Morphine in donkeys: Antinociceptive effect and preliminary pharmacokinetics.

BACKGROUND: Morphine is the prototypical µ-opioid receptor agonist used to provide analgesia in veterinary species. Its effects are well-described in horses but not donkeys. OBJECTIVES: To determine the antinociceptive effects of two doses of morphine in donkeys. To describe preliminary pharmacokinetic parameters of morphine in donkeys. STUDY DESIGN: In vivo experiment. METHODS: Eight adult castrated male donkeys were given intravenous (IV) 0.9% saline, morphine 0.1 mg/kg bwt (LDM), or morphine 0.5 mg/kg bwt (HDM) in a randomised order with a minimum 1-week washout period. Mechanical nociceptive thresholds (MNTs) were determined by a blinded investigator pre-injection and 15, 30, 45, 60, 90, 120, 150, 180, 210, 240, 300, and 360 min post-injection. Venous blood samples were collected pre-injection and 2, 5, 10, 15, 30, 45, 60, 90, and 120 min post-injection. Data were analysed using Friedman's test with Dunn's post hoc test for multiple comparisons. Pharmacokinetic parameters were calculated for the HDM treatment. RESULTS: Baseline MNT was [median (interquartile range)] 8.9 (7.1-10.3) N and did not differ between treatments. Peak MNTs occurred at 60 min for both LDM (16.2 N) and HDM (25.0 N) treatments. MNTs after HDM treatment were higher than saline (p < 0.04) at 15, 60, 90, 120, 150, 180, 240, and 300 min post-injection. MNTs after LDM treatment were higher than baseline (p < 0.05) at 45 and 60 min post-injection. Terminal half-life for HDM was (mean ± SD) 51.0 ± 10.7 min, the volume of distribution at steady-state 2.07 ± 0.33 L/min and clearance 49.2 ± 4.16 ml * min/kg using noncompartmental analysis. The concentration of morphine-3-glucuronide (M3G) was higher than morphine-6-glucuronide (M6G) at all sampled time points. MAIN LIMITATIONS: Short duration of plasma sampling for pharmacokinetic analysis; lack of objective measure of gastrointestinal function. CONCLUSIONS: The HDM treatment provided mechanical antinociception in donkeys with no significant adverse effects.

Effects of two continuous infusion doses of lidocaine on isoflurane minimum anesthetic concentration in chickens.

OBJECTIVE: To assess the effect of two intravenous (IV) doses of lidocaine on the minimum anesthetic concentration (MAC) of isoflurane in chickens. STUDY DESIGN: Blinded, prospective, randomized, experimental crossover study. ANIMALS: A total of six adult female chickens weighing 1.90 ± 0.15 kg. METHODS: Chickens were anesthetized with isoflurane and mechanically ventilated. Isoflurane MAC values were determined (T0) in duplicate using an electrical noxious stimulus and the bracketing method. After MAC determination, a low dose (LD; 3 mg kg-1 followed by 3 mg kg-1 hour-1) or high dose (HD; 6 mg kg-1 followed by 6 mg kg-1 hour-1) of lidocaine was administered IV. MAC determination was repeated at 1.5 (T1.5) and 3 (T3) hours of lidocaine administration and blood was collected for analysis of plasma lidocaine and monoethylglycinexylidide (MEGX) concentrations. Pulse rate, peripheral hemoglobin oxygen saturation, noninvasive systolic arterial pressure and cloacal temperature were recorded at T0, T1.5 and T3. Treatments were separated by 1 week. Data were analyzed using mixed-effects model for repeated measures. RESULTS: MAC of isoflurane (mean ± standard deviation) at T0 was 1.47 ± 0.18%. MAC at T1.5 and T3 was 1.32 ± 0.27% and 1.26 ± 0.09% (treatment LD); and 1.28 ± 0.06% and 1.30 ± 0.06% (treatment HD). There were no significant differences between treatments or times. Maximum plasma lidocaine concentrations at T3 were 496 ± 98 and 1200 ± 286 ng mL-1 for treatments LD and HD, respectively, and were not significantly different from T1.5. With treatment HD, plasma concentration of MEGX was significantly higher at T3 than at T1.5. Physiological variables were not significantly different among times with either treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of lidocaine did not significantly change isoflurane MAC in chickens. Within treatments, plasma lidocaine concentrations were not significantly different at 1.5 and 3 hours.

Anatomical landmarks for a proximal paravertebral thoracolumbar block in sheep: Cadaver and in-vivo study.

The objective of this study was to describe the anatomy of the spinal nerves, specifically the last thoracic nerve (T13) and the first to third lumbar nerves (L1 to L3), in order to safely carry out an accurate proximal paravertebral block (PPVB) in sheep. This study consisted of 2 phases. In Phase 1, 7 sheep cadavers were dissected to identify the path and relevant anatomical landmarks of spinal nerves T13 and L1 to L3. In Phase 2, 2 healthy sheep received bilateral injections of 0.35 mL/kg body weight (BW) for each hemithoracolumbar area (0.088 mL/kg BW per nerve) of a dye-lidocaine solution (50:50) using a PPVB approach and then assessed for 15 min for signs of systemic and local effects of lidocaine. After euthanasia, the infiltrated area was dissected to assess the spread of the dye. Successful nerve staining (> 2 cm in length), macroscopic evidence of intraneural/intravascular injection, and spread to the epidural space and the abdominal cavity were recorded. In Phase 1, each branch of all nerves was easily identified and located using the caudal aspect of the spinous apophysis and the lateral edge of the transverse process of the respective vertebrae. An overlap was observed between the costoabdominal (T13), the iliohypogastric (L1), and ilioinguinal (L2) nerves. In Phase 2, all nerves were stained at least 2 cm from the injection site. There was no diffusion of the dye into the epidural space or abdominal cavity. In conclusion, using the anatomical landmarks described specifically for sheep, the PPVB provided accurate perineural distribution of the injected dye-lidocaine solution, which could result in clinical analgesia of the flank.

