Pharmacokinetics of dexmedetomidine in anaesthetized horses following repeated subcutaneous administration and intravenous constant rate infusion.

BACKGROUND: The inclusion of dexmedetomidine (DEX) within a balanced general anaesthesia protocol is effective in improving the clinical outcome and recovery quality of anaesthesia in horses. This study aimed to determine the pharmacokinetic profile of DEX following repeated subcutaneous (SC) administration at 2 µg/kg every 60 min till the end of the procedure in comparison to intravenous constant rate infusion (CRI) at 1 µg/kg/h in anaesthetized horses undergoing diagnostic procedures up to the end of the diagnostic procedure. RESULTS: In the CRI and SC groups DEX maximum concentrations (Cmax) were 0.83 ± 0.27 ng/mL and 1.14 ± 0.71 ng/mL, respectively, reached at a time (Tmax) of 57.0 ± 13.4 min and 105.5 ± 29.9 min. Mean residence time to the last measurable concentration (MRTlast) was 11.7 ± 6.2 and 55.8 ± 19.7 min for the CRI group and SC groups, respectively. The apparent elimination half-life was 18.0 ± 10.0 min in the CRI group and 94.8 ± 69.8 min for the SC group, whereas the area under the curve (AUC0-last) resulted 67.7 ± 29.3 and 83.2 ± 60.5 min*ng/mL for CRI and SC group, respectively. Clearance was 16.26 ± 8.07 mL/min/kg for the CRI group. No signs of adverse effects were recorded in both groups. CONCLUSIONS: The pharmacokinetic profile of DEX following repeated SC administration in anaesthetized horses was comparable to intravenous CRI administration during the intranaesthetic period and beneficial during the recovery phase from general anaesthesia. The SC route could be considered as an alternative to CRI for improving the recovery quality of equine patients undergoing general anaesthesia.

Use of dexmedetomidine repeated subcutaneous administration for balanced anaesthesia in horses.

BACKGROUND: A balanced anaesthetic protocol is a common concept in modern veterinary anaesthesia and aims to maintain good intraoperative cardiopulmonary function. In horses, alpha-2-agonists produce sedation and analgesia and have been shown to reduce inhalational anaesthetic requirements when administered intravenously. Furthermore, these drugs can improve recovery quality. Preliminary investigations of subcutaneous dexmedetomidine administration in humans demonstrated a reduced haemodynamic impact if compared with the intravenous route suggesting that dexmedetomidine is adequately absorbed with both administration routes. The aim of the study was to compare two different dexmedetomidine (DEX) administration routes: intravenous constant rate infusion (CRI) versus repeated subcutaneous (SC) injections on cardiopulmonary function and recovery in anaesthetized horses. RESULTS: No significant differences between groups in heart rate and systolic arterial pressure were detected. A significantly higher mean and diastolic arterial pressure were detected in the SC group at T25 (p = 0.04; p = 0.02), T75 (p = 0.02; p = 0.009), and T85 (p = 0.001; p = 0.005). In SC group there was a significantly lower dobutamine infusion rate (p = 0.03) and a significantly higher urinary output (p = 0.02). Moreover, recovery quality was higher (p = 0.01). CONCLUSIONS: Cardiopulmonary effects in both groups were comparable and within clinical ranges with less dobutamine requirement in the subcutaneous group. Recovery was of better quality with fewer attempts in horses receiving subcutaneous dexmedetomidine. The present study suggests that intravenous constant rate infusion and subcutaneous repeated administration of dexmedetomidine at indicated dosage can be useful in balanced anaesthesia without any systemic or local adverse effects; moreover, in healthy horses undergoing general anaesthesia, repeated subcutaneous dexmedetomidine administration may be a suitable alternative if constant rate infusion is not feasible.

Clinical pharmacokinetics of a dexmedetomidine-methadone combination in dogs undergoing routine anaesthesia after buccal or intramuscular administration.

