The sedative effects of low-dose medetomidine and butorphanol alone and in combination intravenously in dogs

ObjectiveTo evaluate the sedative effects of intravenous (IV) medetomidine (1 μg kg^?1) and butorphanol (0.1 mg kg^?1) alone and in combination in dogs.Study designProspective, blinded, randomized clinical trial.AnimalsSixty healthy (American Society of Anesthesiologists I) dogs, aged 6.2 ± 3.2 years and body mass 26 ± 12.5 kg.MethodsDogs were assigned to four groups: Group S (sodium chloride 0.9% IV), Group B (butorphanol IV), Group M (medetomidine IV) and Group MB (medetomidine and butorphanol IV). The same clinician assessed sedation before and 12 minutes after administration using a numerical scoring system in which 19 represented maximum sedation. Heart rate (HR), respiratory rate, pulse quality, capillary refill time and rectal temperature were recorded after each sedation score assessment. Sedation scores, sedation score difference (score after minus score before administration) and patient variables were compared using one-way anova for normally distributed variables and Kruskal–Wallis test for variables with skewed distributions and/or unequal variances. Where significance was found, further evaluation used Bonferroni multiple comparisons for pair-wise testing.ResultsBreed, sex, neuter status, age and body mass did not differ between groups. Sedation scores before substance administration were similar between groups (p = 0.2). Sedation scores after sedation were significantly higher in Group MB (mean 9.5 ± SD 5.5) than in group S (2.5 ± 1.8) (p < 0.001), group M (3.1 ± 2.5) (p < 0.001) and group B (3.7 ± 2.0) (p = 0.003). Sedation score difference was significantly higher in Group MB [7 (0–13)] than in Group S [0 (?1 to 4)] (p < 0.001) and Group M [0 (0–6)] (p < 0.001). HR decreased significantly in Groups M and MB compared with Group S (p < 0.05).Conclusion and clinical relevanceLow-dose medetomidine 1 μg kg^?1 IV combined with butorphanol 0.1 mg kg^?1 IV produced more sedation than medetomidine or butorphanol alone. HR was significantly decreased in both medetomidine groups.     

Anaesthesia with medetomidine,midazolam and ketamine in six gorillas after premedication with oral zuclopenthixol dihydrochloride

ObjectiveTo evaluate the effects of medetomidine, midazolam and ketamine (MMK) in captive gorillas after premedication with oral zuclopenthixol.Study designCase series.AnimalsSix gorillas, two males and four females, aged 9–52 years and weighing 63–155 kg.MethodsThe gorillas were given zuclopenthixol dihydrochloride 0.2 ± 0.05 mg kg^?1 per os twice daily for 3 days for premedication. On the day of anaesthesia the dose of zuclopenthixol was increased to 0.27 mg kg^?1 and given once early in the morning. Anaesthesia was induced with medetomidine 0.04 ± 0.004 mg kg^?1, midazolam 0.048 ± 0.003 mg kg^?1 and ketamine 4.9 ± 0.4 mg kg^?1 intramuscularly (IM). Upon recumbency, the trachea was intubated and anaesthesia was maintained on 1–2% isoflurane in oxygen. Physiological parameters were monitored every 10 minutes and arterial blood gas analysis was performed once 30–50 minutes after initial darting. At the end of the procedure, 42–115 minutes after initial darting, immobilisation was antagonized with atipamezole 0.21 ± 0.03 mg kg^?1 and sarmazenil 5 ± 0.4 μg kg^?1 IM.ResultsRecumbency was reached within 10 minutes in five out of six animals. One animal required two additional darts before intubation was feasible. Heart rate ranged from 60 to 85 beats minute^?1, respiratory rate from 17 to 46 breaths minute^?1 and temperature from 36.9 to 38.3 °C. No spontaneous recoveries were observed and anaesthetic level was stable. Blood gas analyses revealed mild respiratory acidosis, and mean PaO₂ was 24.87 ± 17.16 kPa (187 ± 129 mmHg) with all values being above 13.4 kPa (101 mmHg). Recovery was smooth and gorillas were sitting within 25 minutes.Conclusion and clinical relevanceThe drug combination proved to be effective in anaesthetizing captive gorillas of various ages and both sexes, with minimal cardio-respiratory changes.     

