Pharmacokinetics of morphine in combination with dexmedetomidine and maropitant following intramuscular injection in dogs anaesthetized with halothane

The purpose of this study was to evaluate the pharmacokinetics of morphine in combination with dexmedetomidine and maropitant injected intramuscularly in dogs under general anaesthesia. Eight healthy dogs weighing 25.76 ± 3.16 kg and 3.87 ± 1.64 years of age were used in a crossover study. Dogs were randomly allocated to four groups: (1) morphine 0.6 mg/kg; (2) morphine 0.3 mg/kg + dexmedetomidine 5 μg/kg; (3) morphine 0.3 mg/kg + maropitant 1 mg/kg; (4) morphine 0.2 mg/kg + dexmedetomidine 3 μg/kg + maropitant 0.7 mg/kg. Blood samples were collected before, 15 and 30 min, and 1, 2, 3 4, 6 and 8 hr after injection of the test drugs. Plasma concentration of the drugs was determined by liquid chromatography-mass spectrometry. The elimination half-life (T_1/2) of morphine was higher and the clearance rate (CL) was lower when combined with dexmedetomidine (T_1/2 = 77.72 ± 20.27 min, CL = 119.41 ± 23.34 ml kg⁻¹ min⁻¹) compared to maropitant (T_1/2 = 52.73 min ± 13.823 ml kg⁻¹ min⁻¹, CL = 178.57 ± 70.55) or morphine alone at higher doses (T_1/2 = 50.53 ± 12.55 min, CL = 187.24 ± 34.45 ml kg⁻¹ min⁻¹). Combining morphine with dexmedetomidine may increase the dosing interval of morphine and may have a clinical advantage.     

The effects of pre-anesthetic administration of xylazine on the cardiovascular responses to dobutamine in halothane anaesthetized horses

Studies evaluating the effects of dobutamine in horses do not consistently report increases in cardiac output despite increases in arterial blood pressure. The concurrent administration of the α₂ agonist clonidine, in people, inhibited the chronotropic effects of dobutamine and increased left ventricular stroke work ( Zimpfer et al. 1982 ). Our study was performed to determine if pre‐medication with an α₂ agonist affects the response to dobutamine in anaesthetized horses. Eleven horses were anaesthetized on four separate occasions for one of four randomly assigned treatments; (I) no xylazine, no dobutamine (II) xylazine, no dobutamine (III) no xylazine, dobutamine, and (IV) xylazine, dobutamine. Horses received 0.02 mg kg^?1 of butorphanol IV 10 minutes prior to anesthetic induction. Two minutes prior to induction, groups II and IV received 0.5 mg kg^?1 of IV xylazine. Anaesthesia was induced with 6–7 mg kg^?1 of thiopental and maintained with halothane. End‐tidal halothane concentrations were maintained between 1.1 and 1.2% in groups I and III, and 0.9–1.0% for groups II and IV. Heart rate, cardiac output, right atrial pressure, and systolic (SAP), diastolic (DAP) and mean (MAP) arterial pressure were recorded 30 minutes after beginning halothane anaesthesia (T10). Cardiac output was estimated using Lithium dilution ( Linton et al. 2000 ). Baseline measurements were repeated twice, at 5‐minute intervals (T5 and T0). At time 0 (T0), an IV infusion of either saline (100 mL hour^?1) or dobutamine (0.001 mg kg^?1 minute^?1) was started and data recorded at 5‐minute intervals for 30 minutes (T5 – T30). Stroke volume and systemic vascular resistance (SVR) were calculated. Data were analysed using repeated measures anova (p < 0.01 significant) and Newman–Keuls for multiple comparisons. Cardiac output and stroke volume increased over time in groups III and IV. Cardiac index was higher in groups III and IV than in groups I and II from T10 until completion of the study. Estimates of cardiac index at T30 for groups I–IV were 45 ± 9, 46 ± 11, 71 ± 11, and 78 ± 19 mL kg^?1 minute^?1, respectively (mean ± SD). Stroke index was higher in groups III and IV than in groups I and II from T15 to T30. Values for stroke index at T30 for groups I–IV were 0.98 ± 0.19, 1.11 ± 0.18, 1.46 ± 0.21, 1.74 ± 0.33 mL kg^?1. Heart rate decreased from T10–T30 in groups I and II. Heart rate was greater in groups I and III than in groups II and IV at T5 and T0. Values for heart rate at T0 for groups I–IV were 48 ± 5, 42 ± 5, 50 ± 4, 43 ± 4 beats minute^?1. Systolic arterial pressure, DAP and MAP were higher in groups III and IV than in groups I and II from T5 to T30. There were no differences in SVR between groups. Dobutamine at 0.001 mg kg^?1 minute^?1 increased cardiac output, blood pressure, and stroke volume. Premedication with xylazine at 0.5 mg kg^?1 did not appear to affect the response to dobutamine.     

