Isoflurane Minimum Alveolar Concentration Reduction Research Articles

Effect of oral administration of gabapentin on the minimum alveolar concentration of isoflurane in dogs.

To determine the effect of oral administration of gabapentin (20 mg/kg) on the minimum alveolar concentration (MAC) of isoflurane in dogs. 6 healthy adult dogs (3 males and 3 females with a mean ± SD body weight of 24.8 ± 1.3 kg). Each dog was anesthetized twice. Dogs were initially assigned to 1 of 2 treatments (gabapentin [20 mg/kg, PO] followed 2 hours later by anesthesia maintained with isoflurane or anesthesia maintained with isoflurane alone). A minimum of 7 days later, dogs received the other treatment. The MAC of isoflurane was determined by use of an iterative bracketing technique with stimulating electrodes placed in the maxillary buccal mucosa. Hemodynamic variables and vital parameters were recorded at the lowest end-tidal isoflurane concentration at which dogs did not respond to the stimulus. Effect of treatment on outcome variables was analyzed by use of a paired t test. Mean ± SD MAC of isoflurane was significantly lower when dogs received gabapentin and isoflurane (0.71 ± 0.12%) than when dogs received isoflurane alone (0.91 ± 0.26%). Mean reduction in MAC of isoflurane was 20 ± 14%. Hemodynamic variables did not differ significantly between treatments. Mean time to extubation was significantly less when dogs received gabapentin and isoflurane (6 ± 4 minutes) than when dogs received isoflurane alone (23 ± 15 minutes). Oral administration of gabapentin 2 hours before anesthesia maintained with isoflurane had a MAC-sparing effect with no effect on hemodynamic variables or vital parameters of dogs.

Effect of mepivacaine in an infraorbital nerve block on minimum alveolar concentration of isoflurane in clinically normal anesthetized dogs undergoing a modified form of dental dolorimetry

To evaluate the effects of a routinely used infraorbital nerve block, performed for dental procedures, on the anesthetic requirement for isoflurane in dogs. Prospective controlled study. 8 healthy adult Beagles. Dogs were anesthetized with isoflurane, and the minimum alveolar concentration (MAC) of isoflurane was established. A modification of a well-established method of stimulating the dental pulp, dental dolorimetry, was used to deliver a noxious stimulus (electrical stimulation) for isoflurane MAC determination. Once the isoflurane MAC was established, an infraorbital nerve block was performed with mepivacaine. The isoflurane MAC was then determined with the addition of the nerve block. Measurements of heart rate and mean arterial blood pressure were obtained at specified time points (baseline and prevention and elicitation of purposeful movement) during the determination of MAC and in response to the noxious stimulus. The mean ± SD isoflurane MAC without an infraorbital nerve block was 1.12 ± 0.13%. Isoflurane MAC with the regional mepivacaine anesthesia was 0.86 ± 0.11%. A significant reduction in isoflurane MAC (23%) was seen after the infraorbital nerve block, compared with results before the nerve block. With the exception of baseline measurements, no significant differences were found between treatments (isoflurane alone vs isoflurane with regional mepivacaine anesthesia) in heart rate or mean arterial blood pressure before or after the noxious stimulus. The significant reduction in MAC of isoflurane supported the practice of the addition of regional anesthesia for painful dental procedures to reduce the dose-dependent cardiorespiratory effects of general anesthesia.

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

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. To determine the reduction in isoflurane MAC produced by a CRI of lidocaine and ketamine, with or without morphine. Addition of morphine to a lidocaine-ketamine infusion reduces isoflurane requirement and morphine does not impair the anaesthetic recovery of horses. 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. 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. 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.

