Baseline Isoflurane Minimum Alveolar Concentration Research Articles

Evaluation of whether acepromazine maleate causes fentanyl to decrease the minimum alveolar concentration of isoflurane in cats.

To determine whether isoflurane-anesthetized cats with demonstrated resistance to the immobilizing effects of fentanyl would exhibit naltrexone-reversible sparing of the minimum alveolar concentration (MAC) of isoflurane when fentanyl was coadministered with the centrally acting catecholamine receptor antagonist acepromazine. 5 healthy male purpose-bred cats. Anesthesia was induced and maintained with isoflurane in oxygen. Baseline isoflurane MAC was measured by use of a standard tail clamp stimulus and bracketing study design. Afterward, fentanyl was administered IV to achieve a plasma concentration of 100 ng/mL by means of target-controlled infusion, and isoflurane MAC was remeasured. Next, acepromazine maleate (0.1 mg/kg) was administered IV, and isoflurane MAC was remeasured. Finally, isoflurane concentration was equilibrated at 70% of the baseline MAC. Movement of cats in response to tail clamping was tested before and after IV bolus administration of naltrexone. Physiologic responses were compared among treatment conditions. Isoflurane MAC did not differ significantly between baseline and fentanyl infusion (mean ± SD, 1.944 ± 0.111% and 1.982 ± 0.126%, respectively). Acepromazine with fentanyl significantly decreased isoflurane MAC to 1.002 ± 0.056% of 1 atm pressure. When isoflurane was increased to 70% of the baseline MAC, no cats moved in response to tail clamping before naltrexone administration, but all cats moved after naltrexone administration. Acepromazine caused fentanyl to decrease the isoflurane MAC in cats that otherwise did not exhibit altered isoflurane requirements with fentanyl alone. Results suggested that opioid-mediated increases in brain catecholamine concentrations in cats counteract the opioid MAC-sparing effect.

The effect of buprenorphine on isoflurane minimum alveolar concentration in dogs

ObjectiveTo determine the effect of intravenous (IV) buprenorphine on the isoflurane (ISO) minimum alveolar concentration (ISOMAC) in dogs. Study designRandomized, crossover, design. AnimalsSix healthy, adult (2–3 years old), intact dogs (two males and four females) weighing 7.4–11.0 kg. MethodsEach dog was studied on three occasions, 1 week apart, and baseline ISOMAC (MACB) was determined on each occasion. ISOMAC was defined as the mean of the end-tidal ISO concentrations that prevented and allowed purposeful movement in response to a noxious stimulus. After MACB determination, dogs were randomly given buprenorphine (BUP) at either 0.01, 0.05 or 0.1 mg kg−1 IV, and ISOMAC was determined at two time periods after BUP administration. The first post-treatment determination (MACT1) was initiated 45 minutes after BUP administration and the second determination (MACT2) was initiated 4 hours after BUP administration. MAC values were determined in duplicate and the mean values were used for statistical analysis. ResultsIsoflurane minimum alveolar concentration was decreased at 141 minutes (the time of MACT1 determination) by 25%, 35%, and 27% after administration of BUP at 0.01, 0.05, and 0.1 mg kg−1, respectively (p ≤ 0.05). The MAC reductions were not statistically different among doses. The reductions in ISOMAC at 342 minutes (the time of MACT2 determination) ranged from 13 to 16%, and were not statistically different among doses. Conclusions and clinical significanceBuprenorphine at 0.01, 0.05, and 0.1 mg kg−1 significantly decreased ISOMAC in dogs at 141 minutes but not at 342 minutes. When using BUP for MAC reduction re-dosing may be required for procedures of long duration, and there may be no advantage to using the 0.1 mg kg−1 dose.

Effects of lidocaine administration via continuous rate infusion on the minimum alveolar concentration of isoflurane in New Zealand White rabbits (Oryctolagus cuniculus)

