Pharmacokinetics of subcutaneous ketamine administration via the Omnipod® system in dogs.

Ketamine is an injectable anesthetic agent with analgesic and antidepressant effects that can prevent maladaptive pain. Ketamine is metabolized by the liver into norketamine, an active metabolite. Prior rodent studies have suggested that norketamine is thought to contribute up to 30% of ketamine's analgesic effect. Ketamine is usually administered as an intravenous (IV) bolus injection or continuous rate infusion (CRI) but can be administered subcutaneously (SC) and intramuscularly (IM). The Omnipod® is a wireless, subcutaneous insulin delivery device that adheres to the skin and delivers insulin as an SC CRI. The Omnipod® was used in dogs for postoperative administration of ketamine as a 1 mg/kg infusion bolus (IB) over 1 hour (h). Pharmacokinetics (PK) showed plasma ketamine concentrations between 42 and 326.1 ng/mL. The median peak plasma concentration was 79.5 (41.9-326.1) ng/mL with a Tmax of 60 (30-75) min. After the same infusion bolus, the corresponding norketamine PK showed plasma drug concentrations between 22.0 and 64.8 ng/mL. The median peak plasma concentration was 43.0 (26.1-71.8) ng/mL with a median Tmax of 75 min. The median peak ketamine plasma concentration exceeded 100 ng/mL in dogs for less than 1 h post infusion. The Omnipod® system successfully delivered subcutaneous ketamine to dogs in the postoperatively.

Comparison of a blind and an ultrasound-guided technique for Retrobulbar anesthesia in dogs undergoing unilateral subconjunctival enucleation.

OBJECTIVE: This study compared the quality of retrobulbar anesthesia using a blind inferior-temporal palpebral approach (ITP) with an ultrasound-guided supratemporal (ST) technique in dogs undergoing unilateral enucleation. ANIMAL STUDIED: Twenty-one client-owned dogs were undergoing enucleation. PROCEDURES: Dogs were randomly assigned to receive ITP (n = 10) or ST (n = 11) with 0.5% ropivacaine at 0.1 mL/cm of neurocranial length. The anesthetist was blinded to the technique. Intraoperative data included cardiopulmonary variables, inhalant anesthetics requirement, and requirement for rescue analgesia (intravenous fentanyl 2.5 mcg/kg). Postoperative data included pain scores, sedation scores, and need for intravenous hydromorphone (0.05 mg/kg). Treatments were compared using Wilcoxon's rank sum test or Fisher's exact test as appropriate. Comparison of variables over time were tested using a mixed effect linear model on rank. Significance was set at p = 0.05. RESULTS: Intraoperative cardiopulmonary variables and inhalant requirements were not different between groups. Dogs receiving ITP required median (interquartile range, IQR) 1.25 (0, 2.5) mcg/kg intraoperative fentanyl while those receiving ST required none (p < 0.01). Intraoperative fentanyl was required in 5/10 and 0/11 of dogs in the ITP and ST groups, respectively (p = 0.01). Postoperative analgesia requirements were not significantly different between groups; 2/10 and 1/10 dogs in the ITP and ST groups, respectively. Sedation score negatively affected pain score (p < 0.01). CONCLUSIONS: The ultrasound-guided ST technique was more effective at decreasing intraoperative opioid requirements than the blind ITP approach in dogs undergoing unilateral enucleation.

Development of an ultrasound-guided transgluteal injection of the pudendal nerve in cats: a cadaveric study.