L'objectif de cette étude était de décrire l'anatomie des nerfs rachidiens, en particulier le dernier nerf thoracique (T13) et les premier à troisième nerfs lombaires (L1 à L3), afin de réaliser en toute sécurité un bloc paravertébral proximal précis (PPVB) chez les moutons. Cette étude comportait deux phases. Dans la phase 1, sept cadavres de moutons ont été disséqués pour identifier le trajet et les repères anatomiques pertinents des nerfs rachidiens T13 et L1 à L3. Dans la phase 2, deux moutons en bonne santé ont reçu des injections bilatérales de 0,35 mL/kg de poids corporel (PC) pour chaque zone hémithoraco-lombaire (0,088 mL/kg de PC par nerf) d'une solution de colorant-lidocaïne (50:50) en utilisant une approche PPVB, puis évalué pendant 15 min pour des signes d'effets systémiques et locaux de la lidocaïne. Après l'euthanasie, la zone infiltrée a été disséquée pour évaluer la propagation du colorant. Une coloration nerveuse réussie (> 2 cm de longueur), une preuve macroscopique d'injection intraneurale/intravasculaire et une propagation à l'espace épidural et à la cavité abdominale ont été enregistrées. Dans la phase 1, chaque branche de tous les nerfs a été facilement identifiée et localisée en utilisant la face caudale de l'apophyse épineuse et le bord latéral de l'apophyse transverse des vertèbres respectives. Un chevauchement a été observé entre les nerfs costo-abdominal (T13), ilio-hypogastrique (L1) et ilio-inguinal (L2). Dans la phase 2, tous les nerfs ont été colorés à au moins 2 cm du site d'injection. Il n'y a pas eu de diffusion du colorant dans l'espace péridural ou la cavité abdominale. En conclusion, en utilisant les repères anatomiques décrits spécifiquement pour les moutons, le PPVB a fourni une distribution périneurale précise de la solution de colorant-lidocaïne injectée, ce qui pourrait entraîner une analgésie clinique du flanc.(Traduit par Docteur Serge Messier).

Determination of the minimum alveolar concentration of isoflurane in donkeys.

OBJECTIVE: To determine the minimum alveolar concentration (MAC) of isoflurane in donkeys and characterize recovery from anesthesia. ANIMALS: 7 healthy castrated male adult donkeys. PROCEDURES: Anesthesia was induced with propofol and maintained under mechanical ventilation with 1.3% isoflurane end-tidal concentration (ETiso). The MAC of isoflurane was determined after a 60-minute propofol washout period using the bracketing method. A continuous noxious electrical stimulation was applied to the oral mucosa for 1 minute or until the donkey moved. The ETiso was increased or decreased by 10% depending on the response, and MAC was defined as the average of 2 ETiso values allowing and preventing movement in response to stimulation. Arterial blood gases were measured during anesthesia and the recovery period. Unassisted recovery was timed, and a quality score was assigned from 1 (very poor) to 5 (excellent). RESULTS: The mean dose of propofol required for induction was 3.0 ± 0.6 mg/kg. The MAC of isoflurane was 1.44 ± 0.13%. One donkey was excluded from the study because it was still responsive when stimulated at ETiso of 2.8%. Immediately after extubation, the median (range) partial pressure of oxygen in the arterial blood was 63 (minimum to maximum, 46 to 72) mm Hg and 3 donkeys were hypoxemic (partial pressure of arterial oxygen < 60 mm Hg). The median time to standing was 13 (7 to 38) minutes, while the recovery score was 3 (2 to 5). CLINICAL RELEVANCE: The MAC of isoflurane in donkeys is similar to that reported in other species. Oxygen support should be provided to donkeys during recovery from isoflurane anesthesia to prevent hypoxemia.

Describing acid-base balance using three different methods of analysis in a feline acute haemorrhage-resuscitation model.

OBJECTIVE: To describe acid-base status using the Henderson-Hasselbalch, Stewart and semi-quantitative methods of analysis in a feline haemorrhage-resuscitation model. STUDY DESIGN: Randomized crossover study. ANIMALS: A total of six domestic cats (mean age, 21 months; weight, 4.9 kg). METHODS: Venous blood samples were taken before haemorrhage, after haemorrhage at 30 minute intervals during fluid resuscitation and at 24 hours. The cats were anaesthetized and underwent following treatments: no purposeful haemorrhage and resuscitation (NoPHR), purposeful haemorrhage followed by either lactated Ringer's solution (LRS) or 6% tetrastarch 130/0.4 (Voluven) for resuscitation. LRS and Voluven were administered at 60 and 20 mL kg-1 hour-1, respectively, for 120 minutes. Variables used for the analysis methods were measured or calculated from the blood samples and then compared among treatments over time using a general linear mixed model (p < 0.05; data reported as mean and standard deviation). RESULTS: The total blood loss at 120 minutes was 10.2 ± 2.3, 29.3 ± 9.0 and 29.1 ± 6.3 mL kg-1 for NoPHR, LRS and Voluven, respectively. Total volumes of LRS and Voluven administered were 120 and 40 mL kg-1, respectively. All cats became acidaemic during anaesthesia regardless of treatment. The Henderson-Hasselbalch method indicated that anaesthetized cats undergoing severe haemorrhage and resuscitation manifest a mixed acidosis. The Stewart method indicated two counter metabolic processes that contributed to the overall pH-decrease in apparent strong ion difference (acidosis) and decrease in total weak acids (alkalosis). The semi-quantitative method identified the free water and chloride effects as variables causing acidosis and the albumin effect causing alkalosis. CONCLUSIONS AND CLINICAL RELEVANCE: In an experimental haemorrhage and resuscitation model in cats, blood pH was similar among treatments over time regardless of severe haemorrhage and resuscitation with LRS or Voluven or mild haemorrhage and no resuscitation.

