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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 mu g kg(-1) hour(-1)) and after two IV doses of vatinoxan in sequence (90 and 180 mu g 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 180 mu g 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.

BackgroundMeperidine 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.ResultsMeperidine 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).ConclusionsResults 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.

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.

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.

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.

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.

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.

The purpose of this study was to characterize urine flow and biochemical parameters in horses given xylazine (XYL) and anesthetized with ketamine and isoflurane. Nine mares [9 ± 2 (mean ± SE) years; 492 ± 17 kg] were studied. They were anesthetized for 2 hours in support of a campus-approved, laboratory-based orthopedic study. The day prior to anesthesia, a venous blood sample was obtained for biochemical analysis from each unmedicated mare. The urinary bladder was catheterized and emptied, and urine collected over the next three hours to quantitate the pre-drug values. The next day the mares were similarly catheterized. After obtaining urine and venous blood samples, XYL (1.1 mg kg−1 IV) was administered. Anesthesia was induced 5 minutes later with ketamine (2.2 mg kg−1 IV) and diazepam (0.04 mg kg−1 IV) and maintained with isoflurane in O2. Lactated Ringer's solution (10 mL kg−1 hours−1) was administered IV and dobutamine infused as required to maintain mean arterial blood pressure between 70 and 80 mm Hg. Mechanical ventilation maintained PaCO2 between 48 and 52 mm Hg and PaO2 > 200 mm Hg. Blood and urine were collected at 30, 60, and 120 minutes during anesthesia, and at 1 hour postanesthesia. Data were analyzed with RM anova; with p

As a cerebral vasodilator, isoflurane (ISO) can interfere with normal cerebrovascular autoregulation and may exacerbate cerebral perfusion pressure (CPP) changes in horses brought about by drugs that decrease mean arterial pressure (MAP) and by body positions that alter the hydrostatic gradient between brain and heart. It was, therefore, hypothesized that ISO-anesthetized horses in lateral recumbency would have increased intracranial pressure (ICP) and decreased CPP compared to standing, unmedicated horses. Anesthesia was induced and maintained in six healthy horses in left lateral recumbency using only ISO in oxygen. Central venous pressure (CVP) from the right atrium and MAP from the right carotid artery were recorded on a calibrated physiograph. A Codman Microsensor ICP transducer was placed in the subarachnoid space through a right parietal craniotomy. The PaO2, PaCO2, and pHa were obtained using an automated blood gas analyzer with values corrected to tonometrically derived standard curves. Horses were ventilated to 18–22 cm H2O inspiratory pressure and 0–2 cm H2O end-expiratory pressure. End-tidal isoflurane was measured by calibrated gas analyzers and maintained at 1.57%, or 1.2 times minimum alveolar concentration. Measurements in laterally recumbent horses were made at least 20 minutes following constant end-tidal isoflurane conditions. Measurements in awake horses were made 1 hour following standing recovery from anesthesia. The following data were obtained from anesthetized and awake horses, respectively (mm Hg; mean ± SD): MAP = 71 ± 6 and 133 ± 17, CVP = 9 ± 3 and 4 ± 14, ICP = 24 ± 5 and 2 ± 4, CPP = 48 ± 4 and 102 ± 26. Paired t-tests showed significant differences between anesthetized and awake horses for MAP (p

Clinical signs which indicate varying anaesthetic dose, have been reported for spontaneously breathing rats anaesthetized with halothane and isoflurane. This report provides similarly derived data for sevoflurane (SEVO).

