1Department of Anaesthesia, Ghent University, De Pintelaan 185, Gent, Belgium. 2Laboratory of Toxicology, Ghent University, Harelbekestraat 72, B-9000 Gent, Belgium. 3Laboratory of Medical Biochemistry and Clinical Analysis, Ghent University, Harelbekestraat 72, B-9000 Gent, Belgium*Corresponding author
Accepted for publication: October 23, 2000
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Abstract |
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Br J Anaesth 2001; 86: 3458
Keywords: carbon dioxide, absorption, soda lime; model, lung
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Introduction |
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Experimental set-up |
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The Y-piece of a circle system was connected to the artificial lung. A modified PhysioFlex (Dräger, LĪbeck, Germany) closed-circuit anaesthetic machine was used (Figure 1). The built-in fan (for circulating the breathing gases) was switched off and two classical unidirectional valves were placed in the breathing circuit. A respiratory frequency of 10 bpm and a tidal volume of 490 ml were used to obtain a PE'CO2 of 5.4 kPa. In this system the consumed oxygen or volume loss is replaced by an equal (vol/vol) inflow of oxygen, and displayed on the screen of the machine as oxygen consumption. The apparatus was cleaned carefully before each use to eliminate any contamination from a previous study and checked for complete air-tightness. At the start of the study the lowest possible setting of 0.2% sevoflurane had to be set to close the active charcoal canister, which would otherwise have absorbed compound A. After initial equilibration, liquid sevoflurane was given using a syringe pump (Graseby 3500; Watford, UK), injected in a small copper reservoir fitted to the breathing circuit. The aim was an end-tidal sevoflurane concentration of 2.1 vol%.
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Eight runs with fresh Sofnolime and six runs with standard Sodasorb soda lime (Grace, Epernon, France) were carried out in random order. Fresh commercially available soda limes, stored under normal conditions, were used for each run. According to the available information, the Sofnolime contained 3% NaOH, >75% Ca(OH)2 and 1219% H2O and the Sodasorb contained 2.68% NaOH, 3% KOH, 89% Ca(OH)2 and 1219% H2O. Gas samples of 2 ml were taken in airtight syringes for the determination of compound A. The syringes were connected to the breathing circuit by three-way valves and Luer-lock connections, one situated in the inspiratory limb (for compound Ainsp) and one in the expiratory limb (for compound Aexp). The gas samples were immediately transferred to sealed glass head-space vials.
Compound A was assayed by capillary gas chromatography combined with mass-spectrometric detection (HP 6890-5973 MSD). Injection was fully automated by a technique based on head-space sampling (1 ml). In order to place enough analyte mass on to the capillary columm, cryofocusing on Tenax sorbent (liquid nitrogen, 80°C) placed in the injector liner was used. A thick-film capillary column (CP-select 624, a 6% cyanopropylphenyl-dimethylsilicone stationary phase) allowed adequate retention and excellent isothermal separation (38°C). Helium was used as carrier gas at a flow rate of 1 ml min1. The mass-spectrometer detector was operated in the full-scan mode. The mass spectrum (electron ionization mode) of compound A is characterized by prominent peaks at m/z 69, 128, 161 and 180, the last representing the molecular ion (M+). The ion at m/z 128 was selected as the target ion for quantitative purposes. Before each analysis, a standard curve of eight points was prepared and injected. Standards of compound A in the gas phase were prepared, using liquid volumetric dilutions of stock solutions of compound A and sevoflurane in ethyl acetate. 1-Iodo-2,2,2-trifluoroethane was chosen as an internal standard. Good linearity over a range of 0.575 ppm (v/v) was obtained (average correlation coefficient 0.996 (N=10)). Within-day (N=6) and total (N=10) reproducibility were tested at three different concentrations (0.5, 10 and 75 ppm). The coefficients of variation ranged from 4.1 to 10.0%. The limit of detection (LOD), using a signal-to-noise ratio of 3, was 0.1 ppm, whilst the limit of quantification (LOQ) was 0.3 ppm, using a signal-to-noise criterion of 10 and still assayed with adequate reproducibility (CV%<15%).
At the end of the preparation of the apparatus, and 5, 15, 30, 60, 90, 120, 150, 180, 210 and 240 min after the start of sevoflurane administration, we recorded PE'CO2, sevoflurane E', Tin, Tout, compound Ainsp and compound Aexp. The data were analysed using repeated measures Anova and/or MannWitney U-tests. A P value of <0.05 was considered statistically significant.
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Results |
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Discussion |
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In the present study the inspired and expired concentrations of compound A increased sooner with the KOH-free Sofnolime than with the classical Sodasorb; the difference was always significant. However, the curves of these concentrations were similar with time. The peak was seen at 60 min, with a mean compound A difference of 14 ppm between the two carbon dioxide absorbents; the one for Sofnolime was greater. Compound A values decreased slowly up to 240 min, as has also been reported in clinical studies.5 In the early preparation of the circuit, when a very low sevoflurane concentration of 0.2% E' had to be set, to close the activated charcoal canister, a much greater inspired concentration of compound A was found with Sofnolime than with Sodasorb (mean 4.5 and 0.6 ppm, respectively; P<0.05), suggesting that compound A is generated very rapidly with Sofnolime. The canister temperature Tin was initially greater than Tout, but from 30 min onwards Tout was greater than Tin and attained 40°C with both soda limes. No temperature difference was found at any time between either soda lime, showing that the higher compound A concentrations with Sofnolime could not have been generated by a greater canister temperature. This might have been assumed, knowing that a positive correlation has been found between soda lime temperature and compound A generation,6 7 but other, as yet unknown factors must also be involved in the production of compound A. In experimental conditions with dry soda lime, less compound A was generated with Sofnolime than with normal soda lime.8
Our results contrast with those reported in recent clinical low-flow studies.9 10 Higuchi and coworkers10 found that less compound A was generated with KOH-free soda limes Drägersorb 800 Plus and Medisorb, which contain only 0.003% KOH, than with classical Drägersorb 800. The Sofnolime used in our study contained 3% NaOH, whereas Medisorb contained only 1% NaOH and Drägersorb 800 Plus 2% NaOH. The Sodasorb used in our study contained 2.68% NaOH, more than the 2% present in Drägersorb 800. These facts may explain the differences in their results and suggest the importance of the KOH and/or NaOH concentration in the carbon dioxide absorbent. The same considerations apply to the results of Yamakage and colleagues,9 who compared Medisorb with the classical soda lime Wakolime, which contains 2.6% KOH and 1.3% NaOH. These authors report that Drägersorb 800 Plus has a KOH concentration of 3.0%, whereas Higuchi and colleagues10 quote a concentration of 0.003%, making scientific comparison difficult.
We could not support the hypothesis that simply eliminating KOH from soda lime would reduce the formation of compound A. Indeed, we found even higher concentrations than with classical soda lime Sodasorb. Factors other than KOH, such as the concentration of NaOH, are even more important in the generation of compound A. Although our study is entirely experimental, it does simulate carbon dioxide production and oxygen consumption. Our results need to be confirmed in future clinical studies.
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References |
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