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Although morphine has demonstrated antinociceptive effects in horses, its administration has been associated with dose-dependent adverse effects. In humans and rats, part of the analgesic effect of morphine has been attributed to the active metabolite, morphine-6-glucuronide (M6G). Although morphine can cause several undesirable effects, M6G has a more favorable safety profile. The objective of this study was to characterize the pharmacokinetics, tissue distribution, and behavioral and select physiological effects of M6G following intravenous administration to a small group of horses. In Part 1 of the study, 3 horses received a single intravenous administration of saline, 0.5 mg/kg body weight (BW) M6G, or 0.5 mg/kg BW morphine in a 3-way crossover design. Blood samples were collected up to 96 hours post-administration, concentrations of drug and metabolites measured, and pharmacokinetics determined. Behavioral and physiological effects were then recorded. In Part 2 of the study, 2 horses scheduled to be euthanized for other reasons, were administered 0.5 mg/kg BW M6G. Blood, cerebrospinal fluid (CSF), and various tissue samples were collected post-administration and concentrations of drug were determined. The clearance of M6G was more rapid and the volume of distribution at steady state was smaller for M6G compared to morphine. A reaction characterized by head shaking, pawing, and slight ataxia was observed immediately following administration of both morphine and M6G to horses. After M6G administration, these behaviors subsided rapidly and were followed by a longer period of sedation. Following administration, M6G was detected in the kidney, liver, CSF, and regions of the brain. Results of this study encourage further investigation of M6G in order to assess its clinical feasibility as an analgesic in horses., (Copyright and/or publishing rights held by the Canadian Veterinary Medical Association.)

Objective: To evaluate the effects of combined infusions of vatinoxan and dexmedetomidine on inhalant anesthetic requirement and cardiopulmonary function in dogs., Study Design: Prospective experimental study., Methods: A total of six Beagle dogs were anesthetized to determine sevoflurane minimum alveolar concentration (MAC) prior to and after an intravenous (IV) dose (loading, then continuous infusion) of dexmedetomidine (4.5 μg kg -1 hour -1 ) and after two IV doses of vatinoxan in sequence (90 and 180 μg kg -1 hour -1 ). Blood was collected for plasma dexmedetomidine and vatinoxan concentrations. During a separate anesthesia, cardiac output (CO) was measured under equivalent MAC conditions of sevoflurane and dexmedetomidine, and then with each added dose of vatinoxan. For each treatment, cardiovascular variables were measured with spontaneous and controlled ventilation. Repeated measures analyses were performed for each response variable; for all analyses, p < 0.05 was considered significant., Results: Dexmedetomidine reduced sevoflurane MAC by 67% (0.64 ± 0.1%), mean ± standard deviation in dogs. The addition of vatinoxan attenuated this to 57% (0.81 ± 0.1%) and 43% (1.1 ± 0.1%) with low and high doses, respectively, and caused a reduction in plasma dexmedetomidine concentrations. Heart rate and CO decreased while systemic vascular resistance increased with dexmedetomidine regardless of ventilation mode. The co-administration of vatinoxan dose-dependently modified these effects such that cardiovascular variables approached baseline., Conclusions and Clinical Relevance: IV infusions of 90 and 180 μg kg -1 hour -1 of vatinoxan combined with 4.5 μg kg -1 hour -1 dexmedetomidine provide a meaningful reduction in sevoflurane requirement in dogs. Although sevoflurane MAC-sparing properties of dexmedetomidine in dogs are attenuated by vatinoxan, the cardiovascular function is improved. Doses of vatinoxan >180 μg kg -1 hour -1 might improve cardiovascular function further in combination with this dose of dexmedetomidine, but beneficial effects on anesthesia plane and recovery quality may be lost., (Copyright © 2021 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

Although controversial, due to its reported effectiveness in attenuating bleeding associated with exercise-induced pulmonary hemorrhage (EIPH), furosemide is currently a permitted race day medication in most North American racing jurisdictions. The objective of this study was to assess the efficacy of furosemide in reducing the presence and severity of EIPH when administered 24 hr prior to strenuous treadmill exercise. Eight exercised Thoroughbred horses received saline or 250 mg of furosemide either 4 or 24 hr prior to high-speed treadmill exercise in a balanced 3-way cross-over design. Blood samples were collected for determination of furosemide, lactate, hemoglobin, blood gas, and electrolyte concentrations. Heart rate and pulmonary arterial pressure were measured throughout the run and endoscopic examination and bronchoalveolar lavage (BAL) performed. Horses were assigned an EIPH score and the number of red blood cells in BAL fluid determined. Although not significantly different, endoscopic EIPH scores were lower in the 4-hr versus the 24-hr and saline groups. RBC counts were not significantly different between the treatment groups. Pulmonary arterial pressures were significantly increased at higher speeds; however, there were no significant differences between dose groups when controlling for speed. A small sample size and unknown bleeding history warrant a larger-scale study., (© 2020 John Wiley & Sons Ltd.)

Background: Meperidine is a synthetic opioid that belongs to the phenylpiperidine class and is a weak mu receptor agonist. In horses there are a limited number of published studies describing the analgesic effects of systemically administered meperidine in horses. The objective of this study was to describe the pharmacokinetics, behavioral and physiologic effects and effect on thermal threshold of three doses of intravenously administered meperidine to horses. Eight University owned horses (four mares and four geldings, aged 3-8 years were studied using a randomized balanced 4-way cross-over design. Horses received a single intravenous dose of saline, 0.25, 0.5 and 1.0 mg/kg meperidine. Blood was collected before administration and at various time points until 96 hours post administration. Plasma and urine samples were analyzed for meperidine and normeperidine by liquid chromatography-mass spectrometry and plasma pharmacokinetics determined. Behavioral and physiologic data (continuous heart rate, step counts, packed cell volume, total plasma protein and gastrointestinal sounds) were collected at baseline through 6 hours post administration. The effect of meperidine administration on thermal nociception was determined and thermal excursion calculated., Results: Meperidine was rapidly converted to the metabolite normeperidine. The volume of distribution at steady state and systemic clearance (mean ± SD) ranged from 0.829 ± 0.138-1.58 ± 0.280 L/kg and 18.0 ± 1.4-22.8 ± 3.60 mL/min/kg, respectively for 0.5-1.0 mg/kg doses. Adverse effects included increased dose-dependent central nervous excitation, heart rate and cutaneous reactions. Significant effects on thermal nociception were short lived (up to 45 minutes at 0.5 mg/kg and 15 minutes at 1.0 mg/kg)., Conclusions: Results of the current study do not support routine clinical use of IV meperidine at a dose of 1 mg/kg to horses. Administration of 0.5 mg/kg may provide short-term analgesia, however, the associated inconsistent and/or short-term adverse effects suggest that its use as a sole agent at this dose, at best, must be cautiously considered.

The objective of the current study was to describe and characterize the pharmacokinetics and selected pharmacodynamic effects of morphine and its two major metabolites in horses following several doses of morphine. A total of ten horses were administered a single intravenous dose of morphine: 0.05, 0.1, 0.2, or 0.5 mg/kg, or saline control. Blood samples were collected up to 72 hr, analyzed for morphine, and metabolites by LC/MS/MS, and pharmacokinetic parameters were determined. Step count, heart rate and rhythm, gastrointestinal borborygmi, fecal output, packed cell volume, and total protein were also assessed. Morphine-3 glucuronide (M3G) was the predominant metabolite detected, with concentrations exceeding those of morphine-6 glucuronide (M6G) at all time points. Maximal concentrations of M3G and M6G ranged from 55.1 to 504 and 6.2 to 28.4 ng/ml, respectively, across dose groups. The initial assessment of morphine pharmacokinetics was done using noncompartmental analysis (NCA). The volume of distribution at steady-state and systemic clearance ranged from 9.40 to 16.9 L/kg and 23.3 to 32.4 ml min -1  kg -1 , respectively. Adverse effects included signs of decreased gastrointestinal motility and increased central nervous excitation. There was a correlation between increasing doses of morphine, increases in M3G concentrations, and adverse effects. Findings from this study support direct administration of purified M3G and M6G to horses to better characterize the pharmacokinetics of morphine and its metabolites and to assess pharmacodynamic activity of these metabolites., (© 2019 John Wiley & Sons Ltd.)

OBJECTIVE To measure concentrations of trazodone and its major metabolite in plasma and urine after administration to healthy horses and concurrently assess selected physiologic and behavioral effects of the drug. ANIMALS 11 Thoroughbred horses enrolled in a fitness training program. PROCEDURES In a pilot investigation, 4 horses received trazodone IV (n = 2) or orally (2) to select a dose for the full study; 1 horse received a vehicle control treatment IV. For the full study, trazodone was initially administered IV (1.5 mg/kg) to 6 horses and subsequently given orally (4 mg/kg), with a 5-week washout period between treatments. Blood and urine samples were collected prior to drug administration and at multiple time points up to 48 hours afterward. Samples were analyzed for trazodone and metabolite concentrations, and pharmacokinetic parameters were determined; plasma drug concentrations following IV administration best fit a 3-compartment model. Behavioral and physiologic effects were assessed. RESULTS After IV administration, total clearance of trazodone was 6.85 ± 2.80 mL/min/kg, volume of distribution at steady state was 1.06 ± 0.07 L/kg, and elimination half-life was 8.58 ± 1.88 hours. Terminal phase half-life was 7.11 ± 1.70 hours after oral administration. Horses had signs of aggression and excitation, tremors, and ataxia at the highest IV dose (2 mg/kg) in the pilot investigation. After IV drug administration in the full study (1.5 mg/kg), horses were ataxic and had tremors; sedation was evident after oral administration. CONCLUSIONS AND CLINICAL RELEVANCE Administration of trazodone to horses elicited a wide range of effects. Additional study is warranted before clinical use of trazodone in horses can be recommended.

