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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.

BackgroundPrevious 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.ObjectivesTo determine the effects of 2 inhalation anesthetics on the EEG of healthy horses.AnimalsSix healthy horses.MethodsProspective 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.ResultsBurst 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 importanceThe 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.

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.)

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.

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.

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.

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 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 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.

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.

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.

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 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: 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.

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 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.

Background: Fentanyl decreases the minimum alveolar concentration (MAC) of inhaled anaesthetics and has been used clinically to reduce the requirements of other anaesthetic drugs in humans and small animals. We hypothesized that i.v. fentanyl would decrease the MAC of isoflurane in horses in a dose-dependent manner., Methods: Following determination of baseline MAC of isoflurane, fentanyl was administered i.v. to target plasma concentrations of 1, 8 and 16 ng ml(-1). Each horse was randomly assigned two of three target concentrations administered in ascending order. Loading and infusion doses for each horse were determined from previously derived individual pharmacokinetic values. Isoflurane MAC determination began 45 min after fentanyl administration at each target fentanyl concentration. Venous blood was collected at fixed intervals during the infusion for measurement of plasma fentanyl concentrations., Results: Mean actual fentanyl plasma concentrations were 0 (baseline), and 0.72 (SD 0.26), 8.43 (3.22), and 13.31 (6.66) ng ml(-1) for the target concentrations of 1, 8 and 16 ng ml(-1), respectively. The corresponding isoflurane MAC values were a baseline of 1.57 (0.23), and 1.51 (0.24), 1.41 (0.23) and 1.37 (0.09)%, respectively. The fentanyl concentrations of 0.72 and 8.43 ng ml(-1) did not significantly alter the MAC of isoflurane, but an 18 (7)% ISO-MAC reduction was observed at the 13.31 ng ml(-1) concentration., Conclusions: These results cautiously encourage further study of fentanyl as an opioid anaesthetic adjunct to inhalant anaesthesia in horses.

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 (tau) 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 tau 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.

Objective: To evaluate the use of xylazine and ketamine for total i.v. anesthesia in horses., Animals: 8 horses., Procedure: Anesthetic induction was performed on 4 occasions in each horse with xylazine (0.75 mg/kg, i.v.), guaifenesin (75 mg/kg, i.v.), and ketamine (2 mg/kg, i.v.). 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 (microg/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 Pa(O2) 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.

Objective: To quantitate effects of dose of sevoflurane and mode of ventilation on cardiovascular and respiratory function in horses and identify changes in serum biochemical values associated with sevoflurane anesthesia., Animals: 6 healthy adult horses., Procedure: Horses were anesthetized twice: first, to determine the minimum alveolar concentration (MAC) of sevoflurane and second, to characterize cardiopulmonary and serum biochemical responses of horses to 1.0, 1.5, and 1.75 MAC multiples of sevoflurane during controlled and spontaneous ventilation. Results-Mean (+/- SEM) MAC of sevoflurane was 2.84 +/- 0.16%. Cardiovascular performance during anesthesia decreased as sevoflurane increased; the magnitude of cardiovascular depression was more severe during mechanical ventilation, compared with spontaneous ventilation. Serum inorganic fluoride concentration increased to a peak of 50.8 +/- 7.1 micromol/L at the end of anesthesia. Serum creatinine concentration and sorbitol dehydrogenase activity reached their greatest values (2.0 +/- 0.8 mg/dL and 10.2 +/- 1.8 U/L, respectively) at 1 hour after anesthesia and then returned to baseline by 1 day after anesthesia. Serum creatine kinase, aspartate aminotransferase, and alkaline phosphatase activities reached peak values by the first (ie, creatine kinase) or second (ie, aspartate aminotransferase and alkaline phosphatase) day after anesthesia., Conclusions and Clinical Relevance: Sevoflurane causes dose-related cardiopulmonary depression, and mode of ventilation further impacts the magnitude of this depression. Except for serum inorganic fluoride concentration, quantitative alterations in serum biochemical indices of liver- and muscle-cell disruption and kidney function were considered clinically unremarkable and similar to results from comparable studies of other inhalation anesthetics.

