Enantiospecific pharmacokinetics of intravenous dexmedetomidine in beagles.

The goal of this study was to investigate the pharmacokinetic (PK) behaviour of dexmedetomidine in dogs administered as a pure enantiomer versus as part of a racemic mixture. Eight unmedicated intact purpose-bread beagles were included. Two intravenous treatments of either medetomidine or dexmedetomidine were administered at 10- to 14-day intervals. Atipamezole or saline solution was administered intramuscularly 45 min later. Venous blood samples were collected into EDTA collection tubes, and the quantification of dexmedetomidine and levomedetomidine was performed by chiral LC-MS/MS. All dogs appeared sedated after each treatment without complication. Plasma concentrations of levomedetomidine were measured only in the racemic group and were 51.4% (51.4%-56.1%) lower than dexmedetomidine. Non-compartmental analysis (NCA) was performed for both drugs, while dexmedetomidine data were further described using a population pharmacokinetic approach. A standard two-compartment mammillary model with linear elimination with combined additive and multiplicative error model for residual unexplained variability was established for dexmedetomidine. An exponential model was finally retained to describe inter-individual variability on parameters of clearance (Cl1 ) and central and peripheral volumes of distribution (V1 , V2 ). No effect of occurrence, levomedetomidine or atipamezole could be observed on dexmedetomidine PK parameters. Dexmedetomidine did not undergo significantly different PK when administered alone or as part of the racemic mixture in otherwise unmedicated dogs.

Effects of perineural dexmedetomidine combined with ropivacaine on postoperative methadone requirements in dogs after tibial plateau levelling osteotomy: a two-centre study.

OBJECTIVE: To evaluate the efficacy of a perineural injection of dexmedetomidine combined with ropivacaine for reducing postoperative methadone requirements in dogs after tibial plateau levelling osteotomy (TPLO). STUDY DESIGN: A prospective, clinical, randomized and blinded trial. ANIMALS: A total of 58 client-owned dogs. METHODS: Ultrasound-guided midfemoral sciatic and inguinal femoral nerve blocks with ropivacaine (1 mg kg-1 per nerve block) combined with either dexmedetomidine (0.5 µg kg-1 per nerve block; group DEX) or the same volume of saline (group CON) were performed in dogs undergoing TPLO. Pain was assessed 30 minutes, 2 hours and then every 4 hours for 24 hours after surgery with a validated pain scale (4AVet). Meloxicam (0.15 mg kg-1) was administered intravenously (IV) at recovery. Rescue methadone (0.2 mg kg-1 IV) was administered if a score ≥ 6 (maximal score 18) was recorded and the number of postoperative doses was analysed by Fisher exact tests. The study was performed in parallel at a Veterinary Teaching Hospital (VTH) and a private Veterinary Referral Centre (VRC). RESULTS: Dogs received a total of 22 and 31 postoperative doses of methadone in groups DEX (14 doses at VRC, eight doses at VTH) and CON (28 doses at VRC, three doses at VTH), respectively. Overall, there was no difference in the postoperative rescue analgesia requirements between groups (p = 0.244). At the VRC, dogs received less methadone (p = 0.026) in group DEX compared with group CON, whereas at the VTH, there was no difference between groups (p = 0.216). CONCLUSIONS AND CLINICAL RELEVANCE: Perineural dexmedetomidine combined with ropivacaine did not reduce postoperative methadone requirements in dogs after TPLO, but results may differ from one centre to another. This discrepancy might be linked to variations in clinical practices and questions the validity of results obtained from single-centre randomized controlled trials but applied to different clinical settings.

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.

Antinociceptive effects of levomethadone in standing horses sedated with romifidine.

