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 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.     

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 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.     

Effects of adenosine infusion on the minimum alveolar concentration of isoflurane in dogs

OBJECTIVE: To determine the effects of adenosine infusion on the minimum alveolar concentration (MAC) of isoflurane in dogs. STUDY DESIGN: Prospective, randomized crossover study. ANIMALS: Seven adult male and female Beagles weighing 10.9 (7.5, 13.6) kg [median (minimum, maximum)]. METHODS: Each dog was anesthetized with isoflurane in oxygen and randomly assigned to receive either an intravenous (IV) adenosine (0.3 mg kg(-1) minute(-1)) or saline (6 mL kg(-1) hour(-1) IV) infusion. After an interval of 7 days or more, each dog was re-anesthetized and treated with the alternative infusion. Using a tail-clamp technique, MAC was determined before (pre-infusion), during (infusion), and 2 hours after the infusions (post-infusion). RESULTS: The pre-infusion MAC of isoflurane was 1.25 (1.15, 1.35) [median (minimum, maximum)] vol.% for the saline treatment group and 1.25 (1.05, 1.45) vol.% for the adenosine treatment group, and did not differ significantly between the two treatments. The infusion MAC values were not significantly different (p = 0.16) and were 1.25 (0.95, 1.35) vol.% and 1.05 (1.00, 1.25) vol.%, respectively. The post-infusion MAC values differed significantly (p = 0.016); MAC was 1.15 (1.15, 1.35) vol.% and 1.05 (1.05, 1.25) vol.% for the saline and adenosine treatment groups, respectively. During infusion, mean arterial blood pressure decreased significantly (p = 0.008) during adenosine treatment compared with the saline 66 mmHg (52, 72) and 91 mmHg (68, 110), respectively. End-tidal CO2 (Pe'CO2), urine production, hematocrit, and plasma total solids did not differ significantly between the two treatments at any time (all p > 0.05). CONCLUSION: Although the MAC of isoflurane in dogs was not decreased significantly during infusion with adenosine (0.3 mg kg(-1) minute(-1)), it was significantly decreased post-infusion, but only by 0.1 vol.%, an amount not considered clinically important. Adenosine infusion decreased mean arterial pressure by 27% and did not adversely affect renal function.     

Effects of methadone on the minimum alveolar concentration of isoflurane in dogs

ObjectiveTo investigate the effects of methadone on the minimum alveolar concentration of isoflurane (ISO_MAC) in dogs.Study designProspective, randomized cross-over experimental study.AnimalsSix adult mongrel dogs, four males and two females, weighing 22.8 ± 6.6 kg.MethodsAnimals were anesthetized with isoflurane and mechanically ventilated on three separate days, at least 1 week apart. Core temperature was maintained between 37.5 and 38.5 °C during ISO_MAC determinations. On each study day, ISO_MAC was determined using electrical stimulation of the antebrachium (50 V, 50 Hz, 10 mseconds) at 2.5 and 5 hours after intravenous injection of physiological saline (control) or one of two doses of methadone (0.5 or 1.0 mg kg^?1).ResultsMean (±SD) ISO_MAC in the control treatment was 1.19 ± 0.15% and 1.18 ± 0.15% at 2.5 and 5 hours, respectively. The 1.0 mg kg^?1 dose of methadone reduced ISO_MAC by 48% (2.5 hours) and by 30% (5 hours), whereas the 0.5 mg kg^?1 dose caused smaller reductions in ISO_MAC (35% and 15% reductions at 2.5 and 5 hours, respectively). Both doses of methadone decreased heart rate (HR), but the 1.0 mg kg^?1 dose was associated with greater negative chronotropic actions (HR 37% lower than control) and mild metabolic acidosis at 2.5 hours. Mean arterial pressure increased in the MET1.0 treatment (13% higher than control) at 2.5 hours.Conclusions and clinical relevanceMethadone reduces ISO_MAC in a dose-related fashion and this effect is lessened over time. Although the isoflurane sparing effect of the 0.5 mg kg^?1 dose of methadone was smaller in comparison to the 1.0 mg kg^?1 dose, the lower dose is recommended for clinical use because it results in less evidence of cardiovascular impairment.     

