Pharmacokinetics of oral clonazepam in growing commercial pigs (Sus scrofa domestica).

Clonazepam causes sedation and psychomotor impairment in people. Due to similarities between people and swine in response to benzodiazepines, clonazepam may represent a viable option to produce mild-to-moderate tranquillization in pigs. The objective of this study was to determine the pharmacokinetic profile of a single oral dose (0.5 mg/kg) of clonazepam in eight healthy, growing commercial cross pigs. Serial plasma samples were collected at baseline and up to 96 h after administration. Plasma concentrations were quantified using reverse-phase high-performance liquid chromatography, and compartment models were fit to time-concentration data. A one-compartment first-order model best fits the data. Maximum plasma concentration was 99.5 ng/mL, and time to maximum concentration was 3.4 h. Elimination half-life was 7.3 h, mean residence time 7.4 h, and apparent volume of distribution 5.7 L/kg. Achieved plasma concentrations exceeded those associated with psychomotor impairment in people although pharmacodynamic effects have not been investigated in pigs. A simulated oral regimen consisting of 0.35 mg/kg administered every 8 h to pigs would achieve plasma concentrations above 32 ng/mL which are shown to produce psychomotor impairment in people. Further studies to test the clinical efficacy of these dosages in commercial and miniature pigs are warranted.

Pharmacokinetics of a single oral dose of grapiprant in juvenile pigs (Sus scrofa domestica).

Both pet and research pigs can suffer from some degree of pain from surgery, injuries, or osteoarthritis (OA). Despite this, there is a paucity of data on safe and effective analgesia agents in pigs. Grapiprant is an EP4 antagonist that blocks the action of the pro-inflammatory prostanoid, PGE2 . It has shown efficacy in attenuating pain associated with ovariohysterectomy and OA in dogs. However, there are no data regarding grapiprant in pigs. Therefore, the pharmacokinetic profile of orally administered grapiprant to juvenile pigs (Sus scrofa domestica) was evaluated in this study. Seven juvenile pigs received 12 mg/kg grapiprant orally. Blood was collected from an indwelling jugular catheter using the push-pull method at set timepoints up to 48 hours. Sample analysis was performed with high-performance liquid chromatography. Mean grapiprant plasma concentration was 164.3 ± 104.7 ng/mL which occurred at 0.8 ± 0.3 h. This study demonstrated that grapiprant concentrations consistent with analgesia in dogs were reached at this dosage in pigs. Further studies are needed to evaluate the efficacy of grapiprant in pigs.

Pharmacokinetics of intramuscular maropitant in pigs (Sus scrofa domesticus).

Pigs are at risk of vomiting from medical conditions as well as the emetic side effects of drugs administered for peri-operative manipulations, but there is a lack of pharmacokinetic data for potential anti-emetic therapies, such as maropitant, in this species. The main objective of this study was to estimate plasma pharmacokinetic parameters for maropitant in pigs after a single intramuscular (IM) administration dosed at 1.0 mg/kg. A secondary objective was to estimate pilot pharmacokinetic parameters in pigs after oral (PO) administration at 2.0 mg/kg. Maropitant was administered to six commercial pigs at a dose of 1.0 mg/kg IM. Plasma samples were collected over 72 h. After a 7-day washout period, two pigs were administered maropitant at a dose of 2.0 mg/kg PO. Maropitant concentrations were measured via liquid chromatography/mass spectrometry (LC-MS/MS). A non-compartmental analysis was used to derive pharmacokinetics parameters. No adverse events were noted in any of the study pigs after administration. Following single IM administration, maximum plasma concentration was estimated at 412.7 ± 132.0 ng/mL and time to maximum concentration ranged from 0.083 to 1.0 h. Elimination half-life was estimated at 6.7 ± 1.28 h, and mean residence time was 6.1 ± 1.2 h. Volume of distribution after IM administration was 15.9 L/kg. Area under the curve was 1336 ± 132.0 h*ng/mL. The relative bioavailability of PO administration was noted to be 15.5% and 27.2% in the two pilot pigs. The maximum systemic concentration observed in the study pigs after IM administration was higher than what was observed after subcutaneous administration in dogs, cats, or rabbits. The achieved maximum concentration exceeded the concentrations for anti-emetic purposes in dogs and cats; however, a specific anti-emetic concentration is currently not known for pigs. Further research is needed into the pharmacodynamics of maropitant in pigs to determine specific therapeutic strategies for this drug.

The effect of remifentanil infusion on sevoflurane minimum alveolar concentration-no movement (MACNM) and bispectral index in dogs.

