Anesthesia in Sheep With Propofol or With Xylazine-Ketamine Followed by Halothane

Objective- This study evaluates the clinical usefulness and anesthetic effect of propofol, and compares these effects with those of xylazine-ketamine-halothane anesthesia in sheep.
Study Design- Prospective, randomized, clinical trial. Animals or Sample Population- Fourteen healthy adult male sheep.
Methods- Sheep were randomly assigned to two different drug regimens: (1) Bolus injection of propofol (3 mg/kg, intravenously [IV]) followed by continuous intravenous infusion and (2) xylazine (0.11 mg/kg, IV) and ketamine (2.2 mg/kg, IV) for induction followed by halothane anesthesia. Heart rate, respiratory rate, and arterial blood pressures were monitored during anesthesia. Venous blood samples were collected for blood gas analysis. Quality of induction and recovery were also recorded.
Results- The average dose of propofol used to induce and maintain anesthesia was 6.63 ±2.06 mg/kg and 29.3 ±11.7 mg/kg/hr (0.49 ±0.20 mg/kg/min), respectively. The duration of propofol anesthesia was 45.3 ±13.2 minutes and recovery to standing occurred in 14.7 ±5.7 minutes. Sheep receiving xylazine-ketamine-halothane were anesthetized for 35.9 ±4.0 minutes and recovery to standing occurred within 28.5 ±7.5 minutes. Sheep anesthetized with propofol had a significantly higher heart rate, diastolic blood pressure and Pvo₂, and a lower Pvco₂ at 30 minutes and lower BE at 15 and 30 minutes than sheep anesthetized with xylazine-ketamine-halothane.
Conclusions- Propofol anesthesia was characterized by a smooth induction, effective surgical anesthesia and rapid recovery which was comparable to anesthesia with xylazine-ketamine-halothane.
Clinical Relevance- Propofol may be indicated in situations when it is desirable to maintain anesthesia with an intravenous infusion followed by a rapid recovery in healthy sheep.     

Sedative effects of propofol in horses

Objective  We hypothesized that propofol can produce rapidly-reversible, dose-dependent standing sedation in horses.
Study design  Prospective randomized, blinded, experimental trial.
Animals  Twelve healthy horses aged 12 ± 6 years (mean ± SD), weighing 565 ± 20 kg, and with an equal distribution of mares and geldings.
Methods  Propofol was administered as an intravenous bolus at one of three randomized doses (0.20, 0.35 and 0.50 mg kg⁻¹). Cardiovascular and behavioral measurements were made by a single investigator, who was blinded to treatment dose, at 3 minute intervals until subjective behavior scores returned to pre-sedation baseline values. Continuous data were analyzed over time using repeated-measures anova and noncontinuous data were analyzed using Friedman tests.
Results  There were no significant propofol dose or temporal effects on heart rate, respiratory rate, vertical head height, or jugular venous blood gases (pH_v, P_vO₂, P_vCO₂). The 0.35 mg kg⁻¹ dose caused mild sedation lasting up to 6 minutes. The 0.50 mg kg⁻¹ dose increased sedation depth and duration, but with increased ataxia and apparent muscle weakness.
Conclusions and clinical relevance  Intravenous 0.35 mg kg⁻¹ propofol provided brief, mild sedation in horses. Caution is warranted at higher doses due to increased risk of ataxia.     

Evaluation of intraocular and partial CO2 pressure in dogs anesthetized with propofol

The effects of propofol on intraocular pressure (IOP) and end tidal CO₂ (ETCO₂) were studied because an elevation in the latter may alter IOP. Twenty dogs were divided into two groups (G1 and G2). G1 dogs were induced with 10 mg/kg (IV) of propofol followed by a 0.4 mg/kg/min continuous infusion of the same agent diluted in a 0.2% dextrose solution for 1 h. G(CAPS) 2 dogs served as the control group, where only dextrose solution was administered, under the same time intervals as in G1. Applanation tonometry (Tono-Pen) was used to determine IOP and ETCO₂ as a method to determine partial CO₂ pressure. Measurements were taken every 15 min for 1 h, with M1 occurring immediately before IV administration. IOP and ETCO₂ were not statistically significant in either groups. Based on the results, it may be concluded that propofol does not alter IOP and ETCO₂.     