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 1X, 1.5X, and 1.75X 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 (2.63microM/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 1X to 1.5X 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.

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 quantitate the dose- and time-related effects of IV administration of xylazine and detomidine on urine characteristics in horses deprived of feed and water., Animals: 6 horses., Procedure: Feed and water were withheld for 24 hours followed by i.v. administration of saline (0.9% NaCI) solution, xylazine (0.5 or 1.0 mg/kg), or detomidine (0.03 mg/kg). Horses were treated 4 times, each time with a different protocol. Following treatment, urine and blood samples were obtained at 15, 30, 60, 120, and 180 minutes. Blood samples were analyzed for PCV and serum concentrations of total plasma solids, sodium, and potassium. Urine samples were analyzed for pH and concentrations of glucose, proteins, sodium, and potassium., Results: Baseline (before treatment) urine flow was 0.30 +/- 0.03 mL/kg/h and did not significantly change after treatment with saline solution and low-dose xylazine but transiently increased by 1 hour after treatment with high-dose xylazine or detomidine. Total urine output at 2 hours following treatment was 312 +/- 101 mL versus 4,845 +/- 272 mL for saline solution and detomidine, respectively. Absolute values of urine concentrations of sodium and potassium also variably increased following xylazine and detomidine administration., Conclusions and Clinical Relevance: Xylazine and detomidine administration in horses deprived of feed and water causes transient increases in urine volume and loss of sodium and potassium. Increase in urine flow is directly related to dose and type of alpha2-adrenergic receptor agonist. Dehydration in horses may be exacerbated by concurrent administration of alpha2-adrenergic receptor agonists.

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.

Objective: To qualitatively and quantitatively evaluate the characteristics of desflurane with regard to the induction of and recovery from anesthesia in cats., Animals: 6 cats., Procedure: Anesthesia was induced and maintained with desflurane in oxygen. Individual minimum alveolar concentration (MAC) values were determined; anesthesia was maintained at 1.25 x MAC for a total anesthesia time (including MAC determination) of 5 hours. Cats were allowed to recover from anesthesia. Induction and recovery periods were video recorded and later scored by use of a grading scale from 0 to 100 (100 being the best outcome). Timing of events was recorded., Results: The MAC of desflurane was 10.27 +/- 1.06%, and mean dose was 5.6 +/- 0.2 MAC-hours. Times to loss of coordination, recumbency, and endotracheal intubation were 1.3 +/- 0.4, 2.3 +/- 0.3, and 6.4 +/- 1.1 minutes, respectively. Median score for quality of anesthetic induction was 93 (range, 91 to 94). Times to first movement, extubation, standing, and ability to jump and land with coordination were 2.8 +/- 1.0, 3.8 +/- 0.5, 14.3 +/- 3.9, and 26.4 +/- 5.1 minutes, respectively. Alveolar washout of desflurane was rapid. Median score for quality of anesthetic recovery was 94 (range, 86 to 96)., Conclusions and Clinical Relevance: Desflurane was associated with rapid induction of and recovery from anesthesia in cats; assessors rated the overall quality of induction and recovery as excellent. Results appear to support the use of desflurane for induction and maintenance of anesthesia in healthy cats.

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, i.v.) administration followed immediately by i.v. administration of saline (0.9% NaCI) 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.

