Effect of intravenous administration of ketamine on the minimum alveolar concentration of isoflurane in anesthetized dogs

OBJECTIVE: To determine the effect of 6 plasma ketamine concentrations on the minimum alveolar concentration (MAC) of isoflurane in dogs. ANIMALS: 6 dogs. PROCEDURE: In experiment 1, the MAC of isoflurane was measured in each dog and the pharmacokinetics of ketamine were determined in isoflurane-anesthetized dogs after IV administration of a bolus (3 mg/kg) of ketamine. In experiment 2, the same dogs were anesthetized with isoflurane in oxygen. A target-controlled IV infusion device was used to administer ketamine and to achieve plasma ketamine concentrations of 0.5, 1, 2, 5, 8, and 11 microg/mL by use of parameters obtained from experiment 1. The MAC of isoflurane was determined at each plasma ketamine concentration, and blood samples were collected for ketamine and norketamine concentration determination. RESULTS: Actual mean +/- SD plasma ketamine concentrations were 1.07 +/- 0.42 microg/mL, 1.62 +/- 0.98 microg/mL, 3.32 +/- 0.59 microg/mL, 4.92 +/- 2.64 microg/mL, 13.03 +/- 10.49 microg/mL, and 22.80 +/- 25.56 microg/mL for target plasma concentrations of 0.5, 1, 2, 5, 8, and 11 microg/mL, respectively. At these plasma concentrations, isoflurane MAC was reduced by 10.89% to 39.48%, 26.77% to 43.74%, 25.24% to 84.89%, 44.34% to 78.16%, 69.62% to 92.31%, and 71.97% to 95.42%, respectively. The reduction in isoflurane MAC was significant, and the response had a linear and quadratic component. Salivation, regurgitation, mydriasis, increased body temperature, and spontaneous movements were some of the adverse effects associated with the high plasma ketamine concentrations. CONCLUSIONS AND CLINICAL RELEVANCE: Ketamine appears to have a potential role for balanced anesthesia in dogs.     

Effects of morphine,lidocaine, ketamine,and morphine-lidocaine-ketamine drug combination on minimum alveolar concentration in dogs anesthetized with isoflurane

OBJECTIVE: To determine the effects of constant rate infusion of morphine, lidocaine, ketamine, and morphine-lidocaine-ketamine (MLK) combination on end-tidal isoflurane concentration (ET-Iso) and minimum alveolar concentration (MAC) in dogs anesthetized with isoflurane and monitor depth of anesthesia by use of the bispectral index (BIS). ANIMALS: 6 adult dogs. PROCEDURE: Each dog was anesthetized with isoflurane on 5 occasions, separated by a minimum of 7 to 10 days. Individual isoflurane MAC values were determined for each dog. Reduction in isoflurane MAC, induced by administration of morphine (3.3 microg/kg/min), lidocaine (50 microg/kg/min), ketamine (10 microg/kg/min), and MLK, was determined. Heart rate, mean arterial blood pressure, oxygen saturation as measured by pulse oximetry (Spo2), core body temperature, and BIS were monitored. RESULTS: Mean +/- SD isoflurane MAC was 1.38 +/- 0.08%. Morphine, lidocaine, ketamine, and MLK significantly lowered isoflurane MAC by 48, 29, 25, and 45%, respectively. The percentage reductions in isoflurane MAC for morphine and MLK were not significantly different but were significantly greater than for lidocaine and ketamine. The Spo2, mean arterial pressure, and core body temperature were not different among groups. Heart rate was significantly decreased at isoflurane MAC during infusion of morphine and MLK. The BIS was inversely related to the ET-Iso and was significantly increased at isoflurane MAC during infusions of morphine and ketamine, compared with isoflurane alone. CONCLUSIONS AND CLINICAL RELEVANCE: Low infusion doses of morphine, lidocaine, ketamine, and MLK decreased isoflurane MAC in dogs and were not associated with adverse hemodynamic effects. The BIS can be used to monitor depth of anesthesia.     