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

To evaluate the effects of remifentanil on isoflurane minimum alveolar concentration (ISO(MAC)) in dogs. 6 adult mixed-breed dogs. Dogs were anesthetized with isoflurane on 2 occasions. During the first set of experiments, ISO(MAC) was determined before remifentanil infusion (baseline), during constant rate infusion (CRI) of remifentanil (0.15, 0.30, 0.60, and 0.90 microg/kg/min), and 80 minutes after remifentanil infusion. After a 1-week washout period, dogs received a CRI of remifentanil (0.15 microg/kg/min) and ISO(MAC) was redetermined 2, 4, and 6 hours after commencing the infusion. Mean +/- SD baseline ISO(MAC) was 1.24 +/- 0.18%. Remifentanil infusion (0.15, 0.30, 0.60, and 0.90 microg/kg/min) decreased ISO(MAC) by 43 +/- 10%, 59 +/- 10%, 66 +/- 9%, and 71 +/- 9%, respectively. The ISO(MAC) values determined during the 0.30, 0.60, and 0.90 microg/kg/min infusion rates did not differ from each other, but these values were significantly lower, compared with the 0.15 microg/kg/min infusion rate. The ISO(MAC) recorded after remifentanil infusion (1.09 +/- 0.18%) did not differ from baseline ISO(MAC). There was no change in ISO(MAC) throughout the 6-hour period of a CRI of remifentanil. Remifentanil decreased ISO(MAC) in a dose-related fashion; the reduction in ISO(MAC) was stable over the course of a prolonged CRI (6 hours). A dose of 0.30 microg of remifentanil/kg/min resulted in nearly maximal isoflurane-sparing effect in dogs; a ceiling effect was observed at higher infusion rates.

Effect of remifentanil hydrochloride administered via constant rate infusion on the minimum alveolar concentration of isoflurane in cats

To evaluate the effects of increasing doses of remifentanil hydrochloride administered via constant rate infusion (CRI) on the minimum alveolar concentration (MAC) of isoflurane in cats. 6 healthy adult cats. For each cat, 2 experiments were performed (2-week interval). On each study day, anesthesia was induced and maintained with isoflurane; a catheter was placed in a cephalic vein for the administration of lactated Ringer's solution or remifentanil CRIs, and a catheter was placed in the jugular vein for collection of blood samples for blood gas analyses. On the first study day, individual basal MAC (MAC(Basal)) was determined for each cat. On the second study day, 3 remifentanil CRIs (0.25, 0.5, and 1.0 microg/kg/min) were administered (in ascending order); for each infusion, at least 30 minutes elapsed before determination of MAC (designated as MAC(R0.25), MAC(R0.5), and MAC(R1.0), respectively). A 15-minute washout period was allowed between CRIs. A control MAC (MAC(Control)) was determined after the last remifentanil infusion. Mean +/- SD MAC(Basal) and MAC(Control) values at sea level did not differ significantly (1.66 +/- 0.08% and 1.52 +/- 0.21%, respectively). The MAC values determined for each remifentanil CRI did not differ significantly. However, MAC(R0.25), MAC(R0.5), and MAC(R1.0) were significantly decreased, compared with MAC(Basal), by 23.4 +/- 7.9%, 29.8 +/- 8.3%, and 26.0 +/- 9.4%, respectively. The 3 doses of remifentanil administered via CRI resulted in a similar degree of isoflurane MAC reduction in adult cats, indicating that a ceiling effect was achieved following administration of the lowest dose.

Effects of Carprofen and Morphine on the Minimum Alveolar Concentration of Isoflurane in Dogs

The minimum alveolar concentration (MAC) of isoflurane in dogs was determined following carprofen (2.2 mg/kg per os) alone, morphine (1 mg/kg intravenously) alone, carprofen and morphine, and no drug control in eight healthy adult dogs. Isoflurane MAC following administration of morphine alone (0.81%+/-0.18%) or carprofen and morphine (0.68%+/-0.31%) was significantly less than the control MAC (1.24%+/-0.15%). Isoflurane MAC after carprofen alone (1.13%+/-0.13%) was not significantly different from the control value. Results indicated that administration of morphine alone or in combination with carprofen significantly reduced the MAC of isoflurane in dogs. The isoflurane MAC reduction was additive between the effects of carprofen and morphine.

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

ObjectiveTo characterize the shape of the relationship between plasma ketamine concentration and minimum alveolar concentration (MAC) of isoflurane in dogs. Study designRetrospective analysis of previous data. AnimalsFour healthy adult dogs. MethodsThe 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 MACc=MAC0-(MAC0-MACmin)×CγEC50γ+Cγ, where C is the plasma ketamine concentration, MACc is the MAC of isoflurane at plasma ketamine concentration C, MAC0 is the MAC of isoflurane without ketamine, MACmin is the lowest MAC predicted during ketamine administration, EC50 is the plasma ketamine concentration producing 50% of the maximal MAC reduction, and γ is a sigmoidicity factor. Nonlinear regression was used to estimate MACmin, EC50, and γ. ResultsMean ± SEM MACmin, EC50 and γ 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%. ConclusionsThe 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 relevanceThe 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 meloxicam and butorphanol on minimum alveolar concentration of isoflurane in rabbits