Background: The minimum alveolar concentration (MAC) of an inhaled anaesthetic describes its potency as a general anaesthetic. Individuals vary in their sensitivity to anaesthetics and we sought to determine whether an individual animal's sensitivity to inhaled anaesthetics would be maintained across different agents., Methods: Six female mongrel cats, age 2 yr (range 1.8-2.3) and mean weight 3.5 (SD 0.3) kg, were studied on three separate occasions over a 12-month period to determine the MAC of isoflurane, sevoflurane and desflurane. Induction of anaesthesia in a chamber was followed by orotracheal intubation and maintenance of anaesthesia with the inhaled agent in oxygen delivered via a non-rebreathing circuit. MAC was determined in triplicate using standard tail-clamp technique., Results: Mean MAC values for isoflurane, sevoflurane and desflurane were 1.90 (SD 0.18), 3.41 (0.65) and 10.27 (1.06)%, respectively. Body temperature, systolic pressure and Sp(O(2)) recorded at the time of MAC determinations for isoflurane, sevoflurane and desflurane were 38.3 (0.3), 38.6 (0.1) and 38.3 (0.3) degrees C; 71.2 (8.3), 74.6 (15.9) and 88.0 (12.0) mmHg; 99.2 (1.1), 99.1 (1.3) and 99.4 (0.8)%, respectively. Both the anaesthetic agent and the individual cat had significant effects on MAC. Correlation coefficients for comparisons between desflurane and isoflurane, desflurane and sevoflurane, and sevoflurane and isoflurane were 0.90, 0.89 and 0.97, respectively., Conclusions: These findings show that an individual has a consistent degree of sensitivity to a variety of inhaled anaesthetics, suggesting a genetic basis for sensitivity to inhaled anaesthetic effects.

Objective: To test the hypothesis that isoflurane-anesthetized horses during controlled ventilation and spontaneous ventilation exhibit temporal changes in cerebral hemodynamics, as measured by intracranial pressure and cerebral perfusion pressure, that reflect temporal changes in systemic arterial pressure., Animals: 6 healthy adult horses., Procedure: Horses were anesthetized in left lateral recumbency with 1.57% isoflurane in O2 for 5 hours in 2 experiments by use of either controlled ventilation (with normocapnia) or spontaneous ventilation (with hypercapnia) in a randomized crossover design. Intracranial pressure was measured with a subarachnoid strain-gauge transducer. Carotid artery pressure, central venous pressure, airway pressures, blood gases, and minute ventilation also were measured., Results: Intracranial pressure during controlled ventilation significantly increased during constant dose isoflurane anesthesia and thus contributed to decreasing cerebral perfusion pressure. Intracranial pressure was initially higher during spontaneous ventilation than during controlled ventilation, but this difference disappeared over time; no significant differences in cerebral perfusion pressures were observed between horses that had spontaneous or controlled ventilation., Conclusions and Clinical Relevance: Cerebral hemodynamics and their association with ventilation mode are altered over time in isoflurane-anesthetized horses and could contribute to decreased cerebral perfusion during prolonged anesthesia.

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.

Objective: To quantitate dose- and time-related magnitudes of interactive effects of morphine (MOR) and isoflurane (ISO) in horses and to characterize pharmacokinetics of MOR in plasma and the ventilatory response to MOR during administration of ISO., Animals: 6 adult horses., Procedure: Horses were anesthetized 3 times to determine the minimum alveolar concentration (MAC) of ISO in O2 and then to characterize the change in anesthetic requirement as defined by the alteration in ISO MAC following IV administration of saline (0.9% NaCl) solution and 2 doses of MOR (low dose, 0.25 mg/kg; high dose, 2.0 mg/kg). Arterial blood samples were obtained before and after MOR and analyzed., Results: Mean +/- SD baseline ISO MAC was 1.43 +/- 0.06%. The ISO MAC did not change with time after administration of saline solution. Effects of MOR on ISO MAC varied. Maximal change in MAC ranged from -20.2 to +28.3% and -18.9 to +56.2% after low and high doses of MOR, respectively. Typical half-life of MOR in plasma was 40 to 60 minutes and related to dose. Mean PaCO2 increased from 70 mm Hg before MOR to 88 to 102 mm Hg for 30 to 240 minutes after the high dose of MOR. Recovery from anesthesia after administration of the high dose of MOR was considered undesirable and dangerous., Conclusions and Clinical Relevance: Our results do not support routine clinical use of MOR administered IV at dosages of 0.25 or 2.0 mg/kg as an adjuvant to anesthesia in horses administered ISO.