Investigation of biomarkers for impending fluid overload in a feline acute haemorrhage-resuscitation model.

OBJECTIVE: To determine biomarkers for impending fluid overload during intravenous fluid administration in a feline haemorrhage-resuscitation model. STUDY DESIGN: Randomized crossover study. ANIMALS: A group of six domestic cats (mean age and weight: 21 months; 4.9 kg, respectively). METHODS: The cats underwent three treatments, 2 months apart. They were anaesthetized and instrumented to measure a range of physiological, blood gas, haematological and biochemical variables over time. Samples were taken during a health check, before haemorrhage, after haemorrhage and then at 30 minute intervals during fluid resuscitation and 24 hours later. The three treatments were: 1) control, sham haemorrhage and resuscitation; 2) lactated Ringer's solution (LRS); and 3) 6% tetrastarch 130/0.4 (Vol) where the cats underwent a controlled haemorrhage then resuscitation by administering LRS and Vol at 60 and 20 mL kg-1 hour-1, respectively, for 120 minutes. Fluid overload was identified by nasal discharge and radiographic evidence. Biomarkers were variables that exceeded the reference interval for cats during treatment. Potential biomarkers were analysed using receiver operating characteristic curves (p < 0.05). RESULTS: Mean ± standard deviation total blood loss was 10.2 ± 2.3, 29.3 ± 9.0 and 29.1 ± 6.3 mL kg-1 for control, LRS and Vol, respectively. The total volume of LRS and Vol administered was 120 and 40 mL kg-1, respectively. Haematocrit, albumin, magnesium, chloride-to-sodium ratio and sodium-chloride difference were identified as potential biomarkers. These variables exceeded the reference intervals from 30 minutes of resuscitation onwards. A chloride-to-sodium ratio > 0.84 was the most sensitive (90%) and specific (75%) of all potential biomarkers. CONCLUSIONS AND CLINICAL RELEVANCE: Changes in physiological variables, haematocrit and albumin were poor biomarkers of impending fluid overload compared with electrolytes. Finding the ideal biomarker to identify impending fluid overload of commonly used intravenous fluids should improve the safety of their administration in cats.

Comparison of Propofol or Isoflurane Anesthesia Maintenance, Combined with a Fentanyl-Lidocaine-Ketamine Constant-Rate Infusion in Goats Undergoing Abomasotomy.

This study aimed to compare, first, the anesthetic and cardiopulmonary effects of propofol or isoflurane anesthetic maintenance in goats receiving a fentanyl-lidocaine-ketamine infusion undergoing abomasotomy and, secondly, to compare the quality of the recovery from anesthesia. Two groups were used: propofol (TIVA) and isoflurane (PIVA). Goats were premedicated with fentanyl (10 µg/kg intravenously [IV]), lidocaine (2 mg/kg, IV), and ketamine (1.5 mg/kg, IV). Anesthesia was induced with propofol and maintenance consisted of fentanyl (10 µg/kg/h, IV), lidocaine (50 µg/kg/min, IV), and ketamine (50 µg/kg/min, IV) as constant-rate infusions (CRIs), combined with either CRI of propofol at initial dose of 0.3 mg/kg/min, IV (TIVA), or isoflurane with initial end-tidal (FE'Iso) concentration of 1.2% partial intravenous anesthesia (PIVA). The mean effective propofol dose for maintenance was 0.44 ± 0.07 mg/kg/min, while the mean FE'Iso was 0.81 ± 0.2%. Higher systolic arterial pressure (SAP) values were observed in total intravenous anesthesia (TIVA) during some time points. Recovery was smooth in PIVA, while restlessness, vocalizations, and paddling were observed in TIVA. Both protocols produced a satisfactory quality of anesthesia during surgery, with minimal impact on cardiopulmonary function. Nevertheless, recovery after anesthesia in TIVA might be of poor quality.

Oxygen reserve index as a noninvasive indicator of arterial partial pressure of oxygen in anaesthetized donkeys: a preliminary study.

