The effect of intravenous administration of variable-dose midazolam after fixed-dose ketamine in healthy awake cats

The effects of intravenous administration of variable-dose midazolam and ketamine (3 mg/kg) were studied in twelve healthy unmedicated cats from time of administration until full recovery. A range of midazolam doses (0.0, 0.05, 0.5, 1.0, 2.0 and 5.0 mg/kg) was chosen, so that beneficial and/or detrimental effects could be documented and the therapeutic window for further study determined. One minute after administration of ketamine, all cats had assumed a lateral position, mostly with head up. Muscle tone was increased (100%), apneustic breathing pattern evident in 92% of cats, chewing without stimulation of the oropharyngeal area was observed in most cats (97%), but most cats did not salivate (87%). At 2.5 min after completion of ketamine injection and 1 min after administration of saline, a similar picture was observed, except that salivation was evident. All cats chewed or swallowed in response to a finger or laryngoscope placed in the oropharyngeal area and, while most cats were not aware of a noxious stimulus to the tail, some cats were aware of a noxious stimulus to the paw. Recovery from ketamine alone was rapid and smooth with cats rolling into sternal recumbency and then cautiously walking with ataxia. Recovery to walking without incoordination was also rapid (< 2 h) and no abnormal behavioural patterns were observed during recovery. Administration of midazolam after ketamine, had beneficial effects and the therapeutic window for midazolam was found to lie between 0.05 mg/kg and 0.5 mg/kg. Administration of any dose of midazolam after ketamine caused a greater proportion of cats to assume a laterally recumbent position with head down compared with ketamine alone, however, the time period of recumbency was only significantly longer with a midazolam dose of 2.0 mg/kg or above. Doses of midazolam of 0.5 mg/kg or above decreased muscle rigidity but did not affect salivation or respiratory pattern observed in cats which received ketamine alone. A significantly greater proportion of cats which received ketamine and midazolam 0.5 mg/kg or above did not swallow in response to a finger or a laryngoscope placed in the mouth compared with that which received ketamine alone. The length of time in which cats did not swallow was only significantly longer at midazolam doses of 1.0 mg/kg and above. At midazolam doses of 0.5 mg/kg or above, the proportion of cats without a nociceptive response to a tail or paw clamp was significantly greater than cats which received ketamine alone. The time period without nociceptive response, however, was not influenced by midazolam administration. The time taken for cats which received ketamine and midazolam 0.05 mg/kg or 0.5 mg/kg to assume sternal position, walk with ataxia, walk without ataxia, behave normally when approached or restrained and recover normal arousal state was not significantly different from cats which received ketamine alone. Ketamine and midazolam 5.0 mg/kg significantly prolonged all recovery times compared with ketamine alone. Unfortunately, a greater proportion of cats which received ketamine and midazolam 0.5 or 5.0 mg/kg exhibited detrimental behavioural effects. These were more likely to be adverse and included restlessness, vocalization and difficulty approaching and restraining cats. In this study, an     

The optimal intravenous dose of midazolam after intravenous ketamine in healthy awake cats

The effects of intravenous administration of variable-dose midazolam (0, 0.05, 0.075, 0.1, 0.3 and 0.5 mg/kg) and ketamine (3 mg/kg) were studied in twenty-four healthy unmedicated cats from time of administration until full recovery. End-points were chosen to determine the optimal dose to allow a short period of restraint without noxious stimuli, a short period of restraint with noxious stimuli and endotracheal intubation. Recovery characteristics, as well as undesirable behaviours observed during recovery, were also recorded. The dose of midazolam to achieve lateral recumbency with head down was found to be 0.016 mg/kg in 50% of the population (ED₅₀) and 0.054 mg/kg in 95% (ED₉₅) of the population. A midazolam dose of 0.286 mg/kg was required to prevent conscious perception of a stimulus to the ulnar nerve in 50% of the population and 0.652 mg/kg in 95% of the population. The ED₅₀ and ED₉₅ of midazolam required to prevent swallowing in response to a laryngoscope placed on the back of the tongue were found to be 0.265 mg/kg and 0.583 mg/kg, respectively. The ED₅₀ doses of 0.265 mg/kg for intubation and 0.286 mg/kg for restraint with noxious stimulation were close to the tested dose of 0.3 mg/kg. At that dose, the lack of responses lasted 3.67 ± 2.27 min for laryngoscope and 2.50 ± 2.20 min for ulnar nerve stimulation, with recovery to walking with ataxia taking 41.50 ± 15.18 min and complete recovery taking 3.6 ± 1.3 h. The predominant behavioural pattern during recovery was found to be normal, but some cats also exhibited abnormal behavioural patterns. Nine of the twelve cats exhibited an abnormal arousal state, with 4 being restless and 5 being sedated. Seven of the twelve cats exhibited an abnormal behaviour when approached, with three of the cats being more difficult to approach and four of the cats being easier to approach. Eight of the twelve cats exhibited an abnormal behavioural pattern when restrained, with the cats equally divided between more difficult and easier to restrain. Five of the twelve cats vocalized more during the recovery. The ED₅₀ of 0.042 mg/kg to induce chemical restraint without a noxious stimulus is close to the tested dose of 0.05 mg/kg. At that dose, cats remained lateral with head down for 5.49 ± 4.02 min, took 25.96 ± 5.77 min to walk with ataxia and 1.7 ± 0.4 h for complete recovery. The predominant behavioural patterns during recovery were normal, with several cats exhibiting some abnormal patterns. Two cats were sedated, one cat was more difficult to approach, one cat was easier to restrain and three cats were more vocal.     

