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From the Department of Anesthesiology, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan.
Address correspondence to: Dr. Michiaki Yamakage, Department of Anesthesiology, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, Hokkaido, 060-8543, Japan. Phone: 81-11-611-2111 (ext. 3568); Fax: 81-11-631-9683; E-mail: yamakage{at}sapmed.ac.jp
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Abstract |
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Methods: The anesthetic machines tested were ExcelTM 210 SE (Datex-Ohmeda, Louisville, CO), CiceroTM (Dräger, Lübeck, Germany), and AS/3TM ADU (Datex-Ohmeda, Louisville, CO). Anesthesia expected to last more than four hours was maintained with 2.0% sevoflurane and nitrous oxide (0.5 L•min–1) / oxygen (0.5 L•min–1). The concentrations of compound A, obtained from the inspiratory limb of the circle system, were measured using a gas chromatograph.
Results: When ExcelTM and CiceroTM were used, concentrations of compound A increased steadily from the baseline values to 28 and 29 (mean) ppm, respectively, at two hours after exposure to sevoflurane and became constant. There was no significant difference between the concentrations of compound A produced by these anesthetic machines. In contrast, the new anesthetic machine AS/3TM was associated with lower concentrations of compound A (6 ppm at one hour, P <0.05 compared with ExcelTM and CiceroTM), and the concentration did not change significantly thereafter.
Conclusion: In spite of the use of a conventional carbon dioxide (CO2) absorbent with strong bases, the anesthetic machine AS/3TM with a small volume of canister/soda lime (900 ml/700 ml) produced lower concentrations of compound A than those produced by the other machines.
CONVENTIONAL carbon dioxide (CO2) absorbents can degrade sevoflurane to fluomethyl-2,2-difluoro-1-(trifluoromethyl) vinyl ether (compound A).1 Compound A has a dose-dependent nephrotoxic effect in rats,2,3 although clinically significant renal effects of this degradation in humans are still controversial.4–6 Factors that may affect compound A concentration in the anesthetic circuit include the sevoflurane concentration,7–9 CO2 production by the patient,7 ventilation,7 fresh gas flow rate,7,10 temperature of the CO2 absorbent,11 type of CO2 absorbent,8,9 freshness of the CO2 absorbent,9 and water content of the CO2 absorbent.9 Because of environmental pollution and costs of volatile anesthetics, low-flow anesthesia with less than 2 L•min–1 of fresh gas flow has been widely used,12 and various types of anesthetic machines for low-flow anesthesia are now available for clinical use. Although there are some differences between the anesthetic circuit systems and sizes of the canisters in these machines, there have been no prior studies on measurement of concentrations of compound A produced by these machines. We, therefore, compared the concentrations of compound A in inspired gas breathed by patients produced by different types of anesthetic machines under low-flow anesthesia.
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Methods |
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Anesthesia was induced by an iv injection of 2–3 mg•kg–1 propofol, 1–2 µg•kg–1 fentanyl, and muscle paralysis produced by 0.10–0.12 mg•kg–1 vecuronium. Following tracheal intubation, anesthesia was maintained with 2.0% sevoflurane and 50% nitrous oxide (0.5 L•min–1) / 50% oxygen (0.5 L•min–1) along with 1–2 µg•kg–1 fentanyl in incremental doses as required to maintain systolic arterial blood pressure within ± 20% of the baseline value. The inspired sevoflurane concentrations were adjusted as indicated by the calibrated gas monitor (5250 RGMTM, Datex-Ohmeda, Louisville, CO) to 2.0%. Ventilation was controlled with a tidal volume of 10–12 ml•kg–1 with the ventilatory rate adjusted to maintain end-tidal CO2 partial pressure (PETCO2) between 34 and 38 mmHg. The CO2 absorbent used was DrägersorbTM800 (Dräger, Lübeck, Germany), and contained ~ 80% Ca(OH)2, 2.0% NaOH, 3.0% KOH, ~ 14% water, and some other materials [SiO2, Mg(OH)2, and Al(OH)3]. Fresh CO2 absorbent and a new circle system were used for each patient.