OBJECTIVE: To evaluate the oxygen reserve index (ORI) as a noninvasive estimate of the PaO2 during moderate hyperoxaemia [100-200 mmHg (13.3-26.6 kPa)], and to determine ORI values identifying PaO2 > 100, > 150 (20.0 kPa) and > 200 mmHg in anaesthetized donkeys with an inspired fraction of oxygen (FiO2) > 0.95. STUDY DESIGN: Prospective observational study. ANIMALS: A group of 28 adult standard donkeys aged (mean ± standard deviation) 4 ± 2 years and weighing 135 ± 15 kg. METHODS: Donkeys were sedated intramuscularly with xylazine and butorphanol; anaesthesia was induced with ketamine and diazepam and maintained with isoflurane in oxygen. An adhesive sensor probe was applied to the donkey's tongue and connected to a Masimo pulse co-oximeter to determine ORI values. An arterial catheter was inserted into an auricular artery. After ORI signal stabilization, the value was noted and PaO2 determined by blood gas analysis. The Pearson correlation coefficient was used to assess the relationship between ORI and PaO2 for oxygen tension < 200 mmHg (< 26.6 kPa). The Youden index was used to identify the value of ORI that detected PaO2 > 150 and 200 mmHg (20.0 and 26.6 kPa) with the highest sensitivity and specificity. RESULTS: A total of 106 paired measurements were collected. A mild positive correlation was observed between ORI and PaO2 for values < 200 mmHg (26.6 kPa; r = 0.52). An ORI > 0.0, > 0.1 and > 0.3 indicated a PaO2 > 100, > 150 and > 200 mmHg (13.3, 20.0 and 26.6 kPa) with negative predictive values > 94%. CONCLUSIONS AND CLINICAL RELEVANCE: ORI may provide a noninvasive indication of PaO2 > 100, > 150 and > 200 mmHg (13.3, 20.0 and 26.6 kPa) in anaesthetized donkeys with an FiO2 > 0.95, although it does not replace blood gas analysis for assessment of oxygenation.

Development of a severity scoring system for acute haemorrhage in anaesthetized domestic cats: the CABSS score.

OBJECTIVE: To determine whether physiological, haematological, biochemical or electrolyte variables can predict severe haemorrhage in cats. STUDY DESIGN: Randomized crossover study whereby each cat underwent mild and severe haemorrhage, with a 2 month period between events. ANIMALS: A group of six domestic cats aged 21 ± 1 months and weighing 4.9 ± 1.2 kg, mean ± standard deviation. METHODS: Cats were anaesthetized (buprenorphine, alfaxalone, isoflurane in oxygen at a fixed end-tidal concentration of 1.7%) before the haemorrhage event. In total, 34 variables were measured twice (prehaemorrhage and posthaemorrhage). The difference and percent change for each variable were compared between haemorrhage events (paired t test). Significant variables were placed into 13 different ratios (posthaemorrhage value of one variable divided by a posthaemorrhage value of a second variable) and compared (paired t test), and Cohen's d (d) was calculated. Receiver operating characteristic curves were plotted and cut-off values for weak, moderate and strong indicators of severe haemorrhage were obtained. RESULTS: The blood loss was 4.5 ± 1.1 mL kg-1 and 26.8 ± 5.5 mL kg-1 for mild and severe haemorrhage events, respectively. The most significant variables with large effect sizes were heart rate (HR), systolic arterial blood pressure (SAP), end-tidal carbon dioxide (Pe'CO2), serum albumin, haematocrit and actual bicarbonate ion concentration [HCO3-(act)]. The most robust ratios were: 1) shock index (d = -2.8; HR:SAP); 2) HR:Pe'CO2 (d = -2.9); 3) serum albumin: haematocrit (d = 1.5); and 4) HR:HCO3-(act) (d = -1.6). These ratios were included in the final proposed Cat Acute Bleeding Scoring System (CABSS). CONCLUSIONS: and clinical relevance Cats subjected to mild and severe haemorrhage demonstrated statistically and clinically relevant changes whereby four ratios could be created to make up the CABSS. The ratios detected and quantified the presence of severe haemorrhage in anaesthetized cats.

Evaluation of xylazine-alfaxalone anesthesia for field castration in donkey foals.

OBJECTIVE: To evaluate the anesthetic and cardiopulmonary effects of xylazine-alfaxalone anesthesia in donkey foals undergoing field castration. STUDY DESIGN: Prospective clinical study. ANIMALS: A group of seven standard donkeys aged [median (range)] 12 (10-26) weeks, weighing 47.3 (37.3-68.2) kg. METHODS: Donkeys were anesthetized with xylazine (1 mg kg-1) intravenously (IV) followed 3 minutes later by alfaxalone (1 mg kg-1) IV. Additional doses of xylazine (0.5 mg kg-1) and alfaxalone (0.5 mg kg-1) IV were administered as needed to maintain surgical anesthesia. Intranasal oxygen was supplemented at 3 L minute-1. Heart rate (HR), respiratory rate (fR) and mean arterial pressure (MAP) by oscillometry were recorded before drug administration and every 5 minutes after induction of anesthesia. Peripheral oxygen saturation (SpO2) was recorded every 5 minutes after induction. Time to recumbency after alfaxalone administration, time to anesthetic re-dose, time to first movement, sternal and standing after last anesthetic dose and surgery time were recorded. Induction and recovery quality were scored (1, very poor; 5, excellent). RESULTS: Median (range) induction score was 5 (1-5), and recovery score 4 (1-5). Overall, two donkeys were assigned a score of 1 (excitement) during induction or recovery. HR and MAP during the procedure did not differ from baseline. fR was decreased at 5 and 10 minutes but was not considered clinically significant. SpO2 was <90% at one time point in two animals. CONCLUSIONS AND CLINICAL RELEVANCE: Xylazine-alfaxalone anesthesia resulted in adequate conditions for castration in 12 week old donkeys. While the majority of inductions and recoveries were good to excellent, significant excitement occurred in two animals and may limit the utility of this protocol for larger donkeys. Hypoxemia occurred despite intranasal oxygen supplementation.

Effects of chemical and mechanical stimulation on laryngeal motion during alfaxalone, thiopentone or propofol anaesthesia in healthy dogs.