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.     

Effect of oral trazodone on the minimum alveolar concentration of isoflurane in dogs

Objective

To determine the effect of oral trazodone on the minimum alveolar concentration (MAC) of isoflurane in dogs.

The effect of buprenorphine on isoflurane minimum alveolar concentration in dogs

ObjectiveTo determine the effect of intravenous (IV) buprenorphine on the isoflurane (ISO) minimum alveolar concentration (ISOMAC) in dogs.Study designRandomized, crossover, design.AnimalsSix healthy, adult (2–3 years old), intact dogs (two males and four females) weighing 7.4–11.0 kg.MethodsEach dog was studied on three occasions, 1 week apart, and baseline ISOMAC (MAC_B) was determined on each occasion. ISOMAC was defined as the mean of the end-tidal ISO concentrations that prevented and allowed purposeful movement in response to a noxious stimulus. After MAC_B determination, dogs were randomly given buprenorphine (BUP) at either 0.01, 0.05 or 0.1 mg kg^?1 IV, and ISOMAC was determined at two time periods after BUP administration. The first post-treatment determination (MAC_T1) was initiated 45 minutes after BUP administration and the second determination (MAC_T2) was initiated 4 hours after BUP administration. MAC values were determined in duplicate and the mean values were used for statistical analysis.ResultsIsoflurane minimum alveolar concentration was decreased at 141 minutes (the time of MAC_T1 determination) by 25%, 35%, and 27% after administration of BUP at 0.01, 0.05, and 0.1 mg kg^?1, respectively (p ≤ 0.05). The MAC reductions were not statistically different among doses. The reductions in ISOMAC at 342 minutes (the time of MAC_T2 determination) ranged from 13 to 16%, and were not statistically different among doses.Conclusions and clinical significanceBuprenorphine at 0.01, 0.05, and 0.1 mg kg^?1 significantly decreased ISOMAC in dogs at 141 minutes but not at 342 minutes. When using BUP for MAC reduction re-dosing may be required for procedures of long duration, and there may be no advantage to using the 0.1 mg kg^?1 dose.     

The effect of experimentally induced hypothyroidism on the isoflurane minimum alveolar concentration in dogs

ObjectiveTo determine the effect of experimentally induced hypothyroidism on isoflurane (ISO) minimum alveolar concentration (MAC) in dogs.Study designProspective experimental study.AnimalsEighteen adult female mongrel dogs, age 2–4 years and weighing 8.2–13.1 kg.MethodsHypothyroidism was induced in nine dogs by the intravenous administration of 1 mCi kg⁻¹ of ¹³¹Iodine. The remaining nine dogs served as controls. Dogs were studied 9–12 months after the induction of hypothyroidism. Anesthesia was induced with ISO in oxygen via a mask. The trachea was intubated, and anesthesia was maintained using ISO in oxygen using a semi-closed rebreathing circle system. The dogs were mechanically ventilated to maintain an end-tidal carbon dioxide concentration between 35 and 45 mmHg. End-tidal ISO concentrations were measured with an infrared gas analyzer. The MAC was determined in duplicate using a tail clamp technique. The mean values for the groups were compared using a two sample t-test.ResultsThe mean ± SD MAC of isoflurane in the hypothyroid and euthyroid dogs was 0.98 ± 0.31% and 1.11 ± 0.26%, respectively. The mean MAC of isoflurane in hypothyroid dogs was not significantly different from the mean MAC of isoflurane in the control dogs (p=0.3553).Conclusion and clinical relevanceThe MAC of ISO in dogs was not significantly affected by experimentally induced hypothyroidism. The dose of ISO in dogs with hypothyroidism does not need to be altered.     

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.     

