Butorphanol inhibits androgen biosynthesis and metabolism in rat immature Leydig cells in vitro.

Butorphanol is a synthetic opioid analgesic medication that is primarily used for the management of pain. Butorphanol may have an inhibitory effect on androgen biosynthesis and metabolism in rat immature Leydig cells. The objective of this study was to investigate the influence of butorphanol on androgen secretion by rat Leydig cells isolated from the 35-day-old male rats. Rat Leydig cells were cultured with 0.5-50 µM butorphanol for 3 h in vitro. Butorphanol at 5 and 50 µM significantly inhibited androgen secretion in immature Leydig cells. At 50 µM, butorphanol also blocked the effects of luteinizing hormone (LH) and 8bromo-cAMP-stimulated androgen secretion and 22R-hydroxycholesterol- and pregnenolone-mediated androgen production. Further analysis of the results showed that butorphanol downregulated the expression of genes involved in androgen production, including Lhcgr (LH receptor), Cyp11a1 (cholesterol side-chain cleavage enzyme), Srd5a1 (5α-reductase 1), and Akr1c14 (3α-hydroxysteroid dehydrogenase). Additionally, butorphanol directly inhibited HSD3B1 (3ß-hydroxysteroid dehydrogenase 1) and SRD5A1 activity. In conclusion, butorphanol may have side effects of inhibiting androgen biosynthesis and metabolism in Leydig cells.

Correlation of opioid antinociception and hypothermia in dogs-An animal welfare refinement.

The purpose of this study was to assess antinociception and correlation of antinociception and hypothermic effects after intravenous opioids in dogs. Nine healthy male Beagles were enrolled in the study. They were acclimated to a thermal nociceptive device, then received three IV treatments (saline, butorphanol 0.4 mg/kg and methadone 0.5 mg/kg) in a randomized complete block design. Rectal temperature and thermal withdrawals were assessed prior to and 0.5-6 h after drug administration. One dog was excluded due to lack of withdrawal to thermal stimuli. Rectal temperatures were not significantly different between treatments at time 0, but significantly decreased from 0.5 to 5 h for both opioids compared to saline. Withdrawals were significantly decreased, compared to saline, from 0.5 to 4 h for butorphanol and 0.5-5 h for methadone. A significant (p = .0005) and moderate (R2 = .43) correlation between antinociception and hypothermia occurred. Based on these data, intravenous butorphanol (0.4 mg/kg) and methadone (0.5 mg/kg) provided 4 and 5 h of antinociception, respectively. Opioid hypothermia can serve as an easy, noninvasive and humane manner for preclinical assessment of opioid antinociception in dogs prior to evaluation in clinical trials. This is a major refinement in animal welfare for assessing novel opioids, opioid doses and dose intervals in dogs.

RESPONSE AND PHYSIOLOGIC OUTCOMES AFTER BUTORPHANOL, MIDAZOLAM, AND MEDETOMIDINE IMMOBILIZATION AND REVERSAL IN CAPTIVE REINDEER (RANGIFER TARANDUS).

Sedation, recovery response, and physiologic outcomes were evaluated in five captive reindeer (Rangifer tarandus) in Minnesota using a completely reversible immobilization protocol. Reindeer were immobilized with butorphanol (0.23-0.32 mg/kg), midazolam (0.23-0.32 mg/kg), and medetomidine (0.15 mg/kg) (BMM) via IM dart. Induction time (IT), recumbency time (DT), and recovery time (RT) were recorded. Temperature (T), respiratory rate (RR), pulse rate (PR), pulse oximetry (SpO2), arterial blood gas values including oxygen (PaO2), and carbon dioxide (PaCO2) tensions and lactate (Lac) were recorded preoxygen supplementation and 15 min postoxygen supplementation. Reversal was done using naltrexone (2.3-3.0 mg/kg), flumazenil (0.008-0.01 mg/kg) and atipamezole (0.62-0.78 mg/kg) (NFA) IM, limiting recumbency to 1 h. Median IT, DT, and RT were 5 min, 46 min, and 7 min, respectively. SpO2 (92 to 99%, P = 0.125), PaO2 (45.5 to 97 mmHg, P = 0.25), and PaCO2 (46.5 to 54.6 mmHg, P = 0.25) all increased, whereas Lac (3.02 to 1.93 mmol/L, P = 0.25) decreased between baseline and 15 min postoxygen supplementation, without statistical significance. BMM immobilization, and reversal with NFA provided rapid and effective immobilization and recovery, respectively. Oxygen supplementation mitigated hypoxemia in all reindeer.

