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Open Access Publications from the University of California

Scholarly Works (11 results)

  • Article
  • Peer Reviewed
UC Davis Previously Published Works (2021)
This study characterized the pharmacokinetics of butorphanol in cats anesthetized with isoflurane. Six young healthy male neutered cats were used. Cats were anesthetized with isoflurane in oxygen. Catheters were placed in a jugular vein for blood sampling and in a medial saphenous vein for butorphanol and lactated Ringer's solution administration. Butorphanol tartrate (1 mg/kg over 5 min) was administered intravenously. Blood samples were collected prior to butorphanol administration and at various times up to 365 min following administration. Plasma butorphanol concentration was measured using liquid chromatography/tandem mass spectrometry. Compartment models were fitted to the time-concentration data using nonlinear mixed effect modeling. A three-compartment model best fitted the data. Typical value (% interindividual variability) for the three volumes of distribution, the metabolic clearance, and the two distribution clearances were 230 (72), 1095 (not estimated), and 2596 (not estimated) ml/kg, and 18.4 (72), 169.6 (52), and 55.0 (43), respectively. Pharmacokinetic simulation suggested that a loading dose (µg/kg) calculated as 0.287 × target plasma concentration in ng/ml (CT ) followed by intravenous infusions (µg/kg/min) of 0.098 × CT for 20 min, 0.049 × CT for 40 min, and 0.022 × CT thereafter would rapidly achieve and maintain CT  ± 10% for up to 6.5 h.
    Cover page: Pharmacokinetics of butorphanol in male neutered cats anesthetized with isoflurane
    • Article
    • Peer Reviewed
    UC Davis Previously Published Works (2015)

    Objectives

    To describe the allometric scaling principles underlying appropriate indexing of cardiovascular and respiratory measurements obtained in adult mammals, and to propose guidelines for indexing experimental cardiovascular and respiratory data.

    Database used

    PubMed, using the terms 'allometry', 'allometric', 'indexing', 'cardiovascular' and 'respiratory'.