Evaluation of the sedative and cardiorespiratory effects of dexmedetomidine,dexmedetomidine-butorphanol,and dexmedetomidine-ketamine in cats

OBJECTIVE: To determine sedative and cardiorespiratory effects of dexmedetomidine alone and in combination with butorphanol or ketamine in cats. DESIGN: Randomized crossover study. ANIMALS: 6 healthy adult cats. PROCEDURES: Cats were given dexmedetomidine alone (10 microg/kg [4.5 mg/lb], IM), a combination of dexmedetomidine (10 microg/kg, IM) and butorphanol (0.2 mg/kg [0.09 mg/lb], IM), or a combination of dexmedetomidine (10 microg/kg, IM) and ketamine (5 mg/kg [2.3 mg/lb], IM). Treatments were administered in random order, with > or = 1 week between treatments. Physiologic variables were assessed before and after drug administration. Time to lateral recumbency, duration of lateral recumbency, time to sternal recumbency, time to recovery from sedation, and subjective evaluation of sedation, muscle relaxation, and auditory response were assessed. RESULTS: Each treatment resulted in adequate sedation; time to lateral recumbency, duration of lateral recumbency, and time to recovery from sedation were similar among treatments. Time to sternal recumbency was significantly greater after administration of dexmedetomidine-ketamine. Heart rate decreased significantly after each treatment; however, the decrease was more pronounced after administration of dexmedetomidine-butorphanol, compared with that following the other treatments. Systolic and diastolic blood pressure measurements decreased significantly from baseline with all treatments; 50 minutes after drug administration, mean blood pressure differed significantly from baseline only when cats received dexmedetomidine and butorphanol. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that in cats, administration of dexmedetomidine combined with butorphanol or ketamine resulted in more adequate sedation, without clinically important cardiovascular effects, than was achieved with dexmedetomidine alone.     

Sedative effects of midazolam and xylazine with or without ketamine and detomidine alone following intranasal administration in Ring-necked Parakeets

OBJECTIVE: To evaluate the effects of intranasal administration of midazolam and xylazine (with or without ketamine) and detomidine and their specific antagonists in parakeets. DESIGN: Prospective study. ANIMALS: 17 healthy adult Ring-necked Parakeets (Psittacula krameri) of both sexes (mean weight, 128.83+/-10.46 g [0.28+/-0.02 lb]). PROCEDURE: The dose of each drug or ketamine-drug combination administered intranasally that resulted in adequate sedation (ie, unrestrained dorsal recumbency maintained for >or=5 minutes) was determined; the onset of action, duration of dorsal recumbency, and duration of sedation associated with these treatments were evaluated. The efficacy of the reversal agents flumazenil, yohimbine, and atipamezole was also evaluated. RESULTS: In parakeets, intranasal administration of midazolam (7.3 mg/kg [3.32 mg/lb]) or detomidine (12 mg/kg [5.45 mg/lb]) caused adequate sedation within 2.7 and 3.5 minutes, respectively. Combinations of midazolam (3.65 mg/kg [1.66 mg/lb]) and xylazine (10 mg/kg [4.55 mg/lb]) with ketamine (40 to 50 mg/kg [18.2 to 22.7 mg/lb]) also achieved adequate sedation. Compared with detomidine, duration of dorsal recumbency was significantly longer with midazolam. Intranasal administration of flumazenil (0.13 mg/kg [0.06 mg/lb]) significantly decreased midazolam-associated recumbency time. Compared with the xylazineketamine combination, duration of dorsal recumbency was longer after midazolam-ketamine administration. Intranasal administration of flumazenil, yohimbine, or atipamezole significantly decreased the duration of sedation induced by midazolam, xylazine, or detomidine, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Intranasal administration of sedative drugs appears to be an acceptable method of drug delivery in Ring-necked Parakeets. Reversal agents are also effective when administered via this route.     