Comparison of the effect of propofol and sevoflurane on the urethral pressure profile in healthy female dogs

OBJECTIVE: To compare the effects of propofol and sevoflurane on the urethral pressure profile in female dogs. ANIMALS: 10 healthy female dogs. PROCEDURE: Urethral pressure profilometry was performed in awake dogs, during anesthesia with sevoflurane at 1.5, 2.0, and 3.0% end-tidal concentration, and during infusion of propofol at rates of 0.4, 0.8, and 1.2 mg/kg/min. A consistent plane of anesthesia was maintained for each anesthetic protocol. Maximum urethral pressure, maximum urethral closure pressure, functional profile length, and functional area were measured. RESULTS: Mean maximum urethral closure pressure of awake dogs was not significantly different than that of dogs anesthetized with propofol at all infusion rates or with sevoflurane at 1.5 and 2.0% end-tidal concentration. Functional area in awake dogs was significantly higher than in anesthetized dogs. Functional area of dogs during anesthesia with sevoflurane at 3.0% end-tidal concentration was significantly lower than functional area for other anesthetic protocols. Individual differences in the magnitude of effects of propofol and sevoflurane on urethral pressures were observed. CONCLUSIONS AND CLINICAL RELEVANCE: Sevoflurane is an alternative to propofol for anesthesia in female dogs undergoing urethral pressure profilometry. Use of these anesthetics at appropriate administration rates should reliably distinguish normal from abnormal maximum urethral closure pressures and functional areas. Titration of anesthetic depth is a critical component of urodynamic testing.     

Correlation between clinical signs of depth of anaesthesia and cerebral state index responses in dogs with different target-controlled infusions of propofol

ObjectiveTo evaluate if the cerebral state index (CSI), measured by a Cerebral State Monitor (CSM), can predict depth of anaesthesia as assessed clinically or by estimated propofol plasma concentrations.Study designProspective clinical study.AnimalsFourteen mixed breed dogs, weighing 24.5 ± 4.7 kg, scheduled to undergo neutering procedures.MethodsDogs were premedicated with 0.05 mg kg^?1 acepromazine intramuscularly. The CSM and cardiovascular monitoring equipment were attached. Anaesthesia was induced with propofol using a target controlled infusion (TCI) to varying plasma propofol targets (PropCp). Following endotracheal intubation the dogs were ventilated with oxygen. Anaesthetic maintenance was with propofol by TCI. A PropCp of 3 μg dL^?1 was set initially, then PropCps were increased in 1 μg dL^?1 steps to 7, 9 and then 11 μg dL^?1. Each PropCp was held constant for a 5 minute period, at the end of which depth of anaesthesia was classified using a previously evaluated scale of ‘planes’ based on palpebral and corneal reflexes and eye position. Cerebral state index (CSI), burst suppression (BSR) and electromyogram were measured at these time points. The prediction probability (PK) of these variables, or of the PropCp in predicting depth of anaesthesia was calculated.ResultsThe PKs for predicting anaesthetic planes were 0.74, 0.91, 0.76 and 0.78 for CSI, BSR, EMG and PropCp, respectively. The PKs for PropCp to predict CSI, BSR and EMG were 0.65, 0.71 and 0.65 respectively.Conclusion and clinical relevance The Cerebral State Monitor was able to detect very deep planes of anaesthesia when BSR occurs, but was not able to distinguish between the intermediate anaesthetic planes likely to be used in clinical anaesthesia.     