This study aimed to define the pharmacokinetic profiles of dexmedetomidine and methadone administered simultaneously in dogs by either an oral transmucosal route or intramuscular route and to determine the bioavailability of the oral transmucosal administration relative to the intramuscular one of both drugs, so as the applicability of this administration route in dogs. Twelve client-owned dogs, scheduled for diagnostic procedures, were treated with a combination of dexmedetomidine hydrochloride (10 µg/kg) and methadone hydrochloride (0.4 mg/kg) through an oral transmucosal route or intramuscularly. Oral transmucosal administration caused ptyalism in most subjects, and intramuscular administration caused transient peripheral vasoconstriction. The results showed reduced and delayed absorption of both dexmedetomidine and methadone when administered through an oral transmucosal route, with median (range) Cmax values of 0.82 (0.42-1.49) ng/ml and 13.22 (2.80-52.30) ng/ml, respectively. The relative bioavailability was low: 16.34% (dexmedetomidine) and 15.5% (methadone). Intramuscular administration resulted in a more efficient absorption profile, with AUC and Cmax values for both drugs approximately 10 times higher. Dexmedetomidine and methadone administered simultaneously by an oral transmucosal route using injectable formulations were not well absorbed through the oral mucosa. Nevertheless, additional studies on these drugs combination using alternative administration routes are recommended.

A pharmacokinetic model optimized by covariates for propofol target-controlled infusion in dogs.

OBJECTIVE: To develop a population pharmacokinetic model for propofol target-controlled infusion (TCI) in dogs and to evaluate its performance for use in the clinical setting. STUDY DESIGN: Prospective clinical study. ANIMALS: A group of 40 client-owned dogs undergoing general anaesthesia for magnetic resonance imaging. METHODS: Propofol was administered to 26 premedicated dogs and arterial blood samples were collected during the infusion and over 240 minutes after terminating the infusion. Propofol concentrations were measured by high-performance liquid chromatography. A population pharmacokinetic analysis was performed using a nonlinear mixed-effects modelling approach, allowing inter- and intra-individual variability estimation and quantitative evaluation of the influence of the following covariates: weight, body condition score, age, size-related age (Age_size), sex, premedication type, size and contrast agent administration. A final model was obtained using a stepwise approach in which individual covariate effects on each pharmacokinetic variable were incorporated. The performance of the developed TCI model was subsequently evaluated while inducing and maintaining anaesthesia in 14 premedicated dogs and assessed by comparing predicted and measured concentrations at specific time points. RESULTS: Propofol pharmacokinetics was best described by a three-compartment model. Weight, Age_size, premedication and sex showed significant pharmacokinetic effects. Addition of the significant covariate/variable associations to the final model resulted in a reduction of the objective function value from 285.53 to -22.34. The median values of prediction error and absolute performance error were 3.1% and 28.4%, respectively. Induction targets between 4.0 and 6.5 µg mL-1 allowed intubation within 5.0 ± 0.9 minutes. Anaesthesia was achieved with targets between 3.0 and 6.5 µg mL-1. Mean time to extubation was 9.7 ± 2.6 minutes. All dogs recovered smoothly and without complications. CONCLUSIONS AND CLINICAL RELEVANCE: Overall predictive performance of the pharmacokinetic model-driven infusion developed was clinically acceptable for administering propofol to dogs in routine anaesthesia.

A physiologically based model for tramadol pharmacokinetics in horses.

This work proposes an application of a minimal complexity physiologically based pharmacokinetic model to predict tramadol concentration vs time profiles in horses. Tramadol is an opioid analgesic also used for veterinary treatments. Researchers and medical doctors can profit from the application of mathematical models as supporting tools to optimize the pharmacological treatment of animal species. The proposed model is based on physiology but adopts the minimal compartmental architecture necessary to describe the experimental data. The model features a system of ordinary differential equations, where most of the model parameters are either assigned or individualized for a given horse, using literature data and correlations. Conversely, residual parameters, whose value is unknown, are regressed exploiting experimental data. The model proved capable of simulating pharmacokinetic profiles with accuracy. In addition, it provides further insights on un-observable tramadol data, as for instance tramadol concentration in the liver or hepatic metabolism and renal excretion extent.