OBJECTIVE: To evaluate the antinociceptive effect of a bolus of intravenous levomethadone administered to horses during romifidine constant rate infusion (CRI). STUDY DESIGN: Prospective, randomized, masked, crossover experimental study. ANIMALS: A group of eight adult Warmblood horses (seven geldings, one mare) aged 6.6 ± 4.4 years, weighing 548 ± 52 kg [mean ± standard deviation (SD)]. METHODS: Levomethadone 0.1 mg kg-1 or an equivalent volume of saline (control) was administered intravenously to standing horses 60 minutes after starting a romifidine CRI. Blood samples to quantify romifidine and levomethadone plasma concentrations by capillary electrophoresis were collected up to 150 minutes after levomethadone administration. The nociceptive withdrawal reflex threshold (NWRT) was determined continuously using an automated threshold tracking device. Sedation and cardiopulmonary variables were assessed at regular intervals. A pharmacokinetic-pharmacodynamic (PK-PD) model was elaborated. Data are presented as mean ± SD or median (interquartile range, 25%-75%) where appropriate. Differences between groups were considered statistically significant for p < 0.05. RESULTS: Horses exhibited higher NWRTs after levomethadone administration than after saline (123 ± 9% versus 101 ± 9% relative to baseline, p < 0.05). The PK-PD model identified a contribution of levomethadone to the NWRT increase. Effect size was variable among individuals. No adverse reactions to levomethadone administration were observed. A slight effect of levomethadone on sedation scores was evident for the 60 minutes following its administration. CONCLUSIONS AND CLINICAL RELEVANCE: A single injection of levomethadone has the potential to increase the NWRT during romifidine CRI in horses and can be administered in combination with α2-adrencoceptor agonists to enhance antinociception in horses. However, individual variation is marked.

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.

Morphine plasmatic concentration in a pregnant mare and its foal after long term epidural administration.

BACKGROUND: Epidural administration of morphine has been shown to be an effective analgesic strategy in horses; however, the possible occurrence of side effects limits its usage. In order to decrease their frequency, it is important to target the minimal effective plasma concentration and avoid overdosing. As to date species-specific pharmacokinetics data are not available for epidural morphine, the dosing regimen is usually established on the basis of clinical reports and personal experience. In certain physiological conditions, like gestation, the outcome of an empirical dosing scheme can be unpredictable. The aim of this case report is to describe the pharmacological profile of morphine and its metabolites after prolonged epidural administration in a pregnant mare and her foal. CASE PRESENTATION: A 20 years old pregnant mare was presented to our hospital because of severe lameness, 2 months before delivery. Following an ineffective systemic pain treatment, an epidural catheter was inserted and morphine administered (initial dose 0.1 mg/kg every 8 h). Due to its efficacy in controlling pain, it was continued until end of gestation. Plasmatic concentration of morphine and its metabolites were assessed in the mare 6 weeks after starting the treatment, and in both the mare and foal during the first days after delivery. Plasmatic values similar to those previously reported in the literature following morphine short term administration through various routes and not accompanied by side effects were found in the mare, except during an excitatory period. Moreover, no evidence of dangerous drug accumulation or significant milk passage was noticed in the foal. Mild reduction of feces production with no signs of colic and two self-limiting episodes of excitement occurred during treatment in the mare. No side effects occurred during gestation and first phases of life in the foal. CONCLUSION: Prolonged epidural administration of morphine in a pregnant mare allowed good pain control in absence of clinically relevant side effects, in both the mare and her foal. Sudden increase in morphine plasmatic concentration can occur and side effects appear; careful treatment to the lowest effective dose and continuous monitoring of the clinical condition of the treated horse should be performed.

Use of nociceptive threshold testing in cats in experimental and clinical settings: a qualitative review.

OBJECTIVE: The objective of this study was to review the scientific articles on the use of nociceptive threshold testing (NTT) in cats and to summarize the clinical and experimental applications in this species. DATABASES USED: Pertinent literature was searched with PubMed, Scopus, Web of Science, Universitätsbibliothek Basel (swissbib Basel Bern) and Google Scholar. The search was then refined manually based first on article titles and abstracts, and subsequently on full texts. CONCLUSIONS: Of the four classical acute nociceptive models used for NTT, thermal and mechanical are most commonly used in cats. Thermal stimulation is applicable in experimental settings and has been used in pharmacodynamics studies assessing feline antinociception. Although mechanical stimulation is currently less used in cats, in the future it might play a role in the evaluation of clinical feline pain. However, the low response reliability after stimulus repetition within a narrow time interval represents a major limitation for the clinical use of mechanical thresholds in this species. Challenges remain when thermal thresholds are used to investigate analgesics that have the potential to affect skin temperature, such as opioids and α2-adrenergic agonists, and when a model of inflammatory pain is reproduced in experimental cats with the purpose of evaluating non-steroidal anti-inflammatory drugs as analgesics.

