticipated augmentation of sedation and analgesia by medetomidine. All drugs were drawn up separately and administered together as a single IM injection. All cats breathed room air throughout each study period. Body temperatures were maintained between 99.9 F and 11.2 F with two water-circulating heating blankets and towels. The washout period between treatments was 2 to 3 weeks. Time from IM injection to lateral recumbency, orotracheal intubation, recovery, sternal 165

TABLE 1. Central Nervous System Depression and Recovery Scoring System Used to Evaluate Cats Score Description Sedation Anesthesia 1 Reduced activity only 2 Mild sedation: mildly aware of the surrounding environment 3 Moderate sedation: eyes droopy, head down, inactive, sternal recumbency, unable to be intubated Recovery Profound sedation anesthesia: no movement, rapid assumption of lateral recumbency with great muscle relaxation and easy intubation 1 Prolonged struggling, unable to stand without assistance, hyperkinesis in response to manual assistance, increased rectal temperature associated with increased struggling resulting in increased metabolism 2 Some struggling, repeated attempts to stand, assistance required to stand, significant instability and inability to maintain balance while walking, some signs of drug hangover 3 Some struggling, some assistance required to stand, ability to maintain balance once standing, minimal signs of drug hangover Resumption of sternal recumbency with minimal struggling, ability to stand and walk with minimal effort, no signs of drug hangover recumbency, and standing and walking (i.e., not just standing and falling back into sternal recumbency) were recorded. Overall quality of sedation anesthesia was scored, as was quality of recovery (Table 1). Orotracheal intubation was achieved without the aid of topical lidocaine application. A semi-rigid polypropylene urinary catheter (1 Fr; Kendall, Mansfield, MA) was used as a stylet. After the stylet was placed in the laryngeal opening, the endotracheal tube was passed through the stylet coaxially. For each study period, baseline heart rate (HR), respiratory rate (RR), indirect systolic arterial blood pressure (SAP), indirect diastolic arterial blood pressure (DAP), indirect mean arterial blood pressure (MAP), and rectal temperature were measured immediately before drug administration. After baseline data (time ) were collected, cats were immediately given the IM drug combination; SAP, DAP, MAP, HR, RR, and electrocardiographic (ECG) rhythm were then recorded at 5- minute intervals until the cat had recovered to sternal recumbency. End-tidal carbon dioxide (ETCO 2 ) was measured using a sidestream capnograph (Passport, Gas Module, Datascope, Mahwah, NJ) with a 5-Fr rubber urinary catheter (Kendall) inserted coaxially into the endotracheal tube until the tip rested in the thoracic inlet; capnographic measurements started immediately after orotracheal intubation and continued until the cat was extubated. Two methods were used to assess analgesia: algometry and pin prick. The use of an algometer for determination of pain thresholds for pressure application in soft tissue, muscles, and joints has been demonstrated in humans 1 and horses. 11 The algometer used in this study (Somedic Algometer type, Somedic Production AB, Stockholm, Sweden) is equipped with a squeeze handle; when the handle is squeezed, two nontraumatizing sensors exert a noxious pressure (expressed in kilopascals [kpa]; device range: to 2, kpa) on the tissue of the patient being evaluated. Before each study, the 166