Pharmacokinetics of levofloxacin after single intravenous,oral and subcutaneous administration to dogs

The pharmacokinetic properties of the fluoroquinolone levofloxacin (LFX) were investigated in six dogs after single intravenous, oral and subcutaneous administration at a dose of 2.5, 5 and 5 mg/kg, respectively. After intravenous administration, distribution was rapid (T_½dist 0.127 ± 0.055 hr) and wide as reflected by the volume of distribution of 1.20 ± 0.13 L/kg. Drug elimination was relatively slow with a total body clearance of 0.11 ± 0.03 L kg^?1 hr^?1 and a T_½ for this process of 7.85 ± 2.30 hr. After oral and subcutaneous administration, absorption half‐life and T_max were 0.35 and 0.80 hr and 1.82 and 2.82 hr, respectively. The bioavailability was significantly higher (p ? 0.05) after subcutaneous than oral administration (79.90 vs. 60.94%). No statistically significant differences were observed between other pharmacokinetic parameters. Considering the AUC_24 hr/MIC and C_max/MIC ratios obtained, it can be concluded that LFX administered intravenously (2.5 mg/kg), subcutaneously (5 mg/kg) or orally (5 mg/kg) is efficacious against Gram‐negative bacteria with MIC values of 0.1 μg/ml. For Gram‐positive bacteria with MIC values of 0.5 μg/kg, only SC and PO administration at a dosage of 5 mg/kg showed to be efficacious. MIC‐based PK/PD analysis by Monte Carlo simulation indicates that the proposed dose regimens of LFX, 5 and 7.5 mg/kg/24 hr by SC route and 10 mg/kg/24 hr by oral route, in dogs may be adequate to recommend as an empirical therapy against S. aureus strains with MIC ≤ 0.5 μg/ml and E. coli strains with MIC values ≤0.125 μg/ml.     

Pharmacokinetic–pharmacodynamic relationship of marbofloxacin for Escherichia coli and Pasturella multocida following repeated intramuscular administration in goats

The pharmacokinetics (PK) and pharmacodynamics (PD) of marbofloxacin (MBF) were determined in six healthy female goats of age 1.00–1.25 years after repeated administration of MBF. The MBF was administered intramuscularly (IM) at 2 mg kg^?1 day^?1 for 5 days. Plasma concentrations of MBF were determined by high‐performance liquid chromatography, and PK parameters were obtained using noncompartmental analysis. The MBF concentrations peaked at 1 hr, and peak concentration (C_max) was 1.760 µg/ml on day 1 and 1.817 µg/ml on day 5. Repeated dosing of MBF caused no significant change in PK parameters except area under curve (AUC) between day 1 (AUC_0–∞D1 = 7.67 ± 0.719 µg × hr/ml) and day 5 (AUC_0‐∞D5 = 8.70 ± 0.857 µg × hr/ml). A slight difference in mean residence time between 1st and 5th day of administration and accumulation index (AI = 1.13 ± 0.017) suggested lack of drug accumulation following repeated IM administration up to 5 days. Minimum inhibitory concentration (MIC) demonstrated that Escherichia coli (MIC = 0.04 µg/ml) and Pasturella multocida (MIC = 0.05 µg/ml) were highly sensitive to MBF. Time‐kill kinetics demonstrated rapid and concentration‐dependent activity of MBF against these pathogens. PK/PD integration of data for E. coli and P. multocida, using efficacy indices: C_max/MIC and AUC_0–24hr/MIC, suggested that IM administration of MBF at a dose of 2 mg kg^?1 day^?1 is appropriate to treat infections caused by E. coli. However, a dose of 5 mg kg^?1 day^?1 is recommended to treat pneumonia caused by P. multocida in goats. The study indicated that MBF can be used repeatedly at dosage of 2 mg/kg in goats without risk of drug accumulation up to 5 days.     

