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

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

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

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

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

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

Effect of 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.     

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.     

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.     

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

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

Comparison of medetomidine and dexmedetomidine as premedicants in dogs undergoing propofol-isoflurane anesthesia.

OBJECTIVE: To compare 3 dose levels of medetomidine and dexmedetomidine for use as premedicants in dogs undergoing propofol-isoflurane anesthesia. ANIMALS: 6 healthy Beagles. PROCEDURE: Dogs received medetomidine or dexmedetomidine intravenously at the following dose levels: 0.4 microg of medetomidine or 0.2 microg of dexmedetomidine/kg of body weight (M0.4/D0.2), 4.0 microg of medetomidine or 2.0 microg of dexmedetomidine/kg (M4/D2), and 40 microg of medetomidine or 20 microg of dexmedetomidine/kg (M40/D20). Sedation and analgesia were scored before induction. Anesthesia was induced with propofol and maintained with isoflurane. End-tidal isoflurane concentration, heart rate, and arterial blood pressures and gases were measured. RESULTS: Degrees of sedation and analgesia were significantly affected by dose level but not drug. Combined mean end-tidal isoflurane concentration for all dose levels was higher in dogs that received medetomidine, compared with dexmedetomidine. Recovery time was significantly prolonged in dogs treated at the M40/D20 dose level, compared with the other dose levels. After induction, blood pressure decreased below reference range and heart rate increased in dogs treated at the M0.4/D0.2 dose level, whereas blood pressure was preserved in dogs treated at the M40/D20 dose level. However, dogs in these latter groups developed profound bradycardia and mild metabolic acidosis during anesthesia. Treatment at the M4/D2 dose level resulted in more stable cardiovascular effects, compared with the other dose levels. In addition, PaCO2 was similar among dose levels. CONCLUSIONS AND CLINICAL RELEVANCE: Dexmedetomidine is at least as safe and effective as medetomidine for use as a premedicant in dogs undergoing propofol-isoflurane anesthesia.     

Effects of epidural administration of dexmedetomidine on the minimum alveolar concentration of isoflurane in dogs

Objective-To evaluate the effects of epidural administration of 3 doses of dexmedetomidine on isoflurane minimum alveolar concentration (MAC) and characterize changes in bispectral index (BIS) induced by nociceptive stimulation used for MAC determination in dogs. Animals-6 adult dogs. Procedures-Isoflurane-anesthetized dogs received physiologic saline (0.9% NaCl) solution (control treatment) or dexmedetomidine (1.5 [DEX1.5], 3.0 [DEX3], or 6.0 [DEX6] mug/kg) epidurally in a crossover study. Isoflurane MAC (determined by use of electrical nociceptive stimulation of the hind limb) was targeted to be accomplished at 2 and 4.5 hours. Changes in BIS attributable to nociceptive stimulation and cardiopulmonary data were recorded at each MAC determination. Results-With the control treatment, mean +/- SD MAC values did not change over time (1.57 +/- 0.23% and 1.55 +/- 0.25% at 2 and 4.5 hours, respectively). Compared with the control treatment, MAC was significantly lower at 2 hours (13% reduction) but not at 4.5 hours (7% reduction) in DEX1.5-treated dogs and significantly lower at 2 hours (29% reduction) and 4.5 hours (13% reduction) in DEX3-treated dogs. The DEX6 treatment yielded the greatest MAC reduction (31% and 22% at 2 and 4.5 hours, respectively). During all treatments, noxious stimulation increased BIS; but changes in BIS were correlated with increases in electromyographic activity. Conclusions and Clinical Relevance-In dogs, epidural administration of dexmedetomidine resulted in dose-dependent decreases in isoflurane MAC and that effect decreased over time. Changes in BIS during MAC determinations may not represent increased awareness because of the possible interference of electromyographic activity.     

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.     

The cardiovascular effects of dexmedetomidine given by continuous infusion during isoflurane anesthesia in dogs