The patients were randomly divided into three groups (n=6 in each group) according to the type of anesthetic machine used. The anesthetic machines used in this study were ExcelTM 210 SE with a 7800 ventilator (Datex-Ohmeda, Louisville, CO), CiceroTM (Dräger, Lübeck, Germany), and AS/3TM Anesthesia Delivery Unit (Datex-Ohmeda, Louisville, CO). The former one is a conventional anesthetic machine designed for high-flow anesthesia, and the latter two are new anesthetic machines designed for low-flow anesthesia. The components of the circle system were the standard components used for each system.
Gas samples for measurement of degradation products were obtained from the inspiratory limb of the circle system at 0, one, two, and four hours after exposure to sevoflurane. The concentrations of compound A were measured using a gas chromatograph (model GC-7AG, Shimadzu, Kyoto, Japan) equipped with a gas analyzer (model MGS-5, Shimadzu). The gas chromatograph column was 5 m in length and 3.0 mm in internal diameter, and it was filled with 20% dioctyl phthalate and chromosorb WAW (Technolab, Osaka, Japan) with 80/100 mesh. The injection port temperature was 130°C, and the column temperature was 110°C. The carrier gas was nitrogen, and the carrier gas flow rate was 28 ml•min–1. The gas chromatograph was calibrated with a standard calibration gas prepared from a stock solution of compound A (Maruishi Pharmaceutical, Osaka, Japan).
All data are presented as means ± SD. The concentrations of compound A were compared by repeated measures analysis of variance (ANOVA) followed by Scheffe's post hoc test to evaluate statistical significance between any two groups. A P value less than 0.05 was considered statistically significant.
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). Analysis of the gas samples taken from the inspired circuit when the conventional anesthetic machine ExcelTM was used showed that the mean ± SD concentrations of compound A increased steadily from the baseline values (<2 ppm) to 28.3 ± 4.9 ppm at two hours after exposure to sevoflurane and became constant (Figure). When the new anesthetic machine CiceroTM was used, the concentrations of compound A showed a similar time course to and were not significantly different from those using ExcelTM. In contrast, another new anesthetic machine AS/3TM was associated with lower concentrations of compound A (6.1 ± 1.5 ppm at one hour, P <0.05 compared with ExcelTM and CiceroTM), and the concentrations did not significantly change thereafter.
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Discussion |
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In this study, we found that when the AS/3TM anesthetic machine and the conventional CO2 absorbent DrägersorbTM800 were used, concentrations of compound A were significantly lower than when using the anesthetic machines ExcelTM and CiceroTM. AS/3TM and CiceroTM are two new anesthetic machines that can control the ventilatory volume independent of fresh gas flow, whereas the ventilatory volume of the conventional anesthetic machine ExcelTM partially depends on the fresh gas flow. Therefore, the difference between the concentrations of compound A produced by these anesthetic machines does not seem to be due to the system of the anesthetic circuit per se. Because the volumes of canister/soda lime (0.9 L/0.7 L) of AS/3TM are smaller than those of the other two anesthetic machines, ExcelTM (3.0 L/2.8 L) and CiceroTM (1.5 L/1.45 L), it is conceivable that the difference between the concentrations of compound A is, in part, due to the different volumes of soda lime of these anesthetic machines. First, the small volume of soda lime may contribute to the short duration of contact between sevoflurane and soda lime (strong bases), leading to the lesser degradation of sevoflurane. Another possible explanation is the rapid consumption of strong bases. Unfortunately, we did not measure the temperatures of the canisters in this study. Because the fresh gas flow rates7,10 and the production of CO2 by the anesthetized patients7 in this study were constant, the changes in the temperature of the canister mainly depend on the reaction with NaOH (H2CO3 + 2NaOH 
Na2CO3 + 2H2O + heat) and may, at least in part, explain the observed differences in compound A concentrations.