The use of pulsed electromagnetic field (PEMF) therapy to provide post-operative analgesia in the dog

Buprenorphine is an effective analgesic when administered epidurally to humans. The purpose of this study was to compare epidural buprenorphine (B; n = 10) with epidural morphine (M; n = 10) for post‐operative analgesia in dogs undergoing cranial cruciate ligament repair. All dogs were premedicated with acepromazine (0.1 mg kg^?1 IM), induced with propofol (4–6 mg kg^?1 IV) and maintained with halothane in oxygen. Dogs were randomly assigned to receive B (0.004 mg kg^?1) or M (0.1 mg kg^?1) in the lumbosacral epidural space in a total volume of 0.2 mL kg^?1. End‐tidal halothane and CO₂ and temperature were recorded every 15 minutes until extubation (t = 0). A numerical rating pain score (SPS) was recorded at t = 0, 1, 2, 4, 6, 10 and 24 hours by a blinded observer. Dogs received rescue morphine (1.0 mg kg^?1 IM) if indicated by SPS and the time of rescue analgesic administration was recorded. Observable side‐effects such as urinary retention, sedation or pruritus were recorded. Data were analyzed with repeated measures anova . Mean ± SD body weight (kg) and age (yrs) for B dogs was 34.2 ± 10.8 and 5.5 ± 2.8; for M dogs these values were 36.6 ± 13.5 and 5.9 ± 3.3. Mean ± SD SPS for B dogs at t = 0, 1, 2, 4, 6, 10 and 24 hours were 1.2 ± 0.75, 3.2 ± 2.0, 4.5 ± 4.3, 4.6 ± 3.4, 4.7 ± 3.0, 5.0 ± 4.9 and 5.1 ± 3.5. For M dogs these values were 1.7 ± 0.5, 2.6 ± 2.0, 3.7 ± 0.75, 4.2 ± 2.2, 4.1 ± 3.0, 3.1 ± 2.1 and 3.9 ± 1.9. There were no significant differences between B and M with respect to SPS, times or frequency of rescue morphine administration, end‐tidal halothane and CO₂, or esophageal temperature. Fifty per cent of dogs in both groups required rescue morphine. Buprenorphine is as effective as morphine for epidural analgesia in healthy dogs undergoing hindlimb orthopedic surgery.     

Echocardiographic evaluation of dogs receiving 1:1 thiopental/propofol in a clinical setting

The purpose of this study was to compare the echocardiographic Doppler blood pressure and heart rate effects of 1:1 thiopental/propofol with thiopental and propofol, when used as anesthesia‐induction agents. Seven healthy dogs (six Beagles and one Pembroke Welsh Corgi), ranging in age from 1 to 9 years and weighing 14.2 ± 2.4 kg (mean ± SD), were used during the study. In a cross‐over study design with a minimum drug interval of 3 days, each dog received propofol, thiopental, or a mixture of propofol–thiopental IV until each dog received all the three anesthetic agents. An initial dose (propofol 4.9 ± 0.8 mg kg^?1; thiopental 12.9 ± 2.4 mg kg^?1; propofol–thiopental 2.3 ± 0.3 mg kg^?1 (P)?5.7 ± 0.8 mg kg^?1 (T)) of each anesthetic agent was titrated IV until intubation was accomplished. Echocardiographic Doppler blood pressure and heart rate variables were recorded prior to anesthesia and at 1, 5, and 10 minutes after induction of anesthesia. anova and the Bonferroni's t‐test were used to evaluate the groups for differences. Alpha was <0.05. There was no significant effect of treatment on systolic or diastolic ventricular wall thickness, septal thickness, left atrial diameter, or systolic left ventricular diameter. There was a tendency for diastolic left ventricular diameter to decrease over time. There was a tendency for heart rate to increase with a significant difference at the 10‐minute time period between propofol (109 ± 26 beats minute^?1) and thiopental (129 ± 23 beats minute^?1). At the 10‐minute recording period, heart rate following the propofol/thiopental mixture (110 ± 34 beats minute^?1) was closer to that following propofol than to that following thiopental. With all induction agents, indirect blood pressure tended to decrease over time (p = 0.005); however, there was no difference between the groups. The changes observed were not considered to be of clinical significance. The propofol/thiopental mixture produces similar changes in echocardiographic variables when compared to propofol or thiopental, and could be substituted for propofol for induction of anesthesia in dogs.     