OBJECTIVE: To develop an ultrasound-guided interfascial plane technique for injection of the pudendal nerve near its sacral origin in cats. STUDY DESIGN: Prospective, randomized, anatomical study. ANIMALS: A group of 12 feline cadavers. METHODS: Gross and ultrasound anatomy of the ischiorectal fossa, the pudendal nerve relationship with parasacral structures, and the interfascial plane were described. Computed tomography was employed to describe a cranial transgluteal approach to the pudendal nerve. Bilateral ultrasound-guided injections were performed in eight cadavers using low [(LV) 0.1 mL kg-1] or high volume [(HV) 0.2 mL kg-1] of ropivacaine-dye solution. Dissections were performed to determine successful staining of the pudendal nerve (>1 cm) and inadvertent staining of the sciatic nerve, and any rectal, urethral, or intravascular puncture. Pudendal nerve staining in groups LV and HV were compared using Fisher's exact and Wilcoxon rank-sum test as appropriate (p = 0.05). RESULTS: The pudendal nerve and its rectal perineal and sensory branches coursed through the ischiorectal fossa, dorsomedial to the ischiatic spine. The pudendal nerve was not identified ultrasonographically, but the target plane was identified between the sacral transverse process, the ischiatic spine, the pelvic fascia and the rectum, and it was filled with dye solution. Both branches of the pudendal nerve were completely stained 75% and 87.5% in groups LV and HV, respectively (p = 1.00). The dorsal aspect of the sciatic nerve was partially stained in 37% of injections in group HV. Rectal or urethral puncture and intravascular injection were not observed. CONCLUSIONS AND CLINICAL RELEVANCE: In cats, ultrasound-guided cranial transgluteal injection successfully stained the pudendal nerve in at least 75% of attempts, regardless of injectate volume. Group HV had a greater probability of sciatic nerve staining.

Feasibility and repeatability of cold and mechanical quantitative sensory testing in normal dogs.

Feasibility and inter-session repeatability of cold and mechanical quantitative sensory testing (QST) were assessed in 24 normal dogs. Cold thermal latencies were evaluated using a thermal probe (0°C) applied to three pelvic limb sites. Mechanical thresholds were measured using an electronic von Frey anesthesiometer (EVF) and a blunt-probed pressure algometer (PA) applied to the dorsal aspect of the metatarsus. All QST trials were performed with dogs in lateral recumbency. Collection of cold QST data was easy (feasible) in 19/24 (79%) dogs. However, only 18.4%, 18.9% and 13.2% of cold QST trials elicited a response at the medial tibia, third digital pad and plantar metatarsal regions, respectively. Collection of mechanical QST data was easy (feasible) in 20/24 (83%) dogs for both EVF and PA. At consecutive sampling times, approximately 2 weeks apart, the average EVF sensory thresholds were 414 ± 186 g and 379 ± 166 g, respectively, and the average PA sensory thresholds were 1089 ± 414 g and 1028 ± 331 g, respectively. There was no significant difference in inter-session or inter-limb threshold values for either mechanical QST device. The cold QST protocol in this study was achievable, but did not provide consistently quantifiable results. Both mechanical QST devices tested provided repeatable, reliable sensory threshold measurements in normal, client-owned dogs. These findings contribute to the validation of the EVF and PA as tools to obtain repeated QST data over time in dogs to assess somatosensory processing changes.

Mitochondrial-associated endoplasmic reticulum membranes (MAM) form innate immune synapses and are targeted by hepatitis C virus.

RIG-I is a cytosolic pathogen recognition receptor that engages viral RNA in infected cells to trigger innate immune defenses through its adaptor protein MAVS. MAVS resides on mitochondria and peroxisomes, but how its signaling is coordinated among these organelles has not been defined. Here we show that a major site of MAVS signaling is the mitochondrial-associated membrane (MAM), a distinct membrane compartment that links the endoplasmic reticulum to mitochondria. During RNA virus infection, RIG-I is recruited to the MAM to bind MAVS. Dynamic MAM tethering to mitochondria and peroxisomes then coordinates MAVS localization to form a signaling synapse between membranes. Importantly, the hepatitis C virus NS3/4A protease, which cleaves MAVS to support persistent infection, targets this synapse for MAVS proteolysis from the MAM, but not from mitochondria, to ablate RIG-I signaling of immune defenses. Thus, the MAM mediates an intracellular immune synapse that directs antiviral innate immunity.