Plasma pharmacokinetics of alfaxalone after a single intraperitoneal or intravenous injection of Alfaxan(®) in rats.

Alfaxalone (3α-hydroxy-5α-pregnane-11, 20-dione) is a neuroactive steroid with anaesthetic properties and a wide margin of safety. The pharmacokinetic properties of alfaxalone administered intravenously and intraperitoneally in rats (n = 28) were investigated. Mean t(1/2elim) for 2 and 5 mg/kg i.v. was 16.2 and 17.6 min, respectively, but could not be estimated for IP dosing, due to sustained plasma levels for up to 60 min after injection. Clp for i.v. injection was calculated at 57.8 ± 23.6 and 54.3 ± 6.8 mL/min/kg, which were 24.5% and 23% of cardiac output, respectively. The observed C(max) was 3.0 mg/L for IP administration, and 2.2 ± 0.9 and 5.2 ± 1.3 mg/L for 2 and 5 mg/kg i.v. administration, respectively. AUC(0-60) was 96.2 min.mg/L for IP dosing. The relative bioavailability for IP dosing was 26% and 28% compared to i.v. dosing. Differences in t(1/2elim) and Cl(p) from previous pharmacokinetic studies in rats are likely due to variations in alfaxalone formulation rather than sex differences. Alfaxan® given IP caused sustained levels of alfaxalone, no apnoea and longer sleep times than i.v. dosing, although immobilization was not induced in 30% of rats given Alfaxan® IP. A pharmacodynamic study of the effects of combining IP injection of Alfaxan® with other premedication agents is worthwhile, to determine whether improved anaesthesia induction could ultimately provide an alternative anaesthetic regimen for rats.

Alfaxalone and medetomidine intravenous infusion to maintain anaesthesia in colts undergoing field castration.

REASONS FOR PERFORMING THE STUDY: The use of alfaxalone and medetomidine administered as an i.v. infusion to maintain anaesthesia has not previously been reported in the horse. OBJECTIVES: To investigate the use of alfaxalone in hydroxpropyl-beta-cyclodextrin (Alfaxan) and medetomidine infusion as a field anaesthetic for short-term surgical procedures in the horse. HYPOTHESIS: Alfaxalone-medetomidine anaesthesia is suitable for short-term field anaesthesia in horses. METHODS: Eleven healthy colts underwent 45 min of anaesthesia with an i.v. infusion of alfaxalone (2 mg/kg bwt/h) and medetomidine (5 µg/kg bwt/h) for routine field castration. Horses were premedicated with i.v. acepromazine (0.03 mg/kg bwt), medetomidine (7 µg/kg bwt) and guaiphenesin (35 mg/kg bwt) before i.v. induction with alfaxalone (1 mg/kg bwt). Colts were intubated with an endotracheal tube and 100% oxygen insufflated at 10 l/min. The physiological variables monitored included pulse rate, respiratory rate, direct arterial blood pressure, arterial blood gases and the quality of the inductions and recoveries were scored. RESULTS: Overall, the anaesthetic period and surgical conditions were acceptable and the quality of the anaesthetic inductions and recoveries was good to excellent. All colts stood on their first attempt (mean ± s.d.) 37 ± 13.5 min after the infusion was stopped. During anaesthesia, cardiopulmonary data, presented as range of mean values at each time point were: heart rate: 45-47 beats/min; mean blood pressure: 104-112 mmHg; respiratory rate: 8 breaths/min; PaO2 : 117-172 mmHg; PaCO2 : 50-56 mmHg and pH 7.34-7.37. CONCLUSIONS AND POTENTIAL RELEVANCE: The co-administration of alfaxalone and medetomidine as an i.v. infusion after anaesthetic induction with alfaxalone was suitable for short-term field anaesthesia in the horse.

Postoperative pain and perioperative analgesic administration in dogs: practices, attitudes and beliefs of Queensland veterinarians.

