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TECHNOLOGY, COMPUTING, AND SIMULATION

Fires from the Interaction of Anesthetics with Desiccated Absorbent

Department of Anesthesia and Perioperative Care, University of California, San Francisco, California

Address correspondence and reprint requests to Dr. Edmond I Eger II, Department of Anesthesia, S-455, University of California, San Francisco, CA 94143–0464. Address e-mail to egere{at}anesthesia.ucsf.edu

	Abstract

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Rarely, fire and patient injury have resulted from the degradation of sevoflurane by desiccated carbon dioxide absorbent. Desiccated absorbent also can degrade desflurane and isoflurane, and in the present investigation we sought to determine whether a danger of fire also arose with their use in the presence of desiccated absorbent. Baralyme® was desiccated by heating and directing a 10 L/min flow of oxygen through the absorbent. Approximately 1200 g of this desiccated absorbent was used to fill a standard absorber placed in a standard anesthetic circuit to which we directed a 6 L/min flow of oxygen containing 1.5 or 3.0 MAC desflurane, isoflurane, or sevoflurane. A 3-L reservoir bag served as a surrogate lung, and we ventilated this lung with a minute ventilation of 10 L/min. With desflurane or isoflurane, at both 1.5 MAC and 3.0 MAC, temperatures increased in 30 to 70 min to a peak of approximately 100°C and then decreased. With 1.5 MAC sevoflurane (3.0 MAC was not studied), temperatures increased to over 200°C, and in 2 of 5 studies, flames appeared in the anesthetic circuit. In a separate study, we found that concurrent delivery of carbon dioxide and desflurane did not increase peak temperatures. We conclude that the interaction of desflurane or isoflurane with desiccated absorbent is not likely to produce the conflagrations possible with sevoflurane.

IMPLICATIONS: Fire may result from the interaction of sevoflurane, but not desflurane or isoflurane, with desiccated carbon dioxide absorbent, particularly Baralyme®.

	Introduction

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The interaction of desiccated absorbents with sevoflurane can produce absorbent temperatures of several hundred degrees centigrade (1,2). At the extreme, the increase in temperature may produce fires in an anesthetic circuit, and the resulting products may be sufficient to cause patient injury (2). The latest package label (August 2003) for sevoflurane warns of this concern. In addition, a communication to anesthesia practitioners (www.fda.gov/medwatch/SAFETY/2003/ultane_deardoc.pdf) from Abbott Laboratories details several issues surrounding the concern. As indicated by the several-year delay between the introduction of sevoflurane and the reports of fires in clinical practice, fires from the interaction of sevoflurane with desiccated absorbents are extraordinarily rare, comprising perhaps one case in tens of millions of sevoflurane anesthetics.

Although the potential of desiccated absorbents to degrade sevoflurane and increase absorbent temperature has been assessed, it is not known whether similar increases in temperatures and associated fires might be obtained with other potent inhaled anesthetics, particularly desflurane and isoflurane. Both of these anesthetics resist degradation more than sevoflurane (3), and thus we would predict that temperature would increase less with them than with sevoflurane and that fires in the anesthetic circuit would be unlikely, or would not occur. The present investigation examines this prediction.

	Methods

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Anesthetics were obtained from commercial sources: desflurane and isoflurane from Baxter Healthcare Corp. (New Providence, NJ), and sevoflurane from Abbott Laboratories (Abbott Park, IL). The carbon dioxide absorbent, Baralyme®, was obtained from Chemtron, Allied Health Care (St. Louis, MO).

Approximately 3.5 kg of Baralyme® was placed in a 4-L flask capped with a rubber stopper. A plastic tube was directed through the stopper to the bottom of the flask. A second tube through the stopper ended at the top of the flask and allowed the exit of gases from the flask. A 10 L/min flow of oxygen was directed through the flask (i.e., through the Baralyme®). The exit tube was connected to wall vacuum (approximately one third of an atmosphere). To further aid in drying, the flask was warmed with heating pads.