Effects of dobutamine on cardiovascular function and oxygen delivery in standing horses

Dobutamine is routinely used to improve cardiovascular function in anaesthetized horses. However, dobutamine in conscious horses is insufficiently investigated. Ten research horses that were already instrumented for a preceding trial were included into the study. Cardiovascular variables were recorded and blood samples taken after instrumentation (Baseline), before starting dobutamine and after 10 min of dobutamine infusion (2 µg kg⁻¹ min⁻¹). A significant increase in systemic blood pressure, mean pulmonary artery pressure and right atrial pressure, and a decrease in heart rate were observed with dobutamine compared with baseline measurements. Arterial and mixed venous haemoglobin and oxygen content, as well as mixed venous partial pressure of oxygen increased. No significant changes in cardiac output, stroke volume, systemic vascular resistance, arterial partial pressure of oxygen, or oxygen consumption, delivery and extraction ratio were detected. Concluding, dobutamine increased systemic blood pressure without detectable changes in stroke volume, cardiac output or systemic vascular resistance in conscious horses.     

Pharmacokinetics of an intravenous and oral dose of enrofloxacin in white rhinoceros (Ceratotherium simum)

South Africa currently loses over 1000 white rhinoceros (Ceratotherium simum) each year to poaching incidents, and numbers of severely injured victims found alive have increased dramatically. However, little is known about the antimicrobial treatment of wounds in rhinoceros. This study explores the applicability of enrofloxacin for rhinoceros through the use of pharmacokinetic‐pharmacodynamic modelling. The pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin were evaluated in five white rhinoceros after intravenous (i.v.) and after successive i.v. and oral administration of 12.5 mg/kg enrofloxacin. After i.v. administration, the half‐life, area under the curve (AUC_tot), clearance and the volume of distribution were 12.41 ± 2.62 hr, 64.5 ± 14.44 μg ml^?1 hr^?1, 0.19 ± 0.04 L h^?1 kg^?1, and 2.09 ± 0.48 L/kg, respectively. Ciprofloxacin reached 26.42 ± 0.05% of the enrofloxacin plasma concentration. After combined i.v. and oral enrofloxacin administration oral bioavailability was 33.30 ± 38.33%. After i.v. enrofloxacin administration, the efficacy marker AUC₂₄: MIC exceeded the recommended ratio of 125 against bacteria with an MIC of 0.5 μg/mL. Subsequent intravenous and oral enrofloxacin administration resulted in a low Cmax: MIC ratio of 3.1. The results suggest that intravenous administration of injectable enrofloxacin could be a useful drug with bactericidal properties in rhinoceros. However, the maintenance of the drug plasma concentration at a bactericidal level through additional per os administration of 10% oral solution of enrofloxacin indicated for the use in chickens, turkeys and rabbits does not seem feasible.     

Antinociceptive efficacy and plasma concentrations of transdermal buprenorphine in dogs

To assess the antinociceptive efficacy of transdermal (TD) buprenorphine (B) in dogs, a prospective, positive-controlled experimental study was performed in 10 healthy Beagles. In an open label crossover design, the dogs initially received intravenous B (IVB, 0.02 mg kg^?1) as a positive control, followed by TDB (52.5 μg h^?1) 4 months later. Blood was collected at regular intervals for determination of the plasma concentrations of B ([B]) and its metabolite norbuprenorphine. The antinociceptive efficacy was assessed using thermal and mechanical models of nociception. The peak concentration [B] was 1.54 ng mL^?1 (±1.98) 60 h after TDB application, although three dogs had no measurable [B] after TDB. Maximum thermal threshold (TT) was 52.6 °C (±0.48) at 1 h after IVB administration and 51.63 °C (±1.01) 72 h after TDB application. The significant increase in TT indicated that effective antinociception was achieved beyond 36 h after the application of TDB, lasting until patch removal. There was hysteresis between [B] and the antinociceptive effect.     

Efficacy of a mephentermine‐based product as a vasopressor and a cardiac performance enhancer when given intramuscularly to cattle

The goal of this study was to confirm the vasopressor and cardiac effects of POTENAY^® INJETÁVEL (POT), a mephentermine‐based product, given to cattle with induced vascular/cardiac depression. Ten healthy Holstein cattle (206 ± 13 kg) followed a randomized‐complete‐block design (RCBD) utilizing crossover study design. Each animal randomly received (1 ml/25 kg, IM) of either POT (n = 10) or volume‐matched placebo control (0.9%NaCl, CP, n = 10). A subset of animals (n = 5) received POT first (day 0) while the remaining (n = 5) received CP; after a six‐day washout period, cattle received the opposite compound. Animals were anesthetized and catheterized for systemic/left ventricular hemodynamic monitoring. Myocardial dysfunction/hypotension was induced by increasing the end‐tidal isoflurane concentration until arterial blood pressure was 20% lower than at baseline and remained stable. Once the animal was determined to be hypotensive and hemodynamically stable, steady‐state hypotensive baseline data (BL2) were acquired, and treatment with either POT or CP was given. Data were acquired post‐treatment at every 15 min for 90 min. POT improved cardiac output (+68 L/min, ±14%, p < 0.05), MAP (+14 mmHg, ±4%, p < 0.05), HR (+22 bpm, ±8%, p < 0.05), and peak rates of ventricular pressure change during both systole (dP/dt_max: +37 mmHg/s ±13%, p < 0.05) and diastole (dP/dt_min: +31 mmHg/s, ±7%, p < 0.05). No improvements were noted following placebo‐control administration. Results indicate that POT improves cardiac performance and systemic hemodynamics in cattle with induced cardiovascular depression when given as single intramuscular injection.     

