Determination of a safe sedative combination of dexmedetomidine, ketamine and butorphanol for minor procedures in dogs by use of a stepwise optimization method.

BACKGROUND: In veterinary practice, most minor procedures such as radiographs, skin biopsies, and wound treatments require sedation. The combination of butorphanol, ketamine, and dexmedetomidine is commonly used, but the ideal dosages for this combination have not been defined. This randomized prospective clinical 3-phases trial initially tested eight clinically relevant combinations of intramuscular administration in 50 dogs (phase 1). The quality of each combination was rated using a purposefully developed negative score (NS; 0-21.5, the lower the NS the better the quality of sedation) to judge the quality of sedation, the occurrence of side effects, and the need for additional anaesthetics. Based on the results of the NS, the eight combinations were divided into "promising" and "unsatisfactory" subgroups. In phase 2, a new combination (N) was calculated and tested in six dogs replacing the worst of the eight initial combinations. This procedure was repeated until the NS could not be improved any further. In phase 3, the best combination was tested in 100 adult dogs undergoing diagnostic or therapeutic procedures. RESULTS: The optimal combination established was dexmedetomidine 0.005 mg/kg, ketamine 1 mg/kg, and butorphanol 0.3 mg/kg with a median NS of 1.5 (interquartile range 1.5-2.4). In all 112 dogs receiving this combination, the quality of sedation was satisfactory and no severe side effects were detected. CONCLUSIONS: The application of this optimization method allowed the calculation of an optimal drug combination to sedate cardiovascularly healthy dogs. After having being tested in 112 animals, this combination can consequently be considered safe. Therefore, this combination can now be used in daily clinical practice for cardiovascularly healthy adult dogs undergoing minor procedures.

Ultrasound-Guided Block of the Sciatic and the Femoral Nerves in Rabbits-A Descriptive Anatomical Study.

The rabbit is a popular animal model for human biomechanical research involving surgery on the hind limb. Mortality is higher in rabbits when undergoing general anesthesia compared to dogs and cats. Moreover, due to their nature as prey animals, rabbits have a tendency to hide signs of pain, making it challenging to detect discomfort at an early stage. Incorporating regional anesthesia into an anesthetic protocol can greatly reduce the requirements for systemic anesthetic and analgesic drugs, thereby minimizing associated side effects. In other species, a block of the sciatic (ScN) and the femoral nerves (FN) is usually applied in patients undergoing hind limb surgery. In phase 1 of this study, the ScN and the FN have been localized and an appropriate approach has been evaluated under sonographic guidance. In phase 2, a mixture of new methylene blue and lidocaine have been administered to the ScN and the FN in 10 cadavers (20 hind limbs). Staining of the nerves was evaluated by dissection. Ultrasonographically, the ScN appeared as a binocular structure surrounded by a hyperechoic rim. The FN appeared as a hypoechoic structure in the dorsal part of the iliopsoas muscle (IPM), becoming hyperechoic/honey-comb-like in the ventral part. Both nerves could be successfully stained in all animals over a median length of 2.3 cm which was considered effective. This technique allows feasible and accurate access to block the ScN and the FN and may lead to successful analgesia in rabbits undergoing hind limb surgery.

Is a Block of the Femoral and Sciatic Nerves an Alternative to Epidural Analgesia in Sheep Undergoing Orthopaedic Hind Limb Surgery? A Prospective, Randomized, Double Blinded Experimental Trial.

Peripheral nerve blocks are commonly used in human and veterinary medicine. The aim of the study was to compare the analgesic efficacy of a combined block of the femoral and sciatic nerves with an epidural injection of ropivacaine in experimental sheep undergoing orthopaedic hind limb surgery. Twenty-five sheep were assigned to two groups (peripheral nerve block; sciatic and femoral nerves (P); epidural analgesia (E)). In group P 10 mL ropivacaine 0.5% was injected around the sciatic and the femoral nerves under sonographic guidance and 10 mL NaCl 0.9% into the epidural space while in group E 10 mL ropivacaine 0.5% was injected into the epidural space and 10 mL NaCl 0.9% to the sciatic and the femoral nerves. During surgery, heart rate, respiratory rate and mean blood pressure were used as indicators of nociception. In the postoperative phase, nociception was evaluated every hour by use of a purposefully adapted pain score until the animal showed painful sensation at the surgical site. The mean duration of analgesia at the surgical wound was 6 h in group P and 8 h in group E. Mean time to standing was 4 h in group P and 7 h in group E. In conclusion time to standing was significantly shorter in group P while the duration of nociception was comparable in both groups. The peripheral nerve block can be used as an alternative to epidural analgesia in experimental sheep.

