A comparison of the duration and quality of recovery from isoflurane, sevoflurane and desflurane anaesthesia in dogs undergoing magnetic resonance imaging.

OBJECTIVE: To compare the recovery after anaesthesia with isoflurane, sevoflurane and desflurane in dogs undergoing magnetic resonance imaging (MRI) of the brain. STUDY DESIGN: Prospective, randomized clinical trial. ANIMALS: Thirty-eight dogs weighing 23.7 +/- 12.6 kg. METHODS: Following pre-medication with meperidine, 3 mg kg(-1) administered intramuscularly, anaesthesia was induced intravenously with propofol (mean dose 4.26 +/- 1.3 mg kg(-1)), the trachea was intubated, and an inhalational anaesthetic agent was administered in oxygen. The dogs were randomly allocated to one of three groups: group I (n = 13) received isoflurane, group S (n = 12) received sevoflurane and group D (n = 13) received desflurane. Parameters recorded included cardiopulmonary data, body temperature, end-tidal anaesthetic concentration, duration of anaesthesia, and recovery times and quality. Qualitative data were compared using chi-squared and Fisher's exact tests and quantitative data with anova and Kruskal-Wallis test. Post-hoc comparisons for quantitative data were undertaken with the Mann-Whitney U-test. RESULTS: The duration of anaesthesia [mean and standard deviation (SD)] in group I was: 105.3 (27.48) minutes, group S: 120.67 (19.4) minutes, and group D: 113.69 (26.68) minutes (p = 0.32). Times to extubation [group I: 8 minutes, (interquartile range 6-9.5), group S: 7 minutes (IQR 5-7), group D: 5 minutes (IQR 3.5-7), p = 0.017] and to sternal recumbency [group I: 11 minutes (IQR 9.5-13.5), group S: 9.5 minutes (IQR 7.25-11.75), group D: 7 minutes (range 3.5-11.5), p = 0.048] were significantly different, as were times to standing. One dog, following sevoflurane, had an unacceptable quality of recovery, but most other recoveries were calm, with no significant difference between groups. CONCLUSIONS AND CLINICAL RELEVANCE: All three agents appeared suitable for use. Dogs' tracheas were extubated and the dogs recovered to sternal recumbency most rapidly after desflurane. This may be advantageous for animals with some neurological diseases and for day case procedures.

Maintenance of anaesthesia in sheep with isoflurane, desflurane or sevoflurane.

Rapid recovery from anaesthesia is advantageous in small ruminants, to reduce the risk of regurgitation. Theoretically, the least soluble inhalation agents should result in the fastest recoveries, but using additional injectable agents may negate this advantage. This study compared three inhalation agents for the maintenance of anaesthesia in sheep. Eighteen ewes that were to undergo orthopaedic surgery were allocated to one of three groups. Each group was premedicated with xylazine (0.1 mg/kg intramuscularly), anaesthesia was induced using ketamine (2 mg/kg) and midazolam (0.03 mg/kg) intravenously and analgesia provided by buprenorphine (0.008 mg/kg intramuscularly). Anaesthesia was then maintained with either isoflurane, sevoflurane or desflurane. Cardiopulmonary parameters were monitored throughout. All three inhalation agents provided adequate stable anaesthesia and there was no significant difference between the groups in their cardiopulmonary parameters or their recovery times. The mead (sd) postanaesthetic times to first swallow, first chewing attempts and ability to maintain their head lifted for five minutes were, respectively, 3.95 (2.53), 6.37 (3.68) and 32.8 (18.1) minutes for isoflurane, 3.62 (0.98), 7.66 (0.78) and 38.8 (16.6) minutes for sevoflurane, and 4.37 (1.65), 6.95 (1.52) and 29.8 (11.5) minutes for desflurane. Two sheep had poor quality recoveries after the use of sevoflurane, but all the other sheep recovered uneventfully. All three inhalation agents were suitable for the maintenance of anaesthesia in sheep but, as used in this study, there were no differences between them in speed of recovery.