Pharmacokinetics and toxicity of the novel oral demethylating agent zebularine in laboratory and tumor bearing dogs

The purpose of this study was to determine the plasma pharmacokinetics (PK) and toxicity of zebularine, an oral cytidine analog with demethylating activity, in dogs. Plasma zebularine concentrations were determined by HPLC‐MS/MS following an oral zebularine dose of 8 or 4 mg kg^?1. Plasma zebularine clearance was constant. Mean maximum concentration (C_max) was 23 ± 4.8 and 8.6 ± 1.4 µM following 8 and 4 mg kg^?1, respectively. Mean half‐life was 5.7 ± 0.84 and 7.1 ± 2.1 following 8 and 4 mg kg^?1, respectively. A single 8 mg kg^?1 dose was well tolerated. Daily 4 mg kg^?1 treatment in three laboratory dogs resulted in grade 4 neutropenia (n = 3), grade 1 anorexia (n = 2) and grade 1 or 2 dermatologic changes (n = 2). All adverse events resolved with supportive care. A 4 mg kg^?1 dose every 21 days was well tolerated. A follow‐up dose escalation study is in progress with a lower starting dose.     

Pharmacokinetics of sanguinarine,chelerythrine, and their metabolites in broiler chickens following oral and intravenous administration

Sanguinarine (SA) and chelerythrine (CHE) are the main active components of the phytogenic livestock feed additive, Sangrovit®. However, little information is available on the pharmacokinetics of Sangrovit® in poultry. The goal of this work was to study the pharmacokinetics of SA, CHE, and their metabolites, dihydrosanguinarine (DHSA) and dihydrochelerythrine (DHCHE), in 10 healthy female broiler chickens following oral (p.o.) administration of Sangrovit® and intravenous (i.v.) administration of a mixture of SA and CHE. The plasma samples were processed using two different simple protein precipitation methods because the parent drugs and metabolites are stable under different pH conditions. The absorption and metabolism of SA following p.o. administration were fast, with half‐life (t_1/2) values of 1.05 ± 0.18 hr and 0.83 ± 0.10 hr for SA and DHSA, respectively. The maximum concentration (C_max) of DHSA (2.49 ± 1.4 μg/L) was higher that of SA (1.89 ± 0.8 μg/L). The area under the concentration vs. time curve (AUC) values for SA and DHSA were 9.92 ± 5.4 and 6.08 ± 3.49 ng/ml hr, respectively. Following i.v. administration, the clearance (CL) of SA was 6.79 ± 0.63 (L·h^?1·kg^?1) with a t_1/2 of 0.34 ± 0.13 hr. The AUC values for DHSA and DHCHE were 7.48 ± 1.05 and 0.52 ± 0.09 (ng/ml hr), respectively. These data suggested that Sangrovit® had low absorption and bioavailability in broiler chickens. The work reported here provides useful information on the pharmacokinetic behavior of Sangrovit® after p.o. and i.v. administration in broiler chickens, which is important for the evaluation of its use in poultry.     

Comparison between S(+) ketamine–diazepam and S(+) ketamine–midazolam on anesthetic induction and recovery in dogs