Comparison of Manual Restraint With and Without Sedation on Outcomes for Wild Birds Undergoing Decontamination.

The decontamination process for plumage-contaminated wild birds, such as those affected by oil spills, is lengthy and involves manual restraint and manipulation of all body parts. Birds commonly react to this in ways that suggest they are extremely stressed (eg, struggling, vocalizing). We proposed to reduce stress during the wash process using sedation and hypothesized that the use of sedation would not negatively impact survival. Contaminated birds in need of washing were randomly selected to be either sedated (butorphanol 2 mg/kg IM + midazolam 1 mg/kg IM and flumazenil 0.1 mg/kg IM for reversal) or not sedated at 3 US rehabilitation centers over the course of 1 year. Response to sedation was rated on a scale of 0-4 with 0 as no effect to 4 as excessively sedate. Data such as cloacal temperatures at various time points, lengths of various portions of the wash process, preening behavior in the drying pen, and disposition were collected. No statistical differences were found between sedated and nonsedated birds for any of the data points collected, including survival. There was a significant association between birds with higher cloacal temperatures in the drying pen and with birds held longer in the drying pen with improved survival; however, these findings were unrelated to whether the birds were sedated. Our findings show that sedation with butorphanol 2 mg/ kg IM and midazolam 1 mg/kg IM reversed with flumazenil 0.1 mg/kg IM can be used during the wash process for wild birds without adverse effects. Careful attention must be given to heat support for all birds while drying to prevent hypothermia.

Epidural lidocaine, butorphanol, and butorphanol - lidocaine combination in dromedary camels.

BACKGROUND: The use of general anesthesia in dromedary camels is constrained by risks related to decubitus. Caudal epidural analgesia is an alternative convenient technique providing loco-regional analgesia for numerous invasive and noninvasive painful conditions. Lidocaine is probably the most commonly used local anesthetic in clinical practice, but has a relatively short duration and may not provide significant long term analgesic benefits. Epidural administration of an opioid-local anesthetic mixture would improve the quality and length of analgesia and minimizes the adverse motor effects provoked by local anesthetics. Butorphanol (potent agonist-antagonist opioid) has been used to improve the duration of epidural analgesia in some animal species, but not in camels. Therefore, our purpose was to investigate the onset and duration of analgesia as well as the clinical and hemato-biochemical effects produced by the epidural administration of butorphanol (0.04 mg/kg), lidocaine (0.22 mg/ kg), and butorphanol-lidocaine (0.04 mg/kg-0.22 mg/ kg) mixture in nine adult dromedary camels in a crossover experimental study. RESULTS: The onset of analgesia was not statistically different between lidocaine (6.5 ± 2.3 min) and butorphanol-lidocaine (7.3 ± 1.5 min) combination. Delayed onset of analgesia was reported after butorphanol administration (14.7 ± 3.5 min). Butorphanol-lidocaine combination produced marked longer duration (175 ± 8.7 min) than lidocaine (55 ± 6.8 min) and butorphanol (158 ± 5.3 min). Mild ataxia was observed in the butorphanol-lidocaine and lidocaine treated animals and slight sedation was reported after butorphanol and butorphanol-lidocaine administration. A transient significant increase in the glucose levels was recorded after all treatments. CONCLUSIONS: Epidural administration of butorphanol augments the analgesic effects and duration of lidocaine with minimal adverse effects.

Heart rate, arterial pressure and propofol-sparing effects of guaifenesin in dogs.

OBJECTIVE: To evaluate the heart rate (HR) and systemic arterial pressure (sAP) effects, and propofol induction dose requirements in healthy dogs administered propofol with or without guaifenesin for the induction of anesthesia. STUDY DESIGN: Prospective blinded crossover experimental study. ANIMALS: A total of 10 healthy adult female Beagle dogs. METHODS: Dogs were premedicated with intravenous (IV) butorphanol (0.4 mg kg-1) and administered guaifenesin 5% at 50 mg kg-1 (treatment G50), 100 mg kg-1 (treatment G100) or saline (treatment saline) IV prior to anesthetic induction with propofol. HR, invasive sAP and respiratory rate (fR) were recorded after butorphanol administration, after guaifenesin administration and after propofol and endotracheal intubation. Propofol doses for intubation were recorded. Repeated measures analysis of variance (anova) was used to determine differences in propofol dose requirements among treatments, and differences in cardiopulmonary values over time and among treatments with p < 0.05 considered statistically significant. RESULTS: Propofol doses (mean ± standard deviation) for treatments saline, G50 and G100 were 3.3 ± 1.0, 2.7 ± 0.7 and 2.1 ± 0.8 mg kg-1, respectively. Propofol administered was significantly lower in treatment G100 than in treatment saline (p = 0.04). In treatments G50 and G100, HR increased following induction of anesthesia and intubation compared with baseline measurements. HR was higher in treatment G100 than in treatments G50 and saline following induction of anesthesia. In all treatments, sAP decreased following intubation compared with baseline values. There were no significant differences in sAP among treatments. fR was lower following intubation than baseline and post co-induction values and did not differ significantly among treatments. CONCLUSIONS AND CLINICAL RELEVANCE: When administered as a co-induction agent in dogs, guaifenesin reduced propofol requirements for tracheal intubation. HR increased and sAP and fR decreased, but mean values remained clinically acceptable.