The effect of hyoscine on dobutamine requirement in spontaneously breathing horses anaesthetized with halothane.

OBJECTIVE: To determine whether hyoscine has a sparing effect on the volume of dobutamine required to maintain mean arterial pressure (MAP) at 70 mmHg in horses anaesthetized with halothane. STUDY DESIGN: Prospective, randomized, controlled clinical trial. ANIMALS: Twenty adult horses weighing 507 +/- 97 kg (mean +/- SD), aged 10 +/- 5 years. MATERIALS AND METHODS: Pre-anaesthetic medication in all horses was intramuscular (IM) acepromazine (40 mug kg(-1)) and intravenous (IV) detomidine (0.02 mg kg(-1)). Anaesthesia was induced with ketamine (2.2 mg kg(-1) IV) and diazepam (0.02 mg kg(-1) IV), and maintained with halothane in oxygen. Horses breathed spontaneously. Flunixin (1.1 mg kg(-1) IV) was given to provide analgesia. Heart rate, ECG, invasive arterial pressure, respiratory rate, percentage end-tidal carbon dioxide, percentage end-tidal halothane and partial pressure of oxygen and carbon dioxide in arterial blood and blood pH were monitored. Dobutamine was infused by an infusion pump to maintain MAP at 70 mmHg. Horses were randomly assigned to receive saline or hyoscine (0.1 mg kg(-1)) IV 30 minutes after induction. The heart rate, MAP and volume of dobutamine infused over 30-minute periods were measured and analysed statistically using a one-way anova. RESULTS: After administration of hyoscine, heart rate increased for 10 minutes (p < 0.01) and MAP for 5 minutes (p < 0.01). There was no difference in the volume of dobutamine infused over 30 minutes between horses given hyoscine or saline, although there was a wide individual variation in dobutamine requirements. No side effects of hyoscine were seen. CONCLUSIONS: The increase in heart rate and blood pressure that occurs after 0.1 mg kg(-1) hyoscine is given IV in anaesthetized horses, is of short duration and does not significantly alter the amount of dobutamine required to maintain arterial pressure over the next 30 minutes. Clinical relevance The short duration of action of 0.1 mg kg(-1) hyoscine IV may limit its usefulness for correction of hypotension in horses anaesthetized with halothane. Further work is necessary to investigate the effects of higher or repeated doses or constant rate infusions of hyoscine.

Cardiopulmonary effects and pharmacokinetics of i.v. dexmedetomidine in ponies.

REASONS FOR PERFORMING STUDY: Currently available sedatives depress cardiopulmonary function considerably; therefore, it is important to search for new, less depressive sedatives. The study was performed to assess duration and intensity of cardiopulmonary side effects of a new sedative, dexmedetomidine (DEX), in horses. OBJECTIVES: To study pharmacokinetics and cardiopulmonary effects of i.v. DEX. METHODS: Pharmacokinetics of 3.5 microg/kg bwt i.v. DEX were studied in a group of 8 mature (mean age 4.4 years) and 6 old ponies (mean age 20 years). Cardiopulmonary data were recorded in mature ponies before and 5, 10, 20, 30, 45 and 60 mins after administration of DEX 3.5 microg/kg bwt i.v. Data were analysed using ANOVA for repeated measures, and where appropriate Dunnett's t test was used to detect differences from resting values (P < 0.05). RESULTS: Within 2 h after DEX administration, plasma levels were beyond limits of quantification (0.05 ng/ml). Mean values for kinetic parameters for mature and old ponies were: Cmax (ng/ml) 4.6 and 3.8, t 1/2 (min) 19.8 and 28.9 and AUC (ng.min/ml) 34.5 and 44.3, respectively. Heart rate, central venous pressure, pulmonary artery pressure and pulmonary capillary wedge pressure did not change significantly compared to presedation values throughout the 60 min observation period. Compared to presedation values, stroke volume and mixed venous PO2 were reduced for the first 5 mins, paralleled by an increase in systemic and pulmonary vascular resistance. Cardiac index was reduced for the first 10 mins, arterial blood pressures at 20, 30 and 45 mins and respiratory rate throughout the 60 min observation period, but no change in arterial PO2 or PCO2 occurred. CONCLUSIONS: DEX administration i.v. causes similar cardiopulmonary changes to those caused by other alpha-2 adrenoceptor agonists, but of very short duration. DEX is redistributed particularly rapidly. POTENTIAL RELEVANCE: DEX might be safer for sedation of horses because of its very short-lasting cardiopulmonary side effects. For long duration sedation, its kinetics favour its use as a continuous infusion.

