The sedative and analgesic effects of detomidine-butorphanol and detomidine alone in donkeys

Butorphanol and detomidine constitute an effective combination for sedation and analgesia in horses. This trial was undertaken to assess the effectiveness of this combination in donkeys. The detomidine and butorphanol were given intravenously one after the other. A dose of 10 microg/kg of detomidine and 25 microg/kg of butorphanol was used. Sedation is easily extended by additional doses of butorphanol. The average dose of detomidine was 11.24 microg/kg and that of butorphanol was 28.0 microg/kg. Four donkeys in the detomidine group required additional sedation and analgesia. Detomidine alone did not totally eliminate coronary band pain. Heart rates dropped significantly in the first minute after the injection of the combination. One donkey developed an atrioventricular block, while another developed a sino-atrial block. Four donkeys developed a Cheyne-Stokes respiratory pattern. The combination of detomidine and butorphanol is an effective combination for sedation and analgesia of donkeys for standing procedures.     

Evaluation of the sedative,analgesic, clinicophysiological and haematological effects of intravenous detomidine,detomidine‐butorphanol,romifidine and romifidine‐butorphanol in standing donkeys

The aim of this investigation was to determine and evaluate the sedative, analgesic, clinicophysiological and haematological effects of intravenous (i.v.) injection of detomidine, detomidine‐butorphanol, romifidine and romifidine‐butorphanol. Six standing donkeys were used. Each donkey received 4 i.v. treatments and the order of treatment was randomised with a one‐week interval between each treatment. We found that i.v. injection of a combination of detomidine‐butorphanol or romifidine‐butorphanol produced potent neuroleptanalgesic effects thus providing better, safe and effective sedation with complete analgesia in standing donkeys compared with injection of detomidine or romifidine alone. The changes and reduction in pulse rate were within acceptable limits. The changes in clinicophysiological, haematological and biochemical values were mild and transient in these clinically healthy donkeys.     

Analgesic effect of butorphanol in ponies following castration

Reasons for performing study: In the UK butorphanol has a marketing authorisation for administration to horses for sedation in combination with detomidine, and at a higher dose (0.1 mg/kg bwt), for the alleviation of pain. There is only a limited number of clinical studies designed to examine the analgesic effects of butorphanol administration following surgery. Objective: To investigate the effect of premedication with butorphanol on post operative pain following castration under general anaesthesia in ponies. Hypothesis: Ponies receiving butorphanol would experience less pain after castration than ponies that did not receive butorphanol. Methods: A randomised, observer blinded clinical study in which 20 ponies received butorphanol and detomidine (Group B) or detomidine alone (Group C). Anaesthesia was induced with ketamine and diazepam and open castration performed. Pain was assessed by one individual using a dynamic interactive visual analogue scale (DIVAS) 100 mm in length (0 = no pain, 100 mm the maximum possible pain for that procedure). ‘Rescue’ analgesia was administered when DIVAS >50 mm and was butorphanol i.v. On the second occasion DIVAS was >50 mm, flunixin was administered i.v. Data from the DIVAS were analysed using a Mann Whitney Test. Results: Only one animal did not require rescue analgesia after surgery (Group C). DIVAS were not significantly different between groups (P = 0.063). Conclusions and potential relevance: Castration is sufficiently painful that administration of a single preoperative dose of butorphanol does not provide adequate post operative analgesia.     

Preliminary study of the effects of xylazine or detomidine with or without butorphanol for standing sedation in dairy cattle

The sedative effect induced by administering xylazine hydrochloride or detomidine hydrochloride with or without butorphanol tartrate to standing dairy cattle was compared in two groups of six adult, healthy Holstein cows. One group received xylazine (0.02 mg/kg i.v.) followed by xylazine (0.02 mg/kg) and butorphanol (0.05 mg/kg i.v.) 1 week later. Cows in Group B received detomidine (0.01 mg/kg i.v.) followed by detomidine (0.01 mg/kg i.v.) and butorphanol (0.05 mg/kg i.v.) 1 week later. Heart rate, respiratory rate, and arterial blood pressure were monitored and recorded before drugs were administered and every 10 minutes for 1 hour after drug administration. The degree of sedation was evaluated and graded. Cows in each treatment group had significant decreases in heart rate and respiratory rate after test drugs were given. Durations of sedation were 49.0 +/- 12.7 minutes (xylazine), 36.0 +/- 14.1 (xylazine with butorphanol), 47.0 +/- 8.1 minutes (detomidine), and 43.0 +/- 14.0 minutes (detomidine with butorphanol). Ptosis and salivation were observed in cows of all groups following drug administration. Slow horizontal nystagmus was observed from three cows following administration of detomidine and butorphanol. All cows remained standing while sedated. The degree of sedation seemed to be most profound in cows receiving detomidine and least profound in cows receiving xylazine.     

