Pharmacokinetics of propofol infusions, either alone or with ketamine, in sheep premedicated with acepromazine and papaveretum

The pharmacokinetics of propofol were investigated in two groups of five Scottish blackface sheep undergoing surgery for the implantation of subcutaneous tissue pouches. After premedication with acepromazine and papaveretum, anaesthesia was induced with either propofol at 4 mg kg⁻¹ intravenously (group 1) or with a mixture of propofol at 3 mg kg⁻¹ and ketamine at 1 mg kg ⁻¹ intravenously (group 2). Anaesthesia was maintained with a variable infusion rate of either propofol alone (group 1) or propofol and ketamine (group 2). Both regimens produced satisfactory conditions for superficial surgery of the body surface. The mean (SD) duration of anaesthesia was 64·8 (3·1) minutes for group 1 and 60 (0) minutes for group 2; the mean total dose of propofol given to the sheep in group 1 was 801 (84) mg, and the sheep in group 2 received 470 (46) mg of propofol and 267 (30) mg of ketamine. The mean elimination half-life of propofol was 56·6 (13·1) minutes in group 1 and 50·3 (21·4) minutes in group 2; the mean volume of distribution at steady state was 1037 (0480) litre kg⁻¹ in group 1 and 1·515 (0939) litre kg⁻¹ in group 2; the mean body clearance was 85·4 (28·0) ml kg⁻¹ min⁻¹ in group 1 and 1280 (35·0) ml kg⁻¹ min⁻¹ in group 2; the mean residence time corrected for a bolus injection was 12·1 (4·2) minutes in group 1 and 11·9 (6·6) minutes in group 2; for the infusion, the mean residence time was 72·1 (4·2) minutes in group 1 and 69·9 (7·9) minutes in group 2. There were wide variations in the blood propofol concentrations reached in individual sheep by using this standard dosing regimen. All the sheep recovered quickly from anaesthesia; the mean times to extubation, sternal recumbency and standing for the animals in group 1 were 2·8 (0·4) 6·3 (1·2) and 10·9 (1·6) minutes from the end of the infusion, and the times for group 2 were 5·3 (0·9), 11·2 (1·7) and 15·1 (2·2) minutes.     

Pharmacokinetics of ketamine following a short intravenous infusion to isoflurane-anesthetized New Zealand White rabbits (Oryctolagus cuniculus)

ObjectiveTo describe the pharmacokinetics of ketamine following a short intravenous (IV) infusion to isoflurane-anesthetized rabbits.Study designProspective experimental study.AnimalsA total of six adult healthy female New Zealand White rabbits.MethodsAnesthesia was induced with isoflurane in oxygen. Following determination of isoflurane minimum alveolar concentration (MAC), the isoflurane concentration was reduced to 0.75 MAC and ketamine hydrochloride (5 mg kg^–1) was administered IV over 5 minutes. Blood samples were collected before and at 2, 5, 6, 7, 8, 9, 13, 17, 21, 35, 65, 125, 215 and 305 minutes after initiating the ketamine infusion. Samples were processed immediately and the plasma separated and stored at –80 °C until analyzed for ketamine and norketamine concentrations using liquid chromatography–mass spectrometry. Compartment models were fitted to the concentration–time data for ketamine and for ketamine plus norketamine using nonlinear mixed-effects (population) modeling.ResultsA three- and five-compartment model best fitted the plasma concentration–time data for ketamine and for ketamine plus norketamine, respectively. For the ketamine only model, the volume of distribution at steady state (Vss) was 3217 mL kg^–1, metabolic clearance was 88 mL minute^–1 kg^–1 and the terminal half-life was 59 minutes. For the model including both ketamine and norketamine, Vss were 3224 and 2073 mL kg^–1, total metabolic clearance was 107 and 52 mL minute^–1 kg^–1 and terminal half-lives were 52 and 55 minutes for the parent drug and its metabolite, respectively.Conclusions and clinical relevanceThis study characterized the pharmacokinetics of ketamine and norketamine in isoflurane-anesthetized New Zealand White rabbits following short IV infusion. The results obtained herein will be useful to determine ketamine infusion regimens in isoflurane-anesthetized rabbits.     