S(+) ketamine, one of the two enantiomers of racemic ketamine, is a phencyclidine derivative that induces amnesia and analgesia. Its activity is related to blockade of NMDA receptors and some opioid action. We compared anesthetic induction and recovery quality with S(+) ketamine in combination with diazepam or midazolam in 10 dogs (ASA 1) admitted for elective surgery. After all clinical examinations, the dogs were separated into two groups (G I and G II). All animals received acepromazine (0.1 mg kg^?1) and fentanyl (5 µg kg^?1) IM, 20 minutes before induction with S(+) ketamine (6 mg kg^?1) and diazepam (0.5 mg kg^?1) IV (G I) or midazolam 0.2 mg kg^?1 (G II) IV. The doses of diazepam and midazolam were chosen according to the literature. All dogs were intubated and then maintained with halothane in oxygen at a vaporizer setting sufficient to maintain surgical anesthesia. Quality of induction, time needed for intubation, heart rate, respiratory rate, SpO₂, time to extubation, and quality of recovery were evaluated. The results were analyzed by Student's t‐test. Smooth induction and recovery were observed in all animals. The time to intubation was 45 ± 20 (GI) and 25 ± 6 seconds (GII), HR was 122 ± 12 (GI) and 125 ± 7 beats minute^?1 (GII), RR was 17 ± 2 (GI) and 21 ± 3 breaths minute^?1 (GII), SpO₂ was 96 ± 2 (GI) and 94 ± 1% (GII), time to extubation was 7 ± 3 (GI) and 4 ± 1 minutes (GII). No statistical differences were found in analyses, although time to intubation was less in GII. The results suggested that both combinations could be used safely for anesthetic induction in healthy dogs.     

Comparative pharmacokinetics of florfenicol in healthy and Pasteurella multocida‐infected Gaoyou ducks

Pasteurella multocida is the causative agent of fowl cholera, and florfenicol (FF) has potent antibacterial activity against P. multocida and is widely used in the poultry industry. In this study, we established a P. multocida infection model in ducks and studied the pharmacokinetics of FF in serum and lung tissues after oral administration of 30 mg/kg bodyweight. The maximum concentrations reached (C_max) were lower in infected ducks (13.88 ± 2.70 μg/ml) vs. healthy control animals (17.86 ± 1.57 μg/ml). In contrast, the mean residence time (MRT: 2.35 ± 0.13 vs. 2.27 ± 0.18 hr) and elimination half‐life (T_½β: 1.63 ± 0.08 vs. 1.57 ± 0.12 hr) were similar for healthy and diseased animals, respectively. As a result, the area under the concentration curve for 0–12 hr (AUC_0–12 hr) for FF in healthy ducks was significantly greater than that in infected ducks (49.47 ± 5.31 vs. 34.52 ± 8.29 μg hr/ml). The pharmacokinetic differences of FF in lung tissues between the two groups correlated with the serum pharmacokinetic differences. The C_max and AUC_0–12 hr values of lung tissue in healthy ducks were higher than those in diseased ducks. The concentration of FF in lung tissues was approximately 1.2‐fold higher than that in serum both in infected and healthy ducks indicating that FF is effective in treating respiratory tract infections in ducks.     

Measurement of cardiac output by transesophageal Doppler ultrasonography in anesthetized dogs: comparison with thermodilution

Thermodilution (TD) is the standard method for cardiac output (CO) monitoring in human medicine. Although called the ‘gold standard’, TD is related to numerous complications and data misinterpretations. Recently, a noninvasive, continuous, ultrasound‐based technique for CO measurement has been developed (Hemosonic 100, Arrow Intl). This study compared transesophageal Doppler ultrasonography (TED) for measuring CO with TD in anesthetized dogs. In this study, ten dogs were used to simultaneously measure CO by TED and TD. All dogs were pre‐medicated with acepromazine at 0.1 mg kg^?1 IM, induced with thiopental at 10 mg kg^?1 IV, and maintained on isoflurane at end‐tidal concentrations of 1.3%. Baseline and four different levels of CO were used for comparison. Low CO levels were induced by caudal vena cava occlusion. High CO levels were induced by the constant IV infusion of dopamine, dobutamine, or norepinephrine. Each level of CO allowed one comparison between TED and TD. Forty‐nine paired comparisons of CO were determined ranging from 0.73 to 10.9 L minute^?1. Simple linear regression was used to determine the correlation between the two techniques. Correlation coefficient (r²) was 0.53. Bland and Altman statistical method was used for assessing agreement between the two methods. The difference between the TD and TED when all data were included was 0.82 (bias) ± 1.63 L minute^?1 (mean ± SD). At low CO levels (baseline and caudal vena cava occlusion), the correlation coefficient was 0.77, bias was 0.35 ± 0.64 L minute^?1. At high CO levels (dopamine, dobutamine, or norepinephrine), the correlation coefficient was 0.39. It was concluded that TED was not a reliable monitoring method in determining CO when positive inotropes were used. TED might have importance in situations of low CO values; however, further investigation is warranted.     