Combined use of detomidine with opiates in the horse

The effects of administration of one of four opiates (pethidine 1 mg/kg bodyweight (bwt), morphine 0.1 mg/kg bwt, methadone 0.1 mg/kg bwt, and butorphanol 0.05 mg/kg bwt) given intravenously to horses and ponies already sedated with detomidine (10 micrograms/kg bwt) were investigated. Behavioural, cardiovascular and respiratory effects of the combinations were compared with those occurring with detomidine alone. Addition of the opiate increased the apparent sedation and decreased the response of the animal to external stimuli. At doses used, butorphanol produced the most reliable response. Side effects seen were increased ataxia (greatest following methadone and butorphanol) and excitement (usually muzzle tremors and muscle twitching). Following pethidine, generalised excitement was sometimes seen. Marked cardiovascular changes occurred in the first few minutes after morphine or pethidine injection, but within 5 mins cardiovascular changes were minimal. Following morphine or pethidine there was a significant increase in arterial carbon dioxide tension. Fourteen clinical cases were successfully sedated using detomidine/butorphanol combinations.     

Analgesic effect of butorphanol and levomethadone in detomidine sedated horses

The analgesic potency of butorphanol 25 microg/kg bodyweight (BW) and levomethadone 100 microg/kg BW, administered together with detomidine 10 microg/kg BW, was measured in twelve Warmblood horses in a randomized, blinded cross-over study. Detomidine with saline 10 ml 0.9% was used as placebo. The nociceptive threshold was determined using a constant current and a pneumatic pressure model for somatic pair Detomidine alone and in combination with butorphanol or levomethadone caused a significant temporary increase (P < 0.05) of the nociceptive threshold with a maximum effect within 15 min and a return to baseline levels within 90 min. Butorphanol and levomethadone increased the nociceptive threshold and prolonged the duration of anti-nociception significantly from 15 to 75 min (P < 0.05) after drug administration compared with detomidine alone to both test methods. No significant difference between butorphanol and levomethadone was registered. It is concluded that the addition of butorphanol or levomethadone to detomidine increases the nociceptive threshold to somatic pain and prolongs the analgesic effect of detomidine in the horse.     

Chemical restraint for surgery in the standing horse.

Chemical restraint can be a useful pharmacologic tool to assist the veterinarian performing surgery in the standing horse. The agents discussed impose minimal adverse side effects and are considered relatively safe when administered in the doses described. Acetylpromazine, the most widely used tranquilizer, produces mild sedation but no analgesia. The use of tranquilizers for surgical procedures requires the combined use of either a local anesthetic technique or a sedative-hypnotic or opiate to provide analgesia. Sedative-hypnotics such as xylazine and detomidine or opiates such as morphine and butorphanol are commonly used. The sedative-hypnotics also can induce deep CNS depression and may be sufficient alone for many procedures. Opiates may be used to supplement the analgesia produced by sedative-hypnotics or provide analgesia to the tranquilized horse. Opiates are not useful alone because of their potential to cause CNS excitement in the horse. The combination of detomidine and butorphanol is probably the most effective drug combination to facilitate painful surgery in the standing horse.     

