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Summary: Background: Fluid therapy is an important component of equine practice. The choice of intravenous catheter is likely to impact fluid flow rates, which is of relevance in clinical cases. Objectives: (i) To assess fluid flow rates through five different equine catheters; (ii) to evaluate the impact of height on fluid flow rates and (iii) to compare agreement of flow rates achieved through identical catheters. Study design: In vitro experimental study. Methods: Flow rates were measured through five different equine catheters (2 × 14, 13, 12 and 10‐gauge) at 150 and 200 cm from ground level. Each catheter was attached to a standardised fluid administration system, time taken to reach 1000 g of fluids was measured. Three catheters were used to assess the agreement between identical catheters. Statistical analysis: (i) one‐way ANOVA assessed whether catheter type influenced flow rate and a post‐hoc Tukey's test compared mean flow rates with all other flow rates; (ii) two‐way ANOVA assessed whether height and catheter type influenced the flow rate. Finally, (iii) an intraclass correlation assessed how closely flow rates from identical catheters resembled each other. Results: (i) The fastest mean flow rates were achieved through the 10‐gauge catheter at 150 (14.1 L/h) and 200 cm (17.8 L/h). (ii) Mean flow rates through all five catheters increased by a range of 25.4–28.6% at 200 vs. 150 cm. (iii) There was excellent agreement between mean fluid rates through identical catheters (intraclass correlation 0.994–0.998). Main limitations: Flow rates achievable in vivo are likely to be lower. We used water which may have a different viscosity compared with fluids used commonly in equine practice. Conclusions: Fluid flow rates can be increased using wider bore catheters and increasing the height of the fluid bag. There is excellent agreement between fluid flow rates through identical catheters. [ABSTRACT FROM AUTHOR]

Summary: Background: Standing surgery avoids the risks of general anaesthesia in horses. Objectives: To assess sedation, antinociception and gastrointestinal motility in standing horses after a detomidine loading dose and 2‐h constant rate intravenous (i.v.) infusion, with or without methadone. Study design: Blinded, randomised, crossover with seven healthy adult cross‐bred horses, three geldings and four females (404 ± 22 kg). Methods: Five i.v. treatments were administered to all horses with 1‐week washout period: saline (SAL), detomidine low (2.5 μg/kg bwt + 6.25 μg/kg bwt/h) (DL) and high doses (5 μg/kg bwt + 12.5 μg/kg bwt/h) (DH) alone or combined with methadone (0.2 mg/kg bwt + 0.05 mg/kg bwt/h), (DLM) and (DHM), respectively. Height of head above the ground (HHAG), electrical (ET), thermal (TT) and mechanical (MT) nociceptive thresholds and gastrointestinal motility were evaluated at predetermined times between 5 and 240 min. A mixed effect model and Kruskal–Wallis test were used to analyse normally and non‐normally distributed data, respectively. Results: Sedation (<50% basal HHAG) was achieved for the duration of the infusion, and for an additional 15 min in DH and DHM groups. Nociceptive thresholds were higher than baseline, to the greatest degree and the longest duration, with DHM (ET and TT for 135 min and MT for 150 min). After DH, TT was significantly higher than baseline from 30 to 120 min and MT from 15 to 135 min. After DLM, ET was increased at 90 min, TT at 30 min and MT for 120 min. Gastrointestinal motility was reduced for up to 135 min after DL, 150 min after DLM and 210 min after DH and DHM. Main limitations: Nociceptive thresholds are not equivalent to surgical stimuli. Conclusion: Methadone with the highest detomidine dose (DHM) may provide sufficient sedation and analgesia for standing surgical procedures and warrants further investigation. [ABSTRACT FROM AUTHOR]

Summary: Background: Pharmacokinetic (PK)/pharmacodynamic (PD) modelling offers new insights to design protocols for sedation and analgesia in standing horses. Objectives: To evaluate the parameters and interactions between detomidine and methadone when given alone or combined in standing horses. Study design: Randomised, placebo‐controlled, blinded, crossover. Methods: Eight adult healthy horses were given six treatments intravenously: saline (SAL); detomidine (5 μg/kg bwt; DET); methadone (0.2 mg/kg bwt; MET) alone or combined with detomidine (2.5 [MLD], 5 [MMD] or 10 [MHD] μg/kg bwt). Venous blood samples were obtained at predetermined times between 0 and 360 min after drug administration. Plasma detomidine and methadone were measured using a single, liquid/liquid extraction technique by liquid chromatography coupled with a triple quadrupole mass spectrometer (LC‐MS/MS). Sequential PK/PD modelling compared rival models, with and without PK and PD interaction between drugs, to fit the PD data including height of the head above the ground (HHAG), a visual analogue scale for sedation (VAS), electrical (ET), thermal (TT) and mechanical (MT) nociceptive thresholds and gastrointestinal motility (GIM) [1]. Results: Two and three compartment models best described the PK of detomidine and methadone, respectively. Detomidine decreased its own clearance as well as the clearance of methadone. The interaction of methadone on the effect of detomidine revealed an infra‐additive (partial antagonism) effect for HHAG (α = −1.33), VAS (α = −0.98) and GIM (α = −1.05), a positive potentiation for ET (pot = 0.0041) and TT (pot = 0.133) and a synergistic to additive effect for MT (α = 0.78). Main limitations: This is a small experimental study. Conclusions: Different PK/PD interactions were demonstrated for each PD parameter and could be modelled in vivo. The modelling of our data will allow us to simulate and predict the effect of constant rate infusions of both drugs for future investigations. [ABSTRACT FROM AUTHOR]

