Cefazolin in dog: preliminary results for pharmacokinetic and pharmacodynamic parameters

Cefazolin, a first generation cephalosporin, is commonly used in small Cefazolin, a first generation cephalosporin, is commonly used in small animal surgery to avoid post-operative infections. The aims of the study were 1) assess cefazolin pharmacokinetics (PK) in dogs undergoing gonadectomy, 2) correlate PK and pharmacodynamics (PD) parameters and 3) attest the efficacy of dosage regimen through a PK/PD approach. Thirty minutes before surgery, 25 mg/kg of cefazolin were administrated intravenously (IV) to 9 dogs (weight 22±7.5 kg; age 1.3±0.7 years). Blood samples were taken at prefixed times from 0 to 8 h. Quantification of cefazolin concentrations was performed through a validate HPLC method with UV detection (Kunicki, 2012). A two-compartmental model best described the PK profile of cefazolin. Literature MIC50 against canine Pasteurella spp., Staphylococcus spp. and Streptococcus spp. ranged from 0.25 to 0.5 μg/mL (Goldstein, 2012). Distribution and elimination half-lives were 0.3 ± 0.2 h and 3 ± 1.6 h, respectively; area under the curve was 182.3±50.6 h*μg/mL; volume of distribution and clearance at steady state were 383.5±58.1 mL/kg and 150.2±49.8 mL/h/kg, respectively. The PK/PD index for cephalosporins efficacy is time above MIC (T>MIC) for 60% of dosing interval with values 4 times higher the MIC50. Our values of T>MIC, calculated with MIC 0.5 mg/mL, was for 100 % of the observation period from 2 to 6 times higher than MIC. Preliminary results showed a good efficacy of cefazolin against all the bacterial strains evaluated. Therefore, a dosage regimen of 25 mg/kg IV every 8h might represent a valid tool in order to prevent surgical infections in small animal practice

Post vaccinal temporary sensorineural hearing loss

In our systematic research we identified four studies concerning the onset of neurological adverse events following vaccination and two excluding this association. A 33-year-old Italian man, belonging to the Italian Army was hospitalized because he suffered from vertigo, nausea and sudden right hearing loss not classified (NDD), that set in 24 h after the administration of tetanus-diphtheria and meningococcal vaccines. Some neurological events arising after vaccination are very difficult to treat. In our case, the functional recovery on low and medium frequencies was possible about 6 months after the morbid event

Evaluation of an oral transmucosal administration of dexmedetomidine-butorphanol and dexmedetomidine-methadone in dogs.

Oral transmucosal (OTM) delivery is a simple and painless method for sedative administration in veterinary medicine and allows a rapid absorption without a first-pass metabolism by the liver (Porters et al. 2014.). OTM is particularly useful in aggressive animals (Santos et al. 2010). The aim of this study is to evaluate the efficacy of the OTM route in dogs for sedative administration in comparison with intramuscular (IM) injection. 24 mix-bread dogs undergoing soft tissue surgery or diagnostic procedures were randomly divided in 4 groups (n = 6): two groups received OTM administration of dexmedetomidine (10 µg/kg-1) together with butorphanol (0.2 mg/kg-1, BTF-OTM group) or methadone (0.2mg/kg-1, MTD-OTM group); two groups received intramuscular (IM) administration of dexmedetomidine (5 µg/kg-1) together with butorphanol (0.2 m/kg-1, BTF-IM group) or methadone (0.2 mg/kg-1, MTD-IM). Heart rate (HR), respiratory rate (RR), sedation score (Gruney et al. 2009) and side effects were recorded 10 (T10), 20 (T20) and 30 (T30) minutes after premedication. Induction was performed at T30 with titrate-to-effect propofol administration and the dosage required was recorded. At each time point BTF-IM group showed a statistically lower HR compared to BTF-OTM; RR was statistically lower at T10 in MTD-OTM group (21.33 ± 8.64 pm) compared to BTF-OTM (46.16 ± 17.98); Dogs in group MTD-IM reached a higher sedation scores at each time point compared to MTD-OTM. The induction dose of propofol appears comparable among groups. Marked vasoconstriction was observed after OTM administration, as probably related to α2-agonists use. Emesis and sialorrhea occurred in two subjects of MTD-OTM group while only one dog presented sialorrhea in BTF-OTM group. In conclusion, OTM administration appears effective and easy to perform; it takes a longer time to achieve a good sedation score, probably related to a gradual absorption of drugs that also leads to a more gradual hemodynamic effects.