Hormonal, metabolic and physiological effects of laparoscopic surgery using a detomidine-buprenorphine combination in standing horses

Objective To assess the hormonal, metabolic and physiological effects of laparascopic surgery performed under a sedative analgesic combination of detomidine and buprenorphine in standing horses. Study design Prospective study. Animals Eight healthy adult Dutch Warmblood horses and five healthy adult ponies undergoing laparoscopy were studied. Five healthy adult horses not undergoing laparoscopy were used as a control group. Methods The sedative effect of an initial detomidine and buprenorphine injection was maintained using a continuous infusion of detomidine alone. The heart and respiratory rate, arterial blood pH and arterial oxygen and carbon dioxide tensions were monitored, while blood samples were taken for the measurement of glucose, lactate, cortisol, insulin and nonesterified fatty acids (NEFA). The same variables were monitored in a control group of horses which were sedated, but which did not undergo surgery. At the end of the sedation period the effects of detomidine were antagonized using atipamezole. Results The protocol provided suitable conditions for standing laparoscopy in horses. Laparoscopy induced obvious metabolic and endocrine responses which, with the exception of NEFA values, were not significantly different from changes found in the control group. While atipamezole did not produce detectable adverse effects, it is possible that anatagonism may not be essential. Conclusions The technique described reliably produces adequate sedation and analgesia for laparoscopic procedures. The level of sedation/analgesia was controlled by decreasing or increasing the infusion rate. Antagonism of the effects of detomidine may not be necessary in all cases.     

Retrospective analysis of detomidine infusion for standing chemical restraint in 51 horses

Objective To assess the effectiveness of a detomidine infusion technique to provide standing chemical restraint in the horse. Design Retrospective study. Animals Fifty‐one adult horses aged 9.5 ± 6.9 years (range 1–23 years) and weighing 575 ± 290.3 kg. Methods Records of horses presented to our clinic over a 3‐year period in which a detomidine infusion was used to provide standing chemical restraint were reviewed. Information relating to the types of procedure performed, duration of infusion, drug dosages and adjunct drugs administered was retrieved. Results Detomidine was administered as an initial bolus loading dose (mean ± SD) of 7.5 ± 1.87 µg kg^?1. The initial infusion rate was 0.6 µg kg^?1 minute^?1, and this was halved every 15 minutes. The duration of the infusion ranged from 20 to 135 minutes. Twenty horses received additional detomidine or butorphanol during the procedure. All horses undergoing surgery received local anesthesia or epidural analgesia in addition to the detomidine infusion. A wide variety of procedures were performed in these horses. Conclusions Detomidine administered by infusion provides prolonged periods of chemical restraint in standing horses. Supplemental sedatives or analgesics may be needed in horses undergoing surgery. Clinical relevance An effective method that provides prolonged periods of chemical restraint in standing horses is described. The infusion alone did not provide sufficient analgesia for surgery and a significant proportion of animals required supplemental sedatives and analgesics.     

Qualitative and quantitative characteristics of the electroencephalogram in normal horses after sedation

Background

The administration of certain sedatives has been shown to promote sleep in humans. Related agents induce sleep‐like behavior when administered to horses. Interpretation of electroencephalograms (EEGs) obtained from sedated horses should take into account background activity, presence of sleep‐related EEG events, and the animal's behavior.

Hypothesis

Sedatives induce states of vigilance that are indistinguishable on EEGs from those that occur naturally.

Animals

Six healthy horses.

Methods

Digital EEG with video was recorded after administration of 1 of 4 sedatives (acepromazine, butorphanol, xylazine, or detomidine). Serum drug concentrations were measured. Recordings were reviewed, states were identified, and representative EEG samples were analysed. These data were compared with data previously obtained during a study of natural sleep.

Results

Butorphanol was associated with brief episodes resembling slow wave sleep in 1 horse. Acepromazine led to SWS in 3 horses, including 1 that also exhibited rapid eye movement sleep. Periods of SWS were observed in all horses afer xylazine or detomidine administration. Normal sleep‐related EEG events and heart block, occurred in association with SWS regardless of which sedative was used. Spectral data varied primarily by state, but some differences were observed between sedative and natural data.

Conclusions and Clinical Importance

Qualitatively, EEG findings appeared identical whether sedation‐induced or naturally occurring. The startle response and heart block associated with some sedatives may be related to sleep. Alpha₂ agonists can be used to obtain high quality EEGs in horses, but acepromazine does not promote a relaxed state in all animals.     