Sedative effects and changes in cardiac rhythm with intravenous premedication of medetomidine, butorphanol and ketamine in dogs.

OBJECTIVE: To determine the sedative effects and characteristics of cardiac rhythm with intravenous (IV) premedication of medetomidine, butorphanol and ketamine in dogs. STUDY DESIGN: Prospective, blinded, randomized clinical trial. ANIMALS: A total of 116 client-owned healthy dogs undergoing elective surgery. METHODS: Dogs were randomly allocated one of four groups: group M, medetomidine 5 µg kg-1; group B, butorphanol 0.2 mg kg-1; group MB, medetomidine 5 µg kg-1 and butorphanol 0.2 mg kg-1; or group MBK, medetomidine 5 µg kg-1, butorphanol 0.2 mg kg-1 and ketamine 1 mg kg-1 IV. Sedation was assessed using a numerical descriptive scale. Heart rate (HR) and rhythm were monitored; propofol dose (mg kg-1 IV) to allow orotracheal intubation was documented. Data were analysed using anova, accounting for multiple testing with the Tukey honest significant difference test. RESULTS: Sedation scores varied significantly between all groups at all time points, except between groups MB and MBK at four time points. HR decreased in all groups: most in groups M and MB, least in group B. HR was initially higher in group MBK than in groups M and MB. Arrhythmias occurred in all groups: group B showed second-degree atrioventricular blocks occasionally, all other groups showed additionally ventricular escape complexes and bundle branch blocks. Dose of propofol required for orotracheal intubation was significantly higher in group B (5.0 ± 2.0 mg kg-1) than in group M (2.6 ± 0.6 mg kg-1). Although no difference could be demonstrated between groups MB (1.4 ± 0.6 mg kg-1) and MBK (0.9 ± 0.8 mg kg-1), both groups required significantly less propofol than group M. CONCLUSION AND CLINICAL RELEVANCE: Medetomidine-based premedication protocols led to various bradyarrhythmias. Addition of subanaesthetic doses of ketamine to medetomidine-based protocols resulted in higher HRs, fewer bradyarrhythmias and fewer animals that required propofol for intubation without causing side effects in healthy dogs.

ANESTHESIA OF ZOO-MANAGED AFRICAN PAINTED DOGS (LYCAON PICTUS) USING A DEXMEDETOMIDINE-KETAMINEBUTORPHANOL-MIDAZOLAM COMBINATION.

Zoo-managed adult African painted dogs (Lycaon pictus; n = 17) were anesthetized with mean dosages of dexmedetomidine 5 µg/kg, ketamine 1.93 mg/kg, butorphanol 0.2 mg/kg, and midazolam 0.15 mg/kg IM. Times to induction milestones (mean ± SD or median [range]) were initial effects at 2 min (1-4 min), recumbency at 3.2 ± 1.1 min, and intubation at 11.6 ± 1.3 min. Two dogs required isoflurane supplementation for intubation. Anesthesia was antagonized with mean dosages of atipamezole 0.05 mg/kg IM, naltrexone 0.2 mg/kg IM, and flumazenil 0.01 mg/kg IV. Times from antagonist administration to recovery milestones were extubation at 3.9 ± 1.5 min, control of head at 7.6 ± 2.5 min, sternal positioning at 8.8 ± 2.3 min, and standing at 12.1 ± 3.5 min. Animals were judged ready for reunification with conspecifics at 41.5 min (28-127 min), and reunification occurred at 62.1 ± 35.2 min. Paired arterial blood gas samples were obtained (n = 13). There was a significant decrease in temperature and blood pressure and increase in pO2, BEecf, and HCO3- (P < 0.05). Decreased respiratory rate with hypercapnia was occasionally observed. This protocol provided consistent anesthesia using a low dose α-2 agonist and permitted quick pack reunification.