Effects of medetomidine,l‐methadone,and their combination on arterial blood gases in dogs

ObjectiveTo investigate the influence of l–methadone on medetomidine–induced changes in arterial blood gases and clinical sedation in dogs.Study designProspective experimental cross–over study (Latin square design).AnimalsFive 1–year–old purpose bred laboratory beagle dogs of both sexes.MethodsEach dog was treated three times: medetomidine (20 μg kg^?1 IV), l–methadone (0.1 mg kg^?1 IV) and their combination. Arterial blood was collected for blood gas analysis. Heart and respiratory rates were recorded, and clinical sedation and reaction to a painful stimulus were scored before drug administration and at various time points for 30 minutes thereafter.ResultsArterial partial pressure of oxygen decreased slightly after medetomidine administration and further after medetomidine/l–methadone administration (range 55.2–86.7 mmHg, 7.4–11.6 kPa, at 5 minutes). A slight increase was detected in arterial partial pressure of carbon dioxide after administration of l–methadone and medetomidine/l–methadone (42.6 ± 2.9 and 44.7 ± 2.4 mmHg, 5.7 ± 0.4 and 6.0 ± 0.3 kPa, 30 minutes after drug administration, respectively). Arterial pH decreased slightly after administration of l–methadone and medetomidine/l–methadone. Heart and respiratory rates decreased after administration of medetomidine and medetomidine/l–methadone, and no differences were detected between the two treatments. Most dogs panted after administration of l–methadone and there was slight sedation. Medetomidine induced moderate or deep sedation, and all dogs were deeply sedated after administration of medetomidine/l–methadone. Reaction to a noxious stimulus was strong or moderate after administration of methadone, moderate or absent after administration of medetomidine, and absent after administration of medetomidine/l–methadone.Conclusions and clinical relevanceAt the doses used in this study, l–methadone potentiated the sedative and analgesic effects and the decrease in arterial oxygenation induced by medetomidine in dogs, which limits the clinical use of this combination.     

Effects of medetomidine and medetomidine-butorphanol combination on Schirmer tear test 1 readings in dogs

Medetomidine is a commonly used sedative in veterinary medicine whether administered alone or in combination with an opioid such as butorphanol. There are no previous studies that look at the effects of this drug on sequential Schirmer tear test (STT) 1 readings in dogs, including effects on tear production after reversal of the drug. The present study looked at two groups of 10 dogs each that were sedated with intravenous medetomidine or a combination of medetomidine and butorphanol. All dogs had tear readings taken presedation, 15 min postsedation, and 15 min after reversal of medetomidine with atipamezole. Results revealed that intravenous sedation with medetomidine and medetomidine-butorphanol in dogs with no history of ophthalmic disease and presedation STT 1 readings above 15 mm/min, causes a significant decrease in tear production that is measurable at 15 min postsedation. Readings returned to near presedation values within 15 min postreversal in most cases. It is therefore recommended that all eyes be treated with a tear substitute from the time the sedative is given until at least 15 min after reversal.     

Sedative and analgesic effects of medetomidine in beagle dogs infected and uninfected with heartworm

The sedative and analgesic effects of medetomidine were evaluated in heartworm-infected (HW+) and uninfected (HW–) beagle dogs by intravenous (IV) and intramuscular (IM) administration of 30 µg/kg and 40 µg/kg doses, respectively. Posture, response to noise and the pedal reflex were monitored. A procedure for mock radiographic positioning was performed to evaluate its overall clinical use. Observation times were 0, 15, 30, 60, 90, 120 and 180 min. In addition, the times from injection until the dog could not stand on its feet (down time), from lateral to sternal recumbency (sternal recumbency time), and from sternal recumbency to rising again (rising time) were also noted.Medetomidine produced rapid sedation and analgesia by both routes. Down times for the IM and IV routes were similar, which verified the manufacturer's recommended doses. The HW+ dogs had shorter down times, probably owing to increased blood flow to the brain caused by adrenergic alpha-2 activity. Sternal recumbency and rising times did not differ between the groups, suggesting a similar metabolism. Sedation and analgesia were adequate for performing the procedure in all dogs. HW– dogs showed less resistance to handling during the procedure than HW+ dogs. Overall, medetomidine seems to be a suitable agent for short-term chemical restraint in dogs, even with subclinical heartworm infestation.     