OBJECTIVE: To determine the effect of remifentanil infusion on the minimum alveolar concentration of sevoflurane preventing movement (SEVOMACNM) and bispectral index (BIS) in dogs. STUDY DESIGN: Prospective, unmasked study. ANIMALS: A total of 10 adult Beagle dogs weighing 9.0 ± 1.1 kg. METHODS: Dogs were anesthetized with sevoflurane and baseline SEVOMACNM was determined. Remifentanil was infused at 5, 10 and 20 µg kg-1 hour-1, in sequence, with 20 minutes washout between infusions. Variables monitored throughout anesthesia included heart rate (HR), oscillometric blood pressure, end-tidal partial pressure of carbon dioxide, end-tidal sevoflurane concentration (Fe'Sevo) and BIS. SEVOMACNM after remifentanil infusion (SEVOMACNM-REMI) determination started 20 minutes after the start of each infusion. Venous blood samples were collected for plasma remifentanil concentration determination at baseline, SEVOMACNM-REMI determination time points, and 20 minutes after each infusion was stopped. A mixed model analysis was used to determine the effect of remifentanil infusion on response variables. The relationships between BIS and Fe'Sevo, plasma remifentanil concentrations and the percentage decrease in baseline SEVOMACNM were evaluated (p < 0.05). RESULTS: The overall SEVOMACNM at baseline was 2.47 ± 0.11%. Addition of remifentanil at all infusion rates significantly decreased SEVOMACNM, but the medium and high doses resulted in significantly greater decreases in SEVOMACNM than the lower dose. There was no difference in SEVOMACNM percentage change between infusions 10 and 20 µg kg-1 hour-1. Plasma remifentanil concentrations were significantly different in all infusion rates. Baseline BIS value was 70 ± 1 and was lower than the BIS values recorded during all remifentanil infusions. BIS values were not significantly different among infusion rates. HR was lower and mean arterial pressure was higher during remifentanil infusions than at baseline. CONCLUSIONS AND CLINICAL RELEVANCE: All remifentanil infusions decreased SEVOMACNM in dogs. Remifentanil infusion at any rate studied did not reduce BIS values.

Effects of intravenous acepromazine and butorphanol on propofol dosage for induction of anesthesia in healthy Beagle dogs.

OBJECTIVE: To determine the effects of intravenous (IV) premedication with acepromazine, butorphanol or their combination, on the propofol anesthetic induction dosage in dogs. STUDY DESIGN: Prospective, blinded, Latin square design. ANIMALS: A total of three male and three female, healthy Beagle dogs, aged 3.79 ± 0.02 years, weighing 10.6 ± 1.1 kg, mean ± standard deviation. METHODS: Each dog was assigned to one of six IV treatments weekly: 0.9% saline (treatment SAL), low-dose acepromazine (0.02 mg kg-1; treatment LDA), high-dose acepromazine (0.04 mg kg-1; treatment HDA), low-dose butorphanol (0.2 mg kg-1; treatment LDB), high-dose butorphanol (0.4 mg kg-1; treatment HDB); and a combination of acepromazine (0.02 mg kg-1) with butorphanol (0.2 mg kg-1; treatment ABC). Physiologic variables and sedation scores were collected at baseline and 10 minutes after premedication. Then propofol was administered at 1 mg kg-1 IV over 15 seconds, followed by boluses (0.5 mg kg-1 over 5 seconds) every 15 seconds until intubation. Propofol dose, physiologic variables, recovery time, recovery score and adverse effects were monitored and recorded. Data were analyzed using mixed-effects anova (p < 0.05). RESULTS: Propofol dosage was lower in all treatments than in treatment SAL (4.4 ± 0.5 mg kg-1); the largest decrease was recorded in treatment ABC (1.7 ± 0.3 mg kg-1). Post induction mean arterial pressures (MAPs) were lower than baseline values of treatments LDA, HDA and ABC. Apnea and hypotension (MAP < 60 mmHg) developed in some dogs in all treatments with the greatest incidence of hypotension in treatment ABC (4/6 dogs). CONCLUSIONS AND CLINICAL RELEVANCE: Although the largest decrease in propofol dosage required for intubation was after IV premedication with acepromazine and butorphanol, hypotension and apnea still occurred.

Pharmacokinetics of midazolam in sevoflurane-anesthetized cats.