To evaluate the effect of a continuous rate infusion (CRI) of lidocaine on the minimum alveolar concentration (MAC) of isoflurane in rabbits. Five 12-month-old female New Zealand White rabbits (Oryctolagus cuniculus). Rabbits were anesthetized with isoflurane. Baseline isoflurane MAC was determined by use of the tail clamp technique. A loading dose of lidocaine (2.0 mg/kg, IV) was administered followed by a CRI of lidocaine at 50 μg/kg/min. After 30 minutes, isoflurane MAC was determined. Another loading dose was administered, and the lidocaine CRI then was increased to 100 μg/kg/min. After 30 minutes, isoflurane MAC was determined again. Plasma samples were obtained for lidocaine analysis after each MAC determination. Baseline isoflurane MAC was 2.09%, which was similar to previously reported values in this species. Lidocaine CRI at 50 and 100 μg/kg/min induced significant reductions in MAC. The 50 μg/kg/min CRI resulted in a mean plasma lidocaine concentration of 0.654 μg/mL and reduction of MAC by 10.5%. The 100 μg/kg/min CRI of lidocaine resulted in a mean plasma concentration of 1.578 μg/mL and reduction of MAC by 21.7%. Lidocaine also induced significant decreases in arterial blood pressure and heart rate. All cardiopulmonary variables were within reference ranges for rabbits anesthetized with inhalation anesthetics. No adverse effects were detected; all rabbits had an uncomplicated recovery from anesthesia. Lidocaine administered as a CRI at 50 and 100 μg/kg/min decreased isoflurane MAC in rabbits. The IV administration of lidocaine may be a useful adjunct in anesthesia of rabbits.

Naltrexone does not affect isoflurane minimum alveolar concentration in cats

ObjectiveTo test whether naltrexone, an opioid receptor antagonist, affects the minimum alveolar concentration (MAC) of isoflurane in cats, a species that is relatively resistant to the general anesthetic sparing effects of most opioids. Study designRandomized, crossover, placebo-controlled, blinded experimental design. AnimalsSix healthy adult cats weighing 4.9 ± 0.7 kg. MethodsThe cats were studied twice. In the first study, baseline isoflurane MAC was measured in duplicate. The drug (saline control or 0.6 mg kg−1 naltrexone) was administered IV every 40–60 minutes, and isoflurane MAC was re-measured. In the second study, cats received the second drug treatment using identical methods 2 weeks later. ResultsIsoflurane MAC was 2.03 ± 0.12% and was unchanged from baseline following saline or naltrexone administration. Conclusion and clinical relevanceMinimum alveolar concentration was unaffected by naltrexone. Because MAC in cats is unaffected by at least some mu-opioid agonists and antagonists, spinal neurons that are directly modulated by mu-opioid receptors in this species cannot be the neuroanatomic sites responsible for immobility from inhaled anesthetics.

Effects of intraperitoneal administration of gabapentin on the minimum alveolar concentration of isoflurane in adult male rats

Gabapentin has been used to treat a variety of conditions in both human and veterinary medicine, including seizures, neuropathies and chronic pain. However, little information is known about the effects of gabapentin on the minimum alveolar concentration (MAC) of volatile anaesthetics. In this study, we investigated the effect of intraperitoneal administration of gabapentin on isoflurane MAC in adult male rats and hypothesized that gabapentin would decrease MAC in a dose-dependent manner. Using a standard MAC study protocol, we compared five treatment groups (G) receiving 0 (G(0)), 30 (G(30)), 100 (G(100)), 300 (G(300)) and 1000 (G(1000)) mg/kg gabapentin intraperitoneally and compared post-drug MAC values among groups and with corresponding baseline MAC values determined in each group prior to drug testing. The average baseline isoflurane MAC value was 1.45 ± 0.17%, which did not differ significantly between groups (1.47 ± 0.23% [G(30)], 1.46 ± 0.23% [G(100)], 1.48 ± 0.18% [G(300)] and 1.42 ± 0.2% [G(1000)]). In the G(300) and G(1000) groups, the isoflurane MAC value decreased significantly by 19% and 18%, respectively, from corresponding baseline values (P< 0.05, when compared with G(0)). Linear regression analysis revealed a negative correlation between blood gabapentin concentration and percent change in MAC (R(2) = 0.43; P< 0.05) but not dose. In conclusion, high-dose intraperitoneal gabapentin decreased isoflurane MAC. However, the effect was small and not dose-dependent, and is unlikely to be clinically significant.