RETROSPECTIVE COMPARISON OF FIVE DRUG PROTOCOLS FOR IMMOBILIZATION OF CAPTIVE SABLE ANTELOPE (HIPPOTRAGUS NIGER).

Sable antelope (Hippotragus niger), a large, dominant species, often require chemical immobilization for captive management. Despite several recorded protocols, limited objective or subjective data are available to guide chemical immobilization of this species. This study retrospectively compared immobilization drug combinations of carfentanil-xylazine (CX), thiafentanil-xylazine (TX), etorphine-xylazine (EX), carfentanil-acepromazine (CA), and butorphanol-azaperone-medetomidine (BAM) for healthy sable antelope at one institution. Clinically applicable physiologic measures, subjective ratings, and timing of anesthetic milestones of 161 events for 107 individuals revealed the following statistically significant findings (P < 0.05). Induction ratings were best for TX, highest degree of muscle relaxation occurred with BAM and TX, and anesthetic ratings were best for TX and EX. Time to recovery was longest and complications 2.56 times more likely with CX. Time to recumbency was shortest in TX. Heart rate was highest in CA and lowest in BAM. For immobilization procedures, this study suggests TX would be the preferred combination for H. niger. However, all drug combinations evaluated can be used successfully to immobilize H. niger, and certain combinations may be situationally preferred based on desired muscle relaxation, expected induction or recovery times, or anticipated procedure length.

COMPARISON OF KETAMINE-MIDAZOLAM AND KETAMINE-MIDAZOLAM-BUTORPHANOL PREMEDICATION PRIOR TO SEVOFLURANE ANESTHESIA IN WOODCHUCKS (MARMOTA MONAX).

Cardiovascular disease is a frequent cause of death in the critically endangered Vancouver Island marmots (Marmota vancouverensis). This warrants the use of anesthetic protocols with minimal cardiovascular adverse effects. In this study, 12 adult male woodchucks (Marmota monax) were used as models for Vancouver Island marmots. The objective was to compare the physiological effects of two premedication protocols during induction and maintenance of anesthesia with sevoflurane. The two premedications were ketamine 10 mg/kg and midazolam 0.5 mg/kg (KM) or ketamine 10 mg/kg, midazolam 0.5 mg/kg, and butorphanol 1.0 mg/kg (KMB), administered intramuscularly prior to mask induction. Each marmot underwent three anesthetic events and protocols were assigned using a blinded randomized crossover design. Heart rate, respiratory rate, oxygen saturation, and body temperature were recorded throughout, and blood gases were assessed following induction. Resistance to induction was scored and time to induction was recorded. Although mask induction with sevoflurane was successful in all events (mean induction time of 2.1 min), KMB premedication resulted in a faster induction (mean induction time reduced by 1.2 ± 0.3 min) and lower resistance scores. Both protocols resulted in significant cardiovascular and respiratory depression; however, animals that received KMB were more hypercapnic than KM by 8.8 ± 2.8 mm Hg (P = 0.03) (mean venous partial pressure of carbon dioxide [PvCO2] for all: 79.9 mm Hg). In conclusion, if shorter induction times are desired, KMB premedication is preferred. However, cardiorespiratory variables including blood pressure should be monitored, and endotracheal intubation is recommended to allow for ETCO2 monitoring and provision of intermittent positive pressure ventilation.

Comparison of the effect of sedation and general anesthesia on pattern and flash visual evoked potentials in normal dogs.

BACKGROUND: Visual evoked potentials (VEPs) can provide objective functional assessment of the post-retinal visual pathway. This study compared the effects of sedation (butorphanol and dexmedetomidine) and general anesthesia (propofol and sevoflurane) on pattern and flash VEPs. Dogs (n = 13) underwent sedation or anesthesia and VEPs were obtained from 3 subcutaneous recording electrodes placed on the head (O1, Oz, O2). RESULTS: Pattern VEPs could only be recorded under sedation and a maximum of 3 peaks were identified (N75, P100, N135). Flash VEPs could be recorded under both sedation and anesthesia and a maximum of 5 peaks were identified (N1, P1, N2, P2, N3). The latency of the N1 peak and the baseline-N1 amplitude were significantly longer under general anesthesia. CONCLUSION: Visual evoked potentials should be preferentially recorded in dogs sedated with dexmedetomidine and butorphanol, regardless of the stimulus.

Multiple pathways are responsible to the inhibitory effect of butorphanol on OGD/R-induced apoptosis in AC16 cardiomyocytes.