Standing sedation in captive zebra (Equus grevyi and Equus burchellii)

Nine Grevy's zebras (Equus grevyi) and three Burchell's zebras (Equus burchellii) were immobilized in a standing position a total of 70 times for minor, nonpainful procedures over a 9-yr period. Standing sedation was successfully obtained with a combination of detomidine and butorphanol on 47 occasions (67.1%). Detomidine i.m. (median 0.10 mg/kg; range: 0.07-0.21) was administered by dart, followed 10 min later by butorphanol i.m. (median 0.13 mg/kg; range 0.04-0.24). The dosages were varied depending on the initial demeanor of the animal. On 23 occasions (32.9%), small amounts of etorphine (median 2.5 microg/kg; range 1.1-12.3 microg/kg) plus acepromazine (median 10 microg/kg; range 4.4-50 microg/kg) (as in Large Animal-Immobilon) had to be administered i.m. to gain sufficient sedation. In these latter cases, the animals were either excited or known for their aggressive character. The zebras were sufficiently immobilized for the length of most procedures (<45 min) without supplementation. At the end of the procedure, the animals were given atipamezole (2 mg per 1 mg detomidine used) and naltrexone (0.1 mg/kg) to reverse the sedative effects, irrespective of whether etorphine was used or not. Standing sedation, using the combination of the alpha-2 agonist detomidine and the partial agonist-antagonist opioid butorphanol (in some cases supplemented with etorphine + acepromazine), proved to be a very efficacious and safe method to be used in zebras under zoo conditions for short-lasting, nonpainful procedures.     

Detomidine-butorphanol sedation in equine clinical practice

Combinations of detomidine (mean dose rate 13 micrograms/kg) and butorphanol (mean dose rate 26 micrograms/kg) were used to sedate 61 horses for a variety of surgical or diagnostic procedures in general equine practice. Three horses were sedated on more than one occasion. The degree of sedation was graded from 3 to 0 (deep sedation to no effect) and any side effects were recorded. Forty-three per cent of the horses were graded 3, 46 per cent were graded 2, 8 per cent were graded 1 and 3 per cent were graded 0. Bradycardia and ataxia were the major side effects. The combination was judged to be effective and safe for use in general practice. In 56 horses (92 per cent) the necessary procedure was carried out under excellent conditions and in only one horse was the degree of sedation considered to be totally unsatisfactory.     

Serum concentrations and effects of detomidine delivered orally to horses in three different mediums

Objective To compare the effect of orally delivered detomidine on head posture when administered alone or in combination with two different food items, and to determine the serum concentrations of detomidine after oral delivery. Study Design Prospective randomized experimental study. Animals Fifteen adult grade mares weighing 328–537 kg. Methods The horses were randomly assigned to one of the three treatment groups (five horses each). The groups were given detomidine (0.06 mg kg^?1): alone; mixed with 3 mL of an apple sauce and gum mixture; or mixed with 3 mL molasses. Head droop, measured before treatment and at 15, 30, 45, 60, 75, 90, and 105 minutes after treatment, was used to evaluate sedation. Yohimbine (0.1 mg kg^?1 IV) was administered after the 90‐minute evaluation. Blood samples were collected from the detomidine‐alone group before treatment and at 15, 30, 45, 60, 75, and 90 minutes after treatment. Sera were analyzed for detomidine equivalent concentrations by an ELISA. Head droop percentages were compared using a repeated measures analysis of variance. Results Significant mean head droop developed in each treatment group by 30 minutes and persisted until reversal with yohimbine. After yohimbine administration, head positions returned to 87–91% of pre‐treatment levels. There were no significant differences among the oral treatment groups at any time. Mean serum detomidine equivalents increased slowly until 45‐minute post‐administration, but never exceeded 30 ng mL^?1. Conclusions Orally administered detomidine results in measurable serum drug concentrations using any of the delivery mediums investigated, and can be expected to produce profound head droop in horses approximately 45 minutes after administration.     

Effect of sedation with detomidine and butorphanol on pulmonary gas exchange in the horse

Background

Sedation with α₂-agonists in the horse is reported to be accompanied by impairment of arterial oxygenation. The present study was undertaken to investigate pulmonary gas exchange using the Multiple Inert Gas Elimination Technique (MIGET), during sedation with the α₂-agonist detomidine alone and in combination with the opioid butorphanol.