Influence of Area, Age and Sex on Per- and Polyfluorinated Alkyl Substances Detected in Roe Deer Muscle and Liver from Selected Areas of Northern Italy.

Due to their physicochemical properties, per- and polyfluorinated alkyl substances (PFASs) persist and bioaccumulate in living organisms, causing adverse health effects. Since exposure to xenobiotics is influenced by factors related to both the living organism and the considered compounds, biomonitoring PFASs' presence in the environment is of crucial importance. This study aimed to detect and quantify 15 PFASs in the muscle and liver of 40 roe deer from a specific area in Northern Italy by UPLC-HRMS. In the roe deer, liver PFAS concentrations were higher than those seen in muscle (p < 0.05). Although PFAS content in animals from urbanized areas was higher than those found in deer from rural areas, this difference was not statistically significant. In female roe deer, the concentration was higher than in males (p < 0.05); moreover, older animals showed higher concentrations of PFASs in the liver than younger animals (p < 0.05). In conclusion, the amount of PFASs was higher in tissues from roe deer belonging to urbanized areas, showing that this species might serve as a good bioindicator due to its territorial behavior. PFAS content was significantly higher in female roe deer, although the reason is not fully known. Finally, PFAS concentration was higher in the liver of older animals, probably due to compromised hepatic function.

Evaluation of the Difference in the Content of Essential and Non-Essential Elements in Wild Boar and Swine Tissues Sampled in the Same Area of Northern Italy.

This study aimed to investigate the exposure of wild boars and swine from semi-extensive farms in the same area to essential and non-essential elements, measuring their concentration in liver and muscle. Furthermore, the study explored the influence of factors such as sex, age, and the sampling location on wild boars. Higher liver element concentrations were observed in both wild boars and swine. Geographical comparisons revealed minor differences. Young wild boars showed significantly higher Cu, Se, Cd, and Cr levels, while older subjects exhibited elevated Mn levels, reflecting age-related element absorption variations. No significant sex-based variations were noted. Comparing wild boars to swine, wild boars had more non-essential elements due to their foraging behavior and a larger home range. Conversely, swine exhibited a greater prevalence of essential elements, potentially resulting from dietary supplementation.

Use of Hair as Matrix for Trace Elements Biomonitoring in Cattle and Roe Deer Sharing Pastures in Northern Italy.

Intensive cattle breeding's environmental challenges are prompting shifts to extensive, pasture-based systems, influencing nutrient and pollutant uptake. PTEs are essential and non-essential elements, regularly found in the environment and organisms, and in which unbalances lead to health issues. Hair analysis, a non-invasive method, provides retrospective PTE exposure evaluation. This study aims to understand exposure and species-specific accumulation patterns of PTEs in cattle and roe deer sharing pastures in Northern Italy using the hair analysis. Aluminum, As, Cd, Cr, Ni, Pb, Cu, Mg, Fe, and Zn were quantified through the use of ICP-OES. Findings show As levels significantly higher in roe deer due to their selective feeding, while Cd and Pb levels align with other studies. Essential elements like Cu, Fe, and Zn are lower in cattle, possibly due to diet differences. Higher Cr and Ni levels in cattle suggest contamination or physiological differences in accumulation patterns. In conclusion, hair analysis is valuable for monitoring environmental PTE exposure, highlighting significant interspecies differences and the potential of both animals as bioindicators in shared grazing areas.

ENOVAT: the European Network for Optimization of Veterinary Antimicrobial Treatment.