The flask plus stopper and tubes were weighed before and after introduction of the Baralyme®, and at intervals after initiating the 10 L/min flow of oxygen through the absorbent. Flow was continued until the weight of the flask containing the Baralyme® no longer changed (approximately 2–3 days). Once drying was complete, the stopper with tubes was replaced by a stopper without tubes, and the prepared absorbent was stored in the flask until used for study. The prepared absorbent was only used once (for one study).

The lower of two absorbent canisters in a standard anesthetic circuit (Ohio Medical Products, Madison, WI) was modified to allow the introduction of four temperature probes (Omega Engineering, Inc., Stamford, CT). A layer approximately 1 cm deep of desiccated Baralyme® was placed at the bottom of the canister, and the tip of one of the temperature probes was placed in the center of this layer ("bottom temperature"). Baralyme® was added until the canister was half full. The tip of a second temperature probe was placed at the center of this layer ("middle temperature"), and the tip of a third probe was placed at the edge of this layer (i.e., near the wall of the canister; "side temperature"). Baralyme® was added to complete the filling of the lower canister, and the fourth temperature probe was placed in the center of this layer approximately 1 cm from the surface ("top temperature").

The second, upper, canister was left empty. The lower and upper canisters then were arrayed as normally done, and the system was closed. The circuit then was assembled as it would be for anesthetic delivery. A 3-L reservoir bag was used to substitute for the patient’s lungs. The system was connected to the ventilator (rather than the reservoir bag.) Ports in the delivery hose and at the Y-piece allowed measurement of delivered and end-tidal anesthetic concentrations.

All experiments were repeated at least 4 times and usually 5 or 6 times. The study anesthetics (desflurane, isoflurane, sevoflurane) were delivered at 6 L/min in 100% oxygen at 1.5 MAC or 3 MAC (desflurane and isoflurane, only; MAC is the minimum alveolar concentration of anesthetic required to eliminate movement in 50% of subjects in response to noxious stimulation). We assumed the following MAC values: desflurane 6.0% (4,5), isoflurane 1.2% (5,6), and sevoflurane 1.9% (5). As in the study by Holak et al. (2), the ventilator was set to deliver a tidal volume of approximately 660 mL with a rate of 15 breaths per minute so as to produce a 10 L/min minute ventilation. At time zero, the vaporizer was set to deliver the predetermined target concentration of anesthetic in end-tidal gas. Temperatures were usually recorded at 5-min intervals for the next 2 h. Gas was drawn from the sampling ports through an infrared analyzer (5250 RGM, Ohmeda, Louisville, CO), and the concentrations recorded concurrently with the temperature recordings.

To mimic the effect of patient metabolism and the production of carbon dioxide, in a separate experiment with desflurane at 1.5 MAC, we added an inflow of 200 mL/min carbon dioxide to the tail of the bag that substituted for the patient’s lungs. The experiment otherwise was conducted as described above.

Peak and average temperatures achieved during the 2 h of anesthetic delivery were compared by a one-way analysis of variance and a Student-Newman-Keuls test. We compared the percentage of anesthetic degraded as defined by 100 times the difference between the delivered and end-tidal anesthetic concentration divided by the delivered concentration.

	Results

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With desflurane and isoflurane, temperatures increased at all 4 measurement sites, reaching approximately 100°C at the bottom (Fig. 1; Table 1) and middle (Fig. 2; Table 2) probes, and, on average, over 200°C with sevoflurane. Lower temperatures were attained at the remaining two sites (data not shown). Peak temperatures were reached earlier (at approximately 30 min) with desflurane. Approximately twice that time was required with isoflurane, and the time to the highest measured temperatures was approximately twice as long for sevoflurane as for isoflurane. The addition of 200 mL/min of carbon dioxide did not materially affect these times or peak temperatures, but did appear to delay the decay in temperature after the peak temperature had been reached (Fig. 3). Similarly, delivery of 3.0 MAC desflurane or isoflurane rather than 1.5 MAC had little effect on times to peak temperatures or the peak temperatures attained (Fig. 4; Tables 1 and 2), except that the time to peak temperature at the bottom of the absorber was shorter at the larger isoflurane MAC.