Medetomidine-ketamine anaesthesia induction followed by medetomidine-propofol in ponies: infusion rates and cardiopulmonary side effects.

REASONS FOR PERFORMING STUDY: To search for long-term total i.v. anaesthesia techniques as a potential alternative to inhalation anaesthesia. OBJECTIVES: To determine cardiopulmonary effects and anaesthesia quality of medetomidine-ketamine anaesthesia induction followed by 4 h of medetomidine-propofol anaesthesia in 6 ponies. METHODS: Sedation consisted of 7 microg/kg bwt medetomidine i.v. followed after 10 min by 2 mg/kg bwt i.v. ketamine. Anaesthesia was maintained for 4 h with 3.5 microg/kg bwt/h medetomidine and propofol at minimum infusion dose rates determined by application of supramaximal electrical pain stimuli. Ventilation was spontaneous (F(I)O2 > 0.9). Cardiopulmonary measurements were always taken before electrical stimulation, 15 mins after anaesthesia induction and at 25 min intervals. RESULTS: Anaesthesia induction was excellent and movements after pain stimuli were subsequently gentle. Mean propofol infusion rates were 0.89-0.1 mg/kg bwt/min. No changes in cardiopulmonary variables occured over time. Range of mean values recorded was: respiratory rate 13.0-15.8 breaths/min; PaO2 29.1-37.9 kPa; PaCO2 6.2-6.9 kPa; heart rate 31.2-40.8 beats/min; mean arterial pressure 90.0-120.8 mmHg; cardiac index 44.1-59.8 ml/kg bwt/min; mean pulmonary arterial pressure 11.8-16.4 mmHg. Recovery to standing was an average of 31.1 mins and ponies stood within one or 2 attempts. CONCLUSIONS: In this paper, ketamine anaesthesia induction avoided the problems encountered previously with propofol. Cardiovascular function was remarkably stable. Hypoxaemia did not occur but, despite F(I)O2 of > 0.9, minimal PaO2 in one pony after 4 h anaesthesia was 8.5 kPa. POTENTIAL RELEVANCE: The described regime might offer a good, practicable alternative to inhalation anaesthesia and has potential for reducing the fatality rate in horses.

The effects of ephedrine on intramuscular blood flow and other cardiopulmonary parameters in halothane-anesthetized ponies.

OBJECTIVE: To evaluate the effect of ephedrine on intramuscular blood flow and hemodynamic parameters during equine anesthesia. STUDY DESIGN: Prospective experimental study. ANIMALS: Six healthy adult Welsh Mountain ponies (five males, one female, mean weight: 267 kg, range: 213-347 kg). METHODS: Halothane-anesthetized ponies received an IV bolus of ephedrine (0.1 mg kg-1), followed 30 minutes later by a second IV ephedrine injection (0.2 mg kg-1). Changes in intramuscular blood flows (IMBF) in upper and lower triceps brachii were measured by laser Doppler flowmetry. Cardiopulmonary measurements were made at intervals for 30 minutes following each injection. Results were compared with values from a control group, similarly anesthetized but given saline in an earlier study. RESULTS: Ephedrine at either dose increased heart rate, arterial blood pressure (AP), cardiac index (CI) and intramuscular blood flow (IMBF), the effects on these parameters being significant and long-lasting following the higher dose. Systemic vascular resistance remained unchanged, and was significantly lower than in the control saline group. PaO2 decreased significantly immediately following the first injection of ephedrine, then remained unchanged for the remainder of the experiment. PaCO2 increased slowly throughout the anesthetic period. One pony developed supraventricular premature complexes following the second injection. No other side effects were seen. CONCLUSION: Ephedrine at dose rates of 0.2 mg kg-1 IV consistently increased in CI, AP, and IMBF in both forelimbs. CLINICAL RELEVANCE: Ephedrine may be of use to improve AP, CI and IMBF during halothane anesthesia, although the occurrence of an arrhythmia in one pony is of concern.

