Effects of tramadol on the minimum alveolar concentration of sevoflurane in dogs

ObjectiveTo evaluate the effect of tramadol on sevoflurane minimum alveolar concentration (MAC_SEVO) in dogs. It was hypothesized that tramadol would dose-dependently decrease MAC_SEVO.Study designRandomized crossover experimental study.AnimalsSix healthy, adult female mixed-breed dogs (24.2 ± 2.6 kg).MethodsEach dog was studied on two occasions with a 7-day washout period. Anesthesia was induced using sevoflurane delivered via a mask. Baseline MAC (MAC_B) was determined starting 45 minutes after tracheal intubation. A noxious stimulus (50 V, 50 Hz, 10 ms) was applied subcutaneously over the mid-humeral area. If purposeful movement occurred, the end-tidal sevoflurane was increased by 0.1%; otherwise, it was decreased by 0.1%, and the stimulus was re-applied after a 20-minute equilibration. After MAC_B determination, dogs randomly received a tramadol loading dose of either 1.5 mg kg^?1 followed by a continuous rate infusion (CRI) of 1.3 mg kg^?1 hour^?1 (T1) or 3 mg kg^?1 followed by a 2.6 mg kg^?1 hour^?1 CRI (T2). Post-treatment MAC determination (MAC_T) began 45 minutes after starting the CRI. Data were analyzed using a mixed model anova to determine the effect of treatment on percentage change in baseline MAC_SEVO (p < 0.05).ResultsThe MAC_B values were 1.80 ± 0.3 and 1.75 ± 0.2 for T1 and T2, respectively, and did not differ significantly. MAC_T decreased by 26 ± 8% for T1 and 36 ± 12% for T2. However, there was no statistically significant difference in the decrease between the two treatments.Conclusion and clinical relevanceTramadol significantly reduced MAC_SEVO but this was not dose dependent at the doses studied.     

Phenylpiperidine opioid effects on isoflurane minimum alveolar concentration in cats

Different structurally related phenylpiperidine opioids exhibit different isoflurane-sparing effects in cats. Because minimum alveolar concentration (MAC) in cats is affected only by very high plasma concentrations of some phenylpiperidine opioids, we hypothesized these effects are caused by actions on nonopioid receptors. Using a prospective, randomized, crossover design, six cats were anesthetized with isoflurane, intubated, ventilated, and instrumented. Isoflurane MAC was measured in triplicate using a tail-clamp and bracketing technique. A computer-controlled intravenous infusion using prior pharmacokinetic models targeted plasma concentrations of 60 ng/ml fentanyl, 10 ng/ml sufentanil, or 500 ng/ml alfentanil, and isoflurane MAC was measured in duplicate. Next, naltrexone 0.6 mg/kg was administered to cats hourly during the opioid infusion, and isoflurane MAC was measured in duplicate. Blood was collected during MAC determinations to measure opioid concentrations. Responses were analyzed using repeated measures ANOVA with significance at p < .05. Alfentanil and sufentanil decreased isoflurane MAC by 16.4% and 6.4%, respectively, and these effects were completely reversed by naltrexone. Fentanyl had no significant effect on isoflurane MAC. Alfentanil and sufentanil modestly reduce isoflurane MAC via agonist effects on opioid receptors. However, these effects are too small to justify clinical use of phenylpiperidine opioids as single agents to reduce MAC in cats.     

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.     