Effects of a low dose infusion of racemic and S-ketamine on the nociceptive withdrawal reflex in standing ponies

ObjectiveTo investigate the effect of plasma concentrations obtained by a low dose constant rate infusion (CRI) of racemic ketamine or S-ketamine on the nociceptive withdrawal reflex (NWR) in standing ponies.Study designProspective, blinded, cross-over study.AnimalsSix healthy 5-year-old Shetland ponies.MethodsPonies received either 0.6 mg kg⁻¹ racemic ketamine (group RS) or 0.3 mg kg⁻¹ S-ketamine (group S) intravenously (IV), followed by a CRI of 20 μg kg⁻¹minute⁻¹ racemic ketamine (group RS) or 10 μg kg⁻¹minute⁻¹ S-ketamine (group S) for 59 minutes. The NWR was evoked by transcutaneous electrical stimulation of a peripheral nerve before drug administration, 15 and 45 minutes after the start of the bolus injection and 15 minutes after the end of the CRI. Electromyographic responses were recorded and analysed. Arterial blood was collected before stimulation and plasma concentrations of ketamine and norketamine were measured enantioselectively using capillary electrophoresis. Ponies were video recorded and monitored to assess drug effects on behaviour, heart rate (HR), mean arterial blood pressure (MAP) and respiratory rate.ResultsThe NWR was significantly depressed in group RS at plasma concentrations between 20 and 25 ng mL⁻¹ of each enantiomer. In group S, no significant NWR depression could be observed; plasma concentrations of S-ketamine (9–15 ng mL⁻¹) were lower, compared to S-ketamine concentrations in group RS, although this difference was not statistically significant. Minor changes in behaviour, HR and MAP only occurred within the first 5–10 minutes after bolus drug administration in both groups.ConclusionAntinociceptive activity in standing ponies, demonstrated as a depression of the NWR, could only be detected after treatment with racemic ketamine. S-ketamine may have lacked this effect as a result of lower plasma concentrations, a more rapid metabolism or a lower potency of S-ketamine in Equidae so further investigation is necessary.     

Assessment of orocaecal transit time in cats by the breath hydrogen method: the effects of sedation and a comparison of definitions

Oro-caecal transit times (OCTTs) were assessed in 10 healthy adult cats by the lactulose breath hydrogen method with either no sedation (group A), or after the intramuscular administration of three sedative regimens: a combination of acetylpromazine at 0·1 mg kg⁻¹ with buprenorphine at 10 μg kg⁻¹ (group B), ketamine at 5 mg kg⁻¹ with midazolam at 0·1 mg kg⁻¹ (group C), or medetomidine at 50 μg kg⁻¹ (group D). For each test, the OCTT was defined by four methods: a visual assessment, the first maintained 4 ppm increase in hydrogen production, and the first maintained 0·5 ml hr⁻¹ increase in hydrogen production assessed by two cumulative sum methods. Depending on the definition, the median OCTTs of the cats were between 113 and 131·5 minutes in group A, 86·5 and 97·5 minutes in group B, 218 and 235·5 minutes in group C and 86·5 and 97·5 minutes in group D. By two of the definitions, the median OCTTs in group C were significantly longer than in group A (P≤0·037) and approached significance by the other two definitions. The use of sedatives significantly increased the inter-individual variability of the OCTTs, particularly in groups C and D. There were significant differences between the median OCTTs defined by the four different methods, but all the methods were very highly and significantly correlated (r_s≤0·9503, P<0·0001).     

Pharmacokinetics of ketamine and propofol combination administered as ketofol via continuous infusion in cats