Investigation of selected respiratory effects of (dex)medetomidine in healthy Beagles.

OBJECTIVE: To investigate the effects of sedative doses of intravenous (IV) medetomidine (MED) or dexmedetomidine (DEX) on selected respiratory variables in dogs. STUDY DESIGN: Randomized, blinded, crossover study. ANIMALS: A total of eight healthy adult research Beagles. METHODS: Dogs breathing room air had an electrical impedance tomography belt placed around the chest and were maintained in right lateral recumbency. Respiratory rate (fR) in movements minute-1 (mpm) and changes in thoracic impedance (ΔZ) in arbitrary units (AU) were recorded for 120 seconds before (T0) and exactly 10 minutes (T10) after the administration of IV DEX (10 µg kg-1) or MED (20 µg kg-1), with a minimum washout period of 10 days between treatments. Minute ΔZ (ΔZ˙) was calculated by multiplying median ΔZ with fR. Data are presented as median (interquartile range). Significance for an overall effect of drugs (DEX versus MED) or treatment (T0 versus T10) was quantified with a two-way analysis of variance for repeated measures, followed by, when appropriate, Wilcoxon's signed rank test for each factor. RESULTS: Overall, fR decreased from 26 (22-29) mpm at T0 to 13 (10-21) mpm at T10 (p = 0.003) and ΔZ increased from 1.133 (0.856-1.599) AU at T0 to 1.650 (1.273-2.813) AU at T10 (p = 0.007), but ΔZ˙ did not change [30.375 (23.411-32.445) AU minute-1 at T0 and 30.581 (22.487-35.091) AU minute-1 at T10]. There was no difference between DEX and MED. Most dogs developed a peculiar breathing pattern characterized by clusters of breaths followed by short periods of apnoea. CONCLUSIONS AND CLINICAL RELEVANCE: Both drugs caused a change in breathing pattern, reduction in fR and increase in ΔZ but did not affect ΔZ˙. It is likely that (dex)medetomidine resulted in reduction in fR and increase in tidal volume without impacting minute volume.

Pharmacokinetic-pharmacodynamic modelling of the antinociceptive effect of a romifidine infusion in standing horses.

OBJECTIVE: To evaluate the effect of a romifidine infusion on antinociception and sedation, and to investigate its relationship with plasma concentration. STUDY DESIGN: Prospective, experimental, nonrandomized trial. ANIMALS: A total of 10 healthy adult warmblood horses. METHODS: Romifidine (loading dose: 0.08 mg kg-1, infusion: 0.03 mg kg-1 hour-1) was administered intravenously over 120 minutes. Romifidine plasma concentrations were determined by capillary electrophoresis. Sedation quality and nociceptive thresholds were evaluated at regular time points before, during and after romifidine administration. The nociceptive withdrawal reflex was elicited by electrical stimulation at the thoracic limb using a dedicated threshold tracking algorithm and recorded by electromyography at the deltoid muscle. A pharmacokinetic-pharmacodynamic model was established and correlation between romifidine plasma concentration and main output variables tested. RESULTS: A two compartmental model best described the romifidine pharmacokinetic profile. The nociceptive thresholds increased compared with baseline in all horses from 10 to 146 minutes after romifidine administration (p < 0.001). Peak effect reached 5.7 ± 2.3 times the baseline threshold (mean ± standard deviation). The effect/concentration relationship followed a counter-clockwise hysteresis loop. The mean plasma concentration was weakly correlated to nociceptive thresholds (p < 0.0071, r = 0.392). The sedative effects were significant until 160 minutes but variable, not correlated to plasma concentration (p = 0.067), and weakly correlated to nociceptive thresholds (p < 0.0001, r = 0.33). CONCLUSIONS AND CLINICAL RELEVANCE: Romifidine elicited a marked antinociceptive effect. Romifidine-induced antinociception appeared with a delayed onset and lasted longer than sedation after discontinuing its administration.