To determine the effects of meloxicam and butorphanol on minimum alveolar concentration of isoflurane (MAC(ISO)) in rabbits. 10 healthy young adult female rabbits. Rabbits were anesthetized with isoflurane on 3 occasions in a blinded, randomized complete block design to determine the MAC(ISO) associated with administration of meloxicam (0, 0.3, or 1.5 mg/kg, PO) and butorphanol (0.4 mg/kg, IV). The MAC(ISO) was determined by use of a paw clamp technique as the end-tidal concentration of isoflurane halfway between the values that allowed or inhibited purposeful movement. Rectal temperature, end-tidal CO2 concentration, heart rate, oxygen saturation, and arterial blood pressure were measured to evaluate cardiopulmonary function. Mean +/- SE MAC(ISO) in saline (0.9% NaCl) solution-treated rabbits was 2.49 +/- 0.07% and was not significantly different from that associated with administration of meloxicam at 0.3 mg/kg (2.56 +/- 0.07%) or 1.5 mg/kg (2.66 +/- 0.07%). Butorphanol significantly reduced the MAC(ISO) to 2.30 +/- 0.07% when administered with saline solution alone, 2.27 +/- 0.07% when administered with 0.3 mg of meloxicam/kg, and 2.33 +/- 0.07% when administered with 1.5 mg of meloxicam/kg. The percentage reduction in MAC(ISO) was significantly greater for rabbits that received butorphanol and meloxicam at either dose, compared with butorphanol and saline solution. Results indicated that meloxicam does not have a direct isoflurane-sparing effect and does not interfere with the anesthetic-sparing effect of butorphanol in rabbits.

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

To determine the effect of 6 plasma ketamine concentrations on the minimum alveolar concentration (MAC) of isoflurane in dogs. 6 dogs. 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. 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. Ketamine appears to have a potential role for balanced anesthesia in dogs.

Comparisons of the effects of acupuncture, electroacupuncture, and transcutaneous cranial electrical stimulation on the minimum alveolar concentration of isoflurane in dogs

To compare the effects of acupuncture (AP), electroacupuncture (EA), and transcutaneous cranial electrical stimulation (TCES) with high-frequency intermittent currents on the minimum alveolar concentration (MAC) of isoflurane and associated cardiovascular variables in dogs. 8 healthy adult female Beagles. Each dog was anesthetized with isoflurane on 4 occasions, allowing a minimum of 10 days between experiments. Isoflurane MAC values were determined for each dog without treatment (controls) and after treatment with AP and EA (AP points included the Large Intestine 4, Lung 7, Governing Vessel 20, Governing Vessel 14, San Tai, and Baihui) and TCES. Isoflurane MAC values were determined by use of noxious electrical buccal stimulation. Heart rate, mean arterial blood pressure (MAP), arterial blood oxygen saturation (Spo2) measured by use of pulse oximetry, esophageal body temperature, inspired and expired end-tidal isoflurane concentrations, end-tidal carbon dioxide concentration, and bispectral index (BIS) were monitored. Blood samples were collected for determination of plasma cortisol concentration. Mean +/- SD baseline MAC of isoflurane was 1.19 +/- 0.1%. Acupuncture did not significantly change MAC of isoflurane. Treatments with EA and TCES significantly lowered the MAC of isoflurane by 10.1% and 13.4%, respectively. The Spo2, heart rate, MAP, BIS, esophageal body temperature, and plasma cortisol concentration were not significantly different after AP, EA, TCES, and control treatments at any time interval. Use of EA and TCES decreased MAC of isoflurane in dogs without inducing adverse hemodynamic effects. However, the reduction in isoflurane MAC by EA andTCES treatments was not considered clinically relevant.

Meloxicam, a specific COX-2 inhibitor, does not enhance the isoflurane minimum alveolar concentration reduction produced by morphine in the rat.