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., Animal: adult horses of various breeds., Procedures: 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 ICR Hypercapnic spontaneous ventilation caused significant increases in MAP and ICR compared with normocapnic controlled ventilation; no change in CPP was observed., Conclusions 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 opposing influences of a decrease in CCP and cerebral vasodilation.

Objective: To develop a method for surgical placement of a commercial microsensor intracranial pressure (ICP) transducer and to characterize normal ICP and cerebral perfusion pressures (CPP) in conscious adult horses., Animals: 6 healthy castrated male adult horses (1 Holsteiner, 1 Quarter Horse, and 4 Thoroughbreds)., Procedure: Anesthesia was induced and maintained by use of isoflurane as the sole agent. Catheters were inserted percutaneously into the jugular vein and carotid artery. A microsensor ICP transducer was inserted in the subarachnoid space by means of right parietal craniotomy. The burr hole was then sealed with bone wax, the surgical incision was sutured, and the transducer was secured in place. Measurements were collected 1 hour after horses were able to stand during recovery from anesthesia., Results: Mean +/- SD values for ICP and CPP were 2 +/- 4 and 102 +/- 26 mm Hg, respectively., Conclusions and Clinical Relevance: This report describes a relatively facile technique for obtaining direct and accurate ICP measurements for adult horses. The ICP values obtained in this study are within reference ranges established for other species and provide a point of reference for the diagnosis of abnormal ICP in adult horses.

The volatile anaesthetic sevoflurane is degraded to fluoride (F-) and a vinyl ether (Compound A), which have the potential to harm kidney and liver. Whether renal and hepatic injuries can occur in horses is unknown. Cardiopulmonary, biochemical and histopathological changes were studied in six healthy thoroughbred horses undergoing 18 h of low-flow sevoflurane anaesthesia. Serum F- concentrations were measured and clinical laboratory tests performed to assess hepatic and renal function before and during anaesthesia. Necropsy specimens of kidney and liver were harvested for microscopic examination and compared to pre-experimental needle biopsies. Cardiopulmonary parameters were maintained at clinically acceptable levels throughout anaesthesia. Immediately after initiation of sevoflurane inhalation, serum F- levels began to rise, reaching an ongoing 38-45 micromol 1(-1) plateau at 8 h of anaesthesia. Serum biochemical analysis revealed only mild increases in glucose and creatinine kinase and a decrease in total calcium. Beyond 10 h of anaesthesia mild, time-related changes in urine included increased volume, glucosuria and enzymuria. Histological examination revealed mild microscopic changes in the kidney involving mainly the distal tubule, but no remarkable alterations in liver tissue. These results indicate that horses can be maintained in a systemically healthy state during unusually prolonged sevoflurane anaesthesia with minimal risk of hepatocellular damage from this anaesthetic. Furthermore, changes in renal function and morphology observed after sevoflurane inhalation are judged minimal and appear to be clinically irrelevant; they may be the result of anaesthetic duration, physiological stressors, sevoflurane (or its degradation products) or other unkown factors associated with these animals and study conditions.

Objective: To characterize the effect of general anesthesia and minor surgery on renal function in horses., Animals: 9 mares with a mean (+/- SE) age and body weight of 9+/-2 years and 492+/-17 kg, respectively., Procedure: The day before anesthesia, urine was collected (catheterization) for 3 hours to quantitate baseline values, and serum biochemical analysis was performed. The following day, xylazine (1.1 mg/kg, IV) was administered, and general anesthesia was induced 5 minutes later with diazepam (0.04 mg/kg, IV) and ketamine (2.2 mg/kg, IV). During 2 hours of anesthesia with isoflurane, Paco2 was maintained between 48 and 52 mm Hg, and mean arterial blood pressure was between 70 and 80 mm Hg. Blood and urine were collected at 30, 60, and 120 minutes during and at 1 hour after anesthesia., Results: Baseline urine flow was 0.92+/-0.17 ml/kg/h and significantly increased at 30 and 60 minutes after xylazine administration (2.14+/-0.59 and 2.86+/-0.97 ml/kg/h respectively) but returned to baseline values by the end of anesthesia. Serum glucose concentration increased from 12+/-4 to 167+/-8 mg/dl at 30 minutes. Glucosuria was not observed., Conclusions and Clinical Relevance: Transient hyperglycemia and an increase in rine production accompanies a commonly used anesthetic technique for horses. The increase in urine flow is not trivial and should be considered in anesthetic management decisions. With the exception of serum glucose concentration and urine production, the effect of general anesthesia on indices of renal function in clinically normal horses is likely of little consequence in most horses admitted for elective surgical procedures.