Polymelia in a chimeric Simmental calf: nociceptive withdrawal reflex, anaesthetic and analgesic management, anatomic and genetic analysis.

BACKGROUND: Polymelia is a congenital defect characterized by one or more supernumerary legs. The genetics and aetiology of this condition in cattle have not yet been thoroughly investigated even though several case reports do exist. The model of the nociceptive withdrawal reflex (NWR) has been characterized in several species to study spinal nociceptive processing. It is a polysynaptic spinal reflex that can be elicited by noxious electrical stimulation and recorded by electromyography. Thorough nociceptive examination and preventive analgesic management has not yet been an aspect in the perioperative management of polymelia cases. CASE PRESENTATION: A 4-month-old female Simmental calf was presented with notomelia. The animal was in good health and showed no neurologic deficiencies. Preoperatively, computed tomography was performed to gain more detailed anatomical information. To evaluate the sensitivity of the accessory limb, NWR testing was performed and revealed a connection of the afferent reflex pathway of the accessory limb to the efferent of the normal limb. The accessory limb was surgically removed under general anaesthesia. Intensive care included multimodal pain therapy adapted to the pain intensity scored during regular pain assessment. A gross anatomical dissection as well as a genetic analysis of the accessory limb were performed postoperatively. The calf was identified as a chimera. CONCLUSION: This calf was successfully relieved of its accessory limb. Chimerism has not been described in the congenital defect polymelia. As the accessory limb was pain sensitive and a common nociceptive reflex pathway was identified, thorough perioperative pain management was performed with the intention to prevent chronic neuropathic pain development.

Colon constipation in horses after sustained-release buprenorphine administration.

OBJECTIVE: To investigate the pharmacological profile and side effects of buprenorphine administered as a sustained-release formulation in horses. STUDY DESIGN: Pilot trial. ANIMALS: A total of four experimental horses, aged 18-27 years and weighing 508-578 kg. METHODS: Buprenorphine (0.1 mg kg-1) was mixed as a freshly prepared sterile solution with a sustained-release drug carrier. It was administered by the subcutaneous (n = 2) or intramuscular (n = 2) route. During the experiment, the horses were closely monitored, equipped with a step counter and blood samples were collected for quantification of buprenorphine in plasma. RESULTS: All four horses developed colon constipation requiring medical therapy, together with increased locomotor activity. One horse, requiring surgical treatment of colon constipation, was euthanized during recovery from anaesthesia for weakness and severe lower airway obstruction. The three other horses recovered fully within 5-7 days. Plasma buprenorphine concentrations were between 1 and 8 ng mL-1 for approximately 48 hours. No local reaction was observed at the injection sites. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of the sustained-release formulation of buprenorphine at a dose of 0.1 mg kg-1 resulted in plasma concentrations compatible with antinociceptive activity for at least 48 hours. The observed severe and undesirable effects of colon constipation and increased locomotor activity definitely preclude clinical use of sustained-release buprenorphine at this dose.

Ultrasound-guided lateral and subcostal transversus abdominis plane block in calves: a cadaveric study.

