I.A. Gómez de Segura

Guidelines for the veterinary care of laboratory animals: report of the FELASA/ECLAM/ESLAV Joint Working Group on Veterinary Care

Summary Veterinary professionals working in partnership with other competent persons are essential for a successful animal care and use programme. A veterinarians primary responsibilities are defined by their own professional regulatory bodies, but in this area of work there are further opportunities for contribution, which will assist in safeguarding the health and welfare of animals used in research. These guidelines are aimed not only at veterinarians to explain their duties, and outline the opportunities to improve the health and welfare of animals under their care, but also at employers and regulators to help them meet their responsibilities. They describe the desirability for postgraduate education towards specialization in laboratory animal medicine and detail the many competencies necessary to fulfil the role of the laboratory animal veterinarian. They detail the need for veterinary expertise to promote good health and good welfare of animals used in biomedical research during husbandry as well as when under experimental procedures. Regulatory and ethical aspects are covered as are the involvement of the veterinarian in education and training of others working in the animal care and use programme. Managerial aspects, including occupational health and safety, are also areas where the veterinarians input can assist in the successful implementation of the programme.

Effects of constant rate infusion of lidocaine and ketamine, with or without morphine, on isoflurane MAC in horses.

REASONS FOR PERFORMING STUDY Lidocaine and ketamine are administered to horses as a constant rate infusion (CRI) during inhalation anaesthesia to reduce anaesthetic requirements. Morphine decreases the minimum alveolar concentration (MAC) in some domestic animals; when administered as a CRI in horses, morphine does not promote haemodynamic and ventilatory changes and exerts a positive effect on recovery. Isoflurane-sparing effect of lidocaine, ketamine and morphine coadministration has been evaluated in small animals but not in horses. OBJECTIVES To determine the reduction in isoflurane MAC produced by a CRI of lidocaine and ketamine, with or without morphine. HYPOTHESIS Addition of morphine to a lidocaine-ketamine infusion reduces isoflurane requirement and morphine does not impair the anaesthetic recovery of horses. METHODS Six healthy adult horses were anaesthetised 3 times with xylazine (1.1 mg/kg bwt i.v.), ketamine (3 mg/kg bwt i.v.) and isoflurane and received a CRI of lidocaine-ketamine (LK), morphine-lidocaine-ketamine (MLK) or saline (CTL). The loading doses of morphine and lidocaine were 0.15 mg/kg bwt i.v and 2 mg/kg bwt i.v. followed by a CRI at 0.1 mg/kg bwt/h and 3 mg/kg bwt/h, respectively. Ketamine was given as a CRI at 3 mg/kg bwt/h. Changes in MAC characterised the anaesthetic-sparing effect of the drug infusions under study and quality of recovery was assessed using a scoring system. RESULTS Mean isoflurane MAC (mean ± s.d.) in the CTL, LK and MLK groups was 1.25 ± 0.14%, 0.64 ± 0.20% and 0.59 ± 0.14%, respectively, with MAC reduction in the LK and MLK groups being 49 and 53% (P<0.001), respectively. No significant differences were observed between groups in recovery from anaesthesia. CONCLUSIONS AND CLINICAL RELEVANCE Administration of lidocaine and ketamine via CRI decreases isoflurane requirements. Coadministration of morphine does not provide further reduction in anaesthetic requirements and does not impair recovery.

Gait analysis using 3D accelerometry in horses sedated with xylazine

The aim of the present study was to verify the efficacy and sensitivity of an accelerometric device in detecting and quantifying the degree of movement alteration produced in horses sedated with xylazine. Horses (n=6) were randomly administered either xylazine or a control by intravenous injection, with at least 1 week between each treatment. A triaxial accelerometric device was used for the accelerometric gait assessment 15 min before (baseline) and 5, 15, 30, 45, 60, 75, 90, 105 and 120 min after each treatment. Eight different accelerometric parameters were calculated, including speed, stride frequency, stride length, regularity, dorsoventral power, propulsion power, mediolateral power and total power, with the force of acceleration and the dorsoventral, mediolateral and craniocaudal (propulsive) parts of the power then calculated. Administration of xylazine decreased many of the parameters investigated, with significant differences for speed, stride frequency, dorsoventral power, propulsion power and total power at 5, 15, 30 and 45 min after injection. There were no significant differences in stride length values at any time point. Decreases in regularity values were evident with significant differences at every time point from 5 to 120 min following xylazine injection. Force values were also significantly reduced from 5 to 30 min after treatment and a redistribution of the total power was observed 5 min after injection as the mediolateral power increased significantly, while the dorsoventral power decreased. Accelerometry offers a practical, accurate, easy to use, portable and low cost method of objectively monitoring gait abnormalities at the walk in horses after sedation with xylazine.