Relationship of bispectral index to minimum alveolar concentration multiples of sevoflurane in cats

OBJECTIVE: To determine the relationship between bispectral index (BIS) and minimum alveolar concentration (MAC) multiples of sevoflurane in cats. ANIMALS: 8 domestic cats. PROCEDURE: Each cat was anesthetized twice with sevoflurane. First, the MAC of sevoflurane for each cat was determined by use of the tail clamp method. Second, cats were anesthetized with sevoflurane at each of 5 MAC multiples administered in random order. Ventilation was controlled, and after a 15-minute equilibration period at each MAC multiple of sevoflurane, BIS data were collected for 5 minutes and the median value of BIS calculated. RESULTS: The mean (+/- SD) MAC of sevoflurane was 3.3 +/- 0.2%. The BIS values at 0.5 MAC could not be recorded as a result of spontaneous movement in all 8 cats. The BIS values at 2.0 MAC were confounded by burst suppression in all 8 cats. Over the range of 0.8 to 1.5 MAC, BIS values decreased significantly with increasing end-tidal sevoflurane concentrations. Mean (+/- SD) BIS measurements were 30 +/- 3, 21 +/- 3, and 5 +/- 2 at 0.8, 1.0, and 1.5 MAC, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Values of BIS are inversely and linearly related to end-tidal sevoflurane concentrations in anesthetized cats, and BIS may be a useful predictor of CNS depression in this species. The consistently low BIS values recorded in this study suggest that clinical BIS end points used to titrate anesthetic agents in humans may not be applicable to cats.     

A systematic review of sevoflurane and isoflurane minimum alveolar concentration in domestic cats

ObjectiveThe purpose of this systematic review is to summarize the results of studies which have determined the minimum alveolar concentration (MAC) of isoflurane and sevoflurane in domestic cats.Study DesignSystematic review.AnimalsCats.Methods usedA comprehensive search of research literature was performed without language restriction. The search utilized the Pubmed, Google Scholar, and CAB Abstracts electronic databases using a combination of free text terms ‘Minimum alveolar concentration’, ‘sevoflurane’, ‘isoflurane’, ‘anesthetic’, ‘cat’, ‘cats’ or ‘feline’. The search was conducted from November 2010 to June 2012.ResultsThe MAC for isoflurane ranged from 1.20 ± 0.13% to 2.22 ± 0.35% and the MAC for sevoflurane ranged from 2.5 ± 0.2% to 3.95 ± 0.33%. The average MAC for isoflurane was 1.71 ± 0.07% and for sevoflurane was 3.08 ± 0.4%.Conclusions &; Clinical RelevanceThe average MAC for isoflurane was 1.71 ± 0.07% and for sevoflurane was 3.08 ± 0.4%. Methodology differed among studies, and particular attention should be paid in the future to appropriate reporting of methods to allow sound conclusions to be made from the results.     

Effect of lidocaine on the minimum alveolar concentration of sevoflurane in dogs

Objective  To investigate the effects of a low-dose constant rate infusion (LCRI; 50 μg kg⁻¹ minute⁻¹) and high-dose CRI (HCRI; 200 μg kg⁻¹ minute⁻¹) lidocaine on arterial blood pressure and on the minimum alveolar concentration (MAC) of sevoflurane (Sevo), in dogs.
Study design  Prospective, randomized experimental design.
Animals  Eight healthy adult spayed female dogs, weighing 16.0 ± 2.1 kg.
Methods  Each dog was anesthetized with sevoflurane in oxygen and mechanically ventilated, on three separate occasions 7 days apart. Following a 40-minute equilibration period, a 0.1-mL kg⁻¹ saline loading dose or lidocaine (2 mg kg⁻¹ intravenously) was administered over 3 minutes, followed by saline CRI or lidocaine LCRI or HCRI. The sevoflurane MAC was determined using a tail clamp. Heart rate (HR), blood pressure and plasma concentration of lidocaine were measured. All values are expressed as mean ± SD.
Results  The MAC of Sevo was 2.30 ± 0.19%. The LCRI reduced MAC by 15% to 1.95 ± 0.23% and HCRI by 37% to 1.45 ± 0.21%. Diastolic and mean pressure increased with HCRI. Lidocaine plasma concentration was 0.84 ± 0.18 for LCRI and 1.89 ± 0.37 μg mL⁻¹ for HCRI. Seventy-five percent of HCRI dogs vomited during recovery.
Conclusion and clinical relevance  Lidocaine infusions dose dependently decreased the MAC of Sevo, did not induce clinically significant changes in HR or arterial blood pressure, but vomiting was common during recovery in HCRI.     