Systolic Blood Pressure (mm Hg) 18 16 14 12 1 8 6 4 2 16 Overall, Blood Pressure Was Well Maintained in All Groups 5 1 15 2 25 3 35 4 45 5 55 6 65 7 75 8 Time (min) Mean Blood Pressure (mm Hg) 14 12 1 8 6 4 2 Diastolic Blood Pressure (mm Hg) 14 12 1 8 6 4 2 5 1 15 2 25 3 35 4 45 5 55 6 65 7 75 8 Time (min) 5 1 15 2 25 3 35 4 45 5 55 6 65 7 75 8 Time (min) TT TTD TTDA Figure 1. Blood pressure values after IM administration of tiletamine zolazepam butorphanol (TT), tiletamine zolazepam butorphanol medetomidine (TTD), and tiletamine zolazepam butorphanol medetomidine reversed with atipamezole (TTDA) in seven cats. All data are presented as mean ± SEM. Significantly different from other treatment groups. Significantly different from the TTDA group. Significantly different from the TT group. Significantly different from baseline within the treatment group. Significantly different from the 2-minute value within treatment group. 167

algometer was calibrated against a weight to ensure its accuracy. The algometer was applied to a front digit after the cat was anesthetized. As soon as the cat exhibited a sign of pain, including withdrawal of a limb, head lift, or other purposeful movement related to this noxious stimulus, the algometer was released and the pressure recorded. A pin prick with a 22-gauge hypodermic needle was the second method used to assess analgesia. The sequence of needle pricking was front limb along the radial ulnar area followed by the perineal area near the base of the tail. Any gross purposeful movement of the limb or body or constriction of the anus in reaction to the needle pricking was interpreted as lack of analgesia, and the duration of analgesia was recorded. treatments for given time intervals were presented if the overall effect of treatment was significant using a SLICE option in an LSMEANS statement (PROC MIXED). All results are reported as mean ± SEM. RESULTS All three combinations rapidly induced sedation anesthesia and lateral recumbency within 3 minutes after administration (Table 2). No vomiting, myoclonic twitching responses, or other adverse reactions were observed in the time between injection and orotracheal intubation. All cats were intubated with ease within 5 minutes after drug administration, and no laryngeal complications were noted during intubation or recovery despite the fact that the larynx was not desensitized All cats were intubated with ease within 5 minutes after drug administration. Analgesia evaluations occurred immediately after each cardiorespiratory evaluation. All analgesia evaluations occurred in the same order (algometer, then needle prick) at each time point. Statistical Analysis PC SAS (SAS Institute, Cary, NC) was used for all statistical analyses. Analysis of variance techniques (PROC MIXED in SAS, Version 9) were used to assess treatment differences in anesthesia, analgesia, and cardiorespiratory data. When multiple observations were made on the same subject over time, repeated measures models were used with an autoregressive period 1 covariance structure to account for within-subject correlations. Effects of treatments were presented as pairwise t-tests when a significant difference (P <.5) was detected in the analysis of variance. In the case of the repeated measures analyses, simple effects of with lidocaine. There was no significant difference among the three treatment groups in onset of sedation and time from injection to lateral recumbency and intubation. However, the duration of intubation tolerance was significantly shorter in the TTDA group compared with the TTD group. The duration of lateral recumbency, time from injection to resumption of sternal recumbency, and time to resumption of standing and walking were not significantly different between treatment groups (Table 2). The quality of recovery score was significantly lower in the TTDA group than in the TTD group. Baseline SAP, MAP, and DAP were not significantly different between treatment groups. In the TT group, SAP was significantly different from baseline at 5 minutes and DAP was significantly different from baseline at 15 minutes (Figure 1). Overall, blood pressure was 168