The behaviour of healthy awake cats following intravenous and intramuscular administration of midazolam

The onset of action and behavioural effects following intravenous (i.v.) and intramuscular (i.m.) administration of 0.05, 0.5, 1.0, 2.0 and 5.0 mg/kg of midazolam were studied for 2 h in 20 awake, healthy cats. All cats, except one that received 0.05 mg/kg i.m., showed effects of the drug, whereas no effects were observed in cats administered only the vehicle in which midazolam was dissolved. The onset of action was rapid following both i.v. and i.m. administration, some cats became ataxic, while others assumed positions of sternal or lateral recumbency. Even after administration of the highest dose (5.0 mg/kg), anaesthesia was not induced, with swallowing reflexes and conscious perception of a clamp placed on the tail still present in all cats. An abnormal arousal state was observed in many cats after administration of midazolam. During the first hour, restlessness was more commonly observed, while from 1 to 2 h, sedation was more prominent in cats that received the highest dose. Ataxia occurred in all but one cat, was short-lived in cats that received the lower doses, but still present at 2 h in all cats that received 2.0 and 5.0 mg/kg. Midazolam caused some of the cats to behave differently when approached and restrained compared with behavioural patterns identified prior to administration of the drug. The cats were more likely to behave abnormally following i.v. administration rather than i.m. administration and, for the most part, abnormal behaviour was equally distributed between the two extremes; cats being easier to approach and restrain and cats being more difficult to approach and restrain. Food consumption increased significantly, during the 2 h period, following all i.m. doses and all but the highest (5.0 mg/kg) i.v. dose, with most of the food being consumed in the first hour after administration.     

Anaesthetic and cardiopulmonary effects of intramuscular morphine, medetomidine and ketamine administered to telemetered cats

The quality and duration of anaesthesia, cardiorespiratory effects and recovery characteristics of a morphine, medetomidine, ketamine (MMK) drug combination were determined in cats. Six healthy, adult female cats were administered 0.2 mg/kg morphine sulphate, 60 microg/kg medetomidine hydrochloride, and 5 mg/kg ketamine hydrochloride intramuscularly. Atipamezole was administered intramuscularly at 120 min after MMK administration. Time to lateral recumbency, intubation, extubation and sternal recumbency were recorded. Cardiorespiratory variables and response to a noxious stimulus were recorded before and at 3 min and 10 min increments after drug administration until sternal recumbency. The time to lateral recumbency and intubation were 1.9+/-1.2 and 4.3+/-1.2 min, respectively. Body temperature and haemoglobin saturation with oxygen remained unchanged compared to baseline values throughout anaesthesia. Respiratory rate, tidal volume, minute volume, heart rate, and blood pressure were significantly decreased during anaesthesia compared to baseline values. One cat met criteria for hypotension (systolic blood pressure <90 mmHg). End tidal carbon dioxide increased during anaesthesia compared to baseline values. All but one cat remained non-responsive to noxious stimuli from 3 to 120 min. Time to extubation and sternal recumbency following atipamezole were 2.9+/-1.1 and 4.7+/-1.0 min, respectively. MMK drug combination produced excellent short-term anaesthesia and analgesia with minimal cardiopulmonary depression. Anaesthesia lasted for at least 120 min in all but one cat and was effectively reversed by atipamezole.     

Comparison of intranasal and intramuscular ketamine‐midazolam combination in cats

ObjectiveThe aim of the present study was to compare intranasal (INS) and intramuscular (IM) routes of administration of a ketamine-midazolam combination in cats.Study designRandomized block design.AnimalsTwelve healthy mixed breed cats (six males and six females).MethodsThe drug combination was ketamine (14 mg kg⁻¹) and midazolam (0.5 mg kg⁻¹). In the IM group, drugs were injected into quadratus femoris muscle; in the INS. group, the combination dropped equally into the two nostrils. Pulse and respiratory rates, peripheral haemoglobin oxygen saturation (SpO₂) and rectal temperature were monitored before and at intervals after drug administration. Time to onset and duration of sedation and, during recovery to head up, sternal recumbency and recovery were recorded.ResultsThere were no significant differences between the groups in any time measured except for recovery to sternal recumbency, where time was lower in the INS than in the IM (p = 0.034). Respiratory rate was greater in the INS than in the IM group (p = 0.029), but there was no difference between groups in other physiological parameters. In both groups SpO₂ was low before and fell further during sedation.ConclusionsThe results substantiated that INS ketamine-midazolam can produce effective sedation in cats.Clinical relevanceIntranasal (INS) administration of ketamine-midazolam is atraumatic, and its use may avoid the pain of injection of ketamine combinations when this drug is used to induce sedation in cats.     