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.     

Sparing effect of tramadol,lidocaine, dexmedetomidine and their combination on the minimum alveolar concentration of sevoflurane in dogs

BackgroundProblems associated with using inhalational anaesthesia are numerous in veterinary anaesthesia practice. Decreasing the amount of used inhalational anaesthetic agents and minimising of cardiorespiratory disorders are the standard goals of anaesthetists.ObjectiveThis experimental study was carried out to investigate the sparing effect of intravenous tramadol, lidocaine, dexmedetomidine and their combinations on the minimum alveolar concentration (MAC) of sevoflurane in healthy Beagle dogs.MethodsThis study was conducted on six beagle dogs. Sevoflurane MAC was determined by the tail clamp method on five separate occasions. The dogs received no treatment (control; CONT), tramadol (TRM: 1.5 mg kg^-1 intravenously followed by 1.3 mg kg^-1 h^-1), lidocaine (LID: 2 mg kg^-1 intravenously followed by 3 mg kg^-1 h^-1), dexmedetomidine (DEX: 2 μg kg^-1 intravenously followed by 2 μg kg^-1 h^-1), and their combination (COMB), respectively. Cardiorespiratory variables were recorded every five minutes and immediately before the application of a noxious stimulus.ResultsThe COMB treatment had the greatest sevoflurane MAC-sparing effect (67.4 ± 13.9%) compared with the other treatments (5.1 ± 25.3, 12.7 ± 14.3, and 40.3 ± 15.1% for TRM, LID, and DEX treatment, respectively). The cardiopulmonary variables remained within the clinically acceptable range following COMB treatment, although the mean arterial pressure was higher and accompanied by bradycardia.ConclusionsTramadol-lidocaine-dexmedetomidine co-infusion produced a remarkable sevoflurane MAC-sparing effect in clinically healthy beagle dogs and could result in the alleviation of cardiorespiratory depression caused by sevoflurane. Cardiorespiratory variables should be monitored carefully to avoid undesirable side effects induced by dexmedetomidine.     

Determination of minimum alveolar concentration of sevoflurane in juvenile swine

Pigs are important animal models in veterinary and medical research and have been widely used in experiments requiring surgical anesthesia. Sevoflurane is an inhalant anesthetic with unique properties that make it an ideal anesthetic for mask induction and anesthesia maintenance. However, there are relatively few studies reporting the anesthetic requirements for sevoflurane in juvenile swine, an age group that is commonly used in research experiments. Therefore the objective of this study was to determine the Minimum Alveolar Concentration (MAC) for sevoflurane in juvenile swine. Sevoflurane anesthesia was induced in six Yorkshire-cross pigs of approximately 9 weeks-of-age and MAC for sevoflurane was determined. The sevoflurane MAC value was determined to be 3.5+/-0.1% which is notably higher than values reported in the literature for pigs. This discrepancy in MAC values may represent changes in anesthetic requirements between different age groups of pigs and differences in the type of stimulus used to determine MAC.     

Effects of carprofen and meloxicam with or without butorphanol on the minimum alveolar concentration of sevoflurane in dogs

Sparing effects of carprofen and meloxicam with or without butorphanol on the minimum alveolar concentration (MAC) of sevoflurane were determined in 6 dogs. Anesthesia was induced and maintained with sevoflurane in oxygen, and MAC was determined by use of a tail clamp method. The dogs were administered a subcutaneous injection of carprofen (4 mg/kg) or meloxicam (0.2 mg/kg), or no medication (control) one hour prior to induction of anesthesia. Following the initial determination of MAC, butorphanol (0.3 mg/kg) was administered intramuscularly, and MAC was determined again. The sevoflurane MACs for carprofen alone (2.10 +/- 0.26%) and meloxicam alone (2.06 +/- 0.20%) were significantly less than the control (2.39 +/- 0.26%). The sevoflurane MACs for the combination of carprofen with butorphanol (1.78 +/- 0.20%) and meloxicam with butorphanol (1.66 +/- 0.29%) were also significantly less than the control value after the administration of butorphanol (2.12 +/- 0.28%). The sevoflurane sparing effects of the combinations of carprofen with butorphanol and meloxicam with butorphanol were additive.     