The magnitude of respiratory depression in equidae anesthetized with isoflurane has not been thoroughly described. The aim of this study was to quantify changes in ventilation as a function of isoflurane (ISO) dose in the horse. Anesthesia was induced and maintained in five healthy adult horses weighing 564 ± 52 kg (mean ± SD) in left lateral recumbency using only ISO in O2. During spontaneous ventilation, four doses of constant end-tidal ISO measured by a calibrated infra-red analyzer were studied in randomized order: 1.31, 1.57, 1.83, and 2.10%; corresponding to the minimum alveolar concentration (MAC), 1.2 MAC, 1.4 MAC, and 1.6 MAC, respectively. The PaO2 and PaCO2 were measured using an automated blood gas analyzer and corrected to tonometrically derived standard curves. Respiratory rate (f) and tidal volume (VT) were measured via calibrated signal integration from a Silverman-style pneumotachometer; volumes were corrected to BTPS. Minute ventilation (VE) was the calculated product of VT and f. Data were analyzed using a repeated measures anova; Tukey's test was used for pairwise comparisons (p 80 mm Hg. The equations given below express median minute ventilation and median PaCO2 as a function of ISOMAC. Median values at each dose were used instead of mean values owing to the departure from sample variance uniformity. The y-intercepts coincide with published reports of and PaCO2 for awake, unmedicated horses (0 MAC). The x-intercept of Equation 1 predicts respiratory arrest at 2.4 MAC, near the apneic threshold for ISO. Future work directed towards increasing sample size in this study may remedy heterogeneous treatment variances present within the data and permit further refinement of dose–ventilation relationships in the horse. (1) PaCO2 = 22 × MAC + 39(2)

Isoflurane (ISO) is commonly combined with fentanyl (FEN) during maintenance of anaesthesia. There are no reports of the efficacy of this combination in monkeys. This study determined the ISO sparing effect of FEN in male Rhesus monkeys.

Isoflurane (ISO) is the most commonly administered feline inhalant anesthetic in North America. A newer agent, sevoflurane (SEVO), may provide faster induction and recovery from anesthesia based on its physical characteristics. Accordingly, we compared some induction and recovery characteristics of ISO and SEVO in healthy cats. Six female DSH cats (17.9 ± 9.0 (mean ± SD) months, 3.7 ± 0.3 kg) received four randomly assigned treatments: ISO for 1 hour (IS), SEVO for 1 hour (SS), ISO for 5 hours (IL), and SEVO for 5 hours (SL). Anesthesia was induced in a chamber into which ISO or SEVO was delivered at 2.7 times the individual's MAC (determined previously) in 6 L minute−1 O2. Measured (Rascal II, Ohmeda) anesthetic concentration was reported after correction using a multiple gas, standard-defined calibration curve. For induction, time (seconds) from introduction of inhalant to onset of incoordinated movement (IM), recumbency with movement (RM), recumbency without movement, loss of pedal reflex (PD), and intubation (ET) were recorded. Following intubation, anesthesia was maintained for the required time at 1.25 times the individual's MAC. For recovery, time (seconds) from discontinuation of the inhalant (with continuation of O2) to first movement, extubation (EXT), start of incoordinated movement, head-lift, sternal recumbency (SR), crawl, stand/walk with incoordination, and jump without incoordination were recorded. Esophageal normothermia was maintained. Data were analyzed by paired t-test (induction) or One-way Repeated Measures anova followed, when appropriate, by Tukey's test (recovery). p

Alpha-2 agonists cause transient dose-related increase in urine flow in normal horses. Although important clinically, effects of these drugs in dehydrated animals are not known. The purpose of this study was to describe the influence of xylazine (XYL) and detomidine (DET) on urine flow in mares deprived of food and water for 24 hours. Six clinically normal mares [12.5 ± 3.3 (mean ± SE) years] weighing 471 ± 23 kg were each studied four times; each study was separated by at least 7 days. The morning following fasting, the urinary bladder was catheterized (Foley) and emptied. Urine was then collected for 2 hours and a composite urine sample along with a sample of jugular venous blood provided baseline values. Shortly after emptying the bladder, saline, 0.5 or 1.0 mg kg−1 XYL or 0.03 mg kg−1 DET was injected IV (treatment randomly assigned) and urine and blood samples obtained over the next 2 hours. Data were analyzed by RM anova followed by Dunnett's test for pairwise comparisons p

This study evaluated the cardiopulmonary responses during isoflurane (ISO) anaesthesia in llamas.

Summary 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.

Summary 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.

Summary 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.

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 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.

Summary 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.

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 ± 30μM, 101 ± 33μM, 93 ± 28μM, and 80 ± 24μM 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.

To determine the magnitude and duration of sevoflurane minimum alveolar concentration (MAC) reduction following a single intravenous (IV) dose of methadone in cats.Prospective experimental study.Eight (four females and four males) healthy mixed-breed adult (1-2 years) cats weighing 5.82 ± 0.42 kg.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.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.Intravenous methadone (0.3 mg kg(-1)) significantly decreased MAC of sevoflurane in cats but the effect was short-lived.

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.

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.

