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

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

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

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

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

Long-term deep sedation using Zoletil and haloperidol for the treatment of streptococcal pneumonia in an orangutan (Pongo pygmaeus)

A 13-year-old Bornean orangutan diagnosed with life threatening Streptococcus pyogenes broncho-pneumonia was kept in a state of deep sedation for 20 days via continuous intra-venous (IV) infusion of zolazepam -tiletamine and IV haloperidol to allow consistent IV administration of ceftazidime and gatifloxacine. The use of long-term deep sedation allowed carrying out a particularly demanding treatment not generally associated with zoological patients. The treatment was ultimately successful.     

Comparison of intraoperative cardiorespiratory and behavioral responses to medetomidine combined with tramadol or butorphanol during standing laparoscopic ovariectomy in horses

The purpose of this study was to assess the cardiorespiratory and behavioral responses to the combination of medetomidine and tramadol (M-T) or butorphanol (M-B) in standing laparoscopic ovariectomy in horses. One ovary was removed under M-T and the contralateral ovary was removed under M-B with at least 4 weeks between operations at random. Horses were sedated using intravenous medetomidine (5 µg/kg) followed by tramadol (1 mg/kg) or butorphanol (10 µg/kg) after 5 min. Sedation was maintained through the repeated injection of medetomidine (1 µg/kg) and tramadol (0.4 mg/kg) or medetomidine (1 µg/kg) and butorphanol (4 µg/kg) every 15 min. Cardiorespiratory function and behavioral responses, including, sedation, ataxia, and analgesia, were assessed during the surgery. There were no significant differences in cardiorespiratory values and sedation and analgesia scores between M-T and M-B. Ataxia scores were significantly lower in M-T than in M-B. This result suggests that M-T could maintain smooth and stable standing surgery with minimal cardiorespiratory changes in horses.     

Selection of soybean elite cultivars based on phenotypic and genomic characters related to lodging tolerance

Soybean lodging can result in serious yield reduction. Detecting the quantitative trait loci (QTL) associated with lodging tolerance for their further application in marker‐assisted selection (MAS) has the potential to enhance soybean breeding efficiency. In this study, a genome‐wide association analysis (GWAS) was performed to identify soybean accessions that could potentially be used to produce lodging‐tolerant varieties, based on the comprehensive evaluation of lodging scores (LS) obtained for the parental cultivar “Tokachi nagaha” and its 137 derived cultivars. Results showed that genotype, environment and genotype × environment interaction significantly influenced LS. Of the 31 significant SNPs identified, 22 were consistently detected in two or more environments and 27 SNPs were located in or close to agronomically important QTL mapped by linkage analysis. Best linear unbiased predictors (BLUPs) of LS tend to decrease with the elite alleles contained by accessions increasing. Some excellent accessions, with lower BLUPs and D_i (stability coefficients) values and more elite alleles, were selected. This study contributed to understand the genetic mechanism of lodging, providing genetic and phenotypic information for MAS.     

Assessing hygiene proficiency on organic and conventional pig farms regarding pork safety: A pilot study in Finland

A key element in the EU Common Agricultural Policy (CAP) will be a single farm payment system that is linked to compliance with rules on, for instance hygiene standards. However, there are no recommended methods for assessing the hygiene proficiency of pig production farms. The present study was undertaken to develop a method for this purpose. A first implementation was done on pilot scale; with a set of both conventional and organic pig farms (N = 15). Fifty hygiene-related factors were selected, especially with reference to the possible proliferation of enteric pathogens Listeria monocytogenes, Yersinia enterocolitica and Yersinia pseudotuberculosis. The factors were allocated into 8 evaluation categories: (1) general production management, (2) animal density, (3) the outdoor area for pigs, (4) pest and pet animals, (5) general hygiene in the piggery, (6) pen hygiene, (7) feed production hygiene, and (8) feeding hygiene. A farm questionnaire and a supplementary on-site observation form were devised, and one arbitrary scale of hygiene points assigned for each factor. In addition to the mailed questionnaires, one person subsequently visited all the farms, perused the questionnaire with the owners and completed the observation form. The hygiene scores of the farms in each evaluation category were compared both without weighting and with weighting based on expert opinions. The method proved to be feasible and applicable to different types of production.     