Reasons for performing study: Dexmedetomidine has been administered in the equine as a constant-rate infusion (CRI) during inhalation anaesthesia, preserving optimal cardiopulmonary function with calm and coordinated recoveries. Inhalant anaesthetic sparing effects have been demonstrated in other species, but not in horses. Objectives: To determine the effects of a CRI of dexmedetomidine on the minimal alveolar concentration (MAC) of sevoflurane in ponies. Methods: Six healthy adult ponies were involved in this prospective, randomised, crossover, blinded, experimental study. Each pony was anaesthetised twice (3 weeks washout period). After induction with sevoflurane in oxygen (via nasotracheal tube), the ponies were positioned on a surgical table (T0), and anaesthesia was maintained with sevoflurane (expired sevoflurane fraction 2.5%) in 55% oxygen. The ponies were randomly allocated to treatment D (dexmedetomidine 3.5 µg/kg bwt i.v. [T10-T15] followed by a CRI of dexmedetomidine at 1.75 µg/kg bwt/h) or treatment S (bolus and CRI of saline at the same volume and rate as treatment D). After T60, MAC determination, using a classic bracketing technique, was initiated. Stimuli consisted of constant-current electrical stimuli at the skin of the lateral pastern region. Triplicate MAC estimations were obtained and averaged in each pony. Monitoring included pulse oximetry, electrocardiography, anaesthetic gas monitoring, arterial blood pressure measurement and arterial blood gases. Normocapnia was maintained by mechanical ventilation. Analysis of variance (treatment and period as fixed factors) was used to detect differences between treatments (α= 0.05). Results: An intravenous (i.v.) dexmedetomidine CRI decreased mean ± s.d. sevoflurane MAC from 2.42 ± 0.55 to 1.07 ± 0.21% (mean MAC reduction 53 ± 15%). Conclusions and potential relevance: A dexmedetomidine CRI at the reported dose significantly reduces the MAC of sevoflurane. [ABSTRACT FROM AUTHOR]

Objective: To assess the usefulness of a webpage incorporating a real-time error management system for the Confidential Enquiry into Perioperative Equine Fatalities 4 (CEPEF4)., Study Design: An observational, descriptive, retrospective, longitudinal study., Animals: Data sets from 48,075 general anaesthetics and 12,453 standing sedations., Methods: Comparison of three consecutive phases of data collection [phase I: personal document file (PDF) by e-mail, manual revision; phase II: PDF by e-mail, automatic revision; phase III: web system, automatic correction] objectively (number of e-mails sent and received by the data managers related to data correction; number of detected errors by phase) and subjectively (16 questions in Likert format; one open-ended question)., Results: Objectively, the average number of e-mails sent per day was reduced from phase I (3.6) and II (3.9) to 1.7 in phase III. The ratio of e-mails per 100 cases received was reduced from phase I (5.8) and II (4.0) to 2.4 in phase III. Errors remained below 2,000 during phase I, reaching a peak of 5,430 in phase 2 owing to a strengthened error detection strategy. During phase III, errors were reduced from 3,200 to 423 within 94 days. Subjectively, questions evaluating the PDF system indicated that users overall agree/strongly agree (54-84%) with its comfort level versus the (89-99%) of the web system. When compared, users found the web system more comfortable than the PDF system (86-95%)., Conclusions and Clinical Relevance: The transition to a real-time error management system in phase III led to considerably fewer e-mails sent and received plus fewer errors. Users also found the website preferable to the PDF system. Our findings highlight the importance of implementing an error management system to minimize data inaccuracies and to improve the overall efficiency and ease of use of large data set collection in veterinary medicine., (Copyright © 2024 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