Changes in the minimum alveolar concentration of isoflurane and some cardiopulmonary measurements during three continuous infusion rates of dexmedetomidine in dogs

OBJECTIVE: To measure the change in the minimum alveolar concentration of isoflurane associated with three constant rate infusions of dexmedetomidine. STUDY DESIGN: Prospective, randomized, and blinded experimental trial. Animals Six healthy 6-year-old Beagles weighing between 13.0 and 17.7 kg. METHODS: The dogs received each of four treatments; saline or dexmedetomidine at 0.1, 0.5 or 3 microg kg(-1) loading dose given intravenously (IV) over 6 minutes followed by infusions at 0.1, 0.5 or 3 microg kg(-1) hour(-1), respectively. There were 2 weeks between treatments. The dogs were mask-induced with and maintained on isoflurane in oxygen. Acetated Ringer's (5 mL kg(-1) hour(-1)) and saline or dexmedetomidine (each at 0.5 mL kg(-1) hour(-1)) were given IV. Pulse rate, blood pressure, samples for the measurement of blood gases, pH, lactate, packed cell volume (PCV), total protein (TP) and dexmedetomidine concentrations were obtained from an arterial catheter. Sixty minutes after induction minimum alveolar concentration (MAC) was determined by intermittently applying supramaximal electrical stimuli to the thoracic and pelvic limbs. Cardiopulmonary measurements and arterial blood samples were collected before each set of stimuli. Statistical analyses were conducted with analysis of variance or mixed models according to the experimental design. RESULTS: There was a significant decrease in the MAC of isoflurane associated with 0.5 and 3 microg kg(-1) hour(-1) but not with 0.1 mg kg(-1)hour(-1). Serum concentrations of dexmedetomidine were not measurable at the 0.1 mg kg(-1) hour(-1) and averaged 0.198 +/- 0.081 and 1.903 +/-0.621 ng mL(-1) for the 0.5 and 3 microg kg(-1) hour(-1) infusion rates, respectively. Heart rate decreased with increasing doses of dexmedetomidine while blood pressure increased. Packed cell volume increased at 3 microg kg(-1) hour(-1) but not with other doses. CONCLUSIONS AND CLINICAL RELEVANCE: Dexmedetomidine infusions decrease the intra-operative requirement for isoflurane and may be useful in managing dogs undergoing surgery, where the provision of analgesia and limitation of the stress response is desirable.     

Effect of morphine and flunixin meglumine on isoflurane minimum alveolar concentration in goats

OBJECTIVE: To determine the effect of morphine and flunixin meglumine on isoflurane (ISO) minimum alveolar concentration (MAC) in goats. STUDY DESIGN: Prospective, randomized experimental study. ANIMALS: Five adult, wether goats from 1 to 3 years in age, and weighing 24-65 kg. METHODS: Anesthesia was induced using ISO, which was delivered via a mask. Goats were intubated and ventilated to maintain an end-tidal carbon dioxide concentration between 25 and 30 mm Hg (3.3-4 kPa). End-tidal ISO concentration was measured using an infrared analyzer. The baseline ISO MAC that prevented purposeful movement in response to clamping a claw was determined. Following baseline MAC determination, each goat received one of the following four treatments intravenously (IV): morphine (2 mg kg(-1)), flunixin (1.5 mg kg(-1)), flunixin (1.5 mg kg(-1)) plus morphine (2 mg kg(-1)) or saline, and the MAC was re-determined. Goats were studied at weekly intervals, and each goat received each treatment in a randomized fashion. RESULTS: The baseline ISO MAC for the control treatment was 1.43%. Morphine reduced the MAC by 29.7%. Flunixin did not significantly decrease the MAC nor did it potentiate the effect of morphine on MAC. The quality of recovery was good in all cases. CONCLUSIONS: Morphine (2 mg kg(-1), IV) significantly reduced the ISO MAC in goats and did not adversely affect the quality of recovery. CLINICAL RELEVANCE: The use of morphine, at the dose studied, in association with ISO anesthesia, will allow a clinically significant reduction in the concentration of ISO required to maintain general anesthesia in goats.     