View larger version (31K): [in this window] [in a new window]   Figure 1. Temperatures recorded from the bottom of the desiccated absorbent peaked at approximately 100°C with 1.5 MAC desflurane and isoflurane, progressively decreasing thereafter. Temperatures in the sevoflurane experiments increased progressively to over 200°C, and varying increasingly as the sevoflurane experiments progressed (note large standard deviations for the final 3 points plotted). In 2 of the 5 experiments, flames appeared in the anesthetic circuit.

View larger version (31K): [in this window] [in a new window]   Figure 2. Temperature recorded from the middle of the desiccated absorbent peaked at approximately 100°C with 1.5 MAC desflurane and isoflurane, progressively decreasing thereafter. Temperatures in the 5 sevoflurane experiments increased progressively to over 200°C, varying increasingly as the sevoflurane experiments progressed (see standard deviations).

View larger version (27K): [in this window] [in a new window]   Figure 3. The addition of 200 mL/min of carbon dioxide to the "patient lung" did not increase the peak temperatures reached in the middle of the absorbent in the experiments with 1.5 MAC desflurane but did slow the decay of the temperature after the peak had been achieved. Temperatures at the bottom of the absorbent produced similar findings (data not shown).

View larger version (34K): [in this window] [in a new window]   Figure 4. Increasing the delivered desflurane or isoflurane concentrations from 1.5 MAC to 3.0 MAC slightly accelerated the rate of increase of the temperatures at the middle of the absorbent and increased the peak temperatures reached, but the changes were small and, except for the shorter time to peak temperatures with desflurane, were not statistically significant.

The percentage of delivered sevoflurane that was degraded exceeded the overall percentage of isoflurane degraded, although peak percentages degraded did not differ (Fig. 5). Only a small percentage of desflurane degraded.

View larger version (33K): [in this window] [in a new window]   Figure 5. The percent anesthetic degradation during delivery of 1.5 MAC anesthetic equaled 100 times the difference between inflow and end-tidal anesthetic concentrations divided by the inflow concentration. Degradation of sevoflurane greatly exceeded that with desflurane, while degradation of isoflurane lay between that for sevoflurane and desflurane. Note that the anesthetic concentrations in the inflow and end-tidal gases differed considerably (end-tidal desflurane, 9%; isoflurane, 1.8%; and sevoflurane, 2.8%), and thus this graph does not immediately reflect the absolute amounts of anesthetic degraded. For example, the absolute degradation of sevoflurane exceeded that for isoflurane at all points in time, and the relative degradation can be estimated by multiplying each point for sevoflurane in Figure 5 x 2.8/1.8 and comparing the resulting curve with the present curve for isoflurane.

	Discussion

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The results for desflurane and isoflurane differ from those for sevoflurane at 1.5 MAC (Figs. 1 and 2; Tables 1 and 2). Although the action of desiccated absorbent on desflurane and isoflurane increased absorbent temperature, the increases were limited, reaching peak values of approximately 100°C. Further passage of time saw these temperatures decrease, and no fires were observed. The addition of carbon dioxide to 1.5 MAC desflurane did not increase the peak temperatures reached (Fig. 3), but decreased the rate of descent of temperature after the peak temperature had been reached. Doubling the delivered concentration to 3.0 MAC modestly shortened the time to reach peak temperatures with isoflurane but did not increase the peak temperatures reached with desflurane or isoflurane, although a trend to higher temperatures was seen (Fig. 4).

Our results indicate that, although fire can result from the interaction of sevoflurane with desiccated absorbents, fire is far less likely to occur with desflurane or isoflurane. However, it is not possible to prove the absence of something that does not exist (7), and thus we cannot be certain that this indication is correct. One could argue that we should have done the studies with desflurane and isoflurane 50 times rather than 5 times before reaching such a conclusion. This might be true if fires were the sole criteria for the conclusion. We argue that the findings regarding temperature and degradation provide quantitative (as opposed to the either/or end-point of fires) support for the determination that fires will not occur with desflurane or isoflurane; in contrast to the findings with sevoflurane, with desflurane and isoflurane the increases in temperature are much smaller, are not sustained, and are consistent with the lesser amounts of degradation (particularly with desflurane). Furthermore, the imposed conditions are ones most likely to produce degradation and fires; the absorbent chosen contains the greatest percentage of monovalent bases and the absorbent was desiccated. That is, the present experiment provided a stringent test of whether fire might result from the interaction of desflurane or isoflurane in clinical practice.