Cardiopulmonary effects of prolonged anesthesia via propofol-medetomidine infusion in ponies.

OBJECTIVE: To determine cardiopulmonary effects of total IV anesthesia with propofol and medetomidine in ponies and effect of atipamezole on recovery. ANIMALS: 10 ponies. PROCEDURE: After sedation was induced by IV administration of medetomidine (7 microg/kg of body weight), anesthesia was induced by IV administration of propofol 12 mg/kg) and maintained for 4 hours with infusions of medetomidine (3.5 microg/kg per hour) and propofol 10.07 to 0.11 mg/kg per minute). Spontaneous respiration was supplemented with oxygen. Cardiopulmonary measurements and blood concentrations of propofol were determined during anesthesia. Five ponies received atipamezole (60 microg/kg) during recovery. RESULTS: During anesthesia, mean cardiac index and heart rate increased significantly until 150 minutes, then decreased until cessation of anesthesia. Mean arterial pressure and systemic vascular resistance index increased significantly between 150 minutes and 4 hours. In 4 ponies, PaO2 decreased to < 60 mm Hg. Mean blood propofol concentrations from 20 minutes after induction onwards ranged from 2.3 to 3.5 microg/ml. Recoveries were without complications and were complete within 28 minutes with atipamezole administration and 39 minutes without atipamezole administration. CONCLUSIONS AND CLINICAL RELEVANCE: During total IV anesthesia of long duration with medetomidine-propofol, cardiovascular function is comparable to or better than under inhalation anesthesia. This technique may prove suitable in equids in which prompt recovery is essential; however, in some animals severe hypoxia may develop and oxygen supplementation may be necessary.

Infusion of a combination of propofol and medetomidine for long-term anesthesia in ponies.

OBJECTIVE: To determine the minimal infusion rate of propofol in combination with medetomidine for long-term anesthesia in ponies and the effects of atipamezole on recovery. ANIMALS: 12 ponies. PROCEDURE: Ponies were sedated with medetomidine (7 microg/kg of body weight, IV). Ten minutes later, anesthesia was induced with propofol (2 mg/kg, IV). Anesthesia was maintained for 4 hours, using an infusion of medetomidine (3.5 microg/kg per hour, IV) and propofol at a rate sufficient to prevent ponies from moving after electrical stimulation. Arterial blood pressures and blood gas analysis, heart rates, and respiratory rates were monitored. For recovery, 6 ponies were given atipamezole (60 microg/kg, IV). Induction and recovery were scored. RESULTS: Minimal propofol infusion rates ranged from 0.06 to 0.1 mg/kg per min. Mean arterial blood pressure was stable (range, 74 to 86 mm Hg), and heart rate (34 to 51 beats/min) had minimal variations. Variable breathing patterns were observed. Mean PaO2 (range, 116 to 146 mm Hg) and mean PaCO2 (range, 48 to 51 mm Hg) did not change significantly with time, but hypoxemia was evident in some ponies (minimal PaO2, 47 mm Hg). Recovery was fast and uneventful with and without atipamezole (completed in 20.2 and 20.9 minutes, respectively). CONCLUSIONS AND CLINICAL RELEVANCE: Infusion of a combination of medetomidine and propofol was suitable for prolonged anesthesia in ponies. Recovery was rapid and uneventful. A combination of propofol and medetomidine may prove suitable for long-term anesthesia in horses. Monitoring of blood gases is essential because of potential hypoxemia.