Objective: To determine the effects of low and high dose infusions of dexmedetomidine and a peripheral α 2 -adrenoceptor antagonist, MK-467, on sevoflurane minimum alveolar concentration (MAC) in dogs., Study Design: Crossover experimental study., Animals: Six healthy, adult Beagle dogs weighing 12.6±0.9 kg (mean±standard deviation)., Methods: Dogs were anesthetized with sevoflurane in oxygen. After a 60-minute instrumentation and equilibration period, the MAC of sevoflurane was determined in triplicate using the tail clamp technique. PaCO 2 and temperature were maintained at 40±5 mmHg (5.3±0.7 kPa) and 38±0.5 ºC, respectively. After baseline MAC determination, dogs were administered two incremental loading and infusion doses of either dexmedetomidine (1.5 μg kg -1 then 1.5 μg kg -1  hour -1 and 4.5 μg kg -1 then 4.5 μg kg -1  hour -1 ) or MK-467 (90 μg kg -1 then 90 μg kg -1  hour -1 and 180 μg kg -1 then 180 μg kg -1  hour -1 ); loading doses were administered over 10 minutes. MAC was redetermined in duplicate starting 30 minutes after the start of drug administration at each dose. End-tidal sevoflurane concentrations were corrected for calibration and adjusted to sea level. A repeated-measures analysis was performed and comparisons between doses were conducted using Tukey's method. Statistical significance was considered at p<0.05., Results: Sevoflurane MAC decreased significantly from 1.86±0.3% to 1.04±0.1% and 0.57±0.1% with incremental doses of dexmedetomidine. Sevoflurane MAC significantly increased with high dose MK-467, from 1.93±0.3% to 2.29±0.5%., Conclusions and Clinical Relevance: Dexmedetomidine caused a dose-dependent decrease in sevoflurane MAC, whereas MK-467 caused an increase in MAC at the higher infusion dose. Further studies evaluating the combined effects of dexmedetomidine and MK-467 on MAC and cardiovascular function may elucidate potential benefits of the addition of a peripheral α 2 -adrenergic antagonist to inhalation anesthesia in dogs., (Copyright © 2017 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

Background: The effects of anesthesia on the equine electroencephalogram (EEG) after administration of various drugs for sedation, induction, and maintenance are known, but not that the effect of inhaled anesthetics alone for EEG recording., Objective: To determine the effects of isoflurane and halothane, administered as single agents at multiple levels, on the EEG and quantitative EEG (qEEG) of normal horses., Animals: Six healthy horses., Methods: Prospective study. Digital EEG with video and quantitative EEG (qEEG) were recorded after the administration of one of the 2 anesthetics, isoflurane or halothane, at 3 alveolar doses (1.2, 1.4 and 1.6 MAC). Segments of EEG during controlled ventilation (CV), spontaneous ventilation (SV), and with peroneal nerve stimulation (ST) at each MAC multiple for each anesthetic were selected, analyzed, and compared. Multiple non-EEG measurements were also recorded., Results: Specific raw EEG findings were indicative of changes in the depth of anesthesia. However, there was considerable variability in EEG between horses at identical MAC multiples/conditions and within individual horses over segments of a given epoch. Statistical significance for qEEG variables differed between anesthetics with bispectral index (BIS) CV MAC and 95% spectral edge frequency (SEF95) SV MAC differences in isoflurane only and median frequency (MED) differences in SV MAC with halothane only., Conclusions and Clinical Importance: Unprocessed EEG features (background and transients) appear to be beneficial for monitoring the depth of a particular anesthetic, but offer little advantage over the use of changes in mean arterial pressure for this purpose., (Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Reasons for Performing Study: Tramadol is an analgesic agent used in man and a number of veterinary species. The pharmacokinetics and behavioural effects of tramadol and its active metabolite have been described in mature horses, but not in young foals., Objectives: To characterise the pharmacokinetics, metabolism and some induced behavioural and physiological responses following i.v. tramadol administration in the same group of foals on 4 different occasions, from a few days after birth to age 43 days., Study Design: Experimental., Methods: Tramadol was administered i.v. (3 mg/kg bwt) to a group of 8 foals on 4 separate occasions at ages 6–8, 13–15, 20–22 and 40–43 days. Blood samples were collected prior to administration and at multiple times until 48 h post administration. Blood samples were analysed for tramadol and metabolite concentrations and pharmacokinetics determined at each age. Behavioural and physiological effects were also assessed., Results: The average volume of distribution was 5.10, 4.63, 4.02 and 3.84 l/kg bwt and clearance 3.44, 3.08, 3.14 and 2.69 l/h/kg bwt when foals were aged 6–8, 13–15, 20–22 and 40–43 days, respectively. There was not a significant difference in the elimination half-life between age groups (1.52, 1.73, 1.13 and 1.51 for ages 6–8, 13–15, 20–22 and 40–43 days, respectively). The metabolites produced were the same as in mature horses; however, glucuronidation capability, appeared to increase with increasing age. Tramadol administration was well tolerated at all ages studied with sedation noted in the 3 older age groups., Conclusions: Tramadol appears to be consistently well tolerated following i.v. administration of 3 mg/kg bwt to foals ranging in age from 1 to 6 weeks. Although analgesic concentrations in foals have yet to be established, the results of this study support further study of tramadol for clinical use in foals.

Uterine vascular elastosis in mares is characterized by degeneration of uterine vasculature through thickening of the elastin layers. Factors commonly associated with this degeneration include age, parity, and chronic uterine endometritis. Affected mares have also been shown to exhibit decreases in uterine blood flow and perfusion of the uterus. Due to the increased thickness of the elastin layers, we hypothesize that vasodilatation of the uterine vasculature is also impaired. To test the functionality of these vessels, we evaluated the vasodilatory effects of estradiol on the uterine vascular bed in mares with normal vasculature and mares with severe elastosis. Both groups were tested in estrus and diestrus. Fluorescent microspheres were used to determine basal blood perfusion, followed by the intravenous administration of 1.0 μg/kg of 17β-estradiol. After 90 min, perfusion was measured once again to determine the vascular response to estradiol. Control mares in estrus displayed a significant increase in total uterine blood flow after the administration of estradiol when compared to baseline levels. No other group had a significant increase in total blood flow and perfusion after estradiol administration. The administration of estradiol in control mares induced regional increases in perfusion in the uterine horns and uterine body during estrus and only in the uterine horns during diestrus. Mares affected by elastosis exhibited no regional differences in perfusion levels post-estradiol administration. The difference in the vasodilatory response induced by estradiol between reproductively healthy mares and mares affected with elastosis indicates that the functionality of the affected vessels is compromised., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Previous study of the diagnostic validity of electroencephalography (EEG) to detect abnormalities in equine cerebral cortical function relied on the administration of various drugs for sedation, induction, and maintenance of general anesthesia but used identical criteria to interpret recordings., Objectives: To determine the effects of 2 inhalation anesthetics on the EEG of healthy horses., Animals: Six healthy horses., Methods: Prospective study. After the sole administration of one of either isoflurane or halothane at 1.2, 1.4, and 1.6 times the minimum alveolar concentration, EEG was recorded during controlled ventilation, spontaneous ventilation, and nerve stimulation., Results: Burst suppression was observed with isoflurane, along with EEG events that resembled epileptiform discharges. Halothane results were variable between horses, with epileptiform-like discharges and bursts of theta, alpha, and beta recorded intermittently. One horse died and 2 were euthanized as the result of anesthesia-related complications., Conclusions and Clinical Importance: The results of this study indicate that the effects of halothane and isoflurane on EEG activity in the normal horse can be quite variable, even when used in the absence of other drugs. It is recommended that equine EEG be performed without the use of these inhalation anesthetics and that general anesthesia be induced and maintained by other contemporary means., (Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Reasons for Performing Study: Foal responses to a broader range of plasma fentanyl concentrations than currently reported are desirable to support (or not) clinical use., Objectives: To describe fentanyl plasma concentrations following an escalating i.v. fentanyl dosing schedule in foals aged 5-13 days and describe selected, associated dose- and time-related behavioural and physiological responses to plasma fentanyl concentration., Study Design: Experimental., Methods: Fentanyl was administered i.v. in an escalating fashion (2, 4, 8, 16 and 32 μg/kg bwt) at 10-min intervals. Blood samples were collected before and at selected times until 24 h post administration. Blood samples were analysed for fentanyl and metabolite concentrations and correlated with behavioural and physiological observations and selected blood analytes., Results: Foals mostly appeared to be unaffected following 2 μg/kg bwt (1.09 ± 0.41 μg/l; average maximal plasma concentration) of fentanyl, but 6 of the 8 foals appeared to be sedated following 4 μg/kg bwt (3.07 ± 1.11 μg/l). Ataxia with increased locomotor activity, muscle rigidity and head pressing posture was observed in many foals at 8 (7.24 ± 3.22 μg/l) and 16 μg/kg bwt (17.4 ± 5.67 μg/l). All foals were heavily sedated after 32 μg/kg bwt (34.5 ± 10.3 μg/l); 3 of the 8 foals became recumbent. The average (± s.d.) terminal half-life following administration of the final dose was 44.2 ± 9.85 min., Conclusions: Behavioural and physiological responses to i.v. fentanyl in young foals are dose related. As with mature horses, the window of fentanyl plasma concentrations related to possible clinically desirable actions appears relatively narrow., (© 2014 EVJ Ltd.)