Total intravenous anesthesia in greyhounds: pharmacokinetics of propofol and fentanyl--a preliminary study

OBJECTIVE: To evaluate concomitant propofol and fentanyl infusions as an anesthetic regime, in Greyhounds. ANIMALS: Eight clinically normal Greyhounds (four male, four female) weighing 25.58 +/- 3.38 kg. DESIGN: Prospective experimental study. METHODS: Dogs were premedicated with acepromazine (0.05 mg/kg) by intramuscular (i.m.) injection. Forty five minutes later anesthesia was induced with a bolus of propofol (4 mg/kg) by intravenous (i.v.) injection and a propofol infusion was begun (time = 0). Five minutes after induction of anesthesia, fentanyl (2 microg/kg) and atropine (40 microg/kg) were administered i.v. and a fentanyl infusion begun. Propofol infusion (0.2 to 0.4 mg/kg/min) lasted for 90 minutes and fentanyl infusion (0.1 to 0.5 microg/kg/min) for 70 minutes. Heart rate, blood pressure, respiratory rate, end-tidal carbon dioxide, body temperature, and depth of anesthesia were recorded. The quality of anesthesia, times to return of spontaneous ventilation, extubation, head lift, and standing were also recorded. Blood samples were collected for propofol and fentanyl analysis at varying times before, during and after anesthesia. RESULTS: Mean heart rate of all dogs varied from 52 to 140 beats/min during the infusion. During the same time period, mean blood pressure ranged from 69 to 100 mm Hg. On clinical assessment, all dogs appeared to be in light surgical anesthesia. Mean times (+/- SEM), after termination of the propofol infusion, to return of spontaneous ventilation, extubation, head lift and standing for all dogs were 26 +/- 7, 30 +/- 7, 59 +/- 12, and 105 +/- 13 minutes, respectively. Five out of eight dogs either whined or paddled their forelimbs in recovery. Whole blood concentration of propofol for all eight dogs ranged from 1.21 to 6.77 microg/mL during the infusion period. Mean residence time (MRTinf) for propofol was 104.7 +/- 6.0 minutes, mean body clearance (Clb) was 53.35 +/- 0.005 mL/kg/min, and volume of distribution at steady state (Vdss) was 3.27 +/- 0.49 L/kg. Plasma concentration of fentanyl for seven dogs during the infusion varied from 1.22 to 4.54 ng/mL. Spontaneous ventilation returned when plasma fentanyl levels were >0.77 and <1.17 ng/mL. MRTinf for fentanyl was 111.3 +/- 5.7 minutes. Mean body clearance was 29.1 +/- 2.2 mL/kg/min and Vdss was 2.21 +/- 0.19 L/kg. CONCLUSION AND CLINICAL RELEVANCE: In Greyhounds which were not undergoing any surgical stimulation, total intravenous anesthesia maintained with propofol and fentanyl infusions induced satisfactory anesthesia, provided atropine was given to counteract bradycardia. Despite some unsatisfactory recoveries the technique is worth investigating further for clinical cases, in this breed and in mixed breed dogs.     

Comparison of Cerebrospinal Fluid Pressure in Propofol-and Thiopental-anesthetized Eucapnic Dogs

Cerebrospinal fluid pressure (CSF_P) was measured as part of the neurologic assessment of dogs with suspected intracranial disease. Because propofol has not been shown to cause an increase in intracranial pressure in humans, the authors examined its effect on (CSF_P) in dogs to determine if it would be an appropriate substitute for thiopental as an anesthetic agent for the measurement of CSF_P. The CSF pressure in eucapnic propofol-anesthetized dogs (105 ± 5.6 mm H_PO) was not significantly different (p < .05) from CSF_P in eucapnic thiopental-anesthetized dogs (103.8 ± 6.6 mm H_PO).     

Clinical comparison of recovery from total intravenous anesthesia with propofol and inhalation anesthesia with isoflurane in dogs

The characteristics of recovery from total intravenous anesthesia (TIVA) with propofol and inhalation anesthesia with isoflurane was clinically compared in 149 client-owned dogs that anesthetized for surgical or diagnostic procedures. In all dogs, anesthesia was induced with an intravenous injection of propofol following premedication with acepromazine or diazepam. As a result, 58 dogs anesthetized with propofol-TIVA showed slower but smoother recovery than 91 dogs anesthetized with isoflurane anesthesia. The dogs stood at 34.5 +/- 19.3 and 27.7 +/- 17.2 min after propofol-TIVA and isoflurane anesthesia, respectively. Adverse effects, including hypersalivation, neurologic excitement (paddling, muscle tremor/twitching, opisthotonos) and vomiting/retching, were observed in similar infrequent incidences during the recovery from both anesthetic protocols. Propofol-TIVA is suggested to be an alternative anesthetic protocol for canine practice.     