The effects of medetomidine hydrochloride on the electroretinogram of normal dogs

Purpose  To determine the effects of a standardized intravenous dose of an α-2 agonist (Domitor^®, Orion Pharma, distributed by Pfizer Animal Health, Exton, PA) on the electroretinogram (ERG) response in normal dogs.
Methods  Twenty-five normal dogs were used to collect ERG responses including a- and b-wave implicit times (IT) and amplitudes (AMP) before and after administration of medetomidine. Dogs were dark adapted for 20 min and ERGs were obtained using the HMsERG (RetVetCorp Inc., Columbia, MO). The QuickRetCheck protocol (Narfström) was employed to provide the following flash intensities: 10 mcd s/m², 3 cd s/m², and 10 cd s/m². ERGs were repeated after 375 µg/m² of medetomidine intravenously. Statistical analysis of the difference between the responses before and after medetomidine at all flash intensities was performed using a mixed effects model for anova .
Results  The P value for the effect of medetomidine on each of the ERG responses was < 0.01. The estimates of the effect of medetomidine were (+)1.35 ms, (–)23 µV, (+)3.16 ms, and (–)47 µV for the a-wave IT, a-wave AMP, b-wave IT, and the b-wave AMP, respectively.
Conclusions  Medetomidine significantly prolongs the implicit time and lowers the amplitude response of both the a- and b-waves in normal dogs at all flash intensities examined. Clinically, however, medetomidine only minimally affects the retinal responses and is a viable choice for use in dog ERGs.     

Evaluation of urine specific gravity as a predictor of hypotension during anaesthesia in healthy dogs premedicated with dexmedetomidine

ObjectiveTo investigate the relationship between urine specific gravity (USG) and the risk of arterial hypotension during general anaesthesia (GA) in healthy dogs premedicated with dexmedetomidine and methadone.Study designProspective clinical cohort study.AnimalsA total of 75 healthy client-owned dogs undergoing GA for elective tibial plateau levelling osteotomy.MethodsAfter placing an intravenous catheter, dogs were premedicated with dexmedetomidine (5 μg kg^–1) and methadone (0.3 mg kg^–1) intravenously. After induction of GA with alfaxalone to effect, the bladder was expressed and USG measured. An arterial catheter was placed, and residual blood was used to measure packed cell volume (PCV) and total protein (TP). GA was maintained with isoflurane vaporised in oxygen and a femoral and sciatic nerve block were performed. Arterial blood pressure < 60 mmHg was defined as hypotension and recorded by the anaesthetist. Treatment for hypotension was performed in a stepwise manner following a flow chart. Frequency of hypotension, treatment and response to treatment were recorded. Logistic regression modelling was used to assess the association between USG, TP and PCV and incidence of perioperative hypotension; p < 0.05.ResultsData from 14 dogs were excluded. Of the 61 dogs, 16 (26%) were hypotensive during GA, 15 dogs needed treatment of which 12 were responsive to a decrease in inhalant vaporiser setting. The logistic regression model was not statistically significant (p = 0.8). There was no significant association between USG (p = 0.6), TP (p = 0.4), PCV (p = 0.8) and arterial hypotension during GA.Conclusions and clinical relevanceIn healthy dogs premedicated with dexmedetomidine and methadone and maintained under GA with isoflurane and a femoral and sciatic nerve block, there was no relationship between the specific gravity of urine collected after premedication and intraoperative arterial hypotension.     

Effects of medetomidine and xylazine on intraocular pressure and pupil size in healthy Beagle dogs