Effects of a stepwise lung recruitment manoeuvre and positive end-expiratory pressure on lung compliance and arterial blood oxygenation in healthy dogs

This study was performed to evaluate the effects of a stepwise lung recruitment manoeuvre (RM) on dynamic lung compliance (Cdyn) and gas exchange in mechanically ventilated healthy dogs. Fourteen healthy adult dogs, scheduled for elective surgery in dorsal recumbency were employed. After anaesthetic induction, dogs were mechanically ventilated in a volume-controlled mode (tidal volume, VT=10 mL/kg); positive end-expiratory pressure (PEEP)=0 cm H(2)O; oxygen inspired fraction (FiO(2))=0.4 for 30 min (baseline). The dogs were then randomly allocated into two groups, control and RM. The ventilatory mode was maintained during the whole surgical procedure in the control group without any intervention, as in general practice. The RM was performed in a pressure-controlled mode, with progressive increases of PEEP and end-inspiratory pressure of 5 cm H(2)O until 15 cm H(2)O and 30 cm H(2)O, respectively. After RM, PEEP was decreased to 4 cm H(2)O, and the ventilatory mode was returned to volume-control. Arterial blood gases and Cdyn were determined at baseline, 20 and 60 min afterwards. Students t test and the one-way ANOVA test were employed to compare data. Cdyn increased in the RM group (183 ± 30% and 165 ± 24% at 20 and 60 min, respectively; P=0.000). The baseline partial pressure of arterial oxygen to FiO(2) ratio (PaO(2)/FiO(2) ratio) did not change in the control group, but was higher in the RM group (527 ± 41 mm Hg and 511 ± 46 mm Hg at 20 and 60 min, respectively; baseline 371 ± 34 mm Hg, P<0.001). In conclusion, a stepwise RM followed by the use of PEEP improves Cdyn and oxygenation in mechanically ventilated healthy dogs.

Remifentanil and cyclooxygenase inhibitors interactions in the minimum alveolar concentration of sevoflurane in the rat

BACKGROUND Intraoperative opioids reduce anaesthetic requirements and thus limit the side-effects derived from high doses of the latter. Cyclooxygenase (COX) inhibitors can also be given but it remains unclear whether they further reduce the anaesthetic requirements. Our aim was to determine whether COX inhibitors potentiate the effect of remifentanil on the minimum alveolar concentration (MAC) of sevoflurane anaesthetized rats. METHODS Male Wistar rats received remifentanil under sevoflurane anaesthesia, and the MAC was determined before and at two time intervals after, separated by 1.5 h. Rats were randomly allocated to receive paracetamol, metamizole, ketoprofen, or parecoxib just before one of the two studied time intervals. The MAC was determined from alveolar gas samples at the time of tail clamp. Data were analysed with an analysis of variance for repeated measures. RESULTS Paracetamol potentiated the MAC reduction produced by remifentanil in rats (P=0.002), whereas metamizole, ketoprofen, and parecoxib failed to produce such an effect. Furthermore, paracetamol and remifentanil produced a maximum degree of MAC reduction [35 (10)%] even when a tolerance effect to remifentanil was observed in animals given remifentanil alone (P<0.001). A tolerance to remifentanil was not observed when metamizole, ketoprofen, or parecoxib was given once the opioid infusion has been started (P>0.05). CONCLUSIONS COX inhibitors differentially potentiate the analgesic effect produced by remifentanil on the sevoflurane MAC, and paracetamol was the most effective drug. However, since all COX inhibitors prevented a tolerance effect to opioids once it was established, intraoperative rather than preoperative administration of these drugs is suggested.