Clinical effects of dexmedetomidine combined with methadone after intranasal and intramuscular administration in dogs

The intranasal (IN) route shows promise for chemical restraint given the large area offered for drugs absorption. The nasal turbinates increase nasal mucosa surface, which have a greater blood flow than muscle, brain and liver tissue . Aim of the study is to compare the clinical effects and sedation scores following either IN or intramuscular (IM) administration of dexmedetomidine-methadone in dogs. Twenty mixed-breed, client-owned, healthy dogs, undergoing soft tissue surgery or diagnostic procedures, were randomly allocated in two groups (n = 10) to receive dexmedetomidine (0.01 mg kg-1) together with methadone (0.4 mg kg-1) IN (IN-group) or IM (IM-group). Temperament was evaluated before premedication (1 = calm and friendly, 4 = very excitable or nervous) (Maddern et al. 2010). Heart rate (HR), respiratory frequency (fR), body temperature, and side effects were recorded before (T0) and 10 (T10), 20 (T20) and 30 (T30) minutes after premedication. Sedation was scored 3 times (every 10 minutes) after drugs administration using a descriptive sedation scale (0 = no sedation, 13 = extremely sedated). Induction was performed at T30 with titrate-to-effect propofol and the dosage was recorded. Student T-test was performed. Weight, age, temperament, body temperature and propofol dose were not different between groups. At each time point, excluding T0, IM-group showed a statistically lower HR and fRcompared to IN-group. No undesirable effects were observed in both groups. Sedation score in IM-group was significantlyhigher compared to IN-group at each time point. In conclusion, despite statistical differences, IN administration produces a satisfactory clinical sedation with more gradual hemodynamic effects compared to IM injection; this is probably due to a direct transport of drugs from cranial nerves (I-V) to brain with limited systemic absorption. However, the high variability recorded in sedation score between subjects in IN-group (min 1/13; max 13/13 at T30) probably arises from a variable drugs conveyance from nasal mucosae to target cell in CNS by IN administration. 

Pharmacokinetics of ketamine and norketamine following intramuscular administration combined with dexmedetomidine in tigers (Panthera tigris)

In zoo practice, for physical examination or medical procedure in captive tigers, chemical immobilization is needed and ketamine (KET) in association with sedatives is an option frequently used (Clark-Price et al., 2015). Aims of the study is the assessment of the pharmacokinetics of KET and its main metabolite, norketamine (NORKET), after its intramuscular administration in combination with dexmedetomidine in tigers.Nineteen adult captive tigers, from different zoos, were scheduled for periodic physical examination or diagnostic procedures at the Milan University facilities. All animals were administered with a combination of KET at 2 mg/kg and dexmedetomidine at 10 µg/kg, given intramuscularly through blowpipe darts. If necessary, tigers where re-administered with variable doses of KET and dexmedetomidine or other drugs. When animals were sufficiently sedated, blood samples were collected every 5-10 min for the time tigers were safely approachable. Nine animals were assigned to standard protocol group (KET 2 mg/kg and dexmedetomidine 10 µg/kg) and ten animals to non-standard protocol group (tigers administered with different doses of KET, 2 – 2.5 mg/kg, and dexmedetomidine 10 – 30 µg/kg or with any other necessary drug, such as titrate-to-effect propofol and isoflurane, respectively for anaesthesia induction and maintenance). Ketamine and NORKET were extracted from plasma according to a validated HPLC-UV method (Zonca et al., 2012). For pharmacokinetic assessment, KET and NORKET concentrations were analysed with a noncompartmental approach (Phoenix® 7.0, Pharsight). Differences in the pharmacokinetic parameters between groups were statistically analysed (SPSS 25.0, SPSS Inc.).This is the first study that evaluates the pharmacokinetics of KET and NORKET in tigers. Due to the harmful attitude of these animals, samples collection was limited to the period of sedation, a short time for a complete pharmacokinetic evaluation. Nevertheless, we observed a favorable kinetic profile of KET and NORKET and, from a clinical point of view, all animals showed a good recovery, no adverse effects and a good level of sedation.     Standard Protocol              (mean ± s.d.)Non-Standard protocol             (mean ± s.d.)     KetamineHL_Lambda_zmin77.62 ± 54.5076.14 ± 67.32 Tmaxmin27.78 ± 7.9049.70 ± 29.64 Cmaxug/mL0.63 ± 0.170.67 ± 0.19 AUClastmin*ug/mL23.84 ±6.40*35.97 ± 12.84* AUMClastmin*min*ug/mL802.24 ± 331.03*2054.97 ± 1018.88* MRTlastmin32.88 ± 5.71*54.38 ± 19.71*     NorketamineTmaxmin51.89 ± 8.95*77.10 ± 24.41* Cmaxug/mL0.24 ± 0.070.23 ± 0.09 AUClastmin*ug/mL7.30 ± 3.9811.07 ± 5.46 AUMClastmin*min*ug/mL291.94 ± 227.01*701.87 ± 424.80* MRTlastmin36.95 ± 7.32*58.65 ± 19.58*HL_Lambda_z = Elimination Half-Life; Tmax = Time to Maximum concentration; Cmax = Maximum Concentration; AUClast = Area Under the Curve to the last concentration; AUMClast = Area under the first Moment Curve to the last concentration ;MRTlast = Mean Residence Time to the last concentration  Tab.1: Pharmacokinetic parameters of ketamine and norketamine in nineteen adult captive tigers after intramuscular administration of 2 mg/kg of ketamine, with or without variation from the standard protocol, in combination with dexmedetomidine (with * are indicated results with p < 0.05)