Methods

Seven Standardbred trotter horses aged 3–7 years and weighing 380–520 kg, were studied. The protocol consisted of three consecutive measurements; in the unsedated horse, after intravenous administration of detomidine (0.02 mg/kg) and after subsequent butorphanol administration (0.025 mg/kg). Pulmonary function and haemodynamic effects were investigated. The distribution of ventilation-perfusion ratios (V_A/Q) was estimated with MIGET.

Results

During detomidine sedation, arterial oxygen tension (PaO₂) decreased (12.8 ± 0.7 to 10.8 ± 1.2 kPa) and arterial carbon dioxide tension (PaCO₂) increased (5.9 ± 0.3 to 6.1 ± 0.2 kPa) compared to measurements in the unsedated horse. Mismatch between ventilation and perfusion in the lungs was evident, but no increase in intrapulmonary shunt could be detected. Respiratory rate and minute ventilation did not change. Heart rate and cardiac output decreased, while pulmonary and systemic blood pressure and vascular resistance increased. Addition of butorphanol resulted in a significant decrease in ventilation and increase in PaCO₂. Alveolar-arterial oxygen content difference P(A-a)O₂ remained impaired after butorphanol administration, the V_A/Q distribution improved as the decreased ventilation and persistent low blood flow was well matched. Also after subsequent butorphanol no increase in intrapulmonary shunt was evident.

Conclusion

The results of the present study suggest that both pulmonary and cardiovascular factors contribute to the impaired pulmonary gas exchange during detomidine and butorphanol sedation in the horse.     

Clinical effect of buprenorphine or butorphanol,in combination with detomidine and diazepam,on sedation and postoperative pain after cheek tooth extraction in horses

The objective of this study was to compare effects of butorphanol (BUT) or buprenorphine (BUP), in combination with detomidine and diazepam, on the sedation quality, surgical conditions, and postoperative pain control after cheek tooth extraction in horses, randomly allocated to 2 treatment groups (BUT: n = 20; BUP: n = 20). A bolus of detomidine (15 μg/kg, IV) was followed by either BUP (7.5 μg/kg, IV) or BUT (0.05 mg/kg, IV). After 20 min, diazepam (0.01 mg/kg, IV) was administered and sedation was maintained with a detomidine IV infusion (20 μg/kg/h), with rate adjusted based on scores to 5 variables. All horses received a nerve block (maxillary or mandibular), and gingival infiltration with mepivacaine. Sedation quality was assessed by the surgeon from 1 (excellent) to 10 (surgery not feasible). A pain scoring system (EQUUS-FAP) was used to assess postoperative pain. Serum cortisol concentrations and locomotor activity (pedometers) were measured.Horses in BUP and BUT required a median detomidine infusion rate of 30.2 μg/kg/h (20 to 74.4 μg/kg/h) and 32.2 μg/kg/h (20 to 48.1 μg/kg/h), respectively (P = 0.22). Horses in the BUP group had better sedation quality (P < 0.05) during surgery and higher step counts (P < 0.001) postoperatively. Buprenorphine combined with detomidine provided a more reliable sedation than butorphanol. However, the EQUUS-FAP pain scale became unreliable because of BUP-induced excitement behavior.     

Behavioural and cardiovascular effects of medetomidine constant rate infusion compared with detomidine for standing sedation in horses