In a previous study we showed that the MAC of isoflurane was decreased by 18 ± 12% and 59 ± 7% by constant rate infusions of dexmedetomidine at 0.5 and 3 μg kg^–1 hour^–1. The purpose of this study was to document the cardiovascular changes associated with these infusions of dexmedetomidine at 1.3 MAC isoflurane/ dexmedetomidine. Dogs were anesthetized with isoflurane in oxygen given by mask. A cephalic venous catheter, a dorsal pedal arterial catheter and a balloon tipped, Swan–Ganz, pulmonary arterial catheter were placed percutaneously. After instrumentation the dogs were maintained at 1.3 MAC isoflurane for 60 minutes. At this time a set of measurements was made including, heart rate, respiratory rate, core body temperature, pulmonary and systemic arterial blood pressures (SAP, MAP, DAP, CVP, SPAP, MPAP, DPAP and PAOP), cardiac output and arterial and mixed venous blood samples were collected for the measurement of blood gases, pH, hemoglobin concentration, PCV and total protein. Calculated variables included base excess (BE), (HCO₃^?), cardiac index, systemic and pulmonary vascular resistance indices, oxygen delivery, oxygen consumption, oxygen utilization ratio and shunt fraction. After these measurements to dogs were randomly assigned to receive a loading dose of 0.5 or 3 μg kg^–1 of dexmedetomidine given over 6 minutes followed by an infusion of 0.5 (LD) or 3 μg kg^–1 hour^–1 (HD), respectively. The concentration of isoflurane was reduced by the above percentages, respectively, to maintain 1.3 MAC. Full sets of measurements were repeated at 10, 30, 60, 90, 120, 150 and 180 minutes after the start of the loading dose. Measured and calculated variables were compared with baseline using an anova and a post‐hoc Tukey's test. Significance was set at p = 0.05 and results are given as mean ± SD. The initial concentration of isoflurane was 1.73 ± 0.02% and was reduced to 1.41 ± 0.02 and 0.72 ± 0.09% for the LD and HD, respectively. Heart rate decreased with both doses but no other parameter changed significantly with the LD. With the HD there were significant changes in SAP, MAP, DAP, CVP, MPAP, PAOP, CI, SVRI, PCV, DO₂ and shunt fraction. The LD appeared to have minimal effect on the cardiopulmonary values measured, whereas the HD caused typical changes expected with an alpha‐2 agonist.     

Differences in need for hemodynamic support in horses anesthetized with sevoflurane as compared to isoflurane

OBJECTIVE: To study whether hemodynamic function in horses, particularly mean arterial blood pressure (MAP), is better maintained with sevoflurane than isoflurane, thus requiring less pharmacological support. STUDY DESIGN: Prospective randomized clinical investigation. Animals Thirty-nine racehorses undergoing arthroscopy in lateral recumbency. METHODS: Horses were assigned to receive either isoflurane (n = 20) or sevoflurane (n = 19) at 0.9-1.0 minimum alveolar concentration (MAC) for maintenance of anesthesia. Besides routine clinical monitoring, cardiac output (CO) was measured by lithium dilution. Hemodynamic support was prescribed as follows: when MAP decreased to <70 mmHg, patients were to receive infusion of 0.1% dobutamine, which was to be discontinued at MAP >85 mmHg or heart rate >60 beats minute(-1). Statistical analysis of results, given as mean +/- SD, included a clustered regression approach. RESULTS: Average inhalant anesthetic time [91 +/- 35 (isoflurane group) versus 97 +/- 26 minutes (sevoflurane group)] and dose (in MAC multiples), volume of crystalloid solution infused, and cardiopulmonary parameters including CO were similar in the two groups, except heart rate was 8% higher in isoflurane than sevoflurane horses (p < 0.05). To maintain MAP >70 mmHg, isoflurane horses received dobutamine over a significantly longer period (55 +/- 26 versus 28 +/- 21% of total anesthetic time, p < 0.01) and at a 51% higher dose than sevoflurane horses (41 +/- 19 versus 27 +/- 23 microg kg(-1) MAC hour(-1); p = 0.058), with 14/20 isoflurane animals and only 9/19 sevoflurane horses being infused with dobutamine at >30 microg kg(-1) MAC hour(-1) (p < 0.05). Dobutamine infusion rates were consistently lower in the sevoflurane as compared to the isoflurane group, with differences reaching significance level during the 0-30 minutes (p < 0.01) and 61-90 minutes periods (p < 0.05). CONCLUSIONS AND CLINICAL RELEVANCE: Horses under sevoflurane anesthesia may require less pharmacological support in the form of dobutamine than isoflurane-anesthetized horses. This could be due to less suppression of vasomotor tone.     

Isoflurane sparing action of epidurally administered xylazine hydrochloride in anesthetized dogs