OBJECTIVE: To describe and assess the ultrasound-guided transversus abdominis plane (TAP) block feasibility in calf cadavers, to compare two injection volumes and to evaluate possible undesired solution spreads. STUDY DESIGN: Prospective, descriptive, anatomic study. ANIMALS: A group of 15 bovine cadavers weighing 47±11 kg (mean±standard deviation). METHODS: Lateral (n = 24) and subcostal (n = 12) TAP block approaches were assessed. For each approach, two volumes (0.2 or 0.4 mL kg-1) of toluidine blue and contrast medium were injected using both sides of the animals. Nerve staining was assessed by anatomical dissection and spread of injectate by contrast-enhanced computed tomography. Objective and subjective technique feasibility was evaluated by a specific score (poor, good, excellent). RESULTS: Using the lateral approach, 58%, 92% and 25% and 75%, 83% and 25% of the thirteenth thoracic, first and second lumbar nerves were stained by 0.2 and 0.4 mL kg-1, respectively. Craniocaudal and dorsoventral solution spread and number of blocks that adequately stained an individual nerve were not significantly different between the volumes. Using the subcostal approach, 67%, 83%, 67%, 67% and 50%, and 83%, 100%, 83%, 83% and 50% of the eighth, ninth, tenth, eleventh, twelfth thoracic nerves were stained by 0.2 and 0.4 mL kg-1, respectively. With both techniques, no intraspinal and one intraperitoneal spread were observed. Objective and subjective feasibility score was excellent for both approaches in the majority of the cases. CONCLUSIONS AND CLINICAL RELEVANCE: TAP injections were easy to perform with both techniques in calf cadavers. The volume of injectate did not influence spread. The authors conclude that a combination of the two approaches is necessary, but perhaps not sufficient, to stain all of the nerves innervating the ventral abdominal wall. Further studies are required to refine the technique and evaluate its efficacy in preventing nociception in calves.

Does systemic lidocaine reduce ketamine requirements for endotracheal intubation in calves?

OBJECTIVE: To investigate whether an intravenous (IV) lidocaine bolus in calves premedicated with xylazine-butorphanol reduces the amount of ketamine required to allow endotracheal intubation. STUDY DESIGN: Randomized, prospective clinical study. ANIMALS: In total, 41 calves scheduled for elective umbilical surgery. METHODS: Calves were randomly assigned to one of two groups (L: lidocaine or S: saline). The calves were administered xylazine (0.07 mg kg-1) and butorphanol (0.1 mg kg-1) intramuscularly and 10 minutes later lidocaine (2 mg kg-1; group L) or saline (group S) IV over 1 minute. After 2 minutes, ketamine (2.5 mg kg-1) was injected IV. If the depth of anaesthesia was insufficient for intubation, additional ketamine (1 mg kg-1) was administered every minute until intubation was successful. The amount of ketamine required for intubation, respiratory rate, pulse rate, arterial pressures, the depth of sedation and conditions of endotracheal intubation after induction of anaesthesia were compared between the two groups. RESULTS: The calves in group L were sedated more deeply than those in group S; however, neither the median (range) amount of ketamine required for intubation, 3.5 (2.5-4.5) mg kg-1 and 3.5 (2.5-3.5) mg kg-1, respectively, nor the induction quality differed significantly between the groups. CONCLUSION AND CLINICAL RELEVANCE: A bolus of lidocaine (2 mg kg-1) administered 10 minutes after xylazine-butorphanol in calves deepened the degree of sedation but did not decrease the requirement of ketamine for endotracheal intubation. No adverse effects were recorded in the physiological variables measured.

S-ketamine versus racemic ketamine in dogs: their relative potency as induction agents.

OBJECTIVE: To determine the potency ratio between S-ketamine and racemic ketamine as inductive agents for achieving tracheal intubation in dogs. STUDY DESIGN: Prospective, randomized, 'blinded', clinical trial conducted in two consecutive phases. ANIMALS: 112 client-owned dogs (ASA I or II). METHODS: All animals were premedicated with intramuscular acepromazine (0.02 mg kg(-1)) and methadone (0.2 mg kg(-1)). In phase 1, midazolam (0.2 mg kg(-1)) with either 3 mg kg(-1) of racemic ketamine (group K) or 1.5 mg kg(-1) of S-ketamine (group S) was administered IV, for induction of anaesthesia and intubation. Up to two additional doses of racemic (1.5 mg kg(-1)) or S-ketamine (0.75 mg kg(-1)) were administered if required. In phase 2, midazolam (0.2 mg kg(-1)) with 1 mg kg(-1) of either racemic ketamine (group K) or S-ketamine (group S) was injected and followed by a continuous infusion (1 mg kg minute(-1)) of each respective drug. Differences between groups were statistically analyzed via t-test, Fisher exact test and ANOVA for repeated measures. RESULTS: Demographics and quality and duration of premedication, induction and intubation were comparable among groups. During phase 1 it was possible to achieve tracheal intubation after a single dose in more dogs in group K (n = 25) than in group S (n = 16) (p = 0.046). A dose of 3 mg kg(-1) S-ketamine allowed tracheal intubation in the same number of dogs as 4.5 mg kg(-1) of racemic ketamine. The estimated potency ratio was 1.5:1. During phase 2, the total dose (mean ± SD) of S-ketamine (4.02 ±1.56 mg kg(-1)) and racemic ketamine (4.01 ± 1.42) required for tracheal intubation was similar. CONCLUSION AND CLINICAL RELEVANCE: Racemic and S-ketamine provide a similar quality of anaesthetic induction and intubation. S-ketamine is not twice as potent as racemic ketamine and, if infused, the potency ratio is 1:1.