OBJECTIVE: To estimate the pharmacokinetics of midazolam and 1-hydroxymidazolam after midazolam administration as an intravenous bolus in sevoflurane-anesthetized cats. STUDY DESIGN: Prospective pharmacokinetic study. ANIMALS: A group of six healthy adult, female domestic cats. METHODS: Anesthesia was induced and maintained with sevoflurane. After 30 minutes of anesthetic equilibration, cats were administered midazolam (0.3 mg kg-1) over 15 seconds. Venous blood was collected at 0, 1, 2, 4, 8, 15, 30, 45, 90, 180 and 360 minutes after administration. Plasma concentrations for midazolam and 1-hydroxymidazolam were measured using high-pressure liquid chromatography. The heart rate (HR), respiratory rate (fR), rectal temperature, noninvasive mean arterial pressure (MAP) and end-tidal carbon dioxide (Pe'CO2) were recorded at 5 minute intervals. Population compartment models were fitted to the time-plasma midazolam and 1-hydroxymidazolam concentrations using nonlinear mixed effect modeling. RESULTS: The pharmacokinetic model was fitted to the data from five cats, as 1-hydroxymidazolam was not detected in one cat. A five-compartment model best fitted the data. Typical values (% interindividual variability where estimated) for the volumes of distribution for midazolam (three compartments) and hydroxymidazolam (two compartments) were 117 (14), 286 (10), 705 (14), 53 (36) and 334 mL kg-1, respectively. Midazolam clearance to 1-hydroxymidazolam, midazolam fast and slow intercompartmental clearances, 1-hydroxymidazolam clearance and 1-hydroxymidazolam intercompartment clearance were 18.3, 63.5 (15), 22.1 (8), 1.7 (67) and 3.8 mL minute-1 kg-1, respectively. No significant changes in HR, MAP, fR or Pe'CO2 were observed following midazolam administration. CONCLUSION AND CLINICAL RELEVANCE: In sevoflurane-anesthetized cats, a five-compartment model best fitted the midazolam pharamacokinetic profile. There was a high interindividual variability in the plasma 1-hydroxymidazolam concentrations, and this metabolite had a low clearance and persisted in the plasma for longer than the parent drug. Midazolam administration did not result in clinically significant changes in physiologic variables.

Sedative effects and pharmacokinetics of detomidine when administered intravenously and intravaginally as a gel in alpacas.

OBJECTIVES: To evaluate the sedative effects and pharmacokinetics of detomidine gel administered intravaginally to alpacas in comparison with intravenously (IV) administered detomidine. STUDY DESIGN: Randomized, crossover, blinded experiment. ANIMALS: A group of six healthy adult female Huacaya alpacas (70.3 ± 7.9 kg). METHODS: Alpacas were studied on two occasions separated by ≥5 days. Treatments were IV detomidine hydrochloride (70 µg kg-1; treatment DET-IV) or detomidine gel (200 µg kg-1; treatment DET-VAG) administered intravaginally. Sedation and heart rate (HR) were evaluated at intervals for 240 minutes. Venous blood was collected at intervals for 360 minutes after treatment for analysis of detomidine, carboxydetomidine and hydroxydetomidine using liquid chromatography-tandem mass spectrometry. Measured variables were compared between treatments and over time using mixed model analysis. Data are presented as the mean ± standard error of the mean, and a p value of <0.05 was considered significant. RESULTS: Onset of sedation was faster in treatment DET-IV (1.6 ± 0.2 minutes) than in treatment DET-VAG (13.0 ± 2.5 minutes). Time to maximum sedation was shorter in treatment DET-IV (8.3 ± 1.3 minutes) than in treatment DET-VAG (25 ± 4 minutes). Duration of sedation was not different between treatments. There was a significant linear relationship between sedation score and plasma detomidine concentration. HR was less than baseline for 60 and 125 minutes for treatments DET-IV and DET-VAG, respectively. The maximal decrease in HR occurred at 15 minutes for both treatments. The mean maximum plasma concentration of detomidine, time to maximum concentration and bioavailability for treatment DET-VAG were 39.6 ng mL-1, 19.9 minutes and 20%, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Detomidine administration at the doses studied resulted in moderate sedation when administered IV or intravaginally to alpacas.

Evaluation of the sedative effects and pharmacokinetics of detomidine gel administered intravaginally to horses.