OBJECTIVE: To evaluate the influence of epidural administration of xylazine hydrochloride on the minimum alveolar concentration of isoflurane (MAC(ISAO)) and cardiopulmonary system in anesthetized dogs. ANIMALS: 6 clinically normal dogs. PROCEDURE: Dogs were anesthetized with isoflurane in oxygen after randomly being assigned to receive 1 of the following 4 treatments: epidural administration of saline (0.9% NaCl) solution or xylazine at a dose of 0.1, 0.2, or 0.4 mg x kg(-1). Experiments were performed on 5 occasions with at least a 1-week interval between experiments; each dog received all 4 treatments. Following instrumentation, the concentration of isoflurane was maintained constant for 15 minutes at the MAC(ISO) that had been determined for each dog, and data on heart rate, arterial blood pressure, respiratory rate, tidal volume, minute volume, arterial partial pressure of oxygen, arterial partial pressure of carbon dioxide, and arterial pH were collected. The epidural treatment was administered, and 30 minutes later, data were again collected. From this point on, determination of the MAC(ISO) following epidural treatment (ie, MAC(ISO+EPI)) was initiated. Cardiopulmonary data were collected before each electrical supramaximal stimulus during MAC(ISO+EPI) determinations. RESULTS: The mean (+/-SD) MAC(ISO) was 1.29 +/- 0.04%. The epidural administration of xylazine at doses of 0.1, 0.2, and 0.4 mg x kg(-1) decreased the MAC(ISO), respectively, by 8.4 +/- 2.4%, 21.7 +/- 4.9%, and 33.4 +/- 2.64%. Cardiopulmonary effects were limited. CONCLUSIONS AND CLINICAL RELEVANCE: Epidural administration of xylazine decreases the MAC(ISO) in a dose-dependent manner and is associated with few cardiopulmonary effects in anesthetized dogs.     

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.     

The isoflurane-sparing and clinical effects of a constant rate infusion of remifentanil in dogs

OBJECTIVE: To evaluate the isoflurane-sparing and clinical effects of two constant rate infusions of remifentanil in healthy dogs undergoing orthopaedic surgery. STUDY DESIGN: Prospective, randomized clinical study. ANIMALS: Forty-one American Society of Anesthesiologists I-II client-owned dogs (age, 7 months-9 years; body mass 11-59 kg). METHODS: Dogs were randomly assigned to one of three groups and received either: intramuscular (IM) meperidine 2 mg kg(-1) every 2 hours throughout surgery (control group (C); n = 13); remifentanil infused intravenously (IV) at 0.1 microg kg(-1) minute(-1) (low remifentanil group (L); n = 14) or remifentanil infused at 0.25 microg kg(-1) minute(-1) IV (high remifentanil group (H); n = 14). Anaesthesia was induced with thiopental administered to effect and maintained using isoflurane in 100% oxygen. During controlled ventilation when the end-tidal CO(2) was maintained between 4.65 and 5.98 kPa [35-45 mmHg], the end-tidal isoflurane concentration (e'iso%), mean arterial blood pressure (MAP) and heart rate (HR) were measured every 5 minutes. Bradycardia (HR < 40 minute(-1) lasting >5 minutes) was corrected with 0.01 mg kg(-1) IV glycopyrrolate. Data were analysed using the Kruskal-Wallis test with a post-hoc Mann-Whitney U-test and Bonferroni correction. Statistical significance was accepted at < or = 0.05. Data are expressed as mean +/- standard deviation. RESULTS: The e'iso% was reduced in a dose-dependent manner by remifentanil. In C, e'iso% was 1.28 +/-0.13 and was significantly different from L (0.78 +/- 0.17, p < 0.001) and H (0.65 +/- 0.16, p < 0.001). HR was significantly different between groups (p < 0.001). There were no significant differences in MAP between groups. Glycopyrrolate was required in two, three and six dogs in the C, L and H groups respectively. CONCLUSIONS: Remifentanil infusion reduced the isoflurane concentration required for surgical anaesthesia during orthopaedic surgery. CLINICAL RELEVANCE: Remifentanil infusions may be a useful additive to isoflurane anaesthesia in healthy dogs.     

Dexmedetomidine continuous rate infusion during isoflurane anaesthesia in canine surgical patients

OBJECTIVE: To determine the effects of three rates of dexmedetomidine (DMED) constant rate infusion (CRI) on overall tissue perfusion, isoflurane (ISO) requirements, haemodynamics and quality of recovery in canine surgical patients. STUDY DESIGN: Prospective, randomized, blinded clinical study. ANIMALS: Client-owned dogs presented for soft tissue or orthopaedic surgery. METHODS: Following intravenous (IV) pre-medication with DMED (5 microg kg(-1)) and buprenorphine (10 microg kg(-1)) and propofol induction, anaesthesia was maintained with ISO in oxygen/air supplemented with a DMED CRI (1, 2 or 3 microg kg(-1) hour(-1); groups 1, 2 and 3, respectively). Ventilation was controlled in all animals using intermittent positive pressure ventilation (IPPV). Monitoring included end-tidal (ET) gases, ECG, arterial blood pressure, body temperature and sequential arterial blood gas and lactate measurements. Quality of recovery was scored after intramuscular (IM) administration of atipamezole (ATI) (12.5 microg kg(-1)). Immediate post-operative analgesia was provided with carprofen and/or buprenorphine. An analysis of variance was conducted for repeated measurements obtained during 80 minutes after first incision. Categorical data were evaluated with Chi-square analyses. RESULTS: Arterial blood pressure remained stable and within clinically acceptable limits. Mean heart rate in group 2 was significantly lower than in group 1. The incidence of 2nd degree AV block type II was significantly higher in group 3. Mean arterial lactate concentrations remained below 2 mmol/L in all groups during the study, with a significant increase occurring during recovery compared with surgery for group 3. Mean e'ISO% was similar and <1% in all groups. Complete recovery from anaesthesia was achieved after ATI administration and was of good quality in all but three animals. CONCLUSIONS AND CLINICAL RELEVANCE: Dexmedetomidine CRI is a reliable and valuable adjunct to ISO anaesthesia in maintaining surgical anaesthesia in ASA I-II dogs. Data reported indicate adequate overall tissue perfusion and a low ISO requirement while enabling a smooth and rapid recovery following ATI. The DMED CRI of 1 microg kg(-1) hour(-1) following a loading dose of 5 microg kg(-1) produced the most favourable results.     