The global antimicrobial resistance crisis has been the driver of several international strategies on antimicrobial stewardship. For their implementation at the field level, the veterinary sector encounters several specific challenges and in particular: (i) a shortage of experts in key disciplines related to antimicrobial stewardship, (ii) a lack of evidence-based antimicrobial treatment guidelines, and (iii) inferior diagnostic tests available compared to human medicine. The present white paper describes how the COST Action ENOVAT (the European Network for Optimization of Veterinary Antimicrobial Treatment, CA18217), comprising 332 persons from 51 countries, worked towards solutions to these challenges. Initially, surveys were conducted to explore the present state in Europe in terms of existing antimicrobial use guidelines and microbiology practices performed. Concurrently, various research activities were launched to optimize diagnostics, including development of epidemiological cut-offs, clinical breakpoints and matrix-assisted laser desorption ionization time of flight mass spectrometry interpretive criteria. Also, guidelines drafting groups working towards evidence-based antimicrobial treatment guidelines for six conditions in food-producing and companion animals were established. The processes and outcomes, also in terms of capacity building, are summarized in this white paper where emphasis is placed on sustainability of the activities. Although several ENOVAT initiatives and spin-off projects will continue beyond the Action, we recommend that a new European veterinary research agenda is launched focusing on research and funding leading to long-term impacts on veterinary antimicrobial use.

Antimicrobial resistance is an urgent global public health threat that is amplified by over- and misuse of antimicrobials. As a result of antimicrobial resistance, antibiotics and other antimicrobial medicines become ineffective and infections become difficult or impossible to treat. This goes for human infections, but also for infections in animals. In a recently finished European project called ENOVAT we tried to tackle the problem of antimicrobial resistance in animals. We focused on two topics. First we optimized and harmonized diagnostics of bacterial infections in the laboratory, and second we developed evidence-based treatment guidelines to support veterinary practitioners on how and when to use antibiotics in the best way. Improved diagnostics and new treatment guidelines can help veterinary practitioners to a more sensible antibiotic choice and with that less over- and misuse of antimicrobials. This article summarizes the process and progress of the work done in the ENOVAT project. Emphasis is also put on how the project benefitted from a unique consortium encompassing 332 professionals with diverse backgrounds, from 51 countries.

Gabapentin: Clinical Use and Pharmacokinetics in Dogs, Cats, and Horses.

Gabapentin is an anticonvulsant drug, which presents an established clinical efficacy in human patients for the management of refractory partial seizures, secondarily generalized tonic-clonic seizures, and for the control of chronic neuropathic pain. Gabapentin was synthesized as a structural analogue of the inhibitory neurotransmitter GABA, with GABA-mimetic effects, able to cross the blood-brain barrier. In veterinary medicine, is extra-label used in combination with other treatments to control seizures when other drugs are no longer effective or become toxic or for neuropathic pain treatment and anxiety. This review aimed to clarify gabapentin use and pharmacokinetic aspects to promote conscious use in dogs, cats, and horses. In dogs, gabapentin was beneficial in the treatment of epilepsy, as well as chronic, neuropathic, and post-operative pain, as well as anxiety. In cats, it showed efficacy in post-ovariohysterectomy-related pain and in anxiety management. In horses, gabapentin has been administered as an analgesic for chronic pain management. In conclusion, when used in combination with other drugs, gabapentin can be considered an interesting therapeutic option for the treatment of neuropathic diseases and analgesia in postoperative and chronic pain. However, despite its beneficial use in different clinical settings, further trials and pharmacokinetic studies are needed for the definition of an effective dosage regimen through proper pharmacokinetic/pharmacodynamic correlation in dogs, cats, and horses.

Farm Animal Veterinarians' Knowledge and Attitudes toward Antimicrobial Resistance and Antimicrobial Use in the Republic of Serbia.

