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The objectives of this study were (a) to establish a population pharmacokinetic model and (b) to investigate the clinical and physiological effects of a single bolus dose of propofol in common marmosets. In Study 1, pharmacokinetic analysis was performed in six marmosets under sevoflurane anaesthesia. 8 mg/kg of propofol was administrated at a rate of 4 mg kg -1  min -1 . Blood samples were collected 2, 5, 15, 30, 60, 90, 120 or 180 min after starting propofol administration. Plasma concentration was measured, and population pharmacokinetic modelling was performed. A two-compartment model was selected as the final model. The population pharmacokinetic parameters were as follows: V 1  = 1.14 L, V 2  = 77.6 L, CL 1  = 0.00182 L/min, CL 2  = 0.0461 L/min. In Study 2, clinical and physiological parameters were assessed and recorded every 2 min after 12 mg/kg of propofol was administrated at a rate of 4 mg kg -1  min -1 . Immobilization was sustained for 5 min following propofol administration without apparent bradycardia. While combination of propofol and sevoflurane caused apnoea in Study 1, apnoea was not observed following single administration of propofol in Study 2. These data provide bases for further investigation on intravenous anaesthesia using propofol in common marmosets., (© 2020 John Wiley & Sons Ltd.)

Alfaxalone, a synthetic neuroactive steroid, has been attributed with properties including sedation, anaesthesia and analgesia. The clinical relevance of any analgesic properties of alfaxalone has not been demonstrated. This study was a prospective, blinded, randomized, negative control clinical trial in 65 healthy dogs presented for ovariohysterectomy. Anaesthesia was induced and maintained, for Group 1 (TIVA) dogs (n = 30) with intravenous alfaxalone alone and for Group 2 dogs (n = 35) with thiopental followed by isoflurane in 100% oxygen inhalation. After ovariohysterectomy, quantitative measures of pain or nociception were recorded at 15 min intervals for 4 hr using three independent scoring systems, a composite measure pain scale (CMPS), von Frey threshold testing and measures of fentanyl rescue analgesia. The mean CMPS scores of Group 2 (THIO/ISO) dogs remained higher than Group 1 (TIVA) dogs from 15 to 135 min post-surgery but this difference was not statistically significant. There were no significant differences between groups in the proportions of dogs requiring rescue fentanyl analgesia, the total fentanyl dose used or the time to first fentanyl dose. The Von Frey threshold testing was found to be unsuitable for measurement of pain in this experimental model. When administered as total intravenous anaesthesia, alfaxalone did not provide analgesia in the postoperative period., (© 2019 John Wiley & Sons Ltd.)

A 10-year-old, 6-kg male Yorkshire terrier dog was scheduled for routine dental cleaning. No significant problem was observed either during anaesthesia, which was induced with propofol, or during recovery. However, 2 hours after discharge, the dog's owner returned to the clinic, complaining that the animal was lethargic and had had bloody diarrhoea. On physical examination the dog was depressed, dyspnoeic, tachycardic and hypoglycaemic. Despite supportive treatment, the dog deteriorated and died within a few hours.A presumed diagnosis of sepsis was confirmed by laboratory testing. Bacteriological and molecular examinations of both premortem blood samples and the anaesthetic, highlighted the presence of Ochrobactrum anthropi, an opportunistic pathogen usually associated with immunocompromised hosts with indwelling medical devices. To the authors’ knowledge, this is the first case of sepsis in a healthy dog due to contamination of an anaesthetic solution by O. anthropi, suggesting a potential role of this microorganism as an emerging pathogen.

