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 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.     

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 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.     

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.     

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 ketamine and magnesium on the minimum alveolar concentration of isoflurane in goats

OBJECTIVE: To evaluate the effects of ketamine, magnesium sulfate, and their combination on the minimum alveolar concentration (MAC) of isoflurane (ISO-MAC) in goats. ANIMALS: 8 adult goats. PROCEDURES: Anesthesia was induced with isoflurane delivered via face mask. Goats were intubated and ventilated to maintain normocapnia. After an appropriate equilibration period, baseline MAC (MAC(B)) was determined and the following 4 treatments were administered IV: saline (0.9% NaCl) solution (loading dose [LD], 30 mL/20 min; constant rate infusion [CRI], 60 mL/h), magnesium sulfate (LD, 50 mg/kg; CRI, 10 mg/kg/h), ketamine (LD, 1 mg/kg; CRI, 25 microg/kg/min), and magnesium sulfate (LD, 50 mg/kg; CRI, 10 mg/kg/h) combined with ketamine (LD, 1 mg/kg; CRI, 25 microg/kg/min); then MAC was redetermined. RESULTS: Ketamine significantly decreased ISOMAC by 28.7 +/- 3.7%, and ketamine combined with magnesium sulfate significantly decreased ISOMAC by 21.1 +/- 4.1%. Saline solution or magnesium sulfate alone did not significantly change ISOMAC. CONCLUSIONS AND CLINICAL RELEVANCE: Ketamine and ketamine combined with magnesium sulfate, at doses used in the study, decreased the end-tidal isoflurane concentration needed to maintain anesthesia, verifying the clinical impression that ketamine decreases the end-tidal isoflurane concentration needed to maintain surgical anesthesia. Magnesium, at doses used in the study, did not decrease ISOMAC or augment ketamine's effects on ISOMAC.     

Effects of morphine,butorphanol, buprenorphine,and U50488H on the minimum alveolar concentration of isoflurane in cats

OBJECTIVE: To determine whether opioids with varying interactions at receptors induce a reduction in minimum alveolar concentration (MAC) of isoflurane in cats. ANIMALS: 12 healthy, female, spayed cats. PROCEDURE: Cats were anesthetized with isoflurane and instrumented to allow collection of arterial blood and measurement of arterial blood pressure. Each drug was studied separately, and for each drug cats were randomly allocated to receive 2 doses. The drugs studied were morphine (0.1 or 1.0 mg/kg), butorphanol (0.08 or 0.8 mg/kg), buprenorphine (0.005 and 0.05 mg/kg), and U50488H (0.02 and 0.2 mg/kg). All drugs were diluted in 5 ml of saline (0.9% NaCl) solution and infused IV for 5 minutes. The MAC of isoflurane was determined in triplicate, the drug administered, and the MAC of isoflurane redetermined for a period of 3 hours. RESULTS: All drugs had a significant effect on MAC over time. With morphine only, the effect on MAC over time was different between doses. The greatest mean (+/- SD) reductions in MAC of isoflurane in response to morphine, butorphanol, buprenorphine, and U50488H administration were 28 +/- 9, 19 +/- 3, 14 +/- 7, and 11 +/- 7%, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Morphine (1.0 mg/kg) and butorphanol (0.08 and 0.8 mg/kg) induced significant reductions in MAC of isoflurane that were considered clinically important. Although significant, reductions in MAC of isoflurane induced by morphine (0.1 mg/kg), buprenorphine (0.005 and 0.05 mg/kg), and U50488H (0.02 and 0.2 mg/kg) were not considered clinically relevant because they fell within the error of the measurement technique. Administration of morphine or butorphanol decreases the need for potent inhalant anesthetics in cats and could potentially be beneficial in combination with inhalants.     

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.     

Minimal Anesthetic Concentration and Cardiopulmonary Dose Response of Isoflurane in Ducks

The minimal anesthetic concentration (MAC) for isoflurane was determined during spontaneous ventilation in nine male Peking ducks (7 to 12 weeks of age; 3.0 +/- 0.4 kg). While each bird was awake, arterial blood was collected for analysis of pH, PaCO2, and PaO2. After anesthesia was induced with isoflurane in oxygen, MAC was determined for isoflurane in each bird during spontaneous ventilation in a manner similar to MAC determinations in mammals. Pulmonary dose-response data were collected at 1 MAC and 1.5 MAC. Anesthetic index (Al; an index of anesthetic-induced apnea) was calculated from ducks that became apneic. The MAC for isoflurane was 1.30 +/- 0.23% (mean +/- SD). There was a dose-dependent decrease in ventilation as evidenced by a statistically significant increase in PaCO2. Apnea or unacceptable hypercarbia (PaCO2 greater than 110 mm Hg), or both, were common occurrences at end-tidal isoflurane concentrations greater than 1.5 MAC. Anesthetic index calculated from four ducks was 1.65 +/- 0.13 (mean +/- SEM). There was no significant difference between the means of either heart rate or mean arterial blood pressure in birds at 1.0 and 1.5 MAC.     