    Conclusions

    Indexing of cardiopulmonary variables is commonly used in attempts to account for the effects of body size on measurements and to standardize them. Some cardiopulmonary variables have been indexed using various functions of body mass in a process that often ignores the underlying relationship between the variable of interest and body size, as described in the allometry literature. This can result in a failure to ideally reduce the effect of body size on measurements in a manner that highlights differences. We review how commonly measured cardiopulmonary variables are related to body mass in mammalian species according to the allometry literature, and offer suggestions on how this information can be used to appropriately index cardiopulmonary variables in a simple and informative manner.
      Cover page: Indexing cardiovascular and respiratory variables: allometric scaling principles
      • Article
      • Peer Reviewed
      UC Davis Previously Published Works (2014)
      This study reports the pharmacokinetics of hydromorphone after intravenous and intramuscular administration to rhesus macaques (Macaca mulatta). Hydromorphone (0.075 mg/kg) was administered intravenously as a bolus or intramuscularly on separate occasions to healthy, socially housed, socially reared, adult, intact male rhesus macaques (n = 4). Blood samples were collected prior to and until 10 h after administration. Serum hydromorphone concentrations were analyzed with liquid chromatography-mass spectrometry. Compartment models were fit to time-concentration data. A 3-compartment model with input in and elimination from the central compartment best fit intravenous data, whereas a 1-comparment model best fit intramuscular data. After intravenous administration, the median clearance and terminal half-life were 37.7 (range, 33.7 to 47.1) mL/kg/min and 142 (range, 131 to 218) min, respectively. The median (range) elimination half-life after intramuscular administration was 81.5 (77.2 to 92.5) min. Median intramuscular bioavailability was 92% (range, 75% to 104%). Rhesus macaques maintained concentrations greater than or equal to 4.0 ng/mL for at least 2 h after intravenous and intramuscular administration. The disposition of hydromorphone was characterized by a large volume of distribution and moderate clearance. Intramuscular administration resulted in rapid and almost complete drug absorption. Whole-body pruritus, sedation, and decreased appetite were observed in all macaques after initial drug administration.
        Cover page: Pharmacokinetics of hydromorphone after intravenous and intramuscular administration in male rhesus macaques (Macaca mulatta).
        • Article
        • Peer Reviewed
        UC Davis Previously Published Works (2020)
        Different structurally related phenylpiperidine opioids exhibit different isoflurane-sparing effects in cats. Because minimum alveolar concentration (MAC) in cats is affected only by very high plasma concentrations of some phenylpiperidine opioids, we hypothesized these effects are caused by actions on nonopioid receptors. Using a prospective, randomized, crossover design, six cats were anesthetized with isoflurane, intubated, ventilated, and instrumented. Isoflurane MAC was measured in triplicate using a tail-clamp and bracketing technique. A computer-controlled intravenous infusion using prior pharmacokinetic models targeted plasma concentrations of 60 ng/ml fentanyl, 10 ng/ml sufentanil, or 500 ng/ml alfentanil, and isoflurane MAC was measured in duplicate. Next, naltrexone 0.6 mg/kg was administered to cats hourly during the opioid infusion, and isoflurane MAC was measured in duplicate. Blood was collected during MAC determinations to measure opioid concentrations. Responses were analyzed using repeated measures ANOVA with significance at p < .05. Alfentanil and sufentanil decreased isoflurane MAC by 16.4% and 6.4%, respectively, and these effects were completely reversed by naltrexone. Fentanyl had no significant effect on isoflurane MAC. Alfentanil and sufentanil modestly reduce isoflurane MAC via agonist effects on opioid receptors. However, these effects are too small to justify clinical use of phenylpiperidine opioids as single agents to reduce MAC in cats.
          Cover page: Phenylpiperidine opioid effects on isoflurane minimum alveolar concentration in cats.
          • Article
          • Peer Reviewed
          UC Davis Previously Published Works (2023)
          OBJECTIVE: To screen modulators of biogenic amine (BA) neurotransmission for the ability to cause fentanyl to decrease isoflurane minimum alveolar concentration (MAC) in cats, and to test whether fentanyl plus a combination of modulators decreases isoflurane MAC more than fentanyl alone. STUDY DESIGN: Prospective, experimental study. ANIMALS: A total of six adult male Domestic Short Hair cats. METHODS: Each cat was anesthetized in three phases with a 1 week washout between studies. In phase 1, anesthesia was induced and maintained with isoflurane, and MAC was measured in duplicate using a tail clamp stimulus and standard bracketing technique. A 21 ng mL-1 fentanyl target-controlled infusion was then administered and MAC measured again. In phase 2, a single cat was administered a single BA modulator (buspirone, haloperidol, dexmedetomidine, pregabalin, ramelteon or trazodone) in a pilot drug screen, and isoflurane MAC was measured before and after fentanyl administration. In phase 3, isoflurane MAC was measured before and after fentanyl administration in cats co-administered trazodone and dexmedetomidine, the two BA modulator drugs associated with fentanyl MAC-sparing in the screen. Isoflurane MAC-sparing by fentanyl alone, trazodone-dexmedetomidine and trazodone-dexmedetomidine-fentanyl was evaluated using paired t tests with p < 0.05 denoting significant effects. RESULTS: The MAC of isoflurane was 1.87% ± 0.09 and was not significantly affected by fentanyl administration (p = 0.09). In the BA screen, cats administered trazodone or dexmedetomidine exhibited 26% and 22% fentanyl MAC-sparing, respectively. Trazodone-dexmedetomidine co-administration decreased isoflurane MAC to 1.50% ± 0.14 (p < 0.001), and the addition of fentanyl further decreased MAC to 0.95% ± 0.16 (p < 0.001). CONCLUSIONS AND CLINICAL RELEVANCE: Fentanyl alone does not affect isoflurane MAC in cats, but co-administration of trazodone and dexmedetomidine causes fentanyl to significantly decrease isoflurane requirement.
            Cover page: Effects of Trazodone and Dexmedetomidine on Fentanyl-Mediated Reduction of Isoflurane Minimum Alveolar Concentration in CatsCreative Commons 'BY' version 4.0 license
            • Article
            • Peer Reviewed
            UC Davis Previously Published Works (2019)
            Two healthy research cats involved in a randomized, blinded prospective pharmacodynamics study evaluating midazolam continuous-rate infusion as a means to decrease sevoflurane concentrations experienced unexpectedly prolonged recoveries. Midazolam loading doses, infusion rates, and the targeted plasma midazolam concentrations at steady-state were determined by pharmacokinetic modeling based on the results of a preliminary pharmacokinetic study using a single dose of midazolam. In the pharmacodynamics study, cats remained oversedated after recovery from anesthesia, and plasma concentrations of midazolam and its primary metabolite (1-hydroxymidazolam) remained elevated. The use of flumazenil was unsuccessful in timely treatment of oversedation. Administration of intravenous lipid emulsion was used in one of the cats to facilitate recovery and appeared to be effective in both reducing the depth of midazolam-induced oversedation and significantly reducing the plasma concentration of 1-hydroxymidazolam. The effects after the administration of both treatment modalities on clinical signs and plasma drug concentrations in cats are discussed. The observations suggest that cats may eliminate 1-hydroxymidazolam more slowly than expected; consequently dose adjustments may be required when continuous infusion of midazolam is intended. In addition, intravenous lipid emulsion may facilitate recovery from midazolam oversedation, particularly in cases unresponsive to traditional treatment modalities. However, further investigations are warranted to delineate the efficacy of this modality in the treatment of midazolam oversedation.
              Cover page: Prolonged Anesthetic Recovery after Continuous Infusion of Midazolam in 2 Domestic Cats (Felis catus).
              • Article
              • Peer Reviewed
              UC Davis Previously Published Works (2012)