Opioid requirements after locoregional anaesthesia in dogs undergoing tibial plateau levelling osteotomy: a pilot study.

OBJECTIVE: To determine the intraoperative and early postoperative opioid requirement after ultrasound-guided sciatic and/or femoral nerve block or epidural anaesthesia in dogs undergoing tibial plateau levelling osteotomy (TPLO). STUDY DESIGN: Prospective, masked, pilot, randomized, clinical trial. ANIMALS: A total of 40 client-owned dogs undergoing TPLO. METHODS: Each dog was randomly assigned to group SF (combined sciatic and femoral nerve block), group S (sciatic nerve block), group F (femoral nerve block) or group E (epidural anaesthesia). A total of 0.3 mL kg-1 of ropivacaine 0.5% was administered to each nerve or in the epidural space. Intraoperatively, fentanyl (2 µg kg-1) was administered intravenously when heart rate, mean arterial pressure or respiratory rate increased by >30% compared with baseline values. Postoperatively, a visual analogue scale (VAS) and a modified German version of the French pain scale (4AVet) were used to assess pain every 30 minutes for 150 minutes and again once the morning after surgery. Methadone (0.1 mg kg-1) was administered intravenously if the VAS was ≥ 4 cm [maximal value 10 cm; median (interquartile range)] or the composite pain score was ≥5 [maximal value 15; median (interquartile range)]. Significance was defined as p ≤ 0.05. RESULTS: Groups SF and E required less total intraoperative and early postoperative opioid doses compared with groups S and F (p = 0.031). No dogs in group SF had a block failure or required postoperative methadone. A reduced methadone requirement was found in group SF compared with all the other groups up to 150 minutes after recovery (p = 0.041). CONCLUSIONS AND CLINICAL RELEVANCE: Combined sciatic and femoral nerve block and epidural anaesthesia lead to less cumulative consumption of perioperative opioids than single nerve blockade. Sciatic or femoral nerve block alone might be insufficient to control nociception and early postoperative pain in dogs undergoing TPLO.

Two high-risk clones of carbapenemase-producing Klebsiella pneumoniae that cause infections in pets and are present in the environment of a veterinary referral hospital.

OBJECTIVES: Infections with carbapenem-resistant Enterobacterales (CRE) are an emerging problem in pets and a major threat to public health. We determined the genetic relationships among carbapenemase-producing Klebsiella pneumoniae (CPKp) strains causing infections in hospitalized pets in a veterinary clinic and those found in the environment. METHODS: WGS was performed with both the Illumina and Nanopore platforms. Searches of genetic features were performed using several databases and bioinformatics tools, and phylogeny was assessed by whole-genome MLST (wgMLST) using SeqSphere and SNP calling with Snippy. RESULTS: WGS analysis of the CPKp strains identified all environmental and almost all animal strains as the high-risk clone ST11, with the exception of two strains that belonged to ST307. All CPKp belonged to novel complex types (CTs) and carried a conjugative 63 kb IncL plasmid encoding the carbapenemase gene blaOXA-48, yersiniabactin and other virulence factors. Although all CPKp ST11 strains carried additional similar IncR plasmids harbouring multiple antimicrobial resistance genes (ARGs), such as the plasmid-mediated blaDHA-1 AmpC gene, some structural variations were observed. The two ST307 strains carried identical 156 kb MDR IncFIB(K) plasmids with several ARGs, including the blaCTX-M-15 ESBL gene. Both wgMLST and cgSNP analysis confirmed that CPKp strains of the same ST were genetically highly related independent of the source of isolation. CONCLUSIONS: This study demonstrated that the clinical CPKp strains were highly related to those contaminating the clinical environment. These findings confirmed nosocomial spread and highlight veterinary hospitals as a source of CPKp, which may further spread to animals, the environment and humans.