Cardiovascular changes associated with anaesthesia induced by medetomidine combined with ketamine in cats

SUMMARY Fifteen cats had anaesthesia induced by intramuscular injection of medetomidine combined with ketamine. By five minutes after drug administration, heart rate had decreased by 31 per cent, respiratory rate had decreased by 70 per cent and systolic blood pressure had increased by 69 per cent. Atipamezole administration was associated with a decrease in systolic blood pressure and an increase in heart and respiratory rates. Time to first head lift was eight minutes and to sternal recumbency 12 minutes after atipamezole administration. Postoperative analgesia was provided by methadone, administered when the cats adopted sternal recumbency.     

Clinical evaluation of intranasal benzodiazepines, alpha-agonists and their antagonists in canaries

OBJECTIVE: To evaluate the effects of intranasal benzodiazepines (midazolam and diazepam), alpha(2)-agonists (xylazine and detomidine) and their antagonists (flumazenil and yohimbine) in canaries. STUDY DESIGN: Prospective randomized study. ANIMALS: Twenty-six healthy adult domesticated canaries of both sexes, weighing 18.3 +/- 1.0 g. METHODS: In Study 1 an attempt was made to determine the dose of each drug that allowed treated canaries to be laid in dorsal recumbency for at least 5 minutes, i.e. its effective dose. This involved the evaluation of various doses, during which equal volumes of the tested drug were administered slowly into each nostril. In study 2 the onset of action, duration and quality of sedation induced by each drug at its effective dose were evaluated. The efficacy of flumazenil and yohimbine in antagonizing the effects of the sedative drugs was also studied. RESULTS: In study 1 administration of 25 microL per nostril diazepam (5 mg mL(-1) solution) or midazolam (5 mg mL(-1) solution) to each bird caused adequate sedation within 1-2 minutes; birds did not move when placed in dorsal recumbency. After administration of 12 microL per nostril of either xylazine (20 mg mL(-1)) or detomidine (10 mg mL(-1)), birds seemed heavily sedated and assumed sternal recumbency but could not be placed in dorsal recumbency. Higher doses of xylazine (0.5 mg per nostril) or detomidine (0.25 mg per nostril) prolonged sedation but did not produce dorsal recumbency. In study 2 in all treatment groups, onset of action was rapid. Duration of dorsal recumbency was significantly longer (p < 0.05) with diazepam (38.4 +/- 10.5 minutes) than midazolam (17.1 +/- 2.2 minutes). Intranasal flumazenil (2.5 microg per nostril) significantly reduced recumbency time. Duration of sedation was longer with alpha(2)-agonists compared with benzodiazepines. Detomidine had the longest duration of effect (257.5 +/- 1.5 minutes) and midazolam the shortest (36.9 +/- 2.4 minutes). Nasally administered flumazenil significantly reduced the duration of sedation with diazepam and midazolam while yohimbine (120 microg per nostril) effectively antagonized the effects of xylazine and detomidine. CONCLUSION: Intranasal benzodiazepines produce rapid and effective sedation in canaries. Intranasal alpha(2) agonists produce sedation but not sustained recumbency. Specific antagonists are also effective when used by this route. Clinical relevance Intranasal sedative drug administration is an acceptable alternative method of drug delivery in canaries.     

Antagonistic activities of atipamezole, 4-aminopyridine and yohimbine against medetomidine/ketamine-induced anaesthesia in cats