Inhalant anesthetics may interfere with normal cerebrovascular autoregulation. It was, therefore, hypothesized that intracranial pressure (ICP) and cerebral perfusion pressure (CPP) in isoflurane-anesthetized horses would be especially sensitive to body and head position because of the potential for large hydrostatic gradients between the brain and heart in this species. Anesthesia was induced and maintained in six clinically healthy, unmedicated geldings with 1.57% isoflurane in O(2); mechanical ventilation was used to maintain normocapnia. ICP was measured by using a subarachnoid strain-gauge transducer. Blood gases and carotid arterial, right atrial, and airway pressures were also measured. Five body positions were studied in semirandomized order: dorsal recumbency (DR) with head down (HD), DR with head level (HL), lateral recumbency (LR), sternal recumbency (SR) with HL, and SR with head up (HU). Data were analyzed by using paired t-tests. ICP and CPP values, respectively, are as follows (means +/- SD): 36 +/- 4 and 55 +/- 18 mmHg (DR-HD); 34 +/- 6 and 51 +/- 32 mmHg (DR-HL); 24 +/- 5 and 48 +/- 4 mmHg (LR); 19 +/- 11 and 87 +/- 12 mmHg (SR-HL); and -14 +/- 7 and 71 +/- 10 mmHg (SR-HU). Significant differences were found among all positions, except for SR-HL vs. LR. Significant increases in CPP were observed only in sternal positions. In conclusion, ICP in isoflurane-anesthetized horses changes inversely with the brain-to-heart hydrostatic gradient. DR may also cause increases in ICP, irrespective of head position.

Objective: To establish the route of infusion (IV or intraosseous) that results in the highest concentration of amikacin in the synovial fluid of the tibiotarsal joint and determine the duration of peak concentrations., Animals: 21 horses., Procedure: Regional perfusion of a limb on 15 horses was performed. Amikacin sulfate was infused into the saphenous vein or via intraosseous infusion into the distal portion of the tibia (1 g in 56 ml of lactated Ringer's solution) or proximal portion of the metatarsus (1 g of amikacin in 26 ml of lactated Ringer's solution). Amikacin concentrations were measured in sequential samples from tibiotarsal joint synovial fluid and serum. Samples were obtained immediately prior to release of the tourniquet and 0.5, 1, 4, 8, 12, and 24 hours after the tourniquet was released. Radiographic contrast material was infused into the same locations as the antibiotic perfusate to evaluate distribution in 6 other horses., Results: Infusion into the saphenous vein produced the highest concentration of amikacin in the tibiotarsal joint, compared with the distal portion of the tibia (mean +/- SE, 701.8 +/- 366.8 vs 203.8 +/- 64.5 microg/ml, respectively). Use of a lower volume of diluent in the proximal portion of the metatarsus produced a peak value of 72.2 +/- 23.4 microg/ml., Conclusions and Clinical Relevance: For regional perfusion of the tarsus, IV infusion is preferred to intraosseous infusion, because higher concentrations are achieved in the synovial fluid, and the procedure is easier to perform.