DiMaio Knych, H.K., Steffey, E.P., Deuel, J.L., Shepard, R.A., Stanley, S.D. Pharmacokinetics of yohimbine following intravenous administration to horses. J. vet. Pharmacol. Therap.34, 58–63. 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.

DiMaio Knych, H. K., Steffey, E. P., Stanley, S. D. Pharmacokinetics and pharmacodynamics of three intravenous doses of yohimbine in the horse. J. vet. Pharmacol. Therap.34, 359–366. 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.

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 ED50. 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 µg 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 (r2=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 O2. 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 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 μg 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 °C (max. 39.0 °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 μg 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.

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.

Author(s): Williams, DC; Brosnan, RJ; Fletcher, DJ; Aleman, M; Holliday, TA; Tharp, B; Kass, PH; LeCouteur, RA; Steffey, EP | Abstract: BackgroundThe 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.ObjectiveTo determine the effects of isoflurane and halothane, administered as single agents at multiple levels, on the EEG and quantitative EEG (qEEG) of normal horses.AnimalsSix healthy horses.MethodsProspective 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.ResultsSpecific 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 importanceUnprocessed 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.

To assess the changes in colloid osmotic pressure (COP) in horses undergoing surgery for colic.Prospective clinical evaluation.Twenty-nine adult horses presented for emergency laparotomy.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.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, p0.01) 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) (ThomasBrown 1992; Boscan et al. 2007).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 describe a sling recovery system (Anderson Sling) for horses and to evaluate outcome of high-risk horses recovered from general anesthesia by a sling. Study Design— Retrospective study. Sample Population— Horses (n=24) recovered from general anesthesia. Methods— Complete medical and anesthetic records (1996–2003) for horses recovered from general anesthesia using the Anderson Sling system were evaluated retrospectively. Information retrieved included anesthetic protocol, surgical procedure, recovery protocol, recovery time, and quality of the recovery. Horses were recovered from anesthesia supported by the Anderson Sling in a standing position within a traditional padded equine recovery stall. Results— Twenty-four horses had 32 assisted recoveries; 31 events were successful. No complications associated with the sling or recovery system protocol occurred. One horse was intolerant of the sling's support and was reanesthetized and recovered successfully using head and tail ropes. Conclusion— The Anderson Sling recovery system is an effective and safe way to recover horses that are at increased risk for injury associated with adverse events during recovery from general anesthesia. Clinical Relevance— The Anderson Sling system should be considered for assisted recovery of equine patients from general anesthesia.

Objective—To describe the effects of changes in circuit volume and oxygen inflow rate on inspired oxygen concentration for a large animal circle anesthetic system. Study Population—A large animal circle anesthetic system, a 10 L/min flowmeter, and 20- and 40-L breathing bags. Procedure—Circuit volume was determined by a carbon dioxide dilution technique. Oxygen flow rates of 3, 6, and 10 L/min were delivered to the circuit with the large breathing bag, and a flow rate of 6 L/min was used with the small bag. Gas samples were collected during a 20-minute period. The time constant (τ) and half-time (T1/2) were calculated and compared with measured values. Results—Mean ± SEM volume of the breathing circuit with a 20- and 40-L breathing bag was 32.97 ± 0.91 L and 49.26 ± 0.58 L, respectively. The from measurements was 11.97, 6.10, and 3.60 minutes at oxygen flow rates of 3, 6, and 10 L/min, respectively, for the large breathing bag and 3.73 minutes at a flow rate of 6 L/min for the small breathing bag. The T1/2 was 8.29, 4.22, and 2.49 minutes at oxygen flow rates of 3, 6, and 10 L/min, respectively, for the large breathing bag and 2.58 minutes for the small breathing bag. Conclusions and Clinical Relevance—This study emphasizes that there are delays in the rate of increase in the inspired oxygen concentration that accompany use of conventional large animal circle anesthetic systems and low rates of inflow for fresh oxygen. (Am J Vet Res 2005;66:1675–1678)