In the uterus of the mare, data obtained using transrectal Doppler ultrasonography indicate that uterine blood flow (UBF) is dynamic and changes throughout the estrous cycle. Degenerative lesions in the uterus are associated with subfertility and infertility. Among these lesions, vascular elastosis has been reported in aged, multiparous, and infertile mares. Angiosis of the uterine vasculature could potentially compromise UBF. The objectives of this experiment are to determine levels of UBF and perfusion of reproductively healthy mares and compare them to levels of subfertile/infertile mares affected by uterine vascular elastosis. Twenty mares were classified on the basis of degree of vascular degeneration and stage of cycle. A fluorescent microsphere technique was used to measure reproductive organ perfusion, where microspheres were injected into the left ventricle of the heart and became trapped in capillary beds in proportion to blood flow and tissue perfusion. The reproductive tract was removed, sectioned, and the fluorescent intensity evaluated to measure blood flow and perfusion. Additionally, full-thickness samples of the uterine wall were examined postmortem to further assess the degree of vascular degeneration in all layers of uterine wall. The mean value of uterine perfusion for the control mares during estrus (n = 5) was higher (P < 0.01) than that during diestrus (n = 5); 17.6 and 11.9 mL/min/100g, respectively. For the subfertile/infertile mares, the mean value of tissue perfusion was not different (P > 0.05) during estrus (n = 5) and diestrus (n = 5); 5.9 and 7.2 mL/min/100g, respectively. Uterine perfusion in subfertile/infertile mares affected by elastosis was lower than that of control mares during both estrus (P < 0.01) and diestrus (P < 0.01). The differences in baseline levels of perfusion between the control and elastosis groups indicate that elastosis of the uterine vasculature is associated with decreased uterine perfusion during both phases of the estrous cycle. In the uterus, a compromise in UBF could have implications in endometrial glandular development, postbreeding endometritis, uterine clearance, development of the conceptus, and overall fertility., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The aim of the study was to describe the pharmacokinetics and selected pharmacodynamics of intravenous dexmedetomidine in horses. Eight adult horses received 5 μg/kg dexmedetomidine IV. Blood samples were collected before and for 10 h after drug administration to determine dexmedetomidine plasma concentrations. Pharmacokinetic parameters were calculated using noncompartmental analysis. Data from one outlier were excluded from the statistical summary. Behavioral and physiological responses were recorded before and for 6 h after dexmedetomidine administration. Dexmedetomidine concentrations decreased rapidly (elimination half-life of 8.03 ± 0.84 min). Time of last detection varied from 30 to 60 min. Bradycardia was noted at 4 and 10 min after drug administration (26 ± 8 and 29 ± 8 beats/min respectively). Head height decreased by 70% at 4 and 10 min and gradually returned to baseline. Ability to ambulate was decreased for 60 min following drug administration, and mechanical nociceptive threshold was increased during 30 min. Blood glucose peaked at 30 min (134 ± 24 mg/dL) and borborygmi were decreased for the first hour after dexmedetomidine administration. Dexmedetomidine was quickly eliminated as indicated by the rapid decrease in plasma concentrations. Physiological, behavioral, and analgesic effects observed after dexmedetomidine administration were of short duration., (© 2014 John Wiley & Sons Ltd.)

Reasons for Performing Study: The use of fentanyl is limited in adult horses, in part due to potential for central nervous system excitation. The pharmacokinetics and the plasma concentration-related behavioural actions of fentanyl have not been described for young foals., Objectives: The goal of the present study was to describe the pharmacokinetics and behavioural effects of fentanyl following administration to the same group of foals at 3 different ages., Study Design: Experimental study in healthy foals., Methods: Fentanyl was administered i.v. (4 μg/kg bwt) to a group of 9 foals on 3 separate occasions at 6–8, 20–22 and 41–42 days of age. Blood samples were collected prior to administration and at multiple times until 24 h post administration. Blood samples were analysed for fentanyl concentrations and pharmacokinetics determined at each age. Behavioural and physiological effects were also assessed., Results: The average volume of distribution was 3.55, 1.53 and 1.82 l/kg bwt and clearance 50.2, 40.7 and 35.7 ml/min/kg bwt when foals were 6–8, 20–22 and 41–42 days of age, respectively. The elimination half-life was slightly prolonged (49.3 min) at 6–8 days relative to 20–22 and 41–42 days of age (25.8 and 33.7 min, respectively). The primary metabolite detected in blood samples was the same as for adult horses. While the onset and duration varied widely between foals, sedation was observed at all ages studied., Conclusions: Fentanyl appears to be consistently well tolerated following i.v. administration of 4 μg/kg bwt to foals ranging in age from 1 to 6 weeks. The results of this study support further study of fentanyl for clinical use in foals.

The objective of the current study was to describe the pharmacokinetics of morphine and its metabolites following intravenous administration to the horse. A total of eight horses (two per dose group) received a single intravenous dose of 0.05, 0.1, 0.2, or 0.5 mg/kg morphine. Blood samples were collected up to 72 h postdrug administration, analyzed using LC-MS/MS and pharmacokinetic parameters determined. Behavior, step counts, and gastrointestinal activity were also assessed. The beta and gamma half-life for morphine ranged from 0.675 to 2.09 and 6.70 to 18.1 h, respectively, following administration of the four different IV doses. The volume of distribution at steady-state and systemic clearance ranged from 6.95 to 15.8 L/kg and 28.3 to 35.7 mL · min/kg, respectively. The only metabolites identified in blood samples were the primary metabolites identified in other species, 3-morphine-glucuronide and 6-morphine-glucuronide. Muscle fasciculations were observed at 0.2 and 0.5 mg/kg and ataxia noted at 0.5 mg/kg. Gastrointestinal activity was decreased in all dose groups (for up to 8 h in 7/8 horses and 24 h in one horse). This study extends previous studies and is the first report describing the metabolites of morphine in the horse. Plasma concentrations of morphine-3-glucuronide, a metabolite with demonstrated neuro-excitatory activity in mice, far exceeded that of morphine-6-glucuronide. Further study is warranted to assess whether the high levels of the morphine-3-glucuronide contribute to the dose-dependent excitation observed at high morphine doses., (© 2014 John Wiley & Sons Ltd.)

Background: This study investigated the antinociceptive effects of a constant rate infusion (CRI) of lidocaine during xylazine and ketamine anesthesia in horses and aimed to correlate these effects with cardiorespiratory variables, bispectral index (BIS) and plasma lidocaine concentrations. Six adult crossbred mares weighing 320-400 kg were anesthetized on three different occasions. Sedation was performed with xylazine (0.75 mg/kg IV) and anesthetic induction with guaifenesin (75 mg/kg IV) and ketamine (2 mg/kg IV). Anesthesia was maintained with 37.5 μg/kg/min of xylazine and 87.5 μg/kg/min of ketamine both administered intravenously for 75 min. The three treatments consisted of: lidocaine (loading dose: 5 mg/kg, CRI: 100 μg/kg/min; THL); lidocaine (loading dose: 2.5 mg/kg; CRI: 50 μg/kg/min: TLL); and saline (TS); all given 15 min after induction and maintained for 1 h. Antinociception was measured by response to electrical stimulation and bispectral index (BIS) was recorded during anesthesia. Parametric and non-parametric data were compared using ANOVA followed by Student-Newman-Keuls and Friedman tests, respectively., Results: Plasma lidocaine concentrations peaked at the end of lidocaine loading dose and was greater in THL (9.61 ± 2.75 μg/mL) vs TLL (4.50 ± 3.34 μg/mL). Electrical noxious stimulation caused purposeful movement in all horses from TS, but no response in THL. The BIS was decreased in THL only and was less when compared to the other treatments throughout anesthesia. Blood pressure, PaO2 and PaCO2 increased and heart rate (HR), respiratory rate (RR), pH, total plasma protein and temperature decreased during anesthesia in all treatments. PaCO2 and HR were greater and RR and pH less in THL compared to TLL and TS at 30 min during anesthesia. All recoveries were considered excellent. Time to standing was longer after THL (60 ± 20 min) than following TLL and TS (32 ± 17 and 30 ± 15 min, respectively)., Conclusions: At the highest dose administered (THL) lidocaine CRI during xylazine/ketamine anesthesia decreased BIS and motor response to noxious stimulation, and prolonged recovery time without significant added cardiorespiratory depression.