Evaluation of the predictive performance of a pharmacokinetic model for propofol in Japanese macaques (Macaca fuscata fuscata)

Miyabe‐Nishiwaki, T., Masui, K., Kaneko, A., Nishiwaki, K., Nishio, T., Kanazawa, H. Evaluation of the predictive performance of a pharmacokinetic model for propofol in Japanese macaques (Macaca fuscata fuscata). J. vet. Pharmacol. Therap.  36 , 169–173. Propofol is a short‐acting intravenous anesthetic used for induction/maintenance anesthesia. The objective of this study was to assess a population pharmacokinetic (PPK) model for Japanese macaques during a step‐down infusion of propofol. Five male Japanese macaques were immobilized with ketamine (10 mg/kg) and atropine (0.02 mg/kg). A bolus dose of propofol (5 mg/kg) was administrated intravenously (360 mg/kg/h) followed by step‐down infusion at 40 mg/kg/h for 10 min, 20 mg/kg/h for 10 min, and then 15 mg/kg/h for 100 min. Venous blood samples were repeatedly collected following the administration. The plasma concentration of propofol (Cp) was measured by high‐speed LC‐FL. PPK analyses were performed using NONMEM VII. Median absolute prediction error and median prediction error (MDPE), the indices of prediction inaccuracy and bias, respectively, were calculated, and PE ? individual MDPE vs. time was depicted to show the variability of prediction errors. In addition, we developed another population pharmacokinetic model using previous and current datasets. The previous PK model achieved stable prediction of propofol Cp throughout the study period, although it underestimates Cp. The step‐down infusion regimen described in this study would be feasible in macaques during noninvasive procedures.     

Pharmacokinetics of a single bolus intravenous, intramuscular and subcutaneous dose of disodium fosfomycin in horses

Pharmacokinetic parameters of fosfomycin were determined in horses after the administration of disodium fosfomycin at 10 mg/kg and 20 mg/kg intravenously (IV), intramuscularly (IM) and subcutaneously (SC) each. Serum concentration at time zero (C_S0) was 112.21 ± 1.27 μg/mL and 201.43 ± 1.56 μg/mL for each dose level. Bioavailability after the SC administration was 84 and 86% for the 10 mg/kg and the 20 mg/kg dose respectively. Considering the documented minimum inhibitory concentration (MIC₉₀) range of sensitive bacteria to fosfomycin, the maximum serum concentration (Cmax) obtained (56.14 ± 2.26 μg/mL with 10 mg/kg SC and 72.14 ± 3.04 μg/mL with 20 mg/kg SC) and that fosfomycin is considered a time-dependant antimicrobial, it can be concluded that clinically effective plasma concentrations might be obtained for up to 10 h administering 20 mg/kg SC. An additional predictor of efficacy for this latter dose and route, and considering a 12 h dosing interval, could be area under the curve AUC_0-12/MIC₉₀ ratio which in this case was calculated as 996 for the 10 mg/kg dose and 1260 for the 20 mg/kg dose if dealing with sensitive bacteria. If a more resistant strain is considered, the AUC_0-12/MIC₉₀ ratio was calculated as 15 for the 10 mg/kg dose and 19 for the 20 mg/kg dose.     

Pharmacokinetics and pharmacodynamics of meloxicam in piglets

The pharmacokinetics and pharmacodynamics of meloxicam in piglets (16–23 days old) were studied using a stratified parallel group design. One group ( n  = 13) received 0.4 mg/kg meloxicam intravenously, while the other group ( n  = 12) received physiological saline solution. A carrageenan-sponge model of acute inflammation was used to evaluate the effects of meloxicam. The plasma clearance was low (0.061 L/kg/h), the volume of distribution was low (0.19 L/kg) and the elimination half-life was short (2.7 h). At most time points, the mean concentration of meloxicam in plasma exceeded the concentrations in exudate indicating a limited accumulation of the drug at the site of the inflammation. There were significant differences between the groups in the exudate prostaglandin E₂ (PGE₂) concentration, but the inhibition of PGE₂ in the meloxicam group was limited. The inhibition of thromboxane B₂ (TXB₂) production in serum in the meloxicam group was extensive, but of shorter duration than the PGE₂ inhibition in exudate.     