Objective—To evaluate the use of xylazine and ketamine for total IV anesthesia in horses. Animals—8 horses. Procedure—Anesthetic induction was performed on 4 occasions in each horse with xylazine (0.75 mg/kg, IV), guaifenesin (75 mg/kg, IV), and ketamine (2 mg/kg, IV). Intravenous infusions of xylazine and ketamine were then started by use of 1 of 6 treatments as follows for which 35, 90, 120, and 150 represent infusion dosages (µg/kg/min) and X and K represent xylazine and ketamine, respectively: X35+K90 with 100% inspired oxygen (O2), X35+K120-O2, X35+K150-O2, X70+K90-O2, K150-O2, and X35+K120 with a 21% fraction of inspired oxygen (ie, air). Cardiopulmonary measurements were performed. Response to a noxious electrical stimulus was observed at 20, 40, and 60 minutes after induction. Times to achieve sternal recumbency and standing were recorded. Quality of sedation, induction, and recovery to sternal recumbency and standing were subjectively evaluated. Results—Heart rate and cardiac index were higher and total peripheral resistance lower in K150-O2 and X35+K120-air groups. The mean arterial pressure was highest in the X35+K120-air group and lowest in the K150-O2 group (125 ± 6 vs 85 ± 8 at 20 minutes, respectively). Mean PaO2 was lowest in the X35+K120-air group. Times to sternal recumbency and standing were shortest for horses receiving K150-O2 (23 ± 6 minutes and 33 ± 8 minutes, respectively) and longest for those receiving X70+K90-O2 (58 ± 28 minutes and 69 ± 27 minutes, respectively). Conclusions and Clinical Relevance—Infusions of xylazine and ketamine may be used with oxygen supplementation to maintain 60 minutes of anesthesia in healthy adult horses. (Am J Vet Res 2005;66:1002–1007)

Objective—To quantitate the effects of desflurane and mode of ventilation on cardiovascular and respiratory functions and identify changes in selected clinicopathologic variables and serum fluoride values associated with desflurane anesthesia in horses. Animals—6 healthy adult horses. Procedure—Horses were anesthetized on 2 occasions: first, to determine the minimum alveolar concentration (MAC) of desflurane in O2 and second, to characterize cardiopulmonary and clinicopathologic responses to 1×, 1.5×, and 1.75× desflurane MAC during both controlled and spontaneous ventilation. Results—Mean ± SEM MAC of desflurane in horses was 8.06 ± 0.41%; inhalation of desflurane did not appear to cause airway irritation. During spontaneous ventilation, mean PaCO2 was 69 mm Hg. Arterial blood pressure, stroke volume, and cardiac output decreased as the dose of desflurane increased. Conditions of intermittent positive pressure ventilation and eucapnia resulted in further cardiovascular depression. Horses recovered quickly from anesthesia with little transient or no clinicopathologic evidence of adverse effects. Serum fluoride concentration before and after administration of desflurane was below the limit of detection of 0.05 ppm (2.63µM/L). Conclusions and Clinical Relevance—Results indicate that desflurane, like other inhalation anesthetics, causes profound hypoventilation in horses. The magnitude of cardiovascular depression is related to dose and mode of ventilation; cardiovascular depression is less severe at doses of 1× to 1.5× MAC, compared with known effects of other inhalation anesthetics under similar conditions. Desflurane is not metabolized to an important degree and does not appear to prominently influence renal function or hepatic cellular integrity or function. ( Am J Vet Res 2005;66:669–677)

The superficial (SDF) and deep digital flexor (DDF) muscles are critical for equine forelimb locomotion. Knowledge of their mechanical properties will enhance our understanding of limb biomechanics. Muscle contractile properties derived from architectural-based algorithms may overestimate real forces and underestimate shortening capacity because of simplistic assumptions regarding muscle architecture. Therefore, passive and active (=total – passive) force–length properties of the SDF and DDF muscles were measured directly in vivo. Muscles from the right forelimbs of four Thoroughbred horses were evaluated during general anesthesia. Limbs were fixed to an external frame with the muscle attached to a linear actuator and load cell. Each muscle was stretched from an unloaded state to a range of prefixed lengths, then stimulated while held at that length. The total force did not exceed 4000 N, the limit for the clamping device. The SDF and DDF muscles produced 716±192 and 1577±203 N maximum active isometric force ( F max ), had ascending force–length ranges ( R asc ) of 5.1±0.2 and 9.1±0.4 cm, and had passive stiffnesses of 1186±104 and 1132±51 N/cm, respectively. The values measured for F max were much smaller than predicted based on conservative estimates of muscle specific tension and muscle physiological cross-sectional area. R asc were much larger than predicted based on muscle fiber length estimates. These data suggest that accurate prediction of the active mechanical behavior of architecturally complex muscles such as the equine DDF and SDF requires more sophisticated algorithms.