OBJECTIVES: To determine the sedative effects and pharmacokinetic profile of detomidine when administered intravaginally as a gel formulation to horses. STUDY DESIGN: Randomized, crossover, masked experimental design. ANIMALS: A group of six healthy adult mares (494 ± 56 kg). METHODS: Mares were studied on two occasions and were administered either detomidine hydrochloride (10 µg kg-1) intravenously (treatment IV) or detomidine gel (40 µg kg-1) intravaginally (treatment IVG), separated by 1 week. Sedation, ataxia, muzzle-floor distance and heart rate (HR) were evaluated every 15 minutes for 240 minutes. Venous blood samples were collected at 15, 30, 45, 60, 90, 120, 150, 180, 240, 300 and 360 minutes postadministration and were analyzed for detomidine and metabolites using liquid chromatography-tandem mass spectrometry. Measured variables were compared over time and between treatments using mixed model analysis. Correlation between drug plasma concentrations and muzzle-floor distance, and sedation and ataxia scores was determined using the Spearman correlation coefficient. Data are presented as mean ± standard error of the mean and p value was set at <0.05. RESULTS: Sedation was shorter with IV (119 ± 16 minutes) than with IVG (188 ± 22 minutes). Ataxia scores remained greater than baseline for 90 and 135 minutes for treatments IV and IVG, respectively. HR was lower than baseline for 45 and 30 minutes for IV and IVG, respectively, but did not differ between treatments. The mean maximum plasma concentration of detomidine, time to maximum concentration and bioavailability for treatment IVG was 8.57 ng mL-1, 0.37 hour and 25%, respectively. There was a significant correlation (r = 0.68) between plasma detomidine concentrations and sedation score. CONCLUSIONS AND CLINICAL RELEVANCE: Detomidine gel administered intravaginally resulted in clinically important sedation and is a viable method for detomidine gel delivery in mares.

Effect of fentanyl on the induction dose and minimum infusion rate of alfaxalone preventing movement in dogs.

OBJECTIVE: To determine the effect of fentanyl on the induction dose and minimum infusion rate of alfaxalone required to prevent movement in response to a noxious stimulus (MIRNM) in dogs. STUDY DESIGN: Experimental crossover design. ANIMALS: A group of six healthy, adult, intact female mixed-breed dogs, weighing 19.7 ± 1.3 kg. METHODS: Dogs were randomly administered one of three treatments at weekly intervals: premedication with 0.9% saline (treatment A), fentanyl 5 µg kg-1 (treatment ALF) or fentanyl 10 µg kg-1 (treatment AHF), administered intravenously over 5 minutes. Anesthesia was induced 5 minutes later with incremental doses of alfaxalone to achieve intubation and was maintained for 90 minutes in A with alfaxalone (0.12 mg kg-1 minute-1), in ALF with alfaxalone (0.09 mg kg-1 minute-1) and fentanyl (0.1 µg kg-1 minute-1) and in AHF with alfaxalone (0.06 mg kg-1 minute-1) and fentanyl (0.2 µg kg-1 minute-1). The alfaxalone infusion was increased or decreased by 0.006 mg kg-1 minute-1 based on positive or negative response to antebrachium stimulation (50 V, 50 Hz, 10 ms). Data were analyzed using a mixed-model anova and presented as least squares means ± standard error. RESULTS: Alfaxalone induction doses were 3.50 ± 0.13 (A), 2.17 ± 0.10 (ALF) and 1.67 ± 0.10 mg kg-1 (AHF) and differed among treatments (p < 0.05). Alfaxalone MIRNM was 0.17 ± 0.01 (A), 0.10 ± 0.01 (ALF) and 0.07 ± 0.01 mg kg-1 minute-1 (AHF) and differed among treatments. ALF and AHF decreased the MIRNM by 44 ± 8% and 62 ± 5%, respectively (p < 0.05). Plasma alfaxalone concentrations at MIRNM were 5.82 ± 0.48 (A), 4.40 ± 0.34 (ALF) and 2.28 ± 0.09 µg mL-1 (AHF). CONCLUSIONS AND CLINICAL RELEVANCE: Fentanyl, at the doses studied, significantly decreased the alfaxalone induction dose and MIRNM.

Effect of fentanyl on the induction dose and minimum infusion rate of propofol preventing movement in dogs.

OBJECTIVE: To determine the effect of fentanyl on the induction dose of propofol and minimum infusion rate required to prevent movement in response to noxious stimulation (MIRNM) in dogs. STUDY DESIGN: Crossover experimental design. ANIMALS: Six healthy, adult intact male Beagle dogs, mean±standard deviation 12.6±0.4 kg. METHODS: Dogs were administered 0.9% saline (treatment P), fentanyl (5 µg kg-1) (treatment PLDF) or fentanyl (10 µg kg-1) (treatment PHDF) intravenously over 5 minutes. Five minutes later, anesthesia was induced with propofol (2 mg kg-1, followed by 1 mg kg-1 every 15 seconds to achieve intubation) and maintained for 90 minutes by constant rate infusions (CRIs) of propofol alone or with fentanyl: P, propofol (0.5 mg kg-1 minute-1); PLDF, propofol (0.35 mg kg-1 minute-1) and fentanyl (0.1 µg kg-1 minute-1); PHDF, propofol (0.3 mg kg-1 minute-1) and fentanyl (0.2 µg kg-1 minute-1). Propofol CRI was increased or decreased based on the response to stimulation (50 V, 50 Hz, 10 mA), with 20 minutes between adjustments. Data were analyzed using a mixed-model anova and presented as mean±standard error. RESULTS: ropofol induction doses were 6.16±0.31, 3.67±0.21 and 3.33±0.42 mg kg-1 for P, PLDF and PHDF, respectively. Doses for PLDF and PHDF were significantly decreased from P (p<0.05) but not different between treatments. Propofol MIRNM was 0.60±0.04, 0.29±0.02 and 0.22±0.02 mg kg-1 minute-1 for P, PLDF and PHDF, respectively. MIRNM in PLDF and PHDF was significantly decreased from P. MIRNM in PLDF and PHDF were not different, but their respective percent decreases of 51±3 and 63±2% differed (p=0.035). CONCLUSIONS AND CLINICAL RELEVANCE: Fentanyl, at the doses studied, caused statistically significant and clinically important decreases in the propofol induction dose and MIRNM.

