20Objectives The aim of this study was to optimize dexmedetomidine and alfaxalone 21 dosing, for intramuscular administration with butorphanol, to perform minor surgeries 22 in cats. 23Methods Initially, cats were assigned to one of 5 groups, each composed of 6 animals 24 and receiving, in addition to 0.3 mg/kg butorphanol IM, one of the following: A: 0.005 25 mg/kg dexmedetomidine, 2 mg/kg alfaxalone; B: 0.008 mg/kg dexmedetomidine, 1.5 26 mg/kg alfaxalone; C: 0.012 mg/kg dexmedetomidine, 1 mg/kg alfaxalone; D: 0.005 27 mg/kg dexmedetomidine, 1 mg/kg alfaxalone; and E: 0.012 mg/kg dexmedetomidine, 2 28 mg/kg alfaxalone. Thereafter, a modified "direct search" method, conducted in a 29 stepwise manner, was used to optimize drugs dosing. The quality of anaesthesia was 30 evaluated on the basis of composite scores (one for anaesthesia and one for recovery), 31 of Visual Analogue Scales, and of propofol requirement to suppress spontaneous 32 movements. The medians or means of these variables were used to rank the treatments: 33 "unsatisfactory" and "promising" combinations were identified to calculate, through the 34 equation first described by Berenbaum in 1990, new dexmedetomidine and alfaxalone 35 doses to be tested in the next step. At each step, 5 combinations (one new plus the best 36 previous four) were tested. 373 Results None of the tested combinations resulted in adverse effects. Four steps and 120 38 animals were necessary to identify the optimal drug combination (0.014 mg/kg 39 dexmedetomidine, 2.5 mg/kg alfaxalone and 0.3 mg/kg butorphanol). 40Conclusions and relevance The investigated drug mixture, at the doses found with the 41 optimization method, is suitable for cats undergoing minor clinical procedures. 42 43
BackgroundPain accompanying mastitis has gained attention recently as a relevant welfare compromising aspect of disease. Adequate pain recognition and therapy are necessary in the context of a modern and ethically acceptable dairy care. For research purposes mastitis is often induced by intramammary infusion of immunogenic bacterial cell wall components. Lipopolysaccharide (LPS) from Escherichia coli and lipoteichoic acid (LTA) from Staphylococcus aureus are commonly administered to this end. While the immune response to specific immunogenic components has been well characterized, not much is known about their role on the expression of pain indicators. The aim of this study was to trial the effects of an intramammary challenge of LTA or LPS on the degree of pain and discomfort as indicated by both physiological and behavioral variables in cows. The hypothesis was that a similar degree of pain can be identified in LTA as well as in LPS induced mastitis.ResultsOn the challenge day, compared to pre-challenge, total pain index increased for all treatment groups (LPS; LTA and control), the LPS group having significantly higher values than the control group (P = 0.01). Similarly, pain visual analogue scale (VAS) increased significantly in all cows following treatment on the challenge day. Furthermore, compared to baseline, higher VAS were found 3, 4 and 5 h after the challenge in cows of the LPS group (P3h, 4h < 0.001 and P5h = 0.001) and 7 h after the challenge in cows of the LTA group (P7h = 0.002). In the control group, VAS was higher 5 h after the challenge (P5h = 0.001). On the challenge day, udder edema was higher in the LPS than in the control group (P = 0.007). Furthermore, 4 h after the challenge, milk cortisol was significantly higher than at baseline in the LPS group (P < 0.001).ConclusionsWhen administered at equipotent doses targeting a standard somatic cell count increase, intramammary LPS seems to be accompanied by a higher degree of pain and discomfort than LTA, as suggested by the modifications of the outcome variables total pain index, VAS, udder edema and milk cortisol.Electronic supplementary materialThe online version of this article (doi:10.1186/s13028-017-0306-z) contains supplementary material, which is available to authorized users.
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