Reasons for Performing Study: Both the potential analgesic effect and the conflicting reports describing tramadol disposition in the horse warrant further study of the pharmacokinetics of tramadol in this species., Objectives: To describe the pharmacokinetics of tramadol and its metabolites, O-desmethyltramadol and N-desmethyltramadol, following i.v. administration of 3 doses to the horse., Methods: Nine adult horses received a single i.v. dose of 0.5, 1.5 and 3 mg/kg bwt tramadol. Blood samples were collected prior to and at various times up to 72 h post administration. Plasma samples were analysed using liquid chromatography-mass spectrometry and data analysed using noncompartmental analysis. Chin-to-ground distance, heart rate and rhythm, step count and gastrointestinal activity were also assessed., Results: Maximal measured plasma tramadol concentrations were 454 ± 101.6, 1086.7 ± 330.7 and 1697.9 ± 406.1 ng/ml for 0.5, 1.5 and 3 mg/kg bwt, respectively. Depending on the dose administered, the tramadol clearance, volume of distribution and half-life ranged from 24.6 to 25.0 ml/min/kg, 2.66 to 3.33 l/kg and 2.17 to 3.05 h, respectively. Following administration of 0.5, 1.5 and 3 mg/kg bwt tramadol, the maximal measured plasma concentrations of the active metabolite, O-desmethyltramadol, were 3.9 ± 1.9, 9.6 ± 4.8 and 12.9 ± 5.2 ng/ml, respectively. Muscle fasiculations and tremors were seen following administration of the 2 high doses. No significant changes in chin-to-ground distance, heart rate and rhythm, step count and gastrointestinal activity were observed., Conclusions and Potential Relevance: This study confirms and extends previous studies describing the pharmacokinetics of tramadol following i.v. administration to the horse. Plasma tramadol concentrations exceeded those necessary for analgesia in human patients; however, further studies are necessary to determine plasma concentrations of tramadol necessary for analgesic efficacy in the horse. These results support further investigation of the analgesic efficacy of tramadol in the horse., (© 2012 EVJ Ltd.)

Objective: To describe selected pharmacodynamic effects of detomidine and yohimbine when administered alone and in sequence., Study Design: Randomized crossover design., Animals: Nine healthy adult horses aged 9 ± 4 years and weighing 561 ± 56 kg., Methods: Three dose regimens were employed in the current study. 1) 0.03 mg kg(-1) detomidine IV, 2) 0.2 mg kg(-1) yohimbine IV and 3) 0.03 mg kg(-1) detomidine IV followed 15 minutes later by 0.2 mg kg(-1) yohimbine IV. Each horse received all three treatments with a minimum of 1 week between treatments. Blood samples were obtained and plasma analyzed for detomidine and yohimbine concentrations by liquid chromatography-mass spectrometry. Behavioral effects, heart rate and rhythm, glucose, packed cell volume and plasma proteins were monitored., Results: Yohimbine rapidly reversed the sedative effects of detomidine in the horse. Additionally, yohimbine effectively returned heart rate and the percent of atrio-ventricular conduction disturbances to pre-detomidine values when administered 15 minutes post-detomidine administration. Plasma glucose was significantly increased following detomidine administration. The detomidine induced hyperglycemia was effectively reduced by yohimbine administration. Effects on packed cell volume and plasma proteins were variable., Conclusions and Clinical Relevance: Intravenous administration of yohimbine effectively reversed detomidine induced sedation, bradycardia, atrio-ventricular heart block and hyperglycemia., (© 2012 The Authors. Veterinary Anaesthesia and Analgesia. © 2012 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.)

Objective: To test the hypothesis that hypercapnic hyperpnea produced using endotracheal insufflation with 5-10% CO(2) in oxygen could be used to shorten anesthetic recovery time in horses, and that recovery from sevoflurane would be faster than from isoflurane., Study Design: Randomized crossover study design., Animals: Eight healthy adult horses., Methods: After 2 hours' administration of constant 1.2 times MAC isoflurane or sevoflurane, horses were disconnected from the anesthetic circuit and administered 0, 5, or 10% CO(2) in balance O(2) via endotracheal tube insufflation. End-tidal gas samples were collected to measure anesthetic washout kinetics, and arterial and venous blood samples were collected to measure respiratory gas partial pressures. Horses recovered in padded stalls without assistance, and each recovery was videotaped and evaluated by reviewers who were blinded to the anesthetic agent and insufflation treatment used., Results: Compared to isoflurane, sevoflurane caused greater hypoventilation and was associated with longer times until standing recovery. CO(2) insufflation significantly decreased anesthetic recovery time compared to insufflation with O(2) alone without significantly increasing PaCO(2) . Pharmacokinetic parameters during recovery from isoflurane with CO(2) insufflation were statistically indistinguishable from sevoflurane recovery without CO(2). Neither anesthetic agent nor insufflation treatment affected recovery quality from anesthesia., Conclusions and Clinical Relevance: Hypercapnic hyperpnea decreases time to standing without influencing anesthetic recovery quality. Although the lower blood gas solubility of sevoflurane should favor a shorter recovery time compared to isoflurane, this advantage is negated by the greater respiratory depression from sevoflurane in horses., (© 2012 The Authors. Veterinary Anaesthesia and Analgesia. © 2012 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.)

Background: The administration of certain sedatives has been shown to promote sleep in humans. Related agents induce sleep-like behavior when administered to horses. Interpretation of electroencephalograms (EEGs) obtained from sedated horses should take into account background activity, presence of sleep-related EEG events, and the animal's behavior., Hypothesis: Sedatives induce states of vigilance that are indistinguishable on EEGs from those that occur naturally., Animals: Six healthy horses., Methods: Digital EEG with video was recorded after administration of 1 of 4 sedatives (acepromazine, butorphanol, xylazine, or detomidine). Serum drug concentrations were measured. Recordings were reviewed, states were identified, and representative EEG samples were analysed. These data were compared with data previously obtained during a study of natural sleep., Results: Butorphanol was associated with brief episodes resembling slow wave sleep in 1 horse. Acepromazine led to SWS in 3 horses, including 1 that also exhibited rapid eye movement sleep. Periods of SWS were observed in all horses afer xylazine or detomidine administration. Normal sleep-related EEG events and heart block, occurred in association with SWS regardless of which sedative was used. Spectral data varied primarily by state, but some differences were observed between sedative and natural data., Conclusions and Clinical Importance: Qualitatively, EEG findings appeared identical whether sedation-induced or naturally occurring. The startle response and heart block associated with some sedatives may be related to sleep. Alpha(2) agonists can be used to obtain high quality EEGs in horses, but acepromazine does not promote a relaxed state in all animals., (Copyright © 2012 by the American College of Veterinary Internal Medicine.)

Objective: To describe the pharmacokinetics of detomidine and yohimbine when administered in combination., Study Design: Randomized crossover design., Animals: Nine healthy adult horses aged 9 ± 4 years and weighing of 561 ± 56 kg., Methods: Three dose regimens were employed in the current study. 1) 0.03 mg kg(-1) detomidine IV (D), 2) 0.2 mg kg(-1) yohimbine IV (Y) and 3) 0.03 mg kg(-1) detomidine IV followed 15 minutes later by 0.2 mg kg(-1) yohimbine IV (DY). Each horse received all three dose regimens with a minimum of 1 week in between subsequent regimens. Blood samples were obtained and plasma analyzed for detomidine and yohimbine concentrations by liquid chromatography-mass spectrometry. Data were analyzed using both non-compartmental and compartmental analysis., Results: The maximum measured detomidine concentrations were 76.0 and 129.9 ng mL(-1) for the D and DY treatments, respectively. Systemic clearance and volume of distribution of detomidine were not significantly different for either treatment. There was a significant increase in the maximum measured yohimbine plasma concentrations from Y (173.9 ng mL(-1)) to DY (289.8 ng mL(-1)). Both the Cl and V(d) for yohimbine were significantly less (6.8 mL minute(-1) kg(-1) (Cl) and 1.7 L kg(-1) (V(d) )) for the DY as compared to the Y treatments (13.9 mL minute(-1) kg(-1) (Cl) and 2.7 L kg(-1) (V(d))). Plasma concentrations were below the limit of quantitation (0.05 and 0.5 ng mL(-1)) by 18 hours for both detomidine and yohimbine., Conclusion and Clinical Relevance: The Cl and V(d) of yohimbine were affected by prior administration of detomidine. The elimination half life of yohimbine remained unaffected when administered subsequent to detomidine. However, the increased plasma concentrations in the presence of detomidine has the potential to cause untoward effects and therefore further studies to assess the physiologic effects of this combination of drugs are warranted., (© 2012 The Authors. Veterinary Anaesthesia and Analgesia. © 2012 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.)

Objective: To determine whether infusion of xylazine and ketamine or xylazine and propofol after sevoflurane administration in horses would improve the quality of recovery from anesthesia., Animals: 6 healthy adult horses., Procedures: For each horse, anesthesia was induced by administration of xylazine, diazepam, and ketamine and maintained with sevoflurane for approximately 90 minutes (of which the last 60 minutes were under steady-state conditions) 3 times at 1-week intervals. For 1 anesthetic episode, each horse was allowed to recover from sevoflurane anesthesia; for the other 2 episodes, xylazine and ketamine or xylazine and propofol were infused for 30 or 15 minutes, respectively, after termination of sevoflurane administration. Selected cardiopulmonary variables were measured during anesthesia and recovery. Recovery events were monitored and subjectively scored., Results: Cardiopulmonary variables differed minimally among treatments, although the xylazine-propofol infusion was associated with greater respiratory depression than was the xylazine-ketamine infusion. Interval from discontinuation of sevoflurane or infusion administration to standing did not differ significantly among treatments, but the number of attempts required to stand successfully was significantly lower after xylazine-propofol infusion, compared with the number of attempts after sevoflurane alone. Scores for recovery from anesthesia were significantly lower (ie, better recovery) after either infusion, compared with scores for sevoflurane administration alone., Conclusions and Clinical Relevance: Xylazine-ketamine or xylazine-propofol infusion significantly improved quality of recovery from sevoflurane anesthesia in horses. Xylazine-ketamine or xylazine-propofol infusions may be of benefit during recovery from sevoflurane anesthesia in horses for which a smooth recovery is particularly critical. However, oxygenation and ventilation should be monitored carefully.

