Proximal mandibular nerve block using electrolocation in 10 dogs undergoing mandibular surgery: a case series report.

Peripheral nerve block performed using electrical stimulation (i.e. electrolocation) is widely used for perioperative pain management during several surgical procedures in dogs (Campoy 2008), but few data are reported concerning its application to invasive maxillofacial surgery (Carotenuto et al 2011). The aim of this case series report is to evaluate the efficacy of proximal mandibular nerve block (PMNB) in perioperative pain management in dogs undergoing mandibulectomy. Ten dogs of various breeds, (six spayed females and four neutered males of 10.353.09 years and mean weight of 19.5615.19 kg) presenting either neoplasia or mandibular fracture and scheduled for mandibulectomy were premedicated with intramuscular acepromazine maleate (0.02 mg/kg); after induction of general anaesthesia, bilateral PMNB was performed with ropivacaine 0.75% (2 mg/kg) inserting the stimulated needle in temporomandibular joint direction. Whenever intraoperative nociception occurred, intravenous rescue analgesia was provided (fentanyl 3 g/kg). Carprofen was administered subcutaneously as a sole postoperative treatment (3 mg/kg) and postoperative analgesia was assessed for at least 24 hours by a blind operator, accordingly to the Glasgow composite pain scale (Reid et al 2007); when it overcame a threshold of 5/24, intravenous rescue analgesia was administered (methadone, 0.2 mg/kg). In eight out of ten dogs no intraoperative nociception was shown, while in two dogs a single intravenous fentanyl administration was sufficient to provide additional analgesia. No acute and medium term complications were observed and postoperative analgesia lasted for 20.5±6.1 hours. PMNB seems to provide effective perioperative long-lasting analgesia leading to a reduction in intra- and postoperative drug administration

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. 

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.

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)

Physiological response to chemical immobilization: a case study of etorphine-azaperone in free-ranging plains zebra (Equus quagga) in Kenya

Predictable immobilization of wild zebras is challenging and there is massive variation in opiate response within different species.Etorphine combined with azaperone is considered the protocol of choice, but no studies have investigated the physiological response to this procedure of immobilization in plains zebras. Eleven free-ranging plains zebras (Equus quagga) were immobilized in Kenya using a combination of etorphine 0.019 ± 0.003 mg/kg and azaperone 0.27 ± 0.05 mg/kg administered intramuscularly with a projectile dart. After recumbency, an arterial sample was performed for blood gas analysis and physiological parameters were recorded every five minutes.Descriptive scores were given to the exertion resulting from high-speed chasing and to the quality of induction, immobilization and recovery. Diprenorphine or naltrexone were used for opioid antagonism. In all zebras, the combination induced quick inductions within 3.5 ± 0.8 minutes and provided reliable recumbencies without attempts to stand for the entire duration of the immobilization.The average heart rates, respiratory rates and mean arterial blood pressure recorded were 102 ± 42 beats/minute, 18 ± 4 breaths/minute and 145 ± 28 mmHg respectively. Arterial gas analyses demonstrated mild to severe and partially compensated metabolic acidosis and hypoxia, while electrolytes were within equids range. In particular, higher exertion levels during the chasing were significantly correlated to worse immobilization scores (p=0.008) and hyperthermia occurrence (p=0.0012) and non-significantly to more severe acidosis. Recoveries from anaesthesia were smooth, on average 121 ± 38 seconds after diprenorphine/naltrexone administration.           Etorphine-azaperone combination produced physiological alterations in free-ranging plains zebra such as tachycardia, hypertension, metabolic acidosis and hypoxemia. However, these preliminary results indicate that high-speed chase might be responsible for the physiological imbalance and that this drug combination does not suppress the compensatory response. Regardless of the metabolic status, recover from immobilization was uneventful and all zebras went back to normal behavior thereafter

A case of adrenal tumour in a lion (Panthera leo): tomographic and ultrasonographic findings.