Objectives: The aim of this study was to report the management and complications of anaesthesia in dogs undergoing balloon valvuloplasty., Methods: A retrospective review of medical records of dogs that were diagnosed with pulmonic stenosis and undergoing balloon valvuloplasty between 2000 and 2012., Results: Thirty-nine cases were identified (28 males and 11 females). Median (range) age and bodyweight was 6 (4 to 48) months and 11·5 (2·0 to 30·3) kg, respectively. The most commonly represented breeds included mixed breed (n = 7, 17·9%) and English bulldog (n = 6, 15·3%). Anaesthesia was induced most commonly with intravenous administration of ketamine-diazepam (n = 8, 20·5%), propofol-diazepam (n = 8, 20·5%), or propofol-midazolam-lidocaine (n = 6, 15·4%), and maintained with isoflurane in combination with fentanyl or lidocaine. Anaesthetic and surgery times (mean ± sd) were 268·5 ±54 minutes and 193·2 ±50 minutes, respectively. The most common intraoperative complications were hypotension (n = 19, 48·7%), bradycardia (n = 8, 20·5%) and desaturation (n = 7, 17·9%). Cardiac arrhythmias were observed in 21 (53·8%) dogs. Death occurred in one (2·6%) dog due to severe hypotension after ballooning followed by cardiac arrest., Clinical Significance: Successful anaesthesia can be performed in young dogs with pulmonic stenosis undergoing balloon valvuloplasty. Management of anaesthesia requires intense monitoring and immediate treatment of complications. Anaesthetic risk increases during ballooning and may result in cardiac arrest., (© 2014 British Small Animal Veterinary Association.)

This study examined the pharmacokinetics of propofol by infusion in ponies using an analyser for the rapid measurement of propofol concentrations. The analyser (Pelorus 1000; Sphere Medical Ltd., Cambridge, UK) has a measurement cycle of approximately five minutes. Ten Welsh-cross ponies (weighing 135-300 kg) undergoing minor procedures were studied after premedication with acepromazine 0.03 mg/kg and detomidine 0.015 mg/kg. Anaesthesia was induced with ketamine 2 mg/kg and diazepam 0.03 mg/kg, and maintained with an infusion of propofol at an initial rate of 0.16 mg/kg/min for the first thirty minutes, after a bolus of 0.3 mg/kg; and ketamine by infusion (20-40 μg/kg/min). Blood samples (<2 mL) were collected prior to, during and after the infusion, and on assuming standing position. Anaesthesia was uneventful; with the duration of infusion 31-89 min. Blood propofol concentrations during the infusion ranged between 1.52 and 7.65 μg/mL; pseudo-steady state concentrations 3.64-6.78 μg/mL, and concentrations on assuming standing position 0.75-1.40 μg/mL. Propofol clearance and volume of distribution were 31.4 (SD 6.1) mL/min/kg and 220.7 (132.0) mL/kg, respectively. The propofol analyser allows titration of propofol to a given concentration; and may be useful for anaesthesia in animals where kinetics are unknown; in disease states; and where intercurrent therapies affect propofol disposition., (© 2012 Blackwell Publishing Ltd.)

The objective of this study was to evaluate the plasma pharmacokinetics of ketamine and its active metabolite norketamine administered intravenously at a dose of 0.1 mg/kg together with xylazine (0.05 mg/kg) to control the pain associated with castration in calves. A two-compartment model with an additional metabolite compartment linked to the central compartment was used to simultaneously describe the time-concentration profiles of both ketamine and its major metabolite norketamine. Parameter values estimated from the time-concentration profiles observed in this study were volume of the central compartment (V(c) = 132.82 +/- 68.23 mL/kg), distribution clearance (CL(D) = 15.49 +/- 2.56 mL/min/kg), volume of the peripheral compartment (V(T) = 257.05 +/- 41.65 mL/kg), ketamine clearance by the formation of the norketamine metabolite (CL(2M) = 8.56 +/- 7.37 mL/kg/min) and ketamine clearance by other routes (CL(o) = 16.41 +/- 3.42 mL/kg/min). Previously published data from rats suggest that the metabolite norketamine contributes to the analgesic effect of ketamine, with a potency that is one-third of the parent drug. An understanding of the time-concentration relationships and the disposition of the parent drug and its metabolite is therefore important for a better understanding of the analgesic potential of ketamine in cattle.