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.     

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

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

Effects of constant rate infusion of lidocaine and ketamine, with or without morphine, on isoflurane MAC in horses

REASONS FOR PERFORMING STUDY: Lidocaine and ketamine are administered to horses as a constant rate infusion (CRI) during inhalation anaesthesia to reduce anaesthetic requirements. Morphine decreases the minimum alveolar concentration (MAC) in some domestic animals; when administered as a CRI in horses, morphine does not promote haemodynamic and ventilatory changes and exerts a positive effect on recovery. Isoflurane-sparing effect of lidocaine, ketamine and morphine coadministration has been evaluated in small animals but not in horses. OBJECTIVES: To determine the reduction in isoflurane MAC produced by a CRI of lidocaine and ketamine, with or without morphine. HYPOTHESIS: Addition of morphine to a lidocaine-ketamine infusion reduces isoflurane requirement and morphine does not impair the anaesthetic recovery of horses. METHODS: Six healthy adult horses were anaesthetised 3 times with xylazine (1.1 mg/kg bwt i.v.), ketamine (3 mg/kg bwt i.v.) and isoflurane and received a CRI of lidocaine-ketamine (LK), morphine-lidocaine-ketamine (MLK) or saline (CTL). The loading doses of morphine and lidocaine were 0.15 mg/kg bwt i.v and 2 mg/kg bwt i.v. followed by a CRI at 0.1 mg/kg bwt/h and 3 mg/kg bwt/h, respectively. Ketamine was given as a CRI at 3 mg/kg bwt/h. Changes in MAC characterised the anaesthetic-sparing effect of the drug infusions under study and quality of recovery was assessed using a scoring system. Results: Mean isoflurane MAC (mean ± s.d.) in the CTL, LK and MLK groups was 1.25 ± 0.14%, 0.64 ± 0.20% and 0.59 ± 0.14%, respectively, with MAC reduction in the LK and MLK groups being 49 and 53% (P<0.001), respectively. No significant differences were observed between groups in recovery from anaesthesia. Conclusions and clinical relevance: Administration of lidocaine and ketamine via CRI decreases isoflurane requirements. Coadministration of morphine does not provide further reduction in anaesthetic requirements and does not impair recovery.     

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.     

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.     

Cardiovascular effects of propofol alone and in combination with ketamine for total intravenous anesthesia in cats

OBJECTIVE: To compare cardiovascular effects of equipotent infusion doses of propofol alone and in combination with ketamine administered with and without noxious stimulation in cats. ANIMALS: 6 cats. PROCEDURE: Cats were anesthetized with propofol (loading dose, 6.6 mg/kg; constant rate infusion [CRI], 0.22 mg/kg/min) and instrumented for blood collection and measurement of blood pressures and cardiac output. Cats were maintained at this CRI for a further 60 minutes, and blood samples and measurements were taken. A noxious stimulus was applied for 5 minutes, and blood samples and measurements were obtained. Propofol concentration was decreased to 0.14 mg/kg/min, and ketamine (loading dose, 2 mg/kg; CRI, 23 microg/kg/min) was administered. After a further 60 minutes, blood samples and measurements were taken. A second 5-minute noxious stimulus was applied, and blood samples and measurements were obtained. RESULTS: Mean arterial pressure, central venous pressure, pulmonary arterial occlusion pressure, stroke index, cardiac index, systemic vascular resistance index, pulmonary vascular resistance index, oxygen delivery index, oxygen consumption index, oxygen utilization ratio, partial pressure of oxygen in mixed venous blood, pH of arterial blood, PaCO2, arterial bicarbonate concentration, and base deficit values collected during propofol were not changed by the addition of ketamine and reduction of propofol. Compared with propofol, ketamine and reduction of propofol significantly increased mean pulmonary arterial pressure and venous admixture and significantly decreased PaO2. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of propofol by CRI for maintenance of anesthesia induced stable hemodynamics and could prove to be clinically useful in cats.     

Effects of diazepam and flumazenil on minimum alveolar concentrations for dogs anesthetized with isoflurane or a combination of isoflurane and fentanyl