Background: Equine post-operative morbidity represents a significant concern for both veterinary surgeons and horse owners., Objectives: To estimate the prevalence of post-operative complications in horses after elective/non-abdominal surgery or colic surgery., Study Design: Systematic review., Methods: A database search identified eligible studies which reported the prevalence of equine post-operative complications published as a full paper in English in a peer-reviewed journal between 2000 and 2023. Studies were evaluated using the JBI Critical Appraisal Checklist for Prevalence Studies and GRADE (Grading of Recommendations, Assessment, Development and Evaluations) framework. Data for the most commonly reported complications were analysed using Chi-squared analysis of weighted means to answer 13 PICO (Population, Intervention, Comparator and Outcomes) questions., Results: Sixty-seven studies met inclusion criteria. Data for eight post-operative morbidities (colic, surgical site complications, myopathy/neuropathy, laminitis, diarrhoea/colitis, fever/pyrexia, jugular thrombophlebitis/thrombosis, respiratory complications) were sufficient to allow statistical analyses. The weighted mean of the overall proportion of post-operative complications after elective/non-abdominal surgery is 17.48% (95% confidence interval [95% CI]: 13.20-22.92), significantly increasing to 55.62% (95% CI: 45.79-65.03) after colic surgery (odds ratio [OR] 6.63; 95% CI: 5.83-7.56; p < 0.001). The most commonly reported morbidity was post-operative colic, with a weighted mean prevalence of 7.45% (95% CI: 4.83-11.76) after elective/non-abdominal surgery, significantly rising to 26.46% (95% CI: 19.11-35.97) after colic surgery (OR 4.11; 95% CI: 3.60-4.71; p < 0.001). The weighted mean prevalence of surgical site complications, laminitis, diarrhoea/colitis, fever/pyrexia, jugular thrombophlebitis/thrombosis and respiratory complications were significantly higher after colic surgery compared with elective/non-abdominal surgery. Myopathy/neuropathy was the only morbidity where prevalence was not different between groups (OR 1.86; 95% CI: 0.86-4.16; p = 0.16)., Main Limitations: The majority of studies were retrospective. Morbidity definitions, data collection periods, follow-up time and methods varied between studies., Conclusions: Based on current evidence, the prevalence of post-operative colic, surgical site complications, laminitis, diarrhoea/colitis, fever/pyrexia, jugular thrombophlebitis/thrombosis and respiratory complications is significantly higher after colic surgery compared with elective/non-abdominal surgery under general anaesthesia., (© 2024 EVJ Ltd.)

Background: Backfat thickness is an important carcass composition trait for pork production and is commonly included in swine breeding programmes. In this paper, we report the results of a large genome-wide association study for backfat thickness using data from eight lines of diverse genetic backgrounds., Methods: Data comprised 275,590 pigs from eight lines with diverse genetic backgrounds (breeds included Large White, Landrace, Pietrain, Hampshire, Duroc, and synthetic lines) genotyped and imputed for 71,324 single-nucleotide polymorphisms (SNPs). For each line, we estimated SNP associations using a univariate linear mixed model that accounted for genomic relationships. SNPs with significant associations were identified using a threshold of p < 10 -6 and used to define genomic regions of interest. The proportion of genetic variance explained by a genomic region was estimated using a ridge regression model., Results: We found significant associations with backfat thickness for 264 SNPs across 27 genomic regions. Six genomic regions were detected in three or more lines. The average estimate of the SNP-based heritability was 0.48, with estimates by line ranging from 0.30 to 0.58. The genomic regions jointly explained from 3.2 to 19.5% of the additive genetic variance of backfat thickness within a line. Individual genomic regions explained up to 8.0% of the additive genetic variance of backfat thickness within a line. Some of these 27 genomic regions also explained up to 1.6% of the additive genetic variance in lines for which the genomic region was not statistically significant. We identified 64 candidate genes with annotated functions that can be related to fat metabolism, including well-studied genes such as MC4R, IGF2, and LEPR, and more novel candidate genes such as DHCR7, FGF23, MEDAG, DGKI, and PTN., Conclusions: Our results confirm the polygenic architecture of backfat thickness and the role of genes involved in energy homeostasis, adipogenesis, fatty acid metabolism, and insulin signalling pathways for fat deposition in pigs. The results also suggest that several less well-understood metabolic pathways contribute to backfat development, such as those of phosphate, calcium, and vitamin D homeostasis., (© 2021. The Author(s).)

It is almost 20 years since the largest observational, multicentre study evaluating the risks of mortality associated with general anaesthesia in horses. We proposed an internet-based method to collect data (cleaned and analysed with R) in a multicentre, cohort, observational, analytical, longitudinal and prospective study to evaluate peri-operative equine mortality. The objective was to report the usefulness of the method, illustrated with the preliminary data, including outcomes for horses seven days after undergoing general anaesthesia and certain procedures using standing sedation. Within six months, data from 6701 procedures under general anaesthesia and 1955 standing sedations from 69 centres were collected. The results showed (i) the utility of the method; also, that (ii) the overall mortality rate for general anaesthesia within the seven-day outcome period was 1.0%. In horses undergoing procedures other than exploratory laparotomy for colic ( "noncolics" ), the rate was lower, 0.6%, and in "colics" it was higher, at 3.4%. For standing sedations, the overall mortality rate was 0.2%. Finally, (iii) we present some descriptive data that demonstrate new developments since the previous CEPEF2. In conclusion, horses clearly still die unexpectedly when undergoing procedures under general anaesthesia or standing sedation. Our method is suitable for case collection for future studies.