Antimicrobial resistance (AMR) is considered one of the most prevalent global health issues in both veterinarian and human medicine. This complex problem requires a "One Health" approach with the cooperation of all healthcare sectors, as well as agriculture, finance, and consumers. We conducted a survey with the objective to assess the knowledge and attitudes of farm animal veterinarians toward AMR and antimicrobial use in the Republic of Serbia with a small focus on mastitis therapy. A total of 110 respondents completed the questionnaire, which represents a response rate of 27.3%. The majority of our respondents (n = 102, 92.7%) completely agreed that AMR currently represents severe concern in the health sector. Unfortunately, less than one-third (n = 34, 30.9%) of the respondents had only heard about antimicrobial stewardship. Participants showed a positive attitude toward prudent antimicrobial use and were open to solutions to the AMR crisis. We noticed a certain gap between farm veterinarians' desire to improve and perform better in daily practice, while at the same time feeling like they did not have enough guidance, help, and resources.

Pharmacokinetics of Bupivacaine Following Administration by an Ultrasound-Guided Transversus Abdominis Plane Block in Cats Undergoing Ovariohysterectomy.

Bupivacaine is commonly used for peripheral nerve block in veterinary medicine. This study described the pharmacokinetics of two doses of bupivacaine following administration by an ultrasound-guided transversus abdominis plane (TAP) block in cats undergoing ovariohysterectomy. Twelve healthy female adult cats were included in a randomized, prospective, blinded clinical trial. Anaesthetic protocol included acepromazine-buprenorphine-propofol-isoflurane-meloxicam. Each cat received 1 mL/kg of bupivacaine 0.2% or 0.25% (BUPI-2 and BUPI-2.5, respectively) via bilateral two-point TAP block before surgery (n = 6/group). Plasma concentrations of bupivacaine were detected using liquid chromatography-mass spectrometry. A one-compartment model and non-compartmental analysis described the pharmacokinetic parameters. Bupivacaine was detected up to 480 min (335 ± 76 in BUPI-2 and 485 ± 198 ng/mL in BUPI-2.5). For BUPI-2 and BUPI-2.5, maximum plasma concentrations were 1166 ± 511 and 1810 ± 536 ng/mL at 33 ± 14 and 47 ± 22 min, clearance was 5.3 ± 1.8 and 4.9 ± 1.5 mL/min/kg, and elimination half-life were 253 ± 55 and 217 ± 52 min, respectively. The two doses of bupivacaine via TAP block produced concentrations below toxic levels in cats. A dose of 2.5 mg/kg bupivacaine was safe to be administered using this block in healthy cats.

Population Pharmacokinetic Model of Iohexol in Dogs to Estimate Glomerular Filtration Rate and Optimize Sampling Time.

Monitoring iohexol plasma clearance is considered a useful, reliable, and sensitive tool to establish glomerular filtration rate (GFR) and early stages of kidney disease in both humans and veterinary medicine. The assessment of GFR based on iohexol plasma clearance needs repeated blood sampling over hours, which is not easily attainable in a clinical setting. The study aimed to build a population pharmacokinetic (Pop PK) model to estimate iohexol plasma clearance in a population of dogs and based on this model, to indicate the best sampling times that enable a precise clearance estimation using a low number of samples. A Pop PK model was developed based on 5 iohexol plasma samples taken from 5 to 180 minutes (min) after an intravenous iohexol nominal dose of 64.7 mg/kg from 49 client-owned dogs of different breeds, sexes, ages, body weights, and clinical conditions (healthy or presenting chronic kidney disease CKD). The design of the best sampling times could contain either 1 or 2 or 3 sampling times. These were discretized with a step of 30 min between 30 and 180 min. A two-compartment Pop PK model best fitted the data; creatinine and kidney status were the covariates included in the model to explain a part of clearance variability. When 1 sample was available, 90 or 120 min were the best sampling times to assess clearance for healthy dogs with a low creatinine value. Whereas for dogs with CKD and medium creatinine value, the best sampling time was 150 or 180 min, for CKD dogs with a high creatinine value, it was 180 min. If 2 or 3 samples were available, several sampling times were possible. The method to define the best sampling times could be used with other Pop PK models as long as it is representative of the patient population and once the model is built, the use of individualized sampling times for each patient allows to precisely estimate the GFR.