Zonca, A., Ravasio, G., Gallo, M., Montesissa, C., Carli, S., Villa, R., Cagnardi, P. Pharmacokinetics of ketamine and propofol combination administered as ketofol via continuous infusion in cats. J. vet. Pharmacol. Therap.  35 , 580–587. The pharmacokinetics of the extemporaneous combination of low doses of ketamine and propofol, known as ‘ketofol’, frequently used for emergency procedures in humans to achieve safe sedation and analgesia was studied in cats. The study was performed to assess propofol, ketamine and norketamine kinetics in six female cats that received ketamine and propofol (1:1 ratio) as a loading dose (2 mg/kg each, IV) followed by a continuous infusion (10 mg/kg/h each, IV, 25 min of length). Blood samples were collected during the infusion period and up to 24 h afterwards. Drug quantification was achieved by HPLC analysis using UV‐visible detection for ketamine and fluorimetric detection for propofol. The pharmacokinetic parameters were deduced by a two‐compartment bolus plus infusion model for propofol and ketamine and a monocompartmental model for norketamine. Additional data were derived by a noncompartmental analysis. Propofol and ketamine were quantifiable in most animals until 24 and 8 h after the end of infusion, respectively. Propofol showed a long elimination half‐life (t_1/2λ2 7.55 ± 9.86 h), whereas ketamine was characterized by shorter half‐life (t_1/2λ2 4 ± 3.4 h) owing to its rapid biotransformation into norketamine. The clinical significance of propofol’s long elimination half‐life and low clearance is negligible when the drug is administered as short‐term and low‐dosage infusion. The concurrent administration of ketamine and propofol in cats did not produce adverse effects although it was not possible to exclude interference in the metabolism.     

Cardiovascular effects of propofol alone and in combination with ketamine for total intravenous anesthesia in healthy cats

This study was designed to compare the cardiovascular effects of equipotent maintenance of anesthetic doses (determined in a previous study) of propofol and propofol/ketamine, administered with and without noxious stimulation. Six healthy adult cats were anesthetized with propofol (loading dose 6.6 mg kg^?1, infusion 0.22 mg kg^?1 minute^?1), and instrumented to allow determination of blood gas and acid–base balance and measurement of blood pressures and cardiac output. The propofol infusion was continued for a further 60 minutes after which measurements were taken prior to and during application of a noxious stimulus. The propofol infusion was decreased to 0.14 mg kg^?1 minute^?1, and ketamine (loading dose 2 mg kg^?1, infusion 23 µg kg minute^?1) was administered. After a further 60 minutes, measurements were again taken prior to and during application of a noxious stimulus. The data were analyzed, using several Repeated Measures anova (first, ketamine/propofol and noxious stimulation were each treated as within‐subject factors; secondly, the levels of these two factors were combined into a single within‐subject factor). Mean arterial pressure, CVP, PAOP, SI, CI, SVRI, PVRI, oxygen delivery index, oxygen consumption index, oxygen utilization ratio, PvO₂, pHa, PaCO₂, bicarbonate concentration, and BD values collected during propofol administration were not changed by addition of ketamine and reduction of propofol concentration or by application of a noxious stimulus under propofol alone. Application of a noxious stimulus under propofol alone did, however, significantly increase HR and PaO₂, and these responses were not blunted by the addition of ketamine. Compared with propofol, administration of ketamine and reduction of propofol concentration significantly increased PAP and venous admixture, and significantly decreased PaO₂. Although application of a noxious stimulus to cats under propofol alone did not significantly change CVP, SI, CI, PVRI, oxygen delivery index, and oxygen consumption index, significant differences were found in these variables between propofol and propofol/ketamine. In conclusion, propofol alone provided cardiopulmonary stability; addition of ketamine did not improve hemodynamics but did decrease oxygenation.     