There is a need for a device for improved management of the airway of small laboratory animals during general anaesthesia. This report introduces such a device, referred to here as the airway device (AD). The AD has some similarity to the laryngeal mask airway (LMA) developed for human patients, but the mask portion of the device is specifically designed for small laboratory animals. In addition, the device has an oesophageal extension and unlike the LMA does not have a cuff associated with the mask. This report also shares experience of tests of one prototype AD with six New Zealand white rabbits. The AD was used for administering isoflurane and its effectiveness was evaluated during conditions of spontaneous and controlled intermittent positive pressure ventilation. The results provide encouragement for further development of the AD for airway management of small laboratory animals.

Objective—To determine whether high intracranial pressure (ICP) during spontaneous ventilation (SV) in anesthetized horses coincides with an increase in intracranial elastance (ie, change in ICP per unit change of intracranial volume). Animals—6 adult horses. Procedure—Anesthesia was induced and maintained in each horse for 5 hours with isoflurane at a constant dose equal to 1.2 times the minimum alveolar concentration. Direct ICP measurements were obtained by use of a strain gauge transducer inserted in the subarachnoid space, and arterial blood pressure was measured from a carotid artery. Physiologic responses were recorded after 15 minutes of normocapnic controlled ventilation (CV) and then after 10 minutes of SV. Aliquots (3 mL) of CSF were removed from each horse during SV until ICP returned to CV values. Slopes of pressure-volume curves yielded intracranial elastance. Results—Intracranial elastance ranged from 0.2 to 3.7 mm Hg/mL after removal of the first aliquot of CSF. Slopes of pressure-volume curves were largest following removal of the initial CSF aliquot, but shallow portions of curves were detected at relatively high ICPs (25 to 35 mm Hg). A second-order relationship between SV ICP and initial intracranial elastance was found. Conclusions and Clinical Relevance—In horses anesthetized with isoflurane, small changes in intracranial volume can cause large changes in ICP. Increased intracranial elastance could further exacerbate preexisting intracranial hypertension. However, removal of small volumes of CSF may cause rapid compensatory replacement from other intracranial compartments, which suggests steady-state maintenance of an increase in intracranial volume during isoflurane anesthesia in horses. (Am J Vet Res 2004;65:1042–1046)

Objective—To quantitate the dose and time-related effects of morphine sulfate on the anesthetic sparing effect of xylazine hydrochloride in halothane-anesthetized horses and determine the associated plasma xylazine and morphine concentration-time profiles. Animals—6 healthy adult horses. Procedure—Horses were anesthetized 3 times to determine the minimum alveolar concentration (MAC) of halothane in O2 and characterize the anesthetic sparing effect (ie, decrease in MAC of halothane) by xylazine (0.5 mg/kg, IV) administration followed immediately by IV administration of saline (0.9% NaCl) solution, low-dose morphine (0.1 mg/kg), or high-dose morphine (0.2 mg/kg). Selected parameters of cardiopulmonary function were also determined over time to verify consistency of conditions. Results—Mean (± SEM) MAC of halothane was 1.05 ± 0.02% and was decreased by 20.1 ± 6.6% at 49 ± 2 minutes following xylazine administration. The amount of MAC reduction in response to xylazine was time dependent. Addition of morphine to xylazine administration did not contribute further to the xylazine-induced decrease in MAC (reductions of 21.9 ± 1.2 and 20.7 ± 1.5% at 43 ± 4 and 40 ± 4 minutes following xylazine-morphine treatments for low-and high-dose morphine, respectively). Overall, cardiovascular and respiratory values varied little among treatments. Kinetic parameters describing plasma concentration-time curves for xylazine were not altered by the concurrent administration of morphine. Conclusions and Clinical Relevance—Administration of xylazine decreases the anesthetic requirement for halothane in horses. Concurrent morphine administration to anesthetized horses does not alter the anesthetic sparing effect of xylazine or its plasma concentration-time profile. (Am J Vet Res 2004; 65:519–526)

