Minimum Alveolar Concentration Determination Research Articles

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

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

Evaluation of induction characteristics and hypnotic potency of isoflurane and sevoflurane in healthy dogs

To determine induction characteristics and the minimum alveolar concentration (MAC) at which consciousness returned (MACawake) in dogs anesthetized with isoflurane or sevoflurane. 20 sexually intact male Beagles. In experiment 1, 20 dogs were randomly assigned to have anesthesia induced and maintained with isoflurane or sevoflurane. The MAC at which each dog awoke in response to auditory stimulation (MACawake-noise) was determined by decreasing the end-tidal concentration by 0.1 volume (vol %) every 15 minutes and delivering a standard audible stimulus at each concentration until the dog awoke. In experiment 2, 12 dogs received the same anesthetic agent they were administered in experiment 1. After duplicate MAC determination, the end-tidal concentration was continually decreased by 10% every 15 minutes until the dog awoke from anesthesia (MACawake). Mean induction time was significantly greater for isoflurane-anesthetized dogs (212 seconds), compared with the sevoflurane-anesthetized dogs (154 seconds). Mean+/-SD MACawake-noise was 1.1+/-0.1 vol % for isoflurane and 2.0+/-0.2 vol % for sevoflurane. Mean MAC was 1.3+/-0.2 vol % for isoflurane and 2.1+/-0.6 vol % for sevoflurane, and mean MACawake was 1.0+/-0.1 vol % for isoflurane and 1.3+/-0.3 vol % for sevoflurane. Sevoflurane resulted in a more rapid induction than did isoflurane. The MACawake for dogs was higher than values reported for both agents in humans. Care should be taken to ensure that dogs are at an appropriate anesthetic depth to prevent consciousness, particularly when single-agent inhalant anesthesia is used.

Effects of Carprofen and Meloxicam with or without Butorphanol on the Minimum Alveolar Concentration of Sevoflurane in Dogs

Sparing effects of carprofen and meloxicam with or without butorphanol on the minimum alveolar concentration (MAC) of sevoflurane were determined in 6 dogs. Anesthesia was induced and maintained with sevoflurane in oxygen, and MAC was determined by use of a tail clamp method. The dogs were administered a subcutaneous injection of carprofen (4 mg/kg) or meloxicam (0.2 mg/kg), or no medication (control) one hour prior to induction of anesthesia. Following the initial determination of MAC, butorphanol (0.3 mg/kg) was administered intramuscularly, and MAC was determined again. The sevoflurane MACs for carprofen alone (2.10 +/- 0.26%) and meloxicam alone (2.06 +/- 0.20%) were significantly less than the control (2.39 +/- 0.26%). The sevoflurane MACs for the combination of carprofen with butorphanol (1.78 +/- 0.20%) and meloxicam with butorphanol (1.66 +/- 0.29%) were also significantly less than the control value after the administration of butorphanol (2.12 +/- 0.28%). The sevoflurane sparing effects of the combinations of carprofen with butorphanol and meloxicam with butorphanol were additive.

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 perzinfotel on the minimum alveolar concentration of isoflurane in dogs

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

Determination of minimum alveolar concentration of sevoflurane in juvenile swine

Pigs are important animal models in veterinary and medical research and have been widely used in experiments requiring surgical anesthesia. Sevoflurane is an inhalant anesthetic with unique properties that make it an ideal anesthetic for mask induction and anesthesia maintenance. However, there are relatively few studies reporting the anesthetic requirements for sevoflurane in juvenile swine, an age group that is commonly used in research experiments. Therefore the objective of this study was to determine the Minimum Alveolar Concentration (MAC) for sevoflurane in juvenile swine. Sevoflurane anesthesia was induced in six Yorkshire-cross pigs of approximately 9 weeks-of-age and MAC for sevoflurane was determined. The sevoflurane MAC value was determined to be 3.5 ± 0.1% which is notably higher than values reported in the literature for pigs. This discrepancy in MAC values may represent changes in anesthetic requirements between different age groups of pigs and differences in the type of stimulus used to determine MAC.

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.