J. C. H. Ko, L. A. Abbo, A. B. Weil, B. M. Johnson, and M. Payton TABLE 2. Sedation Anesthesia Variables after IM Administration of Tiletamine Zolazepam Butorphanol (TT), Tiletamine Zolazepam Butorphanol Medetomidine (TTD), and Tiletamine Zolazepam Butorphanol Medetomidine Reversed with Atipamezole (TTDA) in Seven Cats Treatment Variable TT (n = 7) TTD (n = 7) TTDA (n = 7) Time from injection to onset of sedation (min) 1.22 ±.15 1.2 ±.12 1.5 ±.17 Time from injection to sternal recumbency (min) 1.7 ±.29 2.1 ±.2 1.8 ±.18 Time from injection to lateral recumbency (min) 1.89 ±.25 1.97 ±.22 2.1 ±.2 Time from injection to orotracheal intubation (min) 3.36 ±.2 3.23 ±. 3.6 ±.51 Duration of intubation (min) 73.71 ± 5.8 a,b 86.86 ±.83 a 6.86 ± 6.5 b Duration of lateral recumbency (min) 16.1 ± 8.33 121.57 ± 8.27 16.71 ± 18.6 Time from injection to resumption of 17.57 ± 8.27 12.86 ± 12.39 19.3 ± 18.29 sternal recumbency (min) Time from injection to standing and walking (min) 123.29 ± 7.5 139.86 ± 13.2 113.71 ± 17.8 Overall quality of sedation 3.95 ±.1. ±.. ±. Overall quality of recovery 2.63 ±.2 a,b 3.7 ±.28 a 2.7 ±.17 b Data presented as mean ± SEM. A row without superscripts indicates no significant difference between treatment groups. Different superscripts within a row indicate a significant difference between treatment groups (P.5). See Table 1 for scoring system to evaluate sedation and recovery. well maintained, with the lowest MAP of 8.1 ± 6.7 mm Hg occurring 35 minutes after TT administration. There was no significant change in SAP after drug administration in either the TTD or TTDA group. DAP and MAP were higher in the TTD and TTDA groups compared with the TT group after 15 and 2 minutes, respectively. After these times, there was no significant difference between treatment groups. MAP was higher in the TTD group than in the TTDA group at 25 and 3 minutes after drug administration. Atipamezole administration resulted in a significant decrease in DAP (from 17.7 ± 12.6 mm Hg to 58. ± 3. mm Hg) in the TTDA-treated cats 5 minutes after injection. A significantly lower DAP was observed in the TTDA group compared with the TTD group between 25 and 5 minutes (Figure 1). Similarly, atipamezole administration resulted in a lower MAP in the TTDA group than in the TTD group at 25 and 3 minutes (Figure 1). Baseline HR was significantly higher in the TT group than the TTDA group. There was no significant change in HR after drug administration in the TT and TTDA groups over time. HR in the TT group was significantly higher than in the other groups at most time points; however, HR in the TTD group decreased significantly from the baseline rate of 17. ± 6.5 bpm to the lowest mean rate of 125. ±.3 bpm 6 minutes after drug administration (Figure 2). HRs in all three treatment groups were maintained above 125 bpm. 169

25 Heart Rates Remained Above 125 bpm in All Three Groups Heart Rate (bpm) 2 15 1 5 Respiratory Rate (breaths/min) 5 45 4 35 3 25 2 15 1 5 5 1 15 2 25 3 35 4 45 5 55 6 65 7 75 8 Time (min) Respiratory Rates Decreased 5 Minutes After Drug Administration in All Three Groups 5 1 15 2 25 3 35 4 45 5 55 6 65 7 75 8 Time (min) TT TTD TTDA Figure 2. Cardiorespiratory values after IM administration of tiletamine zolazepam butorphanol (TT), tiletamine zolazepam butorphanol medetomidine (TTD), and tiletamine zolazepam butorphanol medetomidine reversed with atipamezole (TTDA) in seven cats. All data are presented as mean ± SEM. Significantly different from other treatment groups. Significantly different from the TTDA group. Significantly different from the TT group. Significantly different from baseline within the treatment group. The ECG of one cat in the TT group displayed a ventricular bigeminy rhythm 8 minutes after TT administration. The arrhythmia subsided within a few seconds and did not return, and the cat recovered from anesthesia uneventfully. By 5 minutes after drug administration and continuing through the end of the experiment, RRs decreased significantly from baseline in all three treatment groups. RRs were significantly higher in the TTD group at 3 minutes, but values were not significantly different ETCO 2 17