Influence of Pasteurella multocida infection on the pharmacokinetic behavior of marbofloxacin after intravenous and intramuscular administrations in rabbits

Abo-El-Sooud, K., Goudah, A. Influence of Pasteurella multocida infection on the pharmacokinetic behavior of marbofloxacin after intravenous and intramuscular administrations in rabbits. J. vet. Pharmacol. Therap. 33 , 63–68.
The pharmacokinetic behavior of marbofloxacin was studied in healthy ( n  = 12) and Pasteurella multocida infected rabbits ( n  = 12) after single intravenous (i.v.) and intramuscular (i.m.) administrations. Six rabbits in each group (control and diseased) were given a single dose of 2 mg/kg body weight (bw) of marbofloxacin intravenously. The other six rabbits in each group were given the same dose of the drug intramuscularly. The concentration of marbofloxacin in plasma was determined using high-performance liquid chromatography. The plasma concentrations were higher in diseased rabbits than in healthy rabbits following both routes of injections. Following i.v. administration, the values of the elimination half-life ( t _1/2β), and area under the curve were significantly higher, whereas total body clearance was significantly lower in diseased rabbits. After i.m. administration, the elimination half-life ( t _1/2el), mean residence time, and maximum plasma concentration ( C _max) were higher in diseased rabbits (5.33 h, 7.35 h and 2.24 μg/mL) than in healthy rabbits (4.33 h, 6.81 h and 1.81 μg/mL, respectively). Marbofloxacin was bound to the extent of 26 ± 1.3% and 23 ± 1.6% to plasma protein of healthy and diseased rabbits, respectively. The C _max /MIC (minimum inhibitory concentration) and AUC/MIC ratios were significantly higher in diseased rabbits (28 and 189 h) than in healthy rabbits (23 and 157 h), indicating the favorable pharmacodynamic characteristics of the drug in diseased rabbits.     

The effect of medetomidine premedication upon propofol induction and infusion anaesthesia in the dog

The effect of premedication with four different intramuscular doses of medetomidine (5.0,10.0, 20.0 and 40.0 μg.kg-¹) and a saline placebo were compared in a group of six adult beagle dogs anaesthetised with propofol on five separate occasions. Anaesthesia was induced 30 minutes after premedication and maintained by intravenous injection and continuous infusion of propofol. The effects of medetomidine were reversed with atipamezole 30 minutes after anaesthetic induction. The marked synergistic effects of medetomidine with propofol were demonstrated by a dose related reduction in the induction and infusion requirements for a similar degree of anaesthesia. The effect appeared exponential in nature; lower medetomidine doses produced a disproportionately greater effect.
The maintenance of anaesthesia with propofol following a saline placebo or low doses of medetomidine proved to be difficult. Higher doses of medetomidine required less propofol for induction and infusion and allowed a more stable anaesthesia to be maintained. Propofol produced no statistically significant change in heart rate during infusion. Changes in respiratory rate were markedly group specific. A significant reduction in respiratory rate was seen in dogs given either 5 μg.kg- or 10 μ-g.kg-¹ medetomidine. No change was recorded in dogs given 20 /μg.kg-¹ medetomidine and a significant increase was seen in dogs given 40 μg.kg-¹ medetomidine. Recovery was monitored following the termination of propofol infusion after the reversal of medetomidine using atipamezole at five times the medetomidine dose. Recovery was slower for dogs given lower doses of medetomidine and consequently higher doses of propofol.     