The effect of hypovolemia due to hemorrhage on the minimum alveolar concentration of isoflurane in the dog

ObjectiveTo determine the effect of hypovolemia on the minimum alveolar concentration (MAC) of isoflurane in the dog. Study designRandomized, cross-over trial. Animal populationSix healthy intact mixed breed female dogs weighing 18.2–29.0 kg. MethodsDogs 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 °C (98.6–100.4 °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. ResultsThe 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 relevanceThe 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 i.v. fentanyl administration on the minimum alveolar concentration of isoflurane in horses

Fentanyl decreases the minimum alveolar concentration (MAC) of inhaled anaesthetics and has been used clinically to reduce the requirements of other anaesthetic drugs in humans and small animals. We hypothesized that i.v. fentanyl would decrease the MAC of isoflurane in horses in a dose-dependent manner. Following determination of baseline MAC of isoflurane, fentanyl was administered i.v. to target plasma concentrations of 1, 8 and 16 ng ml(-1). Each horse was randomly assigned two of three target concentrations administered in ascending order. Loading and infusion doses for each horse were determined from previously derived individual pharmacokinetic values. Isoflurane MAC determination began 45 min after fentanyl administration at each target fentanyl concentration. Venous blood was collected at fixed intervals during the infusion for measurement of plasma fentanyl concentrations. Mean actual fentanyl plasma concentrations were 0 (baseline), and 0.72 (SD 0.26), 8.43 (3.22), and 13.31 (6.66) ng ml(-1) for the target concentrations of 1, 8 and 16 ng ml(-1), respectively. The corresponding isoflurane MAC values were a baseline of 1.57 (0.23), and 1.51 (0.24), 1.41 (0.23) and 1.37 (0.09)%, respectively. The fentanyl concentrations of 0.72 and 8.43 ng ml(-1) did not significantly alter the MAC of isoflurane, but an 18 (7)% ISO-MAC reduction was observed at the 13.31 ng ml(-1) concentration. These results cautiously encourage further study of fentanyl as an opioid anaesthetic adjunct to inhalant anaesthesia in horses.

Effect of transdermally administered fentanyl on minimum alveolar concentration of isoflurane in normothermic and hypothermic dogs

To determine whether the minimum alveolar concentration (MAC) of isoflurane was altered by transdermal administration of fentanyl in normothermic and hypothermic dogs. Randomized complete block crossover design. 6 mature healthy dogs. Dogs received each of 4 treatments in random order. Following induction of anesthesia, normothermia was maintained in dogs that were treated with a fentanyl patch (F-NORM) or sham patch (C-NORM), or hypothermia was maintained in dogs that were treated with a fentanyl patch (F-HYPO) or sham patch (C-HYPO). The appropriate patch was applied 24 hours prior to induction of anesthesia. Anesthesia was induced with isoflurane in oxygen; the dogs were intubated and mechanically ventilated. Target esophageal temperatures were maintained within 1 degrees C of baseline values (normothermia) or at 34.5 degrees C (94.1 degrees F; hypothermia) for 1 hour prior to starting MAC determinations. Supramaximal stimulation was achieved with an electrical stimulator attached to needle electrodes placed in the buccal mucosa of the lower jaw of the dog. Mean MAC +/- SEM of isoflurane during C-NORM, C-HYPO, F-NORM, and F-HYPO treatments were 1.20 +/- 0.17, 0.89 +/- 0.18, 0.76 +/- 0.10, and 0.81 +/- 0.17, respectively. The mean MAC during C-NORM was significantly higher than values for the other treatments. There was no significant difference in mean MAC among the C-HYPO, F-NORM, and F-HYPO treatments. Data suggest that transdermal administration of fentanyl significantly reduces isoflurane requirements in normothermic dogs. The isoflurane MAC-sparing effects of transdermal fentanyl are not apparent in hypothermic dogs.