Minimal alveolar concentration of desflurane in combination with an infusion of medetomidine for the anaesthesia of ponies.

The minimum alveolar concentration of desflurane when combined with a continuous infusion of medetomidine at 3.5 microg/kg/hour was measured in seven ponies. Anaesthesia was induced with medetomidine (7 microg/kg intravenously) followed by ketamine (2 mg/kg intravenously) and maintained with desflurane in oxygen. The infusion of medetomidine was started 20 minutes after the induction of anaesthesia. The electrical test stimulus was applied at the coronary band (50 V, 10 ms bursts at 5 Hz for one minute), and heart rates and rhythms, arterial blood pressures, and arterial blood gas tensions were measured at intervals, just before the application of the stimulus. The mean (sd) minimum alveolar concentration of desflurane was 5.3 (1.04) per cent (range 3.2 to 6.4 per cent), 28 per cent less than the previously published value for desflurane alone after the induction of anaesthesia with xylazine and ketamine. The cardiopulmonary parameters remained stable throughout the period of anaesthesia. The mean (sd) time taken by the ponies to stand after the administration of desflurane ceased was 16.5 (6.17) (range 5.8 to 26) minutes, and the quality of recovery was good or excellent. However, one pony died shortly after standing; a postmortem examination revealed that it had chronic left atrial dilatation.

Cardiopulmonary side-effects and pharmacokinetics of an emulsion of propofol (Disoprivan) in comparison to propofol solved in polysorbate 80 in goats.

The aim of this study was to determine whether any pharmacokinetic or pharmacodynamic differences exist in goats between propofol in its currently licensed form (Disoprivan) and a new 1% solution of propofol (NSP) containing polysorbate 80. Nine goats received, on two different occasions in a randomized double-blinded order, 4 mg/kg propofol intravenously (i.v.; Disoprivan or NSP). To detect differences in cardiopulmonary effects and pharmacokinetics, the Wilcoxon signed rank test for paired data was used. In the NSP group the duration of initial apnoea was significantly longer, and 6 and 12 min after drug application PaO2 levels were significantly lower than in the Disoprivan group. Mean cardiovascular parameters did not differ significantly between the groups but in the NSP group in six goats marked changes in blood pressure occurred: systolic arterial pressures fell to a minimum of 40-60 mmHg within the first 10 min. This was followed by a marked increase in blood pressure, with maxima exceeding 300 mmHg. In the NSP group the half-life of propofol was significantly longer, the clearance rate was smaller and the areas under the drug concentration-time curves were larger than in the Disoprivan group. The cardiopulmonary side-effects of NSP suggest that propofol dissolved in polysorbate 80 is not a suitable alternative to the current formulation of propofol.

Pharmacokinetics of medetomidine in ponies and elaboration of a medetomidine infusion regime which provides a constant level of sedation.

The pharmacokinetics of intravenous (i.v.) medetomidine (7 mcg kg(-1)) were best described by a two-compartment model in five ponies. Total body clearance was 4 (SD 0.60) 1 kg h,(-1)t(1/2alpha)7. 6 (0.91) minutes and t(1/2beta)51.3 (13.09) minutes. In one pony the one-compartmental model was best fit, and total body clearance was 4. 2 l kg h(-1)and t(1/2)was 11 minutes. Medetomidine plasma levels had fallen below the limits of quantification (0.05 ng ml(-1)) within 4 hours. Medetomidine 5 mcg kg(-1)i.v. followed by an infusion of 3.5 mcg kg h(-1)for two hours provided a constant level of sedation reaching steady state plasma medetomidine levels of 1-1.5 ng ml(-1)within 30 minutes. Sedation was reversed effectively by atipamezole (60 mcg kg(-1)) i.v. The pharmacokinetics of medetomidine make it suitable for prolonged use by infusion, such as is required as part of a total intravenous anaesthetic technique in horses.

Desflurane and sevoflurane. New volatile anesthetic agents.

