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.     

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.     

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.     

Effects of constant rate infusions of dexmedetomidine,remifentanil and their combination on minimum alveolar concentration of sevoflurane in dogs

ObjectiveTo evaluate the effects of constant rate infusions (CRIs) of dexmedetomidine and remifentanil alone and their combination on minimum alveolar concentration (MAC) of sevoflurane in dogs.Study designRandomized crossover experimental study.AnimalsA total of six (three males, three females) healthy, adult neutered Beagle dogs weighing 12.6 ± 1.4 kg.MethodsAnesthesia was induced with sevoflurane in oxygen until endotracheal intubation was possible and anesthesia maintained with sevoflurane using positive-pressure ventilation. Each dog was anesthetized five times and was administered each of the following treatments: saline (1 mL kg^–1 hour^–1) or dexmedetomidine at 0.1, 0.5, 1.0 or 5.0 μg kg^–1 loading dose intravenously over 10 minutes followed by CRI at 0.1, 0.5, 1.0 or 5.0 μg kg^–1 hour^–1, respectively. Following 60 minutes of CRI, sevoflurane MAC was determined in duplicate using an electrical stimulus (50 V, 50 Hz, 10 ms). Then, CRI of successively increasing doses of remifentanil (0.15, 0.60 and 2.40 μg kg^–1 minute^–1) was added to each treatment. MAC was also determined after 30 minutes equilibration at each remifentanil dose. Isobolographic analysis determined interaction from the predicted doses required for a 50% MAC reduction (ED₅₀) with remifentanil, dexmedetomidine and remifentanil combined with dexmedetomidine, with the exception of dexmedetomidine 5.0 μg kg^–1 hour^–1, obtained using log-linear regression analysis.ResultsThe sevoflurane MAC decreased dose-dependently with increasing infusion rates of dexmedetomidine and remifentanil. Remifentanil ED₅₀ values were lower when combined with dexmedetomidine than those obtained during saline–remifentanil. Synergistic interactions between dexmedetomidine and remifentanil for MAC reduction occurred with dexmedetomidine at 0.5 and 1.0 μg kg^–1 hour^–1.Conclusions and clinical relevanceCombined CRIs of dexmedetomidine and remifentanil synergistically resulted in sevoflurane MAC reduction. The combination of dexmedetomidine and remifentanil effectively reduced the requirement of sevoflurane during anesthesia in dogs.     

Effects of continuous intravenous infusion of morphine and morphine‐tramadol on the minimum alveolar concentration of sevoflurane and electroencephalographic entropy indices in dogs

ObjectiveTo compare the effects of continuous rate infusions (CRIs) of intravenous (IV) morphine and morphine-tramadol on the minimum alveolar concentration (MAC) of sevoflurane, and on electroencephalographic entropy indices in dogs.DesignProspective study.AnimalsEight young, healthy German shepherds, weighing 26.3 ± 3.1 kg (mean ± SD).MethodsAnaesthesia was induced and maintained with sevoflurane. A standard tail-clamp technique was used for MAC determination. Within one anaesthetic period, MAC was first determined during sevoflurane anaesthesia alone (MAC_B); then during morphine infusion (MAC_M), (loading dose 0.5 mg kg⁻¹IM; CRI, 0.2 mg kg⁻¹hour⁻¹⁾ then finally during morphine-tramadol infusion (tramadol loading dose 1.5 mg kg⁻¹IV; CRI, 2.6 mg kg⁻¹ hour⁻¹) (MAC_MT). At each change, periods of 45 minutes were allowed for equilibration. Stated entropy (SE), response entropy (RE), and RE-SE differences were measured five minutes prior to and during tail clamping.ResultsThe MAC_B was 2.1 ± 0.3vol%. The morphine and morphine-tramadol infusions reduced MAC to 1.6 ± 0.3vol% and 1.3 ± 0.3vol%, respectively. MAC was decreased below baseline more during morphine-tramadol than during morphine alone (39 ± 9% versus 25 ± 6%, respectively; p = 0.003). All SE and RE and most RE-SE differences were increased significantly (p < 0.05) over pre-stimulation in all groups when the dogs responded purposefully to noxious stimulation. When no response to noxious stimulation occurred, the entropy indices did not change.Conclusion and clinical relevanceIn dogs, combined morphine-tramadol CRI decreased sevoflurane MAC more than morphine CRI alone. Entropy indices changed during nociceptive responses in anaesthetized animals, suggesting that entropy measurements may be useful in determining anaesthetic depth in dogs.     