OBJECTIVE: To compare the effect of chemical and mechanical stimulation on arytenoid cartilage motion during anaesthetic induction with alfaxalone, thiopentone or propofol. STUDY DESIGN: Masked, randomized, crossover study. ANIMALS: A group of eight adult Beagle dogs. METHODS: Anaesthesia was induced with thiopentone (7.5 mg kg-1), propofol (3 mg kg-1) or alfaxalone (1.5 mg kg-1) intravenously (IV), which were concurrently paired with either chemical (doxapram at 2.5 mg kg-1 IV) or mechanical (gentle pressure to the corniculate process of the right arytenoid cartilage using a cotton bud) stimulation for enhanced assessment of laryngeal motion, in random order, with a 1 week wash-out period between treatments. If deemed inadequately anaesthetized, supplemental boli of thiopentone (1.8 mg kg-1), propofol (0.75 mg kg-1) or alfaxalone (0.4 mg kg-1) were administered. Assessment of number of arytenoid motions and vital breaths, among others, was initiated immediately after induction. Chemical (doxapram) and mechanical stimulation were begun 2 minutes after anaesthetic induction. Data were collected at 2, 3 and 5 minutes after anaesthetic induction and the Friedman rank-sum or repeated-measures analysis of variance tests were used when applicable for statistical analysis. RESULTS: The duration of examination time was shorter among treatments combined with chemical stimulation (p=0.001). Examination time during induction was longer for alfaxalone-chemical (8.9 minutes) and -mechanical (10.9 minutes) compared to both induction with thiopentone-chemical (3.8 minutes) and propofol-chemical (4.0 minutes). The median number of arytenoid motions for both thiopentone (67) and propofol (59) induction combined with chemical stimulation was significantly higher in comparison to that of alfaxalone (1), thiopentone (2) and propofol (2), when combined with mechanical stimulation at 3 minutes after induction. CONCLUSION AND CLINICAL RELEVANCE: Among the regimens for assessing laryngeal motion assessed in the present study, combinations of thiopentone or propofol with doxapram are the most effective means of stimulating arytenoid motion and could improve the accuracy of diagnosis of laryngeal paralysis in dogs.

Effects of hyaluronidase on ropivacaine or bupivacaine regional anaesthesia of the canine pelvic limb.

OBJECTIVE: To determine the effect of hyaluronidase on time to onset and offset of anaesthesia in ropivacaine or bupivacaine femoral-ischiatic nerve blocks. STUDY DESIGN: Blinded randomized crossover trial. ANIMALS: Eight dogs. METHODS: Each dog underwent four treatments separated into two blocks - initially, the ropivacaine treatment block: RS (ropivacaine 0.5% plus saline 0.9%) and RH (ropivacaine 0.5% plus hyaluronidase 100 IU mL-1), followed 3 weeks later by the bupivacaine treatment block: BS (bupivacaine 0.5% plus saline) and BH (bupivacaine 0.5% plus hyaluronidase). The local anaesthetics were administered at 0.1 mL kg-1 per site. Hyaluronidase and saline were administered at 0.02 mL kg-1 per site. Performance of femoral-ischiatic blocks was aided by a combined ultrasound-electrolocation technique. The mechanical nociceptive threshold was measured, until offset or 360 minutes, using an algometer to ascertain baseline, onset and offset of anaesthesia. Onset and offset of anaesthesia were defined as a 25% increase above and as a return to <25% above baseline nociceptive threshold readings, respectively. RESULTS: The median (range) onset of anaesthesia for RS and RH was 21 (3-60) and 12 (3-21) minutes, respectively (p = 0.141), and offset was 270 (90-360) and 180 (30-300) minutes, respectively (p = 0.361). By contrast, the median (range) onset of anaesthesia for BS and BH was 24 (3-60) and 9 (3-27) minutes, respectively (p = 0.394), and offset was 360 (240-360) and 330 (210-360) minutes, respectively (p = 0.456). CONCLUSION AND CLINICAL RELEVANCE: Hyaluronidase had no effect on the onset and offset times of ropivacaine and bupivacaine femoral-ischiatic nerve blocks in dogs compared with saline. The onset and offset times were highly variable in all treatments. Clinically, the high variability of the onset and offset times of the regional anaesthesia of these local anaesthetic drugs means that clinicians must monitor the animal's response and, if required, provide additional analgesic drugs.

The minimum infusion rate of alfaxalone during its co-administration with lidocaine at three different doses by constant rate infusion in goats.

OBJECTIVE: To determine the minimum infusion rate (MIR) of alfaxalone required to prevent purposeful movement in response to standardized stimulation while co-administered with lidocaine at three different doses by constant infusion rate infusion (CRI) in goats. STUDY DESIGN: Prospective, blinded, randomized crossover, experimental. ANIMALS: A total of eight healthy goats: four does and four wethers. METHODS: Anaesthetic induction was with lidocaine at 1 mg kg-1 [low dose of lidocaine (L-Lid)], 2 mg kg-1 [moderate dose (M-Lid)] or 4 mg kg-1 [high dose (H-Lid)] and alfaxalone at 2 mg kg-1. Anaesthetic maintenance was with alfaxalone initially at 9.6 mg kg-1 hour-1 combined with one of three lidocaine treatments: 3 mg kg-1 hour-1 (L-Lid), 6 mg kg-1 hour-1 (M-Lid) or 12 mg kg-1 hour-1 (H-Lid). The MIR of alfaxalone was determined by testing for responses to a stimulation in the form of clamping on a digit with a Vulsellum forceps every 30 minutes during lidocaine CRI. Basic cardiopulmonary parameters were measured. RESULTS: The alfaxalone MIRs were 8.64 (6.72-10.56), 6.72 (6.72-8.64) and 6.72 (6.72-6.72) mg kg-1 hour-1 during L-Lid, M-Lid and H-Lid, respectively, without any significant differences among treatments. Compared to the initial rate of 9.6 mg kg-1 hour-1, these reductions in MIR are equivalent to 10, 30 and 30%, respectively. Significant increases in heart rate (HR) and arterial carbon dioxide partial pressure (PaCO2) and decreases in arterial haemoglobin saturation (SaO2), arterial oxygen partial pressure (PaO2) and respiratory frequency (fR) immediately after induction were observed during all lidocaine treatments. CONCLUSIONS AND CLINICAL RELEVANCE: Lidocaine reduces the alfaxalone MIR by up to 30% with a tendency towards a plateauing in this effect at high CRIs. Immediate oxygen supplementation might be required to prevent hypoxaemia.