Desflurane and sevoflurane, recently licensed for use in humans, have kinetics that result in rapid induction and easy maintenance of a stable level of anesthesia. Recovery is also rapid. Cardiopulmonary effects are similar to those of isoflurane. In humans, desflurane can cause airway irritation and sympathetic stimulation, but these side effects have not caused problems in animal trials. Metabolites of sevoflurane and breakdown products from its reaction with carbon dioxide absorbents theoretically could result in hepatic and renal damage, but such toxicity has not occurred despite extensive medical use. Clinical trials in animals are now in progress.

Characterisation of the cardiovascular pharmacology of medetomidine in the horse and sheep.

Medetomidine was administered to sheep and horses at a dose rate of 5 microg kg(-1) (i.v.). Heart rate and blood pressure were recorded. Medetomidine induced bradycardia and a biphasic blood pressure response consisting of a transient hypertension followed by hypotension. Administration of prazosin (an alpha1 adrenoceptor antagonist; 100 microg kg(-1), i.v.) had no effect on the cardiovascular response to medetomidine (5 microg kg(-1), i.v.), but inhibited the cardiovascular response of methoxamine (an alpha1 adrenoceptor agonist; 75 microg kg(-1), i.v.). L-659,066 (an alpha2 adrenoceptor antagonist which does not cross the blood brain barrier; 264 microg kg(-1), i.v.) attenuated the medetomidine induced bradycardia, but had no effect on the cardiovascular response to methoxamine. L659,066 also reduced the medetomidine induced hypertension in sheep, but had less effect on the horse. It is concluded that both alpha1 and alpha2 adrenoceptors are important in the control of cardiovascular function in horses and sheep. Medetomidine appears to act on alpha2 adrenoceptors alone in the sheep. The cardiovascular effects of medetomidine in the horse are complex and may be influenced by central alpha2 adrenoceptor regulation or effects on other receptor subtypes as well as direct stimulation of peripheral alpha2 adrenoceptors.

Effects of dopamine, dobutamine, dopexamine, phenylephrine, and saline solution on intramuscular blood flow and other cardiopulmonary variables in halothane-anesthetized ponies.

OBJECTIVE: To evaluate the effect on intramuscular blood flow (IMBF) and hemodynamic variables of 4 antihypotensive agents given during anesthesia. ANIMALS: 8 ponies. PROCEDURE: Halothane-anesthetized ponies (n = 6) positioned in lateral recumbency received, on separate occasions, infusions of each of the following 4 agents in serially increasing dosages or saline solution: phenylephrine hydrochloride (0.25, 0.5, 1, and 2 microg/kg of body weight), dopamine (2.5, 5, 10, and 20 microg/kg), dobutamine (1, 2.5, 5, and 10 microg/kg), and dopexamine (0.5, 1, 5, and 10 microg/kg). Changes in IMBF (by laser-Doppler flowmetry) in nondependent and dependent triceps brachii muscles and cardiopulmonary variables were measured. RESULTS: Phenylephrine at all dosages failed to improve IMBF or cardiac index (CI), but increased mean arterial pressure (MAP) and systemic vascular resistance (SVR); 2 ponies had forelimb lameness on recovery. Dopamine (10 microg/kg/min) increased CI, MAP, and IMBF in the dependent muscle. A higher dose (20 microg/kg/min) caused cardiac arrhythmias and muscular tremor. Dobutamine increased Cl, MAP, and IMBF of both forelimbs, effects being significant for 2.5 microg/kg/min, with further improvement as the dosage increased. In 2 ponies, 10 microg of dobutamine/kg/min caused cardiac arrhythmias. Dopexamine (1 and 5 microg/kg/min) increased CI, MAP, and IMBF in the nondependent muscle, and 10 microg/kg/min caused muscular tremor, sweating, and arrhythmias. SVR was reduced after infusion of dopamine, dobutamine, or dopexamine. CONCLUSION: During anesthesia of equids, an increase in Cl and MAP is necessary to improve IMBF in the dependent forelimb. CLINICAL RELEVANCE: Of the agents investigated, dobutamine proved the most consistent in improving IMBF.