Total intravenous anesthesia with ketamine–medetomidine–propofol in horses

Propofol is a potentially useful intravenous anesthetic agent for total intravenous anesthesia (TIVA) in horses. The purpose of this study was to compare the anesthetic and cardiorespiratory effects of TIVA following the administration of propofol alone(P–TIVA) and ketamine–medetomidine–propofol (KM–P–TIVA) in adult horses. The carotid artery was translocated to a subcutaneous position during TIVA with P–TIVA (n = 6) or KM–P–TIVA (n = 6). All horses were premedicated with medetomidine [0.005 mg kg^–1, intravenously (IV)]. Anesthesia was induced with midazolam (0.04 mg kg^–1 IV) and ketamine (2.5 mg kg IV). All horses were orotracheally intubated and breathed 100% oxygen. The KM drug combination (ketamine 40 mg mL^–1 and medetomidine 0.05 mg mL^–1) was infused at a rate of 0.025 mL kg^–1 hour^–1. Subsequently, a loading dose of propofol (0.5 mg kg^–1, bolus IV) was administered to all horses; surgical anesthesia (determined by horse response to incision and surgical manipulation, positive response being purposeful or spontaneous movement of limbs or head) was maintained by varying the propofol infusion rate as needed. Arterial blood pressure and HR were also monitored. Both methods of producing TIVA provided excellent general anesthesia for the surgical procedure. Anesthesia time was 115 ± 17 (mean ± SD) and 112 ± 11 minutes in horses anesthetized with KM–P–TIVA and P–TIVA, respectively. The infusion rate of propofol required to maintain surgical anesthesia with KM–P–TIVA was significantly less than for P–TIVA (mean infusion rate of propofol during anesthesia; KM–P–TIVA 0.15 0.02 P–TIVA 0.23 ± 0.03 mg kg^–1 minute^–1, p = 0.004). Apnea occurred in all horses lasting 1–2 minutes and intermittent positive pressure ventilation was started. Cardiovascular function was maintained during both methods of producing TIVA. There were no differences in the time to standing after the cessation of anesthesia (KM–P–TIVA 62 ± 10 minutes versus P–TIVA 87 ± 36 minutes, p = 0.150). The quality of recovery was good in KM–P–TIVA and satisfactory in P–TIVA. KM–P–TIVA and P–TIVA produced clinically useful general anesthesia with minimum cardiovascular depression. Positive pressure ventilation was required to treat respiratory depression. Respiratory depression and apnea must be considered prior to the use of propofol in the horse.     

Minimum infusion rate and hemodynamic effects of propofol, propofol-lidocaine and propofol-lidocaine-ketamine in dogs

ObjectiveTo evaluate the effects of a constant rate infusion (CRI) of lidocaine alone or in combination with ketamine on the minimum infusion rate (MIR) of propofol in dogs and to compare the hemodynamic effects produced by propofol, propofol-lidocaine or propofol-lidocaine-ketamine anesthesia.Study designProspective, randomized cross-over experimental design.AnimalsFourteen adult mixed-breed dogs weighing 15.8 ± 3.5 kg.MethodsEight dogs were anesthetized on different occasions to determine the MIR of propofol alone and propofol in combination with lidocaine (loading dose [LD] 1.5 mg kg^?1, CRI 0.25 mg kg^?1 minute^?1) or lidocaine (LD 1.5 mg kg^?1, CRI 0.25 mg kg^?1 minute^?1) and ketamine (LD 1 mg kg^?1, CRI 0.1 mg kg^?1 minute^?1). In six other dogs, the hemodynamic effects and bispectral index (BIS) were investigated. Each animal received each treatment (propofol, propofol-lidocaine or propofol-lidocaine-ketamine) on the basis of the MIR of propofol determined in the first set of experiments.ResultsMean ± SD MIR of propofol was 0.51 ± 0.08 mg kg^?1 minute^?1. Lidocaine-ketamine significantly decreased the MIR of propofol to 0.31 ± 0.07 mg kg^?1 minute^?1 (37 ± 18% reduction), although lidocaine alone did not (0.42 ± 0.08 mg kg^?1 minute^?1, 18 ± 7% reduction). Hemodynamic effects were similar in all treatments. Compared with the conscious state, in all treatments, heart rate, cardiac index, mean arterial blood pressure, stroke index and oxygen delivery index decreased significantly, whereas systemic vascular resistance index increased. Stroke index was lower in dogs treated with propofol-lidocaine-ketamine at 30 minutes compared with propofol alone. The BIS was lower during anesthesia with propofol-lidocaine-ketamine compared to propofol alone.Conclusions and clinical relevanceLidocaine-ketamine, but not lidocaine alone, reduced the MIR of propofol in dogs. Neither lidocaine nor lidocaine in combination with ketamine attenuated cardiovascular depression produced by a continuous rate infusion of propofol.     