Determination of the minimum infusion rate of propofol required to prevent purposeful movement of the extremities in response to a standardized noxious stimulus in goats.

OBJECTIVE: To determine the minimum infusion rate (MIR) of propofol required to prevent purposeful movement in response to a standardized stimulus in goats. STUDY DESIGN: Prospective, experimental study. ANIMALS: Eight healthy goats (four does, four wethers). METHODS: Anaesthesia was induced with 4 mg kg(-1) propofol intravenously (IV). A continuous IV infusion of propofol at 0.6 mg kg(-1)  minute(-1) was initiated immediately to maintain anaesthesia. Following endotracheal intubation, goats breathed spontaneously via a circle breathing system delivering supplementary oxygen. The initial propofol infusion rate was maintained for 30 minutes before responses to noxious stimulation provided by clamping the proximal part of the claw with a Vulsellum forceps for 60 seconds were tested. In the presence or absence of purposeful movements of the extremities, the infusion rate was increased or reduced by 0.1 mg kg(-1)  minute(-1) and held constant for 30 minutes before claw clamping was repeated. The propofol MIR for each goat was calculated as the mean of the infusion rates that allowed and abolished movement. Basic cardiopulmonary parameters were monitored, recorded and tested for statistical significance using Wilcoxon's signed rank test with Bonferroni adjustment for multiple testing. The quality of recovery from anaesthesia was assessed and scored. RESULTS: The median MIR of propofol was 0.45 mg kg(-1)  minute(-1) (range: 0.45-0.55 mg kg(-1)  minute(-1) ). Induction and recovery were free of adverse behaviour. No statistically significant cardiopulmonary changes in comparison with baseline were observed, but clinically relevant hypoxaemia at 2 minutes after induction of anaesthesia was consistently observed. Chewing during anaesthesia was observed in three goats. Median times to extubation and standing were 3 minutes (range: 2-6 minutes) and 10 minutes (range: 7-21 minutes), respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Propofol induction and maintenance of general anaesthesia minimally compromise cardiopulmonary function when oxygen is supplemented in goats.

Determination of the minimum infusion rate of alfaxalone during its co-administration with fentanyl at three different doses by constant rate infusion intravenously in goats.

OBJECTIVE: To determine the minimum infusion rate (MIR) of alfaxalone required to prevent purposeful movement of the extremities in response to standardized noxious stimulation during its co-administration with fentanyl at three different doses by constant rate infusion (CRI) intravenously (IV) in goats. STUDY DESIGN: Prospective, blinded, randomized crossover, experimental. ANIMALS: Eight healthy goats; four does and four wethers. METHODS: For induction of anaesthesia, a bolus of fentanyl was administered at 0.005 mg kg(-1) (LFent), 0.015 mg kg(-1) (MFent) or 0.03 mg kg(-1) (HFent) followed by alfaxalone at 2.0 mg kg(-1) . For maintenance, the goats received alfaxalone at an initial infusion rate of 9.6 mg kg(-1)  hour(-1) and one of three fentanyl treatments: 0.005 mg kg(-1)  hour(-1) (LFent), 0.015 mg kg(-1)  hour(-1) (MFent) or 0.03 mg kg(-1) hour(-1) (HFent). The MIR of alfaxalone was determined during fentanyl CRI by testing for responses to stimulation (clamping on a digit with Vulsellum forceps) every 30 minutes. Some cardiopulmonary parameters were measured. RESULTS: The alfaxalone MIR median (range) was 6.7 (6.7-8.6), 2.9 (1.0-6.7) and 1.0 (1.0-4.8) mg kg(-1)  hour(-1) during LFent, MFent and HFent, respectively. Alfaxalone MIR was significantly lower during MFENT and HFENT compared to LFENT. Significantly low oxygen haemoglobin saturation (SaO2 ) and arterial oxygen partial pressure (PaO2 ), observed 2 minutes into anaesthesia after all fentanyl treatments, were the most remarkable adverse cardiopulmonary effects observed. Recovery from anaesthesia was severely affected by high doses of fentanyl with excitatory behavioural signs predominant for up to 2 hours post-administration after MFent and HFent. CONCLUSIONS AND CLINICAL RELEVANCE: Fentanyl reduces alfaxalone MIR in goats in a dose-dependent manner. Immediate oxygen supplementation after induction of general anaesthesia is recommended to prevent hypoxaemia. Doses of fentanyl equal to or greater than 0.015 mg kg(-1)  hour(-1) tend to be associated with severe excitatory behaviour and should be avoided when fentanyl is administered to goats.

Determination of the minimum infusion rate (MIR) of alfaxalone required to prevent purposeful movement of the extremities in response to a standardised noxious stimulus in goats.