The influence of the choice of preemptive analgesia on long-term postsurgical pain after tibial plateau leveling osteotomy in dogs.

OBJECTIVE: To evaluate the prevalence of chronic postsurgical pain (CPSP) after tibial plateau leveling osteotomy (TPLO) in dogs and to determine the influence of preemptive locoregional analgesia on CPSP. STUDY DESIGN: Retrospective study. ANIMALS: One hundred twenty client-owned dogs. METHODS: Medical records of dogs that underwent TPLO between 2012 and 2016 were reviewed for demographic information and type of preemptive analgesia. Owners were contacted to retrospectively assess the quality of life of their dogs by using the Helsinki Chronic Pain Index (HCPI) before and 6 months after surgery and at the time of questioning. An HCPI score > 12 was considered indicative of CPSP. Medical records were reviewed for demographic information and type of preemptive analgesia. A cumulative logit model was used to assess correlation of type of perioperative analgesia, HCPI, and demographic data. RESULTS: The HCPI score was consistent with CPSP in 41 of 101 dogs with long-term follow-up (2.9 ± 1.5 years after surgery). Chronic postsurgical pain was documented in 11 of 32 and 13 of 28 dogs that received a spinal or epidural injection, respectively, or in 28 of 80 and 25 of 67 dogs with sciatic-femoral block at 6 months or with long-term follow-up after TPLO, respectively (P > .05). A negative correlation was found between HCPI and both weight and age 6 months after surgery. Only weight remained negatively correlated 2.9 years after surgery. CONCLUSION: Forty-one percent of dogs that were evaluated exhibited HCPI values compatible with CPSP long-term after TPLO, regardless of the type of preemptive analgesia. Increased body weight was a negative prognostic factor for CPSP development. CLINICAL SIGNIFICANCE: Additional studies are required to evaluate CPSP development after TPLO.

Fentanyl Plasma Concentrations after Application of a Transdermal Patch in Three Different Locations to Refine Postoperative Pain Management in Rabbits.

Transdermal patches allow a noninvasive and "stress free" analgesia in rabbits. As fentanyl uptake is dependent on exogenous and endogenous factors of the area where the patch is applied, this study investigated three different locations (neck, inner and outer surfaces of the ear) for fentanyl patch application to provide adequate and reliable fentanyl plasma concentrations above those previously shown to be analgesic. Fentanyl plasma concentration was measured at different time points (3, 6, 9, 12, 18, 24, 36, 48, 72, 96, 120 h) and rabbits were assessed for their general conditions and treatment-related side effects. Practicability of the proposed methods was evaluated. Following patch application on the neck, fentanyl plasma concentrations equal to or above the analgesic value were measured in all rabbits between 6 and 72 h. Comparable concentrations were reached between 9 and 48 h in all animals for the outer ear surface. However, for the inner ear surface, analgesic concentrations were not reached, even if practicability was considered the best for this location. Preparation of the neck skin was judged as the most cumbersome due to the clipping of the dense fur and patch removal resulted in erythema. In summary, the application of the fentanyl patch on the neck and outer ear surface allowed the reach of reliable plasma concentrations above the analgesic threshold in rabbits. When applied on the neck, fentanyl patches provided the longest duration of analgesic plasma concentrations, whereas patch application and removal were easier on the outer ear surface.

Poor infection prevention and control standards are associated with environmental contamination with carbapenemase-producing Enterobacterales and other multidrug-resistant bacteria in Swiss companion animal clinics.