OBJECTIVE: The aim of this study was to describe the practices, attitudes and beliefs of Queensland veterinarians in relation to postoperative pain and perioperative analgesia in dogs. METHODS: One veterinarian from each of the 50 randomly selected Queensland veterinary practices was enrolled after selection by convenience sampling. RESULTS: The study response rate was 94.3%. Demeanour, vocalisation and heart rate were the most common postoperative pain assessment tools used, even though the most sensitive tools were considered to be demeanour, heart rate and respiratory rate. Only 20% of respondents used formalised pain scoring systems. Preoperative analgesic administration was always used by 72% of respondents. There was marked variability in the frequency with which analgesia was administered perioperatively for ovariohysterectomy. Only 24% of veterinarians discharged animals with ongoing analgesia even though 38% agreed that pain is still present 7 days postoperatively. Multimodal analgesia was used by 82% of respondents. Epidural and local anaesthetic analgesic techniques were not being utilised by any respondents. Conclusions These results indicate that management of postoperative pain in dogs in Queensland is frequently suboptimal and, at times, is not consistent with the veterinarian's attitudes and beliefs. Continuing education into analgesic use and pain evaluation may be effective in addressing this.

Effect of intravenous dose escalation with alfaxalone and propofol on occurrence of apnoea in the dog.

Spontaneous ventilation after induction of anaesthesia with intravenous alfaxalone or propofol was evaluated in a dose escalation study using 6 dogs. Each dog was dosed at 1×, 2×, 5×, 10× and 20× multiples of the labelled doses (2mg/kg for alfaxalone; 6.5mg/kg for propofol), until apnoea was observed. For each administration, the entire calculated dose was delivered over 1 min. All 6 dogs ventilated spontaneously after labelled (1×) doses of each drug but became apnoeic at 5× dose of propofol versus 20× dose of alfaxalone. For propofol at 2× and 5× doses, 4 and 0 dogs ventilated spontaneously respectively. For alfaxalone at 2×, 5× and 10× doses all 6, 4 and 1 dog ventilated spontaneously, respectively. The median dose which induced apnoea was higher for alfaxalone (5×) than for propofol (2×) (p=0.05). We concluded that induction of anaesthesia with propofol is more likely to induce apnoea than with alfaxalone.

Changes to porcine blastocyst vitrification methods and improved litter size after transfer.

The objective was to improve the protocol that was used to obtain the first reported piglets from transferred vitrified and warmed zona-intact blastocysts. Blastocysts were collected from superovulated sows and gilts, centrifuged to polarize lipid, vitrified, warmed and cultured for 24h or transferred immediately. Removing the zona pellucida after warming increased the number of cells in the surviving blastocysts (zona-free 60.8+/-4.3, zona-intact 39.1+/-2.8; P<0.05). Thinning the zona pellucida produced similar results to zona removal. Changing the basal medium of the vitrification and warming solutions from modified PBS to phosphate buffered NCSU-23 increased the number of cells (44.7+/-2.2 versus 56.0+/-3.9, respectively; P<0.05). Reducing the plunge temperature of the liquid nitrogen from -196 degrees C to less than -204 degrees C improved the embryo survival rate (61.9% versus 82.9%, respectively; P<0.05). These modifications were incorporated into the vitrification protocol that was used to vitrify and warm 105 blastocysts (that were subsequently transferred into four recipients). Three recipients became pregnant, farrowing three litters (average litter size, 5.3; 18.8% embryo survival in farrowing sows). Changing the warming protocol to using sucrose rather than ethylene glycol resulted in a trend towards improved embryo survival (73.5% versus 91.2%) but this was not statistically significant. Incorporating this modification, 203 blastocysts were vitrified, warmed and transferred into seven recipients. Five became pregnant and 36 fetuses were recovered (average litter size 7.2; 24.8% embryo survival in pregnant sows) at Day 40 of pregnancy. In conclusion, changes made to the vitrification protocol improved pregnancy rate and in vivo embryo survival compared to an earlier study using the original protocol.