Alfaxalone anesthesia by immersion in oriental fire-bellied toads (Bombina orientalis).

OBJECTIVES: To establish an effective alfaxalone concentration to be used for bath immersion of fire-bellied toads (Bombina orientalis) and to describe its effects. STUDY DESIGN: Prospective experimental study. ANIMALS: Thirteen oriental fire-bellied toads. METHODS: The study was carried out in two phases. The pilot phase involved five animals and aimed to identify an alfaxalone concentration capable of producing induction of anesthesia, defined as immobility with a head down position and loss of responsiveness to stimulation with a stick. The following trial in an additional eight toads used the effective alfaxalone concentration established during the pilot phase. Data from 11 animals (three toads in the pilot study and the eight additional toads) were analyzed. Twenty minutes after immersion in the anesthetic solution, the toads were removed from the bath, and heart rate, respiratory rate, the righting, myotactic and the nociceptive withdrawal reflexes were evaluated every 5 minutes. The loss of both righting and nociceptive withdrawal reflexes was considered indicative of a surgical depth of anesthesia. The time elapsed from anesthetic induction to return of righting reflex, the quality of recovery and the occurrence of undesired effects were observed and recorded. RESULTS: Immersion was found to be a suitable anesthetic technique for oriental fire-bellied toads and 200 mg L(-1) alfaxalone concentration produced anesthetic induction in 10 out of 11 toads. Side effects, such as skin irritation, erythema and changes in cutaneous pigmentation, were not observed in any animal. The duration of anesthesia ranged from 10 to 30 minutes after removal of the toads from the alfaxalone bath, and surgical depth of anesthesia was never achieved. CONCLUSIONS AND CLINICAL RELEVANCE: It was concluded that alfaxalone anesthesia induced by immersion in a concentration of 200 mg L(-1) is only suitable for toads undergoing non-invasive short procedures.

Antinociceptive effect of buprenorphine and evaluation of the nociceptive withdrawal reflex in foals.

OBJECTIVE: To elicit and evaluate the NWR (nociceptive withdrawal reflex) in 2 and 11 day old foals, to investigate if buprenorphine causes antinociception and determine if the NWR response changes with increasing age. The effect of buprenorphine on behaviour was also evaluated. STUDY DESIGN: Prospective, experimental cross-over trial. ANIMALS: Nine Norwegian Fjord research foals. METHODS: Buprenorphine, 10 µg kg(-1) was administered intramuscularly (IM) to the same foal at 2 days and at 11 days of age. The NWR and the effect of buprenorphine were evaluated by electromyograms recorded from the left deltoid muscle following electrical stimulation of the left lateral palmar nerve at the level of the pastern. Mentation, locomotor activity and respiratory rate were recorded before and after buprenorphine administration. RESULTS: We were able to evoke the NWR and temporal summation in foals using this model. Buprenorphine decreased the root mean square amplitude following single electrical stimulation (p < 0.001) in both age groups, and increased the NWR threshold following single electrical stimulation in 2 day old foals (p = 0.0012). Repeated electrical stimulation at 2 Hz was more effective to elicit temporal summation compared to 5 Hz (p < 0.001). No effect of age upon the NWR threshold was found (p = 0.34). Sedation when left undisturbed (11 occasions), increased locomotor activity when handled (9 occasions) and tachypnea (13 occasions) were common side-effects of buprenorphine. CONCLUSION AND CLINICAL RELEVANCE: These findings indicate that buprenorphine has antinociceptive effect in foals. Opioid side effects often recognized in adult horses also occur in foals.

