Carbon Monoxide Production from Desflurane, Enflurane, Halothane
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Anesthesiology 2001; 95:1205–12 © 2001 American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins, Inc. Carbon Monoxide Production from Desflurane, Enflurane, Halothane, Isoflurane, and Sevoflurane with Dry Soda Lime Heimo Wissing, M.D., Ph.D.,* Iris Kuhn, M.D., Uwe Warnken, Ph.D.,‡ Rafael Dudziak, M.D., Ph.D.§ Background: Previous studies in which volatile anesthetics propensity of the various volatile anesthetics to form CO were exposed to small amounts of dry soda lime, generally and the potential mechanisms of CO formation have controlled at or close to ambient temperatures, have demon- strated a large carbon monoxide (CO) production from desflu- been investigated in elaborate experimental settings. rane and enflurane, less from isoflurane, and none from halo- However, there are inconsistencies between laboratory Downloaded from http://pubs.asahq.org/anesthesiology/article-pdf/95/5/1205/332601/0000542-200111000-00026.pdf by guest on 25 September 2021 thane and sevoflurane. However, there is a report of increased findings and clinical experience. CO hemoglobin in children who had been induced with sevoflu- There are case reports of increased CO hemoglobin rane that had passed through dry soda lime. Because this clin- concentrations in two anesthetized children, where ical report appears to be inconsistent with existing laboratory work, the authors investigated CO production from volatile sevoflurane had contact with dry soda lime (14-yr-old anesthetics more realistically simulating conditions in clinical girl, weight: 51 kg, CO hemoglobin: 4.4%; 2-yr-old boy, absorbers. CO hemoglobin: 8.4%; both with a circle system with Methods: Each agent, 2.5 or 5% in 2 l/min oxygen, were the fresh gas inlet upstream of the absorber canister).1 passed for 2 h through a Dräger absorber canister (bottom to top) filled with dried soda lime (Drägersorb 800). CO concen- Laboratory investigations, however, have reported ei- 2 3 trations were continuously measured at the absorber outlet. CO ther minimal or no degradation of sevoflurane to form production was calculated. Experiments were performed in CO. Various mechanisms have been postulated to ex- ambient air (19–20°C). The absorbent temperature was not plain CO production from desflurane, enflurane, and controlled. Results: Carbon monoxide production peaked initially and isoflurane, but thus far none is compatible with CO 3 was highest with desflurane (507 ؎ 70, 656 ؎ 59 ml CO), production from halothane and sevoflurane. In most followed by enflurane (460 ؎ 41, 475 ؎ 99 ml CO), isoflurane previous laboratory investigations, volatile anesthetics ml CO), sevoflurane (34 ؎ 1, 104 ؎ 4ml were exposed to only small amounts of soda lime. Only 21 ؎ 227 ,2.8 ؎ 176) ؎ ؎ ؎ CO), and halothane (22 3, 20 1 ml CO) (mean SD at 2.5 slight temperature changes were allowed to occur, as and 5%, respectively). Conclusions: The absorbent temperature increased with all the small absorbent containers were placed in a water anesthetics but was highest for sevoflurane. The reported mag- bath maintained at 60°C or less.2,4,5 With equimolar and nitude of CO formation from desflurane, enflurane, and isoflu- equimac concentrations of the respective agents, CO rane was confirmed. In contrast, a smaller but significant CO production was highest for desflurane and enflurane and formation from sevoflurane was found, which may account for the CO hemoglobin concentrations reported in infants. With all less so for isoflurane. Halothane produced almost no 2,3 agents, CO formation appears to be self-limited. CO. However, with real absorber systems, 2% isoflu- rane and enflurane produced the same amount of CO CARBON monoxide (CO) poisoning is a potential life- (CO peak, 3,500 and 3,800 ppm, respectively, with al- threatening complication that may occur when volatile most the identical time course),6 Halothane produced up anesthetics have contact with anhydrous soda lime or to 450 ppm CO.6 baralyme (Chemetron Medical Divisions, Allied Health In the aforementioned clinical case reports, the inves- Care Products, St. Louis, MO) in an anesthetic circle. The tigators described surprisingly high temperatures of the soda lime— so high that they could not touch the can- ister. Temperatures higher than 300°C were found in This article is featured in “This Month in Anesthesiology.” animal experiments with actual anesthesia machines 7 ᭛ Please see this issue of ANESTHESIOLOGY, page 5A. with sevoflurane and anhydrous baralyme (Chemetron) and more than 120°C in laboratory experiments with actual absorber systems and dry soda lime.8,9 These au- * Associate Professor, § Professor, Director, Clinic of Anesthesiology, In- thors demonstrated that all modern volatile anesthetics, tensive Care and Pain Therapy, ‡ Chemist, Department of Experimental Anesthesiology. particularly sevoflurane, react with dry soda lime in an Received from the Clinic of