The objectives of this trial were to determine the ability of atipamezole, 4-aminopyridine and yohimbine to reverse the anaesthetic effects of a combination of medetomidine and ketamine in cats. Forty healthy cats were anaesthetised with 80 micrograms/kg medetomidine combined with 5 mg/kg ketamine. Thirty minutes later atipamezole (200 or 500 micrograms/kg), 4-aminopyridine (500 or 1000 micrograms/kg) or yohimbine (250 or 500 micrograms/kg) were injected intramuscularly. The doses of antagonists were randomised, so that each dose was administered to five cats, and 10 cats were injected only with physiological saline. Atipamezole clearly reversed the anaesthesia and bradycardia induced by medetomidine and ketamine. The mean (+/- sd) arousal times were 28 (+/- 4.7), 5.8 (+/- 1.8) and 7 (+/- 2.1) minutes in the placebo group, and the groups receiving 200 and 500 micrograms/kg atipamezole, respectively. The heart rates of the cats receiving 200 micrograms/kg atipamezole rapidly returned to values close to the initial ones, but 15 minutes after the injection of 500 micrograms/kg atipamezole a significant tachycardia was observed. All the cats showed moderate signs of ataxia during the recovery period. A dose of 500 micrograms/kg yohimbine also clearly reversed the anaesthetic effects of medetomidine/ketamine but 250 micrograms/kg was not effective. The dose of 500 micrograms/kg allowed a smooth recovery with no particular side effects except for some signs of incomplete antagonism of the ketamine effects, ie, ataxia and muscular incoordination. With 4-aminopyridine there were no statistically significant effects on the recovery, or the heart and respiratory rates of the cats anaesthetised with medetomidine/ketamine.     

Partial antagonization of midazolam-medetomidine-ketamine in cats--atipamezole versus combined atipamezole and flumazenil

Two different methods, administered both subcutaneously and intravenously, to reverse intramuscular midazolam-medetomidine-ketamine, are evaluated. Eighteen cats were anaesthetized twice each 5 min after premedication with atropine 0.04 mg/kg using midazolam 0.5 mg/kg, medetomidine 0.02 mg/kg and ketamine 2.0 mg/kg intramuscularly in one syringe. Because this study was conducted in co-operation with a dental prophylaxis project, cats had to be immobilized for approximately 1 h. Therefore, anaesthesia was prolonged with propofol to effect, if necessary. After 68+/-11 min on average, immobilization was partially reversed by either atipamezole 0.05 mg/kg subcutaneously (group A/SC, n=7) or intravenously (group A/IV, n=10), or by atipamezole 0.05 mg/kg and flumazenil 0.05 mg/kg subcutaneously (group AF/SC, n=10) or intravenously (group AF/IV, n=9), respectively. These four groups were additionally compared with a non-reversed group. Recovery time and total time of immobilization (until cats regained a standing position) were not significantly shortened using the antagonists. However, unconsciousness and sedation (expressed through parameters like the time taken to head lifting, crawling, sitting and the return of righting reflex) were significantly shortened by the antagonists, especially if administered intravenously. Abnormal behaviour, such as vocalization, licking, hyperaesthesia, restlessness or salivation, was observed in all groups. However, excitation and hyperaesthesia were not observed in group AF/IV, whereas in this group only intensified salivation occurred. The addition of flumazenil showed no significant difference to atipamezole alone, but subcutaneous administration of atipamezole alone was not sufficient in the dosage used to show an advantage compared to non-reversed cats.     

Effects of dissociative anesthesia opioid-free protocols combined with local anesthesia,with or without flumazenil or atipamezole postoperatively,for orchiectomy in cats

ObjectiveTo evaluate the anesthetic effects of two drug combinations with local anesthesia, with or without postoperative antagonists, for orchiectomy in cats.Study designProspective, randomized blinded clinical study.AnimalsA total of 64 healthy cats.MethodsCats were assigned to four equal groups: ketamine (5 mg kg^–1) and dexmedetomidine (10 μg kg^–1) were administered intramuscularly (IM), followed postoperatively with intravenous (IV) saline (5 mL; group KDS) or atipamezole (50 μg kg^–1; group KDA); and ketamine (14 mg kg^–1) with midazolam (0.5 mg kg^–1) and acepromazine (0.1 mg kg^–1) IM, with postoperative IV saline (5 mL; group KMAS) or flumazenil (0.1 mg kg^–1; group KMAF). Lidocaine (2 mg kg^–1) was divided between subcutaneous and intratesticular injection. Physiologic variables were recorded at time points during anesthesia. Ketamine rescue dose was recorded. The degree of sedation and the quality of recovery were evaluated postoperatively.ResultsTime to loss of pedal reflex was longer in groups KMAS and KMAF than in groups KDS and KDA (p = 0.010). Total rescue dose of ketamine was higher in KMAS and KMAF than in KDS and KDA (p = 0.003). Heart rate (HR) during anesthesia was higher in KMAS and KMAF than in KDS and KDA (p = 0.001). Times to head up (p = 0.0005) and to sternal recumbency (p = 0.0003) were shorter in KDA than in KDS, KMAS and KMAF. Lower sedation scores were assigned sooner to KDA than KDS, KMAS and KMAF (p < 0.001). Recovery quality scores were good in all groups.Conclusions and clinical relevanceBoth anesthetic protocols allowed the performance of orchiectomy. Groups KMAS and KMAF required higher rescue doses of ketamine before injecting lidocaine. HR and oscillometric systolic pressure were minimally changed in groups KD and tachycardia was recorded in groups KMA. Only atipamezole shortened the anesthetic recovery.     

