Carbon monoxide production
For this study we developed a method in which a gas chromatograph sampled automatically every five minutes during each experiment, therefore providing the most accurate and reliable CO measurement. To our knowledge this is the first time this kind of setup was used.
In this study the findings of Fang et al[
7] concerning the fact that desflurane produces more CO than enflurane and isoflurane respectively, were confirmed. However, instead of using small vials of 30 ml, we used a patient model, therefore measuring the maximum amounts of CO in completely dry sodalime at a concentration equivalent of approximately 1 MAC of volatile anesthetic using a oxygen/nitrous oxide mixture. Regarding the toxicity of CO, the Henderson and Haggard's Index of Toxic effect[
12] indicates that one hour of exposure of more than 1500 ppm of CO is dangerous to life. However one should also take into consideration that the CO is not continuously produced in this model in contrast with this index and that CO absorption by a patient is not included in this model. Therefore we can only conclude from our findings that in these extreme conditions very high CO concentrations can be reached for desflurane and enflurane and that isoflurane can produce significant concentrations of CO as well. One should take into consideration that the use of Baralyme
® will produce higher levels of CO[
7,
13], and that carbon dioxide absorption, fresh gas flow and minute volume have small effects on CO production as shown by Woehlck et al. [
13]. Because of the relative small effect of carbon dioxide absorption on CO production we didn't add carbon dioxide to our model.
As for the clinical relevancy, one could say that this model uses completely dry sodalime which is not seen very frequently in common anesthetic practice. However, there are reports of severe CO intoxications [
2,
3] recently published by Berry et al. [
14] with desflurane as anesthetic agent. The highest risk develops when fresh gas flow is maintained in a anesthesia system for a few days. After 41 hours with a 7 l/min fresh gas flow, the soda lime will become critically dry as published by Soro et al. [
15]. As there is always a potential risk, one should consider a safety protocol to maintain a proper humidity level inside the carbon dioxide absorbent as proposed by Woehlck et.al [
16], especially when using anesthetic agents like desflurane and enflurane. One could also consider the use of more accurate electrochemical CO monitors [
17,
18] which can detect CO by continuous measuring in the anesthetic circuit. Another possibility is the use of different carbon dioxide absorbents, particularly absorbents with less Ba(OH)
2, KOH and NaOH [
19,
20] that produce relatively safe amounts of CO or have no CO production at all[
21,
22].
During the desflurane experiments the infrared anesthetic vapor analyzer reported a concentration of enflurane up to 1.0 vol%, which correlated significantly with the measured CO concentration (Spearman's r: 0.805; p < 0.001). This reported enflurane concentration is probably attributable to the production of trifluoromethane that is simultaneously produced with CO[
23] and is known to be detected as enflurane by this vapor analyzer[
24]. The enflurane detection disappears below a CO concentration of 3400 ppm, which explains why in the isoflurane experiments no 'enflurane' was detected. In case of a 'mixed gas' warning or a unexpected 'enflurane' detection during anesthesia using desflurane, one should consider the possibility of a (high) CO production.
Contrary to reports in literature[
7], we found significant amounts of CO with halothane and sevoflurane. Also CO production by both substances is not explained by the mechanism postulated by Baxter et al[
23]. Previously, CO production was reported by Strauss et al. [
25] for halothane and Wissing et al[
10] for both sevoflurane and halothane. They reported higher concentrations of CO than found in our study, but at higher concentrations of these two volatile anesthetics and with use of a KOH containing absorber. Our reported amounts of CO are not dangerous for several hours in healthy individuals, but could be clinically relevant for anemic patients or small children[
26,
27].
Temperature measurements
No clinically relevant temperature increase was measured during the experiments with dry sodalime and desflurane, enflurane, isoflurane and halothane. This is not concurrent with findings of other authors [
10,
28]. Our explanation for these differences is the use of higher concentrations of vapor and a higher fresh gas flow used in the experiments of these studies which would give a more exothermic reaction than in our study. We did however measure a forty degrees Celsius temperature increase in the experiments with sevoflurane and dry sodalime. Simultaneously, we noticed a high degree of sevoflurane degradation because of the discrepancy between dial setting of the vaporizer and the measured sevoflurane concentrations in the circle system. This confirms the report of instability of sevoflurane in desiccated sodalime by Funk et.al[
29]. We concluded that temperature measurement in the sodalime container is a very poor predictor of CO production because of the high CO production with desflurane with a small increase of temperature and the other way round for sevoflurane. However a study from Holak et.al. [
27] demonstrated that clinically relevant CO concentrations with the use of Baralyme
® do not occur until the absorbent temperature exceeds 80°C. Because of the use of a combination of sevoflurane and nitrous oxide in this study we cannot rule out that higher concentrations of sevoflurane without nitrous oxide would increase the absorbent temperature above a certain threshold where sodalime could also be capable of production of high concentrations of CO or even result in fire or explosions as recently reported with the use of dessicated Baralyme
® and sevoflurane [
30‐
32]. Further studies using sevoflurane and other absorbents with temperature measurement inside the absorbents [
33] should be performed to determine if these reactions can also occur with other absorbents than Baralyme
®.