GABAA receptor antagonism increases NMDA receptor inhibition by isoflurane at a minimum alveolar concentration

ObjectiveAt the minimum alveolar concentration (MAC), isoflurane potentiates GABAA receptor currents and inhibits NMDA receptor currents, and these actions may be important for producing anesthesia. However, isoflurane modulates GABAA receptors more potently than NMDA receptors. The objective of this study was to test whether isoflurane would function as a more potent NMDA receptor antagonist if its efficacy at GABAA receptors was decreased. Study designProspective experimental study. AnimalsFourteen 10-week-old male Sprague–Dawley rats weighing 269 ± 12 g. MethodsIndwelling lumbar subarachnoid catheters were surgically placed in isoflurane-anesthetized rats. Two days later, the rats were anesthetized with isoflurane, and artificial CSF containing either 0 or 1 mg kg−1 picrotoxin, a GABAA receptor antagonist, was infused intrathecally at 1 μL minute−1. The baseline isoflurane MAC was then determined using a standard tail clamp technique. MK801 (dizocilpine), an NMDA receptor antagonist, was then administered intravenously at 0.5 mg kg−1. Isoflurane MAC was re-measured. ResultsPicrotoxin increased isoflurane MAC by 16% compared to controls. MK801 significantly decreased isoflurane MAC by 0.72% of an atmosphere in controls versus 0.47% of an atmosphere in rats receiving intrathecal picrotoxin. Conclusions and clinical relevanceA smaller MK801 MAC-sparing effect in the picrotoxin group is consistent with greater NMDA antagonism by isoflurane in these animals, since it suggests that fewer NMDA receptors are available upon which MK801 could act to decrease isoflurane MAC. Decreasing isoflurane GABAA potentiation increases isoflurane NMDA antagonism at MAC. Hence, the magnitude of an anesthetic effect on a given channel or receptor at MAC may depend upon effects at other receptors.

Effects of fentanyl on isoflurane minimum alveolar concentration and cardiovascular function in mechanically ventilated goats

The effects of fentanyl on the minimum alveolar concentration (MAC) of isoflurane and cardiovascular function in mechanically ventilated goats were evaluated using six healthy goats (three does and three wethers)....

Effects of midazolam on isoflurane minimum alveolar concentration in goats

The effects of midazolam on the minimum alveolar concentration (MAC) of isoflurane in mechanically ventilated goats were evaluated. Six healthy goats (3 does and 3 wethers) were used in a randomized crossover design. General anaesthesia was induced with isoflurane. Endotracheal intubation was performed after which anaesthesia was maintained with isoflurane. Baseline isoflurane MAC was determined. The goats then received, on separate occasions, one of three midazolam treatments intravenously: bolus dose of 0.1 mg/kg followed by a maintenance dose of 0.1 mg/kg/h (Treatment LMID), bolus dose of 0.3 mg/kg followed by a maintenance dose of 0.3 mg/kg/h (Treatment MMID), bolus dose of 0.9 mg/kg followed by a maintenance dose of 0.9 mg/kg/h (Treatment HMID) intravenously. Isoflurane MAC was then re-determined for each midazolam treatment. The baseline [median (inter-quartile range)] isoflurane MAC in goats was 1.40 (1.38–1.41)%. Baseline isoflurane MAC was statistically significantly reduced ( P < 0.05) following Treatment LMID, Treatment MMID and Treatment HMID by 16.8%, 35.1% and 54.7%, respectively. Quality of recovery from anaesthesia was good following all midazolam treatments. Midazolam, administered by constant rate infusion, significantly reduces isoflurane MAC in goats.

Effects of propofol on isoflurane minimum alveolar concentration and cardiovascular function in mechanically ventilated goats

ObjectiveTo evaluate the effects of propofol, on isoflurane minimum alveolar concentration (MAC) and cardiovascular function in mechanically ventilated goats. Study designProspective, randomized, crossover experimental study. AnimalsSix goats, three does and three wethers. MethodsGeneral anaesthesia was induced with isoflurane in oxygen. Following endotracheal intubation, anaesthesia was maintained with isoflurane in oxygen. Intermittent positive pressure ventilation was applied. Baseline isoflurane MAC was determined, the noxious stimulus used being clamping a claw. The goats then received, on separate occasions, three propofol treatments intravenously: bolus of 0.5 mg kg−1 followed by a constant rate infusion (CRI) of 0.05 mg kg−1 minute−1 (treatment LPROP); bolus of 1.0 mg kg−1 followed by a CRI of 0.1 mg kg−1 minute−1 (treatment MPROP), bolus of 2.0 mg kg−1 followed by a CRI of 0.2 mg kg−1 minute−1 (treatment HPROP). Isoflurane MAC was re-determined following propofol treatments. Plasma propofol concentrations at the time of MAC confirmation were measured. Cardiopulmonary parameters were monitored throughout the anaesthetic period. Quality of recovery was scored. The Friedman test was used to test for differences between isoflurane MACs. Medians of repeatedly measured cardiovascular parameters were tested for differences between and within treatments using repeated anova by ranks (p < 0.05 for statistical significance). ResultsIsoflurane MAC [median (interquartile range)] was 1.37 (1.36–1.37) vol%. Propofol CRI significantly reduced the isoflurane MAC, to 1.15 (1.08–1.15), 0.90 (0.87–0.93) and 0.55 (0.49–0.58) vol% following LPROP, MPROP and HPROP treatment, respectively. Increasing plasma propofol concentrations strongly correlated (Spearman rank correlation) with decrease in MAC (Rho = 0.91). Cardiovascular function was not affected significantly by propofol treatment. Quality of recovery was satisfactory. Conclusions and clinical relevanceIn goats, propofol reduces isoflurane MAC in a dose-dependent manner with minimal cardiovascular effects.