Anesthesiology, Intensive Care and Pain Therapy, extremely exothermic reaction, a feature that could not University Hospital Frankfurt, Frankfurt am Main, Germany. Submitted for pub- be observed in laboratory studies with small amounts lication May 1, 2000. Accepted for publication June 4, 2001. Supported by 3 Andros, Oberkirch, Germany, and Dräger, Lübeck, Germany. Presented in part at of soda lime and where temperature was tightly the annual meeting of the European Society of Anesthesiologists, Amsterdam, controlled.2 The Netherlands, May 29–June 1, 1999. In view of the questions raised by inconsistencies Address correspondence to Dr. Wissing: University Hospital Frankfurt, KAIS, Theodor-Stern-Kai 7, D-60590 Frankfurt, Germany. Address electronic mail to: among laboratory investigations, and between laboratory [email protected]. Reprints will not be available from the authors. investigations and clinical experience, we reinvestigated Individual article reprints may be purchased through the Journal Web site, www.anesthesiology.org. CO formation from anesthetic agents using a clinical Anesthesiology, V 95, No 5, Nov 2001 1205 1206 WISSING ET AL. absorber system in which temperature change was electrochemical method was used (Dräger PAC III; permitted. range, 0–2,000 ppm; Dräger AG), which is based on the ϩ 3 ϩ ϩ ϩ Ϫ following reaction: CO H2O CO2 2H 2e ; ϩ ϩ ϩ Ϫ 3 14 1/2O2 2H 2e H2O). Higher concentrations Materials and Methods were validated by a chemical method using appropriate Dräger tubes based on the following reaction: 5 CO ϩ 3 ϩ 15 The inhalational anesthetics and the soda lime (Dräger- I2O5 I2 5CO2). All methods used are standard for sorb 800, composition: 2.2% KOH, 2.1% NaOH, 80.1% CO measurement. IR absorption is the only continuous 10 Ca(OH)2 ) were obtained from commercial sources. method available covering the required concentration Fresh absorbent was placed in Dräger ISO absorbers range. Each method is based on a different principle. (volume, 1 l; Dräger AG, Lübeck, Germany) and dried in Agreement between the methods along with the use of Downloaded from http://pubs.asahq.org/anesthesiology/article-pdf/95/5/1205/332601/0000542-200111000-00026.pdf by guest on 25 September 2021 a continuous oxygen flow (Ն 12 l/min) for at least 72 h the traps and filters make it highly unlikely that other until weight remained constant. Drying was considered compounds (reactants or products) affected the CO to be complete when there was no further weight loss measurements. (Ͻ 0.05% of wet weight) for 24 h. Weight was measured Helium containing analyzed amounts of 100 ppm Ϯ with a precision balance (MC1 LC 4800 P; range, 5%, 1,000 ppm Ϯ 5%, and 99,200 ppm Ϯ 2% of CO 0–1,600 g; resolution, 0.02 g; Sartorius, Göttingen, Ger- provided by Alltech (Munich, Germany) and nitrogen many). To achieve complete and homogeneous drying, containing analyzed amounts of 100 ppm Ϯ 2% provided the soda lime was mixed in the absorber at the time of by Messer Griesheim (Frankfurt, Germany) were used each weighing. This may simulate a worst-case scenario. for calibration. The dried absorbent was stored in an oxygen flow of Baseline CO production was determined using dry 2 l/min until use, at which time weight was measured soda lime and a flow of 2 l/min oxygen with no volatile again. anesthetic and using fresh (wet) soda lime and a flow of To sample soda lime temperature, thermocouples 2 l/min with 5% anesthetic. The total amount of CO were placed in the center of a Dräger ISO absorber 3 and produced during the 2-h observation period was calcu- 7.5 cm above the bottom of the canister. The canister lated from the gas flow through the canister, and the was filled with a measured amount of dry soda lime that concentrations as measured by IR absorption. All exper- covered the upper thermocouple by 1 cm. Temperature iments were performed in triplicate. at the two sites was recorded in 5-s intervals by a com- Additional experiments were conducted to confirm puterized data acquisition system. the sevoflurane results because the magnitude of the CO The experimental procedure was similar to that previ- production was unexpected and because of the poten- ously described for investigations on sevoflurane de- tial of a large variety of breakdown products,9–12 some struction11–13 and on heat production from the reaction not yet identified. In these experiments we simulta- of volatile anesthetics with dry soda lime.8 Inhalational neously used IR absorption, the electrochemical anesthetics from calibrated vaporizers at a concentration method, and gas chromatography. Gas chromatography of 2.5 or 5% in a carrier gas of 2 l/min oxygen were used a thermal conductivity detector (Perkin Elmer Auto passed through the Dräger ISO absorber filled with dry System, Norwalk, CT; Alltech steel column diameter: 1⁄8 soda lime for 2 h. We chose to use equal concentrations inch, 6-foot length; packed with P/W washed molecular of all anesthetics rather than clinically equivalent con- sive, 13 ϫ 80/100; carrier gas, helium).