Butorphanol Tartrate for Partial Reversal of Oxymorphone-Induced Postoperative Respiratory Depression in the Dog

A randomized, blinded, crossover study was designed to evaluate the respiratory, cardiovascular, and behavioral effects of butorphanol given postoperatively to oxymorphone-premedicated and surgically stimulated dogs. Nine healthy adult dogs were premedicated intramuscularly with atropine (0.04 mg/kg), acepromazine (0.10 mg/kg), and oxymorphone (0.2 mg/kg). Anesthesia was induced with thiamylal (12 mg/kg) and maintained with halothane in oxygen. According to the protocol of a concurrent study, all dogs had percutaneous endoscopic gastrostomy (PEG) feeding tubes placed during the first anesthetic episode and removed during the second anesthetic episode. All dogs received postoperatively either butorphanol tartrate (0.2 mg/kg) or an isovol-umetric dose of saline placebo, both given intravenously. Respiratory rate (RR), tidal volume (TV), minute ventilation (MV), end-tidal CO₂ concentration (ET_CO2). heart rate (HR), and indirect diastolic (DP), systolic (SP) and mean arterial (MAP) blood pressures were measured at times 0, 2, 5, 10, 20, 40, 80, and 120 minutes after injection. The time from injection of the test drug until extubation was recorded. RR, MV, HR, and DP were significantly ( P < .05) increased, while ET_co2 was significantly decreased, for a minimum of 30 minutes in butorphanol-treated dogs compared with saline controls. TV, SP, and MAP were transiently (≤15 minutes) increased in butorphanol-treated dogs compared with saline controls. There was no significant difference between the times to extubation in the butorphanol-treated dogs versus the saline control dogs.     

Effect of metoclopramide on gastro-esophageal reflux in anesthetized dogs

Administration of morphine before anesthesia leads to gastro-esophageal reflux (GER) in over 50% of dogs during the subsequent anesthetic. This GER is clinically silent but can lead to aspiration pneumonitis, esophagitis and esophageal stricture. In this prospective clinical study we aimed to determine the effect of metoclopramide on gastro-esophageal reflux (GER) in dogs undergoing elective orthopedic surgery. Dogs were admitted to the study if they were healthy, and had no history of vomiting or dysphagia. Dogs were fasted for an average of 18.2 ± 4.3 (mean ± SD) hours prior to induction of anesthesia. Anesthesia in all dogs included acepromazine, morphine, thiopental and isoflurane in oxygen. By random allocation, half the dogs received metoclopramide (M) as an IV bolus (0.4 mg kg^–1) and then infusion (0.3 mg kg^–1hour^–1), the others received equivalent volumes of saline (S). To measure esophageal pH a sensor-tipped catheter was placed with the tip 5–7 cm cranial to the lower esophageal sphincter, and connected to a computer for continual data collection. The pH of any fluid running from the mouth or nose was measured. Gastro-esophageal reflux was defined as a decrease in esophageal pH below 4 or an increase above 7.5. Fisher's Exact test was used to test significance of differences in incidence between groups. Separate multivariable logistic regression models were created for each outcome to assess the effects of risk factors on outcome. There were seven cases of GER in 16 dogs receiving M and 8/14 in those receiving S. There were no significant differences between M and S treated dogs in age, weight, duration of anesthesia and fasting, thiopental dose or incidence of vomiting. The administration of metoclopramide at this dose did not significantly reduce the incidence of GER in these anesthetized dogs.     

Clinical usefulness of propofol as an anesthetic induction agent in dogs and cats

Propofol was used as an induction agent of general anesthesia in 77 dogs and 64 cats, all client owned, for a variety of surgeries/treatments or diagnostic procedures. The mean intravenous doses of propofol required to achieve endotracheal intubation in dogs and cats were 6.5 +/- 1.4 mg/kg and 10.1 +/- 2.8 mg /kg, respectively. Most of the animals could be induced to anesthesia smoothly by the administration of propofol with a high incidence of apnea. Propofol is a clinically valuable anesthetic induction agent in both dogs and cats, however, care must be taken for apnea.     