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.     

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.     

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.     

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.     

Determination of the minimum alveolar concentration (MAC) and cardiopulmonary effects of sevoflurane in sheep

Objective

To determine sevoflurane’s minimum alveolar concentration (MAC_SEVO) and its cardiopulmonary effects in sheep.

The effect of cannabidiol on sevoflurane minimum alveolar concentration reduction produced by morphine in rats

ObjectiveTo investigate the effect of cannabidiol (CBD) on sevoflurane minimum alveolar concentration (MAC_SEV) reduction produced by morphine in rats.Study designRandomized, blinded trial.AnimalsA total of 75 male Wistar Han rats weighing 276 ± 23 g (mean and standard deviation), aged 3 months.MethodsCannabidiol (CBD) was prepared in an ethanol-solutol-saline vehicle. Animals were randomly divided into 15 groups and given an intraperitoneal bolus of 1, 3, 5, 6.5, 7.5 or 10 mg kg^?1 of CBD alone (CBD1, CBD3, CBD5, CBD6.5, CBD7.5 and CBD10 respectively) or combined with 5 mg kg^?1 of morphine (MOR+CBD1, MOR+CBD3, MOR+CBD5, MOR+CBD6.5, MOR+CBD7.5 and MOR+CBD10). While three controls groups: MOR+saline, MOR+vehicle and vehicle were given an intraperitoneal bolus of morphine with saline, morphine with vehicle or vehicle alone respectively. The MAC_SEV was determined from alveolar gas samples at the time of tail clamp application. The MAC_SEV reduction was analyzed using a one-way ANOVA followed by Tukey’s test. Additionally, Kruskal-Wallis test for non-normally-distributed data was performed. Data are presented as mean ± standard deviation. P < 0.05ResultsThe mean MAC_SEV was not reduced by the action of CBD administered alone, but the addition of morphine to the different doses of CBD significantly reduced the MAC_SEV. That reduction was greatest in the MOR+CBD1, MOR+CBD7.5 and MOR+CBD10 groups (29 ± 5%, 32 ± 5% and 30 ± 6% respectively), less in MOR+CBD3 and MOR+CBD6.5 groups (24 ± 3% and 26 ± 4% respectively) and least in MOR+CBD5 group (17 ± 2%). However, only the MOR+CBD5 group was statistically significantly different from MOR+CBD1, MOR+CBD7.5 and MOR+CBD10 groups.Conclusions and clinical relevanceMAC_SEV in rat was unaltered by the action of CBD alone, the reduction in MAC_SEV produced by morphine was not enhanced by the addition of CBD at the doses studied.     

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 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.     

Effect of maropitant,a neurokinin‐1 receptor antagonist,on the minimum alveolar concentration of sevoflurane during stimulation of the ovarian ligament in cats

ObjectiveDetermine if maropitant decreases the minimum alveolar concentration (MAC) of sevoflurane during stimulation of the ovarian ligament in cats.Study designProspective study.AnimalsFifteen, female cats weighing 2.5 ± 0.6kg (mean ± SD).MethodsAnesthesia was induced and maintained with sevoflurane. The right ovary was accessed via laparoscopy. A suture around the ovary and ovarian ligament was exteriorized through the abdominal wall for stimulation. A stimulus–response curve was created to identify the optimal force for MAC comparisons. In 10 cats, MAC was determined with only sevoflurane (baseline) then after 1 and 5 mg kg^?1 intravenous maropitant administration. The stimulation tension force used was 4.9 N. Repeated measures anova was used to compare the groups. MAC was defined as the average of the cross‐over concentrations and reported MAC is adjusted to sea‐level and depicted as mean ± SD.ResultsThe stimulus‐response curve was hyperbolic and plateaued at 4.3 ± 3 N. The optimal tension force chosen to compare MAC was 4.9 N. The baseline sevoflurane MAC was 2.96 ± 0.3%. Maropitant, 1 mg kg^?1, decreased the MAC to 2.51 ± 0.3% (15%, p < 0.01). The higher maropitant dose of 5 mg kg^?1 did not change MAC further when compared to the low dose (2.46 ± 0.4%, p = 0.33).Conclusion and clinical relevanceThe ovarian ligament stimulation model is suitable to determine MAC during visceral stimulation in cats. Maropitant decreased the anesthetic requirements during visceral ovarian and ovarian ligament stimulation in cats. Maropitant (1 mg kg^?1) decreases MAC by 15%; a higher dose had no additional effect.     