ObjectiveTo determine the effects of intramuscular (IM) administration of medetomidine and xylazine on intraocular pressure (IOP) and pupil size in normal dogs.Study designProspective, randomized, experimental, crossover trial.AnimalsFive healthy, purpose-bred Beagle dogs.MethodsEach dog was administered 11 IM injections of, respectively: physiological saline; medetomidine at doses of 5, 10, 20, 40 and 80 μg kg⁻¹, and xylazine at doses of 0.5, 1.0, 2.0, 4.0 and 8.0 mg kg⁻¹. Injections were administered at least 1 week apart. IOP and pupil size were measured at baseline (before treatment) and at 0.25, 0.50, 0.75, 1, 2, 3, 4, 5, 6, 7, 8 and 24 hours post-injection.ResultsA significant decrease in IOP was observed at 6 hours after 80 μg kg⁻¹ medetomidine compared with values at 0.25 and 0.50 hours, although there were no significant changes in IOP from baseline. In dogs treated with 8.0 mg kg⁻¹ xylazine, significant reductions in IOP were observed at 4 and 5 hours compared with that at 0.25 hours after administration. In dogs treated with 5, 10, 20 and 40 μg kg⁻¹ medetomidine and 0.5, 1.0 and 2.0 mg kg⁻¹ xylazine, there were no significant changes in IOP. Pupil size did not change significantly after any of the medetomidine or xylazine treatments compared with the baseline value.Conclusions and clinical relevanceLow or moderate doses of medetomidine or xylazine did not induce significant changes in IOP or pupil size. In contrast, high doses of medetomidine or xylazine induced significant changes up to 8 hours after treatment, but values remained within the normal canine physiological range. The results of this study suggest a lack of significant change in IOP and pupil size in healthy dogs administered low or moderate doses of xylazine or medetomidine.     

The suitability of medetomidine sedation for intradermal skin testing in dogs

The objective of this study was to determine the suitability of medetomidine sedation for facilitating intradermal skin testing in dogs. Quality of sedation and immobilization, and effects of sedation on responses to intradermally injected histamine were evaluated. Ten clinically normal dogs were injected intradermally before and after medetomidine sedation (10 μg kg^?1 intravenously) with diminishing concentrations of histamine (100–10^?5μg mL^?1) and a negative control. Mean wheal responses at injection sites were compared before and during sedation, and no significant suppression of responses occurred during sedation. Medetomidine produced sedation that notably increased the ease of performing multiple intradermal injections in all dogs and sedative effects were rapidly reversed by the antagonist atipamezole. It was concluded that medetomidine may be an excellent sedative for facilitating intradermal skin testing in dogs provided further studies similarly reveal no inhibition of responses to intradermally injected allergens in atopic dogs.     

Evaluation of butorphanol, medetomidine and midazolam as a reversible narcotic combination in free-ranging African lions (Panthera leo)

ObjectiveTo evaluate the effects of the combination butorphanol, medetomidine and midazolam (BMM) and its reversibility in lions.Study designProspective clinical trial.AnimalsThirty free-ranging lions, 10 male and 20 female, weighing 81-210 kg.MethodsLions were immobilised with butorphanol mean 0.31 ± SD 0.034 mg kg^?1, medetomidine 0.052 ± 0.006 mg kg^?1, midazolam 0.21 ± 0.024 mg kg^?1 and hyaluronidase 1250 IU administered intramuscularly with a dart gun. Upon recumbency, physiological parameters and anaesthetic depth were monitored 10-15 minutes after darting (T1) and repeated every 10 minutes for a further 30 minutes (T2, T3, T4). Arterial blood gas analyses were performed at T1 and T4. At the end of the procedure, 45-60 minutes after initial darting, immobilisation was reversed with naltrexone 0.68 ± 0.082 mg kg^?1, atipamezole 0.26 ± 0.031 mg kg^?1, and flumazenil 0.0032 ± 0.0007 mg kg^?1 administered intravenously and subcutaneously.ResultsThe BMM combination rapidly induced immobilisation and lateral recumbency was reached within 7.25 ± 2.3 minutes. Median induction score [scored 1 (excellent) to 4 (poor)] was 1.4 (range 1-2). Cardio-respiratory parameters were stable. Heart rate varied from 32 to 72 beats per minute, respiratory rate from 14 to 32 breaths minute^?1 and rectal temperature from 36.6 to 40.3 °C. No sudden arousals were observed. Arterial blood gas analyses revealed a mean pH of 7.33, PaCO₂ of 33 mmHg and PaO₂ of 87 mmHg. Mild to moderate hypoxemia was seen in four lions. Recovery was smooth and lions were walking within 4.4 ± 4.25 minutes. Median recovery score [scored 1 (excellent) to 4 (poor)] was 1.3 (range 1-2).Conclusion and clinical relevanceThe drug combination proved to be effective in immobilising free-ranging healthy lions of both sexes with minimal cardio-respiratory changes.     