Anaesthesia with midazolam/medetomidine/fentanyl in chinchillas (Chinchilla lanigera) compared to anaesthesia with xylazine/ketamine and medetomidine/ketamine

We studied four different drug regimes for anaesthetic management in chinchillas and evaluated and compared their cardiovascular and respiratory effects. In this randomized, cross-over experimental study, seven adult chinchillas, five females, two males [515 +/- 70 (SD) g] were randomly assigned to one of the following groups: group 1 [midazolam, medetomidine and fentanyl (MMF), flumazenil, atipamezole and naloxone (FAN); MMF-FAN] received 1.0 mg/kg midazolam, 0.05 mg/kg medetomidine and 0.02 mg/kg fentanyl i.m., and for reversal 0.1 mg/kg flumazenil, 0.5 mg/kg atipamezole and 0.05 mg/kg naloxone s.c. after 45 min; group 2 (MMF) 1.0 mg/kg midazolam, 0.05 mg/kg medetomidine and 0.02 mg/kg fentanyl i.m.; group 3 [xylazine/ketamine (X/K)] 2.0 mg/kg xylazine and 40.0 mg/kg ketamine i.m.; and group 4 [medetomidine/ketamine (M/K)] 0.06 mg/kg medetomidine and 5.0 mg/kg ketamine i.m. Reflexes were judged to determine anaesthetic stages and planes. Anaesthesia with X/K and M/K was associated with a prolonged surgical tolerance and recovery period. By reversing MMF, recovery period was significantly shortened (5 +/- 1.3 min versus 40 +/- 10.3 min in MMF without FAN, 73 +/- 15.0 min in X/K, and 31 +/- 8.5 min in M/K). Without reversal, MMF produced anaesthesia lasting 109 +/- 16.3 min. All combinations decreased respiratory and heart rate but compared with X/K and M/K, respiratory and cardiovascular complications were less in the MMF groups. Focussing on the clinical relevance of the tested combinations, completely reversible anaesthesia showed two major advantages: anaesthesia can be antagonized in case of emergency and routinely shortens recovery. In small animals particularly these advantages lead to less complications and discomfort and thus often can be lifesaving. As all analgesic components (medetomidine and fentanyl) are reversed, postoperative analgesia should be provided before reversal of anaesthesia.     

A combination of methotrimeprazine, midazolam and guaiphenesin, with and without ketamine, in an anaesthetic procedure for horses.

A combination of 0.5 mg/kg of methotrimeprazine, 0.1 mg/kg of midazolam and 100 mg/kg of a 10 per cent guaiphenesin solution was investigated for the induction of recumbency in 15 horses; the addition of 1.6 mg/kg of ketamine was also evaluated in 15 horses and anaesthesia was maintained with halothane in oxygen. The horses became recumbent quickly and smoothly and they recovered quietly, with little ataxia. Tachycardia occurred after induction, but no other changes from pre-operative values were observed until halothane in oxygen had been given, when hypothermia, hypotension, bradypnoea, hyperoxaemia, respiratory acidosis and decreased respiratory minute volume developed. Horses given ketamine in addition to methotrimeprazine, midazolam and guaiphenesin were easier to intubate and recovered more quickly than horses receiving only methotrimeprazine, midazolam and guaiphenesin.     

Induction of Anesthesia with Diazepam-Ketamine and Midazolam-Ketamine in Greyhounds

Anesthesia was induced in 14 greyhounds with a mixture of diazepam or midazolam (0.28 mg/kg) and ketamine (5.5 mg/kg), and maintained with halothane. There were no significant differences in weight, age, or duration of anesthesia between the treatment groups. Time to intubation with diazepam-ketamine (4.07 +/- 1.43 min) was significantly longer than with midazolam-ketamine (2.73 +/- 0.84 min). Heart rate, respiratory rate, PaCO2, and arterial pH did not vary significantly during anesthesia in either treatment group. Arterial blood pressures, PaO2, halothane vaporizer setting, and body temperature changed significantly from baseline values in both treatment groups during anesthesia. Times to sternal recumbency and times to standing were not significantly different. These data suggest that both diazepam-ketamine and midazolam-ketamine are useful anesthetic combinations in greyhounds. In combination with ketamine, midazolam offers little advantage over diazepam.     