Effects of ketamine and magnesium on the minimum alveolar concentration of isoflurane in goats

OBJECTIVE: To evaluate the effects of ketamine, magnesium sulfate, and their combination on the minimum alveolar concentration (MAC) of isoflurane (ISO-MAC) in goats. ANIMALS: 8 adult goats. PROCEDURES: Anesthesia was induced with isoflurane delivered via face mask. Goats were intubated and ventilated to maintain normocapnia. After an appropriate equilibration period, baseline MAC (MAC(B)) was determined and the following 4 treatments were administered IV: saline (0.9% NaCl) solution (loading dose [LD], 30 mL/20 min; constant rate infusion [CRI], 60 mL/h), magnesium sulfate (LD, 50 mg/kg; CRI, 10 mg/kg/h), ketamine (LD, 1 mg/kg; CRI, 25 microg/kg/min), and magnesium sulfate (LD, 50 mg/kg; CRI, 10 mg/kg/h) combined with ketamine (LD, 1 mg/kg; CRI, 25 microg/kg/min); then MAC was redetermined. RESULTS: Ketamine significantly decreased ISOMAC by 28.7 +/- 3.7%, and ketamine combined with magnesium sulfate significantly decreased ISOMAC by 21.1 +/- 4.1%. Saline solution or magnesium sulfate alone did not significantly change ISOMAC. CONCLUSIONS AND CLINICAL RELEVANCE: Ketamine and ketamine combined with magnesium sulfate, at doses used in the study, decreased the end-tidal isoflurane concentration needed to maintain anesthesia, verifying the clinical impression that ketamine decreases the end-tidal isoflurane concentration needed to maintain surgical anesthesia. Magnesium, at doses used in the study, did not decrease ISOMAC or augment ketamine's effects on ISOMAC.     

Pharmacokinetics of ketamine and its metabolite, norketamine, after intravenous administration of a bolus of ketamine to isoflurane-anesthetized dogs

OBJECTIVE: To determine the pharmacokinetics of ketamine and norketamine in isoflurane-anesthetized dogs. Animals-6 dogs. PROCEDURE: The minimum alveolar concentration (MAC) of isoflurane was determined in each dog. Isoflurane concentration was then set at 0.75 times the individual's MAC, and ketamine (3 mg/kg) was administered IV. Blood samples were collected at various times following ketamine administration. Blood was immediately centrifuged, and the plasma separated and frozen until analyzed. Ketamine and norketamine concentrations were measured in the plasma samples by use of liquid chromatography-mass spectrometry. Ketamine concentration-time data were fitted to compartment models. Norketamine concentration-time data were examined by use of noncompartmental analysis. RESULTS: The MAC of isoflurane was 1.43 +/- 0.18% (mean +/- SD). A 2-compartment model best described the disposition of ketamine. The apparent volume of distribution of the central compartment, the apparent volume of distribution at steady state, and the clearance were 371.3 +/- 162 mL/kg, 4,060.3 +/- 2,405.7 mL/kg, and 58.2 +/- 17.3 mL/min/kg, respectively. Norketamine rapidly appeared in plasma following ketamine administration and had a terminal half-life of 63.6 +/- 23.9 minutes. A large variability in plasma concentrations, and therefore pharmacokinetic parameters, was observed among dogs for ketamine and norketamine. CONCLUSIONS AND CLINICAL RELEVANCE: In isofluraneanesthetized dogs, a high variability in the disposition of ketamine appears to exist among individuals. The disposition of ketamine may be difficult to predict in clinical patients.     

The effects of ketamine on the minimum alveolar concentration of isoflurane in cats

OBJECTIVES: To determine the minimum alveolar concentration (MAC) of isoflurane during the infusion of ketamine. STUDY DESIGN: Prospective, experimental trial. ANIMALS: Twelve adult spayed female cats weighing 5.1 +/- 0.9 kg. METHODS: Six cats were anesthetized with isoflurane in oxygen, intubated and attached to a circle-breathing system with mechanical ventilation. Catheters were placed in a peripheral vein for the infusion of fluids and ketamine, and the jugular vein for blood sampling for the measurement of ketamine concentrations. An arterial catheter was placed to allow blood pressure measurement and sampling for the measurement of PaCO2, PaO2 and pH. PaCO2 was maintained between 29 and 41 mmHg (3.9-5.5 kPa) and body temperature was kept between 37.8 and 39.3 degrees C. Following instrumentation, the MAC of isoflurane was determined in triplicate using a tail clamp method. A loading dose (2 mg kg(-1) over 5 minutes) and an infusion (23 microg kg(-1) minute(-1)) of ketamine was started and MAC was redetermined starting 30 minutes later. Two further loading doses and infusions were used, 2 mg kg(-1) and 6 mg kg(-1) with 46 and 115 microg kg(-1) minute(-1), respectively and MAC was redetermined. Cardiopulmonary measurements were taken before application of the noxious stimulus. The second group of six cats was used for the measurement of steady state plasma ketamine concentrations at each of the three infusion rates used in the initial study and the appropriate MAC value determined from the first study. RESULTS: The MAC decreased by 45 +/- 17%, 63 +/- 18%, and 75 +/- 17% at the infusion rates of 23, 46, and 115 microg kg(-1) minute(-1). These infusion rates corresponded to ketamine plasma concentrations of 1.75 +/- 0.21, 2.69 +/- 0.40, and 5.36 +/- 1.19 microg mL(-1). Arterial blood pressure and heart rate increased significantly with ketamine. Recovery was protracted. CONCLUSIONS AND CLINICAL RELEVANCE: The MAC of isoflurane was significantly decreased by an infusion of ketamine and this was accompanied by an increase in heart rate and blood pressure. Because of the prolonged recovery in our cats, further work needs to be performed before using this in patients.     