Objective: To evaluate sevoflurane as an inhalation anesthetic for thoracotomy in horses., Animals: 18 horses between 2 and 15 years old., Procedure: 4 horses were used to develop surgical techniques and were euthanatized at the end of the procedure. The remaining 14 horses were selected, because they had an episode of bleeding from their lungs during strenuous exercise. General anesthesia was induced with xylazine (1.0 mg/kg of body weight, IV) followed by ketamine (2.0 mg/kg, IV). Anesthesia was maintained with sevoflurane in oxygen delivered via a circle anesthetic breathing circuit. Ventilation was controlled to maintain PaCO2 at approximately 45 mm Hg. Neuromuscular blocking drugs (succinylcholine or atracurium) were administered to eliminate spontaneous breathing efforts and to facilitate surgery. Cardiovascular performance was monitored and supported as indicated., Results: 2 of the 14 horses not euthanatized died as a result of ventricular fibrillation. Mean (+/- SD) duration of anesthesia was 304.9 +/- 64.1 minutes for horses that survived and 216.7 +/- 85.5 minutes for horses that were euthanatized or died. Our subjective opinion was that sevoflurane afforded good control of anesthetic depth during induction, maintenance, and recovery., Conclusions and Clinical Relevance: Administration of sevoflurane together with neuromuscular blocking drugs provides stable and easily controllable anesthetic management of horses for elective thoracotomy and cardiac manipulation.

Objective: To quantitate dose- and time-related anesthetic-sparing effects of xylazine hydrochloride (XYL) during isoflurane-induced anesthesia in horses and to characterize selected physiologic responses of anesthetized horses to administration of XYL., Animals: 6 healthy adult horses., Procedure: Horses were anesthetized 2 times to determine the minimum alveolar concentration (MAC) of isoflurane in O2 and to characterize the anesthetic-sparing effect (MAC reduction) after IV administration of XYL (0.5 and 1 mg/kg of body weight, random order). Selected measures of cardiopulmonary function, blood glucose concentrations, and urinary output also were measured during the anesthetic studies., Results: Isoflurane MAC (mean +/- SEM) was reduced by 24.8 +/- 0.5 and 34.2 +/- 1.9% at 42 +/- 7 and 67 +/- 10 minutes, respectively, after administration of XYL at 0.5 and 1 mg/kg. Amount of MAC reduction by XYL was dose- and time-dependent. Overall, cardiovascular and respiratory values varied little among treatments. Administration of XYL increased blood glucose concentration; the magnitude of change was dose- and time-dependent. Urine volume increased but not significantly., Conclusions and Clinical Relevance: Administration of XYL reduced the anesthetic requirement for isoflurane in horses. The magnitude of the decrease is dose- and time-dependent. Administration of XYL increases blood glucose concentration in anesthetized horses in a dose-related manner.

A captive 590-kg (1,298-lb) 22-year-old castrated male Kodiak brown bear was evaluated because of a soft tissue mass in the right carpal and antebrachial regions. General anesthesia was deemed necessary on 3 occasions for various procedures including radiographic evaluation and biopsy, excision, and radiation treatment. The bear was given carfentanil orally to induce sedation, followed by i.m. administration of tiletamine-zolazepam (on 1 occasion) and atropine. Anesthesia was maintained by administration of isoflurane in oxygen. After each procedure, effects of carfentanil were reversed by administration of naltrexone. Although there was some variability, blood pressure, nasal temperature, heart rate, respiratory rate, oxygen saturation, PO2, and PCO2 remained within a clinically acceptable ranges.