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.     

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.     

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.

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

OBJECTIVE: To determine the influence of a low-dose constant rate infusion (LCRI; 50 microg kg(-1) minute(-1)) and high-dose CRI (HCRI; 200 microg kg(-1) minute(-1)) lidocaine infusion on the minimum alveolar concentration (MAC) of isoflurane (I) in dogs. STUDY DESIGN: Prospective experimental study. ANIMALS: Ten mongrel dogs (four females, six males), weighing 20-26.3 kg. METHODS: Dogs were anesthetized with I in oxygen and their lungs mechanically ventilated. Baseline MAC was determined using mechanical or electrical stimuli. Lidocaine (2 mg kg(-1) IV) was administered over 3 minutes, followed by the LCRI and MAC determination commenced 30 minutes later. Once MAC was determined following LCRI, the lidocaine infusion was stopped for 30 minutes. A second bolus of lidocaine (2 mg kg(-1), IV) was administered, followed by the HCRI and MAC re-determined. Concentrations of lidocaine and its metabolites were measured at end-tidal I concentrations immediately above and below MAC. Heart rates and blood pressures were measured. RESULTS: Minimum alveolar concentration of I was 1.34 +/- 0.11 (%; mean +/- SD) for both types of stimulus. The LCRI significantly reduced MAC to 1.09 +/- 0.13 (18.7% reduction) and HCRI to 0.76 +/- 0.10 (43.3% reduction). Plasma concentrations (ng mL(-1), median; value below and above MAC, respectively) for LCRI were: lidocaine, 1465 and 1537; glycinexylidide (GX), 111 and 181; monoethylglycinexylidide (MEGX), 180 and 471 and for HCRI were: lidocaine, 4350 and 4691; GX, 784 and 862; MEGX, 714 and 710. Blood pressure was significantly increased at 30 minutes after high dose infusion. CONCLUSION AND CLINICAL RELEVANCE: Lidocaine infusions reduced the MAC of I in a dose-dependent manner and did not induce clinically significant changes on heart rate or blood pressure.     

The effect of fentanyl on the end‐tidal sevoflurane concentration needed to prevent motor movement in dogs

ObjectiveThe objectives of this study were to determine the effects of fentanyl on the end-tidal concentration of sevoflurane needed to prevent motor movement (MAC_NM) in response to noxious stimulation, and to evaluate if acute tolerance develops.Study designRandomized cross-over experimental study.AnimalsSix healthy, adult (2–3 years old), intact male, mixed-breed dogs weighing 16.2 ± 1.1 kg.MethodsSix dogs were randomly assigned to receive one of three separate treatments over a 3 week period. After baseline sevoflurane MAC_NM (MAC_NM-B) determination, fentanyl treatments (T) were administered as a loading dose (Ld) and constant rate infusion (CRI) as follows: T1-Ld of 7.5 μg kg^?1 and CRI at 3 μg kg^?1 hour^?1; T2-Ld of 15 μg kg^?1 and CRI at 6.0 μg kg ^?1 hour^?1; T3-Ld of 30 μg kg^?1 and CRI at 12 μg kg^?1 hour^?1. The MAC_NM was defined as the minimum end-tidal sevoflurane concentration preventing motor movement. The first post-treatment MAC_NM (MAC_NM-I) determination was initiated 90 minutes after the start of the CRI, and a second MAC_NM (MAC_NM-II) determination was initiated 3 hours after MAC_NM-I was established.ResultsThe overall least square mean MAC_NM-B for all groups was 2.66%. All treatments decreased (p < 0.05) MAC_NM, and the decrease from baseline was 22%, 35% and 41% for T1, T2 and T3, respectively. Percentage change in T1 differed (p < 0.05) from T2 and T3; however, T2 did not differ from T3. MAC_NM-I was not significantly different from MAC_NM-II within treatments.Conclusions and clinical relevanceFentanyl doses in the range of 3–12 μg kg^?1 hour^?1 significantly decreased the sevoflurane MAC_NM. Clinically significant tolerance to fentanyl did not occur under the study conditions.