Pharmacokinetics of ceftiofur sodium in Peekapoo dogs following a single intravenous and subcutaneous injection

The present study aimed to determine the pharmacokinetic profiles of ceftiofur (as measured by ceftiofur and its active metabolites concentrations) in a small-size dog breed, Peekapoo, following a single intravenous or subcutaneous injection of ceftiofur sodium. The study population comprised of five clinically healthy Peekapoo dogs with an average body weight (BW) of 3.4 kg. Each dog received either intravenous or subcutaneous injection, both at 5 mg/kg BW (calculated as pure ceftiofur). Plasma samples were collected at different time points after the administration. Ceftiofur and its active metabolites were extracted from plasma samples, derivatized, and further quantified by high-performance liquid chromatography. The concentrations versus time data were subjected to noncompartmental analysis to obtain the pharmacokinetic parameters. The terminal half-life (t_1/2λz) was calculated as 7.40 ± 0.79 and 7.91 ± 1.53 hr following intravenous and subcutaneous injections, respectively. After intravenous treatment, the total body clearance (Cl) and volume of distribution at steady-state (V_SS) were determined as 39.91 ± 4.04 ml hr⁻¹ kg⁻¹ and 345.71 ± 28.66 ml/kg, respectively. After subcutaneous injection, the peak concentration (C_max; 10.50 ± 0.22 μg/ml) was observed at 3.2 ± 1.1 hr, and the absorption half-life (t_1/2ka) and absolute bioavailability (F) were calculated as 0.74 ± 0.23 hr and 91.70%±7.34%, respectively. The pharmacokinetic profiles of ceftiofur and its related metabolites demonstrated their quick and excellent absorption after subcutaneous administration, in addition to poor distribution and slow elimination in Peekapoo dogs. Based on the time of concentration above minimum inhibitory concentration (T > MIC) values calculated here, an intravenous or subcutaneous dose at 5 mg/kg of ceftiofur sodium once every 12 hr is predicted to be effective for treating canine bacteria with a MIC value of ≤4.0 μg/ml.     

The cardiopulmonary effects of anesthetic induction with isoflurane,ketamine‐diazepam or propofol‐diazepam in the hypovolemic dog

ObjectiveTo evaluate and compare the cardiopulmonary effects of induction of anesthesia with isoflurane (Iso), ketamine–diazepam (KD), or propofol–diazepam (PD) in hypovolemic dogs.Study designProspective randomized cross–over trial.AnimalsSix healthy intact, mixed breed, female dogs weighing 20.7 ± 4.2 kg and aged 22 ± 2 months.MethodsDogs had 30 mL kg^?1 of blood removed at a rate of 1.5 mL kg^?1 minute^?1 under isoflurane anesthesia. Following a 30–minute recovery period, anesthesia was reinduced. Dogs were assigned to one of three treatments: isoflurane via facemask using 0.5% incremental increases in the delivered concentration every 30 seconds, 1.25 mg kg^?1 ketamine and 0.0625 mg kg^?1 diazepam intravenously (IV) with doses repeated every 30 seconds as required, and 2 mg kg^?1 propofol and 0.2 mg kg^?1 diazepam IV followed by 1 mg kg^?1 propofol increments IV every 30 seconds as required. Following endotracheal intubation all dogs received 1.7% end–tidal isoflurane in oxygen. Cardiopulmonary variables were recorded at baseline (before induction) and at 5 or 10 minute intervals following endotracheal intubation.ResultsInduction time was longer in Iso (4.98 ± 0.47 minutes) compared to KD (3.10 ± 0.47 minutes) or PD (3.22 ± 0.45 minutes). To produce anesthesia, KD received 4.9 ± 2.3 mg kg^?1 ketamine and 0.24 ± 0.1 mg kg^?1 diazepam, while PD received 2.2 ± 0.4 mg kg^?1 propofol and 0.2 mg kg^?1 diazepam. End–tidal isoflurane concentration immediately following intubation was 1.7 ± 0.4% in Iso. Arterial blood pressure and heart rate were significantly higher in KD and PD compared to Iso and in KD compared to PD. Arterial carbon dioxide partial pressure was significantly higher in PD compared to KD and Iso immediately after induction.Conclusions and clinical relevanceIn hypovolemic dogs, KD or PD, as used in this study to induce anesthesia, resulted in less hemodynamic depression compared to isoflurane.     

Effects of constant rate infusions of dexmedetomidine or MK-467 on the minimum alveolar concentration of sevoflurane in dogs

Objective

To determine the effects of low and high dose infusions of dexmedetomidine and a peripheral α₂-adrenoceptor antagonist, MK-467, on sevoflurane minimum alveolar concentration (MAC) in dogs.