J. C. H. Ko, L. A. Abbo, A. B. Weil, B. M. Johnson, and M. Payton TABLE 3. Effects of Anesthesia on End-Tidal Carbon Dioxide (ETCO 2 ) and Hemoglobin Oxygen Saturation as Measured by Pulse Oximetry (SpO 2 ) in cats (n = 7) Tiletamine Tiletamine Tiletamine Zolazepam Zolazepam Butorphanol Time Zolazepam Butorphanol Butorphanol Medetomidine Medetomidine Atipamezole (min) ETCO 2 SpO 2 ETCO 2 SpO 2 ETCO 2 SpO 2 NA 98. ±. a NA 99.1 ±.3 a NA 98.9 ±. a 5 6.6 ± 1.7 85.7 ± 3.1 b 2.9 ± 2.5 88.9 ± 6.5 e.3 ± 1.9 91.3 ± 2.5 a 1 5. ± 1. 85.6 ±.3 b. ± 2. 89.1 ±. d,e 7.3 ±.5 93.7 ± 1.9 a 15 51.1 ± 1.5 86.7 ±.6 b 3.7 ± 2.9 91. ± 2.8 c,d,e 8.9 ± 2.3 92.7 ± 2.5 a 2 5.6 ±.9 92.1 ± 2.1 a. ± 3.6 92.7 ± 1.9 b,c,d,e 9.6 ± 1.9 93.9 ± 2.2 a 25 9.9 ± 1.5 97. ±.9 a 5.3 ±.5 92.7 ± 2.3 b,c,d,e 8.6 ± 1.8 98.3 ± 1. a 3 5. ± 1.8 97.1 ± 1.3 a.3 ±. 9.9 ± 1.8 a,b,c,d 9. ± 1. 9.9 ±.8 a 35 9.6 ± 1.8 98. ±.9 a 7. ± 3.8 92.2 ± 1.7 b,c,d,e 6.9 ± 2.1 96.3 ±.8 a 8.7 ± 1.8 96. ± 1.3 a. ± 5.3 93. ± 1.7 b,c,d,e 6.1 ± 2.2 96. ± 1.1 a 5 7.7 ± 1.7 97.7 ±.8 a 8.6 ± 1.6 9.3 ± 1.3 a,b,c,d,e.3 ± 2. 9.7 ± 1.2 a 5 6.6 ± 1.6 97.3 ± 1.2 a 3.7 ±.5 95.2 ± 1.2 a,b,c,d 5. ± 2.2 96. ±.3 a 55 6.1 ± 1.5 97. ±.9 a 6.6 ± 1.3 96.7 ± 1.5 a,b,c,d. ± 2.1 98. ± 1.2 a 6 5.7 ± 1.8 97.9 ± 1. a. ± 2.5 96.3 ± 1.3 a,b,c,d 2.8 ± 3.3 97.5 ± 1. a 65.6 ± 1.9 99. ±.8 a 5.6 ± 1.3 97.2 ±.7 a,b,c.3 ± 3. 98.3 ±.7 a 7 3.6 ± 2. 98.2 ±.7 a 1.5 ± 2.3 98.3 ±.7 a,b 5. ±. 99. ± 1. a 75 6. ± 1. 1. ±. a. ±.7 97. ± 1.5 a,b,c,d.5 ± 3.5 9.5 ±.5 a 8 5. ±. 1. ±. a.3 ± 1.7 95.3 ± 1.9 a,b,c,d 3.5 ±.5 99. ± 1. a There were no significant differences in ETCO 2 and SpO 2 between treatment groups at each time point. a,b,c,d,e Values with different letters in a given column are significantly different. NA = not applicable. between treatment groups throughout the experiment (Figure 2 and Table 3). At least one SpO 2 (hemoglobin oxygen saturation as measured by pulse oximetry) reading of less than 9% was observed in the initial 1 minutes after administration of TTD and TTDA and in the initial 15 minutes after administration of TT. Thereafter, SpO 2 readings were consistently higher than 9% throughout the study (Table 3). Body temperatures were well maintained in the cats and were not significantly different between treatment groups throughout the study. Atipamezole administration at 2 minutes in the TTDA group did not significantly change HRs and RRs (Figure 2) or ETCO 2 concentrations (Table 3); however, significant reductions in DAP and MAP compared with values at 2 minutes (i.e., when atipamezole was administered) were noted in this group be- 171

Algometric Pressure Digit (kpa) 2, 1,8 1,6 1,4 1,2 1, 8 6 4 2 No Differences in Tolerance to Pressure Were Noted in the First 45 Minutes 5 1 15 2 25 3 35 4 45 5 55 6 65 7 75 8 Time (min) TT TTD TTDA Figure 3. Analgesia evaluation via algometer after IM administration of tiletamine zolazepam butorphanol (TT), tiletamine zolazepam butorphanol medetomidine (TTD), and tiletamine zolazepam butorphanol medetomidine reversed with atipamezole (TTDA) in seven cats. All data are presented as mean ± SEM. Significantly different from other treatment groups. Significantly different from the TTDA group. Significantly different from the TT group. Significantly different from the 5-minute value within the treatment group. ginning at 25 minutes and continuing through 75 minutes. There was no statistically significant difference in time from drug administration to recovery, sternal recumbency, or standing and walking between treatment groups (Table 2), although the TTDA group did show increased signs of central nervous system arousal (including more frequent head lifts and attempts to assume sternal recumbency) minutes after administration of atipamezole compared with the TTD group at the same time point (i.e., 6 minutes after initial TTD administration). These signs of arousal were not indicative of severe agitation. Algometric assessment revealed no difference in