Objective: To describe the pharmacodynamics and pharmacokinetics following an intravenous (IV) bolus dose of medetomidine in the horse., Study Design: Prospective experimental trial., Animals: Eight, mature healthy horses age 11.7 ± 4.6 (mean ± SD) years, weighing 557 ± 54 kg., Methods: Medetomidine (10 μg kg(-1) ) was administered IV. Blood was sampled at fixed time points from before drug administration to 48 hours post administration. Behavioral, physiological and biochemical data were obtained at predetermined time points from 0 minutes to 24 hours post administration. An algometer was also used to measure threshold responses to noxious stimuli. Medetomidine concentrations were determined by liquid chromatography-Mass Spectrometry and used for calculation of pharmacokinetic parameters using noncompartmental and compartmental analysis., Results: Pharmacokinetic analysis estimated that medetomidine peaked (8.86 ± 3.87 ng mL(-1) ) at 6.4 ± 2.7 minutes following administration and was last detected at 165 ± 77 minutes post administration. Medetomidine had a clearance of 39.6 ± 14.6 mL kg(-1) minute(-1) and a volume of distribution of 1854 ± 565 mL kg(-1). The elimination half-life was 29.1 ± 12.5 minutes. Glucose concentration reached a maximum of 176 ± 46 mg dL(-1) approximately 1 hour post administration. Decreased heart rate, respiratory rate, borborygmi, packed cell volume, and total protein concentration were observed following administration. Horses lowered their heads from 107 ± 12 to 20 ± 10 cm within 10 minutes of drug administration and gradually returned to normal. Horse mobility decreased after drug administration. An increased mechanical threshold was present from 10 to 45 minutes and horses were less responsive to sound., Conclusion and Clinical Relevance: Behavioral and physiological effects following intravenous administration positively correlate with pharmacokinetic profiles from plasma medetomidine concentrations. Glucose concentration gradually transiently increased following medetomidine administration. The analgesic effect of the drug appeared to have a very short duration., (© 2011 The Authors. Veterinary Anaesthesia and Analgesia. © 2011 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.)

Objective: To determine the anesthetic-sparing effect of maropitant, a neurokinin 1 receptor antagonist, during noxious visceral stimulation of the ovary and ovarian ligament in dogs., Animals: Eight 1-year-old female dogs., Procedures: Dogs were anesthetized with sevoflurane. Following instrumentation and stabilization, the right ovary and ovarian ligament were accessed by use of laparoscopy. The ovary was stimulated with a traction force of 6.61 N. The minimum alveolar concentration (MAC) was determined before and after 2 doses of maropitant., Results: The sevoflurane MAC value was 2.12 ± 0.4% during stimulation without treatment (control). Administration of maropitant (1 mg/kg, IV, followed by 30 μg/kg/h, IV) decreased the sevoflurane MAC to 1.61 ± 0.4% (24% decrease). A higher maropitant dose (5 mg/kg, IV, followed by 150 μg/kg/h, IV) decreased the MAC to 1.48 ± 0.4% (30% decrease)., Conclusions and Clinical Relevance: Maropitant decreased the anesthetic requirements during visceral stimulation of the ovary and ovarian ligament in dogs. Results suggest the potential role for neurokinin 1 receptor antagonists to manage ovarian and visceral pain.

Objective: To evaluate whether guaifenesin can prevent adverse anesthetic induction events caused by propofol and whether a guaifenesin-propofol induction combination has brief cardiovascular effects commensurate with rapid drug washout., Animals: 8 healthy adult horses., Procedures: Guaifenesin was administered IV for 3 minutes followed by IV injection of a bolus of propofol (2 mg/kg). Additional propofol was administered if purposeful movement was detected. Anesthesia was maintained for 2 hours with isoflurane or sevoflurane at 1.2 times the minimum alveolar concentration with controlled normocapnic ventilation. Normotension was maintained via a dobutamine infusion. Plasma concentrations of propofol and guaifenesin were measured every 30 minutes., Results: Mean ± SD guaifenesin and propofol doses inducing anesthesia in half of the horses were 73 ± 18 mg/kg and 2.2 ± 0.3 mg/kg, respectively. No adverse anesthetic induction events were observed. By 70 minutes, there was no significant temporal change in the dobutamine infusion rate required to maintain normotension for horses anesthetized with isoflurane or sevoflurane. Mean plasma guaifenesin concentrations were 122 ± 30 μM, 101 ± 33 μM, 93 ± 28 μM, and 80 ± 24 μM at 30, 60, 90, and 120 minutes after anesthetic induction, respectively. All plasma propofol concentrations were below the limit of quantitation., Conclusions and Clinical Relevance: Guaifenesin prevented adverse anesthetic induction events caused by propofol. Guaifenesin (90 mg/kg) followed by propofol (3 mg/kg) should be sufficient to immobilize > 99% of calm healthy adult horses. Anesthetic drug washout was rapid, and there was no change in inotrope requirements after anesthesia for 70 minutes.

Yohimbine is an alpha 2 adrenergic receptor antagonist, which has been shown to counteract the CNS depressant effects of alpha 2 receptor agonists in a number of species. Recently, our laboratory identified yohimbine in the absence of detectable concentrations of an alpha 2 agonist in a regulatory sample collected from a horse racing in California. This coupled with anecdotal reports of CNS stimulation and documented reports of cardiovascular changes when administered in conjunction with an agonist led us to investigate the pharmacokinetics and pharmacodynamics of yohimbine when administered alone. Nine healthy adult horses received a single intravenous dose of 0.1, 0.2, and 0.4 mg/kg yohimbine. Blood samples were collected at time 0 (prior to drug administration) and at various times up to 24 h postdrug administration. Plasma samples were analyzed using liquid chromatography-mass spectrometry (LC-MS), and resulting data analyzed using both noncompartmental and compartmental analysis. Peak plasma concentrations were 106.0 ± 28.9, 156.7 ± 34.3, and 223.0 ± 44.5 ng/mL for doses of 0.1, 0.2, and 0.4 mg/kg, respectively. Immediately following administration, two horses showed signs of sedation, one horse appeared excited, while the other six appeared behaviorally unaffected. Episodes of tachycardia were noted within minutes of administration for all horses at all doses; however, there was no correlation between behavioral responses and episodes of increased heart rate. Sixty-three percent of the horses (8, 6, and 4 of the 9 horses in the 0.1, 0.2, and 0.4 mg/kg dose groups, respectively) exhibited second-degree atrial-ventricular conduction blocks and bradycardia prior to drug administration that transiently improved or disappeared upon administration of yohimbine. Gastrointestinal sounds were transiently increased following all doses., (© 2010 Blackwell Publishing Ltd.)

Objective: To determine the magnitude and duration of sevoflurane minimum alveolar concentration (MAC) reduction following a single intravenous (IV) dose of methadone in cats., Study Design: Prospective experimental study., Animals: Eight (four females and four males) healthy mixed-breed adult (1-2 years) cats weighing 5.82 ± 0.42 kg., Methods: Anesthesia was induced and maintained with sevoflurane. Intravenous catheters facilitated administration of methadone and lactated Ringer's solution. After baseline MAC determination in triplicate using a tail clamp technique, 0.3 mg kg(-1) of methadone was administered IV. End-tidal sevoflurane concentration (e'SEVO) was reduced and MAC was redetermined. In an effort to determine the duration of MAC reduction, measurements were repeated in a stepwise manner until MAC values returned to baseline. After the last stimulation, the e'SEVO was increased to 1.2 individual MAC for 15 minutes, then sevoflurane was discontinued and cats were allowed to recover from anesthesia., Results: Baseline sevoflurane MAC was 3.18 ± 0.06%. When compared with baseline the sevoflurane MAC after methadone administration was significantly reduced by 25, 15 and 7% at 26, 76 and 122 minutes, respectively. The final MAC value (3.09 ± 0.07%) determined 156 minutes after methadone administration was not significantly different from baseline., Conclusions and Clinical Relevance: Intravenous methadone (0.3 mg kg(-1)) significantly decreased MAC of sevoflurane in cats but the effect was short-lived., (© 2011 The Authors. Veterinary Anaesthesia and Analgesia. © 2011 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.)

Objective: A dog model was developed to study visceral pain by stimulating the ovarian ligament., Study Design: Prospective experimental trial., Animals: Twelve 1-year old female hound dogs weighing 25.7 ± 3.6 kg., Methods: Dogs were anesthetized with sevoflurane. The right ovary was accessed via laparoscopy. A suture was placed around the ovarian ligament and exteriorized through the abdominal wall for stimulation. The noxious stimulus consisted of pulling the ovary and ovarian ligament with a force transducer. The response to noxious stimulation was determined using the anesthetic minimum alveolar concentration requirement (MAC) for sevoflurane. The ovarian MAC was compared to the standardized somatic noxious stimulation tail clamp MAC. The results are depicted as mean ± SD and corrected to sea-level., Results: The stimulus-response curve during ovarian stimulation in three dogs was hyperbolic and best represented by a three-parameter logistic growth curve model. The curve plateaued at 7.12 ± 4.19 N. From the stimulus-response curve, we chose 6.61 N to test the consistency and repeatability of the model in nine dogs. The ovarian stimulation MAC for sevoflurane in these dogs was 2.16 ± 0.46%. The ovarian stimulation confidence interval and limits are comparable to the results from tail stimulation MAC. The tail stimulation MACs before and after laparoscopy surgery were not different (1.86 ± 0.28% and 1.77 ± 0.38% respectively; p > 0.05) but lower when compared to the ovarian MAC (p < 0.01). The dogs recovered from anesthesia without complications., Conclusions and Clinical Relevance: The ovarian stimulation model is an adequate and repeatable means of producing visceral stimulation to determine MAC. The model may provide a humane mechanism to study the effectiveness of analgesics for acute ovarian pain., (© 2011 The Authors. Veterinary Anaesthesia and Analgesia © 2011 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.)