OBJECTIVE: To determine the minimum infusion rate (MIR) of alfaxalone required to prevent purposeful movement of the extremities in response to noxious stimulation. STUDY DESIGN: Prospective, experimental. ANIMALS: Eight healthy goats; four does and four wethers. METHODS: Anaesthesia was induced with alfaxalone 3 mg kg(-1) intravenously (IV). A continuous IV infusion of alfaxalone, initially at 0.2 mg kg(-1)  minute(-1) , was initiated. Following endotracheal intubation the goats breathed spontaneously via a circle breathing circuit delivering supplementary oxygen. The initial infusion rate was maintained for 30 minutes before testing for responses. The stimulus was clamping on the proximal (soft) part of one digit of the hoof with Vulsellum forceps for 60 seconds. In the absence or presence of purposeful movement of the extremities, the infusion rate was reduced or increased by 0.02 mg kg(-1)  minute(-1) and held constant for 30 minutes before claw-clamping again. Alfaxalone MIR was calculated as the mean of the infusion rates that allowed and abolished movement. Cardio-respiratory parameters were measured. Recovery from general anaesthesia was timed and quality scored. Results are presented as median (range). RESULTS: The MIR of alfaxalone was 0.16 (0.14-0.18) mg kg(-1)  minute(-1) or 9.6 (8.4-10.8) mg kg(-1)  hour(-1) . Induction of and recovery from anaesthesia were excitement-free. Cardio-respiratory changes were minimal, although compared to baseline HR increased, and at 2 minutes post-induction, (prior to oxygen supplementation), PaO2 decreased significantly from 84 (80-88) to 70 (51-72) mmHg [11.2 (10.7-11.7) to 9.3 (6.8-9.6) kPa]. Sporadic muscle twitches, unrelated to depth of anaesthesia, were observed during the period of general anaesthesia. Time (minutes) to sternal recumbency and standing were 4.0 (3.0-10.0) and 41.5 (25.0-57.0) respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Alfaxalone can be used for total intravenous anaesthesia (TIVA) in goats and is associated with minimal adverse effects. Oxygen supplementation is advised, especially when working at higher altitudes.

Antinociceptive effects of epidural magnesium sulphate alone and in combination with morphine in dogs.

OBJECTIVE: To compare the antinociceptive effects of magnesium sulphate (MgSO(4)) when administered epidurally alone and in combination with morphine. STUDY DESIGN: Experimental, randomized, 'blinded', crossover study. ANIMALS: Six healthy adult Beagle dogs. METHODS: Evaluated treatments were MgSO(4) (2.5 mg kg(-1)) alone (Mg), morphine (0.1 mg kg(-1)) alone (Mo), MgSO(4) in combination with morphine (Mm), and sterile water (0.115 mL kg(-1) ; Co) that were injected in the lumbosacral epidural space using an epidural catheter. Antinociception was measured using the von Frey mechanical threshold device applied to the carpal pads, both sides of the thorax and metatarsi. Measurements were obtained at time points: before treatment (baseline) and 0.5, 1, 2, 4, 6, 12, 18 and 24 hours after the epidural injection. Sedation, behaviour score and presence of motor deficits were assessed. Data were analyzed using a linear mixed model and Bonferroni adjustments, with significance set at p < 0.05. RESULTS: There were significant effects of treatment and time in all regions. Overall threshold values in grammes force [median (interquartile range)] when stimulation regions were combined were significantly higher in Mg [164 (135-200)], Mo [156 (129-195)] and Mm [158 (131-192)] compared to Co [145 (120-179)]. Thresholds were significantly higher compared to Co in Mg, Mo and Mm at the thorax and metatarsi, but only in Mg and Mo at the carpal pads. No motor deficits were observed at any time point. Thresholds (combined regions) were increased from baseline at one or more time points with all treatments, including control. CONCLUSION AND CLINICAL RELEVANCE: Epidural MgSO(4) produced an antinociceptive effect characterised by an increase in the mechanical thresholds of similar magnitude to that produced by epidural morphine, compared with the control group, without causing any motor deficits. No potentiation of morphine antinociception was observed. The onset and offset times of antinociception could not be clearly established. To what extent these results can be extrapolated to clinical cases requires further investigation.

Anaesthetic, analgesic and cardiorespiratory effects of intramuscular medetomidine-ketamine combination alone or with morphine or tramadol for orchiectomy in cats.

OBJECTIVES: To compare the anaesthetic, analgesic and cardiorespiratory effects of intramuscular (IM) medetomidine and ketamine administered alone or combined with morphine or tramadol, for orchiectomy in cats. STUDY DESIGN: Randomised, blinded, prospective clinical study. ANIMALS: Thirty client-owned cats. MATERIALS AND METHODS: Cats (n = 10 in each group) received a combination of medetomidine (60 µgkg(-1) ) and ketamine (10 mg kg(-1) ) alone (MedK); combined with morphine (0.2 mg kg(-1) ) (MedKM), or combined with tramadol (2 mg kg(-1) ) (MedKT) IM. Time of induction, surgical and recovery events were recorded, and physiological parameters measured and recorded. Analgesia was evaluated with a visual analogue scale, a composite scoring system and the von Frey mechanical threshold device, every hour from three to eight hours post-drug administration injection. Data were analyzed with a linear mixed model, Kruskal-Wallis or Chi-square tests (p < 0.05). RESULTS: Median (IQR) induction and recovery times (minutes) were not significantly (p = 0.125) different between groups: 5.6 (2.7-8.0), 7.4 (5.1-9.6) and 8.0 (5.8-14.9) for induction and 128.5 (95.1-142.8), 166.4 (123.1-210.0) and 142.9 (123.4-180.2) for recovery, with MedK, MedKT and MedKM, respectively. Two cats (MedKM) required alfaxalone for endotracheal intubation. In all groups, three or four cats required additional isoflurane for surgery. Arterial oxygen tension overall (mean ± SD: 66 ± 2 mmHg) was low. Surgery resulted in increased systolic arterial blood pressure (p < 0.001), haemoglobin saturation (p < 0.001), respiratory (p = 0.003) and heart rates (p = 0.002). Pain scores did not differ significantly between groups. Von Frey responses decreased over time; changes over time varied by treatment (p < 0.001), MedK returning to baseline values more rapidly than MedKM and MedKT. No cat required rescue analgesics. CONCLUSION AND CLINICAL RELEVANCE: All three protocols can provide adequate anaesthesia and analgesia for orchiectomy in cats. However, rescue intervention to maintain surgical anaesthesia may be required in some cats. Oxygen supplementation is advised.