tolerance to pressure among treatment groups until 5 minutes after drug administration, at which point the TTD cats had significantly higher levels of analgesia (Figure 3). The TTD group had no significant changes in tolerance to pressure over the 8-minute duration. Starting 25 minutes after atipamezole injection (i.e., 5 minutes after TTD injection) and continuing for an additional 2 minutes (i.e., until 65 minutes after TTD injection), the level of anesthesia was lower in the TTDA group compared with the TTD group. The duration of lack of response to needle pricking on the front limb was similar between treatment groups. The duration of lack of response to needle pricking in the perineum was significantly shorter in the TTDA group beginning 5 minutes after atipamezole administration (Figure ). DISCUSSION This study demonstrated that both the TT and TTD combinations were effective for inducing and maintaining anesthesia and providing analgesia in cats. Cats in both groups as- 172

J. C. H. Ko, L. A. Abbo, A. B. Weil, B. M. Johnson, and M. Payton Analgesia Duration (min) Duration of Lack of Response in the Perineum Was Shorter in the TTDA Group 9 8 7 6 5 4 3 2 1 Front Limb Perineum Anatomic Location TT TTD TTDA Figure 4. Analgesia evaluation via needle prick after IM administration of tiletamine zolazepam butorphanol (TT), tiletamine zolazepam butorphanol medetomidine (TTD), and tiletamine zolazepam butorphanol medetomidine reversed with atipamezole (TTDA) in seven cats. All data are presented as mean ± SEM. Significantly different from other treatment groups. sumed lateral recumbency and allowed orotracheal intubation to be easily accomplished within 5 minutes after drug administration. Occasional vomiting and myoclonic twitching responses have been reported cats following medetomidine administration, 9,12 1 but these responses were not observed in any cat during this study. The use of lidocaine to desensitize the larynx via either direct topical application or an aerosol spray has been reported to facilitate orotracheal intubation in cats. 15,16 Reportedly, aerosol application of lidocaine can induce a degree of tissue edema and cellular damage, and at least 9 seconds are needed for lidocaine application to be effective. 15,16 Our clinical observation indicates that many anesthesia providers do not wait this long before attempting intubation. As a result, the exact effect of lidocaine in facilitating intubation in cats is often questionable in clinical practice. In the current study, orotracheal intubation was achieved without the aid of topical lidocaine by using a semi-rigid plastic catheter as soon as the cats became laterally recumbent. No postanesthetic airway problems were observed in any cat. With the use of TT or TTD combinations, the key components to successful orotracheal intubation in these cats seem to be a semi-rigid plastic catheter and a laryngoscope. In a preliminary clinical study, we compared algometer readings in cats anesthetized with TTD for elective surgical procedures such as onychectomy, ovariohysterectomy, and castration. We found that an algometer reading on the front paws exceeding 85 kpa corresponded to analgesia sufficient for performing these surgical procedures; that is, cats that do not respond to an algometer-induced pressure of 85 kpa or higher would not respond to these surgical stimulations, whereas cats that had readings below 85 kpa would more likely react to surgical tissue manipulations. In the current study, the level of anesthesia analgesia as assessed by algometer was considered to be adequate (algometer readings above 85 kpa) during the first 25 minutes in the TT group, whereas the readings remained above 1, kpa for at least 65 minutes in the TTD group. Medetomidine reversal with atipamezole 2 minutes after TTD administration (TTDA group) resulted in a significant decrease in algometer readings 1 minutes later (i.e., 3 minutes after TTD administration); 2 minutes after atipamezole administration, the algometer reading was less than 85 kpa and remained so until the end of the experiment. This result indicates that medetomidine either directly contributed to or indirectly enhanced the analgesia induced by tiletamine and butorphanol in the TTD combination. Medetomidine provides α 2 receptor mediated analgesia in cats 17,18 and has 173