Effects of oxymorphone and hydromorphone on the minimum alveolar concentration of isoflurane in dogs

OBJECTIVES: To quantify the change in the minimum alveolar concentration (MAC) of isoflurane (ISO) associated with oxymorphone (OXY) or hydromorphone (HYDRO) in dogs. DESIGN: Randomized crossover study with at least 1 week between assessments. ANIMALS: Six young, healthy, mixed-breed dogs (1-3 years old), weighing 24.7 +/- 4.70 kg. METHODS: Following mask induction, anesthesia was maintained with ISO in 100% O(2) using mechanical ventilation. The dogs received 0.05 mg kg(-1) OXY, 0.1 mg kg(-1) HYDRO, or 1 mL saline (control) IV. Following equilibration (15 minutes) at each percentage ISO tested, a supramaximal electrical stimulus was applied to the toe web and the response was assessed. Two separate MAC determinations were carried out during 4.5 hours of anesthesia, with completion of the evaluations at 1.5-2 and 4-4.5 hours after drug administration. A two-factor anova was used to determine whether there was a time or treatment effect on MAC and a Tukey test compared the drug effects at each time. Significance is reported at p < 0.05. RESULTS: The mean MAC values (+/-SD) were 1.2 +/- 0.18 and 1.2 +/- 0.16% for control, 0.7 +/-0.15 and 1.0 +/- 0.15% for OXY, and 0.6 +/- 0.14 and 0.8 +/- 0.17% for HYDRO. The initial MAC with OXY and the MAC determined at both times with HYDRO were significantly different from the control MAC values. CONCLUSIONS: Both OXY and HYDRO significantly reduced the MAC of ISO in dogs at 2 hours. At approximately 4.5 hours, HYDRO had a significant MAC-sparing effect, whereas OXY did not. CLINICAL RELEVANCE: Although both OXY and HYDRO resulted in a significant reduction in the MAC of ISO at approximately 2 hours, HYDRO may be preferred for procedures of long duration and rarely needs repeated dosing before 4.5 hours.     

Anaesthetic potency of isoflurane in cattle: determination of the minimum alveolar concentration

Objective To determine the minimum alveolar concentration (MAC) of isoflurane in cattle.
Study design Prospective study.
Animals Sixteen healthy adult female Holstein-Friesian cattle weighing 612 ± 17 kg (× ± SEM) and aged 5.7 ± 0.9 years old.
Methods The unsedated cattle were restrained in right lateral recumbency using a rope harness technique. Anaesthesia was induced with isoflurane (ISO) in oxygen via a face mask connected to a large-animal, semiclosed anaesthetic circle system. Each cow was intubated with a cuffed orotracheal tube (25 mm ID). Inspired and end-tidal ISO were monitored using a calibrated infra red analyser with a methane filter. The MAC of ISO that prevented gross purposeful movement in response to a tail and dewclaw clamp was determined. The time from the start of ISO administration to intubation, the time interval between discontinuance of ISO and the time the animal regained sternal recumbency, were recorded. Time to standing and quality of recovery were also recorded.
Results The time from the start of ISO administration to tracheal intubation was 18.68 ± 2.77 minutes. The MAC of ISO in these cattle was 1.27 ± 0.03% (1.14 ± 0.01% corrected to sea level). Time to sternal recumbency after 90 ± 16 minutes of anaesthesia from intubation was 4.60 ± 0.58 minutes and time to standing was 6.70 ± 1.02 minutes. All cattle were extubated when they regained sternal recumbency.
Conclusion The MAC of isoflurane in these cattle was 1.27 ± 0.03% (1.14 ± 0.01% corrected to sea level). ISO provided a smooth induction to, and rapid recovery from, anaesthesia.
Clinical relevance Knowledge of the MAC of ISO in cattle will facilitate its appropriate clinical use.     

Effects of propofol on isoflurane minimum alveolar concentration and cardiovascular function in mechanically ventilated goats

