Pharmacokinetic properties of tramadol and M1 metabolite in Northeast Brazilian donkeys (Equus asinus).

There is currently little information available on the pharmacokinetics and pharmacodynamics of the analgesic opioid tramadol when used in the veterinary medicine of domestic species. In this study, we aimed to determine the pharmacokinetics of tramadol and its active metabolite M1 following intravenous administration of 2 (T2) and 4 (T4) mg/kg to Northeast Brazilian donkeys. Tramadol and M1 plasma levels were quantified using a validated liquid chromatography-tandem mass spectrometry method. We found that plasma levels of tramadol and M1 were higher than those reported as clinically meaningful in humans for at least 3 hr. However, the pharmacokinetic parameter calculation corrected by dose analysis identified no proportional increase with dose for the AUC of tramadol (T2: 2,663 ± 1,827 vs. T4: 2,964 ± 1,038 ng*h/ml) and M1 (T2: 378 ± 237 vs. T4: 345 ± 142 ng*h/ml). This finding appears to be attributable to a significant increase in clearance and a reduction in the terminal half-life of tramadol. The frequency of adverse effects observed at the higher dose indicates that 2 mg/kg administered intravenously would be suitable for donkeys. Clinical studies are required to determine the implications of these observations regarding the pharmacodynamic response to tramadol in Northeast Brazilian donkeys.

Are locally adapted goats able to recover homeothermy, acid-base and electrolyte equilibrium in a semi-arid region?

The objective of this study was to evaluate the thermoregulatory responses, acid-basic and electrolytic equilibrium of locally adapted goats under natural heat conditions in a semi-arid region. Ten (10) Canindé goats aged between 2 and 3 years, non-lactating, non-pregnant and having a body weight (BW) of 22.90 ± 2.70 kg were used in this study. Air temperature (AT) and relative humidity (RH) were measured, and the radiant heat load (RHL) was subsequently calculated. Rectal temperature (RT), respiratory rate (RR), sweating rate (SR) and heat shock (S) were recorded at 1-h intervals for 24 continuous hours. Hydrogen potential (pH), partial pressure of carbon dioxide (PCO2), partial pressure of oxygen (PO2), bicarbonate (HCO3), base excess (BE), total carbon dioxide concentration (TCO2), oxygen saturation (SO2), sodium (Na+) and potassium (K+) were recorded at three moments during the day (5 a.m.; 1 p.m.; 6 p.m.). There were also significant differences between the means of hours of the day for AT and RH. RR was the thermoregulatory response which most closely followed RHL, with important elevations in the periods between 10 a.m. to noon. It was observed that the goats activated their SR mechanism before RR, more precisely between the hours of 9 a.m. and 1 p.m. The acid-base and electrolytic equilibrium for the goats which showed great association with the first components contributed the most to the total variation of the data. The most important variables in the adaptive profile of these animals in order of importance were: SO2, PO2, RR, RT, SR, HCO3, BE, TCO2 and pH. An association between all variables grouped in each period was observed, where the thermoregulatory responses in the periods of 5 a.m. and 6 p.m. were closer than when compared to 1 p.m., showing a physiological return to the initial state. Therefore, the variation in thermoregulatory responses, acid-base and electrolytic equilibrium indicated that the goats have the ability to recover after a challenging environmental condition.

Validation of the Donkey Pain Scale (DOPS) for Assessing Postoperative Pain in Donkeys.

This study aimed to validate a scale for assessing acute pain in donkeys. Forty-four adult donkeys underwent castration after sedation with intravenous (IV) xylazine, induction with guaifenesin and thiopental IV, local anesthetic block, and maintenance with isoflurane. The scale was constructed from a pilot study with four animals combined with algetic behaviors described for equines. After content validation, the scale was evaluated in 40 other donkeys by three blinded and one reference evaluator, by means of edited videos referring to the preoperative and postoperative periods: before anesthesia, 3-4 h after recovery from anesthesia, 5-6 h after recovery from anesthesia (2 h after analgesia with flunixin-1.1 mg/kg, dipyrone-10 mg/kg, and morphine-0.2 mg/kg) IV, and 24 h after recovery. Content validity, sensitivity, specificity, and responsiveness of behaviors were investigated to refine the scale. Intra- and inter-evaluator reliabilities were investigated by the weighted kappa coefficient, criterion validity by comparing the scale with the visual analog scale (VAS), internal consistency by Cronbach's α coefficient, item-total correlation by the Spearman coefficient, and intervention point for rescue analgesic by the receiver operating characteristics curve and Youden index. The scale showed very good intra-evaluator reliability (0.88-0.96), good to moderate (0.56-0.66) inter-evaluator reliability, responsiveness for all items, good criterion validity vs. VAS (0.75), acceptable internal consistency (0.64), adequate item-total correlation, except for head position and direction, and according to the principal component analysis, good association among items. The accuracy of the point for rescue analgesic was excellent (area under the curve = 0.91). The rescue analgesic score was ≥ 4 of 11 points. The scale can diagnose and quantify acute pain in donkeys submitted to castration, as the instrument is reliable and valid, with a defined intervention analgesic score.

Post-operative pain behaviour associated with surgical castration in donkeys (Equus asinus).

BACKGROUND: Recognising pain in donkeys is challenging because they are stoic. OBJECTIVES: To identify the responses of donkeys before and after surgical pain. STUDY DESIGN: Prospective, short-term longitudinal pre- and post-intervention observations. METHODS: Forty adult donkeys underwent surgical castration after sedation with intravenous (IV) xylazine, induction with guaiphenesin/thiopental IV and maintenance of anaesthesia with isoflurane and local anaesthetic blockade. Four hours after recovery from anaesthesia, flunixin meglumine 1.1 mg/kg, dipyrone 10 mg/kg and morphine 0.2 mg/kg IV were administered. Behavioural responses exhibited by the animals housed in individual stalls were recorded in four 30-min videos: before castration (M0), and 3.5-4.0 hours (M1), 5.5-6.0 hours (M2) and 23.5-24.0 hours after recovery from anaesthesia (M3). To exclude the influence of insects, the behaviour of six apparently pain-free donkeys was compared with and without the presence of faeces and urine in the stall. RESULTS: When compared with presurgical baseline behaviours (M0), after surgery (M1) donkeys raised their pelvic limbs more (P = .003). When compared with M1, after analgesia (M2), the median frequencies of ear movements (44 vs 16; P < .001), head shaking (7 vs 1; P < .001), head turning (5 vs 0; P < .001) and lifting of the both limbs (7 vs 0; P = .008) decreased; feeding (0 vs 29; P < .001) and water intake (0 vs 0, range 0-1 vs 0-7; P = .05) increased. The dirty stall increased tail (53 vs 80; P = .03), head (16 vs 30; P = .03) and ear movements (50 vs 78; P = .04). MAIN LIMITATIONS: The dirty stall and presence of insects possibly contributed to the expression of behaviours unrelated to pain. CONCLUSION: Lifting the pelvic limbs was the only specific pain behaviour after castration in donkeys. Analgesia restored appetite and water intake and reduced the frequency of head shaking and turning, ear movement and lifting the limbs. Tail, head and ear movements are unspecific responses related both to pain and a dirty stall, and are confounding factors when pain is assessed in donkeys in the presence of insects.