Evaluation of different doses of propofol in xylazine pre-medicated horses

Objective To characterize responses to different doses of propofol in horses pre‐medicated with xylazine. Animals Six adult horses (five females and one male). Methods Each horse was anaesthetized four times with either ketamine or propofol in random order at 1‐week intervals. Horses were pre‐medicated with xylazine (1.1 mg kg^?1 IV over a minute), and 5 minutes later anaesthesia was induced with either ketamine (2.2 mg kg^?1 IV) or propofol (1, 2 and 4 mg kg^?1 IV; low, medium and high doses, respectively). Data were collected continuously (electrocardiogram) or after xylazine administration and at 5, 10 and 15 minutes after anaesthetic induction (arterial pressure, respiratory rate, pH, PaO₂, PaCO₂ and O₂ saturation). Anaesthetic induction and recovery were qualitatively and quantitatively assessed. Results Differences in the quality of anaesthesia were observed; the low dose of propofol resulted in a poorer anaesthetic induction that was insufficient to allow intubation, whereas the high dose produced an excellent quality of induction, free of excitement. Recorded anaesthesia times were similar between propofol at 2 mg kg^?1 and ketamine with prolonged and shorter recovery times after the high and low dose of propofol, respectively (p < 0.05; ketamine, 38 ± 7 minutes; propofol 1 mg kg^?1, 29 ± 4 minutes; propofol 2 mg kg^?1, 37 ± 5 minutes; propofol 4 mg kg^?1, 50 ± 7 minutes). Times to regain sternal and standing position were longest with the highest dose of propofol (32 ± 5 and 39 ± 7 minutes, respectively). Both ketamine and propofol reversed bradycardia, sinoatrial, and atrioventricular blocks produced by xylazine. There were no significant alterations in blood pressure but respiratory rate, and PaO₂ and O₂ saturation were significantly decreased in all groups (p < 0.05). Conclusion The anaesthetic quality produced by the three propofol doses varied; the most desirable effects, which were comparable to those of ketamine, were produced by 2 mg kg^?1 propofol.     

Pharmacokinetics of oxytetracycline after intramuscular administration with lidocaine in sheep, comparison with a conventional formulation

The pharmacokinetic behaviour of oxytetracycline (OTC) was studied in 11 sheep after intravenous and intramuscular administration at a single dosage of 20 mg kg⁻¹ bodyweight. A conventional formulation was injected by the intravenous route and two different preparations were administered by the intramuscular route: a conventional formulation (T-100) and an aqueous solution of OTC with lidocaine (1 per cent) (OTC-Q. The objective was to determine whether there are differences between both formulations in the disposition kinetics of OTC after intramuscular administration to sheep. After intravenous administration of the conventional formulation, plasma oxytetracycline concentrations were best fitted to an open two-compartment model. Mean apparent volume of distribution was 0·77±0·02 litre kg⁻¹ and the harmonic mean half-life was three hours. The OTC transfer process between central and peripheral compartments was fast and that did not influence the elimination process. After intramuscular administrations of both formulations, half-lives were longer than after intravenous administration (mean values of 14·1 and 58·2 hours for T-100 and OTC-L respectively). In both cases, a biphasic absorption, a ‘flip-flop’ model and a complete bioavailability were found. OTC-L provided therapeutic plasma concentrations over 0·5 μg ml⁻¹ (the minimum inhibitory concentration for most susceptible pathogens) for a longer period of time than T-100 (72 hours compared with 36 or 48 hours).     

A comparison of the effects of two different doses of ketamine used for co-induction of anaesthesia with a target-controlled infusion of propofol in dogs

ObjectiveTo assess the cardiorespiratory and hypnotic-sparing effects of ketamine co-induction with target-controlled infusion of propofol in dogs.Study designProspective, randomized, blinded clinical study.AnimalsNinety healthy dogs (ASA grades I/II). Mean body mass 30.5 ± SD 8.6 kg and mean age 4.2 ± 2.6 years.MethodsAll dogs received pre-anaesthetic medication with acepromazine (0.03 mg kg^?1) and morphine (0.2 mg kg^?1) administered intramuscularly 30 minutes prior to induction of anaesthesia. Heart rate and respiratory rate were recorded prior to pre-medication. Animals were allocated into three different groups: Group 1 (control) received 0.9% NaCl, group 2, 0.25 mg kg^?1 ketamine and group 3, 0.5 mg kg^?1 ketamine, intravenously 1 minute prior to induction of anaesthesia, which was accomplished using a propofol target-controlled infusion system. The target propofol concentration was gradually increased until endotracheal intubation was possible and the target concentration at intubation was recorded. Heart rate, respiratory rate and noninvasive blood pressure were recorded immediately prior to induction, at successful intubation and at 3 and 5 minutes post-intubation. The quality of induction was graded according to the amount of muscle twitching and paddling observed. Data were analysed using a combination of chi-squared tests, Fisher's exact tests, Kruskal–Wallis, and anova with significance assumed at p< 0.05.ResultsThere were no significant differences between groups in the blood propofol targets required to achieve endotracheal intubation, nor with respect to heart rate, noninvasive blood pressure or quality of induction. Compared with the other groups, the incidence of post-induction apnoea was significantly higher in group 3, but despite this dogs in this group had higher respiratory rates overall.Conclusions and clinical relevanceUnder the conditions of this study, ketamine does not seem to be a useful agent for co-induction of anaesthesia with propofol in dogs.     