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.     

Haemodynamic changes during sedation in ponies

The cardiovascular changes induced by several sedatives were investigated in five ponies with a subcutaneously transposed carotid artery by means of cardiac output determinations (thermodilution technique), systemic and pulmonary artery pressure measurements (direct intravascular method) and arterial blood analysis (blood gases and packed cell volume). The cardiovascular depression (decrease in systemic blood pressure and cardiac output) was long lasting (greater than 90 min) after administration of propionylpromazine (0.08 mg/kg intravenous (i.v.)) together with promethazine (0.08 mg/kg i.v.). The phenothiazine-induced sedation was not optimal. alpha 2-Agonists (xylazine (0.60 mg/kg i.v.) and detomidine (20 micrograms/kg i.v.)) induced initial but transient cardiovascular effects with an increase in systemic blood pressure and a decrease in cardiac output for about 15 min. Second degree atrioventricular blocks and bradycardia were seen during this period. The cardiovascular depression was more pronounced during detomidine sedation. Atropine (0.01 mg/kg i.v.) induced a tachycardia with a decrease in stroke volume but did not alter the cardiac output or other cardiovascular parameters. It prevented the occurrence of the bradycardia and heart blocks normally induced by xylazine or detomidine. Atropine potentiated the initial hypertension induced by the alpha 2-agonistic sedatives (especially detomidine). The decrease in cardiac output induced by xylazine, and to a lesser extent by detomidine, was partially counteracted when atropine was given in advance. The atropine-xylazine combination seemed the best premedication protocol before general anaesthesia as it only resulted in minor and transient cardiovascular changes.     

Determination of the effective dosage of tiletamine–zolazepam–ketamine–xylazine,with or without methadone,in dogs

ObjectiveTo determine the effective dosage of the combination tiletamine–zolazepam–ketamine–xylazine (TKX), with or without methadone, in dogs.Study designProspective, randomized, experimental study.AnimalsA total of 29 dogs.MethodsDogs were randomly administered TKX (group TKX, n = 13) or combined with 0.3 mg kg^–1 of methadone (group TKXM, n = 16) intramuscularly. The TKX solution contained tiletamine (50 mg mL^–1), zolazepam (50 mg mL^–1), ketamine (80 mg mL^–1) and xylazine (20 mg mL^–1). The effective dosages for immobility in 50% and 95% of the population (ED₅₀ and ED₉₅) were estimated using the up-and-down method. Approximately 20 minutes after drug administration, a skin incision was performed and the response was judged as positive or negative if the dogs moved or did not move, respectively. The TKX volume for the subsequent dog in the same group was increased or decreased by 0.005 mL kg^–1 if the response of the previous dog was positive or negative, respectively. Heart and respiratory rates, and sedation/anesthesia scores (range 0–21) were recorded before and 15 minutes after drug administration.ResultsEstimated ED₅₀ and ED₉₅ (95% confidence intervals) were: TKX, 0.025 (0.020–0.029) and 0.026 (0.010–0.042) mL kg^–1; TKXM, 0.022 (0.018–0.025) and 0.033 (0.017–0.049) mL kg^–1. Median (interquartile range) scores for sedation/anesthesia were 17 (16–18) and 17 (15–20), and times until lateral recumbency were 5 (4–6) and 6 (4–10) minutes in TKX and TKXM, respectively (p > 0.05). In both groups heart and respiratory rates decreased, but values remained acceptable for anesthetized dogs.Conclusions and clinical relevanceThe results provide a guide for volumes of TKX and TKXM in dogs requiring restraint for minimally invasive procedures. Inclusion of methadone in the TKX combination did not influence ED₅₀.