In summary, our clinical study shows that, in spite of the use of a conventional CO2 absorbent with strong bases, the anesthetic machine AS/3TM with a small volume of canister/soda lime produced lower concentrations of compound A than those produced by the other machines.
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Footnotes |
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Accepted for publication January 15, 2001.
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2 Gonsowski CT, Laster MJ, Eger II EI, Ferrell LD, Kerschmann RL. Toxicity of compound A in rats. Effect of increasing duration of administration. Anesthesiology 1994; 80: 566–73.[Medline]
3 Gonsowski CT, Laster MJ, Eger II EI, Ferrell LD, Kerschmann RL. Toxicity of compound A in rats. Effect of a 3-hour administration. Anesthesiology 1994; 80: 556–65.[Medline]
4 Bito H, Ikeuchi Y, Ikeda K. Effects of low-flow sevoflurane anesthesia on renal function. Comparison with high-flow sevoflurane anesthesia and low-flow isoflurane anesthesia. Anesthesiology 1997; 86: 1231–7.[Medline]
5 Kharasch ED, Frink EJ Jr, Zager R, Bowdle TA, Artru A, Nogami WM. Assessment of low-flow sevoflurane and isoflurane effects on renal function using sensitive markers of tubular toxicity. Anesthesiology 1997; 86: 1238–53.[Medline]
6 Mazze RJ, Jamison RL. Low-flow (1 l/min) sevoflurane. Is it safe? (Editorial). Anesthesiology 1997; 86: 1225–7.[Medline]
7 Fang ZX, Eger II EI . Factors affecting the concentration of compound A resulting from the degradation of sevoflurane by soda lime and Baralyme® in a standard anesthetic circuit. Anesth Analg 1995; 81: 564–8.[Abstract]
8 Bito H, Ikeda K. Long-duration, low-flow sevoflurane anesthesia using two carbon dioxide absorbents. Quantification of degradation products in the circuit. Anesthesiology 1994; 81: 340–5.[Medline]
9 Fang ZX, Kandel L, Laster MJ, Ionescu P, Eger II EI. Factors affecting production of compound A from the interaction of sevoflurane with Baralyme® and soda lime. Anesth Analg 1996; 82: 775–81.[Abstract]
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Bito H, Ikeda K. Effect of total flow rate on the concentration of degradation products generated by reaction between sevoflurane and soda lime. Br J Anaesth 1995; 74: 667–9.
11 Ruzicka JA, Hidalgo JC, Tinker JH, Baxter MT. Inhibition of volatile sevoflurane degradation product formation in an anesthesia circuit by a reduction in soda lime temperature. Anesthesiology 1994; 81: 238–44.[Medline]
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Baxter AD. Low and minimal flow inhalational anaesthesia. Can J Anaesth 1997; 44: 643–53.
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Neumann MA, Laster MJ, Weiskopf RB, et al. The elimination of sodium and potassium hydroxides from desiccated soda lime diminishes degradation of desflurane to carbon monoxide and sevoflurane to compound A but does not compromise carbon dioxide absorption. Anesth Analg 1999; 89: 768–73.
14 Murray JM, Renfrew CW, Bedi A, et al. Amsorb. A new carbon dioxide absorbent for use in anesthetic breathing systems. Anesthesiology 1999; 91: 1342–8.[Medline]
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Yamakage M, Yamada S, Chen X, Iwasaki S, Tsujiguchi N, Namiki A. Carbon dioxide absorbents containing potassium hydroxide produce much larger concentrations of compound A from sevoflurane in clinical practice. Anesth Analg 2000; 91: 220–4.
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Higuchi H, Adachi Y, Arimura S, Kanno M, Satoh T. Compound A concentrations during low-flow sevoflurane anesthesia correlate directly with the concentrations of monovalent bases in carbon dioxide absorbents. Anesth Analg 2000; 91: 434–9.
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