ObjectiveTo evaluate the effects of propofol, on isoflurane minimum alveolar concentration (MAC) and cardiovascular function in mechanically ventilated goats.Study designProspective, randomized, crossover experimental study.AnimalsSix goats, three does and three wethers.MethodsGeneral anaesthesia was induced with isoflurane in oxygen. Following endotracheal intubation, anaesthesia was maintained with isoflurane in oxygen. Intermittent positive pressure ventilation was applied. Baseline isoflurane MAC was determined, the noxious stimulus used being clamping a claw. The goats then received, on separate occasions, three propofol treatments intravenously: bolus of 0.5 mg kg^?1 followed by a constant rate infusion (CRI) of 0.05 mg kg^?1 minute^?1 (treatment LPROP); bolus of 1.0 mg kg^?1 followed by a CRI of 0.1 mg kg^?1 minute^?1 (treatment MPROP), bolus of 2.0 mg kg^?1 followed by a CRI of 0.2 mg kg^?1 minute^?1 (treatment HPROP). Isoflurane MAC was re-determined following propofol treatments. Plasma propofol concentrations at the time of MAC confirmation were measured. Cardiopulmonary parameters were monitored throughout the anaesthetic period. Quality of recovery was scored. The Friedman test was used to test for differences between isoflurane MACs. Medians of repeatedly measured cardiovascular parameters were tested for differences between and within treatments using repeated anova by ranks (p < 0.05 for statistical significance).ResultsIsoflurane MAC [median (interquartile range)] was 1.37 (1.36–1.37) vol%. Propofol CRI significantly reduced the isoflurane MAC, to 1.15 (1.08–1.15), 0.90 (0.87–0.93) and 0.55 (0.49–0.58) vol% following LPROP, MPROP and HPROP treatment, respectively. Increasing plasma propofol concentrations strongly correlated (Spearman rank correlation) with decrease in MAC (Rho = 0.91). Cardiovascular function was not affected significantly by propofol treatment. Quality of recovery was satisfactory.Conclusions and clinical relevanceIn goats, propofol reduces isoflurane MAC in a dose-dependent manner with minimal cardiovascular effects.     

Effect of fentanyl,with or without treatment of bradycardia,on the minimum alveolar concentration of isoflurane and cardiovascular function in dogs

ObjectiveTo determine the effect of fentanyl on the minimum alveolar concentration of isoflurane (MAC_ISO) and cardiovascular variables in dogs, and how the treatment of bradycardia affects them.Study designProspective, randomized crossover-controlled trial.AnimalsA total of six male Beagle dogs weighing 9.9 ± 0.7 kg (mean ± standard deviation) and aged 13 months.MethodsTo each dog, two treatments were assigned on different days: fentanyl (FENTA) or fentanyl plus glycopyrrolate (FENTA_glyco) to maintain heart rate (HR) between 100 and 132 beats minute^?1. Determinations of MAC_ISO were performed with 10 plasma fentanyl target concentrations ([Fenta]_Target (0, 0.16, 0.32, 0.64, 1.25, 2.5, 5.0, 10.0, 20.0 and 40.0 ng mL^?1) for FENTA and 5 [Fenta]_Target (0, 1.25, 2.5, 5.0, 10.0 ng mL^?1)) for FENTA_glyco. During each MAC_ISO determination, cardiovascular variables [mean arterial pressure (MAP), HR and cardiac index (CI)] were measured, and systemic vascular resistance index (SVRI) calculated. Pharmacodynamic models were used to describe the plasma fentanyl concentration [Fenta]–response relationship for the effect on MAC_ISO and cardiovascular variables. A mixed-model analysis of variance followed by Dunnett’s or Tukey’s test, and the Bonferroni adjustment were used for comparisons within and between each treatment, respectively. Significance was set as p < 0.05.ResultsFentanyl decreased MAC_ISO by a maximum of 84%. The [Fenta] producing 50% decrease in MAC, HR and CI were 2.64, 3.65 and 4.30 ng mL^?1 (typical values of population model), respectively. The prevention of fentanyl-mediated bradycardia caused no significant effect on MAC_ISO, but increased HR, MAP and CI, and decreased SVRI when compared with isoflurane alone.Conclusions and clinical relevanceFentanyl caused a plasma concentration-dependent decrease in MAC_ISO, HR and CI and an increase in SVRI. Cardiovascular improvements associated with fentanyl in isoflurane-anesthetized dogs only occurred when the fentanyl-mediated bradycardia was prevented.     

