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

This study evaluated the effects of IV lidocaine (L) and ketamine (K), alone and in combination (LK), on the isoflurane MAC (ISO_MAC) in goats. It was hypothesized that L and K would reduce ISO_MAC and that the effect of LK would be additive. Eight adult goats (24–51 kg) were used in the study. Each goat was studied on four occasions, at weekly intervals, using a randomized crossover design. Anesthesia was induced with isoflurane (ISO) in O₂ and goats were intubated and ventilated to normocapnia. End‐tidal ISO (ET_ISO) and CO₂ were monitored with a calibrated infrared analyzer. Body temperature was maintained in the normal range using a heating pad. Approximately 45 minutes after intubation, and with the ET_ISO having been held constant for at least 20 minutes, determination of the baseline MAC (MAC_B) was initiated. A noxious stimulus, which consisted of clamping a claw between the jaws of a 10‐inch Vulsellum forceps, was administered for 60 seconds or until purposeful movement occurred. If purposeful movement occurred, the ET_ISO was increased by 0.1 vols% otherwise it was decreased by 0.1 vols% and the stimulus was reapplied following a 20 minute equilibration period. Following MAC_B determination treatments were administered as a loading dose (Ld) in 10 mL 0.9% NaCl over 3 minutes followed by a constant rate infusion to a final volume of 60 mL hour^–1 in 0.9% NaCl, as follows: L (Ld 2.5 mg kg^–1 + 100 μg kg^–1 minutes^–1); K (Ld 1.5 mg kg^–1 + 50 μg kg^–1minutes); LK or 0.9% NaCl. Post‐treatment MAC (MAC_T) determination began 45 minutes after the start of the loading dose. MAC_B and MAC_T were determined in triplicate and the mean value was used for data analysis. Difference in percent change in MAC was tested using a mixed‐model anova . Means separation among levels of treatment was tested using the Tukey‐Kramer method. The mean MAC_B for all treatments was 1.13 ± 0.03 vols%. L, K and LK reduced (p < 0.05) MAC_B by 19%, 49% and 69%, respectively. No change (p > 0.05) occurred with saline. It was concluded that L and K caused clinically significant decreases in ISO_MAC; however, the percent MAC reduction with L was less than expected given the MAC reduction reported with L for other species. The combination (LK) caused a profound decrease in ISO_MAC and this effect was 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.     

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.     

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 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.     

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.     

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.     

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 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.     

The effect of epidural morphine on the minimum alveolar concentration of isoflurane in cats

This study was undertaken to evaluate the effect of 3 different doses of epidurally administered morphine sulphate on the minimum alveolar concentration (MAC) of isoflurane in healthy cats. Five 4-year-old, spayed female cats weighing 4.7 ± 0.8 kg were allocated randomly to receive one of 3 doses of morphine on each study day. The 3 doses of morphine were 0.05, 0.1 and 0.2 mg/kg bwt and each cat was studied 3 times so that each cat received all doses. On each study day, cats were anaesthetised with isoflurane and instrumented. The MAC of isoflurane was determined in triplicate and morphine sulphate was administered via an epidural catheter chronically implanted prior to the study. Maximum MAC reduction was determined over the following 2 h. At the end of the study cats were allowed to recover. There was a significant reduction in MAC of isoflurane, with all doses of epidural morphine (P<0.05). The maximum reduction in MAC of isoflurane after 0.05 mg/kg bwt, 0.10 mg/kg bwt and 0.20 mg/kg bwt morphine was 21.4 ± 9.796, 30.8 ± 9.696, and 30.2 ± 6.8%, respectively, with no significant difference between doses. Systolic, mean and diastolic blood pressure, heart rate, respiratory rate and arterial pH decreased significantly whereas arterial carbon dioxide tension increased significantly after morphine administration (P<0.05). The means for all variables returned to pre-morphine values when the end-tidal isoflurane concentration was reduced to the new MAC point. In conclusion, epidural morphine decreased the concentration of isoflurane required to prevent movement in response to noxious mechanical stimulation to the tail base. A similar effect may be seen clinically allowing lower doses of isoflurane to be used to provide surgical anaesthesia for procedures involving the hind limbs, pelvis and tail.     