Objective—To characterize halothane and sevoflurane anesthesia in spontaneously breathing rats. Animals—16 healthy male Sprague-Dawley rats. Procedure—8 rats were anesthetized with halothane and 8 with sevoflurane. Minimum alveolar concentration (MAC) was determined. Variables were recorded at anesthetic concentrations of 0.8, 1.0, 1.25, and 1.5 times the MAC of halothane and 1.0, 1.25, 1.5, and 1.75 times the MAC of sevoflurane. Results—Mean (± SEM) MAC for halothane was 1.02 ± 0.02% and for sevoflurane was 2.99 ± 0.19%. As sevoflurane dose increased from 1.0 to 1.75 MAC, mean arterial pressure (MAP) decreased from 103.1 ± 5.3 to 67.9 ± 4.6 mm Hg, and PaCO2 increased from 58.8 ± 3.1 to 92.2 ± 9.2 mm Hg. As halothane dose increased from 0.8 to 1.5 MAC, MAP decreased from 99 ± 6.2 to 69.8 ± 4.5 mm Hg, and PaCO2 increased from 59.1 ± 2.1 to 75.9 ± 5.2 mm Hg. Respiratory rate decreased in a dose-dependent fashion from 88.5 ± 4.5 to 58.5 ± 2.7 breaths/min during halothane anesthesia and from 42.3 ± 1.8 to 30.5 ± 4.5 breaths/min during sevoflurane anesthesia. Both groups of rats had an increase in eyelid and pupillary aperture with an increase in anesthetic dose. Conclusions and Clinical Relevance—An increase in PaCO2 and a decrease in MAP are clinical indicators of an increasing halothane and sevoflurane dose in unstimulated spontaneously breathing rats. Increases in eyelid aperture and pupil diameter are reliable signs of increasing depth of halothane and sevoflurane anesthesia. Decreasing respiratory rate is a clinical indicator of an increasing dose of halothane. (Am J Vet Res 2003;64:470–474)

Objective—To measure the effects of isoflurane end-tidal concentration and mode of ventilation (spontaneous vs controlled) on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) in horses. Animals—6 adult horses of various breeds. Procedure—Anesthesia was induced and maintained with isoflurane in O2 in 6 healthy, unmedicated, adult horses. Using a subarachnoid strain gauge transducer, ICP was measured. Blood gas tensions and carotid artery pressures also were measured. Four isoflurane doses were studied, corresponding to the following multiples of the minimum alveolar concentration (MAC): 1.0 MAC, 1.2 MAC, 1.4 MAC, and 1.6 MAC. Data were collected during controlled ventilation and spontaneous ventilation at each dose. Results—Increasing isoflurane end-tidal concentration induced significant dose-dependent decreases in mean arterial pressure (MAP) and CPP but no change in ICP. Hypercapnic spontaneous ventilation caused significant increases in MAP and ICP, compared with normocapnic controlled ventilation; no change in CPP was observed. Conclusion and Clinical Relevance—Hypercapnia likely increases cerebral blood flow (CBF) by maintaining CPP in the face of presumed cerebral vasodilation in healthy anesthetized horses. The effect of isoflurane dose on CBF, however, remains unresolved because it depends on the opposinginfluences of a decrease in CCP and cerebral vasodilation. (Am J Vet Res 2003;64:21–25)

The effects of intravenous administration of variable-dose flumazenil (0, 0.001, 0.005, 0.01, and 0.1 mg/kg) after ketamine (3 mg/kg) and midazolam (0.0 and 0.5 mg/kg) were studied in 18 healthy unmedicated cats from time of administration until full recovery. End-points were chosen to determine whether flumazenil shortened the recovery period and/or modified behaviors previously identified and attributed to midazolam. Overall, flumazenil administration had little effect on recovery or behaviors. One minute after flumazenil administration, all cats were recumbent but a greater proportion of cats which received the highest dose assumed sternal recumbency with head up than any other group. Although not significant, those cats that received the highest flumazenil dose also had shorter mean times for each of the initial recovery stages (lateral recumbency with head up, sternal recumbency with head up and walking with ataxia) than any of the other treatment groups that received midazolam. For complete recovery, flumazenil did decrease the proportion of the cats that was sedated, but did not shorten the time to walking without ataxia. Based on this study, the administration of flumazenil in veterinary practice, at the doses studied, to shorten and/or improve the recovery from ketamine and midazolam in healthy cats cannot be recommended.