Effects of oxymorphone and hydromorphone on the minimum alveolar concentration of isoflurane in dogs

ObjectivesTo quantify the change in the minimum alveolar concentration (MAC) of isoflurane (ISO) associated with oxymorphone (OXY) or hydromorphone (HYDRO) in dogs. DesignRandomized crossover study with at least 1 week between assessments. AnimalsSix young, healthy, mixed-breed dogs (1–3 years old), weighing 24.7 ± 4.70 kg. MethodsFollowing mask induction, anesthesia was maintained with ISO in 100% O2 using mechanical ventilation. The dogs received 0.05 mg kg−1 OXY, 0.1 mg kg−1 HYDRO, or 1 mL saline (control) IV. Following equilibration (15 minutes) at each percentage ISO tested, a supramaximal electrical stimulus was applied to the toe web and the response was assessed. Two separate MAC determinations were carried out during 4.5 hours of anesthesia, with completion of the evaluations at 1.5–2 and 4–4.5 hours after drug administration. A two-factor anova was used to determine whether there was a time or treatment effect on MAC and a Tukey test compared the drug effects at each time. Significance is reported at p < 0.05. ResultsThe mean MAC values (±SD) were 1.2 ± 0.18 and 1.2 ± 0.16% for control, 0.7 ±0.15 and 1.0 ± 0.15% for OXY, and 0.6 ± 0.14 and 0.8 ± 0.17% for HYDRO. The initial MAC with OXY and the MAC determined at both times with HYDRO were significantly different from the control MAC values. ConclusionsBoth OXY and HYDRO significantly reduced the MAC of ISO in dogs at 2 hours. At approximately 4.5 hours, HYDRO had a significant MAC-sparing effect, whereas OXY did not. Clinical relevanceAlthough both OXY and HYDRO resulted in a significant reduction in the MAC of ISO at approximately 2 hours, HYDRO may be preferred for procedures of long duration and rarely needs repeated dosing before 4.5 hours.

Measuring Minimum Alveolar Concentration

Measuring Minimum Alveolar Concentration

The influence of transdermally administered fentanyl on isoflurane requirements in normothermic and hypothermic dogs

Intraoperative reductions in serum fentanyl concentrations during transdermal fentanyl (TDF) administration in dogs with induced moderate hypothermia have been reported. The impact of these reductions on any anesthetic sparing effect has not been evaluated in dogs. The objective of this investigation was to determine whether the minimum alveolar concentration (MAC) of isoflurane is altered in the presence of transdermal fentanyl in normothermic and hypothermic dogs. Six mature, healthy, mixed breed dogs were anesthetized on four separate occasions, and received each of the four following treatments in random order: (i) Sham patch-normothermia (C-NORM), (ii) Sham patch-hypothermia (C-HYPO), (iii) TDF-normothermia (F-NORM), 4. TDF-hypothermia (F-HYPO). Twenty-four hours prior to induction of anesthesia, a sham or a 75 μg hour–1 fentanyl patch was applied. Following induction with isoflurane, the dogs were intubated and mechanically ventilated. Animals in the hypothermia group were cooled to 34.5 °C; normothermia was maintained in the other group. MAC determinations were performed using a current (50 cycles second–1, 6.5 milliseconds duration, 40 volts) applied to needle electrodes placed 4 cm apart in the buccal mucosa of the lower jaw of the dog. The MAC (±SD) for C-NORM, C-HYPO, F-NORM and F-HYPO was 1.196 ± 0.167, 0.855 ± 0.183, 0.763 ± 0.097, and 0.830 ± 0.172, respectively. MAC for C-NORM was significantly higher than the other groups. There was a significant difference between C-NORM and F-NORM. There was no significant difference between C-HYPO, F-NORM, and F-HYPO. TDF in hypothermic dogs appears to provide no greater anesthetic sparing effect than that associated with moderate hypothermia. These findings suggest that reductions in serum fentanyl concentrations seen with moderate hypothermia are the result of a decrease of drug uptake rather than a shift of the active drug to the biophase.