Effect of dexmedetomidine on the minimum infusion rate of propofol preventing movement in dogs.

OBJECTIVE: To determine the effect of dexmedetomidine on induction dose and minimum infusion rate of propofol preventing movement (MIRNM). STUDY DESIGN: Randomized crossover, unmasked, experimental design. ANIMALS: Three male and three female healthy Beagle dogs weighing 10.2 ± 2.8 kg. METHODS: Dogs were studied on three occasions at weekly intervals. Premedications were 0.9% saline (treatment P) or dexmedetomidine (1 µg kg-1, treatment PLD; 2 µg kg-1, treatment PHD) intravenously. Anesthesia was induced with propofol (2 mg kg-1 and then 1 mg kg-1 every 15 seconds) until intubation. Anesthesia was maintained for 90 minutes in P with propofol (0.5 mg kg-1 minute-1) and saline, in PLD with propofol (0.35 mg kg-1 minute-1) and dexmedetomidine (1 µg kg-1 hour-1), and in PHD with propofol (0.3 mg kg-1 minute-1) and dexmedetomidine (2 µg kg-1 hour-1). The stimulus (50 V, 50 Hz, 10 ms) was applied to the antebrachium, and propofol infusion was increased or decreased by 0.025 mg kg-1 minute-1 based on a positive or negative response, respectively. Data were analyzed using a mixed-model anova and presented as mean ± standard error. RESULTS: Propofol induction doses were 8.68 ± 0.57 (P), 6.13 ± 0.67 (PLD) and 4.78 ± 0.39 (PHD) mg kg-1 and differed among treatments (p < 0.05). Propofol MIRNM values were 0.68 ± 0.13, 0.49 ± 0.16 and 0.26 ± 0.05 mg kg-1 minute-1 for P, PLD and PHD, respectively. Propofol MIRNM decreased 59% in PHD (p < 0.05). Plasma propofol concentrations were 14.04 ± 2.30 (P), 11.30 ± 4.30 (PLD) and 7.96 ± 0.72 (PHD) µg mL-1 and dexmedetomidine concentrations were 0.68 ± 0.12 (PLD) and 0.89 ± 0.08 (PHD) ng mL-1 at MIRNM determination. CONCLUSIONS AND CLINICAL RELEVANCE: Dexmedetomidine (1 and 2 µg kg-1) decreased propofol induction dose. Dexmedetomidine (2 µg kg-1 hour-1) resulted in a significant decrease in propofol MIRNM.

Antinociceptive and selected physiological effects of morphine and xylazine on tiletamine-zolazepam anesthesia in llamas.

OBJECTIVE: Evaluate antinociception, anesthesia, and recovery in llamas given tiletamine-zolazepam (TZ) with either morphine, xylazine, morphine and xylazine, or saline. STUDY DESIGN: Randomized crossover experimental study. ANIMALS: Six healthy, adult intact male llamas. METHODS: Llamas were given each of four treatments intramuscularly with a 1-week washout: TZ (2 mg kg(-1) ) combined with either morphine (0.5 mg kg(-1) ; M), xylazine (0.15 mg kg(-1) ; X), morphine (0.5 mg kg(-1) ) and xylazine (0.15mg kg(-1) ) (MX), or saline (C). Llamas breathed room air during the experiment. Characteristics of anesthesia, recovery, and selected cardiopulmonary variables were recorded. Antinociception was assessed by clamping a claw at 5-minute intervals. Data were analyzed using a mixed-model anova and Tukey-Kramer test, and are expressed as least squares mean ± SEM. Significance was set at p < 0.05. RESULTS: No llama in the control group demonstrated antinociception. Antinociception was longest with treatment MX, followed by treatments X and M, respectively. Heart rates in llamas given treatments X and MX were significantly lower than with other treatments. The respiratory rate in llamas given treatment C was greater (p < 0.05) than for all other treatments, however, the respiratory rate was not significantly different among treatments X, M and MX. The PaO2 for llamas given MX remained <60 mmHg throughout the 20 minute period of blood gas analysis. Mean arterial blood pressure in llamas in treatment MX was less than for treatments M or C. CONCLUSION AND CLINICAL RELEVANCE: The combination of morphine (0.5 mg kg(-1) ) and xylazine (0.15 mg kg(-1) ) increased the duration of antinociception compared with xylazine alone, in TZ-anesthetized llamas. Treatments X, M and MX were associated with hypoxemia (PaO2 < 60 mmHg).