A synergistic effect of nonselective cyclooxygenase (COX) inhibitors on morphine-induced decrease of isoflurane minimum alveolar concentration (MAC(ISO)) has been observed in the rat. We studied the influence of specific COX-2 inhibitors on this decrease of MAC. Sixty-four female rats were anesthetized with isoflurane in oxygen. The animals were grouped into saline solution, aspirin (30 mg/kg), morphine (1 mg/kg), morphine (1 mg/kg) + aspirin (30 mg/kg), meloxicam (1 and 3 mg/kg), and morphine (1 mg/kg) + meloxicam (1 and 3 mg/kg). Then the MAC(ISO) was determined from alveolar gas samples at the time of tail clamp. The groups treated with saline solution, aspirin, and 1 and 3 mg/kg meloxicam did not express any statistically relevant changes among them. The administration of morphine + meloxicam 1 or 3 mg/kg significantly reduced the MAC(ISO) just as in the group where only morphine was administered (morphine 1.35% +/- 0.07%, morphine + 1 mg/kg meloxicam 1.36% +/- 0.04%, and morphine + 3 mg/kg meloxicam 1.37% +/- 0.08%). The greatest reduction of MAC(ISO) was after administration of morphine + aspirin (1.19% +/- 0.05%). The administration of meloxicam does not potentiate the morphine-induced decrease of MAC(ISO) in the rat. A synergistic effect between morphine and aspirin on isoflurane minimum alveolar concentration has been observed in the rat--an effect that does not occur between morphine and meloxicam.

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

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). 6 adult dogs. 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. 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. 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.

Design, synthesis, and evaluation of analogues of 3,3,3-trifluoro-2-hydroxy-2-phenyl-propionamide as orally available general anesthetics.

We have recently discovered a novel class of compounds that have oral general anesthetic activity, potent anticonvulsant activity, and minimal hemodynamic effects. The 3,3,3-trifluoro-2-hydroxy-2-phenyl-propionamide (1) demonstrated potent ability to reduce the minimum alveolar concentration (MAC) of isoflurane, with no effects on heart rate or blood pressure at therapeutic concentrations. Analogue 1 also had potent oral anticonvulsant activity against maximal electroshock (MES) and subcutaneous metrazol (scMET) models with a therapeutic index of 10 for MES activity. In this study, we further synthesized nine new racemic analogues and evaluated these compounds for effects on isoflurane MAC reduction and blood pressure. Preliminary data demonstrate potent reduction in the isoflurane MAC for two new compounds. Current mechanistic studies were unrevealing for effects on voltage-gated ion channels as a putative mechanism. Liposomal partitioning studies using (19)F NMR reveal that the aromatic region partitions into the core of the lipid. This partitioning correlated with general anesthetic activity of this class of compounds. Further, compound 1 was used at a concentration of 1 mM and slightly enhanced GABA(A) current in hippocampal neurons at 10 microM. Altogether, 3,3,3-trifluoro-2-hydroxy-2-phenyl-propionamide exhibited excellent oral general anesthetic activity and appears devoid of significant side effects (i.e., alterations in blood pressure or heart rate).

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

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. 8 mixed-breed adult dogs. 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. 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. 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.

MAGNESIUM POTENTIATES KETAMINE-INDUCED CHANGES IN THE THRESHOLD FOR ISOFLURANE ANESTHESIA IN THE RAT

S354 INTRODUCTION: Magnesium sulfate (MgSO4), used in obstetrics to inhibit premature labor and in the therapy of pre-eclampsia and eclampsia, has been demonstrated to alter the minimum alveolar concentration (MAC) of halothane at clinically relevant concentrations [1]. The interactions of ketamine and volatile anesthetics have been reported previously [2]. This study was undertaken to examine the potential anesthetic interactions of MgSO4 and ketamine during isoflurane anesthesia. METHODS: After institutional animal care committee approval had been obtained, we examined the reduction of the MAC of isoflurane in response to increasing doses of ketamine and in the presence and absence of elevated serum magnesium concentrations. Briefly, forty-six male Sprague-Dawley rats were anesthetized with isoflurane in oxygen. Control MAC was established according to the methods reported previously [3]. Following the administration of either ketamine (10, 25, 50, 75, or 100 mg/kg via i.v. injection), or MgSO4 (at a rate of 5.0 mg/kg/min for at least 30 min), or both MgSO4 and ketamine (10, 25, or 50 mg/kg), isoflurane MAC was again determined. Alveolar gas concentrations, hemodynamic monitoring, and arterial blood gas measurements were obtained as described previously [3]. RESULTS: Ketamine dose-dependently reduced the MAC for isoflurane (39.6 +/- 5.7% at the 100 mg/kg dose), while exhibiting no ceiling effect. MgSO4 produced an approximately 14% reduction in the MAC for isoflurane at plasma concentrations of 6 to 8 mg/dL. The combination of MgSO4 and ketamine resulted in a significant enhancement in the isoflurane MAC reduction, which was especially pronounced at the lower ketamine concentrations. (Figure 1)Figure 1DISCUSSION: We confirmed the MAC reducing effect of MgSO4, as was previously shown for halothane anesthesia. Ketamine dosedependently reduced the MAC for isoflurane, however, 2 of 4 animals died at the highest dose (100 mg/kg). This is consistent with the LD50 of ketamine in rats. The significant enhancement in the isoflurane MAC reduction by the combination of MgSO4 and ketamine, which was especially pronounced at the lower ketamine concentrations, was devoid of any significant side effects and was hemodynamically well tolerated. The mechanism of this enhanced MAC reduction is under further investigation. Supported by a FAER/Zeneca Anesthesiology Young Investigator Award

Aspirin synergistically potentiates isoflurane minimum alveolar concentration reduction produced by morphine in the rat.