Propofol formulated in a mixed medium-chain and long-chain triglycerides emulsion has been recently introduced for clinical use as an alternative to the conventional long-chain triglycerides formulation. This prospective multicentric study evaluated the clinical effectiveness and the complications associated with the use of this new formulation of propofol in dogs. Forty-six Spanish veterinary clinics participated in this study. A total of 541 anaesthesias (118 ASA I, 290 ASA II, 101 ASA III and 32 ASA IV) performed for various diagnostic and therapeutic purposes were evaluated. The anaesthetic protocol was not controlled, with the exception that propofol had to be used at least for induction of anaesthesia. The induction dose of propofol and the incidence of anaesthetic complications throughout the procedure were recorded. A chi-square test compared the incidence of complications according to the maintenance agent used (propofol vs. inhalatory anaesthesia), anaesthetic risk (ASA classification) and the reason for the anaesthesia. The patients premedicated with alpha2 agonists needed lower doses (mean +/- SD, 2.9 +/- 1.3 mg/kg i.v.) than the animals premedicated with phenothiazines (3.9 +/- 1.4 mg/kg i.v.) or benzodiazepines (4.0 +/- 1.4 mg/kg i.v.). The most frequent complications were difficult endotracheal intubation (1.3%), postinduction apnoea (11.3%), cyanosis (0.6%), bradypnoea (2.6%), tachypnoea (2.8%), bradycardia (2%), tachycardia (2.6%), hypotension (0.2%), shock (0.2%), vomiting (4.6%), epileptiform seizures (2.8%), premature awakening (7.4%) and delayed recovery (0.9%). There were no cases of pain on injection or aspiration pneumonia. Three dogs died (0.55%), one during induction and two during recovery from anaesthesia. This study demonstrates that the new formulation of propofol is an useful and effective drug to induce general anaesthesia in dogs.

Six Welsh gelding ponies (weight 246 +/- 6 kg) were premedicated with 0.03 mg/kg of acepromazine intravenously (i.v.) followed by 0.02 mg/kg of detomidine i.v. Anaesthesia was induced with 2 mg/kg of ketamine i.v. Ponies were intubated and lay in left lateral recumbency. On one occasion anaesthesia was maintained for 2 h using 1.2% halothane in oxygen. The same group of ponies were anaesthetized 1 month later using the same induction regime and anaesthesia was maintained with a combination of detomidine, ketamine and guaiphenesin, while the ponies breathed oxygen-enriched air. Electrocardiogram, heart rate, mean arterial blood pressure, cardiac output, respiratory rate, blood gases, temperature, haematocrit, glucose, lactate and cortisol were measured and cardiac index and systemic vascular resistance were calculated in both groups. Beta-endorphin, met-enkephalin, dynorphin, arginine vasopressin (AVP), adrenocorticotrophic hormone (ACTH) and catecholamines were measured in the halothane anaesthesia group only and 11-deoxycortisol during total intravenous anaesthesia (TIVA) only. Cardiorespiratory depression was more marked during halothane anaesthesia. Hyperglycaemia developed in both groups. Lactate and AVP increased during halothane anaesthesia. Cortisol increased during halothane and decreased during TIVA. There were no changes in the other hormones during anaesthesia. Recovery was smooth in both groups. TIVA produced better cardiorespiratory performance and suppressed the endocrine stress response observed during halothane anaesthesia.