BACKGROUND: Intensive medical care in companion animal clinics could pose a risk for the selection and dissemination of multidrug-resistant organisms (MDROs). Infection prevention and control (IPC) concepts are key measures to reduce the spread of MDROs, but data on IPC standards in companion animal clinics is sparse. The study assessed IPC standards in seven companion animal clinics and practices in Switzerland by structured IPC audits and combined results with environmental MDRO contamination and MDRO carriage of the personnel. METHODS: IPC audits were held between August 2018 and January 2019. The observations in 34 IPC areas were scored based on predefined criteria (not fulfilled/partially fulfilled/fulfilled = score 0/1/2). Environmental swabs and nasal and stool samples from veterinary personnel were tested for methicillin-resistant (MR) staphylococci and macrococci and for colistin-resistant, extended-spectrum ß-lactamase- and carbapenemase-producing (CP) Enterobacterales (CPE). Species was identified by MALDI-TOF MS, antimicrobial resistance determined by microdilution and ß-lactam resistance gene detection, and genetic relatedness assessed by REP-/ERIC-PCR and multilocus sequence typing. RESULTS: Of a maximum total IPC score of 68, the institutions reached a median (range) score of 33 (19-55). MDROs were detected in median (range) 8.2% (0-33.3%) of the sampling sites. Clinics with low IPC standards showed extensive environmental contamination, i.e. of intensive care units, consultation rooms and utensils. CPE were detected in two clinics; one of them showed extensive contamination with CP Klebsiella pneumoniae (ST11, blaOXA-48) and MR Staphylococcus pseudintermedius (ST551, mecA). Despite low IPC scores, environmental contamination with MDROs was low in primary opinion practices. Three employees were colonized with Escherichia coli ST131 (blaCTX-M-15, blaCTX-M-27, blaCTX-M-14). Two employees carried CP E. coli closely related to environmental (ST410, blaOXA-181) and patient-derived isolates (ST167, blaNDM-5). MR Staphylococcus aureus (ST225, mecA) and MR S. pseudintermedius (ST551, mecA) of the same sequence types and with similar resistance profiles were found in employees and the environment in two clinics. CONCLUSIONS: The study indicates that IPC standards in companion animal clinics are variable and that insufficient IPC standards could contribute to the evolution of MDROs which can be transferred between the environment and working personnel. The implementation of IPC concepts in companion animal clinics should urgently be promoted.

Prospective Validation of Facial Nerve Monitoring to Prevent Nerve Damage During Robotic Drilling.

Facial nerve damage has a detrimental effect on a patient's life, therefore safety mechanisms to ensure its preservation are essential during lateral skull base surgery. During robotic cochlear implantation a trajectory passing the facial nerve at <0.5 mm is needed. Recently a stimulation probe and nerve monitoring approach were developed and introduced clinically, however for patient safety no trajectory was drilled closer than 0.4 mm. Here we assess the performance of the nerve monitoring system at closer distances. In a sheep model eight trajectories were drilled to test the setup followed by 12 trajectories during which the ENT surgeon relied solely on the nerve monitoring system and aborted the robotic drilling process if intraoperative nerve monitoring alerted of a distance <0.1 mm. Microcomputed tomography images and histopathology showed prospective use of the technology prevented facial nerve damage. Facial nerve monitoring integrated in a robotic system supports the surgeon's ability to proactively avoid damage to the facial nerve during robotic drilling in the mastoid.

Sciatic nerve block in dogs: description and evaluation of a modified ultrasound-guided parasacral approach.

OBJECTIVE: To develop a modified ultrasound-guided parasacral approach to the sciatic nerve and compare the effects of a volume of 0.2 mL kg-1 of 0.5% levobupivacaine with an equivalent volume of 0.9% saline injected near the sciatic nerve. STUDY DESIGN: Cadaveric and experimental, blinded, randomized study. ANIMALS: Seven canine cadavers and seven experimental Beagle dogs. METHODS: Both sciatic nerves of seven cadavers were identified using a modified in-plane ultrasound-guided approach. Methylene blue solution (0.2 mL) was injected perineurally, and success was evaluated through dissection. The same approach was repeated in seven Beagle dogs sedated with dexmedetomidine (50 µg kg-1) injected intramuscularly (IM). After randomization, 0.2 mL kg-1 of 0.5% levobupivacaine (limb L) and 0.2 mL kg-1 of 0.9% saline (limb C) were injected perineurally on either right or left limb. Block success was determined by sensory deficits every hour for 8 hours after an atipamezole injection (0.2 mg kg-1) IM. Reaction to pinprick (binary score) over the course of the sciatic nerve (four locations) and locomotion were assessed. RESULTS: The overall sciatic nerve block success was 93% in cadavers and 86% in sedated dogs. It was impossible to localize the sciatic nerves in one obese sedated dog. Significant differences between limb L and limb C were observed for pinprick at great trochanter, caudal thigh and lateral tarsal joint (p < 0.0001). Reaction to pinprick was absent in all dogs at great trochanter and caudal thigh up to at least 3 hours on limb L. Locomotion was impaired in all but one dog for 60 (30-210) minutes (median; interquartile range). No complications were observed. CONCLUSIONS AND CLINICAL RELEVANCE: A volume of ≥0.2 mL kg-1 and a concentration of 0.5% levobupivacaine can be recommended when using a modified ultrasound-guided parasacral approach to the sciatic nerve in dogs.