Renal effects of carprofen administered to healthy dogs anesthetized with propofol and isoflurane

OBJECTIVE: To evaluate renal effects of carprofen in healthy dogs following general anesthesia. DESIGN: Randomized clinical trial. ANIMALS: 10 English hound dogs (6 females and 4 males). PROCEDURE: Dogs were randomly assigned to control (n = 5) or carprofen (5) groups. Anesthesia was induced with propofol (6 to 8 mg/kg [2.7 to 3.6 mg/lb] of body weight, i.v.) and maintained with isoflurane (end-tidal concentration, 2.0%). Each dog underwent two 60-minute anesthetic episodes with 1 week between episodes, and mean arterial blood pressure was maintained between 60 and 90 mm Hg during each episode. Dogs in the carprofen group received carprofen (2.2 mg/kg [1 mg/lb], p.o.) at 9:00 AM and 6:00 PM the day before and at 7:00 AM the day of the second anesthetic episode. Glomerular filtration rates (GFR) were determined during each anesthetic episode by use of renal scintigraphy. Serum creatinine and BUN concentrations and the urine gamma-glutamyltransferase-to-creatinine concentration (urine GGT:creatinine) ratio were determined daily for 2 days before and 5 days after general anesthesia. RESULTS: Significant differences were not detected in BUN and serum creatinine concentrations, urine GGT:creatinine ratio, and GFR either between or within treatment groups over time. CONCLUSIONS AND CLINICAL RELEVANCE: Carprofen did not significantly alter renal function in healthy dogs anesthetized with propofol and isoflurane. These results suggest that carprofen may be safe to use for preemptive perioperative analgesia, provided that normal cardiorespiratory function is maintained.     

Pharmacokinetics and bioequivalence of parenterally administered doramectin in cattle

Plasma concentrations of doramectin in 40 cattle dosed by subcutaneous (sc) or intramuscular (i.m.) injection (200 μg/kg) were compared to assess the bioequivalence of the two routes of administration. Peak concentration ( C _max), and areas under the concentration curve ( AUC_0– ) were determined from plasma concentrations. Animals treated by the sc route showed a mean AUC_0– of 457 ± 66 ng±day/mL (± SD) and a mean C _max of 27.8 ± 7.9 ng/mL. Results from the i.m. treatment group showed a mean AUC _0– of 475 ± 82 ng-day/mL and a mean C _max of 33.1 ± 9.0 ng/mL Absorption constants ( k _a) determined by modelling were 0.542 ± 0.336 day^-1after sc administration and 0.710 ± 0.357 day^-1after i.m. administration. The 90% confidence limits on the difference between mean AUC _0– values for the sc and i.m. groups fell within 20% of the mean value for the subcutaneous group. C _max was somewhat greater for the i.m. route. The 90% confidence limits on the difference in mean In ( T _max+1) also fell within 20% of the mean sc value. Based on this analysis, bioequivalence of the sc and i.m. formulation has been established.     

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.     

The effects of pentoxifylline infusion on plasma 6-keto-prostaglandin F1α and ex vivo endotoxin-induced tumour necrosis factor activity in horses

Pentoxifylline (7.5 mg/kg) was bolused intravenously to eight healthy horses and was immediately followed by infusion (1.5 mg/kg/h) for 3 h. Clinical parameters were recorded and blood samples were collected for 24 h. Plasma was separated and concentrations of pentoxifylline, its reduced metabolite I, and 6-keto-prostaglandin F_1α were determined. Heparinized whole blood was also incubated ex vivo with 1 ng Escherichi coli endotoxin/mL blood for 6 h before determination of plasma tumour necrosis factor activity. The peak plasma concentrations of pentoxifylline and metabolite I occurred at 15 min after bolus injection and were 9.2± 1.4 and 7.8± 4.3 μg/mL, respectively. The half-life of elimination ( t _½β) of pentoxifylline was 1.44 h and volume of distribution ( V d_area) was 0.94 L/kg. The mean plasma concentration of 6-keto-prostaglandin F_1α increased over time, with a significant increase occurring 30 min after the bolus administration. Ex vivo plasma endotoxin-induced tumour necrosis factor activity was significantly decreased at 1.5 and 3 h of infusion. These results indicate that infusion of pentoxifylline will increase 6-keto-prostaglandin F_1α and significantly suppress endotoxin-induced tumour necrosis factor activity in horses during the period of infusion.