been shown to augment analgesia in injectable anesthetic combinations in other species. 18,19 In this study, it was hypothesized that the reversal of medetomidine by atipamezole in the TTDA group would shorten recovery time without affecting recovery quality. Our intention was to administer atipamezole 2 minutes after TTD administration to simulate a short surgical procedure and to see if recovery would be shortened after antagonism of medetomidine-induced sedation. Although treatment with atipamezole did not significantly shorten the time for cats to assume sternal recumbency or walking, these cats did show more signs of arousal, including earlier extubation, more head lifting, and increased attempts to assume sternal recumbency, between 6 and 11 minutes compared with the TTDtreated cats. The increased attempts to assume sternal recumbency in the TTDA group, based on the criteria used in this study, were considered to be indicative of a poor recovery. This was reflected in the overall significantly lower recovery score versus the TTD group. Atipamezole administration also reduced the intensity of the analgesia in the TTDA-treated cats, as discussed previously. Based on this information, we recommend that if a short (lasting less than 2 minutes), minimally painful procedure is performed on a cat anesthetized with a TTD combination, the medetomidine can be reversed with atipamezole so that the cat does not have a long duration of profound central nervous system depression. The lack of significant shortening of recovery duration after atipamezole administration may mainly be the result of residual anesthetic or sedative effects of tiletamine zolazepam and butorphanol. This explanation is supported by the similar recovery durations observed in the TTD- and TT-treated cats. In this study, a possible bias might be introduced in the analgesia, recovery, or sedation scoring because the observers were not blinded to which treatment each cat received. In the current study, blood pressure was well maintained in all three treatment groups, with the lowest MAP (83.3 ±.8 mm Hg) occurring 6 minutes after TTDA administration (i.e., minutes after atipamezole administration). The addition of medetomidine significantly increased DAP in the TTD-treated cats compared with the TT group. Medetomidine is known to increase systemic vascular resistance via its α 2 -adrenoceptor activity in cats, 2 which could partially explain the increase in DAP seen in this study. This is further supported by the observation that when atipamezole was admin- The quality of recovery score was significantly lower in the TTDA group than in the TTD group. istered to the TTD-treated cats (TTDA group), DAP significantly decreased from 17.7 ± 12.6 mm Hg to 58. ± 3. mm Hg and remained in this range until the end of the study. HRs were well maintained in cats in all three treatment groups, and an anticholinergic agent was not used. Tiletamine administration has been reported to increase HR in cats, 1 3 and HRs were significantly higher in cats in the TT groups throughout the study compared with cats in the other two groups. One possible explanation for the HRs observed in the TT-treated cats is a higher sympathetic tone induced by the higher dose of tiletamine in the TT group. Medetomidine has been demonstrated to significantly reduce heart rate in cats. 2 The lower HRs observed in the TTD- and TTDA-treated cats were likely a result of medetomidine- and butorphanol-mediated baroreflex and en- 17