Temperature Prediction Model for Bone Drilling Based on Density Distribution and In Vivo Experiments for Minimally Invasive Robotic Cochlear Implantation.

Surgical robots have been proposed ex vivo to drill precise holes in the temporal bone for minimally invasive cochlear implantation. The main risk of the procedure is damage of the facial nerve due to mechanical interaction or due to temperature elevation during the drilling process. To evaluate the thermal risk of the drilling process, a simplified model is proposed which aims to enable an assessment of risk posed to the facial nerve for a given set of constant process parameters for different mastoid bone densities. The model uses the bone density distribution along the drilling trajectory in the mastoid bone to calculate a time dependent heat production function at the tip of the drill bit. Using a time dependent moving point source Green's function, the heat equation can be solved at a certain point in space so that the resulting temperatures can be calculated over time. The model was calibrated and initially verified with in vivo temperature data. The data was collected in minimally invasive robotic drilling of 12 holes in four different sheep. The sheep were anesthetized and the temperature elevations were measured with a thermocouple which was inserted in a previously drilled hole next to the planned drilling trajectory. Bone density distributions were extracted from pre-operative CT data by averaging Hounsfield values over the drill bit diameter. Post-operative [Formula: see text]CT data was used to verify the drilling accuracy of the trajectories. The comparison of measured and calculated temperatures shows a very good match for both heating and cooling phases. The average prediction error of the maximum temperature was less than 0.7 °C and the average root mean square error was approximately 0.5 °C. To analyze potential thermal damage, the model was used to calculate temperature profiles and cumulative equivalent minutes at 43 °C at a minimal distance to the facial nerve. For the selected drilling parameters, temperature elevation profiles and cumulative equivalent minutes suggest that thermal elevation of this minimally invasive cochlear implantation surgery may pose a risk to the facial nerve, especially in sclerotic or high density mastoid bones. Optimized drilling parameters need to be evaluated and the model could be used for future risk evaluation.

A Neuromonitoring Approach to Facial Nerve Preservation During Image-guided Robotic Cochlear Implantation.

HYPOTHESIS: A multielectrode probe in combination with an optimized stimulation protocol could provide sufficient sensitivity and specificity to act as an effective safety mechanism for preservation of the facial nerve in case of an unsafe drill distance during image-guided cochlear implantation. BACKGROUND: A minimally invasive cochlear implantation is enabled by image-guided and robotic-assisted drilling of an access tunnel to the middle ear cavity. The approach requires the drill to pass at distances below 1  mm from the facial nerve and thus safety mechanisms for protecting this critical structure are required. Neuromonitoring is currently used to determine facial nerve proximity in mastoidectomy but lacks sensitivity and specificity necessaries to effectively distinguish the close distance ranges experienced in the minimally invasive approach, possibly because of current shunting of uninsulated stimulating drilling tools in the drill tunnel and because of nonoptimized stimulation parameters. To this end, we propose an advanced neuromonitoring approach using varying levels of stimulation parameters together with an integrated bipolar and monopolar stimulating probe. MATERIALS AND METHODS: An in vivo study (sheep model) was conducted in which measurements at specifically planned and navigated lateral distances from the facial nerve were performed to determine if specific sets of stimulation parameters in combination with the proposed neuromonitoring system could reliably detect an imminent collision with the facial nerve. For the accurate positioning of the neuromonitoring probe, a dedicated robotic system for image-guided cochlear implantation was used and drilling accuracy was corrected on postoperative microcomputed tomographic images. RESULTS: From 29 trajectories analyzed in five different subjects, a correlation between stimulus threshold and drill-to-facial nerve distance was found in trajectories colliding with the facial nerve (distance <0.1  mm). The shortest pulse duration that provided the highest linear correlation between stimulation intensity and drill-to-facial nerve distance was 250  µs. Only at low stimulus intensity values (≤0.3  mA) and with the bipolar configurations of the probe did the neuromonitoring system enable sufficient lateral specificity (>95%) at distances to the facial nerve below 0.5  mm. However, reduction in stimulus threshold to 0.3  mA or lower resulted in a decrease of facial nerve distance detection range below 0.1  mm (>95% sensitivity). Subsequent histopathology follow-up of three representative cases where the neuromonitoring system could reliably detect a collision with the facial nerve (distance <0.1  mm) revealed either mild or inexistent damage to the nerve fascicles. CONCLUSION: Our findings suggest that although no general correlation between facial nerve distance and stimulation threshold existed, possibly because of variances in patient-specific anatomy, correlations at very close distances to the facial nerve and high levels of specificity would enable a binary response warning system to be developed using the proposed probe at low stimulation currents.