The effects of urethane on the isoflurane minimum alveolar concentration in rats

Urethane is often used as a sole anaesthetic agent for non-recovery studies in laboratory animals. However, the use of urethane is controversial, in part, because the electroencephalogram after urethane administration is similar to the electroencephalogram recorded from unanaesthetized animals. Here, we assessed the minimum alveolar concentration (MAC)-sparing effects of urethane by measuring the effect of two doses of urethane on the MAC of isoflurane in male Sprague Dawley rats. Isoflurane MAC was measured before and after intravenous administration of urethane at 1.0 g/kg (Group G₁, n = 6) and 1.5 g/kg (Group G₁.₅, n = 6), or an equal volume of 0.9% saline (Group Gs, n = 6). Baseline isoflurane MAC was not statistically different between groups (isoflurane concentration: 1.47 ± 0.08%, 1.40 ± 0.19% and 1.42 ± 0.12% for G₁, G₁.₅ and Gs, respectively). Intravenous injection of saline did not alter isoflurane MAC (post-saline MAC: 1.43 ± 0.11%). After urethane administration, isoflurane MAC decreased in a dose-dependent manner (new MAC G₁: 0.19 ± 0.06%; G₁.₅: 0.03 ± 0.01%; P < 0.05). The isoflurane MAC after 1.5 g/kg urethane was not significantly different from room air isoflurane concentrations (0.01 ± 0.01%), demonstrating a 100% MAC reduction at this dose. In conclusion, high-dose urethane (1.5 g/kg intravenously) was suitable as a sole anaesthetic agent to prevent gross purposeful movement during the conditions of the study, whereas low-dose urethane (1.0 g/kg intravenously) was not.

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.

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.

Effect of morphine and flunixin meglumine on isoflurane minimum alveolar concentration in goats

ObjectiveTo determine the effect of morphine and flunixin meglumine on isoflurane (ISO) minimum alveolar concentration (MAC) in goats. Study designProspective, randomized experimental study. AnimalsFive adult, wether goats from 1 to 3 years in age, and weighing 24–65 kg. MethodsAnesthesia was induced using ISO, which was delivered via a mask. Goats were intubated and ventilated to maintain an end-tidal carbon dioxide concentration between 25 and 30 mm Hg (3.3–4 kPa). End-tidal ISO concentration was measured using an infrared analyzer. The baseline ISO MAC that prevented purposeful movement in response to clamping a claw was determined. Following baseline MAC determination, each goat received one of the following four treatments intravenously (IV): morphine (2 mg kg−1), flunixin (1.5 mg kg−1), flunixin (1.5 mg kg−1) plus morphine (2 mg kg−1) or saline, and the MAC was re-determined. Goats were studied at weekly intervals, and each goat received each treatment in a randomized fashion. ResultsThe baseline ISO MAC for the control treatment was 1.43%. Morphine reduced the MAC by 29.7%. Flunixin did not significantly decrease the MAC nor did it potentiate the effect of morphine on MAC. The quality of recovery was good in all cases. ConclusionsMorphine (2 mg kg−1, IV) significantly reduced the ISO MAC in goats and did not adversely affect the quality of recovery. Clinical relevanceThe use of morphine, at the dose studied, in association with ISO anesthesia, will allow a clinically significant reduction in the concentration of ISO required to maintain general anesthesia in goats.