Evaluation of the analgesic efficacy of grapiprant compared with robenacoxib in cats undergoing elective ovariohysterectomy in a prospective, randomized, masked, non-inferiority clinical trial.

OBJECTIVES: The main objective of this study was to compare the postoperative analgesic effects of grapiprant with those of robenacoxib in cats undergoing ovariohysterectomy (OVH). METHODS: In total, 37 female cats (age range 4 months-10 years, weighing ⩾2.5 kg) were enrolled in a prospective, randomized, masked, non-inferiority (NI) clinical trial. Cats received oral robenacoxib (1 mg/kg) or grapiprant (2 mg/kg) 2 h before OVH. Analgesia was assessed via the Feline Grimace Scale (FGS), the Glasgow Composite Measure Pain Scale-Feline (CMPS-F), von Frey monofilaments (vFFs) and pressure algometry (ALG) 2 h before treatment administration, at extubation, and 2, 4, 6, 8, 18 and 24 hours after extubation. Hydromorphone (<8 h postoperatively) or buprenorphine (>18 h postoperatively) were administered to cats with scores of ⩾5/20 on CMPS-F and/or ⩾4/10 on FGS. NI margins for CMPS-F and vFFs were set at 3 and -0.2, respectively. A mixed-effect ANOVA was used for FGS scores (P <0.05). Data are reported as mean ± SEM. RESULTS: The data from 33 cats were analyzed. The upper limit of the 95% confidence interval (CI) (0.35) was less than the NI margin of 3 for CMPS-F, and the lower limit of the 95% CI (0.055) was greater than the NI margin of -0.2 for vFFs, indicating NI of grapiprant. The FGS scores were greater than baseline at extubation for both treatments (1.65 ± 0.63; P = 0.001); however, there was no difference between treatments. There was no difference between treatments, nor treatment by time interaction, for vFFs (P <0.001). The CMPS-F scores for both treatments were higher at extubation but returned to baseline after 4 h (P <0.001). For ALG, there was no difference in treatment or treatment by time interaction. The robenacoxib group had lower pressure readings at extubation and 6 h compared with baseline. CONCLUSIONS AND RELEVANCE: These results indicate that grapiprant was non-inferior to robenacoxib for mitigating postsurgical pain in cats after OVH performed via ventral celiotomy. The impact of grapiprant for analgesia in OVH via the flank is unknown.

The effect of fentanyl on the end-tidal sevoflurane concentration needed to prevent motor movement in dogs.

OBJECTIVE: The objectives of this study were to determine the effects of fentanyl on the end-tidal concentration of sevoflurane needed to prevent motor movement (MACNM ) in response to noxious stimulation, and to evaluate if acute tolerance develops. STUDY DESIGN: Randomized cross-over experimental study. ANIMALS: Six healthy, adult (2-3 years old), intact male, mixed-breed dogs weighing 16.2 ± 1.1 kg. METHODS: Six dogs were randomly assigned to receive one of three separate treatments over a 3 week period. After baseline sevoflurane MACNM (MACNM-B) determination, fentanyl treatments (T) were administered as a loading dose (Ld) and constant rate infusion (CRI) as follows: T1-Ld of 7.5 µg kg(-1) and CRI at 3 µg kg(-1) hour(-1); T2-Ld of 15 µg kg(-1) and CRI at 6.0 µg kg (-1) hour(-1); T3-Ld of 30 µg kg(-1) and CRI at 12 µg kg(-1) hour(-1). The MACNM was defined as the minimum end-tidal sevoflurane concentration preventing motor movement. The first post-treatment MACNM (MACNM-I) determination was initiated 90 minutes after the start of the CRI, and a second MACNM (MACNM - II) determination was initiated 3 hours after MACNM-I was established. RESULTS: The overall least square mean MACNM-B for all groups was 2.66%. All treatments decreased (p < 0.05) MACNM, and the decrease from baseline was 22%, 35% and 41% for T1, T2 and T3, respectively. Percentage change in T1 differed (p < 0.05) from T2 and T3; however, T2 did not differ from T3. MACNM-I was not significantly different from MACNM-II within treatments. CONCLUSIONS AND CLINICAL RELEVANCE: Fentanyl doses in the range of 3-12 µg kg(-1) hour(-1) significantly decreased the sevoflurane MACNM. Clinically significant tolerance to fentanyl did not occur under the study conditions.