Ultrasound-guided proximal paravertebral anaesthesia in cattle.

OBJECTIVE: To develop and evaluate a method for ultrasound-guidance in performing the proximal paravertebral block for flank anaesthesia in cattle through a cadaveric study, followed by clinical application. STUDY DESIGN: prospective experimental cadaveric study and clinical series. ANIMALS: Previously frozen lumbar sections of cows without known spinal abnormalities were used. The clinical case group comprised of ten animals for which a right flank laparotomy was indicated. METHODS: Twenty cow cadavers were used to perform ultrasound-guided bilateral injections of 1.0 mL dye (1.0 mL 1% Toluidine Blue in 1% Borax) at the intervertebral foramen at the level of T13, L1 and L2 spinal nerves. Distance and depth of injection, staining of the dorsal and ventral nerve branches, and deviation from the target were evaluated. The investigator's confidence as to visualisation and expected success at staining the nerve was assessed. Ten clinical cases received the ultrasound-guided proximal paravertebral anaesthesia. Analgesic success was evaluated using a 4-grade scoring system at 10 minutes after the injection and during surgery, respectively. Categorical variables were described using frequencies and proportions. RESULTS: Both dorsal and ventral branches of the spinal nerves T13, L1 or L2 were at least partially stained in 41% of injections, while in 77% of injections one of the branches was stained. Five out of ten clinical cases had a satisfactory anaesthesia. There was no significant association between confidence at injection and either staining or analgesic success. CONCLUSION: Results from the cadaveric and clinical study suggest no significant improvement using ultrasound guidance to perform proximal paravertebral block in cows compared to our previous clinical experience and to references in the literature using the blind method. CLINICAL RELEVANCE: Further research should be conducted to improve the ultrasound-guided technique described in this study.

Spatio-temporal electroencephalographic power distribution in experimental pigs receiving propofol.

INTRODUCTION: When assessing the spatio-temporal distribution of electroencephalographic (EEG) activity, characteristic patterns have been identified for several anesthetic drugs in humans. A shift in EEG power from the occipital to the prefrontal regions has been widely observed during anesthesia induction. This has been called "anteriorization" and has been correlated with loss of consciousness in humans. The spatio-temporal distribution of EEG spectral power in pigs and its modulation by anesthetics have not been described previously. The aim of the present study was to analyze EEG power across an anterior-posterior axis in pigs receiving increasing doses of propofol to 1) characterize the region of highest EEG power during wakefulness, 2) depict its spatio-temporal modification during propofol infusion, and 3) determine the region demonstrating the most significant modulations across different doses administered. MATERIALS AND METHODS: Six pigs with a body weight of 33.3 ± 3.6 kg and aged 11.3 ± 0.5 weeks were included in a prospective experimental study. Electroencephalographic activity was collected at the occipital, parietal and prefrontal regions at increasing doses of propofol (starting at 10 mg kg-1 h-1 and increasing it by 10 mg kg-1 h-1 every 15 minutes). The EEG power was assessed using a generalized linear mixed model in which propofol doses and regions were treated as fixed effects, whereas pig was used as a random effect. Pairwise comparisons of marginal linear predictions were used to assess the change in power when the specific propofol dose (or region) was considered. RESULTS: During both wakefulness and propofol infusion, the highest EEG power was located in the prefrontal region (p<0.001). The EEG power, both total and for each frequency band, mostly followed the same pattern, increasing from awake until propofol 20 mg kg-1 h-1 and then decreasing at propofol 30 mg kg-1 h-1. The region showing the strongest differences in EEG power across propofol doses was the prefrontal. CONCLUSION: In juvenile pigs receiving increasing doses of propofol, the prefrontal region showed the highest EEG power both during wakefulness and propofol administration and was the area in which the largest frequency-band specific variations were observed across different anesthetic doses. The assessment of the spectral EEG activity at this region could be favorable to distinguish DoA levels in pigs.