Farrowing rates and litter size following transfer of vitrified porcine embryos into a commercial swine herd.

The objective was to determine farrowing rates and litter sizes that could be achieved in a typical farm-to-farm porcine embryo transfer program using vitrified blastocysts that were zona pellucida intact when cryopreserved. The embryos were transferred surgically on-farm into recipient sows that were managed throughout gestation and farrowing under the same conditions as other sows in the herd. Twenty recipient sows (mean parity 2.1) received a total of 568 embryos; seven received 203 embryos derived from donor sows, five received 139 embryos from gilts and eight received a mixture of 161 embryos from sows and 65 from gilts. Sixteen sows (80%) were confirmed pregnant at approximately 35 days gestation, 15 farrowed at full term (farrowing rate 75%). One sow died during gestation (with a total of 18 fetuses in utero). A total of 123 piglets were born (mean, 8.2), of which 115 were born alive (mean, 7.7). Of the 568 embryos transferred to all 20 sows, 21.6% resulted in piglets born and 29.0% survived to produce piglets in sows that farrowed. There were no significant differences in embryo survival among sow, gilt or mixed sow and gilt embryos. The ratio of males to females was 71/52 and the mean birth weight was 1.6 kg (range 0.6-2.6 kg). In conclusion, vitrified zona pellucida intact embryos can be used to transfer genetic material from farm-to-farm with acceptable reproductive performance.

Intraarticular and periarticular opioid binding in inflamed tissue in experimental canine arthritis.

UNLABELLED: Small-dose (1 mg) intraarticular morphine has been used successfully in many studies to provide long-lasting analgesia after arthroscopic knee surgery. We used radioligand binding to determine whether these effects could be mediated by opioid binding sites in the joint, particularly after the induction of inflammation. Inflammation was induced by the injection of oleyl alcohol (20 microL) in sterile peanut oil (0.25 mL) into the left radiocarpal joint of 27 dogs, and the dogs were euthanized at 12 h. The articular and periarticular tissues from both treated and control joints were collected, and membranes were prepared for equilibrium binding assays. The density of specific opioid binding was markedly enhanced (P < 0.05) in homogenates prepared from the treated relative to those from the control joint. The binding affinities (KD values) for morphine and naloxone (mean +/- SEM) were approximately one one-hundredth (79 +/- 17 nM and 124 +/- 5.5 nM, respectively) that of the corresponding published affinities in brain tissue. However, the binding site densities were approximately one hundred times larger (Bmax = 1032 +/- 265 and 543 +/- 51 fmol/mg of protein) than the respective published values in brain tissue. These findings imply that the opioid binding sites, found in the inflamed articular and periarticular tissues in this study, are similar to those of putative mu 3-opioid binding sites that appear to be present on cultured thymocytes and in the airways of rats and humans. IMPLICATIONS: The high density of opioid binding sites found in inflamed canine joint tissue supports the clinical use of intraarticular opioids in the treatment of postoperative and chronic inflammatory joint pain.

Electromyography of some respiratory muscles in the horse.

To investigate activity in respiratory muscles, insulated wire electrodes were used to record electromyographic activity in the costal diaphragm and in the intercostal, serratus ventralis, internal abdominal oblique, transversalis and rectus abdominis muscles in conscious horses and in the same animals when anaesthetised. Electromyographic activity was related to respiratory phases as recorded by a stethograph around the chest wall. The costal diaphragm showed tonic and inspiratory activity in both conscious and anaesthetised animals. The principal muscle actively involved in expiration was the transversalis muscle. Intercostal muscle activity, and any increased activity in the second part of either inspiration or expiration recorded in the conscious animal, was absent under anaesthesia. The very marked tonic activity found in the serratus ventralis muscle in standing horses disappeared during anaesthesia. It was concluded that any stabilisation of the chest wall contributed by activity in the serratus ventralis and intercostal muscles in conscious, standing horses is greatly reduced during anaesthesia.