Assessment of Intramedullary Spinal Pressure in Small Breed Dogs With Thoracolumbar Disk Extrusion Undergoing Hemilaminectomy.

OBJECTIVE: To assess intramedullary spinal pressure (IMP) in small breed dogs with thoracolumbar disk extrusion. STUDY DESIGN: Prospective cohort study. ANIMALS: Small breed dogs (n = 14) with thoracolumbar disk extrusion undergoing hemilaminectomy and healthy chondrodystrophic laboratory dogs (control; n = 3) without spinal disease. METHODS: Diagnosis was based on clinical and neurological examinations and magnetic resonance imaging (MRI) and was confirmed intraoperatively. A standardized anesthesia protocol and surgical procedure were used to minimize factors that could influence IMP. Intramedullary pressure was measured through a minidurotomy at the site of spinal cord compression using a fiber optic catheter inserted perpendicular to the longitudinal axis of the spinal cord. Measurements were taken after hemilaminectomy and again after removal of extruded disk material. RESULTS: Affected dogs had significantly higher IMP compared to control dogs (P = .008) and IMP decreased significantly post-decompression compared with initial values (P < .001). No correlation was found between IMP and neurologic grade, degree of spinal cord compression on MRI, or signal intensity changes on MRI. CONCLUSION: Acute thoracolumbar disk extrusion is associated with increased IMP in small breed dogs and surgical decompression results in an immediate decrease of IMP.

Assessment of Intrathecal Pressure in Chondrodystrophic Dogs With Acute Thoracolumbar Disk Disease.

OBJECTIVES: To assess intrathecal pressure (ITP) in chondrodystrophic dogs with thoracolumbar disk extrusion. STUDY DESIGN: Prospective cohort study. ANIMALS: Group 1: 11 chondrodystrophic dogs with thoracolumbar disk extrusion and present deep pain sensation. Group 2 (control): 3 healthy chondrodystrophic laboratory dogs without spinal disease. METHODS: Diagnosis was based on neurologic signs, magnetic resonance imaging (MRI) findings, and surgical confirmation. Blood pressure was maintained within physiologic range during anesthesia. A standardized surgical procedure was applied to minimize factors that could influence measurement readings. An extended hemilaminectomy was performed and ITP was measured with a fiber optic catheter. The catheter was inserted in the subarachnoid space 1 spinal segment caudal to the level of herniation and its tip was advanced to the site of compression. RESULTS: Significantly higher ITP occurred in chondrodystrophic dogs with acute thoracolumbar disk disease compared with controls. ITP was not associated with duration of clinical signs, neurologic status, outcome, degree of spinal cord compression, or signal intensity changes as assessed by MRI. CONCLUSION: Acute thoracolumbar disk disease leads to elevated ITP in chondrodystrophic dogs, which may contribute to increased compression of spinal cord parenchyma.

Repeated electrical stimulations as a tool to evoke temporal summation of nociceptive inputs in healthy, non-medicated experimental sheep.