Microbial community composition and antimicrobial resistance in agricultural soils fertilized with livestock manure from conventional farming in Northern Italy.

Antimicrobials are commonly used in conventional livestock production and manure is widely applied to agricultural lands as fertilizer. This practice raises questions regarding the effects of fertilization on (i) soil microbiota composition and (ii) spread of antimicrobials and antimicrobial resistance (AMR) in the environment. This study was conducted in a high-density farming area of Northern Italy and aimed at assessing the impact of (dairy cattle, chickens and swine) manure application on soil microbiome, antimicrobial concentrations and antimicrobial resistance gene (ARG) abundance. We found the microbial community composition in manure to be different and less diverse than in soil, with manure application altering only marginally the soil microbiome. Exceptions were the phyla Firmicutes, Tenericutes and Cloacimonetes, which significantly enriched in fertilized soil. Of the antimicrobials investigated, only flumequine concentrations increased after manure application, albeit non-significantly. ARGs were more abundant in manure, with ermA, ermB, blaOXA-1 and oqxA being significantly enriched in fertilized soil. Positive correlations between oqxA and qnrS abundances and flumequine concentrations were observed, together with the co-occurrence of some ARGs and microbial taxa (e.g. oqxA correlated with Acidobacteria and Gemmatimonadetes). This study showed that manure application has little effect on soil microbiome but may contribute to the dissemination of specific ARGs into the environment. Moreover, flumequine residues seem to enhance the emergence of oqxA and qnrS in soil.

Dexmedetomidine and ketamine simultaneous administration in tigers (Panthera tigris): pharmacokinetics and clinical effects.

BACKGROUND: The study determines the pharmacokinetic profiles of dexmedetomidine (DEX), ketamine (KET) and its active metabolite, norketamine (NORKET), after simultaneous administration. Moreover, the study evaluates the sedative effects of this protocol, its influence on the main physiological variables and the occurrence of adverse effects. METHODS: Eighteen captive tigers were initially administered with a mixture of DEX (10 µg/kg) and KET (2 mg/kg) by remote intramuscular injection. In case of individual and specific needs, the protocol was modified and tigers could receive general anaesthesia, propofol or additional doses of DEX and KET. RESULTS: Based on the immobilisation protocol, nine animals were assigned to the standard protocol group and the other nine to the non-standard protocol group. Higher area under the first moment curve (AUMC0-last) and longer mean residence time (MRT0-last) (P<0.05) were observed in the non-standard protocol group for DEX, KET and NORKET, and higher area under the concentration-time curve from administration to the last measurable concentration (AUC0-last) only for KET. The KET metabolisation rate was similar (P=0.296) between groups. No differences between groups were detected in terms of stages of sedation and recoveries. All physiological variables remained within normality ranges during the whole observation period. During the hospitalisation period, no severe adverse reactions and signs of resedation were observed. CONCLUSION: The simultaneous administration of 10 µg/kg of DEX and 2 mg/kg of KET can be considered an effective protocol for chemical immobilisation of captive tigers, along with dosage adjusments or when other drugs are needed.

Oral Transmucosal or Intramuscular Administration of Dexmedetomidine-Methadone Combination in Dogs: Sedative and Physiological Effects.

The aim of this study was to compare the sedative and physiological effects following either oral transmucosal (OTM) or intramuscular administration of dexmedetomidine-methadone combination in healthy dogs. Thirty dogs were randomly assigned to receive a dexmedetomidine-methadone combination either by the OTM (n = 15) or intramuscular (n = 15) route. Sedation was scored 10, 20, and 30 min after drugs administration. Heart rate (HR), non-invasive blood pressure (NIBP), respiratory rate (fR), and body rectal temperature were recorded before drugs administration and then every 10 min for 30 min. Propofol dose required for orotracheal intubation was recorded. Sedation scores increased over time within both groups with higher values in intramuscular group (p < 0.05). Within each group, HR decreased significantly compared with baseline (p < 0.001) and was significantly lower in intramuscular group compared with the OTM group (p < 0.001). In both groups, NIBP increased significantly compared with baseline (p < 0.05). In the intramuscular group, fR was lower compared with the OTM group at all the observational time points (p < 0.001). Propofol dose was lower in the intramuscular group (p < 0.05). Compared to intramuscular dexmedetomidine-methadone, OTM combination produced lower but effective sedation in healthy dogs.

