Reactions with absorbents Part 2

Carbon Monoxide production in anaesthesia

Reports concerning CO (Carbon Monoxide) toxicity from the interaction of halogenated ether anaesthetics and C02 (Carbon Dioxide) absorbents have received a great deal of attention. The experimental conditions in which this phenomenon can be induced on a lab bench involve absorbents deliberately dried to a very abnormally low (or absent) water content a highly unusual situation. Questions have been raised as to what all this means.

Clinical decisions are most difficult when there is incomplete scientific knowledge. This is currently the situation the clinician faces in deciding how to react, if at all, to recent reports of the potential threat of anaesthesia-induced carbon monoxide toxicity.

Carbon monoxide 'CO' is toxic in very low concentrations. The severity of toxicity depends both on the duration of exposure and on the concentration inhaled. Other influencing factors include the level of exercise and coexisting medical conditions. From a practical standpoint, exposure to greater than 50 ppm (parts per million) for eight hours should be avoided. Even brief exposure to greater that 200 ppm is considered hazardous. Carbon monoxide reacts with haemoglobin (Oxygen transporting protein in red blood cells) to form deoxyhemoglobin (haemoglobin without oxygen). Textbooks of environmental medicine provide standard tables that predict carboxyhemoglobin (Haemoglobin that has 'CO' bound to it instead of Oxygen) level as a function of carbon monoxide concentration in inspired air and of duration of exposure. For example, exposure to 1,000 ppm for one hour would be expected to produce 30% carboxyhemoglobin.

The toxicity of carbon monoxide is by no means limited to direct replacement of oxygen on haemoglobin. Even a small concentration of carboxyhemoglobin causes the oxygen-haemoglobin dissociation curve to shift sharply to the left, thereby preventing the normal unloading of oxygen in the capillary bed. Thus, the patient can suffer tissue hypoxia (lack of oxygen) while the blood partial pressure of oxygen is high. Moreover, carbon monoxide also poisons the cytochrome enzyme system, further depressing the utilization of oxygen.

It is difficult to know exactly at what carboxyhemoglobin levels mortality occurs because most victims receive therapeutic oxygen between the time of exposure and arrival at a health care facility where the carboxyhemoglobin level is determined. However, the peak level can be estimated. It is generally thought that death may result from carboxyhemoglobin levels of 50 percent in young healthy victims. Patients with underlying cardiovascular disease may be at risk from significantly lower levels.

In recent years, anaesthesiologists have not concerned themselves very much with iatrogenic (Iatros means physician in Greek, and -genic, meaning induced by) carbon monoxide poisoning. This is in part because closed circle anaesthesia fell out of favour after cyclopropane disappeared from clinical use. With closed circle anaesthesia, there had been occasional reports of carbon monoxide build up in the anaesthetic circuit, especially in patients who had required significant blood transfusions. Smoking by the blood donor and haemoglobin destruction were thought to be factors.

A case of unanticipated carbon monoxide toxicity (the patient was receiving desflurane). The case occurred Monday morning and it was postulated that something happened to the anaesthesia system during prolonged disuse which ultimately led to the release of carbon monoxide.

It has been reported, however, that clinically insignificant amounts of carbon monoxide were found after experimentally exposing anaesthetic agents to soda lime. It was postulated that carbon monoxide might be absorbed by soda lime and then released after a period of disuse. Flushing the system with a high fresh gas flow seemed reasonable.

Recent clinical reports of increased carbon monoxide (CO) haemoglobin concentrations in children anaesthetized with sevoflurane that had passed through dry soda lime seem to contradict the laboratory experience with this anaesthetic. To examine discrepancies between laboratory investigations and clinical experiences, Experiments have been carried out to measure CO formation from five different volatile anaesthetics passed through an absorber system that permitted temperature changes. (Wissing BMC Anesthesiology 2005, 5:6 doi:10.1186/1471-2253-5-6 )

Experiments were conducted in triplicate. Either 2.5% or 5% of five inhalational anaesthetics (desflurane, enflurane, isoflurane, halothane, and sevoflurane) were passed for 2 hours through an absorber canister filled with dried soda lime. Baseline CO production was first determined using dry soda lime and a flow of 2 l/min O2 with no volatile anaesthetic and using fresh wet soda lime and a flow of 2 l/min with 5% anaesthetic. CO concentrations were continuously measured at the absorber outlet. Additional experiments were conducted to confirm the sevoflurane results because the magnitude of CO production was unexpected and because of the potential of various breakdown products. CO was detected with all anaesthetics passed through dry soda lime, but the time course and rate of CO production and the time course of temperature changes differed between the agents. Measurable amounts of CO were found immediately after desflurane, enflurane, or isoflurane came in contact with the soda lime; with sevoflurane, there was a time delay between contact and CO production. CO production peaked initially and was highest with desflurane, followed by enflurane, isoflurane, sevoflurane, and halothane. The temperature of the absorbent increased with all anaesthetics, but was highest for sevoflurane. As a result of these experiments, the researchers caution that although CO production is clearly higher than with other agents, some CO-in possibly relevant amounts-is produced by sevoflurane. Adequate precautions should be taken to ensure that soda lime in absorbers does not become desiccated.