Ischemic heart disease is the leading cause of cardiovascular mortality, which is related to cardiac myocyte apoptosis. Butorphanol is an opioid receptor agonist with potential cardioprotective function. The purpose of this work is to explore the function and mechanism of butorphanol in oxygen and glucose deprivation/reperfusion (OGD/R)-induced cardiomyocyte apoptosis. The overlapping targets of ischemic heart disease and butorphanol were analyzed according to GeneCards, ParmMapper, Cytoscape, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Human cardiomyocyte AC16 cells were incubated with butorphanol and then stimulated with OGD/R. Cell injury was investigated by Cell Counting Kit-8, lactate dehydrogenase (LDH) assay kit, TUNEL staining, caspase-3 activity assay kit, and Western blotting. The proteins in signaling pathways were measured using Western blotting. A total of 93 overlapping targets of ischemic heart disease and butorphanol were obtained. Pathway analysis exhibited that these targets might be involved in multiple signaling pathways. Butorphanol alone showed little cytotoxicity to cardiomyocytes, and it protected against OGD/R-induced viability inhibition, LDH release, cell apoptosis, and increase of caspase-3 activity and expression levels of cleaved caspase-3 and Bim. Butorphanol promoted the activation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/forkhead box O (FoxO) and hypoxia-inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) pathways and attenuated the activation of the mitogen-activated protein kinase (MAPK) signaling in OGD/R-treated cardiomyocytes. In conclusion, butorphanol prevents OGD/R-induced cardiomyocyte apoptosis through activating the PI3K/Akt/FoxO and HIF-1α/VEGF pathways and inactivating the MAPK pathway.

Effect of intravenous butorphanol infusion on the minimum alveolar concentration of isoflurane in cats.

OBJECTIVE: To determine the effect of butorphanol, administered by intravenous (IV) infusion, on the minimum alveolar concentration of isoflurane (MACISO) in cats and to examine the dosage dependence of this effect. STUDY DESIGN: Randomized, placebo-controlled, crossover experimental study. ANIMALS: A group of six healthy adult male neutered cats. METHODS: Cats were anesthetized with isoflurane in oxygen. A venous catheter was placed for fluid and drug administration, and an arterial catheter was placed for measurement of arterial pressure and blood sampling. Four treatments were administered at random with at least 2 week interval between treatments: saline (control), butorphanol low dosage (treatment LD; 0.25 mg kg-1 IV bolus followed by 85 µg kg-1 minute-1 for 20 minutes, then 43 µg kg-1 minute-1 for 40 minutes, then 19 µg kg-1 minute-1), medium dosage (treatment MD, double the dosages in LD) and high dosage (treatment HD, quadruple the dosages in LD). MACISO was determined in duplicate using the bracketing technique and tail clamping. Pulse rate, arterial pressure, hemoglobin oxygen saturation, end-tidal partial pressure of carbon dioxide and arterial blood gas and pH were measured. RESULTS: Butorphanol reduced MACISO in a dosage-dependent manner, by 23 ± 8%, 37 ± 12% and 68 ± 10% (mean ± standard deviation) in treatments LD, MD and HD, respectively. The main cardiopulmonary effect observed was a decrease in pulse rate, significant in treatment HD compared with control. CONCLUSIONS AND CLINICAL RELEVANCE: Butorphanol caused a dosage-dependent MACISO reduction in cats. IV infusion of butorphanol may be of interest for partial IV anesthesia in cats.

Effects of intravenous acepromazine and butorphanol on propofol dosage for induction of anesthesia in healthy Beagle dogs.

OBJECTIVE: To determine the effects of intravenous (IV) premedication with acepromazine, butorphanol or their combination, on the propofol anesthetic induction dosage in dogs. STUDY DESIGN: Prospective, blinded, Latin square design. ANIMALS: A total of three male and three female, healthy Beagle dogs, aged 3.79 ± 0.02 years, weighing 10.6 ± 1.1 kg, mean ± standard deviation. METHODS: Each dog was assigned to one of six IV treatments weekly: 0.9% saline (treatment SAL), low-dose acepromazine (0.02 mg kg-1; treatment LDA), high-dose acepromazine (0.04 mg kg-1; treatment HDA), low-dose butorphanol (0.2 mg kg-1; treatment LDB), high-dose butorphanol (0.4 mg kg-1; treatment HDB); and a combination of acepromazine (0.02 mg kg-1) with butorphanol (0.2 mg kg-1; treatment ABC). Physiologic variables and sedation scores were collected at baseline and 10 minutes after premedication. Then propofol was administered at 1 mg kg-1 IV over 15 seconds, followed by boluses (0.5 mg kg-1 over 5 seconds) every 15 seconds until intubation. Propofol dose, physiologic variables, recovery time, recovery score and adverse effects were monitored and recorded. Data were analyzed using mixed-effects anova (p < 0.05). RESULTS: Propofol dosage was lower in all treatments than in treatment SAL (4.4 ± 0.5 mg kg-1); the largest decrease was recorded in treatment ABC (1.7 ± 0.3 mg kg-1). Post induction mean arterial pressures (MAPs) were lower than baseline values of treatments LDA, HDA and ABC. Apnea and hypotension (MAP < 60 mmHg) developed in some dogs in all treatments with the greatest incidence of hypotension in treatment ABC (4/6 dogs). CONCLUSIONS AND CLINICAL RELEVANCE: Although the largest decrease in propofol dosage required for intubation was after IV premedication with acepromazine and butorphanol, hypotension and apnea still occurred.