In vitro analysis and in vivo assessment of fracture complications associated with use of locking plate constructs for stabilization of caprine tibial segmental defects.

PURPOSE: Locking plate fixation of caprine tibial segmental defects is widely utilized for translational modeling of human osteopathology, and it is a useful research model in tissue engineering and orthopedic biomaterials research due to its inherent stability while maintaining unobstructed visualization of the gap defect and associated healing. However, research regarding surgical technique and long-term complications associated with this fixation method are lacking. The goal of this study was to assess the effects of surgeon-selected factors including locking plate length, plate positioning, and relative extent of tibial coverage on fixation failure, in the form of postoperative fracture. METHODS: In vitro, the effect of plate length was evaluated using single cycle compressive load to failure mechanical testing of locking plate fixations of caprine tibial gap defects. In vivo, effects of plate length, positioning, and relative tibial coverage were evaluated using data from a population of goats enrolled in ongoing orthopedic research which utilized locking plate fixation of 2 cm tibial diaphyseal segmental defects to evaluate bone healing over 3, 6, 9, and 12 months. RESULTS: In vitro, no significant differences in maximum compressive load or total strain were noted between fixations using 14 cm locking plates and 18 cm locking plates. In vivo, both plate length and tibial coverage ratio were significantly associated with postoperative fixation failure. The incidence of any cortical fracture in goats stabilized with a 14 cm plate was 57%, as compared with 3% in goats stabilized with an 18 cm plate. Craniocaudal and mediolateral angular positioning variables were not significantly associated with fixation failure. Decreasing distance between the gap defect and the proximal screw of the distal bone segment was associated with increased incidence of fracture, suggesting an effect on proximodistal positioning on overall fixation stability. CONCLUSIONS: This study emphasizes the differences between in vitro modeling and in vivo application of surgical fixation methods, and, based on the in vivo results, maximization of plate-to-tibia coverage is recommended when using locking plate fixation of the goat tibial segmental defect as a model in orthopedic research.

Laparoscopic-assisted ovariectomy of tigers (Panthera tigris) with the use of the LigaSure device.

Laparoscopic ovariectomy was performed in seven tigers with the use of a vessel-sealing device and a three-port technique. A comparison group of seven tigers that underwent traditional ovariohysterectomy was assembled with the use of a medical records search. Mean operative times for laparoscopic ovariectomy were compared to standard ovariohysterectomy, and mean combined laparoscopic incision length compared to standard ovariohysterectomy incision lengths. Significance was set at P < or = 0.05. Mean surgical time for laparoscopic ovariectomy (82 min, range 71-126 min) was significantly shorter than standard ovariohysterectomy surgical time (129 min, range 80-165 min, P = 0.007). Mean combined laparoscopic incision length (8.07 cm, range 3.80-9.50 cm) was significantly shorter than the mean incision length for standard ovariohysterectomy (13.57 cm, range 12.00-20.00 cm, P = 0.009). There were no clinically important complications observed in either group. Laparoscopic ovariectomy has a significantly shorter surgical time and combined incision length compared to standard ovariohysterectomy in tigers, and appears to be a safe and rapid sterilization method for tigers. Equipment cost and the necessity for advanced training may limit its use in some institutions. Further prospective evaluation is warranted to determine whether it is associated with decreased morbidity, mortality, or cost.

Miniature Companion Pig Sedation and Anesthesia.

With their increase in popularity in North America as pets, miniature companion pigs are in need of veterinary professionals familiar with sedation and anesthesia for the species. This article provides a review of the agents used for sedation, premedication, induction, and maintenance of anesthesia for miniature companion pigs. This review also covers species-specific anatomic and physiologic factors of miniature companion pigs with respect to administration of anesthetics, endotracheal intubation, anesthetic maintenance, and common complications so that the reader can make an informed anesthetic plan for the species.

Evaluation of the perioperative analgesic effects of grapiprant compared with carprofen in dogs undergoing elective ovariohysterectomy.