Peribulbar block in equine isolated heads. Development of a single needle technique and tomographic evaluation

Peribulbar block (PPB) has been used in humans as a safer alternative to retrobulbar block (RBB). PBB, depends on the diffusion of anaesthetic solution into the muscle across the connective tissue and it is performed introducing the needle within the extraconal space. The advantages are fewer complications and palpebral akinesia. In Veterinary Medicine few studies describe this technique in dogs (Ahn J 2013) and cats (Shilo-Benjamini et al. 2013). Based on literature the aim of the study is to determinate, in equine specimens, feasibility of inferior PBB with single needle injection, by using contrast medium (CM), and to evaluate thought Computed Tomography (CT) the distribution around the optic nerve (degrees). PBB was performed in 6 orbits. The mixture injected consisted of 20 ml of physiological solution and iodinated CM at 25%. Each periorbital area underwent three CT scans. A basal acquisition to assess the needle position before the injection, a second and third scan were performed immediately after injection, and after application of pressure on the periorbital surface area to promote CM diffusion. The needle position was measured from the tip to the optic nerve with a mean distance of 2,27 mm ± 0,28. The mean volume distribution before pressure application was 23,56 cm3 ± 2,58 and after pressure application was 27,56 cm3 ± 4,8.  The CM distribution, was defined (Nouvellon et al. 2010) “successful” in 4 orbits (>270°) and “inadequate” in 2 orbits (<180°). The present study demonstrates feasibility of inferior PBB by single injection in horses for its simple and practical execution. Inferior PPB is a potential alternative to systemic administration of neuromuscular blocking agents for ophthalmic surgery. However, this approach needs to be evaluate in clinical trials to assess its feasibility and effectiveness in clinical practice for standing procedures

Helical Hydro-Computed Tomography in the diagnosis of pyloric stenosis in two foals

Pyloric stenosis is rarely reported in horses (Bart et al 1980; Bezdecova et al. 2009). Congenital and acquired conditions have been described (Church et al 1986; Heidmann et al 2004; Laing et al. 1992; McGill et al. 1984) clinical suspicion is based on clinical findings while definitive diagnosis is reached by exploratory laparotomy and gastroscopy. The use of other diagnostic techniques has never been described. Two foals were admitted for recurrent abdominal pain. Clinical and ultrasonographic (US) examinations were performed.  Foals underwent Computed Tomography (CT) of the abdomen, both native and Helical Hydro-CT. US revealed mild stomach distension, mild small bowel wall thickening; small intestine obstruction was suspected in both foals. Case 1, two-month old Thoroughbred filly 130 kg of weight: CT showed segmental concentric pylorus stenosis, at the pyloric duodenal junction level. Mild liquid distension of the pyloric antrum and mixed gas and fluid distension of the cranial duodenum. During necroscopy the pyloric antrum showed stenosis due to an inelastic constricting ring reducing the lumen of the pyloric canal. The glandular part presented mild acute catarrhal gastritis. Case 2, three-month old Italian Saddle colt 142 kg of weigh: CT showed small amount of intraluminal hyperattenuanting material within the gastric fundus and duodenum. Hydro-CT highlighted the presence of mild pylorus narrowing, mild distension and moderate mucosal irregularities of the pyloric antrum. An acquired pyloric stenosis secondary to chronic gastritis of unknown origin was suspected. Explorative laparotomy was performed; the antrum was mildly distended and the pylorus appeared narrowed and hard on palpation; gastrojejunostomy was performed. Ante-mortem diagnosis of pyloric stenosis in horses is challenging because aspecific clinical signs. Native CT allowed to investigate both the stomach and the small intestine and, in one case, outlined the presence of pylorus stenosis. In case 2, only Helical Hydro-CT allowed better evaluation of the pyloric thickness. CT and Helical Hydro-CT can be considered a useful diagnostic tool in foal with clinical suspicion of pyloric stenosis.