Effects of vatinoxan in dogs premedicated with medetomidine and butorphanol followed by sevoflurane anaesthesia: a randomized clinical study.

OBJECTIVE: To investigate effects of vatinoxan in dogs, when administered as intravenous (IV) premedication with medetomidine and butorphanol before anaesthesia for surgical castration. STUDY DESIGN: A randomized, controlled, blinded, clinical trial. ANIMALS: A total of 28 client-owned dogs. METHODS: Dogs were premedicated with medetomidine (0.125 mg m-2) and butorphanol (0.2 mg kg-1) (group MB; n = 14), or medetomidine (0.25 mg m-2), butorphanol (0.2 mg kg-1) and vatinoxan (5 mg m-2) (group MB-VATI; n = 14). Anaesthesia was induced 15 minutes later with propofol and maintained with sevoflurane in oxygen (targeting 1.3%). Before surgical incision, lidocaine (2 mg kg-1) was injected intratesticularly. At the end of the procedure, meloxicam (0.2 mg kg-1) was administered IV. The level of sedation, the qualities of induction, intubation and recovery, and Glasgow Composite Pain Scale short form (GCPS-SF) were assessed. Heart rate (HR), respiratory rate (fR), mean arterial pressure (MAP), end-tidal concentration of sevoflurane (Fe'Sevo) and carbon dioxide (Pe'CO2) were recorded. Blood samples were collected at 10 and 30 minutes after premedication for plasma medetomidine and butorphanol concentrations. RESULTS: At the beginning of surgery, HR was 61 ± 16 and 93 ± 23 beats minute-1 (p = 0.001), and MAP was 78 ± 7 and 56 ± 7 mmHg (p = 0.001) in MB and MB-VATI groups, respectively. No differences were detected in fR, Pe'CO2, Fe'Sevo, the level of sedation, the qualities of induction, intubation and recovery, or in GCPS-SF. Plasma medetomidine concentrations were higher in group MB-VATI than in MB at 10 minutes (p = 0.002) and 30 minutes (p = 0.0001). Plasma butorphanol concentrations were not different between groups. CONCLUSIONS AND CLINICAL RELEVANCE: In group MB, HR was significantly lower than in group MB-VATI. Hypotension detected in group MB-VATI during sevoflurane anaesthesia was clinically the most significant difference between groups.

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.

Effet clinique de la buprénorphine ou du butorphanol, en association avec la détomidine et le diazépam, sur la sédation et la douleur postopératoire après extraction de dents jugales chez le cheval. L'objectif de cette étude était de comparer les effets du butorphanol (BUT) ou de la buprénorphine (BUP), en association avec la détomidine et le diazépam, sur la qualité de la sédation, les conditions chirurgicales et la gestion de la douleur postopératoire après extraction des dents jugales chez les chevaux, répartis au hasard dans deux groupes de traitement (BUT : n = 20; BUP : n = 20). Un bolus de détomidine (15 µg/kg, IV) a été suivi soit de BUP (7,5 µg/kg, IV) soit de BUT (0,05 mg/kg, IV). Après 20 min, du diazépam (0,01 mg/kg, IV) a été administré et la sédation a été maintenue avec une perfusion IV de détomidine (20 µg/kg/h), avec un taux ajusté en fonction des scores de cinq variables. Tous les chevaux ont reçu un bloc nerveux (maxillaire ou mandibulaire) et une infiltration gingivale avec de la mépivacaïne. La qualité de la sédation a été évaluée par le chirurgien de 1 (excellent) à 10 (chirurgie impossible). Un système de notation de la douleur (EQUUS-FAP) a été utilisé pour évaluer la douleur postopératoire. Les concentrations sériques de cortisol et l'activité locomotrice (podomètres) ont été mesurées.Les chevaux en BUP et BUT ont nécessité un débit médian de perfusion de détomidine de 30,2 µg/kg/h (20 à 74,4 µg/kg/h) et 32,2 µg/kg/h (20 à 48,1 µg/kg/h), respectivement (P = 0,22). Les chevaux du groupe BUP avaient une meilleure qualité de sédation (P < 0,05) pendant la chirurgie et un nombre de pas plus élevé (P < 0,001) après l'opération. La buprénorphine associée à la détomidine a fourni une sédation plus fiable que le butorphanol. Cependant, l'échelle de douleur EQUUS-FAP est devenue peu fiable en raison du comportement d'excitation induit par le BUP.(Traduit par Dr Serge Messier).