Adrenal gland tumors are common in humans and in several animal species. Studies concerning this neoplasia in human medicine indicate that clinical signs have a high variability. Adrenal adenomas can be occasionally observed in asymptomatic patients during tomographic studies while estrogen-secreting tumors, known as "feminizing adrenal tumors" (FATs), have been rarely reported. The aim of this study is to describe for the first time the Imaging findings of a captivity lion affected by a neoplastic secreting adrenal tumour. An 8 year-old male lion with progressive lack of secondary sex characteristics, disorexia and weight loss was referred to our Institution. The patient was chemically immobilized to undergo general clinical evaluation, hematologic, serum biochemical and hormonal profile, FIV and FeLV tests. Three months later a total body computed tomography and abdominal ultrasonography were performed. Liver and left adrenal lesions FNABs were performed. Imaging findings showed the presence of an extended expansive neoplastic lesion on the left adrenal gland (40x39x37 mm) with right adrenal gland atrophy. Generalized hepatopathy associated with a suspected intrahepatic cholestasis was confirmed by ultrasonography. Cytological evaluation ruled out the presence of neuroendocrine cells without malignancy evidences compatible with the adenomatous nature of the lesion, associated with moderate degenerative hepatopathy. Blood tests reported an estradiol concentration of 462 ng/dl. To our knowledge, this is the first description of adrenal mass in a lion associated with secondary feminization, inappetence and high values of hematic estradiol, referable to a feminizing adrenal tumor (FAT).

Clinical pharmacokinetics of tramadol and main metabolites in horses undergoing orchiectomy.

Tramadol is a synthetic codeine analogue used as an analgesic in human and veterinary medicine. It is not approved for use in horses, but could represent a valid tool for pain treatment in this species.The serum pharmacokinetic profile and urinary excretion of tramadol and its metabolites (O-desmethyltramadol [M1], N-desmethyltramadol [M2] and N,O-desmethyltramadol [M5]) was investigated in a multidrug anaesthetic and analgesic approach for orchiectomy in horses. The evaluation of the degree of cardiovascular stability, the intraoperative effect and postoperative analgesia obtained by the visual analogue scale are also reported. Animal and methods: Tramadol (4 mg/kg BW) was administered intravenously to eight male yearlings as a bolus over 60 seconds, 5 min after intubation and 15 min prior to surgery. Drug quantification was performed in serum and urine for tramadol, M1, M2 and M5 by high-performance liquid chromatography with fluorimetric detection.Mean tramadol concentration was 14.87 ± 11.14 μg/mL at 0.08 h, and 0.05 ± 0.06 μg/mL at 10 h. Serum concentrations of M1 and M2 metabolites were quite limited. For M1 and M2, median maximum concentration (Cmax) and time to achieve maximum concentration (Tmax) were 0.05 μg/mL and 0.75 h, and 0.08 μg/mL and 2 h, respectively; M5 was never detected. In urine, tramadol was the most recovered compound, followed by M1, M2 and M5.Showing no adverse events and based on the kinetic behaviour, pre-operative tramadol IV at a dose of 4 mg/kg BW might be useful and safe as analgesic in horses undergoing surgery

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

Pharmacokinetics of dexmedetomidine combined with methadone following oral-transmucosal and intramuscular administration in dogs

Oral-transmucosal (OTM) drug delivery refers to noninvasive and painless administration of medical preparations through any oral cavity membrane to achieve systemic effects (Sattar et al., 2014). Regarding sedative drugs, OTM administration is very attractive in veterinary medicine, especially for patients difficult to inject and restrain (Messenger et al., 2016). This study aims to compare the pharmacokinetics of dexmedetomidine after OTM and intramuscular (IM) administration combined with methadone. After obtaining Ethical Committee approval and owner’s written consent, eight dogs, were administered with dexmedetomidine (10 mg/kg) and methadone (0.4 mg/kg) by OTM and other 4 dogs by IM route. Blood samples were collected at prefixed times up to four hours. Dexmedetomidine was quantified by a validated HPLC-MS method. On dexmedetomidine concentrations, a pharmacokinetic analysis was carried out with a noncompartmental approach (Phoenix WinNonlin® 7.0, Pharsight, Cary, NC). Mean ± SD terminal half-lives of dexmedetomidine were 187.42 ± 109.66 and 94.78 ± 34.08 min after OTM and IM administration, respectively. Maximum serum (Cmax) concentrations were 0.83 ± 0.32 and 9.09 ± 2.46 ng/mL for OTM and IM administration, respectively. Time to maximum concentration (Tmax) were 44.38 ± 32.16 and 21.25±11.39 min by OTM and IM administration, respectively. Area under the curve from 0 to the last measured concentration (AUClast) were 103.75 ± 30.23 and 614.87 ± 77.15 min*ng/mL for OTM and IM administration, respectively. Cmax, Tmax and AUClast values by OTM route demonstrate a lower and delayed absorption of the drug compared to IM. To complete the study, the pharmacokinetic analysis of methadone is foreseen, so as a clinical trial to compare the clinical effects of the combination of dexmedetomidine and methadone by OTM and IM administration and to establish an effective dosage of oral-transumucosal route in dogs for this association

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