Objective: To compare cardiovascular effects of sevoflurane alone and sevoflurane plus an IV infusion of lidocaine in horses. Animals-8 adult horses., Procedures: Each horse was anesthetized twice via IV administration of xylazine, diazepam, and ketamine. During 1 anesthetic episode, anesthesia was maintained by administration of sevoflurane in oxygen at 1.0 and 1.5 times the minimum alveolar concentration (MAC). During the other episode, anesthesia was maintained at the same MAC multiples via a reduced concentration of sevoflurane plus an IV infusion of lidocaine. Heart rate, arterial blood pressures, blood gas analyses, and cardiac output were measured during mechanical (controlled) ventilation at both 1.0 and 1.5 MAC for each anesthetic protocol and during spontaneous ventilation at 1 of the 2 MAC multiples., Results: Cardiorespiratory variables did not differ significantly between anesthetic protocols. Blood pressures were highest at 1.0 MAC during spontaneous ventilation and lowest at 1.5 MAC during controlled ventilation for either anesthetic protocol. Cardiac output was significantly higher during 1.0 MAC than during 1.5 MAC for sevoflurane plus lidocaine but was not affected by anesthetic protocol or mode of ventilation. Clinically important hypotension was detected at 1.5 MAC for both anesthetic protocols., Conclusions and Clinical Relevance: Lidocaine infusion did not alter cardiorespiratory variables during anesthesia in horses, provided anesthetic depth was maintained constant. The IV administration of lidocaine to anesthetized nonstimulated horses should be used for reasons other than to improve cardiovascular performance. Severe hypotension can be expected in nonstimulated horses at 1.5 MAC sevoflurane, regardless of whether lidocaine is administered.

Objective: To determine effects of a continuous rate infusion of lidocaine on the minimum alveolar concentration (MAC) of sevoflurane in horses., Animals: 8 healthy adult horses., Procedures: Horses were anesthetized via IV administration of xylazine, ketamine, and diazepam; anesthesia was maintained with sevoflurane in oxygen. Approximately 1 hour after induction, sevoflurane MAC determination was initiated via standard techniques. Following sevoflurane MAC determination, lidocaine was administered as a bolus (1.3 mg/kg, IV, over 15 minutes), followed by constant rate infusion at 50 μg/kg/min. Determination of MAC for the lidocaine-sevoflurane combination was started 30 minutes after lidocaine infusion was initiated. Arterial blood samples were collected after the lidocaine bolus, at 30-minute intervals, and at the end of the infusion for measurement of plasma lidocaine concentrations., Results: IV administration of lidocaine decreased mean ± SD sevoflurane MAC from 2.42 ± 0.24% to 1.78 ± 0.38% (mean MAC reduction, 26.7 ± 12%). Plasma lidocaine concentrations were 2,589 ± 811 ng/mL at the end of the bolus; 2,065 ± 441 ng/mL, 2,243 ± 699 ng/mL, 2,168 ± 339 ng/mL, and 2,254 ± 215 ng/mL at 30, 60, 90, and 120 minutes of infusion, respectively; and 2,206 ± 329 ng/mL at the end of the infusion. Plasma concentrations did not differ significantly among time points., Conclusions and Clinical Relevance: Lidocaine could be useful for providing a more balanced anesthetic technique in horses. A detailed cardiovascular study on the effects of IV infusion of lidocaine during anesthesia with sevoflurane is required before this combination can be recommended.

Digital perfusion pressure (DPP) equals mean arterial pressure (MAP) at the hoof coronet minus digital interstitial pressure (DIP) within the hoof. To test whether lamellar blood flow (LBF) changes proportionately to DPP, anesthesia was induced and maintained with isoflurane in six horses to target a MAP of 60 mmHg. Arterial, venous, and hoof interstitial pressures were measured in each pelvic limb. LBF was measured using fluorescent microspheres during dobutamine infusions targeting either 60 (low), 80 (medium), or 100 (high) mmHg MAP. Following euthanasia, hoof lamina was collected for microsphere isolation. To reduce intra-individual variability, medium and high pressures and flows were divided by their respective low pressure and flow baseline values, yielding indexed variables of ΔLBF and ΔDPP. The ΔLBF correlated negatively with the ΔDPP. We conclude that LBF was not solely determined by passive pressure-flow relationships and that systemic hypertension may not effectively increase dermal LBF in horses., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Yohimbine is an alpha 2 adrenergic receptor antagonist used most commonly in veterinary medicine to reverse the effects of the alpha 2 receptor agonists, xylazine and detomidine. Most notably, yohimbine has been shown to counteract the CNS depressant effects of alpha 2 receptor agonists in a number of species. The recent identification of a yohimbine positive urine sample collected from a horse racing in California has led to the investigation of the pharmacokinetics of this compound. Eight healthy adult horses received a single intravenous dose of 0.12 mg/kg yohimbine. Blood samples were collected at time 0 (prior to drug administration) and at various times up to 72 h post drug administration. Plasma samples were analyzed using liquid chromatography-mass spectrometry (LC-MS) and data analyzed using both noncompartmental and compartmental analysis. Peak plasma concentration was 114.5 + 31.8 ng/mL and occurred at 0.09 + 0.03 h. Mean ± SD systemic clearance (Cls) and steady-state volume of distribution (Vdss) were 13.5 + 2.1 mL/min/kg and 3.3 + 1.3 L/kg following noncompartmental analysis. For compartmental analysis, plasma yohimbine vs. time data were best fitted to a two compartment model. Mean ± SD Cls and Vdss of yohimbine were 13.6 ± 2.0 mL/min/kg and 3.2 ± 1.1 L/kg, respectively. Mean ± SD terminal elimination half-life was 4.4 ± 0.9 h following noncompartmental analysis. Immediately following administration, two horses showed signs of sedation, while the other six appeared behaviorally unaffected. Gastrointestinal sounds were moderately increased compared to baseline while fecal consistency appeared normal., (© 2010 Blackwell Publishing Ltd.)

Objective: To test a hypothesis predicting that isoflurane would interfere with cerebrovascular autoregulation in horses and to evaluate whether increased mean arterial blood pressure (MAP) would increase cerebral blood flow and intracranial pressure (ICP) during isoflurane anesthesia., Animals: 6 healthy adult horses., Procedures: Horses were anesthetized with isoflurane at a constant end-tidal concentration sufficient to maintain MAP at 60 mm Hg. The facial, carotid, and dorsal metatarsal arteries were catheterized for blood sample collection and pressure measurements. A sub-arachnoid transducer was used to measure ICP Fluorescent microspheres were injected through a left ventricular catheter during MAP conditions of 60 mm Hg, and blood samples were collected. This process was repeated with different-colored microspheres at the same isoflurane concentration during MAP conditions of 80 and 100 mm Hg achieved with IV administration of dobutamine. Central nervous system tissue samples were obtained after euthanasia to quantify fluorescence and calculate blood flow., Results: Increased MAP did not increase ICP or blood flow in any of the brain tissues examined. However, values for blood flow were low for all tested brain regions except the pons and cerebellum. Spinal cord blood flow was significantly decreased at the highest MAP., Conclusions and Clinical Relevance: Results suggested that healthy horses autoregulate blood flow in the CNS at moderate to deep planes of isoflurane anesthesia. Nonetheless, relatively low blood flows in the brain and spinal cord of anesthetized horses may increase risks for hypoperfusion and neurologic injury.

Objective: To characterize cardiovascular, respiratory and biochemical effects and recovery behavior associated with a 3-hour continuous infusion of a micellar microemulsion propofol formulation in horses., Study Design: Prospective experimental trial., Animals: Six healthy adult horses, 9 +/- 2 years old and weighing 557 +/- 14 kg., Methods: All horses received xylazine (1 mg kg(-1), IV) 5 minutes prior to anesthetic induction. Each horse was anesthetized on two occasions with a 5% micellar microemulsion propofol formulation (2 mg kg(-1), IV); first as a single bolus (phase I) and then as a 3-hour continuous infusion (phase II). Propofol pharmacokinetics were obtained from phase I and used to determine the starting infusion rates in phase II. Anesthetic induction and recovery characteristics were quantitatively and qualitatively assessed. Cardiovascular, respiratory and biochemical parameters were monitored during anesthesia and recovery., Results: Induction quality varied, ranging from good to poor. Standing and overall recovery quality scores were consistently excellent in phase I but more variability was observed among horses in phase II. Heart rate (HR) and mean arterial pressure (MAP) were adequately maintained but marked hypoventilation developed. There were only minimal changes in blood biochemical analytes following anesthesia., Conclusions and Clinical Relevance: The micellar microemulsion propofol formulation, administered as a 3-hour continuous infusion, showed similar results compared to those previously described with a commercially available propofol preparation. However, based on present findings, use of propofol as a primary anesthetic in horses for prolonged periods of anesthesia requires further study to determine the limits of safety and clinical applicability.