Influence of prior determination of baseline minimum alveolar concentration (MAC) of isoflurane on the effect of ketamine on MAC in dogs

The objective of this study was to determine if prior measurement of the minimum alveolar concentration (MAC) of isoflurane influences the effect of ketamine on the MAC of isoflurane in dogs. Eight mixed-breed dogs were studied on 2 occasions. Anesthesia was induced and maintained using isoflurane. In group 1 the effect of ketamine on isoflurane MAC was determined after initially finding the baseline isoflurane MAC. In group 2, the effect of ketamine on isoflurane MAC was determined without previous measure of the baseline isoflurane MAC. In both groups, MAC was determined again 30 min after stopping the CRI of ketamine. Plasma ketamine concentrations were measured during MAC determinations.In group 1, baseline MAC (mean ± SD: 1.18 ± 0.14%) was decreased by ketamine (0.88 ± 0.14%; P < 0.05). The MAC after stopping ketamine was similar (1.09 ± 0.16%) to baseline MAC and higher than with ketamine (P < 0.05). In group 2, the MAC with ketamine (0.79 ± 0.11%) was also increased after stopping ketamine (1.10 ± 0.17%; P < 0.05). The MAC values with ketamine were different between groups (P < 0.05). Ketamine plasma concentrations were similar between groups during the events of MAC determination.The MAC of isoflurane during the CRI of ketamine yielded different results when methods of same day (group-1) versus separate days (group-2) are used, despite similar plasma ketamine concentrations with both methods. However, because the magnitude of this difference was less than 10%, either method of determining MAC is deemed acceptable for research purposes.     

Comparisons of the effects of acupuncture, electroacupuncture, and transcutaneous cranial electrical stimulation on the minimum alveolar concentration of isoflurane in dogs

OBJECTIVE: To compare the effects of acupuncture (AP), electroacupuncture (EA), and transcutaneous cranial electrical stimulation (TCES) with high-frequency intermittent currents on the minimum alveolar concentration (MAC) of isoflurane and associated cardiovascular variables in dogs. ANIMALS: 8 healthy adult female Beagles. PROCEDURE: Each dog was anesthetized with isoflurane on 4 occasions, allowing a minimum of 10 days between experiments. Isoflurane MAC values were determined for each dog without treatment (controls) and after treatment with AP and EA (AP points included the Large Intestine 4, Lung 7, Governing Vessel 20, Governing Vessel 14, San Tai, and Baihui) and TCES. Isoflurane MAC values were determined by use of noxious electrical buccal stimulation. Heart rate, mean arterial blood pressure (MAP), arterial blood oxygen saturation (Spo2) measured by use of pulse oximetry, esophageal body temperature, inspired and expired end-tidal isoflurane concentrations, end-tidal carbon dioxide concentration, and bispectral index (BIS) were monitored. Blood samples were collected for determination of plasma cortisol concentration. RESULTS: Mean +/- SD baseline MAC of isoflurane was 1.19 +/- 0.1%. Acupuncture did not significantly change MAC of isoflurane. Treatments with EA and TCES significantly lowered the MAC of isoflurane by 10.1% and 13.4%, respectively. The Spo2, heart rate, MAP, BIS, esophageal body temperature, and plasma cortisol concentration were not significantly different after AP, EA, TCES, and control treatments at any time interval. CONCLUSIONS AND CLINICAL RELEVANCE: Use of EA and TCES decreased MAC of isoflurane in dogs without inducing adverse hemodynamic effects. However, the reduction in isoflurane MAC by EA andTCES treatments was not considered clinically relevant.     