Proper pain therapy requires adequate pain assessment. This study evaluated the reliability and validity of the Unesp-Botucatu horse acute pain scale (UHAPS), the Orthopedic Composite Pain Scale (CPS) and unidimensional scales in horses admitted for orthopedic and soft tissue surgery. Forty-two horses were assessed and videotaped before surgery, up to 4 hours postoperatively, up to 3 hours after analgesic treatment, and 24 hours postoperatively (168 video clips). After six evaluators viewing each edited video clip twice in random order at a 20-day interval, they chose whether analgesia would be indicated and applied the Simple Descriptive, Numeric and Visual Analog scales, CPS, and UHAPS. For all evaluators, intra-observer reliability of UHAPS and CPS ranged from 0.70 to 0.97. Reproducibility was variable among the evaluators and ranged from poor to very good for all scales. Principal component analysis showed a weak association among 50% and 62% of the UHAPS and CPS items, respectively. Criterion validity based on Spearman correlation among all scales was above 0.67. Internal consistency was minimally acceptable (0.51-0.64). Item-total correlation was acceptable (0.3-0.7) for 50% and 38% of UHAPS and CPS items, respectively. UHAPS and CPS were specific (90% and 79% respectively), but both were not sensitive (43 and 38%, respectively). Construct validity (responsiveness) was confirmed for all scales because pain scores increased after surgery. The cut-off point for rescue analgesia was ≥ 5 and ≥ 7 for the UHAPS and CPS, respectively. All scales presented adequate repeatability, criterion validity, and partial responsiveness. Both composite scales showed poor association among items, minimally acceptable internal consistency, and weak sensitivity, indicating that they are suboptimal instruments for assessing postoperative pain. Both composite scales require further refinement with the exclusion of redundant or needless items and reduction of their maximum score applied to each item or should be replaced by other tools., Competing Interests: Professor Bernd Driessen and Associate Professors Klaus Hopster and Laura Zarucco are shareholders of Narkovet Consulting®, LLC, which provided parts of the funding for the present study. However, Narkovet Consulting®, LLC did not in any way or form impact these authors’ adherence to all PLOS ONE policies on sharing data and materials as detailed in the online guide for authors (http://journals.plos.org/plosone/s/competing-interests) or had any influence on data presentation and interpretation. All other authors declare that they have no conflicts of interest.

Recovery remains the most dangerous phase of general anaesthesia in horses. The objective of this publication was to perform a structured literature review including levels of evidence (LoE) of each study with the keywords " recovery anaesthesia horse ", entered at once, in the search browsers PubMed and Web of Science. The two authors independently evaluated each candidate article. A final list with 444 articles was obtained on 5 April 2021, classified as: 41 " narrative reviews/expert opinions ", 16 " retrospective outcome studies ", 5 " surveys ", 59 " premedication/sedation and induction drugs ", 27 " maintenance with inhalant agents ", 55 " maintenance with total intravenous anaesthesia (TIVA) ", 3 " TIVA versus inhalants ", 56 " maintenance with partial intravenous anaesthesia (PIVA) ", 27 " other drugs used during maintenance ", 18 " drugs before/during recovery ", 18 " recovery systems ", 21 " respiratory system in recovery ", 41 " other factors ", 51 " case series/reports " and 6 " systems to score recoveries ". Of them, 167 were LoE 1, 36 LoE 2, 33 LoE 3, 110 LoE 4, 90 LoE 5 and 8 could not be classified based on the available abstract. This review can be used as an up-to-date compilation of the literature about recovery after general anaesthesia in adult horses that tried to minimise the bias inherent to narrative reviews.

Although facial characteristics are used to estimate horse sedation, there are no studies measuring their reliability and validity. This randomised controlled, prospective, horizontal study aimed to validate a facial sedation scale for horses (FaceSed). Seven horses received detomidine infusion i.v. in low or high doses/rates alone (DL 2.5 μg/kg+6.25 μg/kg/h; DH 5 μg/kg+12.5 μg/kg/h) or combined with methadone (DLM and DHM, 0.2 mg/kg+0.05 mg/kg/h) for 120 min, or acepromazine boli i.v. in low (ACPL 0.02 mg/kg) or high doses (ACPH 0.09 mg/kg). Horses' faces were photographed at i) baseline, ii) peak, iii) intermediate, and iv) end of sedation. After randomisation of moments and treatments, photos were sent to four evaluators to assess the FaceSed items (ear position, orbital opening, relaxation of the lower and upper lip) twice, within a one-month interval. The intraclass correlation coefficient of intra- and interobserver reliability of FaceSed scores were good to very good (0.74-0.94) and moderate to very good (0.57-0.87), respectively. Criterion validity based on Spearman correlation between the FaceSed versus the numerical rating scale and head height above the ground were 0.92 and -0.75, respectively. All items and the FaceSed total score showed responsiveness (construct validity). According to the principal component analysis all FaceSed items had load factors >0.50 at the first dimension. The high internal consistency (Cronbach´s α = 0.83) indicated good intercorrelation among items. Item-total Spearman correlation was adequate (rho 0.3-0.73), indicating homogeneity of the scale. All items showed sensitivity (0.82-0.97) to detect sedation, however only orbital opening (0.79) and upper lip relaxation (0.82) were specific to detect absence of sedation. The limitations were that the facial expression was performed using photos, which do not represent the facial movement and the horses were docile, which may have reduced specificity. The FaceSed is a valid and reliable tool to assess tranquilisation and sedation in horses., Competing Interests: The authors have declared that no competing interests exist.