Thermographic imaging of superficial temperature in dogs sedated with medetomidine and butorphanol with and without MK‐467 (L‐659’066)

ObjectiveTo record, with a thermal camera, peripheral temperature changes during different sedation protocols and to relate the results to changes in the rectal temperature.Study designRandomized crossover part-blinded experimental study.AnimalsEight healthy purpose-bred neutered Beagles (two females and six males) weight 14.5 ± 1.6 kg (mean ± SD) and aged 3–4 years.MethodsEach dog was sedated four times. Treatments were medetomidine 20 μg kg^?1 and butorphanol 0.1 mg kg^?1 (MB) with or without MK-467 500 μg kg^?1 (MK). Both drug combinations were administered IV and IM as separate treatments. A thermal camera (T425, FLIR) with a resolution of 320 by 240 was used for imaging.The dogs were placed in lateral recumbency on an insulated mattress. Digital (DFT) and metatarsal footpad temperatures (MFT) were measured with thermography. Thermograms and rectal temperature (RT) were taken before and at 3, 10, 20, 30, 45 and 60 minutes after treatment.ResultsAt 60 minutes after drug administration, MFT was higher (p < 0.001) after MB+MK (34.5 ± 1.1 IV, 34.8 ± 0.5 IM) than MB (31.1 ± 2.9 IV, 30.5 ± 3.6 IM), DFT was higher (p < 0.001) after MB+MK (33.6 ± 1.4 IV, 34.0 ± 0.6 IM) than MB (26.7 ± 1.4 IV, 26.7 ± 2.5 IM), and RT was lower (p < 0.001) after MB+MK (36.7 ± 0.8 IV, 36.9 ± 0.3 IM) than MB (37.5 ± 0.3 IV, 37.4 ± 0.4 IM), with both routes. The change from baseline was greater with MB+MK than MB in all variables.ConclusionsSuperficial temperature changes can be seen and detected with thermography. MK-467 used with MB resulted in increased superficial temperatures and a decline in rectal temperature compared to MB alone.Clinical relevanceThe sedation protocol may influence core temperature loss, and may also have an effect on thermographic images.     

Effects of midazolam before or after alfaxalone for co-induction of anaesthesia in healthy dogs

Objective

To study the effect of alternating the order of midazolam and alfaxalone administration on the incidence of behavioural changes, alfaxalone induction dose and some cardiorespiratory variables in healthy dogs.

Chemical restraint by medetomidine and medetomidine–midazolam and its reversal by atipamezole in Japanese macaques (Macaca fuscata)

Objective To evaluate the sedative effects of medetomidine, and a medetomidine–midazolam combination, in Japanese macaques and the antagonism of medetomidine–midazolam with atipamezole. Study design Prospective randomized study. Animals Thirteen healthy Japanese macaques between 3 and 21 years old and weighing between 4.3 and 15.1 kg. Methods Medetomidine (120 µg kg^?1) alone or a medetomidine (30 µg kg^?1) plus midazolam (0.3 mg kg^?1) mixture were injected intramuscularly in the hind limb of 12 animals (n = 6 for each group) and their effects, particularly behavioural changes, response to external stimuli, sedative onset time, time to lateral recumbency and time in lateral recumbency, were monitored for 120 minutes. Another group (n = 7) were given medetomidine–midazolam and injected 30 minutes later with atipamezole (120 µg kg^?1). Behavioural changes and responses to external stimuli were assessed as before. Results Animals given medetomidine became sedated but could be aroused by external stimuli. Despite the lower (25%) dose of medetomidine involved, the effects of medetomidine–midazolam were more marked. Macaques given this combination became sedated in 4 ± 2 minutes (mean ± SD) and remained unresponsive to external stimuli for at least 60 minutes. Five out of six macaques became laterally recumbent for 74 ± 37 minutes. Intramuscular atipamezole effectively reversed sedation, shortening the arousal and total recovery time. The recovery from sedation was rapid and smooth, being completed 19 ± 11 minutes after antagonism. Conclusions The medetomidine–midazolam combination described provided useful chemical restraint and may prove useful in macaques undergoing some experimental, diagnostic or therapeutic procedures. The use of atipamezole as an antagonist increases the value of this technique in macaques.     