Effect of dexmedetomidine on the minimum alveolar concentration of isoflurane in cats

This study reports the effects of dexmedetomidine on the minimum alveolar concentration of isoflurane (MAC(iso) ) in cats. Six healthy adult female cats were used. MAC(iso) and dexmedetomidine pharmacokinetics had previously been determined in each individual. Cats were anesthetized with isoflurane in oxygen. Dexmedetomidine was administered intravenously using target-controlled infusions to maintain plasma concentrations of 0.16, 0.31, 0.63, 1.25, 2.5, 5, 10, and 20 ng/mL. MAC(iso) was determined in triplicate at each target plasma dexmedetomidine concentration. Blood samples were collected and analyzed for dexmedetomidine concentration. The following model was fitted to the concentration-effect data: [Formula in text] where MAC(iso.c) is MAC(iso) at plasma dexmedetomidine concentration C, MAC(iso.0) is MAC(iso) in the absence of dexmedetomidine, I(max) is the maximum possible reduction in MAC(iso), and IC(50) is the plasma dexmedetomidine concentration producing 50% of I(max). Mean ± SE MAC(iso.0), determined in a previous study conducted under conditions identical to those in this study, was 2.07 ± 0.04. Weighted mean ± SE I(max), and IC(50) estimated by the model were 1.76 ± 0.07%, and 1.05 ± 0.08 ng/mL, respectively. Dexmedetomidine decreased MAC(iso) in a concentration-dependent manner. The lowest MAC(iso) predicted by the model was 0.38 ± 0.08%, illustrating that dexmedetomidine alone is not expected to result in immobility in response to noxious stimulation in cats at any plasma concentration.     

Effect of intravenous lidocaine and ketamine on the minimum alveolar concentration of isoflurane in goats

OBJECTIVE: To evaluate the effects of i.v. lidocaine (L) and ketamine (K), alone and in combination (LK), on the minimum alveolar concentration (MAC) of isoflurane (ISO) in goats. STUDY DESIGN: Randomized crossover design. ANIMALS: Eight, adult mixed breed castrated male goats, aged 1-2 years weighing 24-51 kg. METHODS: Anesthesia was induced with ISO that was delivered via a mask. The tracheas were intubated and the animals ventilated to maintain an end-tidal carbon dioxide partial pressure between 25 and 30 mmHg (3.3-4 kPa). Baseline MAC (MAC(B)) that prevented purposeful movement in response to clamping a claw was determined in triplicate. After MAC(B) determination, each goat received one of the following treatments, which were administered as a loading (LD) dose followed by a constant rate infusion, IV: L (2.5 mg kg(-1); 100 microg kg(-1) minute(-1)), K (1.5 mg kg(-1); 50 microg kg(-1) minute(-1)), L and K combination or saline, and the MAC (MAC(T)) was re-determined in triplicate. Plasma concentrations of L and K were measured around each MAC point and the values averaged. RESULTS: The least-squares mean MAC(B) for all treatments was 1.13 +/- 0.03%. L, K, and LK reduced (p < 0.05) MAC(B) by 18.3%, 49.6% and 69.4%, respectively. Plasma concentrations for L, K, and LK were 1617 +/- 385, 1535 +/- 251 and 1865 +/- 317/1467 +/- 185 ng mL(-1), respectively. No change (p > 0.05) occurred with saline. CONCLUSION: Lidocaine and K caused significant decreases in the MAC of ISO. The combination (LK) had an additive effect. However, the plasma L concentrations were less than predicted, as was the MAC reduction with L. CLINICAL RELEVANCE: The use of L, K and the combination, at the doses studied, will allow a clinically important reduction in the concentration of ISO required to maintain general anesthesia in goats.     

Minimum alveolar concentration of isoflurane in mechanically ventilated Dumeril monitors

OBJECTIVE: To determine minimum alveolar concentration (MAC) of isoflurane in mechanically ventilated Dumeril monitors (Varanus dumerili). DESIGN: Prospective study. ANIMALS: 10 healthy adult Dumeril monitors. PROCEDURE: Anesthesia was induced with isoflurane in oxygen delivered through a face mask. Monitors were endotracheally intubated, and end-tidal and inspired isoflurane concentrations were continuously measured. After equilibration at an end-tidal-to-inspired isoflurane concentration ratio of >0.9 for 20 minutes, an electrical stimulus (50 Hz, 50 V) was delivered to the ventral aspect of the tail for up to 1 minute and the monitor was observed for purposeful movement. End-tidal isoflurane concentration was then decreased by 10%, and equilibration and stimulation were repeated. The MAC was calculated as the mean of the lowest end-tidal isoflurane concentration that prevented positive response and the highest concentration that allowed response. A blood sample for blood gas analysis was collected from the tail vein at the beginning and end of the anesthetic period. RESULTS: Mean +/- SD MAC of isoflurane was 1.54 +/- 0.17%. Mean heart rates at the upper and lower MAC values were 32.4 +/- 3 beats/min and 34 +/- 4.5 beats/min, respectively. During the experiment, PaCo2 decreased significantly from 43.1 mm Hg to 279 mm Hg and blood pH and HCO3 concentration increased significantly from 7.33 to 7.64 and from 25.3 to 32.9 mmol/L, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: The MAC of isoflurane in Dumeril monitors was similar to that reported in mammals but lower than values reported in other reptiles. This difference may be reflective of the more advanced cardiovascular physiologic features of monitor lizards.     