Background: Standing surgery in horses combining intravenous sedatives, analgesics and local anaesthesia is becoming more popular. Ultrasound guided (USG) peribulbar nerve block (PB) has been described in dogs and humans for facial and ocular surgery, reducing the risk of complications versus retrobulbar nerve block (RB)., Objective: To describe a technique for USG PB in horse cadavers., Methods: Landmarks and PB technique were described in two equine cadaver heads ( Phase 1 ), with computed tomography (CT) imaging confirming contrast location and spread. In Phase 2 , ten equine cadaver heads were randomised to two operators naïve to the USG PB, with moderate experience with ultrasonography and conventional "blind" RB. Both techniques were demonstrated once. Subsequently, operators performed five USG PB and five RB each, unassisted. Contrast location and spread were evaluated by CT. Injection site success was defined for USG PB as extraconal contrast, and for RB intraconal contrast., Results: Success was 10/10 for USG PB and 0/10 for RB ( p < 0.001). Of the RB injections, eight resulted in extraconal contrast and two in the masseter muscle ( p = 0.47)., Conclusions: The USG PB had a high injection site success rate compared with the RB technique; however, we cannot comment on clinical effect. The USG technique was easily learnt, and no potential complications were seen. The USG PB nerve block could have a wide application for use in horses for ocular surgeries (enucleations, eyelid, corneal, cataract surgeries, and ocular analgesia) due to reduced risk of iatrogenic damage. Further clinical studies are needed., Competing Interests: The authors declare no conflicts of interest., (© 2021 The Korean Society of Veterinary Science.)

The lack of standardization of sedation scales in horses limits the reproducibility between different studies. This prospective, randomized, blinded, horizontal and controlled trial aimed to validate a scale for sedation in horses (EquiSed). Seven horses were treated with intravenous detomidine in low/high doses alone (DL 2.5 μg/kg + 6.25 μg/kg/h; DH 5 μg/kg +12.5 μg/kg/h) or associated with methadone (DLM and DHM, 0.2 mg/kg + 0.05 mg/kg/h) and with low (ACPL 0.02 mg/kg) or high (ACPH 0.09 mg/kg) doses of acepromazine alone. Horses were filmed at (i) baseline (ii) peak, (iii) intermediate, and (iv) end of sedation immediately before auditory, visual and pressure stimuli were applied and postural instability evaluated for another study. Videos were randomized and blindly evaluated by four evaluators in two phases with 1-month interval. Intra- and interobserver reliability of the sum of EquiSed (Intraclass correlation coefficient) ranged between 0.84-0.94 and 0.45-0.88, respectively. The criterion validity was endorsed by the high Spearman correlation between the EquiSed and visual analog (0.77), numerical rating (0.76), and simple descriptive scales (0.70), and average correlation with head height above the ground (HHAG) (-0.52). The Friedman test confirmed the EquiSed responsiveness over time. The principal component analysis showed that all items of the scale had a load factor ≥ 0.50. The item-total Spearman correlation for all items ranged from 0.3 to 0.5, and the internal consistency was good (Cronbach's α = 0.73). The area under the curve of EquiSed HHAG as a predictive diagnostic measure was 0.88. The sensitivity of the EquiSed calculated according to the cut-off point (score 7 of the sum of the EquiSed) determined by the receiver operating characteristic curve, was 96% and specificity was 83%. EquiSed has good intra- and interobserver reliabilities and is valid to evaluate tranquilization and sedation in horses., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Oliveira, Gozalo-Marcilla, Ringer, Schauvliege, Fonseca, Trindade, Puoli Filho and Luna.)