Clinical assessment of repeated propofol-associated anesthesia in cats

OBJECTIVE: To assess the effects of repeated episodes of propofol-associated anesthesia on quality of recovery from anesthesia, clinical status, and erythrocyte physiology in cats. DESIGN: Original study. ANIMALS: 37 cats undergoing short-duration anesthesia for radiotherapy. PROCEDURES: Twice daily on 5 consecutive days, 13 cats with squamous cell carcinoma of the nasal planum (group 1) underwent anesthesia: first via administration of propofol or a midazolam (0.2 mg/kg [0.09 mg/lb])-propofol combination and then via administration of ketamine and midazolam each day (latter data were not analyzed). During a 19-day period, 24 cats with vaccine associated sarcoma (group 2) were anesthetized 12 times with propofol or a midazolam-propofol combination. Anesthesia was maintained with propofol in both groups. Hematologic analysis was performed before, during, and on completion of radiotherapy; changes in Hct and hemoglobin concentration between groups were compared. RESULTS: Mean duration of anesthesia was 8.1 minutes (range, 5 to 20 minutes); no adverse events were detected during recovery. Total dose of propofol administered did not differ between groups 1 (6.34 mg/kg [2.88 mg/lb]) and 2 (4.71 mg/kg [2.14 mg/lb]). Midazolam administration decreased the propofol dose by 26%. Overall decreases from baseline in Hct and hemoglobin concentration were not significantly different between the 2 groups, nor clinically important; however, compared with baseline, values in group 2 were significantly lower after 6 and 12 anesthetic episodes for both protocols. Heinz bodies were identified in low numbers in both groups during radiotherapy. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that repeated propofol-associated short-duration anesthesia does not lead to clinically relevant hematologic changes in cats undergoing short-duration radiotherapy.     

Pharmacokinetics and effects of alfaxalone after intravenous and intramuscular administration to cats

AIMS: To determine the pharmacokinetics, and anaesthetic and sedative effects of alfaxalone after I/V and I/M administration to cats.

METHODS: Six European shorthair cats, three males and three females, with a mean weight of 4.21 (SD 0.53) kg and aged 3.8 (SD 0.9) years were enrolled in this crossover, two–treatment, two-period study. Alfaxalone at a dose of 5?mg/kg was administered either I/V or I/M. Blood samples were collected between 2–480 minutes after drug administration and analysed for concentrations of alfaxalone by HPLC. The plasma concentration-time curves were analysed by non-compartmental analysis. Sedation scores were evaluated between 5–120 minutes after drug administration using a numerical rating scale (from 0–18). Intervals from drug administration to sit, sternal and lateral recumbency during the induction phase, and to head-lift, sternal recumbency and standing position during recovery were recorded.

RESULTS: The mean half-life and mean residence time of alfaxalone were longer after I/M (1.28 (SD 0.21) and 2.09 (SD 0.36) hours, respectively) than after I/V (0.49 (SD 0.07) and 0.66 (SD 0.16) hours, respectively) administration (p<0.05). Bioavailability after I/M injection of alfaxalone was 94.7 (SD 19.8)%. The mean intervals to sternal and lateral recumbency were longer in the I/M (3.73 (SD 1.99) and 6.12 (SD 0.90) minutes, respectively) compared to I/V (0 minutes for all animals) treated cats (p<0.01). Sedation scores indicative of general anaesthesia (scores >15) were recorded from 5–15 minutes after I/V administration and deep sedation (scores 11–15) at 20 and 30 minutes. Deep sedation was observed from 10–45 minutes after I/M administration. One cat from each group showed hyperkinesia during recovery, and the remainder had an uneventful recovery.

CONCLUSIONS AND CLINICAL RELEVANCE: Alfaxalone administered I/V in cats provides rapid and smooth induction of anaesthesia. After I/M administration, a longer exposure to the drug and an extended half life were obtained compared to I/V administration. Therefore I/M administration of alfaxalone could be a reliable, suitable and easy route in cats, taking into account that alfaxalone has a slower onset of sedation than when given I/V and achieves deep sedation rather than general anaesthesia.     