              To determine cardiopulmonary effects of incremental doses of dopamine and phenylephrine during isoflurane-induced hypotension in cats with hypertrophic cardiomyopathy (HCM).

              6 adult cats with severe naturally occurring HCM.

              Each cat was anesthetized twice (once for dopamine treatment and once for phenylephrine treatment; treatment order was randomized). Hypotension was induced by increasing isoflurane concentration. Cardiopulmonary data, including measurement of plasma concentration of cardiac troponin I (cTnI), were obtained before anesthesia, 20 minutes after onset of hypotension, and 20 minutes after each incremental infusion of dopamine (2.5, 5, and 10 μg/kg/min) or phenylephrine (0.25, 0.5, and 1 μg/kg/min).

              Mean ± SD end-tidal isoflurane concentration for dopamine and phenylephrine was 2.44 ± 0.05% and 2.48 ± 0.04%, respectively. Cardiac index and tissue oxygen delivery were significantly increased after administration of dopamine, compared with results after administration of phenylephrine. Systemic vascular resistance index was significantly increased after administration of phenylephrine, compared with results after administration of dopamine. Oxygen consumption remained unchanged for both treatments. Systemic and pulmonary arterial blood pressures were increased after administration of both dopamine and phenylephrine. Acid-base status and blood lactate concentration did not change and were not different between treatments. The cTnI concentration increased during anesthesia and infusion of dopamine and phenylephrine but did not differ significantly between treatments.

              Dopamine and phenylephrine induced dose-dependent increases in systemic and pulmonary blood pressure, but only dopamine resulted in increased cardiac output. Hypotension and infusions of dopamine and phenylephrine caused significant increases in cTnI concentrations.

                Cover page: Cardiovascular and respiratory effects of incremental doses of dopamine and phenylephrine in the management of isoflurane-induced hypotension in cats with hypertrophic cardiomyopathy.
                • Article
                • Peer Reviewed
                UC Davis Previously Published Works (2017)

                Objective

                To determine plasma bupivacaine concentrations after retrobulbar or peribulbar injection of bupivacaine in cats.