OBJECTIVE: To evaluate and compare postoperative analgesic effects of grapiprant and carprofen in dogs undergoing ovariohysterectomy. ANIMALS: 42 sexually intact female healthy dogs (< 35 kg and 0.5 to 7 years old) were enrolled. PROCEDURES: In a masked, randomized, noninferiority clinical trial, dogs received either 2 mg/kg of grapiprant or 4.4 mg/kg of carprofen orally 2 hours prior to ovariohysterectomy. Postoperative pain was assessed using the Glasgow Composite Pain Scale-Short Form (GCPS-SF) at extubation and 2, 4, 6, 8, 18, and 24 hours postextubation and compared to baseline. After each pain scoring, mechanical nociceptive testing with von Frey monofilaments (vF) was performed to assess hyperalgesia. Hydromorphone (0.05 mg/kg, IM) was administered to any dog with a GCPS-SF of ≥ 5/24. The noninferiority limit (NI) for the GCPS-SF was Δ = 3. The NI for vF was Δ = -0.2. Following noninferiority, a mixed-effect ANOVA and post hoc comparisons were made with the Tukey correction method (P < .05). RESULTS: 3 dogs required rescue analgesia and were excluded from statistical analysis. Of the remaining 39 dogs, the upper CI for GCPS-SF was below the NI of 3 and the lower CI for vF was greater than the NI of -0.2, indicating noninferiority of grapiprant as compared to carprofen. There was no difference between treatment (P = .89) nor treatment by time (P = .62) for GCPS-SF. There was no difference between groups at any time point or over time when vF were used. CLINICAL RELEVANCE: Our study results support the use of grapiprant as an analgesic alternative to carprofen in dogs undergoing ovariohysterectomy.

The effect of midazolam on the end-tidal concentration of isoflurane necessary to prevent movement in dogs.

OBJECTIVE: To determine the possible additive effect of midazolam, a GABA(A) agonist, on the end-tidal concentration of isoflurane that prevents movement (MAC(NM) ) in response to noxious stimulation. STUDY DESIGN: Randomized cross-over experimental study. ANIMALS: Six healthy, adult intact male, mixed-breed dogs. METHODS: After baseline isoflurane MAC(NM) (MAC(NM-B) ) determination, midazolam was administered as a low (LDS), medium (MDS) or high (HDS) dose series of midazolam. Each series consisted of two dose levels, low and high. The LDS was a loading dose (Ld) of 0.2 mg kg(-1) and constant rate infusion (CRI) (2.5 µg kg(-1) minute(-1)) (LDL), followed by an Ld (0.4 mg kg(-1)) and CRI (5 µg kg(-1) minute(-1)) (LDH). The MDS was an Ld (0.8 mg kg(-1)) and CRI (10 µg kg(-1) minute(-1)) (MDL) followed by an Ld (1.6 mg kg(-1)) and CRI (20 µg kg(-1) minute(-1)) (MDH). The HDS was an Ld (3.2 mg kg(-1)) and CRI (40 µg kg(-1) minute(-1)) (HDL) followed by an Ld (6.4 mg kg(-1)) and CRI (80 µg kg(-1) minute(-1)) (HDH). MAC(NM) was re-determined after each dose in each series (MAC(NM-T)). RESULTS: The median MAC(NM-B) was 1.42. MAC(NM-B) did not differ among groups (p > 0.05). Percentage reduction in MAC(NM) was significantly less in the LDS (11 ± 5%) compared with MDS (30 ± 5%) and HDS (32 ± 5%). There was a weak correlation between the plasma midazolam concentration and percentage MAC(NM) reduction (r = 0.36). CONCLUSION AND CLINICAL RELEVANCE: Midazolam doses in the range of 10-80 µg kg(-1) minute(-1) significantly reduced the isoflurane MAC(NM) . However, doses greater than 10 µg kg(-1) minute(-1) did not further decrease MAC(NM) indicating a ceiling effect.

Temporal Changes in Reverse Torque of Locking-Head Screws Used in the Locking Plate in Segmental Tibial Defect in Goat Model.

The objective of this study was to evaluate changes in peak reverse torque (PRT) of the locking head screws that occur over time. A locking plate construct, consisting of an 8-hole locking plate and 8 locking screws, was used to stabilize a tibia segmental bone defect in a goat model. PRT was measured after periods of 3, 6, 9, and 12 months of ambulation. PRT for each screw was determined during plate removal. Statistical analysis revealed that after 6 months of loading, locking screws placed in position no. 4 had significantly less PRT as compared with screws placed in position no. 5 (p < 0.05). There were no statistically significant differences in PRT between groups as a factor of time (p > 0.05). Intracortical fractures occurred during the placement of 151 out of 664 screws (22.7%) and were significantly more common in the screw positions closest to the osteotomy (positions 4 and 5, p < 0.05). Periosteal and endosteal bone reactions and locking screw backout occurred significantly more often in the proximal bone segments (p < 0.05). Screw backout significantly, negatively influenced the PRT of the screws placed in positions no. 3, 4, and 5 (p < 0.05). The locking plate-screw constructs provided stable fixation of 2.5-cm segmental tibia defects in a goat animal model for up to 12 months.