Objective: To determine pharmacokinetics and selected cardiopulmonary effects of fentanyl in isoflurane-anesthetized rhesus monkeys., Animals: 6 adult male rhesus monkeys., Procedure: Fentanyl (8 mg/kg of body weight, IV) was administered to 6 monkeys anesthetized with isoflurane. End-tidal isoflurane concentration and esophageal temperature were kept constant, and ventilation was mechanically assisted. Heart rate, rhythm, aortic blood pressure, and blood pH, gas, and fentanyl concentrations were determined before and for 8 hours after administration of fentanyl. Pharmacokinetics of fentanyl were derived by use of noncompartmental methods based on statistical moment theory., Results: Heart rate and mean arterial pressure decreased transiently following fentanyl administration. Maximal decreases were observed 5 to 15 minutes after administration. Arterial pH, Paco2, and Pao2 ranged from 7.46 +/- 0.04 to 751 +/- 0.05 units, 29.2 +/- 3 to 34.6 +/- 4.4 mm Hg, and 412.6 +/- 105.3 to 482.9 +/- 71.2 mm Hg, respectively. The clearance, volume of distribution area, volume of distribution steady state, mean residence time, area under the curve, elimination rate constant, and half-life were 32.5 +/- 2.48 ml/kg/min, 9.04 +/- 1.91 L/kg, 70 +/- 1.2 L/kg, 218.5 +/- 35.5 min, 0.247 +/- 0.019 mg/ml/min, 0.004 + 0.001/min, and 192.0 +/- 33.5 min, respectively., Conclusions and Clinical Relevance: Transient but potentially clinically important decreases in heart rate and mean arterial pressure were observed following fentanyl administration. Distribution and clearance data were similar to those reported for dogs and humans.

An Asian elephant (Elephas maximus) required general anesthesia for orthopedic foot surgery. The elephant was unable to lie down, so it was placed in a custom-made sling, administered i.m. etorphine hydrochloride in the standing position, and lowered to lateral recumbency. General anesthesia was maintained with isoflurane administered through an endotracheal tube. After surgery, the isoflurane anesthesia was terminated, with immobilization maintained with additional i.v. etorphine. The elephant was lifted to the vertical position, and the immobilizing effects of etorphine were reversed with naltrexone. The suspension system and hoist for the sling were designed specifically for the elephant house.

Background: Patients in the intensive care unit may have muscle weakness in the recovery phase, and disuse atrophy may play a role in this weakness. To assess this problem, the authors measured changes in the potency of the nondepolarizing neuromuscular blocking agent metocurine in a canine model that involved 3 weeks of intensive care, nonparalyzing anesthesia with pentobarbital, and positive-pressure ventilation., Methods: Six dogs were anesthetized with pentobarbital to a sufficient depth that spontaneous and reflex muscle movements were absent. Their tracheas were intubated, their lungs were mechanically ventilated, and they received round-the-clock intensive medical and nursing care for 3 weeks. Transduced gastrocnemius muscle responses to metocurine were determined weekly. A 4- to 15-min infusion of 148-4,300 microg/min (longer durations and greater concentrations on progressive weeks) yielded more than 80% paralysis. Serial metocurine plasma concentrations during the onset of the block and recovery provided data to determine pharmacokinetics using NONMEM. Metocurine plasma concentrations and the degree of paralysis were used to model the effect compartment equilibration constant, and the Hill equation was used to yield the slope factor and potency within the effect compartment., Results: The metocurine effect compartment concentration associated with a 50% diminution of twitch height after 3 weeks was 1,716+/-1,208 ng/ml (mean +/- SD), which was significantly different from 257+/-34 ng/ml, the value on day 0. There were no pharmacokinetic differences., Conclusion: The absence of muscle tone and reflex responsiveness for 3 weeks was associated with exaggerated resistance to the neuromuscular blocker metocurine.

Propofol and pentobarbital were used for deep sedation during prolonged mechanical ventilation (3 weeks) and nutritional supplementation in 17 clinically normal dogs in an intensive care setting. Tolerance developed to both drugs. Propofol, in combination with pentobarbital, at an infusion rate of 75 micrograms/kg of body weight per minute was preferred. Pentobarbital infusion alone, begun at the rate of 5 to 6 mg.kg-1.h-1, was satisfactory. The combination of both drugs provided smooth, stable anesthesia and required minimal interventions by intensive care unit personnel. Blood gas tensions and electrolyte, parathyroid hormone (PTH), and metabolite concentrations were generally stable throughout, unless condition of the dog deteriorated (e.g., infection, pneumothorax). Hematocrit and red blood cell count decreased with time, likely attributable principally to multiple blood sample collections. White blood cell count, alkaline phosphatase, phosphate, fibrinogen, cholesterol, and triglyceride values increased with time, in association with pentobarbital and the combination of pentobarbital and propofol. Some of these changes appear to have been related to generic responses to stress and inflammation, some to altered metabolism, and some to the lipid solvent of propofol. The increase in triglyceride concentration was greater when propofol was used. Mortality was 47%, with death occurring between days 2 and 18.