Behavioral responses following eight anesthetic induction protocols in horses

Objective To compare behavioral characteristics of induction and recovery in horses anesthetized with eight anesthetic drug protocols. Study design Randomized prospective experimental study. Animals Eight horses, 5.5 ± 2.4 years (mean ± SD) of age, and weighing 505 ± 31 kg. Methods After xylazine pre‐medication, each of eight horses was anesthetized on four occasions using one of eight different anesthetic induction protocols which incorporated various combinations of ketamine (KET), propofol (PRO), and thiopental (THIO): THIO 8 mg kg^?1; THIO 6 mg kg^?1 + PRO 0.5 mg kg^?1; THIO 4 mg kg^?1 + PRO 1 mg kg^?1; THIO 2 mg kg^?1 + PRO 1.5 mg kg^?1; KET 2 mg kg^?1; KET 1.5 mg kg^?1 + PRO 0.5 mg kg^?1; KET 1 mg kg^?1 + PRO 1 mg kg^?1; KET 0.5 mg kg^?1 + PRO 1.5 mg kg^?1. Quality of induction and recovery were scored from 1 (poor) to 5 (excellent), and time taken to achieve lateral recumbency, first movement, sternal recumbency, and standing were evaluated. Results Time taken to achieve lateral recumbency after drug administration differed significantly (p < 0.0001) among the various combinations, being shortest in horses receiving THIO‐8 (mean ± SD, 0.5 ± 0.3 minutes) and longest in horses receiving KET‐2 (1.4 ± 0.2 minutes). The best scores for induction quality were associated with KET‐1.5 + PRO‐0.5, and the worst scores for induction quality were associated with KET‐2, although the difference was not significant. Time to first movement varied significantly among drug protocols (p = 0.0133), being shortest in horses receiving KET‐2 (12.7 ± 3.6 minutes) and longest in horses receiving THIO‐8 (29.9 ± 1.5 minutes). Horses receiving THIO‐8 made the greatest number of attempts to attain sternal posture (6.5 ± 4.7) and to stand (1.6 ± 0.8). Horses in the THIO‐8 treatment also received the poorest recovery scores (3.3 ± 1.0 and 3.0 ± 0.7 for sternal and standing postures, respectively). The best recovery scores were associated with combinations comprised mainly of propofol. Conclusions Combining propofol with either ketamine or thiopental modifies behaviors associated with use of the individual drugs. Clinical relevance Quality of early anesthesia recovery in horses may be improved by some combinations of propofol with either thiopental or ketamine.     

Influence of calcium chloride on the cardio‐respiratory effects of a bolus of enoximone in isoflurane anaesthetized ponies

ObejctiveTo investigate the influence of calcium chloride (CaCl₂) on the cardio–respiratory effects of enoximone in isoflurane anaesthetized ponies.Study designProspective consecutive experimental trial.AnimalsSix healthy ponies, weighing 287 ± 55 kg were included in this study.MethodsAfter sedation (romifidine, 80 μg kg^?1), anaesthesia was induced with midazolam (0.06 mg kg^?1) and ketamine (2.2 mg kg^?1) and maintained with isoflurane in oxygen. The ponies’ lungs were ventilated to maintain normocapnia. After 90 minutes, a bolus of enoximone (0.5 mg kg^?1) was administered, followed by a CaCl₂ infusion (0.5 mg kg^?1 minute^?1 over 10 minutes) (treatment EC). Sodium, potassium, ionized and total calcium concentrations, cardiovascular variables and blood–gases were measured in the 120 minutes after treatment. Using a mixed model anova, the results were compared to those of a previous report [Vet Anaesth Analg, 34 (2007) 416], evaluating the effects of 0.5 mg kg^?1 enoximone in the same ponies and under identical circumstances (treatment E). Both an overall comparison and comparisons at specific time points after treatment were performed (α = 0.05).ResultsAlthough ionized and total calcium concentrations were higher during treatment EC, the cardio–respiratory effects of enoximone were comparable for both treatments. A small but significant difference in packed cell volume was detected.Conclusions and clinical relevanceCalcium chloride did not enhance the effects of enoximone in normocalcaemic anaesthetized ponies.     