The correlation between pharmacokinetics and dynamics of furosemide was investigated in anaesthetized dogs. After intravenous administration (i.v.) of furosemide (5 mg/kg), the plasma concentration declined rapidly with bioexponential decay. The half-life (t1/2 beta) of the late phase of elimination was 0.931 +/- 0.187 h and the apparent volume of distribution at steady state was 0.25 +/- 0.043 l/Kg. The total clearance (Cltot) was 0.435 +/- 0.031 l/h/kg, in which the renal clearance was 0.260 +/- 0.020 (about 60% of Cltot). The change in rate of urinary excretion of furosemide was similar to the plasma concentration decay curve. The diuretic effect of furosemide was accompanied by an extreme increase in the excretion rate of sodium and chloride, but not potassium. The relationships between the diuretic response and the plasma concentration or the urinary excretion rate of furosemide was depicted by sigmoidal dose-response curves in both cases. The half-maximum effect was obtained at 1.5 micrograms/ml of plasma concentration or at 80 micrograms/min of excretion rate of furosemide.

This study was performed to investigate the possible mechanisms underlying prolongation of anesthesia times in sheep caused by the sequential administration of thiamylal and pentobarbital. Sodium thiamylal was injected as an intravenous bolus dose (13.2 mg/kg) followed in 7 min by sodium pentobarbital (14.3 mg/kg) by the same route to seven sheep. Separate studies were conducted for each of the two drugs administered separately to the same animals at the same doses. Mean anesthesia times (to the return of the palpebral reflex) were 7.89 min (thiamylal), 5.39 min (pentobarbital) and 34.1 min (the sequential combination). The kinetic parameters Vd(area), Vd(ss), t 1/2 beta, and ClB for either drug were not affected by the other when given in combination. The t 1/2 alpha was shorter, and the Vc was smaller, for pentobarbital when administered with thiamylal, while there were no changes in thiamylal disposition for the combination regimen. Computer-generated curves, associated with the two-compartment open model showing the fraction of dose in each compartment as a function of time, illustrated that pentobarbital rapidly achieved higher concentrations in the peripheral compartment after prior thiamylal administration. Protein-binding studies showed that this could not be attributed to displacement of pentobarbital from plasma albumin by thiamylal. Calculation of total and free drug concentrations at the time of awakening showed that, when the drugs were combined, the concentration of each drug was less than half of that observed at awakening when they were studied separately. It can be concluded that the prolonged sleeping times associated with the sequential combination of the two agents were not due to an alteration in kinetic parameters of either drug caused by the other, but rather to an additive effect of the subanesthetic concentrations of the two drugs when combined. The fact that sleeping times were supra-additive is attributed to a shift of awakening time from the distribution (alpha) phase, when given independently, to the elimination (beta) phase when administered in combination.

Thiopentone pharmacokinetics and electrocorticogram patterns were studied in a group of six sheep given thiopentone intravenously (20 mg/kg). Plasma concentrations were determined using a high-performance liquid chromatography method. A three-compartment open model was selected to describe the disposition kinetics of thiopentone. The drug had an apparent volume of distribution of 1005 +/- 196 ml/kg; body clearance was 3.5 +/- 0.8 ml/min-kg and the half-life, based on the slope of the terminal portion of the curve, was 196 +/- 64 min. From the electrocorticogram pattern, it seems likely that the highest concentrations in brain occurred between 47 and 217 sec after commencing administration and a brain penetration half-time of 26.5 +/- 2.87 sec was calculated. At the time of awakening (36.6 +/- 6.36 min) 24.1 +/- 6.3% of the dose was located in the central compartment, 12.6 +/- 8.2 was in the shallow peripheral compartment, 38.8 +/- 14.1 was in the deep peripheral compartment and 24.6 +/- 10.3 had been eliminated. Using simulated curves, it appeared that suppression of the shallow peripheral compartment (muscle) did not change the time of awakening; in contrast when elimination-rate constant was decreased, awakening was delayed. It was suggested that the relatively short duration of thiopentone anaesthesia in sheep should be attributed mainly to elimination of the drug by hepatic metabolism and uptake by body fat. This hypothesis, which differs from the widely accepted view that the duration of thiopentone anaesthesia is independent of the rate of hepatic metabolism, is discussed in terms of differences in regional blood flow between sheep and monogastric species.