Effect of intravenous butorphanol infusion on the minimum alveolar concentration of isoflurane in cats

ObjectiveTo determine the effect of butorphanol, administered by intravenous (IV) infusion, on the minimum alveolar concentration of isoflurane (MAC_ISO) in cats and to examine the dosage dependence of this effect.Study designRandomized, placebo-controlled, crossover experimental study.AnimalsA group of six healthy adult male neutered cats.MethodsCats were anesthetized with isoflurane in oxygen. A venous catheter was placed for fluid and drug administration, and an arterial catheter was placed for measurement of arterial pressure and blood sampling. Four treatments were administered at random with at least 2 week interval between treatments: saline (control), butorphanol low dosage (treatment LD; 0.25 mg kg^–1 IV bolus followed by 85 μg kg^–1 minute^–1 for 20 minutes, then 43 μg kg^–1 minute^–1 for 40 minutes, then 19 μg kg^–1 minute^–1), medium dosage (treatment MD, double the dosages in LD) and high dosage (treatment HD, quadruple the dosages in LD). MAC_ISO was determined in duplicate using the bracketing technique and tail clamping. Pulse rate, arterial pressure, hemoglobin oxygen saturation, end-tidal partial pressure of carbon dioxide and arterial blood gas and pH were measured.ResultsButorphanol reduced MAC_ISO in a dosage-dependent manner, by 23 ± 8%, 37 ± 12% and 68 ± 10% (mean ± standard deviation) in treatments LD, MD and HD, respectively. The main cardiopulmonary effect observed was a decrease in pulse rate, significant in treatment HD compared with control.Conclusions and clinical relevanceButorphanol caused a dosage-dependent MAC_ISO reduction in cats. IV infusion of butorphanol may be of interest for partial IV anesthesia in cats.     

Determination of the minimum alveolar concentration of sevoflurane in Holstein steers

ObjectiveTo determine the minimum alveolar concentration (MAC) of sevoflurane in Holstein steers using electric stimulation.Study designProspective experimental study.AnimalsA total of 15 Holstein steers aged 7.3 ± 1.2 months and weighing 121 ± 25 kg.MethodsAnimals were anesthetized with sevoflurane at 8% in oxygen at 5 L minute^–1 via facemask and were intubated with an orotracheal tube of a compatible size. After 15 minutes of stabilization of the initial expired concentration of sevoflurane (Fe′Sevo) at 2.6%, electrical stimulation on the thoracic limb was initiated with a sequence of 2 × 10 ms followed by 2 × 3 second electrical currents of 50 V and 50 Hz, 5 seconds apart. Following each stimulus with a negative response, the Fe′Sevo was decreased by 0.2% and a 15 minute interval was awaited before the next stimulus. The procedure was repeated until the first Fe′Sevo value with a positive motor response was obtained. The Fe′Sevo was then increased by 0.1%, followed by a new stimulus, until a negative response was obtained. The value of MAC was calculated as the arithmetic mean between the lowest Fe′Sevo associated with a negative motor response and the highest Fe′Sevo associated with a positive response.ResultsThe mean MAC for the 15 steers was 2.0 ± 0.3%, which corresponds to 2.1 ± 0.3% at sea level.ConclusionsBased on the proposed methodology, the MAC of sevoflurane for healthy Holstein steers is 2.1 ± 0.3% at sea level.Clinical relevanceThis Fe′Sevo value can be used to guide depth of anesthesia in steers weighing approximately 120 kg in clinical practice.     