Effects of a constant rate infusion of magnesium sulphate in healthy dogs anaesthetized with isoflurane and undergoing ovariohysterectomy.

OBJECTIVE: To determine the effects of intravenous (IV) magnesium sulphate (MgSO(4) ) as a bolus followed by a constant rate infusion (CRI) on anaesthetic requirements, neuroendocrine stress response to surgery, haemostasis and postoperative analgesia in healthy dogs undergoing ovariohysterectomy. STUDY DESIGN: Blinded randomized clinical trial. ANIMALS: Sixteen female dogs. METHODS: After intramuscular premedication with acepromazine (0.05 mg kg(-1) ) and morphine (0.3 mg kg(-1) ), anaesthesia was induced with diazepam (0.2 mg kg(-1) ) and propofol (2 mg kg(-1) ) intravenously and maintained with isoflurane in oxygen in all dogs. Dogs were randomly assigned to two groups, M and C. Group M received MgSO(4) (50 mg kg(-1) over 15 minutes, followed by a 15 mg kg(-1) hour(-1) CRI). Group C received an equivalent bolus and CRI of lactated Ringer's solution. In addition, all dogs received lactated Ringer's solution (10 mL kg(-1) over 15 minutes followed by 10 mL kg(-1) hour(-1) ). End-tidal isoflurane and carbon dioxide tensions, cardio-respiratory variables, arterial blood gases, electrolytes, ACTH and cortisol concentrations were measured at different time points. Thromboelastography (TEG) was performed pre- and post-anaesthesia. Postoperative pain was evaluated using the short form of the Glasgow Composite Pain Scale. Data were analysed with repeated measures anova and Mann-Whitney U tests (p < 0.05). RESULTS: No statistically significant differences between groups were found in any of the measured variables. However, the alpha angle and maximal amplitude recorded by TEG in group M were significantly increased post-anaesthesia, but remained within the reference interval. One dog in Group M and two in Group C received rescue analgesia during recovery. CONCLUSIONS AND CLINICAL RELEVANCE: As used in this study, MgSO(4) failed to decrease isoflurane requirements, postoperative pain and stress hormone concentrations; however, it did not produce any cardio-respiratory or major haemostatic side effects. Administration of intravenous MgSO(4) together with an opioid during ovariohysterectomy in dogs does not seem to provide any clinical advantage.

Comparison of alfaxalone and propofol administered as total intravenous anaesthesia for ovariohysterectomy in dogs.

OBJECTIVE: To compare the anaesthetic and cardiopulmonary effects of alfaxalone with propofol when used for total intravenous anaesthesia (TIVA) during ovariohysterectomy in dogs. STUDY DESIGN: A prospective non-blinded randomized clinical study. ANIMALS: Fourteen healthy female crossbred bitches, aged 0.5-5 years and weight 16-42 kg. METHODS: Dogs were premedicated with acepromazine 0.01 mg kg(-1) and morphine 0.4 mg kg(-1). Anaesthesia was induced and maintained with either propofol or alfaxalone to effect for tracheal intubation followed by an infusion of the same agent. Dogs breathed spontaneously via a 'circle' circuit, with oxygen supplementation. Cardiopulmonary parameters (respiratory and heart rates, end-tidal carbon dioxide, tidal volume, and invasive blood pressures) were measured continuously and recorded at intervals related to the surgical procedure. Arterial blood samples were analysed for blood gas values. Quality of induction and recovery, and recovery times were determined. Non-parametric data were tested for significant differences between groups using the Mann-Whitney U-test and repeatedly measured data (normally distributed) for significant differences between and within groups by anova. RESULTS: Both propofol and alphaxalone injection and subsequent infusions resulted in smooth, rapid induction and satisfactory maintenance of anaesthesia. Doses for induction (mean ± SD) were 5.8 ± 0.30 and 1.9 ± 0.07 mg kg(-1) and for the CRIs, 0.37 ± 0.09 and 0.11 ± 0.01 mg kg(-1) per minute for propofol and alfaxalone respectively. Median (IQR) recovery times were to sternal 45 (33-69) and 60 (46-61) and to standing 74 (69-76) and 90 (85-107) for propofol and alphaxalone respectively. Recovery quality was good. Cardiopulmonary effects did not differ between groups. Hypoventilation occurred in both groups. CONCLUSIONS AND CLINICAL RELEVANCE: Following premedication with acepromazine and morphine, both propofol and alphaxalone produce good quality anaesthesia adequate for ovariohysterectomy. Hypoventilation occurs suggesting a need for ventilatory support during prolonged infusion periods with either anaesthetic agent.