Propofol anaesthesia for surgery in late gestation pony mares

Objective To characterize propofol anaesthesia in pregnant ponies. Animals Fourteen pony mares, at 256 ± 49 days gestation, undergoing abdominal surgery to implant fetal and maternal vascular catheters. Materials and methods Pre‐anaesthetic medication with intravenous (IV) acepromazine (20 µg kg^?1), butorphanol (20 µg kg^?1) and detomidine (10 µg kg^?1) was given 30 minutes before induction of anaesthesia with detomidine (10 µg kg^?1) and ketamine (2 mg kg^?1) IV Maternal arterial blood pressure was recorded (facial artery) throughout anaesthesia. Arterial blood gas values and plasma concentrations of glucose, lactate, cortisol and propofol were measured at 20‐minute intervals. Anaesthesia was maintained with propofol infused initially at 200 µg kg^?1 minute^?1, and at 130–180 µg kg^?1 minute^?1 after 60 minutes, ventilation was controlled with oxygen and nitrous oxide to maintain PaCO₂ between 5.0 and 6.0 kPa (37.6 and 45.1 mm Hg) and PaO₂ between 13.3 and 20.0 kPa (100 and 150.4 mm Hg). During anaesthesia flunixin (1 mg kg^?1), procaine penicillin (6 IU) and butorphanol 80 µg kg^?1 were given. Lactated Ringer's solution was infused at 10 mL kg^?1 hour^?1. Simultaneous fetal and maternal blood samples were withdrawn at 85–95 minutes. Recovery from anaesthesia was assisted. Results Arterial blood gas values remained within intended limits. Plasma propofol levels stabilized after 20 minutes (range 3.5–9.1 µg kg^?1); disposition estimates were clearance 6.13 ± 1.51 L minute^?1 (mean ± SD) and volume of distribution 117.1 ± 38.9 L (mean ± SD). Plasma cortisol increased from 193 ± 43 nmol L^?1 before anaesthesia to 421 ± 96 nmol L^?1 60 minutes after anaesthesia. Surgical conditions were excellent. Fetal umbilical venous pH, PO₂ and PCO₂ were 7.35 ± 0.04, 6.5 ± 0.5 kPa (49 ± 4 mm Hg) and 6.9 ± 0.5 kPa (52 ± 4 mm Hg); fetal arterial pH, PO₂ and PCO₂ were 7.29 ± 0.06, 3.3 ± 0.8 kPa (25 ± 6 mm Hg) and 8.7 ± 0.9 kPa (65 ± 7 mm Hg), respectively. Recovery to standing occurred at 46 ± 17 minutes, and was generally smooth. Ponies regained normal behaviour patterns immediately. Conclusions and clinical relevance Propofol anaesthesia was smooth with satisfactory cardiovascular function in both mare and fetus; we believe this to be a suitable anaesthetic technique for pregnant ponies.     

Propofol–medetomidine–ketamine total intravenous anaesthesia in thiafentanil–medetomidine-immobilized impala (Aepyceros melampus)

Objective

To characterize a propofol–medetomidine-ketamine total intravenous anaesthetic in impala (Aepyceros melampus).

Plasma levels of a low-dose constant-rate-infusion of ketamine and its effect on single and repeated nociceptive stimuli in conscious dogs

This study quantitatively investigated the analgesic action of a low-dose constant-rate-infusion (CRI) of racemic ketamine (as a 0.5 mg kg⁻¹ bolus and at a dose rate of 10 μg kg⁻¹ min⁻¹) in conscious dogs using a nociceptive withdrawal reflex (NWR) and with enantioselective measurement of plasma levels of ketamine and norketamine. Withdrawal reflexes evoked by transcutaneous single and repeated electrical stimulation (10 pulses, 5 Hz) of the digital plantar nerve were recorded from the biceps femoris muscle using surface electromyography.Ketamine did not affect NWR thresholds or the recruitment curves after a single nociceptive stimulation. Temporal summation (as evaluated by repeated stimuli) and the evoked behavioural response scores were however reduced compared to baseline demonstrating the antinociceptive activity of ketamine correlated with the peak plasma concentrations. Thereafter the plasma levels at pseudo-steady-state did not modulate temporal summation. Based on these experimental findings low-dose ketamine CRI cannot be recommended for use as a sole analgesic in the dog.     