Background: To define the pharmacokinetic profile of propofol 5% microemulsion formulation in horses., Methods: First, propofol was administered as bolus injection (2 mg kg(-1)) to six xylazine-sedated horses. Secondly, after sedation and bolus injection, propofol was maintained with continuous infusion for 3 h [8.1 (sd 3.2) mg kg(-1) h(-1)] to the same six horses. Thirdly, in two horses, a commercial propofol was used for comparison. Response to noxious stimulation was used to evaluate analgesia. Venous blood samples were obtained to measure propofol plasma concentration using liquid chromatography-mass spectrometry analysis. The plasma concentrations were related to the anaesthesia characteristics to determine the ED(50)., Results: The pharmacokinetic profile of propofol is best characterized by a non-compartmental model. The mean (confidence interval) for area under plasma concentration-time curve, elimination half-life, mean residence time, and clearance was 41 min microg ml(-1) (+/-7.7), 44.8 min (+/-21.3), 13.7 min (+/-3.2), and 45.8 ml min(-1) kg(-1) (+/-6.5), respectively. Linear regression analysis showed a correlation between plasma concentration and infusion rate (r(2)=0.47). Most propofol infusion rates did not inhibit the response to noxious stimulation and rates above 11.9 mg kg(-1) h(-1) caused involuntary muscle contractions. Better recoveries were associated with lower propofol plasma concentrations. Propofol plasma concentration frequently increased when horses woke from anaesthesia., Conclusions: Caution is warranted when propofol is used for continuous infusion due to variable kinetics, myoclonal activity, poor analgesia, and less desirable recovery quality.

Objective: To characterize the behavior of horses recovering in the Anderson Sling Suspension System after 4 hours of desflurane anesthesia and postdesflurane intravenous (IV) administration of propofol and xylazine., Study Design: Experimental study., Animals: Healthy horses (n=6), mean+/-SEM age 12.3+/-1.8 years; mean weight 556+/-27 kg., Methods: Each horse was anesthetized with xylazine, diazepam, and ketamine IV and anesthesia was maintained with desflurane in O(2). At the end of 4 hours of desflurane, each horse was positioned in the sling suspension system and administered propofol-xylazine IV. Recovery events were quantitatively and qualitatively assessed. Venous blood was obtained before and after anesthesia for biochemical and propofol analyses., Results: Anesthetic induction and maintenance were without incident. Apnea commonly accompanied propofol administration. All horses had consistent recovery behavior characterized by a smooth, careful, atraumatic return to a standing posture., Conclusions: Results of this study support careful, selective clinical use of desflurane, propofol-xylazine, and the Anderson Sling Suspension System to atraumatically transition horses with high anesthetic recovery risk to a wakeful standing posture., Clinical Relevance: Technique choices to facilitate individualized, atraumatic recovery of horses from general anesthesia are desirable. Use of IV propofol and xylazine to transition horses from desflurane anesthesia during sling recovery to standing posture may facilitate improved recovery management of high-injury risk equine patients requiring general anesthesia.

Objective: To verify the isoflurane anesthetic minimum alveolar concentration (MAC)-sparing effect of a previously administered target plasma fentanyl concentration of 16 ng/mL and characterize an anticipated further sparing in isoflurane MAC associated with higher target plasma fentanyl concentrations., Animals: 8 horses., Procedures: Horses were assigned 2 of 3 target plasma fentanyl concentrations (16, 24, and 32 ng/mL), administered in ascending order. Following determination of baseline MAC, horses received a loading dose of fentanyl followed by a constant rate infusion; MAC determination was performed in triplicate at baseline and at each fentanyl concentration. Venous blood samples were collected throughout the study for determination of actual plasma fentanyl concentrations. Recovery from anesthesia was monitored, and behaviors were rated as excellent, good, fair, or poor., Results: Mean + or - SD fentanyl plasma concentrations were 13.9 + or - 2.6 ng/mL, 20.1 + or - 3.6 ng/mL, and 24.1 + or - 2.4 ng/mL for target concentrations of 16, 24, and 32 ng/mL, respectively. The corresponding changes in the MAC of isoflurane were -3.28%, -6.23%, and +1.14%. None of the changes were significant. Recovery behavior was variable and included highly undesirable, potentially injurious excitatory behavior., Conclusions and Clinical Relevance: Results of the study did not verify an isoflurane-sparing effect of fentanyl at a plasma target concentration of 16 ng/mL. Furthermore, a reduction in MAC was not detected at higher fentanyl concentrations. Overall, results did not support the routine use of fentanyl as an anesthetic adjuvant in adult 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(v)O(2), P(v)CO(2)). 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.

Objective: To compare characteristics of horses recovering from 4 hours of desflurane anesthesia with and without immediate postanesthetic IV administration of propofol and xylazine. Animals-8 healthy horses (mean +/- SEM age, 6.6 +/- 1.0 years; mean body weight, 551 +/- 50 kg)., Procedures: Horses were anesthetized twice. Both times, anesthesia was induced with a combination of xylazine hydrochloride, diazepam, and ketamine hydrochloride and then maintained for 4 hours with desflurane in oxygen. Choice of postanesthetic treatment was randomly assigned via a crossover design such that each horse received an IV injection of propofol and xylazine or saline (0.9% NaCl) solution after the anesthetic episode. Recovery events were quantitatively and qualitatively assessed. Venous blood samples were obtained before and after anesthesia for determination of serum creatine kinase activity and plasma propofol concentration., Results: Anesthetic induction and maintenance were unremarkable in all horses. Compared with administration of saline solution, postanesthetic administration of propofol and xylazine resulted in an increased interval to emergence from anesthesia but improved quality of recovery-related transition to standing. Compared with administration of saline solution, administration of propofol also delayed the rate of decrease of end-tidal concentrations of desflurane and carbon dioxide and added to conditions promoting hypoxemia and hypoventilation., Conclusions and Clinical Relevance: Propofol and xylazine administered IV to horses after 4 hours of desflurane anesthesia improved the quality of transition from lateral recumbency to standing but added potential for harmful respiratory depression during the postanesthetic period.

Objective: To test the hypothesis that head-down positioning in anesthetized horses increases intracranial pressure (ICP) and decreases cerebral and spinal cord blood flows., Animals: 6 adult horses., Procedures: For each horse, anesthesia was induced with ketamine hydrochloride and xylazine hydrochloride and maintained with 1.57% isoflurane in oxygen. Once in right lateral recumbency, horses were ventilated to maintain normocapnia. An ICP transducer was placed in the subarachnoid space, and catheters were placed in the left cardiac ventricle and in multiple vessels. Blood flow measurements were made by use of a fluorescent microsphere technique while each horse was in horizontal and head-down positions. Inferential statistical analyses were performed via repeated-measures ANOVA and Dunn-Sidak comparisons., Results: Because 1 horse developed extreme hypotension, data from 5 horses were analyzed. During head-down positioning, mean +/- SEM ICP increased to 55+/-2 mm Hg, compared with 31+/-2 mm Hg during horizontal positioning; cerebral perfusion pressure was unchanged. Compared with findings during horizontal positioning, blood flow to the cerebrum, cerebellum, and cranial portion of the brainstem decreased significantly by approximately 20% during head-down positioning; blood flows within the pons and medulla were mildly but not significantly decreased. Spinal cord blood flow was low (9 mL/min/100 g of tissue) and unaffected by position., Conclusions and Clinical Relevance: Head-down positioning increased heart-brain hydrostatic gradients in isoflurane-anesthetized horses, thereby decreasing cerebral blood flow and, to a greater extent, increasing ICP. During anesthesia, CNS regions with low blood flows in horses may be predisposed to ischemic injury induced by high ICP.

Objective: To characterize the pharmacokinetics of fentanyl and the tolerance of foals to the drug following a single application of a commercially available transdermal system (TS)., Study Design: Prospective experimental study., Animals: Six (two male, four female) foals aged 4-8 days, weighing 56-74 kg., Methods: After placement of a jugular sampling catheter, one fentanyl TS (FTS) containing 10.2 mg fentanyl, released at 100 microg hour(-1), was applied for 72 hours. Blood samples were withdrawn over the course of 90 hours for fentanyl plasma analysis. Before and after the study, weight, complete blood count and blood chemistry values were obtained. During the study, tolerance and safety were monitored by physical examination and assessment of behavior., Results: Fentanyl was detected as early as 20 minutes after FTS placement. Peak plasma concentrations were variable (0.1-28.7 ng mL(-1)), were reached after 14.3 +/- 7.6 hours (mean +/- SD), and returned to baseline concentrations 12 hours after FTS removal. All foals satisfactorily tolerated the FTS application and no significant adverse effects were observed. Rectal temperature increased above 38.5 degrees C (max. 39.0 degrees C) in all foals, although this did not correlate with fentanyl plasma concentrations. Results of hematological and biochemical analyses were within reference ranges., Conclusion and Clinical Relevance: Our data show that 100 microg hour(-1) fentanyl administered by an FTS results in time-related but variable plasma concentrations in foals. The FTS was easy to apply and was well tolerated.