Prior determination of baseline minimum alveolar concentration (MAC) of isoflurane does not influence the effect of ketamine on MAC in rabbits

The objective of this study was to compare the effect on the minimum alveolar concentration (MAC) of isoflurane when ketamine was administered either after or without prior determination of the baseline MAC of isoflurane in rabbits. Using a prospective randomized crossover study, 8 adult, female New Zealand rabbits were allocated to 2 treatment groups. Anesthesia was induced and maintained with isoflurane. Group 1 (same-day determination) had the MAC-sparing effect of ketamine [1 mg/kg bodyweight (BW) bolus followed by a constant rate infusion (CRI) of 40 μg/kg BW per min, given by intravenous (IV)], which was determined after the baseline MAC of isoflurane was determined beforehand. A third MAC determination was started 30 min after stopping the CRI. Group 2 (separate-day determination) had the MAC-sparing effect of ketamine determined without previous determination of the baseline MAC of isoflurane. A second MAC determination was started 30 min after stopping the CRI. In group 1, the MAC of isoflurane (2.15 ± 0.09%) was significantly decreased by ketamine (1.63 ± 0.07%). After stopping the CRI, the MAC was significantly less (2.04 ± 0.11%) than the baseline MAC of isoflurane and significantly greater than the MAC during the CRI. In group 2, ketamine decreased isoflurane MAC (1.53 ± 0.22%) and the MAC increased significantly (1.94 ± 0.25%) after stopping the CRI. Minimum alveolar concentration (MAC) values did not differ significantly between the groups either during ketamine administration or after stopping ketamine. Under the study conditions, prior determination of the baseline isoflurane MAC did not alter the effect of ketamine on MAC. Both methods of determining MAC seemed to be valid for research purposes.     

Effects of ketamine infusion on halothane minimal alveolar concentration in horses.

Eight adult horses were used in a study to determine ketamine's ability to reduce halothane requirement. To obtain steady-state plasma concentrations of 0.5, 1.0, 2.0, 4.0, and 8.0 micrograms/ml, loading doses and constant infusions for ketamine were calculated for each horse on the basis of data from other studies in which the pharmacokinetic properties of ketamine were investigated. Blood samples for determination of plasma ketamine concentrations were collected periodically during each experiment. Plasma ketamine concentrations were determined by capillary gas chromatography/mass spectrometry under electron-impact ionization conditions, using lidocaine as the internal standard. Halothane minimal alveolar concentration (MAC; concentration at which half the horses moved in response to an electrical stimulus) and plasma ketamine concentration were determined after steady-state concentrations of each ketamine infusion had been reached. Plasma ketamine concentrations > 1.0 microgram/ml decreased halothane MAC. The degree of MAC reduction was correlated directly with the square root of the plasma ketamine concentration, reaching a maximum of 37% reduction at a plasma ketamine concentration of 10.8 +/- 2.7 micrograms/ml. Heart rate, mean arterial blood pressure, and the rate of increase of right ventricular pressure did not change with increasing plasma ketamine concentration and halothane MAC reduction. Cardiac output increased significantly during ketamine infusions and halothane MAC reduction. Our findings suggest that plasma ketamine concentrations > 1.0 micron/ml reduce halothane MAC and produce beneficial hemodynamic effects.     

Effect of transdermally administered fentanyl on the minimum alveolar concentration of isoflurane in cats