Cardiopulmonary effects and recovery characteristics of horses anesthetized with xylazine–ketamine with midazolam or propofol

Objective

To evaluate cardiopulmonary and recovery characteristics of horses administered total intravenous anesthesia (TIVA) with xylazine and ketamine combined with midazolam or propofol.

Pharmacokinetics and pharmacodynamics of l-methadone in isoflurane-anaesthetized and mechanically ventilated ponies

ObjectiveTo evaluate the pharmacokinetics and selected pharmacodynamic effects of a commercially available l-methadone/fenpipramide combination administered to isoflurane anaesthetized ponies.Study designProspective single-group interventional study.AnimalsA group of six healthy adult research ponies (four mares, two geldings).MethodsPonies were sedated with intravenous (IV) detomidine (0.02 mg kg^–1) and butorphanol (0.01 mg kg^–1) for an unrelated study. Additional IV detomidine (0.004 mg kg^–1) was administered 85 minutes later, followed by induction of anaesthesia using IV diazepam (0.05 mg kg^–1) and ketamine (2.2 mg kg^–1). Anaesthesia was maintained with isoflurane in oxygen. Baseline readings were taken after 15 minutes of stable isoflurane anaesthesia. l-Methadone (0.25 mg kg^–1) with fenpipramide (0.0125 mg kg^–1) was then administered IV. Selected cardiorespiratory variables were recorded every 10 minutes and compared to baseline using the Wilcoxon signed-rank test. Adverse events were recorded. Arterial plasma samples for analysis of plasma concentrations and pharmacokinetics of l-methadone were collected throughout anaesthesia at predetermined time points. Data are shown as mean ± standard deviation or median and interquartile range (p < 0.05).ResultsPlasma concentrations of l-methadone showed a rapid initial distribution phase followed by a slower elimination phase which is best described with a two-compartment model. The terminal half-life was 44.3 ± 18.0 minutes, volume of distribution 0.43 ± 0.12 L kg^–1 and plasma clearance 7.77 ± 1.98 mL minute^–1 kg^–1. Mean arterial blood pressure increased from 85 (±16) at baseline to 100 (±26) 10 minutes after l-methadone/fenpipramide administration (p = 0.031). Heart rate remained constant. In two ponies fasciculations occurred at different time points after l-methadone administration.Conclusions and clinical relevanceAdministration of a l-methadone/fenpipramide combination to isoflurane anaesthetized ponies led to a transient increase in blood pressure without concurrent increases in heart rate. Pharmacokinetics of l-methadone were similar to those reported for conscious horses administered racemic methadone.     

Penetration of amoxycillin into the respiratory tract tissues and secretions in pigs

The pharmacokinetic properties of amoxycillin, and its penetration into respiratory tract tissues (alveolar macrophages, bronchial secretions, bronchial mucosa, lung tissue and lymph nodes), were determined in 20 healthy female pigs weighing 29 to 55 kg, after a single intravenous dose of 8·6 mg kg ⁻¹ bodyweight. Following intravenous administration the plasma concentration-time curves were best described by a three-compartment open model. The elimination half-life and the mean residence time were 2·5 and 1.4 hours, respectively. The volume of distribution at steady state was 0·52 litres kg ⁻¹, and the body clearance was 0·40 litres hour⁻¹ kg⁻¹. In all structures (except alveolar macrophages) amoxycillin concentration peaked at the first sampling point, one hour after drug administration. The tissue to plasma ratio (based on AUC values) were 0·33 for bronchial secretions, 0·37 for bronchial mucosa, 0·39 for lung tissue and 0·68 for lymph nodes. Traces of amoxycillin were found in alveolar macrophages, but the concentrations were below the limit of quantification. The concentration of amoxycillin in secretions and tissue decreased by a slower rate than the concentration in plasma, resulting in increasing secretion- and tissue-to-plasma concentration ratios.