ObjectiveTo compare the efficacy of a medetomidine constant rate infusion (CRI) with a detomidine CRI for standing sedation in horses undergoing high dose rate brachytherapy.Study designRandomized, controlled, crossover, blinded clinical trial.AnimalsA total of 50 horses with owner consent, excluding stallions.MethodsEach horse was sedated with intravenous acepromazine (0.02 mg kg^–1), followed by an α₂-adrenoceptor agonist 30 minutes later and then by butorphanol (0.1 mg kg^–1) 5 minutes later. A CRI of the same α₂-adrenoceptor agonist was started 10 minutes after butorphanol administration and maintained for the treatment duration. Treatments were given 1 week apart. Each horse was sedated with detomidine (bolus dose, 10 μg kg^–1; CRI, 6 μg kg^–1 hour^–1) or medetomidine (bolus dose, 5 μg kg^–1; CRI, 3.5 μg kg^–1 hour^–1). If sedation was inadequate, a quarter of the initial bolus of the α₂-adrenoceptor agonist was administered. Heart rate (HR) was measured via electrocardiography, and sedation and behaviour evaluated using a previously published scale. Between treatments, behaviour scores were compared using a Wilcoxon signed-rank test, frequencies of arrhythmias with chi-square tests, and HR with two-tailed paired t tests. A p value <0.05 indicated statistical significance.ResultsTotal treatment time for medetomidine was longer than that for detomidine (p = 0.04), and ear movements during medetomidine sedation were more numerous than those during detomidine sedation (p = 0.03), suggesting there may be a subtle difference in the depth of sedation. No significant differences in HR were found between treatments (p ≥ 0.09). Several horses had arrhythmias, with no difference in their frequency between the two infusions.Conclusions and clinical relevanceMedetomidine at this dose rate may produce less sedation than detomidine. Further studies are required to evaluate any clinical advantages to either drug, or whether a different CRI may be more appropriate.     

Influence of detomidine on echocardiographic function parameters and cardiac hemodynamics in horses with and without heart murmur

30 warmblood horses were examined before and after sedation with 20 micrograms/kg BW detomidine, to determine changes of cardiac function parameters, using B-mode, M-mode and Doppler echocardiography. 15 horses showed a heart murmur, but no clinical signs of cardiac heart failure, 15 horses had neither a heart murmur nor other signs of cardiac disease. After sedation with detomidine we could recognise a significant increase of end-diastolic left atrium diameter, an increase of end-systolic left ventricular diameter and aortic root diameter. The end-systolic thickness of papillary muscle and interventricular septum showed a decrease. Fractional shortening and amplitude of left ventricular wall motion was decreased after sedation. The mitral valve echogram revealed a presystolic valve closure and an inflection in the Ac slope (B-notch) in xy horses before sedation. Both increased after sedation with detomidine. Doppler echocardiography showed a decrease of blood flow velocity and velocity time integral (VTI) in the left and right ventricular outflow tract after sedation. Regurgitant flow signals were intensified following sedation in xy horses, especially at the mitral valve.     

Quantitative electroencephalography of medetomidine,medetomidine-midazolam and medetomidine-midazolam-butorphanol in dogs

The purpose of this study was to evaluate the effects of the administration of an alpha2-adrenoceptor agonist alone and in combination with other derivatives on brain wave activity. In addition, the diagnostic values of the electroencephalogram (EEG) for judging the depth of the balanced anaesthesia with an alpha2-adrenoceptor agonist was evaluated. The treatments comprised 20 microg/kg medetomidine (Me-20), 80 microg/kg medetomidine (Me-80), 20 microg/kg medetomidine and 0.5 mg/kg midazolam (Me-Mi) administered intramuscularly, and 20 microg/kg medetomidine with 0.5 mg/kg midazolam and 0.1 mg/kg butorphanol (Me-Mi-Bu). The EEG was recorded continuously at pre-administration, and at 7, 10, 20, 30, 45 and 60 min after administration. The recorded data were analysed by separating the power spectrum into 1-3, 4-7, 8-13 and 14-30 Hz bands. Spectral-edge analysis was used to calculate the spectral edge frequency 90 (SEF90) and the median edge frequency (MEF). Time-related changes in power spectrum analysis showed a significant increase in the Me-80 group in the 1-3 Hz band. The power for 1-3 Hz in the Me-80 group was significantly higher than in all the other groups. In the 14-30 Hz band, there was a significant reduction of power in all groups following administration of the agents. The SEF90 frequencies were significantly reduced in all groups except for the Me-20 group after administration of the agents. The SEF90 frequencies in the Me-20, Me-Mi and Me-Mi-Bu were all significantly higher than those in the Me-80 group. However, there was no significant difference between the Me-20, Me-Mi and Me-Mi-Bu groups in any analyses. Our results demonstrated that the changes in quantitative EEG made by the Me-Mi-Bu and Me-Mi groups were similar to those made by Me-20 groups. Present results suggest that the EEG should be interpreted with caution in assessing the anaesthetic level in balanced anaesthesia in dogs.