Objective: To perform a literature review of the thermal and mechanical antinociceptive devices used in pharmacological studies in standing horses published after 2011 (2012-2019). To complete a full literature review about electrical stimulation used for evaluation in similar studies., Databases Used: PubMed, Google Scholar and Web of Science., Conclusions: A high level of standardization has been reached in antinociceptive studies in standing horses using thermal and mechanical stimuli in most recent years. Commercially available testing devices to deliver thermal, mechanical and electrical stimuli, with observation of aversive responses to these stimuli, are reliable, sensitive and specific. For electrical stimulus testing, there is evidence that the resistance between the electrodes should be measured and should not exceed 3 kΩ to guarantee consistent and reproducible stimuli. The specific analysis of electromyographic activity after an electrical stimulus provides more detailed information about the neurons stimulated., (Copyright © 2019 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

The alpha(α) 2 -agonist detomidine is used for equine sedation with opioids such as methadone. We retrieved the data from two randomized, crossover studies where detomidine and methadone were given intravenously alone or combined as boli (STUDY 1) (Gozalo-Marcilla et al., 2017, Veterinary Anaesthesia and Analgesia, 2017, 44, 1116) or as 2-hr constant rate infusions (STUDY 2) (Gozalo-Marcilla et al., 2019, Equine Veterinary Journal, 51, 530). Plasma drug concentrations were measured with a validated tandem Mass Spectrometry assay. We used nonlinear mixed effect modelling and took pharmacokinetic (PK) data from both studies to fit simultaneously both drugs and explore their nonlinear kinetics. Two significant improvements over the classical mammillary two-compartment model were identified. First, the inclusion of an effect of detomidine plasma concentration on the elimination clearances (Cls) of both drugs improved the fit of detomidine (Objective Function Value [OFV]: -160) and methadone (OFV: -132) submodels. Second, a detomidine concentration-dependent reduction of distributional Cls of each drug further improved detomidine (OFV: -60) and methadone (OFV: -52) submodel fits. Using the PK data from both studies (a) helped exploring hypotheses on the nonlinearity of the elimination and distributional Cls and (b) allowed inclusion of dynamic effects of detomidine plasma concentration in the model which are compatible with the pharmacology of detomidine (vasoconstriction and reduction in cardiac output)., (© 2019 John Wiley & Sons Ltd.)

Objective: To determine the required rate of a detomidine infusion (loading dose 5 μg kg -1 ; initial rate 12.5 μg kg -1 hour -1 ) added to a constant infusion of methadone (0.2 mg kg -1 ; 0.05 mg kg -1 hour -1 ) for sedation in standing horses and ponies undergoing elective surgeries with appropriate local anaesthetic techniques., Study Design: Prospective, clinical study., Animals: Adult, healthy, client-owned, non-food-producing horses or ponies sedated for elective standing surgeries longer than 45 minutes., Methods: At baseline (in the stables before administration of sedative agents), at 10 minutes after sedation and every 5 minutes thereafter, ataxia, sedation and surgical condition were evaluated; each scored 0-3. These scores were used to adjust the detomidine administration rate using the Ghent Sedation Algorithm. A 10 cm visual analogue scale (VAS) was used by the main surgeon at the end of the procedure to evaluate the surgical conditions. Heart rate, systolic arterial pressure and respiratory frequency were also recorded at each time point. For statistical analysis, anova for normal, Kruskal-Wallis H-test for non-normal variables, and Mann-Whitney U test for VAS were used., Results: From the 42 horses/ponies included in this study, 28 underwent dental procedures and 14 other types of procedures. Overall, dental procedures required higher mean detomidine rates compared with other types of surgeries (16.9 ± 4.5 versus 9.0 ± 1.9 μg kg -1 hour -1 ) (p < 0.001). Dental procedures were assigned similar VAS scores, median (range), of 7.8 (5.8-10) with other procedures, 8.7 (2.8-10). Cardiovascular changes were not clinically significant. No signs or behavioural changes of abdominal pain were observed postoperatively., Conclusions and Clinical Relevance: Satisfactory surgical conditions were achieved using a combination of detomidine and methadone infusions with locoregional anaesthesia, with no adverse effects. Dental procedures required higher detomidine dose rates compared with other surgeries., (Copyright © 2019 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

Objective: To summarize the different methods used to assess sedation and/or adjust the dose or administration rate of alpha-2 agonists in horses and to propose an algorithm to adjust the administration rate of a constant rate infusion of an alpha-2 agonist in horses., Databases Used: PubMed and Web of Science; search terms: horse, sedation and score., Conclusions: Most authors distinguish between sedation depth, sedation quality and degree of ataxia. These three features are evaluated using scoring systems similar to those classically used to assess pain, i.e. simple descriptive scales, numerical rating scales (NRS), visual analogue scales and/or multifactorial sedation scales. In addition, head height above the ground is often used as a measure of the depth of sedation. Very few authors have described how to adjust the administration rate or dose of alpha-2 agonists. Based on the available literature, the Ghent Sedation Algorithm was developed, which assigns scores (NRS) for degree of ataxia, sedation depth and surgical conditions, and uses these to prescribe changes in the administration rate of constant rate infusions of alpha-2 agonists. Studies are needed to validate this algorithm., (Copyright © 2018. Published by Elsevier Ltd.)