The nociceptive withdrawal reflex (NWR) model is used in animal pain research to quantify nociception. The aim of this study was to evaluate the NWR evoked by repeated stimulations in healthy, non-medicated standing sheep. Repeated electrical stimulations were applied at 5 Hz for 2s to the digital nerves of the right thoracic and the pelvic limbs of 25 standing sheep. The stimulation intensities applied were fractions (0.5, 0.6, 0.7, 0.8, 0.9 and 1) of the individual previously determined nociceptive threshold (It) after single stimulation. Surface-electromyographic activity (EMG) was recorded from the deltoid, the femoral biceps or the peroneus tertius muscles. The repeated stimulation threshold (RS It) was reached if at least one stimulus in the train was followed by a reflex with a minimal root-mean-square-amplitude (RMSA) of 20 µV. The behavioural reaction following each series of stimulations was scored on a scale from 0 (no reaction) to 5 (vigorous whole-body reaction). For the deltoid muscle, RS It was 2.3 mA (1.6-3 mA) with a reaction score of 2 (1-2) and at a fraction of 0.6 (0.5-0.8)×It. For the biceps femoris muscle, RS It was 2.9 mA (2.6-4 mA) with a reaction score of 1 (1-2) at a fraction of and 0.55 (0.4-0.7)×It while for the peroneus tertius muscle RS It was 3 mA (2.8-3.5 mA) with a reaction score of 1 (1-2) and at a fraction of 0.8 (0.8-0.95)×It. Both, RMSA and reaction scores increased significantly with increasing stimulation intensities in all muscles (p<0.001). The repeated application of electrical stimuli led to temporal summation of nociceptive inputs and therefore a reduction of the stimulus intensity evoking a withdrawal reaction in healthy, standing sheep. Data achieved in this study can now serve as reference for further clinical or experimental applications of the model in this species.

Use of a perineural coiled catheter at the sciatic nerve in dogs after tibial plateau levelling osteotomy - preliminary observations.

The analgesic effects of peripheral nerve blocks can be prolonged with the placement of perineural catheters allowing repeated injections of local anaesthetics in humans. The objectives of this study were to evaluate the clinical suitability of a perineural coiled catheter (PCC) at the sciatic nerve and to evaluate pain during the early post-operative period in dogs after tibial plateau levelling osteotomy. Pre-operatively, a combined block of the sciatic and the femoral nerves was performed under sonographic guidance (ropivacaine 0.5%; 0.3 mL kg-1 per nerve). Thereafter, a PCC was placed near the sciatic nerve. Carprofen (4 mg kg-1 intravenously) was administered at the end of anaesthesia. After surgery, all dogs were randomly assigned to receive four injections of ropivacaine (group R; 0.25%, 0.3 mL kg-1) or NaCl 0.9% (group C; 0.3 mL kg-1) every 6 h through the PCC. Pain was assessed by use of a visual analogue scale (VAS) and a multi-dimensional pain score (4Avet) before surgery (T-1), for 390 min (T0, T30, T60, T120, T180, T240, T300, T360 and T390) as well as 1 day after surgery (Day 1). Methadone (0.1 mg kg-1) was administered each time the VAS was ≥40 mm or the 4Avet was ≥5. At T390 dogs received buprenorphine (0.02 mg kg-1). Data were compared using Mann-Whitney rank sum tests and repeated measures analysis of variance. Regardless of group allocation, 55% of dogs required methadone. VAS was significantly lower at T390 (P = 0.003), and at Day 1 (P = 0.002) and so was 4Avet at Day 1 (P = 0.012) in group R than in group C. Bleeding occurred in one dog at PCC placement and PCC dislodged six times of 47 PCCs placed. Minor complications occurred with PCC but allowed four repeated administrations of ropivacaine or saline over 24 h in 91.5% of the cases.

Quantitative assessment of the nociceptive withdrawal reflex in healthy, non-medicated experimental sheep.

This study aimed to characterize the nociceptive withdrawal reflex (NWR) and to define the nociceptive threshold in 25 healthy, non-medicated experimental sheep in standing posture. Electrical stimulation of the dorsal lateral digital nerves of the right thoracic and the pelvic limb was performed and surface-electromyography (EMG) from the deltoid (all animals) and the femoral biceps (18 animals) or the peroneus tertius muscles (7 animals) was recorded. The behavioural reaction following each stimulation was scored on a scale from 0 (no reaction) to 5 (strong whole body reaction). A train-of-five 1ms constant-current pulse was used and current intensity was stepwise increased until NWR threshold intensity was reached. The NWR threshold intensity (It) was defined as the minimal stimulus intensity able to evoke a reflex with a minimal Root-Mean-Square amplitude (RMSA) of 20µV, a minimal duration of 10ms and a minimal reaction score of 1 (slight muscle contraction of the stimulated limb) within the time window of 20 to 130ms post-stimulation. Based on this value, further stimulations were performed below (0.9It) and above threshold (1.5It and 2It). The stimulus-response curve was described. Data are reported as medians and interquartile ranges. At the deltoid muscle It was 4.4mA (2.9-5.7) with an RMSA of 62µV (30-102). At the biceps femoris muscle It was 7.0mA (4.0-10.0) with an RMSA of 43µV (34-50) and at the peroneus tertius muscle It was 3.4mA (3.1-4.4) with an RMSA of 38µV (32-46). Above threshold, RMSA was significantly increased at all muscles. Below threshold, RMSA was only significantly smaller than at It for the peroneus tertius muscle but not for the other muscles. Data achieved in this study serve as reference for experimental or clinical applications of the conscious sheep model.