A comparison in dogs of medetomidine,with or without MK‐467, and the combination acepromazine‐butorphanol as premedication prior to anaesthesia induced by propofol and maintained with isoflurane

ObjectiveTo compare the haemodynamic effects of three premedicant regimens during propofol-induced isoflurane anaesthesia.Study designProspective, randomized cross-over study.AnimalsEight healthy purpose-bred beagles aged 4 years and weighing mean 13.6 ± SD 1.9 kg.MethodsThe dogs were instrumented whilst under isoflurane anaesthesia prior to each experiment, then allowed to recover for 60 minutes. Each dog was treated with three different premedications given intravenously (IV): medetomidine 10 μg kg^?1 (MED), medetomidine 10 μg kg^?1 with MK-467 250 μg kg^?1 (MMK), or acepromazine 0.01 mg kg^?1 with butorphanol 0.3 mg kg^?1 (AB). Anaesthesia was induced 20 minutes later with propofol and maintained with isoflurane in oxygen for 60 minutes. Heart rate (HR), cardiac output, arterial blood pressures (ABP), central venous pressure (CVP), respiratory rate, inspired oxygen fraction, rectal temperature (RT) and bispectral index (BIS) were measured and arterial and venous blood gases analyzed. Cardiac index (CI), systemic vascular resistance index (SVRI), oxygen delivery index (DO₂I), systemic oxygen consumption index (VO₂I) and oxygen extraction (EO₂) were calculated. Times to extubation, righting, sternal recumbency and walking were recorded. The differences between treatment groups were evaluated with repeated measures analysis of covariance.ResultsHR, CI, DO₂I and BIS were significantly lower with MED than with MMK. ABP, CVP, SVRI, EO₂, RT and arterial lactate were significantly higher with MED than with MMK and AB. HR and ABP were significantly higher with MMK than with AB. However, CVP, CI, SVRI, DO₂I, VO₂I, EO₂, T, BIS and blood lactate did not differ significantly between MMK and AB. The times to extubation, righting, sternal recumbency and walking were significantly shorter with MMK than with MED and AB.Conclusions and clinical relevanceMK-467 attenuates certain cardiovascular effects of medetomidine in dogs anaesthetized with isoflurane. The cardiovascular effects of MMK are very similar to those of AB.     

Anaesthesia with a combination of ketamine and medetomidine in the rabbit: effect of premedication with buprenorphine

ObjectiveTo assess the effects of premedication with buprenorphine on the characteristics of anaesthesia induced with ketamine/medetomidine.Study designProspective crossover laboratory study.AnimalsSix female New Zealand White rabbits.MethodsRabbits received, on occasions separated by 7 days, either buprenorphine (0.03 mg kg^?1) or saline subcutaneously (SC) as premedication, followed 1 hour later by SC ketamine (15 mg kg^?1) and medetomidine (0.25 mg kg^?1) (K/M). At pre-determined time points reflex responses and cardiopulmonary parameters were recorded and arterial blood samples taken for analysis. Total sleep time was the duration of loss of the righting reflex. Duration of surgical anaesthesia was the time of suppression of the ear pinch and pedal withdrawal reflexes. Wilcoxon signed-ranks tests were used to compare data before (T₀) and 10 minutes after (T₁₀) injection with K/M.ResultsAll animals lost all three reflex responses within 10 minutes of injection of K/M. The duration of loss of these reflexes significantly increased in animals that received buprenorphine. At induction, animals that had received buprenorphine tended to have a lower respiration rate but there were no significant differences in arterial PCO₂, PO₂ or pH between treatments. Hypoxaemia [median PaO₂ < 6.0 kPa (45 mmHg)] developed in both treatments at T₁₀ but there was no significant difference between treatments. Mean arterial pressure (MAP) was lower at T₁₀ in animals that had received buprenorphine.Conclusion and clinical relevancePremedication with buprenorphine significantly increased the duration of anaesthesia induced by K/M, with no significant depression of respiration further to the control treatment within the first 10 minutes of anaesthesia. The MAP decreased but this was not reflected in a difference in other physiological parameters. These data show that premedication with buprenorphine, before K/M anaesthesia in the rabbit, has few negative effects and may provide beneficial analgesia.