Dexmedetomidine (DEX) alone, or combined with butorphanol (BUT), may be administered by constant rate infusions (CRIs) in standing horses. This blinded, randomised, crossover study in six healthy adult horses aimed to determine the sedative and cardiopulmonary effects of DEX (dexmedetomidine (3.5 µg/kg+5 µg/kg/hour CRI) and DEX/BUT (dexmedetomidine (3.5 µg/kg+3.5 µg/kg/hour CRI) and butorphanol (20 µg/kg+24 µg/kg/hour CRI)). Head height above ground (HHAG), ataxia, responses to tactile/auditory stimuli and cardiopulmonary variables were recorded before, at 5/15/30/60/90 minutes and after CRIs terminated (15/30/60 minutes). Repeated measures analysis of variance with Tukey-Kramer test were used for cardiopulmonary values (mean±SD) and HHAG reduction (per cent), and Friedman's and Dunn's for non-parametric data (P<0.05). Maximum HHAG reductions of 54 per cent (DEX) and 58 per cent (DEX/BUT) occurred at 15 minutes, with ataxia for 15 minutes in both treatments. Responses to stimuli were reduced for 30 minutes in both treatments, and auditory up to 60 minutes in DEX. Cardiopulmonary effects typical of α 2 -agonists were observed, with no differences between treatments. At the doses and rates reported here, both regimens provided clinically sufficient sedation for only 30 minutes., Competing Interests: Competing interests: None declared., (© British Veterinary Association (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objective: To evaluate intravenous (IV) detomidine with methadone in horses to identify a combination which provides sedation and antinociception without adverse effects., Study Design: Randomized, placebo-controlled, blinded, crossover., Animals: A group of eight adult healthy horses aged (mean ± standard deviation) 7 ± 2 years and 372 ± 27 kg., Methods: A total of six treatments were administered IV: saline (SAL); detomidine (5 μg kg -1 ; DET); methadone (0.2 mg kg -1 ; MET) alone or combined with detomidine [2.5 (MLD), 5 (MMD) or 10 (MHD) μg kg -1 ]. Thermal, mechanical and electrical nociceptive thresholds were measured, and sedation, head height above ground (HHAG), cardiopulmonary variables and intestinal motility were evaluated at 5, 15, 30, 45, 60, 75, 90, 120 and 180 minutes. Normal data were analyzed by mixed-model analysis of variance and non-normal by Kruskal-Wallis (p < 0.05)., Results: Nociceptive thresholds in horses administered methadone with the higher doses of detomidine (MMD, MHD) were increased above baseline to a greater degree and for longer duration (MMD: 15-30 minutes, MHD: 30-60 minutes) than in horses administered low dose with methadone or detomidine alone (MLD, DET: 5-15 minutes). No increases in nociceptive thresholds were recorded in SAL or MET. Compared with baseline, HHAG was lower for 30 minutes in MMD and DET, and for 45 minutes in MHD. No significant sedation was observed in SAL, MET or MLD. Intestinal motility was reduced for 75 minutes in MHD and for 30 minutes in all other treatments., Conclusions: Methadone (0.2 mg kg -1 ) potentiated the antinociception produced by detomidine (5 μg kg -1 ), with minimal sedative effects., Clinical Relevance: Detomidine (5 μg kg -1 ) with methadone (0.2 mg kg -1 ) produced antinociception without the adverse effects of higher doses of detomidine., (Copyright © 2017 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

Objective: To review the literature with regard to the use of different intravenous agents as supplements to inhalational anaesthesia in horses. The Part 2 of this review will focus in the use of opioids and α2 -agonists., Databases Used: Pubmed and Web of Science. Search terms: horse, inhalant anaesthesia, balanced anaesthesia, partial intravenous anaesthesia, opioids, morphine, pethidine, butorphanol, methadone, fentanyl, alfentanil, remifentanil, sufentanil, xylazine, romifidine, detomidine, medetomidine and dexmedetomidine., Conclusions: Different drugs and their combinations can be administered systemically in anaesthetized horses aiming to reduce the amount of the volatile agent while improving the recovery qualities and providing a multimodal analgesic approach. However, full studies as to whether these techniques improve cardiopulmonary status are not always available and potential disadvantages should also be considered., (© 2014 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.)

Objective: To review the literature with regard to the use of different intravenous agents as supplements to inhalational anaesthesia in horses. These drugs include lidocaine, ketamine, opioids and α2 -agonists. The Part 1 of this review will focus in the use of lidocaine and ketamine., Databases Used: Pubmed & Web of Science. Search terms: horse, inhalant anaesthesia, balanced anaesthesia, partial intravenous anaesthesia, lidocaine, ketamine., Conclusions: Different drugs and their combinations can be administered systemically in anaesthetized horses, with the aim of reducing the amount of the volatile agent whilst improving the recovery qualities and providing a multimodal analgesic approach. However, full studies as to whether these techniques improve cardiopulmonary status are not always available and potential disadvantages should also be considered., (© 2014 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.)