Ketoprofen reduces the minimum alveolar concentration (MAC) in dogs anaesthetized with isoflurane and fentanyl

Non‐steroidal anti‐inflammatory drugs may potentiate the opioid induced reduction in volatile anaesthetic requirements ( Gomez de Segura et al. 1998 ). This study determined the reduction in the MAC of isoflurane (ISO) produced by ketoprofen (KETO) in dogs anaesthetized with fentanyl (FENT) and ISO. Six healthy female crossbred dogs, weighing 13.5 ± 1.3 (mean ± SD) kg and aged 3.0 ± 0.9 years were studied. Approval of the study was obtained from the institutional ethics committee. Anaesthesia was induced in all dogs via a facemask with 5% ISO in 5 L minute^?1 oxygen. The dogs' trachea were intubated and lungs were ventilated to maintain normocapnia (Pe ′CO₂ 4.7–6 kPa, 35–45 mm Hg). A heating pad was used to maintain body temperature. The animals were anaesthetized four times at one week intervals with the following anaesthetic and analgesic protocols randomly administered. Study 1, MAC (ISO); Isoflurane MAC. Study 2, MAC (ISO + FENT); dogs anaesthetized with ISO received a loading dose of 30 µg kg^?1 FENT IV over 20 minutes followed by a maintenance infusion of 0.2 µg kg^?1 minute^?1 FENT. Study 3, MAC (ISO + FENT + KETO1); as study 2 plus 1 mg kg^?1 KETO. Study 4, MAC (ISO + FENT + KETO2); as study 2 plus 2 mg kg^?1 KETO. The MAC was determined in duplicate by applying a standard electrical stimulus (50 V, 50 H₂ over 60 seconds via two needles placed SC over the tarsus). The stimulus was applied 15 minutes after every step change in anesthetic concentration. The Wilcoxon test was applied to data to determine significant differences among MAC measurements. Fentanyl significantly decreased MAC (ISO) from 1.27% ± 0.02% to 0.73% ± 0.08%, a reduction of 42% (p < 0.05). Ketoprofen 1 mg kg^?1 further decreased the MAC value (although not statistically significantly) with a reduction of 47% from MAC (ISO) (0.67% ± 0.13%) and 8% from MAC (ISO + FENT). When KETO 2 mg kg^?1 was given, the reduction in MAC was 50% compared to MAC (ISO) (0.63% ± 0.08%; p < 0.05) and 14% compared to MAC (ISO + FENT) p < 0.05. Administration of KETO further reduces MAC (ISO) compared to levels observed with FENT alone. The observed reduction may have clinical advantages.     

Sedative effects of hydromorphone or oxymorphone with or without acepromazine in dogs

Hydromorphone is an agonist opioid with potency approximately five times that of morphine and half that of oxymorphone. The purpose of this study was to compare hydromorphone with oxymorphone, with or without acepromazine, for sedation in dogs, and to measure plasma histamine before and after drug administration. Ten dogs received IM hydromorphone (H; 0.2 mg kg^?1), oxymorphone (O; 0.1 mg kg^?1), hydromorphone with acepromazine (H; 0.2 mg kg^?1, A; 0.05 mg kg^?1) or oxymorphone with acepromazine (O; 0.1 mg kg^?1, A; 0.05 mg kg^?1) in a randomized Latin‐square design. Sedation score, heart rate, respiratory rate, blood pressure, and SpO₂ were recorded at baseline and every 5 minutes after drug administration up to 25 minutes. Plasma histamine was measured at baseline and at 25 minutes post‐drug administration. Data were analyzed with repeated measures anova . Mean ± SD body weight was 21.62 ± 1.54 kg. Mean ± SD age was 1.07 ± 0.19 years. Sedation score was significantly greater for OA after 5 minutes than O alone (4.1 ± 3.5 versus 1.9 ± 1.5) and for HA after 15 minutes than H alone (8.6 ± 2.9 versus 5.9 ± 2.5). There was no significant difference in sedation between H and O at any time point. There was no significant difference between groups at any time with respect to heart rate, respiratory rate, blood pressure or SpO₂. Mean ± SD plasma histamine (nM ml^?1) for all groups was 1.72 ± 2.69 at baseline and 1.13 ± 1.18 at 25 minutes. There was no significant change in plasma histamine concentration in any group. Hydromorphone is effective for sedation in dogs and does not cause measurable increase in histamine. Sedation with hydromorphone is enhanced by acepromazine.