Effects of Intramuscular Alfaxalone and Midazolam Compared With Midazolam and Butorphanol in Rhode Island Red Hens (Gallus gallus domesticus).

Chickens (Gallus gallus domesticus) often undergo veterinary procedures requiring sedation; however, there is little published research evaluating the efficacy of sedation protocols in this species. The objective of this study was to assess the effects of intramuscular alfaxalone and midazolam compared with intramuscular butorphanol and midazolam in chickens. In a complete crossover study, 11 healthy adult hens were randomly administered midazolam 2.5 mg/kg IM combined with either alfaxalone 15 mg/kg IM (AM, n = 11) or butorphanol 3 mg/kg IM (BM, n = 11), with a 35-day washout period between groups. Time to first effects, recumbency, standing, and recovery were recorded. Physiologic parameters and sedation scores were recorded every 5 minutes by 2 blinded investigators. Fifteen minutes after injection, positioning for sham whole body radiographs was attempted. At 30 minutes, flumazenil 0.05 mg/kg IM was administered to all hens. Peak total sedation score was significantly higher for AM compared with BM (P < 0.001). Mean ± SD or median (range) time to initial effects, recumbency, standing, and recovery in AM and BM were 1.9 ± 0.6 and 2.6 ± 0.9 (P = 0.02), 3.5 (1.6-7.6) and 4.8 (2.2-13.0) (P = 0.10), 40.3 (28.0-77.8) and 33.2 (5.2-41.3) (P = 0.15), and 71.2 (45.7-202.3) and 39.9 (35.9-45.9) minutes (P = 0.05), respectively. Radiographic positioning was successful in 6 of 11 (54.5%) and 0 of 11 (0%) birds in the AM and BM groups at 15 minutes, respectively. Heart and respiratory rates remained within acceptable clinical limits for all birds. Intramuscular AM resulted in significantly faster onset of sedative effects, significantly longer duration of recumbency, significantly higher peak sedation, and improved success of radiographic positioning compared with intramuscular BM. Intramuscular AM produces clinically effective sedation in chickens without clinically significant cardiorespiratory effects.

Effects of isoflurane and sevoflurane alone and in combination with butorphanol or medetomidine on the bispectral index in chickens.

BACKGROUND: The bispectral index (BIS) is an anaesthesia monitoring technique able to assess the level of central nervous system depression in humans and various animal species. In birds, it has been validated in chickens undergoing isoflurane anaesthesia. The aim of this study was to evaluate in an avian species the influence of isoflurane and sevoflurane on BIS, each at different minimum anaesthetic concentrations (MAC) multiples, alone or combined with butorphanol or medetomidine. Ten chickens (5 males and 5 females) underwent general anaesthesia with isoflurane or sevoflurane alone, and combined with either intramuscular administration of butorphanol (1 mg/kg) or medetomidine (0.1 mg/kg), in a prospective and cross-over study (i.e., 6 treatments per animal). BIS measurements were compared to heart rate (HR), non-invasive blood pressure (NIBP) and to a visual analogue scale (VAS) of anaesthesia depth. RESULTS: HR was significantly increased, and both NIBP and VAS were significantly reduced, with higher gas concentrations. NIBP (but not HR or VAS) was additionally affected by the type of gas, being lower at higher concentrations of sevoflurane. Butorphanol had no additional effect, but medetomidine led to differences in HR, NIBP, and in particular a reduction in VAS. With respect to deeper level of hypnosis at higher concentrations and the absence of difference between gases, BIS measurements correlated with all other measures (except with HR, where no significant relationship was found) The difference in BIS before (BISpre) and after stimulation (BISpost) did not remain constant, but increased with increasing MAC multiples, indicating that the BISpost is not suppressed proportionately to the suppression of the BISpre values due to gas concentration. Furthermore, neither butorphanol nor medetomidine affected the BIS. CONCLUSIONS: The difference of degree of central nervous system depression monitored by BIS compared with neuromuscular reflexes monitored by VAS, indicate that BIS records a level of anaesthetic depth different from the one deducted from VAS monitoring alone. BIS provided complementary information such as that medetomidine suppressed spinal reflexes without deepening the hypnotic state. As a consequence, it is concluded that BIS improves the assessment of the level of hypnosis in chickens, improving anaesthesia monitoring and anaesthesia quality in this species.