                Study design

                Randomized, crossover, experimental trial with a 2 week washout period.

                Animals

                Six adult healthy cats, aged 1-2 years, weighing 4.6 ± 0.7 kg.

                Methods

                Cats were sedated by intramuscular injection of dexmedetomidine (36-56 μg kg-1) and were administered a retrobulbar injection of bupivacaine (0.75 mL, 0.5%; 3.75 mg) and iopamidol (0.25 mL), or a peribulbar injection of bupivacaine (1.5 mL, 0.5%; 7.5 mg), iopamidol (0.5 mL) and 0.9% saline (1 mL) via a dorsomedial approach. Blood (2 mL) was collected before and at 5, 10, 15, 22, 30, 45, 60, 120, 240 and 480 minutes after bupivacaine injection. Atipamezole was administered approximately 30 minutes after bupivacaine injection. Plasma bupivacaine and 3-hydroxybupivacaine concentrations were determined using liquid chromatography-mass spectrometry. Bupivacaine maximum plasma concentration (Cmax) and time to Cmax (Tmax) were determined from the data.

                Results

                The bupivacaine median (range) Cmax and Tmax were 1.4 (0.9-2.5) μg mL-1 and 17 (4-60) minutes, and 1.7 (1.0-2.4) μg mL-1, and 28 (8-49) minutes, for retrobulbar and peribulbar injections, respectively. In both treatments the 3-hydroxybupivacaine peak concentration was 0.05-0.21 μg mL-1.

                Conclusions and clinical relevance

                In healthy cats, at doses up to 2 mg kg-1, bupivacaine peak plasma concentrations were approximately half that reported to cause arrhythmias or convulsive electroencephalogram (EEG) activity in cats, and about one-sixth of that required to produce hypotension.
                  Cover page: Plasma bupivacaine concentrations following orbital injections in cats
                  • Article
                  • Peer Reviewed
                  UC Davis Previously Published Works (2024)
                    Cover page: Ultrasound-guided trigeminal nerve approach at the level of the pterygopalatine fossa in cat cadavers.
                    • Article
                    • Peer Reviewed
                    UC Davis Previously Published Works (2014)

                    Objective

                    To compare effectiveness and complications associated with peribulbar and retrobulbar anesthesia with bupivacaine in cats.

                    Animals

                    6 healthy adult cats.

                    Procedures

                    Cats were sedated with dexmedetomidine and received a peribulbar injection of 0.5% bupivacaine (1.5 mL), iopamidol (0.5 mL), and saline (0.9% NaCl) solution (1 mL) or retrobulbar injection of 0.5% bupivacaine (0.75 mL) and iopamidol (0.25 mL) in a crossover study with ≥ 2 weeks between treatments. The contralateral eye was the control. Injectate distribution was evaluated with CT. After atipamezole administration, periocular and corneal sensations, intraocular pressure (IOP), and ocular reflexes and appearance were evaluated for 24 hours.

                    Results

                    All peribulbar and 3 of 6 retrobulbar injections resulted in CT evidence of intraconal injectate. Corneal sensation and periocular skin sensation were absent or significantly reduced relative to that for control eyes for 3 hours after peribulbar injection. Mean ± SD IOP immediately after injection was significantly higher for eyes with peribulbar injections (33 ± 12 mm Hg) than for control eyes or eyes with retrobulbar injections (both 14 ± 4 mm Hg) but 10 minutes later decreased to 18 ± 3 mm Hg. Exophthalmos, chemosis, and ptosis were evident in most injected eyes, and irritation was evident in 3 of 6 peribulbar-injected and 1 of 6 retrobulbar-injected eyes. All conditions resolved within 14 hours.

                    Conclusions and clinical relevance

                    Peribulbar injection resulted in intraconal deposition of bupivicaine in a higher percentage of cats than did retrobulbar injection and induced notable anesthesia relative to that for the control eye; however, IOP increased temporarily.
                      Cover page: Comparison of peribulbar and retrobulbar regional anesthesia with bupivacaine in cats.
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