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.     

Response of hypotensive dogs to dopamine hydrochloride and dobutamine hydrochloride during deep isoflurane anesthesia

OBJECTIVE: To evaluate the dose-related cardiovascular and urine output (UrO) effects of dopamine hydrochloride and dobutamine hydrochloride, administered individually and in combination at various ratios, and identify individual doses that achieve target mean arterial blood pressure (MAP; 70 mm Hg) and cardiac index (CI; 150 mL/kg/min) in dogs during deep isoflurane anesthesia. ANIMALS: 10 young clinically normal dogs. PROCEDURES: Following isoflurane equilibration at a baseline MAP of 50 mm Hg on 3 occasions, dogs randomly received IV administration of dopamine (3, 7, 10, 15, and 20 microg/kg/min), dobutamine (1, 2, 4, 6, and 8 microg/kg/min), and dopamine-dobutamine combinations (3.5:1, 3.5:4, 7:2, 14:1, and 14:4 microg/kg/min) in a crossover study. Selected cardiovascular and UrO effects were determined following 20-minute infusions at each dose. RESULTS: Dopamine caused significant dose-dependent responses and achieved target MAP and CI at 7 microg/kg/min; dobutamine at 2 microg/kg/min significantly affected only CI values. At any dose, dopamine significantly affected UrO, whereas dobutamine did not. Target MAP and CI values were achieved with a dopamine-dobutamine combination at 7:2 microg/kg/min; a dopamine-related dose response for MAP and dopamine- and dobutamine-related dose responses for CI were identified. Changes in UrO were associated with dopamine only. CONCLUSIONS AND CLINICAL RELEVANCE: In isoflurane-anesthetized dogs, a guideline dose for dopamine of 7 microg/kg/min is suggested; dobutamine alone did not improve MAP. Data regarding cardiovascular and UrO effects indicated that the combination of dopamine and dobutamine did not provide greater benefit than use of dopamine alone in dogs.     

Clinical effects and pharmacokinetics of medetomidine and its enantiomers in dogs

The clinical effects and pharmacokinetics of medetomidine (MED) and its enanti-omers, dexmedetomidine (DEX) and levomedetomidine (LEVO) were compared in a group of six beagle dogs. The dogs received intravenously (i.v.) a bolus of MED (40 microg/kg), DEX (20 and 10 microg/kg), LEVO (20 and 10 microg/kg), and saline placebo in a blinded, randomized block study in six separate sessions. Sedation and analgesia were scored subjectively, and the dogs were monitored for heart rate, ECG lead II, direct blood pressure, respiratory rate, arterial blood gases, and rectal body temperature. Blood samples for drug analysis were taken. Peak sedative and analgesic effects were observed at mean (+/- SD) plasma levels of 18.5 +/- 4.7 ng/mL for MED40, 14.0 +/- 4.5 ng/mL for DEX20, and 5.5 +/- 1.3 ng/mL for DEX10. The overall level of sedation and cardiorespiratory effects did not differ between MED40, DEX20 and DEX10 during the first hour, apparently due to a ceiling effect. However, the analgesic effect of DEX20 lasted longer than the effect of the corresponding dose of racemic medetomidine, suggesting greater potency for dexmedetomidine in dogs. Levomedetomidine had no effect on cardio-vascular parameters and caused no apparent sedation or analgesia. The pharmacokinetics of dexmedetomidine and racemic medetomidine were similar, but clearance of levomedetomidine was more rapid (4.07 +/- 0.69 L/h/kg for LEVO20 and 3.52 +/- 1.03 for LEVO10) than of the other drugs (1.26 +/- 0.44 L/h/kg for MED40, 1.24 +/- 0.48 for DEX20, and 0.97 +/- 0.33 for DEX10).