Effects of intravenous lidocaine on the minimum alveolar concentration of isoflurane in cats

Lidocaine has been reported to decrease the minimum alveolar concentration (MAC) of inhalation anesthetics in several species and has been used clinically to reduce the requirements for other anesthetic drugs. This study examined the effects of intravenous lidocaine on isoflurane MAC in cats. Six cats were studied. In experiment 1, the MAC of isoflurane was determined. An intravenous bolus of lidocaine 2 mg kg–1 was then administrated and venous plasma lidocaine concentrations measured to determine pharmacokinetic values. In experiment 2, lidocaine was administered to achieve target plasma concentrations between 1 and 11 μg mL–1 and the MAC of isoflurane was determined in triplicate at each lidocaine plasma concentration, using the tail-clamp method. End-tidal isoflurane concentration was determined using a calibrated infrared analyzer. Systolic blood pressure (Doppler), SpO2 and end-tidal PCO2 (calibrated Raman spectrometer) were measured prior to each MAC determination. Body temperature was maintained between 38.5 and 39.5 °C by supplying external heat as needed. MAC values at the different lidocaine plasma concentrations were analyzed by a repeated measures ANOVA, using the Huynh–Feldt correction. The MAC of isoflurane in these cats was 2.21 ± 0.17. For the target concentrations of 1, 3, 5, 7, 9, and 11 μg mL–1, the actual lidocaine plasma concentrations was 1.06 ± 0.12, 2.83 ±0.39, 4.93 ± 0.64, 6.86 ± 0.97, 8.86 ± 2.10, and 9.84 ± 1.34 μg mL–1, respectively. At these target concentrations, the MAC of isoflurane was 2.14 ± 0.14, 1.88 ± 0.18, 1.66 ± 0.16, 1.47 ±0.13, 1.33 ± 0.23, and 1.06 ± 0.19%, respectively. Lidocaine, at target plasma concentrations of 1, 3, 5, 7, 9, and 11 μg mL–1, linearly decreased isoflurane MAC by –6 to 6, 7 to 28, 19 to 35, 28 to 45, 29 to 53, and 44 to 59%, respectively. Lidocaine significantly dose-dependently and linearly decreases the requirements for isoflurane in cats. No ceiling effect was observed within the range of plasma concentrations studied.

Effect of the neuronal nitric oxide synthase inhibitor 7-nitroindazole on the righting reflex ED50 and minimum alveolar concentration during sevoflurane anaesthesia in rats.

The aim was to determine the effect of acute and chronic administration of 7-nitroindazole, a selective neuronal nitric oxide synthase inhibitor, on the righting reflex ED50 and the minimum alveolar concentration during sevoflurane anaesthesia in rats. 7-Nitroindazole was acutely (0, 50 and 100 mg kg(-1)) and chronically (0 and 150 mg kg(-1) day(-1), 4 days) administered to rats. After the preparation, the minimum alveolar concentration and the righting reflex ED50 were measured. The concentration of cGMP in the brain, cerebellum and spinal cord was also measured. Acute administration reduced the minimum alveolar concentration (50 mg kg(-1), 58.8% (95% CI: 50.3-67.3%) of the baseline value, P < 0.01; 100 mg kg(-1), 55.8 (46.9-64.7), P < 0.01) and the righting reflex ED50 (50 mg kg(-1), 27.2 (17.2-37.2), P < 0.01; 100 mg kg(-1), 14.3 (6.6-22.0), P < 0.01). Chronic administration did not reduce the minimum alveolar concentration; however, it reduced the righting reflex ED50 (65.3 (52.9-77.7), P < 0.01). Overall, the reduction in minimum alveolar concentration in the acute and chronic protocol did not correlate with that of the righting reflex ED50. 7-Nitroindazole (100 mg kg(-1), acute) reduced the cGMP concentration within the cerebellum by 55.4%; however, it did not decrease concentrations in the brain or spinal cord. Different mechanisms are responsible for the observed alterations to the minimum alveolar concentration and the righting reflex ED50 following treatment with 7-nitroindazole. The nitric oxide-cGMP pathway might play a less important role in the determination of minimum alveolar concentration than the righting reflex ED50.