How may the differences among anesthetics be explained? A major factor is differences in resistance to degradation. Other experiments have shown a particular vulnerability of sevoflurane relative to desflurane or isoflurane, even with moist absorbents (3). Our studies confirm a difference in vulnerability to degradation by desiccated absorbents (Fig. 5). Desflurane underwent the least degradation, isoflurane far more, and sevoflurane the most. Temperature increased most rapidly and peaked earlier with desflurane, in part, probably, because the larger concentrations used drove the degradation reactions to completion earlier with desflurane.

Other investigations suggest that anesthetic degradation by desiccated absorbent results from the action of a minor component of the bases in the absorbent, namely the monovalent bases sodium hydroxide and potassium hydroxide (8–10). This fits the observations that we obtained for desflurane and isoflurane. Thus, we postulate that the interaction with a monovalent base (particularly potassium hydroxide) resulted in the temperature increases seen, and that the peak temperatures were reached with exhaustion of this component of the absorbent. As evidenced by the shorter time to reach the peak temperature, exhaustion of the potassium hydroxide occurred earlier with desflurane than with isoflurane because of the larger concentration of desflurane that was applied (9% desflurane versus 2.8% isoflurane). Furthermore, note the difference in the decay from the peak temperatures for desflurane versus isoflurane (Figs. 1 and 2). The decay is more rapid with desflurane, despite the continued delivery of 9% desflurane. We suggest that the slower decay with isoflurane reflects a continuing, albeit decreasing, degradation of the isoflurane (Figs. 1 and 2), perhaps by the larger fraction of base components (calcium hydroxide and barium hydroxide). In contrast, degradation of desflurane ceases after the initial exhaustion of the potassium hydroxide (Fig. 3).

Similar reasoning may also explain the findings with sevoflurane. We hypothesize that the initial rapid increase in absorbent temperature reflects the interaction of sevoflurane with the potassium hydroxide. Once the potassium hydroxide has been depleted, further degradation of sevoflurane results from the action of the calcium hydroxide and barium hydroxide, an action that (in contrast to the case with isoflurane or desflurane) produces sufficient heat to further increase temperature. The increase in temperature accelerates the reaction of sevoflurane with the calcium and barium hydroxide (i.e., produces positive feedback), in some cases resulting in conflagration. Even if a conflagration does not result, the potentially >300°C temperatures may, as we found, damage the absorbent housing.

We chose to study the effect of desiccated Baralyme® because previous studies suggested that it produces the greatest degradation of anesthetic and has the largest monovalent base content (5.3% potassium hydroxide) (9). Thus, it would provide the severest test of whether, like sevoflurane, the interaction of desflurane or isoflurane with desiccated absorbent might produce excessive heat and fires. We did not study other absorbents such as soda lime or Amsorb® because they have smaller amounts of or no monovalent bases (9), and thus they would provide a less severe test of the potential flammability of desflurane and isoflurane.

Not shown is one of our findings with coadministration of desflurane and carbon dioxide. Although the degradation of desflurane may have ceased because of exhaustion of the potassium hydroxide, carbon dioxide absorption was not affected; the inspired concentration of carbon dioxide equaled zero throughout the experiments. The slower decay of the temperature curve with the coadministration of desflurane and carbon dioxide (Fig. 3) also reflects the continued exothermic absorption of carbon dioxide.

If correct, our reasoning suggests that under some circumstances, greater temperatures than those found in the present experiment might be obtained with isoflurane because of its continuing degradation by calcium and barium hydroxide. Such circumstances might include the delivery of larger concentrations at lower inflow rates (i.e., concentrations sufficient to sustain the end-tidal concentration). Greater temperatures might be reached in such a case because less heat would be carried away by the slower inflow rate. Co-delivery of carbon dioxide to the absorbent also might produce greater temperatures because of the added heat produced by absorption of the carbon dioxide (i.e., the carbon dioxide would be less diluted by the inflow rate).