OBJECTIVE: To determine the effect of a constant-rate infusion of fentanyl on minimum alveolar concentration (MAC) of isoflurane and to determine the interaction between fentanyl and a benzodiazepine agonist (diazepam) and antagonist (flumazenil) in isoflurane-anesthetized dogs. ANIMALS: 8 mixed-breed adult dogs. PROCEDURE: Dogs were anesthetized with isoflurane 3 times during a 6-week period. After a 30-minute equilibration period, each MAC determination was performed in triplicate, using standard techniques. Fentanyl was administered as a bolus (10 microg/kg of body weight, IV) that was followed by a constant infusion (0.3 microg/kg per min, IV) throughout the remainder of the experiment. After determining isoflurane-fentanyl MAC in triplicate, each dog received saline (0.9% NaCl) solution, diazepam, or flumazenil. After 30 minutes, MAC was determined again. RESULTS: Fentanyl significantly decreased isoflurane MAC (corrected to a barometric pressure of 760 mm Hg) from 1.80+/-0.21 to 0.85+/-0.14%, a reduction of 53%. Isoflurane-fentanyl-diazepam MAC (0.48+/-0.29%) was significantly less than isoflurane-fentanyl-saline MAC (0.79+/-0.21%). Percentage reduction in isoflurane MAC was significantly greater for fentanyl-diazepam (74%), compared with fentanyl-saline (54%) or fentanyl-flumazenil (61%). Mean fentanyl concentrations for the entire experiment were increased over time and were higher in the diazepam group than the saline or flumazenil groups. CONCLUSIONS AND CLINICAL RELEVANCE: Fentanyl markedly decreased isoflurane MAC in dogs. Diazepam, but not flumazenil, further decreased isoflurane-fentanyl MAC. Our results indicate that diazepam enhances, whereas flumazenil does not affect, opioid-induced CNS depression and, possibly, analgesia in dogs.     

Prior determination of baseline minimum alveolar concentration (MAC) of isoflurane does not influence the effect of ketamine on MAC in rabbits

The objective of this study was to compare the effect on the minimum alveolar concentration (MAC) of isoflurane when ketamine was administered either after or without prior determination of the baseline MAC of isoflurane in rabbits. Using a prospective randomized crossover study, 8 adult, female New Zealand rabbits were allocated to 2 treatment groups. Anesthesia was induced and maintained with isoflurane. Group 1 (same-day determination) had the MAC-sparing effect of ketamine [1 mg/kg bodyweight (BW) bolus followed by a constant rate infusion (CRI) of 40 μg/kg BW per min, given by intravenous (IV)], which was determined after the baseline MAC of isoflurane was determined beforehand. A third MAC determination was started 30 min after stopping the CRI. Group 2 (separate-day determination) had the MAC-sparing effect of ketamine determined without previous determination of the baseline MAC of isoflurane. A second MAC determination was started 30 min after stopping the CRI. In group 1, the MAC of isoflurane (2.15 ± 0.09%) was significantly decreased by ketamine (1.63 ± 0.07%). After stopping the CRI, the MAC was significantly less (2.04 ± 0.11%) than the baseline MAC of isoflurane and significantly greater than the MAC during the CRI. In group 2, ketamine decreased isoflurane MAC (1.53 ± 0.22%) and the MAC increased significantly (1.94 ± 0.25%) after stopping the CRI. Minimum alveolar concentration (MAC) values did not differ significantly between the groups either during ketamine administration or after stopping ketamine. Under the study conditions, prior determination of the baseline isoflurane MAC did not alter the effect of ketamine on MAC. Both methods of determining MAC seemed to be valid for research purposes.     

Effects of acepromazine on the cardiovascular actions of dopamine in anesthetized dogs

OBJECTIVE: To evaluate the effects of acepromazine maleate on the cardiovascular changes induced by dopamine in isoflurane-anesthetized dogs. STUDY DESIGN: Prospective, randomized cross-over experimental design. ANIMALS: Six healthy adult spayed female dogs weighing 16.4 +/- 3.5 kg (mean +/- SD). METHODS: Each dog received two treatments, at least 1 week apart. Acepromazine (0.03 mg kg(-1), IV) was administered 15 minutes before anesthesia was induced with propofol (7 mg kg(-1), IV) and maintained with isoflurane (1.8% end-tidal). Acepromazine was not administered in the control treatment. Baseline cardiopulmonary parameters were measured 90 minutes after induction. Thereafter, dopamine was administered intravenously at 5, 10, and 15 microg kg(-1) minute(-1), with each infusion rate lasting 30 minutes. Cardiopulmonary data were obtained at the end of each infusion rate. RESULTS: Dopamine induced dose-related increases in cardiac index (CI), stroke index, arterial blood pressure, mean pulmonary arterial pressure, oxygen delivery index (DO(2)I) and oxygen consumption index. In the control treatment, systemic vascular resistance index (SVRI) decreased during administration of 5 and 10 microg kg(-1) minute(-1) of dopamine and returned to baseline with the highest dose (15 microg kg (-1) minute(-1)). After acepromazine treatment, SVRI decreased from baseline during dopamine administration, regardless of the infusion rate, and this resulted in a smaller increase in blood pressure at 15 microg kg (-1) minute(-1). During dopamine infusion hemoglobin concentrations were lower following acepromazine and this contributed to significantly lower arterial O(2) content. CONCLUSIONS: Acepromazine prevented the return in SVRI to baseline and reduced the magnitude of the increase in arterial pressure induced by higher doses of dopamine. However, reduced SRVI associated with lower doses of dopamine and the ability of dopamine to increase CI and DO(2)I were not modified by acepromazine premedication. CLINICAL RELEVANCE: Previous acepromazine administration reduces the efficacy of dopamine as a vasopressor agent in isoflurane anesthetized dogs. Other beneficial effects of dopamine such as increased CO are not modified by acepromazine.