OBJECTIVE: To determine the effect of two doses of fentanyl, administered transdermally, on the minimum alveolar concentration (MAC) of isoflurane in cats. STUDY DESIGN: Prospective, randomized study. ANIMALS: Five healthy, spayed, female cats. METHODS: Each cat was studied thrice with at least 2 weeks between each study. In study 1, the baseline isoflurane MAC was determined in triplicate for each cat. In studies 2 and 3, isoflurane MAC was determined 24 hours after placement of either a 25 or 50 microg hour(-1) fentanyl patch. In each MAC study, cats were instrumented to allow collection of arterial blood and measurement of arterial blood pressure. Twenty-four hours prior to studies 2 and 3, a catheter was placed and secured in the jugular vein and either a 25 or 50 microg hour(-1) fentanyl patch was placed in random order on the left thorax. Blood samples for plasma fentanyl determination were collected prior to patch placement and at regular intervals up to 144 hours. After determination of MAC in studies 2 and 3, naloxone was administered as a bolus dose (0.1 mg kg(-1)) followed by an infusion (1 mg kg(-1) hour(-1)) and MAC redetermined. RESULTS: The baseline isoflurane MAC was 1.51 +/- 0.21% (mean +/- SD). Fentanyl (25 and 50 micro g hour(-1)) administered transdermally significantly reduced MAC to 1.25 +/- 0.26 and 1.22 +/- 0.16%, respectively. These MAC reductions were not significantly different from each other. Isoflurane MAC determined during administration of fentanyl 25 micro g hour(-1) and naloxone (1.44 +/- 0.16%) and fentanyl 50 micro g hour(-1) and naloxone (1.51 +/- 0.19%) was not significantly different from baseline MAC (1.51 +/- 0.21%). CONCLUSIONS AND CLINICAL RELEVANCE: Fentanyl patches are placed to provide long-lasting analgesia. In order to be effective postoperatively, fentanyl patches must be placed prior to surgery. Plasma fentanyl concentrations achieved intraoperatively decrease the need for potent inhalant anesthetics in cats.     

Effect of transdermally administered fentanyl on minimum alveolar concentration of isoflurane in normothermic and hypothermic dogs

OBJECTIVE: To determine whether the minimum alveolar concentration (MAC) of isoflurane was altered by transdermal administration of fentanyl in normothermic and hypothermic dogs. DESIGN: Randomized complete block crossover design. ANIMALS: 6 mature healthy dogs. PROCEDURE: Dogs received each of 4 treatments in random order. Following induction of anesthesia, normothermia was maintained in dogs that were treated with a fentanyl patch (F-NORM) or sham patch (C-NORM), or hypothermia was maintained in dogs that were treated with a fentanyl patch (F-HYPO) or sham patch (C-HYPO). The appropriate patch was applied 24 hours prior to induction of anesthesia. Anesthesia was induced with isoflurane in oxygen; the dogs were intubated and mechanically ventilated. Target esophageal temperatures were maintained within 1 degrees C of baseline values (normothermia) or at 34.5 degrees C (94.1 degrees F; hypothermia) for 1 hour prior to starting MAC determinations. Supramaximal stimulation was achieved with an electrical stimulator attached to needle electrodes placed in the buccal mucosa of the lower jaw of the dog. RESULTS: Mean MAC +/- SEM of isoflurane during C-NORM, C-HYPO, F-NORM, and F-HYPO treatments were 1.20 +/- 0.17, 0.89 +/- 0.18, 0.76 +/- 0.10, and 0.81 +/- 0.17, respectively. The mean MAC during C-NORM was significantly higher than values for the other treatments. There was no significant difference in mean MAC among the C-HYPO, F-NORM, and F-HYPO treatments. CONCLUSIONS AND CLINICAL RELEVANCE: Data suggest that transdermal administration of fentanyl significantly reduces isoflurane requirements in normothermic dogs. The isoflurane MAC-sparing effects of transdermal fentanyl are not apparent in hypothermic dogs.     

Minimum alveolar concentration of isoflurane in green iguanas and the effect of butorphanol on minimum alveolar concentration

OBJECTIVE: To determine minimum alveolar concentration (MAC) of isoflurane in green iguanas and effects of butorphanol on MAC. DESIGN: Prospective randomized trial. ANIMALS: 10 healthy mature iguanas. PROCEDURE: in each iguana, MAC was measured 3 times: twice after induction of anesthesia with isoflurane and once after induction of anesthesia with isoflurane and IM administration of butorphanol (1 mg/kg [0.45 mg/lb]). A blood sample was collected from the tail vein for blood-gas analysis at the beginning and end of the anesthetic period. The MAC was determined with a standard bracketing technique; an electrical current was used as the supramaximal stimulus. Animals were artificially ventilated with a ventilator set to deliver a tidal volume of 30 mL/kg (14 mL/lb) at a rate of 4 breaths/min. RESULTS: Mean +/- SD MAC values during the 3 trials (2 without and 1 with butorphanol) were 2.0 +/- 0.6, 2.1 +/- 0.6, and 1.7 +/- 0.7%, respectively, which were not significantly different from each other. Heart rate and end-tidal partial pressure of CO2 were also not significantly different among the 3 trials. Mean +/- SD heart rate was 48 +/- 10 beats/min; mean end-tidal partial pressure of CO2 was 22 +/- 10 mm Hg.There were no significant differences in blood-gas values for samples obtained at the beginning versus the end of the anesthetic period. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that the MAC of isoflurane in green iguanas is 2.1% and that butorphanol does not have any significant isoflurane-sparing effects.     