Naltrexone does not affect isoflurane minimum alveolar concentration in cats

ObjectiveTo test whether naltrexone, an opioid receptor antagonist, affects the minimum alveolar concentration (MAC) of isoflurane in cats, a species that is relatively resistant to the general anesthetic sparing effects of most opioids.Study designRandomized, crossover, placebo-controlled, blinded experimental design.AnimalsSix healthy adult cats weighing 4.9 ± 0.7 kg.MethodsThe cats were studied twice. In the first study, baseline isoflurane MAC was measured in duplicate. The drug (saline control or 0.6 mg kg^?1 naltrexone) was administered IV every 40–60 minutes, and isoflurane MAC was re-measured. In the second study, cats received the second drug treatment using identical methods 2 weeks later.ResultsIsoflurane MAC was 2.03 ± 0.12% and was unchanged from baseline following saline or naltrexone administration.Conclusion and clinical relevanceMinimum alveolar concentration was unaffected by naltrexone. Because MAC in cats is unaffected by at least some mu-opioid agonists and antagonists, spinal neurons that are directly modulated by mu-opioid receptors in this species cannot be the neuroanatomic sites responsible for immobility from inhaled anesthetics.     

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.     

Effects of constant rate infusions of dexmedetomidine or MK-467 on the minimum alveolar concentration of sevoflurane in dogs

Objective

To determine the effects of low and high dose infusions of dexmedetomidine and a peripheral α₂-adrenoceptor antagonist, MK-467, on sevoflurane minimum alveolar concentration (MAC) in dogs.

Effects of intravenous lidocaine on the minimum alveolar concentration of isoflurane in cats

Lidocaine has been reported to decrease the minimum alveolar concentration (MAC) of inhalation anesthetics in several species and has been used clinically to reduce the requirements for other anesthetic drugs. This study examined the effects of intravenous lidocaine on isoflurane MAC in cats. Six cats were studied. In experiment 1, the MAC of isoflurane was determined. An intravenous bolus of lidocaine 2 mg kg^–1 was then administrated and venous plasma lidocaine concentrations measured to determine pharmacokinetic values. In experiment 2, lidocaine was administered to achieve target plasma concentrations between 1 and 11 μg mL^–1 and the MAC of isoflurane was determined in triplicate at each lidocaine plasma concentration, using the tail‐clamp method. End‐tidal isoflurane concentration was determined using a calibrated infrared analyzer. Systolic blood pressure (Doppler), SpO2 and end‐tidal PCO2 (calibrated Raman spectrometer) were measured prior to each MAC determination. Body temperature was maintained between 38.5 and 39.5 °C by supplying external heat as needed. MAC values at the different lidocaine plasma concentrations were analyzed by a repeated measures ANOVA , using the Huynh–Feldt correction. The MAC of isoflurane in these cats was 2.21 ± 0.17. For the target concentrations of 1, 3, 5, 7, 9, and 11 μg mL^–1, the actual lidocaine plasma concentrations was 1.06 ± 0.12, 2.83 ±0.39, 4.93 ± 0.64, 6.86 ± 0.97, 8.86 ± 2.10, and 9.84 ± 1.34 μg mL^–1, respectively. At these target concentrations, the MAC of isoflurane was 2.14 ± 0.14, 1.88 ± 0.18, 1.66 ± 0.16, 1.47 ±0.13, 1.33 ± 0.23, and 1.06 ± 0.19%, respectively. Lidocaine, at target plasma concentrations of 1, 3, 5, 7, 9, and 11 μg mL^–1, linearly decreased isoflurane MAC by –6 to 6, 7 to 28, 19 to 35, 28 to 45, 29 to 53, and 44 to 59%, respectively. Lidocaine significantly dose‐dependently and linearly decreases the requirements for isoflurane in cats. No ceiling effect was observed within the range of plasma concentrations studied.     

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.