Sevoflurane MAC and hemodynamics in pigs Otsuki DA et al. CLINICS 2010;65(5):531-7 Table 4 - MAC (means±SD) results and methods employed in previous studies of pigs on sevoflurane. Weight (Kg) 2.1±0.4 23±2 30.8±2.6 58.7±1.8 19±4 20.1±0.7 Anesthesia protocol mask induction after ketamine and propofol 3 h after azaperone, 45 min after propofol mask induction mask induction 90 min after propofol Nociceptive stimulation hoof coronary ligament clamping dewclaw clamping dewclaw clamping tail clamping dewclaw clamping dewclaw clamping Temperature (°C) 37.5-38.5 38.6±0.6 38.1 39.7±0.1 38.1 38.0±0.2 MAC (%) 2.12±0.39 2.4 2.53±0.47 2.66±0.6 3.5±0.17 4.4±0.1 Reference Lerman et al.8 Allaouchiche et al. 9 Hecker et al. 10 Manohar and Parks11 Moeser et al. 12 Holmström and Åkeson 13 NS=not stated. Age (weeks) newborn 12-14 NS 22-25 9 NS levels of carbon dioxide, which may influence cardiovascular function. The decreases in the oxygenation parameters, verified with the increases in MAC, may be associated with cardiovascular depression. The changes were more pronounced when MAC was raised to 1.5, contributing to a significant decrease in SvO2 and PvO2, while the oxygen extraction rate increased. Lactate remained unchanged with 1.0 MAC and increased slightly with 1.5. No lung histopathological changes were associated with the two compositions of sevoflurane tested. The literature describes how sevoflurane may be degraded by metallic substances resulting in fluoridric acid, which may cause damage to the respiratory tract mucous membrane when inhaled, and many other fluoride-degrading products. To inhibit acid formation, substances such as water and, more recently, propylene glycol have been added to sevoflurane. A test conducted with a sevoflurane sample with 260 ppm of propylene glycol, heated to a temperature above 60°C in the presence of alumina, did not show significant change in the content of individual and total impurities when compared to those of the dry sevoflurane. The fluoride content of this sample was 0.051 µg/mL, which complied REFERENCES 1. Eger EI, 2nd. New inhaled anesthetics. Anesthesiology. 1994;80:906-22. 2. Cristalia, inventor WO/2005/023175. Stable pharmaceutical composition of fluoroether compound for anesthetic use, method for stabilizing a fluoroether compound, use of stabilizer agent for precludind the degradation of a fluoroether compound. 2005 17.03.2005. 3. FDA U. Database of Select Committee on GRAS Substances (SCOGS) Reviews. 1973. 4. Shoemaker W. Invasive and noninvasive physiologic monitoring. In: Shoemaker WA S, Grenvik A, Holbrook PR, Thompson, WL, ed. Textbook of Critical Care. 3rd ed. Philadelphia: WB Saunders Company. 1995:252-66. 536 with specifications set by the USP Pharmacopoeia Forum, which determines a maximum fluoride limit of 2 µg/mL.2 The exact mechanism through which propylene glycol stabilizes sevoflurane is not entirely clear, but it is possible to infer that propylene glycol and the Lewis acid form a compound that is highly efficient for blocking the action of metallic impurities on sevoflurane. With regard to the possible toxicological effects of propylene glycol, hyperosmolality lactic acidosis, a central nervous system dysfunction, and cardiovascular disturbances were observed in patients receiving etomidate in a 35% propylene glycol vehicle.21, 22 In the present investigation, the sevoflurane contained 0.026% of propylene glycol, which is far less than the amount contained in etomidate formulation. Moreover, after a study conducted by Bau et al. in which propylene glycol was a constituent of an aerosol formulation, the authors concluded that, under normal conditions of exposure, propylene glycol via inhalation is of limited toxicological relevance.23 In conclusion, propylene glycol as a sevoflurane additive can be used as safely as water as an additive, at least in terms of hemodynamic and pulmonary effects. 5. Guyton AJ, CE, Coleman, TG. Normal cardiac output and its variation. In: Guyton AJ, CE; Coleman TG, ed. Cardiac output and its regulation. 2nd ed. Philadelphia: WB Saunders Company. 1973:3-29. 6. Eger EI, 2nd, Johnson BH, Weiskopf RB, Holmes MA, Yasuda N, Targ A, et al. Minimum alveolar concentration of I-653 and isoflurane in pigs: definition of a supramaximal stimulus. Anesthesia and analgesia. 1988;67:1174-6. 7. Quasha AL, Eger EI, 2nd, Tinker JH. Determination and applications of MAC. Anesthesiology. 1980;53:315-34. Copyright © 2010 CLINICS