Objective: To compare the effects of a constant rate infusion (CRI) of dexmedetomidine and morphine to those of morphine alone on the minimum end-tidal sevoflurane concentration necessary to prevent movement (MACNM ) in ponies., Study Design: Prospective, randomized, crossover, 'blinded', experimental study., Animals: Five healthy adult gelding ponies were anaesthetized twice with a 3-week washout period., Methods: After induction of anaesthesia with sevoflurane in oxygen (via nasotracheal tube), the ponies were positioned on a surgical table (T0), and anaesthesia was maintained with sevoflurane (Fe'SEVO 2.5%) in 55% oxygen. Monitoring included pulse oximetry, electrocardiography and measurement of anaesthetic gases, arterial blood pressure and body temperature. The ponies were mechanically ventilated and randomly allocated to receive IV treatment M [morphine 0.15 mg kg⁻¹ (T10-T15) followed by a CRI (0.1 mg kg⁻¹ hour⁻¹)] or treatment DM [dexmedetomidine 3.5 μg kg⁻¹ plus morphine 0.15 mg kg⁻¹ (T10-T15) followed by a CRI of dexmedetomidine 1.75 μg kg⁻¹ hour⁻¹ and morphine 0.1 mg kg⁻¹ hour⁻¹]. At T60, a stepwise MACNM determination was initiated using constant current electrical stimuli at the skin of the lateral pastern region. Triplicate MACNM estimations were obtained and then averaged in each pony. Wilcoxon signed-rank test was used to detect differences in MAC between treatments (α = 0.05)., Results: Sevoflurane-morphine MACNM values (median (range) and mean ± SD) were 2.56 (2.01-4.07) and 2.79 ± 0.73%. The addition of a continuous infusion of dexmedetomidine significantly reduced sevoflurane MACNM values to 0.89 (0.62-1.05) and 0.89 ± 0.22% (mean MACNM reduction 67 ± 11%)., Conclusion and Clinical Relevance: Co-administration of dexmedetomidine and morphine CRIs significantly reduced the MACNM of sevoflurane compared with a CRI of morphine alone at the reported doses., (© 2013 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.)

Twenty adult healthy horses undergoing elective surgery were involved in this prospective, blinded, clinical study. Horses were randomly allocated to receive a constant rate infusion (CRI) of morphine or dexmedetomidine. After induction, anaesthesia was maintained with isoflurane in oxygen/air and mechanical ventilation applied. The end-tidal isoflurane concentration (FÉISO) was initially set at 0.9% and adjusted by the anaesthetist, to maintain a light surgical plane of anaesthesia, according to an objective flow-chart. The cardiopulmonary function was only minimally different between groups and maintained within clinically normal ranges. Less ketamine was required, FÉISO was lower after 1h and fewer alterations in the anaesthetic depth were needed in horses receiving dexmedetomidine, with better recoveries. One horse receiving morphine developed post-operative colic and pulmonary oedema and two showed box-walking behaviour. This study showed that a dexmedetomidine CRI produced a more stable anaesthetic depth, reduced isoflurane requirements and better recoveries, without post-operative complications compared with a morphine CRI., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Reasons for Performing Study: No studies have been reported on the effects of enoximone in anaesthetised colic horses., Objective: To examine whether enoximone improves cardiovascular function and reduces dobutamine requirement in anaesthetised colic horses., Methods: Forty-eight mature colic horses were enrolled in this prospective, randomised clinical trial. After sedation (xylazine 0.7 mg/kg bwt) and induction (midazolam 0.06 mg/kg bwt, ketamine 2.2 mg/kg bwt), anaesthesia was maintained with isoflurane in oxygen and a lidocaine constant rate infusion (15 mg/kg bwt, 2 mg/kg/h). Horses were ventilated (PaCO2 < 8.00 kPa). If hypotension occurred, dobutamine and/or colloids were administered. Ten minutes after skin incision, horses randomly received an i.v. bolus of enoximone (0.5 mg/kg bwt) or saline. Monitoring included respiratory and arterial blood gases, heart rate (HR), arterial pressure and cardiac index (CI). Systemic vascular resistance (SVR), stroke index (SI) and oxygen delivery index (DO2I) were calculated. For each variable, changes between baseline and T10 within each treatment group and/or colic type (small intestines, large intestines or mixed) were analysed and compared between treatments in a fixed effects model. Differences between treatments until T30 were investigated using a mixed model (a = 0.05)., Results: Ten minutes after enoximone treatment, CI (P = 0.0010), HR (P = 0.0033) and DO2I (P = 0.0007) were higher and SVR lower (P = 0.0043) than at baseline. The changes in CI, HR and SVR were significantly different from those after saline treatment. During the first 30 min after enoximone treatment, DO2I (P = 0.0224) and HR (P = 0.0003) were higher than after saline administration. Because the difference in HR between treatments was much clearer in large intestine colic cases, an interaction was detected between treatment and colic type in both analyses (P = 0.0076 and 0.0038, respectively)., Conclusions: Enoximone produced significant, but short lasting, cardiovascular effects in colic horses., Potential Relevance: Enoximone's cardiovascular effects in colic horses were of shorter duration than in healthy ponies.