Unlabelled: Nonimmobilizers (inhaled compounds that do not suppress movement in response to a noxious stimulus) resemble anesthetics in their capacity to suppress memory, but unlike anesthetics, they can cause convulsions. Higher concentrations of nonimmobilizers may cause death, even with apparent suppression of convulsions by the concurrent administration of conventional inhaled anesthetics. We hypothesized that nonimmobilizers can depress ventilation and can cause death by adding to the depression of ventilation produced by conventional anesthetics. To test these hypotheses, we administered 1,2-dichlorohexafluorocyclobutane (2N) to four pigs anesthetized with desflurane. The addition of 2N decreased PaCO2 and tended to increase the slope of the ventilatory response to imposed increases in PETCO2. Limited results from study of two other nonimmobilizers (2,3-dichlorooctafluorobutane and perfluoropentane), in two pigs each, were consistent with the findings for 2N. However, experimental limitations (e.g., toxicity of 2,3-dichlorooctafluorobutane, and hypoxia from perfluoropentane) confound interpretation of these latter results. Our findings do not support our hypotheses--2N (and presumably all nonimmobilizers) seems to be a respiratory stimulant, not a depressant., Implications: A new class of inhaled compounds, nonimmobilizers, allow tests of how inhaled anesthetics act. Nonimmobilizers may act like anesthetics (e.g., impair learning) or may not (e.g., do not prevent movement in response to a noxious stimulus). The present work shows that, unlike anesthetics,nonimmobilizers do not depress breathing.

Unlabelled: In a model anesthetic circuit, dehydration of Baralyme brand carbon dioxide absorbent increases degradation of sevoflurane to CF2=C(CF3)OCH2F, a nephrotoxic vinyl ether called Compound A. In the present study, we quantified this increase using "conditioned" Baralyme in a circle absorbent system to deliver sevoflurane anesthesia to swine. Mimicking continuing oxygen delivery for 2 days after completion of an anesthetic, we directed a conditioning fresh gas flow of 5 L/min retrograde through fresh absorbent in situ in a standard absorbent system for 40 h. The conditioned absorbent was subsequently used (without mixing of the granules) in a standard anesthetic circuit to deliver sevoflurane to swine weighing 78 +/- 2 kg. The initial inflow rate of fresh gas flow was set at 10 L/min with the vaporizer at 8% to achieve the target end-tidal concentration of 3.0%-3.2% sevoflurane in approximately 20 min. The flow was later decreased to 2 L/min, and the vaporizer concentration was decreased to sustain the 3.0%-3.2% value for a total of 2 h (three pigs) or 4 h (eight pigs). Inspired Compound A increased over the first 30 +/- 60 min to a peak concentration of 357 +/- 49 ppm (mean +/- SD), slowly decreasing thereafter to 74 +/- 6 ppm at 4 h. The average concentration over 2 h was 208 +/- 25 ppm, and the average concentration over 4 h was 153 +/- 19 ppm. Pigs were killed 1 or 4 days after anesthesia. The kidneys from pigs anesthetized for both 2 h and 4 h showed mild inflammation but little or no tubular necrosis. These results suggest that dehydration of Baralyme may produce concentrations of Compound A that would have nephrotoxic effects in humans in a shorter time than would be the case with normally hydrated Baralyme., Implications: The vapor known as Compound A can injure the kidney. Dehydration of Baralyme, a standard absorbent of carbon dioxide in inhaled anesthetic delivery systems, can cause a 5- to 10-fold increase in Compound A concentrations produced from the inhaled anesthetic, sevoflurane, given at anesthetizing concentrations in a conventional anesthetic system.