A comparison of two intramuscular doses of xylazine-ketamine combination and tolazoline reversal in llamas

OBJECTIVE: To evaluate the anesthetic and cardiorespiratory effects of two doses of intramuscular xylazine/ketamine in llamas, and to determine if an intramuscular injection of tolazoline would shorten the anesthesia recovery time. STUDY DESIGN: Prospective randomized study. ANIMALS: Six castrated male llamas. METHODS: Each llama received a low dose (LD) (0.4 mg kg(-1) xylazine and 4 mg kg(-1) ketamine) and high dose (HD) (0.8 mg kg(-1) xylazine and 8 mg kg(-1) ketamine). Time to sedation, duration of lateral recumbency and analgesia, pulse, respiratory rate, hemoglobin oxygen saturation, arterial blood pressure, blood gases, and the electrocardiogram were monitored and recorded during anesthesia. Three llamas in each treatment were randomized to receive intramuscular tolazoline (2 mg kg(-1)) after 30 minutes of lateral recumbency. RESULTS: Onset of sedation, lateral recumbency, and analgesia was rapid with both treatments. The HD was able to provide at least 30 minutes of anesthesia in all six llamas. The LD provided only 30 minutes of anesthesia in two out of six llamas. Respiratory depression and hypoxemia were seen in the HD treatment during the first 10 minutes of lateral recumbency. Two llamas were severely hypoxemic during this period and were given nasal oxygen for five minutes. Heart rate decreased, but there were no significant changes in blood pressure. Tolazoline significantly shortened the duration of recumbency in the HD treatment. CONCLUSIONS: The HD provided more consistent clinical effects in llamas than did the LD. Intramuscular tolazoline shortens the duration of lateral recumbency in llamas anesthetized with this combination. CLINICAL RELEVANCE: Both doses appear to be very effective in providing restraint in llamas. The LD may be used for procedures requiring a short period of anesthesia or restraint. The HD could be used when a longer duration of anesthesia is desired. Supplemental oxygen should be available if using the HD. Tolazoline (IM) shortened the recovery time with this combination in llamas.     

Clinical evaluation of Alfaxan-CD® as an intravenous anaesthetic in young cats

Objective   To describe and evaluate the use of Alfaxan-CD ® as an intravenous anaesthetic in young cats.
Design   Thirty-five Domestic Short-hair cats aged from 3 to 12 months were admitted into the University Veterinary Teaching Hospital-Sydney for elective surgery. Anaesthesia was induced with Alfaxan-CD® and maintained with isoflurane: 22 cats received no premedication and 13 cats received acepromazine (0.03 mg/kg) and butorphanol (0.3 mg/kg) subcutaneously 30 min prior to induction.
Qualitative and quantitative data for induction and recovery were recorded. Physiological parameters were recorded at 0, 2 and 5 min post induction, and every 5 min thereafter until the end of the procedure.
Results   Intravenous injection of Alfaxan-CD® resulted in rapid induction of anaesthesia with a mean time to intubation of 122 s. The mean dose of Alfaxan-CD® used was 4.2 mg/kg in unpremedicated cats and 2.7 mg/kg in premedicated cats. All cats maintained a heart rate above 95 beats/min. No cat developed hypoxaemia. Hypercapnoea was detected in 4 cats and hypotension was observed in 18 cats. Time to extubation ranged from 1 to 9 min. The mean time to sternal recumbency for premedicated cats was 11 min; 77% of premedicated cats and 23% of unpremedicated cats had a recovery score of 1 or 2.
Conclusion   Alfaxan-CD® is an effective anaesthetic agent in young healthy cats, providing a smooth induction and rapid recovery. Cats that were premedicated with acepromazine and butorphanol prior to induction with Alfaxan-CD® had better recovery scores than those that were not premedicated.     

Evaluation of Three Midazolam-Xylazine Mixtures Preliminary Trials in Dogs

The depressant effects of midazolam and xylazine on the central nervous system (CNS) were evaluated in 12 dogs. Xylazine was administered to six dogs (1.1 mg/kg intravenously [IV]) followed in 5 minutes by midazolam (1.0 mg/kg intramuscularly [IM]). In a second group of six dogs, xylazine (2.2 mg/kg IM) was followed in 5 minutes by midazolam (1.0 mg/kg IV). Both drug regimens induced rapid and profound sedation or anesthesia. Duration of action varied with the doses and routes of administration. Dogs given the high dose of xylazine IM had an arousal time of 95.4 +/- 8.9 minutes and a walking time of 155.4 +/- 8.8 minutes. These values exceeded the IV xylazine values threefold. Partial reversal of CNS depression was accomplished with either a benzodiazepine antagonist (flumazenil) or an alpha-2 antagonist (yohimbine). In a separate trial, a mixture of xylazine (0.55 mg/kg), midazolam (1.0 mg/kg), and butorphanol (0.1 mg/kg) with and without glycopyrrolate was evaluated in eight dogs. As with the xylazine-midazolam combinations, the CNS depressant effect of this mixture was clinically indistinguishable from anesthesia achieved with other rapid-acting injectable agents. Clinical signs of CNS depression were readily and completely antagonized by the simultaneous injection of flumazenil and yohimbine.