Anaesthetic and cardiorespiratory effects of a constant-rate infusion of alfaxalone in desflurane-anaesthetised sheep.

A prospective, randomised, blinded controlled study was performed to determine the anaesthetic and cardiorespiratory effects of a constant-rate infusion (CRI) of alfaxalone in 12 sheep anaesthetised with desflurane, and undergoing experimental orthopaedic surgery. Sheep were sedated with dexmedetomidine (4 μg/kg, intravenously) and butorphanol (0.3 mg/kg, intravenously). Anaesthesia was induced with alfaxalone (1 mg/kg/minute to effect, intravenously) and maintained with desflurane in oxygen and alfaxalone 0.07 mg/kg/minute or saline for 150 minutes (range 150–166 minutes). The anaesthetic induction dose of alfaxalone, the desflurane expiratory fraction required for anaesthetic maintenance, cardiorespiratory measurements and blood-gases were recorded at predetermined intervals. Quality of sedation, anaesthetic induction and recovery were assessed. The alfaxalone induction dose was 1.7 mg/kg (1.2 to 2.6 mg/kg). The desflurane expiratory fraction was lower (22 per cent) in sheep receiving alfaxalone CRI (P = 0). Also, heart rate (P = 0), cardiac index (P = 0.002), stroke index (P = 0) and contractility (P = 0) were higher, and systemic vascular resistance (P = 0.002) was lower. Although respiratory rate tended to be higher with alfaxalone, there was no difference in PCO2 between the groups. Recovery times were significantly longer in sheep given alfaxalone (25.4 v 9.5 minutes) but recovery quality was similar. Alfaxalone reduced requirements of desflurane and maintained similar cardiorespiratory function, but recovery time was more prolonged.

Comparison of sedation scores and propofol induction doses in dogs after intramuscular administration of dexmedetomidine alone or in combination with methadone, midazolam, or methadone plus midazolam.

The objectives of this study were to determine: (1) the sedative effects of dexmedetomidine in combination with methadone, midazolam, or both, and (2) the propofol dose required to achieve endotracheal intubation in healthy dogs. Seven healthy Beagle dogs were included in a prospective experimental, crossover, randomised and masked design. All dogs received four treatments IM, with at least 1 week between sessions, as follows: dexmedetomidine 5 µg/kg (D) alone, or combined with methadone 0.3 mg/kg (DMe), midazolam 0.3 mg/kg (DMi), or both (DMeMi). The degree of sedation was evaluated using a numerical scale (maximum 15 points). The dose of propofol required for intubation was also calculated for each group. Recovery time and quality were determined. Statistical analysis was performed using parametric (ANOVA) and nonparametric tests (Friedman, Cochran Q), as appropriate. The degree of sedation obtained with DMe and DMeMi (13, [7-14]; 13, [6-14], respectively) was significantly higher than in the control group (2, [1-4]; P = 0.023, P = 0.006, respectively). The required dose of propofol was lower in all groups (DMi, 1.5 ± 0.5 mg/kg, P = 0.002; DMe, 1.2 ± 0.5 mg/kg, P <0.001; DMeMi, 0.9 ± 0.3 mg/kg) than in the control group (2.9 ± 0.9 mg/kg; P <0.001). Recovery quality was not different between groups (P = 0.137). In healthy dogs, the addition of midazolam did not enhance the sedative effects of dexmedetomidine or a dexmedetomidine-methadone combination at the doses studied, and propofol requirements were reduced. The sedative effect of dexmedetomidine was enhanced with methadone, and the required dose of propofol was reduced.

Evaluation of an oesophageal Doppler device for monitoring cardiac output in anaesthetised healthy normotensive dogs