J. C. H. Ko, L. A. Abbo, A. B. Weil, B. M. Johnson, and M. Payton hanced vagal activity offsetting a tiletamine-induced sympathomimetic effect. RRs decreased in all three treatment groups after drug administration. All three drug combinations had a significant effect on SpO 2, which significantly decreased from baseline after all treatments. The reduction of SpO 2 in the treated cats may be partially due to hypoventilation because partial pressure of arterial carbon dioxide was slightly higher than normal reported values. In discussing the effects of the drug combinations on RR and SpO 2 it should be noted that the sidestream capnometer used in the study drew a continuous sample of gas from the cat s endotracheal tube. A question was raised whether the sampling rate could be sufficiently high to possibly affect the fraction of inspired oxygen and therefore SpO 2. The sampling rate of the sidestream capnometer was 12 ± 2 ml/min based on the manufacturer s specification. While it is possible to have a negative effect on the fraction of inspired oxygen and SpO 2, we do not think a direct interference from the sidestream capnometer is likely because the SpO 2 was consistently above 92% in the latter part of the experiment and because the rate of gas sampling was constant. Because hypoxia occurred in all three treatment groups, it is advised that 1% oxygen be provided via face mask insufflation or endotracheal intubation. CONCLUSION In conclusion, a single IM injection of TT or TTD induced suitable anesthesia in healthy cats. The anesthetic duration of these combinations was approximately 7 to 9 minutes, with adequate surgical analgesic durations of 25 minutes for TT and 65 minutes for TTD. Cardiorespiratory changes were characterized by well-maintained blood pressure and mild respiratory depression with occasional hypoxia. Reversal of medetomidine with atipamezole was not entirely effective in shortening the total duration of recovery but did allow the cats to become alert somewhat earlier. ACKNOWLEDGMENT The authors thank Constance Nicklin for her technical assistance with this study. REFERENCES 1. Forsyth S: Administration of a low dose tiletamine-zolazepam combination to cats. N Z Vet J 3(3):11 13, 1995. 2. Sendler K, Lendl C, Henke I, et al: Anesthesia in cats using tiletamine/zolazepam in minimal doses [in German]. Tierarztl Prax 22(3):286 29, 199. 3. Hellyer P, Muir WW, Hubbell JA, Sally J: Cardiorespiratory effects of the intravenous administration of tiletamine-zolazepam to cats. Vet Surg 17(2):15 11, 1988.. Faggella AM, Aronsohn MG: Anesthetic techniques for neutering 6- to 1-week-old kittens. JAVMA 22(1):56 62, 1993. 5. Lin HC, Benson GJ, Thurmon JC, et al: Influence of anesthetic regimens on the perioperative catecholamine response associated with onychectomy in cats. Am J Vet Res 5(1):1721 172, 1993. 6. Ko JCH, Thurmon JC, Benson GJ, Tranquilli WJ: An alternative drug combination for use in declawing and castrating cats. Vet Med 88(11):161 165, 1993. 7. Williams LS, Levy JK, Robertson SA, et al: Use of the anesthetic combination of tiletamine, zolazepam, ketamine, and xylazine for neutering feral cats. JAVMA 22(1):191 195, 22. 8. Cistola AM, Golder FJ, Centonze LA, et al: Anesthetic and physiologic effects of tiletamine, zolazepam, ketamine, and xylazine combination (TKX) in feral cats undergoing surgical sterilization. J Feline Med Surg 6(5):297 33, 2. 9. Verstegen J, Fargetton X, Ectors F: Medetomidine/ketamine anaesthesia in cats. Acta Vet Scand Suppl 85:117 123, 1989. 1. Bernhardt O, Schiffman EL, Look JO: Reliability and validity of a new fingertip-shaped pressure algometer for assessing pressure pain thresholds in the temporomandibular joint and masticatory muscles. J Orofac Pain 21(1):29 38, 27. 11. Varcoe-Cocks K, Sagar KN, Jeffcott LB, McGowan CM: Pressure algometry to quantify muscle pain in racehorses with suspected sacroiliac dysfunction. Equine Vet J 38(6):558 562, 26. 12. Granholm M, McKusick BC, Westerholm FC, Aspe- 175

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