GABA(A) receptor antagonism increases NMDA receptor inhibition by isoflurane at a minimum alveolar concentration

ObjectiveAt the minimum alveolar concentration (MAC), isoflurane potentiates GABA_A receptor currents and inhibits NMDA receptor currents, and these actions may be important for producing anesthesia. However, isoflurane modulates GABA_A receptors more potently than NMDA receptors. The objective of this study was to test whether isoflurane would function as a more potent NMDA receptor antagonist if its efficacy at GABA_A receptors was decreased.Study designProspective experimental study.AnimalsFourteen 10-week-old male Sprague–Dawley rats weighing 269 ± 12 g.MethodsIndwelling lumbar subarachnoid catheters were surgically placed in isoflurane-anesthetized rats. Two days later, the rats were anesthetized with isoflurane, and artificial CSF containing either 0 or 1 mg kg^?1 picrotoxin, a GABA_A receptor antagonist, was infused intrathecally at 1 μL minute^?1. The baseline isoflurane MAC was then determined using a standard tail clamp technique. MK801 (dizocilpine), an NMDA receptor antagonist, was then administered intravenously at 0.5 mg kg^?1. Isoflurane MAC was re-measured.ResultsPicrotoxin increased isoflurane MAC by 16% compared to controls. MK801 significantly decreased isoflurane MAC by 0.72% of an atmosphere in controls versus 0.47% of an atmosphere in rats receiving intrathecal picrotoxin.Conclusions and clinical relevanceA smaller MK801 MAC-sparing effect in the picrotoxin group is consistent with greater NMDA antagonism by isoflurane in these animals, since it suggests that fewer NMDA receptors are available upon which MK801 could act to decrease isoflurane MAC. Decreasing isoflurane GABA_A potentiation increases isoflurane NMDA antagonism at MAC. Hence, the magnitude of an anesthetic effect on a given channel or receptor at MAC may depend upon effects at other receptors.     

Isoflurane minimum alveolar concentration sparing effects of fentanyl in the dog

Objective

To characterize the isoflurane-sparing effects of a high and a low dose of fentanyl in dogs, and its effects on mean arterial pressure (MAP) and heart rate (HR).

Characteristics of the relationship between plasma ketamine concentration and its effect on the minimum alveolar concentration of isoflurane in dogs

OBJECTIVE: To characterize the shape of the relationship between plasma ketamine concentration and minimum alveolar concentration (MAC) of isoflurane in dogs. STUDY DESIGN: Retrospective analysis of previous data. ANIMALS: Four healthy adult dogs. METHODS: The MAC of isoflurane was determined at five to six different plasma ketamine concentrations. Arterial blood samples were collected at the time of MAC determination for measurement of plasma ketamine concentration. Plasma concentration/effect data from each dog were fitted to a sigmoid inhibitory maximum effect model in which MAC(c)= MAC(0) - (MAC(0)-MAC(min)) x C(gamma)/EC(50)(gamma)+C(gamma), where C is the plasma ketamine concentration, MAC(c) is the MAC of isoflurane at plasma ketamine concentration C, MAC(0) is the MAC of isoflurane without ketamine, MAC(min) is the lowest MAC predicted during ketamine administration, EC(50) is the plasma ketamine concentration producing 50% of the maximal MAC reduction, and gamma is a sigmoidicity factor. Nonlinear regression was used to estimate MAC(min), EC(50), and gamma. RESULTS: Mean +/- SEM MAC(min), EC(50) and gamma were estimated to be 0.11 +/- 0.01%, 2945 +/- 710 ng mL(-1) and 3.01 +/- 0.84, respectively. Mean +/- SEM maximal MAC reduction predicted by the model was 92.20 +/- 1.05%. CONCLUSIONS: The relationship between plasma ketamine concentration and its effect on isoflurane MAC has a classical sigmoid shape. Maximal MAC reduction predicted by the model is less than 100%, implying that high plasma ketamine concentrations may not totally abolish gross purposeful movement in response to noxious stimulation in the absence of inhalant anesthetics. CLINICAL RELEVANCE: The parameter estimates reported in this study will allow clinicians to predict the expected isoflurane MAC reduction from various plasma ketamine concentrations in an average dog.