Contamination of Italian parks with canine helminth eggs and health risk perception of the public

Abstract The contamination of public areas by dog faeces is a social behaviour and public health problem. In fact, the most frequently isolated intestinal helminths in dogs are distributed worldwide, and most of them have zoonotic potential (i.e., ascarids and ancylostomatids). The aims of this survey were to evaluate citizen awareness of health risks for animals and humans related to canine faecal pollution and to estimate the presence and prevalence of intestinal helminths in dog faeces collected in green public areas in three municipalities of Italy (Padua, Rome and Teramo). The awareness of citizens about the health risks related to faecal pollution was evaluated using questionnaires submitted to 313 dog owners and 159 non-dog owners in Padua (n = 341) and Rome (n = 131). Most dog owners (85.4%) declared they picked up their dog's faeces every time, and these data were confirmed by operators secretly observing dog owners. Moreover, 84.3% participants were aware of the existence of a municipal regulation concerning the correct management of animals in public areas with no significant differences between dog owners and non-dog owners, whereas Rome citizens were significantly more aware than Padua citizens. Nonetheless, only 10.9% (51/469) of responders knew the health risks related to canine faecal pollution, with no significant differences between dog and non-dog owners. A total of 677 dog stool samples were collected and copromicroscopically analysed. Forty-eight (7.1%) samples were positive for at least one parasite species, with significantly lower prevalence values in Padua (2.2%) than in Rome (11.9%) and Teramo (8.6%). The highest prevalence was detected for Trichuris vulpis (4.4%), followed by Toxocara canis (1.9%); T. vulpis presented significantly lower prevalence in Padua than in the other cities. Other helminths were found with values under 0.5% in the investigated cities. This survey shows that most citizens are unaware of the health risk related to abandoned canine faeces on public soils. Nevertheless, laboratory results suggest a limited risk for dog and human health, but the zoonotic risk due to the high vitality of infective helminths eggs in the soil should always be considered

Ultrasound-guided epidural catheter placement with a new technique: preliminary cadaveric study.

Several methods are described in veterinary medicine to perform and assess correct epidural needle placement to provide effective epidural analgesia (Adami et al 2017). The aim of this study is to evaluate the feasibility of an ultrasound longitudinal sagittal approach to epidural catheter placement using a biopsy needle guide. Seven dog cadavers were used in the study. With the cadaver in sternal recumbence, a 5-8 MHz microconvex transducer provided with a 16-gauge biopsy guide was positioned to obtain a longitudinal sagittal scan of the spinal process of L7 and the sacral crest; the epidural space was identified between two parallel hyperechoic lines and, as the trajectory of the biopsy guide crossed them, a 17G Tuohy needle was used to insert a 19G epidural catheter. Correct catheter placement was visualised through a resection of the column between L2 and L3. Firstly, an expert echographist (operator C1) visualised the ultrasonographic landmarks, while catheter placement was performed by an expert anaesthetist (operator A), a student (operator B) and another expert echographist (operator C2) (double-operator technique); secondly, operator A and C2 performed alone the whole procedure (single-operator technique); lastly all operators performed a blind procedure (Jones 2001). Operator A failed 2/7 single-operator procedures; time to perform the blind technique was statistically lower than the double-operator technique (75 ± 132.4 vs 91.6 ± 79.3 seconds). Operator C2 failed 3/7 blind procedures, scoring the higher total time of performance (329.3 ± 271.2 seconds), but was able to perform both the double- and single-operator technique without significant difference with operator A, despite a faster time in positioning the probe. Operator B showed a higher repositioning attempts of the needle with the double-operator procedure compared to the blind one. Ultrasound guidance appears to be a promising technique to ease catheter placement also by operators inexperienced of locoregional techniques