The effect of hypovolemia due to hemorrhage on the minimum alveolar concentration of isoflurane in the dog

OBJECTIVE: To determine the effect of hypovolemia on the minimum alveolar concentration (MAC) of isoflurane in the dog. STUDY DESIGN: Randomized, cross-over trial. ANIMAL POPULATION: Six healthy intact mixed breed female dogs weighing 18.2-29.0 kg. METHODS: Dogs were randomly assigned to determine the MAC of isoflurane in a normovolemic or hypovolemic state with a minimum of 18 days between trials. On both occasions, anesthesia was initially induced and maintained for 40 minutes with isoflurane delivered in oxygen while vascular catheters were placed in the cephalic vein and dorsal metatarsal artery. In dogs assigned to the hypovolemic group, 30 mL kg(-1) of blood was removed at 1 mL kg(-1) minute(-1) from the arterial catheter. All dogs were allowed to recover from anesthesia. Thirty minutes after the discontinuation of isoflurane, anesthesia was re-induced with isoflurane in oxygen delivered by face mask. The tracheas were intubated, and connected to an anesthetic machine with a Bain anesthetic circuit. Mechanical ventilation was instituted at a rate of 10 breaths minute(-1) with the tidal volume set to deliver 10-15 mL kg(-1). Airway gases were monitored continuously and tidal volume was adjusted to maintain an end-tidal carbon dioxide level of 35-40 mmHg (4.67-5.33 kPa). Body temperature was maintained at 37-38 degrees C (98.6-100.4 degrees F). The MAC determination was performed using an electrical stimulus applied to the toe web and MAC was defined as the mean value of end-tidal isoflurane between the concentrations at which a purposeful movement did and did not occur in response to the electrical stimulus. The MAC values were compared between groups using a Student's t-test. RESULTS: The MAC of isoflurane was significantly less in hypovolemic dogs (0.97 +/- 0.03%) compared with normovolemic dogs (1.15 +/- 0.02%) (p < 0.0079). CONCLUSIONS AND CLINICAL RELEVANCE: The MAC of isoflurane is reduced in dogs with hypovolemia resulting from hemorrhage. Veterinarians should be prepared to deliver a lower percentage of isoflurane to maintain anesthesia in hypovolemic dogs during diagnostic and therapeutic procedures.     

Effect of medetomidine administration on bispectral index measurements in dogs during anesthesia with isoflurane

OBJECTIVE: To determine the relationship between bispectral index (BIS) and minimum alveolar concentration (MAC) multiples of isoflurane after IM injection of medetomidine or saline (0.9% NaCl) solution in anesthetized dogs. ANIMALS: 6 dogs. PROCEDURE: Each dog was anesthetized 3 times with isoflurane. First, the MAC of isoflurane for each dog was determined by use of the tail clamp method. Second, anesthetized dogs were randomly assigned to receive an IM injection of medetomidine (8 microg x kg(-1)) or an equal volume of isotonic saline (0.9% NaCl) solution 30 minutes prior to beginning BIS measurements. Last, anesthetized dogs received the remaining treatment (medetomidine or isotonic saline solution). Dogs were anesthetized at each of 4 MAC multiples of isoflurane. Ventilation was controlled and atracurium (0.2 mg/kg followed by 6 microg/kg/min as a continuous infusion, IV) administered. After a 20-minute equilibration period at each MAC multiple of isoflurane, BIS data were collected for 5 minutes and median values of BIS calculated. RESULTS: BIS significantly decreased with increasing MAC multiples of isoflurane over the range of 0.8 to 2.0 MAC. Mean (+/- SD) MAC of isoflurane was 1.3 +/- 0.2%. During isoflurane-saline anesthesia, mean BIS measurements at 0.8, 1.0, 1.5, and 2.0 MAC were 65 +/- 8, 60 +/- 7 52 +/- 3, and 31 +/- 28, respectively. During isoflurane-medetomidine anesthesia, mean BIS measurements at 0.8, 1.0, 1.5, and 2.0 MAC were 77 +/- 4, 53 +/- 7, 31 +/- 24, and 9 +/- 20, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: BIS monitoring in dogs anesthetized with isoflurane has a predictive value in regard to degree of CNS depression. During isoflurane anesthesia, our results support a MAC-reducing effect of medetomidine.     