Background: The influence of sleep on the equine electroencephalogram (EEG) has not been well documented., Hypothesis: The objectives were to develop a noninvasive method of electrode placement for recording the EEG in horses and to establish normal EEG parameters for the various states of vigilance. Findings are compared with previously published reports on equine sleep based on electrocorticography (ECoG)., Animals: Five neurologically normal horses., Methods: Overnight EEGs were recorded digitally in association with simultaneous videotaping of the horses' behavior. Data were analyzed by visual inspection, states of vigilance were identified, and representative segments were quantitatively processed. Transient EEG events were examined., Results: Slow wave sleep (SWS) was significantly different (P < .05) in frequency and power from drowsiness and rapid eye movement (REM) sleep. Second-degree heart block was associated with SWS as were transient events commonly recognized in EEGs of humans. Drowsiness and REM sleep were similar. In both, background activity was low-amplitude beta activity admixed with prominent activity of approximately 4 Hz. Standing REM sleep was associated with numerous partial collapses in 1 horse., Conclusions and Clinical Importance: Normative data for several states were described and probable benign variants identified. This information will serve as control data for sedative and anesthetic studies in this species. The sleep patterns observed during this study are those of horses removed from their usual surroundings, and thus may represent those encountered in a clinical environment.

Objective: To determine whether infusion of xylazine (XYL) and ketamine (KET) for 30 minutes after isoflurane administration in horses would result in improved quality of recovery from anesthesia, without detrimental cardiopulmonary changes., Study Design: Randomized, blinded experimental trial., Animals: Seven healthy adult horses aged 6.4 +/- 1.9 years and weighing 506 +/- 30 kg., Methods: Horses were anesthetized twice, at least 1 week apart. On both occasions, anesthesia was induced by the administration of XYL, diazepam, and KET, and maintained with isoflurane for approximately 90 minutes, the last 60 minutes of which were under steady-state conditions (1.2 times the minimum alveolar concentration isoflurane). On one occasion, horses were allowed to recover from isoflurane anesthesia, while on the other, XYL and KET were infused for 30 minutes after termination of isoflurane administration. Heart rate, respiratory rate, arterial blood pressure, pH, and blood-gases were measured and recorded at set intervals during steady-state isoflurane anesthesia and XYL-KET infusion. Recovery events were timed and subjectively scored by one nonblinded and two blinded observers. Data were analyzed using a restricted maximum likelihood-based mixed effect model repeated measures analysis., Results: Infusion of XYL and KET resulted in longer recovery times, but there was no significant improvement in recovery quality score., Conclusions: Under the conditions of this study, infusion of XYL and KET does not positively influence recovery from isoflurane anesthesia in horses., Clinical Relevance: This study does not support the routine use of XYL and KET infusions in horses during the transition from isoflurane anesthesia to recovery.

Objective: To assess the changes in colloid osmotic pressure (COP) in horses undergoing surgery for colic., Study Design: Prospective clinical evaluation., Animals: Twenty-nine adult horses presented for emergency laparotomy., Methods: Horses were premedicated with intravenous (IV) xylazine and anesthesia was induced with ketamine, diazepam and guaifenesin and was maintained with isoflurane as required. Lactated Ringer's solution (LRS) was given to all horses during anesthesia. Blood was collected in heparin before, and every 30 minutes during, anesthesia to measure COP, total protein concentration (TP), osmolality, packed cell volume, electrolytes, glucose and lactate. In addition, COP was estimated using different formulas previously described for horses., Results: Before anesthesia, COP and TP were 18.7 +/- 2.2 mmHg (2.49 +/- 0.29 kPa) and 6.3 +/- 0.7 g dL(-1), respectively. The horses received a mean +/- SD of 19.5 +/- 3.9 mL kg(-1) hour(-1) (range 15-25 mL kg(-1)hour(-1)) of LRS during anesthesia. The COP and TP decreased linearly (R(2) = 0.99, p < 0.01) during anesthesia and reached the lowest point at the end of anesthesia with a COP of 11.6 +/- 1.6 mmHg (1.55 +/- 0.21 kPa) and TP of 4.4 +/- 0.4 g dL(-1). The Pearson correlation coefficient for COP versus TP was r(2) = 0.78. Calculation of COP from TP concentrations showed that two formulas could predict COP to within 1 mmHg (0.13 kPa) (Thomas & Brown 1992; Boscan et al. 2007)., Conclusions and Clinical Relevance: Colloid osmotic pressure, like TP, decreased greatly over the course of crystalloid fluid infusion during anesthesia for laparotomy in horses with colic. This change may predispose the animal to tissue edema with subsequent morbidity.

Objective: To investigate the changes in colloid osmotic pressure (COP) and total protein concentrations during routine general anesthesia in horses., Study Design: Prospective, clinical study., Animals: Twelve adult healthy horses aged 9.1 +/- 4.7 years and weighing 474 +/- 79 kg presented for elective surgery and 14 adult horses aged 8.7 +/- 7.3 years and weighing 510 +/- 85 kg., Methods: All horses were premedicated with xylazine and anesthesia induced with ketamine, diazepam and guaifenesin, and maintained with isoflurane for 2.5 hours. Lactate Ringer's solution was administered at 11 mL kg(-1) hour(-1). Osmolality, COP, electrolytes, glucose, and lactate were measured with specific commercial analyzers. Total protein (TP) was determined with a refractometer and packed cell volume with centrifuged capillary tubes. In the second group of 14 horses samples were taken from both venous and arterial sites simultaneously and the above measurements performed., Results: Before anesthesia, COP and TP were 22.2 +/- 2 mmHg and 6.9 +/- 0.4 g dL(-1), respectively. Within 15 minutes of anesthetic induction, COP and TP decreased significantly (19.9 +/- 1.9 mmHg and 6.3 +/- 1.9 g dL(-1); p < 0.01). During anesthesia COP and TP decreased in a linear form (COP r2 = 0.96 and TP r2 = 0.97). The COP and TP were 15 +/- 1.3 mmHg and 5.1 +/- 0.2 g dL(-1) at the end of anesthesia. Calculation of COP from TP values failed to accurately predict measured COP. Simultaneous arterial and venous samples in the 14 anesthetized horses yielded no differences for COP or TP., Conclusions and Clinical Relevance: The data indicate that COP, like TP, decreases over the course of routine anesthetic management of horses and venous versus arterial samples should reveal comparable information.

Reasons for Performing Study: In order to evaluate its potential as an adjunct to inhalant anaesthesia in horses, the pharmacokinetics of fentanyl must first be determined., Objectives: To describe the pharmacokinetics of fentanyl and its metabolite, N-[1-(2-phenethyl-4-piperidinyl)maloanilinic acid (PMA), after i.v. administration of a single dose to horses that were awake in Treatment 1 and anaesthetised with isoflurane in Treatment 2., Methods: A balanced crossover design was used (n = 4/group). During Treatment 1, horses received a single dose of fentanyl (4 microg/kg bwt, i.v.) and during Treatment 2, they were anaesthetised with isoflurane and maintained at 1.2 x minimum alveolar anaesthetic concentration. After a 30 min equilibration period, a single dose of fentanyl (4 microg/kg bwt, i.v.) was administered to each horse. Plasma fentanyl and PMA concentrations were measured at various time points using liquid chromatography-mass spectrometry., Results: Anaesthesia with isoflurane significantly decreased mean fentanyl clearance (P < 0.05). The fentanyl elimination half-life, in awake and anaesthetised horses, was 1 h and volume of distribution at steady state was 0.37 and 0.26 l/kg bwt, respectively. Anaesthesia with isoflurane also significantly decreased PMA apparent clearance and volume of distribution. The elimination half-life of PMA was 2 and 1.5 h in awake and anaesthetised horses, respectively., Conclusions and Potential Relevance: Pharmacokinetics of fentanyl and PMA in horses were substantially altered in horses anaesthetised with isoflurane. These pharmacokinetic parameters provide information necessary for determination of suitable fentanyl loading and infusion doses in awake and isoflurane-anaesthetised horses.

Objective: To compare anesthesia-related events associated with IV administration of 2 novel micellar microemulsion preparations (1% and 5%) and a commercially available formulation (1%) of propofol in horses. Animals-9 healthy horses., Procedures: On 3 occasions, each horse was anesthetized with 1 of the 3 propofol formulations (1% or 5% microemulsion or 1% commercial preparation). All horses received xylazine (1 mg/kg, IV), and anesthesia was induced with propofol (2 mg/kg, IV). Induction and recovery events were quantitatively and qualitatively assessed. Venous blood samples were obtained before and at intervals following anesthesia for quantification of clinicopathologic variables., Results: Compared with the commercial formulation, the quality of anesthesia induction in horses was slightly better with the micellar microemulsion formulas. In contrast, recovery characteristics were qualitatively and quantitatively indistinguishable among treatment groups (eg, time to stand after anesthesia was 34.3 +/- 7.3 minutes, 34.1 +/- 8.8 minutes, and 39.0 +/- 7.6 minutes in horses treated with the commercial formulation, 1% microemulsion, and 5% microemulsion, respectively). During recovery from anesthesia, all horses stood on the first attempt and walked within 5 minutes of standing. No clinically relevant changes in hematologic and serum biochemical analytes were detected during a 3-day period following anesthesia., Conclusions and Clinical Relevance: Results suggest that the micellar microemulsion preparation of propofol (1% or 5%) has similar anesthetic effects in horses, compared with the commercially available lipid propofol formulation. Additionally, the micellar microemulsion preparation is anticipated to have comparatively low production costs and can be manufactured in various concentrations.