The combination of opioids and nonsteroidal antiinflammatory drugs is more analgesic than the summed effect of each drug administered separately. This synergism has been used to obtain analgesia in the postoperative period at doses at which side effects are minimal. The aim of this study is to evaluate the analgesic interaction between aspirin and morphine in the rat during isoflurane anesthesia. The reduction in minimum alveolar concentration of isoflurane (MAC(ISO)) was used as an objective measure of the analgesic potency of individual drugs and their use in combination. Thirty-seven male Wistar rats were anesthetized with isoflurane in oxygen, and the MAC(ISO) was determined before and after the intravenous administration of aspirin and morphine. Rats were administered morphine alone (1, 3, and 10 mg/kg) or morphine (1 and 3 mg/kg) and aspirin (30 mg/kg). The MAC(ISO) was determined from alveolar gas samples at the time of tail clamp. The duration of MAC(ISO) reduction was recorded. Aspirin did not have an effect on MAC(ISO), (average, 1.35+/-0.1%), whereas the combination of morphine (1 and 3 mg/kg) and aspirin (30 mg/kg) produced a reduction in the dose of morphine needed to produce the same degree of MAC(ISO) reduction. Actual MAC(ISO+drug) data were as follows: 1 mg/kg morphine, 1.17+/-0.14%; 3 mg/kg morphine, 0.98+/-0.15%; 1 mg/kg morphine plus aspirin, 0.90+/-0.04%; 10 mg/kg morphine, 0.63+/-0.13%; and 3 mg/kg morphine plus aspirin, 0.64+/-0.06%. The synergistic effects of aspirin and morphine allow a clinically significant reduction in the requirements of isoflurane and isoflurane plus morphine, and these drug combinations may decrease the side effects associated with the use of single higher, equianalgesic doses of these drugs.

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.

Effect of alfentanil on the minimum alveolar concentration of isoflurane in cats

SUMMARY Objective To evaluate effect of incremental doses of alfentanil on isoflurane minimum alveolar concentration (MAC) in cats to determine whether alfentanil reduces isoflurane MAC and, if so, maximal isoflurane MAC reduction. Animals 6 healthy spayed female cats. Procedure Cats were anesthetized with isoflurane and instrumented to allow collection of arterial blood for measurement of gas tensions, pH, and plasma alfentanil concentration and to measure arterial blood pressure. Isoflurane MAC was determined in triplicate, and alfentanil was administered IV, using a computer-driven syringe pump to achieve estimated plasma alfentanil concentrations of 50, 100, 250, 500, 750, and 1,000 ng/ml; isoflurane MAC was determined at each alfentanil concentration. Cats were allowed to recover, and the process was graded as poor, good, or excellent. Results Alfentanil had a significant dose effect on isoflurane MAC reduction. Significant regression was found for normalized isoflurane MAC versus estimated plasma alfentanil concentration. A quadratic term was necessary to fit the model and, using this curve, MAC reduction (35.0 ± 6.6%) was estimated to be maximal at a plasma alfentanil concentration of 500 ng/ml. Significant differences were evident in rectal temperature, bicarbonate concentration, base deficit, arterial carbon dioxide and oxygen tensions, and arterial pH between isoflurane alone and some plasma alfentanil concentration and the corresponding reduction in isoflurane concentration. Conclusions Infusion of alfentanil resulted in maximal MAC reduction midway between that reported for horses and dogs. At such plasma alfentanil concentration, adverse effects were minimal, but included increase in rectal temperature, metabolic acidosis, and decrease in Pao2. Provided cats were not handled during the recovery period, recovery was smooth and quiet. Clinical Relevance Infusion of alfentanil decreases the need for potent inhalant anesthetics in cats and could potentially be a clinically useful anesthetic regimen in sick cats. (Am J Vet Res 1997;58:1274–1279)