Diagnostic potential of simplified methods for measuring glomerular filtration rate to detect chronic kidney disease in dogs.

BACKGROUND: Glomerular filtration rate (GFR) is the most sensitive indicator of initial renal function decline during chronic kidney disease (CKD), but conventional protocols for measuring GFR are labor-intensive and stressful for the dog. OBJECTIVES: To assess the diagnostic potential for detecting CKD with simplified GFR protocols based on iohexol plasma clearance. ANIMALS: Seventeen CKD-positive and 23 CKD-negative dogs of different breeds and sex. METHODS: Prospective nonrandomized study. Plasma iohexol was measured 5, 15, 60, 90, and 180 minutes after injection. Glomerular filtration rate was calculated using 5 samples (GFR5 ) or simplified protocols based on 1, 2, or 3 samples. The GFR5 and simplified GFR were compared by Bland-Altmann and concordance correlation coefficient (CCC) analysis, and diagnostic accuracy for CKD by receiver operating characteristic curves. A gray zone for each protocol was bounded by the fourth quartile of the CKD-positive population (lower cutoff) and the first quartile of the CKD-negative population (upper cutoff). RESULTS: All simplified protocols gave reliable GFR measurements, comparable to reference GFR5 (CCC >0.92). Simplified protocols which included the 180-minutes sampling granted the best GFR measure (CCC: 0.98), with strong diagnostic potential for CKD (area under the receiver operating characteristic curve ± SE: 0.98 ± 0.01). A double cutoff including a zone of CKD uncertainty guaranteed reliable diagnosis outside the gray area and identified borderline dogs inside it. CONCLUSIONS: The simplified GFR protocols offer an accurate, hands-on tool for CKD diagnosis in dogs. The gray zone might help decision-making in the management of early kidney dysfunction.

Maternal and neonatal wellbeing during elective C-section induced with a combination of propofol and dexmedetomidine: How effective is the placental barrier in dogs?

Anaesthetics administered during C-section (CS) can cross the placenta and the foetal blood-brain barrier contributing to distress up to neonatal mortality. Therefore, to prevent neonatal risks, sedatives and analgesics are not commonly administered to the bitch until all pups are delivered. This study aims to evaluate the effect of a new anaesthetic and analgesic protocol for elective CS in dogs, focused on both maternal and neonatal wellbeing. General anaesthesia was induced by a combination of propofol (PPF) and dexmedetomidine (DEX) and maintained with isoflurane. DEX was added to PPF in order to provide analgesia and to reduce PPF dose. Propofol and DEX concentrations in maternal blood, amniotic fluid, and placenta were correlated to maternal and neonatal parameters. Maternal pain score was assessed with Glasgow Composite Measure Pain Scale short-form. Nine healthy purebred dogs scheduled for elective CS delivered 54 pups. The 77.8% of pups were vigorous at birth and assigned to the highest Apgar score (AS). The lowest AS was recorded in pups from mothers receiving additional doses of PPF (p < 0.001). Apgar scores improved with the increase in time between induction and pups' extraction, starting from 30 min after induction (p < 0.01). This study could contribute to clarify the controversy about the optimal extraction's time of pups after induction i.e. the best time between PPF administration and birth. No bitch showed post-operative pain or required additional analgesic doses based on their pain score. Maternal blood PPF and DEX, as well as placental PPF concentrations, decreased over time (p < 0.01). Conversely, placental DEX was fair uniformly detected in littermate pups. Both PPF and DEX were not detectable in amniotic fluid. Placenta resulted an effective barrier against foetal DEX exposure, making this protocol safe, analgesic and advisable for elective CS in dogs.