Ultrasound-guided block of sciatic and femoral nerves: an anatomical study.

The sheep is a popular animal model for human biomechanical research involving invasive surgery on the hind limb. These painful procedures can only be ethically justified with the application of adequate analgesia protocols. Regional anaesthesia as an adjunct to general anaesthesia may markedly improve well-being of these experimental animals during the postoperative period due to a higher analgesic efficacy when compared with systemic drugs, and may therefore reduce stress and consequently the severity of such studies. As a first step 14 sheep cadavers were used to establish a new technique for the peripheral blockade of the sciatic and the femoral nerves under sonographic guidance and to evaluate the success rate by determination of the colorization of both nerves after an injection of 0.5 mL of a 0.1% methylene blue solution. First, both nerves were visualized sonographically. Then, methylene blue solution was injected and subsequently the length of colorization was measured by gross anatomical dissection of the target nerves. Twenty-four sciatic nerves were identified sonographically in 12 out of 13 cadavers. In one animal, the nerve could not be ascertained unequivocally and, consequently, nerve colorization failed. Twenty femoral nerves were located by ultrasound in 10 out of 13 cadavers. In three cadavers, signs of autolysis impeded the scan. This study provides a detailed anatomical description of the localization of the sciatic and the femoral nerves and presents an effective and safe yet simple and rapid technique for performing peripheral nerve blocks with a high success rate.

Comparison of the effects of the alpha-2 agonists detomidine, romifidine and xylazine on nociceptive withdrawal reflex and temporal summation in horses.

OBJECTIVE: To evaluate and compare the antinociceptive effects of the three alpha-2 agonists, detomidine, romifidine and xylazine at doses considered equipotent for sedation, using the nociceptive withdrawal reflex (NWR) and temporal summation model in standing horses. STUDY DESIGN: Prospective, blinded, randomized cross-over study. ANIMALS: Ten healthy adult horses weighing 527-645 kg and aged 11-21 years old. METHODS: Electrical stimulation was applied to the digital nerves to evoke NWR and temporal summation in the left thoracic limb and pelvic limb of each horse. Electromyographic reflex activity was recorded from the common digital extensor and the cranial tibial muscles. After baseline measurements a single bolus dose of detomidine, 0.02 mg kg(-1), romifidine 0.08 mg kg(-1), or xylazine, 1 mg kg(-1), was administered intravenously (IV). Determinations of NWR and temporal summation thresholds were repeated at 10, 20, 30, 40, 60, 70, 90, 100, 120 and 130 minutes after test-drug administration alternating the thoracic limb and the pelvic limb. Depth of sedation was assessed before measurements at each time point. Behavioural reaction was observed and recorded following each stimulation. RESULTS: The administration of detomidine, romifidine and xylazine significantly increased the current intensities necessary to evoke NWR and temporal summation in thoracic limbs and pelvic limbs of all horses compared with baseline. Xylazine increased NWR thresholds over baseline values for 60 minutes, while detomidine and romifidine increased NWR thresholds over baseline for 100 and 120 minutes, respectively. Temporal summation thresholds were significantly increased for 40, 70 and 130 minutes after xylazine, detomidine and romifidine, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Detomidine, romifidine and xylazine, administered IV at doses considered equipotent for sedation, significantly increased NWR and temporal summation thresholds, used as a measure of antinociceptive activity. The extent of maximal increase of NWR and temporal summation thresholds was comparable, while the duration of action was drug-specific.