OBJECTIVES To compare cardiac output measured by oesophageal Doppler and by thermodilution monitoring and to correlate the Doppler cardiac output-generated minute distance with thermodilution cardiac output in healthy anaesthetised beagle dogs. MATERIALS AND METHODS Prospective experimental study. Six healthy adult beagle dogs were pre-medicated with intramuscular acepromazine (0 · 05 mg/kg) and methadone (0 · 3 mg/kg). Anaesthesia was induced with intravenous propofol (dose-effect) and maintained with isoflurane in oxygen. Simultaneously, a constant rate infusion of dopamine (3 µg/kg/minute) was administered to the dogs to prevent hypotension. The minute distance, Doppler and thermodilution cardiac outputs were assessed at three different end-tidal concentrations of isoflurane (1 · 0, 1 · 3 and 2 · 0%). RESULTS Correlation between Doppler and thermodilution cardiac output (r(2)  = 0 · 582) and between minute distance and thermodilution cardiac output (r(2)  = 0 · 658) were moderately good, but the limits of agreement between Doppler and thermodilution cardiac outputs were above the recommended values (±39%, for a recommended value up to 30%). CLINICAL SIGNIFICANCE Doppler and minute distance cannot be considered as an alternative method to thermodilution to monitor cardiac output in the healthy anaesthetised dog.

Anaesthetic effects in the ferret of alfaxalone alone and in combination with medetomidine or tramadol: a pilot study.

Alfaxalone is a neurosteroid with anaesthetic effects and it has been used successfully in several animal species. However, there are no data, to our knowledge, about its efficacy and safety in ferrets (Mustela putorius furo). We evaluated a variety of anaesthetic regimens in ferrets, namely, alfaxalone at 20, 10 and 5 mg/kg (n = 1, 10 and 9, respectively; intravenously); medetomidine at 20 µg/kg (n = 3; intramuscularly); medetomidine (20 µg/kg, intramuscularly) plus alfaxalone (2.5 mg/kg, intravenously; n = 7); and tramadol (5 mg/kg, intramuscularly) plus alfaxalone (5 mg/kg, intravenously; n = 2). Two animals treated with alfaxalone at 10 mg/kg and 20 mg/kg, respectively, died. At 5 mg/kg alfaxalone produced anaesthesia with a similar onset but a shorter duration of anaesthesia and analgesia than alfaxalone at 10 mg/kg. The medetomidine–alfaxalone combination produced anaesthesia and analgesia of a longer duration than alfaxalone administered alone at 5 mg/kg (P < 0.0001 and P < 0.001, respectively). Under this anaesthetic regimen, there was a progressive decrease in pulse rate during the first 30 min before the pulse rate stabilized. Respiratory parameters were maintained at acceptable levels. When tramadol was administered, all the animals exhibited a strong excitation reaction and in no case was the toe-pinch reflex clearly abolished. Thus, alfaxalone plus medetomidine provided safe and effective anaesthesia in ferrets. Alfaxalone, alone or in combination with tramadol, did not produce satisfactory results for use as an anaesthetic for this species.

Effects of fluid load on cardiovascular function during stepwise lung recruitment manoeuvre in healthy dogs.

The aim of this study was to evaluate the effects of a stepwise lung recruitment manoeuvre (RM) on cardiac output (CO) in mechanically ventilated dogs, with or without a previous fluid load. Eight healthy adult Beagle dogs were enrolled in a prospective crossover study. Following sedation with dexmedetomidine and methadone, anaesthesia was induced with propofol and maintained with isoflurane. CO (thermodilution method) and direct arterial blood pressure were monitored. The dogs were mechanically ventilated in a volume-controlled mode (tidal volume, VT = 10 mL/kg; positive end-expiratory pressure [PEEP] = 0 cm H2O) until normocapnia was achieved (end tidal CO2 35-45 mmHg). The RM was then performed in a pressure-controlled mode, with progressive increases of the PEEP and end-inspiratory pressure of 5 cm H2O, until 15 cm H2O and 30 cm H2O were reached, respectively. After the RM, the ventilatory mode was returned to volume-control, and the PEEP was sequentially decreased to 10, 5 and 0 cm H2O. Baseline ventilation was maintained for 30 min. Next, 10 mL/kg of lactated Ringers solution was administered within 10 min, prior to a second RM. The CO was determined before each RM (baseline) and at each pressure step. A repeated measures ANOVA test was used to compare data. Compared to baseline, CO decreased during the RM in both groups. However, there was a significantly higher CO during the second RM at the highest pressure step (P<0.05) and during all decreasing pressure steps (P<0.05). In conclusion, a previous crystalloid fluid load could reduce the impact of a RM on CO in healthy dogs.