Population Pharmacokinetic Study of Cefazolin Used Prophylactically in Canine Surgery for Susceptibility Testing Breakpoint Determination.

This study aimed to determine the population pharmacokinetic (Pop PK) parameters of cefazolin administered prophylactically at 25 mg/kg intravenously (IV) 30 min before surgery in a canine population of 78 dogs and assess whether covariates, such as sex, age, body weight (BW), breed, health status, creatinine level, and surgery time, have an influence on cefazolin disposition. The ultimate goal was to compute PK/PD cut off values and subsequently establish a specific clinical breakpoint (CBP) for the development of an antimicrobial susceptibility test (AST) of cefazolin in dogs according to the VetCAST approach. Two to 11 blood samples were collected from each dog from 5 to 480 min after cefazolin administration. A two-compartment model was selected, and parameterization was in terms of serum clearance (CL), intercompartmental CL(s) (Q) and volume(s) of distribution (V). The percentage of cefazolin binding to serum protein was 36.2 ± 5.3%. Population primary parameter estimates V1, V2, CL, and Q were (typical value ± SE) 0.116 ± 0.013 L/kg, 0.177 ± 0.011 L/kg, 0.0037 ± 0.0002 L/kg/min, and 0.0103 ± 0.0013 L/kg/min, respectively. Cefazolin presented rapid distribution and elimination half-lives (mean ± SE) 4.17 ± 0.77 min and 57.93 ± 3.11 min, respectively. The overall between-subject variability (BSV) for estimated primary parameters ranged from 36 to 42%, and none of the seven explored covariates were able to reduce this variability by an amplitude clinically relevant. By Monte Carlo simulation, the probability of a PK/PD target attainment (here to achieve a free serum concentration exceeding the MIC for 50% of the dosing interval in 90% of dogs) was computed with a dosage of 25 mg/kg administered IV every 6 h for 4 administrations in 24 h. The computed PK/PD cut off value was 2 mg/L. In conclusion, cefazolin administered prophylactically in surgical dogs at 25 mg/kg IV every 6 h was deemed effective against pathogens with a MIC value ≤ 2 mg/L and from a PK/PD perspective, can be recommended in a wide range of canine patient populations with no necessary dose adjustment for special dog subpopulations.

Detection of perfluoroalkyl acids and sulphonates in Italian eel samples by HPLC-HRMS Orbitrap.

Perfluoroalkyl substances (PFASs) contain one or more carbon-bound hydrogens substituted by fluorine. Since the 1950s, these compounds have been used to manufacture fat- and water-resistant fabrics, paper and food containers, and to produce photographic films, firefighting foams, detergents and insecticides. The widespread use and global distribution of PFASs, have led to their accumulation in the environment. Food, particularly fish and other seafood, is considered the main route of human exposure to PFASs. Consequently, the European Food Safety Authority (EFSA) recommends that more data be collected, to build a database on the contamination levels of the individual PFASs in food, to evaluate a reliable chronic risk to the European consumers. This requires high-sensitivity analytical methods, to increase the number of quantifiable samples and, thereby, improve the credibility of exposure assessments. In this context, the aim of the present research is to develop and validate a sensitive and specific method based on high-performance liquid chromatography-high resolution mass spectrometry (HPLC-HRMS) analysis, to monitor the presence of 16 PFASs in Italian eels (Anguilla anguilla) from the Italian Lake Garda. The detection limits (CCα) and detection capability (CCß) in the order of pg g-1, the recoveries between 80 and 101% and the other validation parameters fulfilled the requirements of Commission Decision 657/2002/EC. The identification and quantification of PFASs, up to 11 in the same sample, showed a similar distribution among 90 eels. Perfluorooctane sulphonic acid (PFOS) and perfluorobutanoic acid (PFBA) were the analytes more frequently found in the eel samples (94 and 82%, respectively).