Previous studies, in which volatile anaesthetics were exposed to small amounts of dry soda lime, generally controlled at or close to ambient temperatures, have demonstrated a large carbon monoxide (CO) production from desflurane and enflurane, less from isoflurane, and none from halothane and sevoflurane.

However, there is a report (Anesthesiology: Volume 95(5) November 2001 pp 5A-6A Henkel, Gretchen) of increased CO haemoglobin in children who had been induced with sevoflurane that had passed through dry soda lime. Because this clinical report appears to be inconsistent with existing laboratory work, the authors investigated CO production from volatile anaesthetics more realistically simulating conditions in clinical absorbers.

Methods :

Each agent, 2.5 or 5% in 2 l/min oxygen, were passed for 2 h through a Drager absorber canister (bottom to top) filled with dried soda lime (Dragersorb 800). CO concentrations were continuously measured at the absorber outlet. CO production was calculated. Experiments were performed in ambient air (19-20[degrees]C). The absorbent temperature was not controlled.

Results :

Carbon monoxide production peaked initially and was highest with desflurane (507 +/- 70, 656 +/- 59 ml CO), followed by enflurane (460 +/- 41, 475 +/- 99 ml CO), isoflurane (176 +/- 2.8, 227 +/- 21 ml CO), sevoflurane (34 +/- 1, 104 +/- 4 ml CO), and halothane (22 +/- 3, 20 +/- 1 ml CO) (mean +/- SD at 2.5 and 5%, respectively).

Conclusions :

The absorbent temperature increased with all anaesthetics but was highest for sevoflurane. The reported magnitude of CO formation from desflurane, enflurane, and isoflurane was confirmed. In contrast, a smaller but significant CO formation from sevoflurane was found, which may account for the CO haemoglobin concentrations reported in infants. With all agents, CO formation appears to be self-limited.

Volatile anaesthetic degradation

Consequences of volatile anaesthetic degradation by carbon dioxide absorbents that contain strong base include formation of compound A from sevoflurane, formation of carbon monoxide (CO) and CO toxicity from desflurane, enflurane and isoflurane, delayed inhalation induction, and increased anaesthetic costs. Amsorb (Armstrong Ltd., Coleraine, Northern Ireland) is a new absorbent that does not contain strong base and does not form CO or compound A in vitro. An investigation compared Amsorb, Baralyme (Chemetron Medical Division, Allied Healthcare Products, St. Louis, MO), and sodalime effects on CO (from desflurane and isoflurane) and compound A formation, carboxyhemoglobin (COHb) concentrations, and anaesthetic degradation in a clinically relevant porcine in vivo model.

METHODS:

Pigs were anesthetized with desflurane, isoflurane, or sevoflurane, using fresh or partially dehydrated Amsorb, Baralyme, and new and old formulations of sodalime. Anaesthetic concentrations in the fresh (preabsorber), inspired (postabsorber), and end-tidal gas were measured, as were inspired CO and compound A concentrations and blood oxyhemoglobin and COHb concentrations. RESULTS: For desflurane and isoflurane, the order of inspired CO and COHb formation was dehydrated Baralyme >> soda-lime > Amsorb. For desflurane and Baralyme, peak CO was 9,700 +/- 5,100 parts per million (ppm), and the increase in COHb was 37 +/- 14%. CO and COHb increases were undetectable with Amsorb. Oxyhemoglobin desaturation occurred with desflurane and Baralyme but not Amsorb or sodalime. The gap between inspired and end-tidal desflurane and isoflurane did not differ between the various dehydrated absorbents. Neither fresh nor dehydrated Amsorb caused compound A (Compound formed from chemical reactions between the agent and CO2 absorbent) formation from sevoflurane. In contrast, Baralyme and sodalime caused 20-40 ppm compound A. The gap between inspired and end-tidal sevoflurane did not differ between fresh absorbents, but was Amsorb < sodalime < Baralyme with dehydrated absorbents.

CONCLUSION:

Amsorb caused minimal if any CO formation, minimal compound A formation regardless of absorbent hydration, and the least amount of sevoflurane degradation. An absorbent like Amsorb, which does not contain strong base or cause anaesthetic degradation and formation of toxic products, may have benefit with respect to patient safety, inhalation induction, and anaesthetic consumption (cost).

Submitted by John Sandham [30/06/05]

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