Intrathecal picrotoxin minimally alters electro‐encephalographic responses to noxious stimulation during halothane and isoflurane anesthesia

Isoflurane and halothane act in the spinal cord to blunt ascending transmission of impulses to the brain resulting from noxious stimulation. Because intrathecal picrotoxin (an antagonist at the gamma-aminobutyric acid-A receptor) partially reverses the immobilizing effect of isoflurane and halothane, we hypothesized that the electroencephalographic response to noxious stimulation would likewise be partially reversed by intrathecal picrotoxin. Rats were anesthetized with isoflurane (n = 8) or halothane (n = 8) and a laminectomy performed. Following determination of minimum alveolar concentration (MAC), the electroencephalogram (EEG) was recorded during separate applications of a hindpaw clamp, tail clamp and electrical current to the tail at 0.8 and 1.2 MAC. Picrotoxin was then applied to the exposed spinal cord and the EEG response to noxious stimulation again determined. The EEG was more active during halothane anesthesia than isoflurane (spectral edge frequency for 95% power: 25.6 +/- 2.1 Hz vs. 23.1 +/- 1.6 Hz, P < 0.05). Noxious stimulation usually caused the EEG to shift to higher frequencies (e.g. for 0.8 MAC halothane, median edge frequency for 50% power: from 7.6 +/- 3.1 Hz to 10.7 +/- 2.6 Hz, P < 0.05). Picrotoxin minimally affected this response. Noxious stimulation evokes an EEG response that is minimally altered by intrathecal picrotoxin. This suggests that isoflurane and halothane do not have GABAergic actions in the spinal cord that indirectly suppress the EEG response.

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

ObjectiveTo determine the influence of a low-dose constant rate infusion (LCRI; 50 μg kg−1 minute−1) and high-dose CRI (HCRI; 200 μg kg−1 minute−1) lidocaine infusion on the minimum alveolar concentration (MAC) of isoflurane (I) in dogs. Study designProspective experimental study. AnimalsTen mongrel dogs (four females, six males), weighing 20–26.3 kg. MethodsDogs 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. ResultsMinimum 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 relevanceLidocaine infusions reduced the MAC of I in a dose-dependent manner and did not induce clinically significant changes on heart rate or blood pressure.

Cardiopulmonary bypass reduces the minimum alveolar concentration for isoflurane

Objective: The purpose of this investigation was to determine the influence of cardiopulmonary bypass (CPB) on the minimum alveolar concentration (MAC) of isoflurane in a rat model of CPB. Design: Prospective. Setting: University research laboratory. Participants: Sprague-Dawley rats. Interventions: Using tail-clamp methodology, the pre- and post-CPB MAC for isoflurane was studied. Methods and main results: Rats were anesthetized with isoflurane, intubated, ventilated, and surgically prepared for CPB, after which they were randomized to either Sham-operated or CPB groups. The CPB group (n = 10) underwent 90 minutes of normothermic nonpulsatile CPB. The Sham group (n = 13) were cannulated but did not undergo CPB. Pre- and post-CPB MAC determinations were compared within groups using a paired Student t test. The CPB group had a pre-CPB baseline isoflurane MAC of 1.09% ± 0.11% versus 1.09% ± 0.08% in the Sham group ( p = 0.90). Twenty minutes after CPB, the CPB group exhibited a decrease in MAC to 0.98% ± 0.14% ( p = 0.0026, compared with baseline). The MAC in the Sham group was unchanged ( p = 0.5852, compared with baseline). Two hours after CPB, the MAC in the CPB group remained lower compared with baseline at 0.99% ± 0.14% ( p = 0.0032). Conclusions: CPB resulted in a small (10%) but significant reduction in the MAC for isoflurane. The mechanism behind this reduction in MAC is not clear but may be related to CPB-induced cerebral injury.

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

ObjectiveTo determine the effect of two doses of fentanyl, administered transdermally, on the minimum alveolar concentration (MAC) of isoflurane in cats. Study designProspective, randomized study. AnimalsFive healthy, spayed, female cats. MethodsEach 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 μg 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 μg 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. ResultsThe baseline isoflurane MAC was 1.51 ± 0.21% (mean ± SD). Fentanyl (25 and 50 μg 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 μg hour−1 and naloxone (1.44 ± 0.16%) and fentanyl 50 μg hour−1 and naloxone (1.51 ± 0.19%) was not significantly different from baseline MAC (1.51 ± 0.21%). Conclusions and clinical relevanceFentanyl 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.