Evaluation of induction characteristics and hypnotic potency of isoflurane and sevoflurane in healthy dogs

OBJECTIVE: To determine induction characteristics and the minimum alveolar concentration (MAC) at which consciousness returned (MACawake) in dogs anesthetized with isoflurane or sevoflurane. ANIMALS: 20 sexually intact male Beagles. PROCEDURES: In experiment 1, 20 dogs were randomly assigned to have anesthesia induced and maintained with isoflurane or sevoflurane. The MAC at which each dog awoke in response to auditory stimulation (MACawake-noise) was determined by decreasing the end-tidal concentration by 0.1 volume (vol %) every 15 minutes and delivering a standard audible stimulus at each concentration until the dog awoke. In experiment 2, 12 dogs received the same anesthetic agent they were administered in experiment 1. After duplicate MAC determination, the end-tidal concentration was continually decreased by 10% every 15 minutes until the dog awoke from anesthesia (MACawake). RESULTS: Mean induction time was significantly greater for isoflurane-anesthetized dogs (212 seconds), compared with the sevoflurane-anesthetized dogs (154 seconds). Mean+/-SD MACawake-noise was 1.1+/-0.1 vol % for isoflurane and 2.0+/-0.2 vol % for sevoflurane. Mean MAC was 1.3+/-0.2 vol % for isoflurane and 2.1+/-0.6 vol % for sevoflurane, and mean MACawake was 1.0+/-0.1 vol % for isoflurane and 1.3+/-0.3 vol % for sevoflurane. CONCLUSIONS AND CLINICAL RELEVANCE: Sevoflurane resulted in a more rapid induction than did isoflurane. The MACawake for dogs was higher than values reported for both agents in humans. Care should be taken to ensure that dogs are at an appropriate anesthetic depth to prevent consciousness, particularly when single-agent inhalant anesthesia is used.     

Effect of electroacupuncture on minimum alveolar concentration of isoflurane in dogs

The effect of electroacupuncture (EA) on minimum alveolar concentration (MAC) of isoflurane was evaluated in dogs. After determination of baseline MAC, EA was applied at each acupoints (LI-4, SP-6, ST-36 and TH-8) and nonacupoint for 30 min. MAC was determined again. EA at acupoints significantly lowered the MAC of isoflurane in dogs (17.5 +/- 3.1%, 21.3 +/- 8.0%, 21.2 +/- 7.5% and 15.4 +/- 3.1%, respectively). In control group and nonacupoint electrical stimulation group MAC were not decreased significantly. From these results, electroacupuncture at each acupoints used in the present study would have an advantage in isoflurane anesthesia with reducing its requirement.     

Effects of diazepam and flumazenil on minimum alveolar concentrations for dogs anesthetized with isoflurane or a combination of isoflurane and fentanyl

OBJECTIVE: To determine the effect of a constant-rate infusion of fentanyl on minimum alveolar concentration (MAC) of isoflurane and to determine the interaction between fentanyl and a benzodiazepine agonist (diazepam) and antagonist (flumazenil) in isoflurane-anesthetized dogs. ANIMALS: 8 mixed-breed adult dogs. PROCEDURE: Dogs were anesthetized with isoflurane 3 times during a 6-week period. After a 30-minute equilibration period, each MAC determination was performed in triplicate, using standard techniques. Fentanyl was administered as a bolus (10 microg/kg of body weight, IV) that was followed by a constant infusion (0.3 microg/kg per min, IV) throughout the remainder of the experiment. After determining isoflurane-fentanyl MAC in triplicate, each dog received saline (0.9% NaCl) solution, diazepam, or flumazenil. After 30 minutes, MAC was determined again. RESULTS: Fentanyl significantly decreased isoflurane MAC (corrected to a barometric pressure of 760 mm Hg) from 1.80+/-0.21 to 0.85+/-0.14%, a reduction of 53%. Isoflurane-fentanyl-diazepam MAC (0.48+/-0.29%) was significantly less than isoflurane-fentanyl-saline MAC (0.79+/-0.21%). Percentage reduction in isoflurane MAC was significantly greater for fentanyl-diazepam (74%), compared with fentanyl-saline (54%) or fentanyl-flumazenil (61%). Mean fentanyl concentrations for the entire experiment were increased over time and were higher in the diazepam group than the saline or flumazenil groups. CONCLUSIONS AND CLINICAL RELEVANCE: Fentanyl markedly decreased isoflurane MAC in dogs. Diazepam, but not flumazenil, further decreased isoflurane-fentanyl MAC. Our results indicate that diazepam enhances, whereas flumazenil does not affect, opioid-induced CNS depression and, possibly, analgesia in dogs.