The need to avoid fire in the anesthetic circuit is obvious. The danger of burns and smoke inhalation is clear. In addition, with increased temperatures, there may be an increase in the production of toxic degradation products such as carbon monoxide (2,11) or nephrotoxins (12). (But note that the last referenced study is in rats and may not apply to humans). We conclude: a) that degradation of sevoflurane by desiccated absorbents may lead to temperatures exceeding 200°C and to fire in the anesthetic circuit; b) that degradation of desflurane or isoflurane may lead to temperatures of approximately 100°C in the anesthetic circuit, but such degradation and temperatures are not likely to lead to fire in the anesthetic circuit; and c) that avoidance of degradation is easily accomplished by ensuring hydration of the absorbent [by replacing desiccated absorbent with fresh absorbent or by pouring water into the desiccated absorbent (13)]. As anesthesia clinicians extend their care outside of the traditional operating room setting into remote hospital and office locations, greater vigilance and care is needed to ensure that the moisture content of absorbents is adequate.

	Acknowledgments

 
Dr. Eger is a paid consultant to Baxter Healthcare Corp. Baxter Healthcare Corp. donated the desflurane and isoflurane used in these studies.

	Footnotes

 
Accepted for publication

	References

Top Abstract Introduction Methods Results Discussion References

 

1. Eger EI, II, Ionescu P, Laster MJ, Weiskopf RB. Baralyme® dehydration increases and soda lime dehydration decreases the concentration of compound A resulting from sevoflurane degradation in a standard anesthetic circuit. Anesth Analg 1997; 85: 892–8.[Abstract]
2. Holak EJ, Mei DA, Dunning MB III, et al. Carbon monoxide production from sevoflurane breakdown: modeling of exposures under clinical conditions. Anesth Analg 2003; 96: 757–64.[Abstract/Free Full Text]
3. Eger EI, II. Stability of I-653 in soda lime. Anesth Analg 1987; 66: 983–5.[Abstract/Free Full Text]
4. Rampil IJ, Lockhart S, Zwass M, et al. Clinical characteristics of desflurane in surgical patients: minimum alveolar concentration. Anesthesiology 1991; 74: 429–33.[Web of Science][Medline]
5. Eger EI, II. Age, minimum alveolar anesthetic concentration, and minimum alveolar anesthetic concentration-awake. Anesth Analg 2001; 93: 947–53.[Abstract/Free Full Text]
6. Stevens WC, Dolan WM, Gibbons RT et al. Minimum alveolar concentrations (MAC) of isoflurane with and without nitrous oxide in patients of various ages. Anesthesiology 1975; 42: 197–200.[Web of Science][Medline]
7. Eger EI, II. Dragons and other scientific hazards. Anesthesiology 1979; 50: 1.[Web of Science][Medline]
8. 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.[Abstract/Free Full Text]
9. Stabernack CR, Brown R, Laster MJ, et al. Absorbents differ enormously in their capacity to produce compound A and carbon monoxide. Anesth Analg 2000; 90: 1428–35.[Abstract/Free Full Text]
10. 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.[Web of Science][Medline]
11. Fang ZX, Eger EI, II, Laster MJ, et al. Carbon monoxide production from degradation of desflurane, enflurane, isoflurane, halothane, and sevoflurane by soda lime and Baralyme®. Anesth Analg 1995; 80: 1187–93.[Abstract]
12. Stabernack CR, Eger EI, II, Warnken UH, et al. Sevoflurane degradation by carbon dioxide absorbents may produce more than one nephrotoxic compound in rats. Can J Anaesth 2003; 50: 249–52.[Medline]
13. Baxter PJ, Kharasch ED. Rehydration of desiccated Baralyme prevents carbon monoxide formation from desflurane in an anesthesia machine. Anesthesiology 1997; 86: 1061–5.[Web of Science][Medline]

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Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999