Comparison of sedation quality and safety of detomidine and romifidine as a continuous rate infusion for standing elective laparoscopic ovariectomy in mares.

OBJECTIVE: To compare efficacy and safety of a continuous rate infusion of detomidine hydrochloride and romifidine hydrochloride for standing elective bilateral laparoscopic ovariectomy in mares. STUDY DESIGN: Blinded, randomized prospective clinical study. ANIMALS: Eighteen healthy mares presenting for elective bilateral ovariectomy METHODS: Mares were randomly assigned to one of two sedation protocols. Prior to surgery, baseline head height, heart rate, respiratory rate, and postural sway were recorded. An IV loading dose of α2-agonist (46 µg/kg romifidine or 13.9 µg/kg detomidine) was administered. Standing sedation was maintained with a continuous rate infusion of the respective α2-agonist (126 µg/kg/h romifidine or 37.8 µg/kg/h detomidine). Intraoperative measurements included respiratory rate, heart rate, head height, postural sway, and response to surgical stimulus. Postoperatively, fecal output was recorded, and pain scoring was performed using composite pain score and visual analog scales. RESULTS: Three of 18 horses required additional α-2 agonists: one detomidine and two romifidine and butorphanol. Head height during surgery was lower (p < .001) in mares receiving detomidine. Postural sway around the vertical axis was greater in mares sedated with detomidine rather than romifidine (p = .013). No differences were detected in intraoperative heart rate, postoperative pain scores or postoperative fecal output between sedation techniques. CONCLUSION: Comparable scores for surgical stimulation and sedation were measured in both sedation groups. No differences in postoperative analgesia or manure production were identified. CLINICAL SIGNIFICANCE: Romifidine appears suitable as an alternative to detomidine and may limit ataxia and head drop in sedated horses.

Immobilization, cardiopulmonary and blood gas effects of ketamine-butorphanol-medetomidine versus butorphanol-midazolam-medetomidine in free-ranging serval (Leptailurus serval).

OBJECTIVE: To compare ketamine-butorphanol-medetomidine (KBM) with butorphanol-midazolam-medetomidine (BMM) immobilization of serval. STUDY DESIGN: Blinded, randomized trial. ANIMALS: A total of 23 captures [KBM: five females, six males; 10.7 kg (mean); BMM: 10 females, two males; 9.6 kg]. METHODS: Serval were cage trapped and immobilized using the assigned drug combination delivered via a blow dart into gluteal muscles. Prior to darting, a stress score was assigned (0: calm; to 3: markedly stressed). Drug combinations were dosed based on estimated body weights: 8.0, 0.4 and 0.08 mg kg-1 for KBM and 0.4, 0.3 and 0.08 mg kg-1 for BMM, respectively. Time to first handling, duration of anaesthesia and recovery times were recorded. Physiological variables including blood glucose and body temperature were recorded at 5 minute intervals. Atipamezole (5 mg mg-1 medetomidine) and naltrexone (2 mg mg-1 butorphanol) were administered intramuscularly prior to recovery. Data, presented as mean values, were analysed using general linear mixed model and Spearman's correlation (stress score, glucose, temperature); significance was p < 0.05. RESULTS: Doses based on actual body weights were 8.7, 0.4 and 0.09 mg kg-1 for KBM and 0.5, 0.4 and 0.09 mg kg-1 for BMM, respectively. Time to first handling was 10.2 and 13.3 minutes for KBM and BMM, respectively (p = 0.033). Both combinations provided cardiovascular stability during anaesthesia that lasted a minimum of 35 minutes. Recovery was rapid and calm overall, but ataxia was noted in KBM. Stress score was strongly correlated to blood glucose (r2 = 0.788; p = 0.001) and temperature (r2 = 0.634; p = 0.015). CONCLUSIONS AND CLINICAL RELEVANCE: Both combinations produced similar effective immobilization that was cardiovascularly stable in serval. Overall, BMM is recommended because it is fully antagonizable. A calm, quiet environment before drug administration is essential to avoid capture-induced hyperglycaemia and hyperthermia.