Effects of epidural administration of morphine and buprenorphine on the minimum alveolar concentration of isoflurane in cats

OBJECTIVE: To determine effects of epidural administration of morphine and buprenorphine on the minimum alveolar concentration of isoflurane in cats. Animals-6 healthy adult domestic shorthair cats. PROCEDURES: Cats were anesthetized with isoflurane in oxygen. Morphine (100 microg/kg diluted with saline [0.9% NaCl] solution to a volume of 0.3 mL/kg), buprenorphine (12.5 microg/kg diluted with saline solution to a volume of 0.3 mL/kg), or saline solution (0.3 mL/kg) was administered into the epidural space according to a Latin square design. The minimum alveolar concentration (MAC) of isoflurane was measured in triplicate by use of the tail clamp technique. At least 1 week was allowed between successive experiments. RESULTS: The MAC of isoflurane was 2.00 +/- 0.18%, 2.13 +/- 0.11%, and 2.03 +/- 0.09% in the morphine, buprenorphine, and saline solution groups, respectively. No significant difference in MAC was detected among treatment groups. CONCLUSIONS AND CLINICAL RELEVANCE: A significant effect of epidural administration of morphine or buprenorphine on the MAC of isoflurane in cats could not be detected. Further studies are needed to establish whether epidural opioid administration has other benefits when administered as a component of general anesthesia in cats.     

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.     

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

OBJECTIVE: To determine the effect of IV administration of perzinfotel on the minimum alveolar concentration (MAC) of isoflurane in dogs. Animals-6 healthy sexually intact male Beagles. PROCEDURES: Dogs were instrumented with a telemetry device that permitted continuous monitoring of heart rate, arterial blood pressure, and body temperature. Dogs were anesthetized with propofol (4 to 6 mg/kg, IV) and isoflurane for 30 minutes before determination of MAC of isoflurane. Isoflurane MAC values were determined 4 times, separated by a minimum of 7 days, before and after IV administration of perzinfotel (0 [control], 5, 10, and 20 mg/kg). Bispectral index and percentage hemoglobin saturation with oxygen (SpO(2)) were monitored throughout anesthesia. RESULTS: Isoflurane MAC was 1.32 +/- 0.14%. Intravenous administration of perzinfotel at 0, 5, 10, and 20 mg/kg decreased isoflurane MAC by 0%, 24%, 30%, and 47%, respectively. Perzinfotel significantly decreased isoflurane MAC values, compared with baseline and control values. The bispectral index typically increased with higher doses of perzinfotel and lower isoflurane concentrations, but not significantly. Heart rate, body temperature, and SpO(2) did not change, but systolic, mean, and diastolic arterial blood pressures significantly increased with decreases in isoflurane MAC after administration of perzinfotel at 10 and 20 mg/kg, compared with 0 and 5 mg/kg. CONCLUSIONS AND CLINICAL RELEVANCE: IV administration of perzinfotel decreased isoflurane MAC values. Improved hemodynamics were associated with decreases in isoflurane concentration.     

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.     

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 intravenous lidocaine, ketamine, and the combination on the minimum alveolar concentration of sevoflurane in dogs

ObjectiveTo evaluate the effects of intravenous lidocaine (L) and ketamine (K) alone and their combination (LK) on the minimum alveolar concentration (MAC) of sevoflurane (SEVO) in dogs.Study designProspective randomized, Latin-square experimental study.AnimalsSix, healthy, adult Beagles, 2 males, 4 females, weighing 7.8 – 12.8 kg.MethodsAnesthesia was induced with SEVO in oxygen delivered by face mask. The tracheas were intubated and the lungs ventilated to maintain normocapnia. Baseline minimum alveolar concentration of SEVO (MAC_B) was determined in duplicate for each dog using an electrical stimulus and then the treatment was initiated. Each dog received each of the following treatments, intravenously as a loading dose (LD) followed by a constant rate infusion (CRI): lidocaine (LD 2 mg kg⁻¹, CRI 50 μg kg⁻¹minute⁻¹), lidocaine (LD 2 mg kg⁻¹, CRI 100 μgkg⁻¹ minute⁻¹), lidocaine (LD 2 mg kg⁻¹, CRI 200 μg kg⁻¹ minute⁻¹), ketamine (LD 3 mg kg⁻¹, CRI 50 μg kg⁻¹ minute⁻¹), ketamine (LD 3 mgkg⁻¹, CRI 100 μg kg⁻¹ minute⁻¹), or lidocaine (LD 2 mg kg⁻¹, CRI 100 μg kg⁻¹ minute⁻¹) + ketamine (LD 3 mg kg⁻¹, CRI 100 μg kg⁻¹ minute⁻¹) in combination. Post-treatment MAC (MAC_T) determination started 30 minutes after initiation of treatment.ResultsLeast squares mean ± SEM MAC_B of all groups was 1.9 ± 0.2%. Lidocaine infusions of 50, 100, and 200 μg kg⁻¹ minute⁻¹ significantly reduced MAC_B by 22.6%, 29.0%, and 39.6%, respectively. Ketamine infusions of 50 and 100 μg kg⁻¹ minute⁻¹ significantly reduced MAC_B by 40.0% and 44.7%, respectively. The combination of K and L significantly reduced MAC_B by 62.8%.Conclusions and clinical relevanceLidocaine and K, alone and in combination, decrease SEVO MAC in dogs. Their use, at the doses studied, provides a clinically important reduction in the concentration of SEVO during anesthesia in dogs.     

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

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