Carbon Monoxide Toxicity in Emergency Medicine 

Carbon monoxide (CO) is a colorless, odorless gas produced by incomplete combustion of carbonaceous material. Commonly overlooked or misdiagnosed, CO intoxication often presents a significant challenge, as treatment protocols, especially for hyperbaric oxygen therapy, remain controversial because of a paucity of definitive clinical studies.

CO is formed as a by-product of burning organic compounds. Although most fatalities result from fires, stoves, portable heaters, and automobile exhaust cause approximately one third of deaths. These often are associated with malfunctioning or obstructed exhaust systems and suicide attempts. Cigarette smoke is a significant source of CO. Natural gas contains no CO, but improperly vented gas water heaters, kerosene space heaters, charcoal grills, hibachis, and Sterno stoves all emit CO. Other sources of CO exposure include propane-fueled forklifts, gas-powered concrete saws, inhaling spray paint, indoor tractor pulls, and swimming behind a motorboat.

CO intoxication also occurs by inhalation of methylene chloride vapors, a volatile liquid found in degreasers, solvents, and paint removers. Dermal methylene chloride exposure may not result in significant systemic effects but can cause significant dermal burns. Rarely, methylene chloride is ingested, and can result in delayed CO toxicity. Liver metabolizes as much as one third of inhaled methylene chloride to CO. A significant percentage of methylene chloride is stored in the tissues, and continued release results in elevated CO levels for at least twice as long as with direct CO inhalation.

Children riding in the back of enclosed pickup trucks seem to be at particularly high risk. Industrial workers at pulp mills, steel foundries, and plants producing formaldehyde or coke are at risk for exposure, as are personnel at fire scenes and individuals working indoors with combustion engines or combustible gases.

CO toxicity causes impaired oxygen delivery and utilization at the cellular level. CO affects several different sites within the body but has its most profound impact on the organs (eg, brain, heart) with the highest oxygen requirement.

Toxicity primarily results from cellular hypoxia caused by impedance of oxygen delivery. CO reversibly binds hemoglobin, resulting in relative functional anemia. Because it binds hemoglobin 230-270 times more avidly than oxygen, even small concentrations can result in significant levels of carboxyhemoglobin (HbCO).

An ambient CO level of 100 ppm produces an HbCO of 16% at equilibration, which is enough to produce clinical symptoms. Binding of CO to hemoglobin causes an increased binding of oxygen molecules at the 3 other oxygen-binding sites, resulting in a leftward shift in the oxyhemoglobin dissociation curve and decreasing the availability of oxygen to the already hypoxic tissues.

CO binds to cardiac myoglobin with an even greater affinity than to hemoglobin; the resulting myocardial depression and hypotension exacerbates the tissue hypoxia. Decrease in oxygen delivery is insufficient, however, to explain the extent of the CO toxicity. Clinical status often does not correlate well with HbCO level, leading some to postulate an additional impairment of cellular respiration.

CO binds to cytochromes c and P450 but with a much lower affinity than that of oxygen; in experimental studies, it was shown that exposure to CO produces marked decrease in cytochrome oxidase suggesting direct toxic effects.

Studies have indicated that CO may cause brain lipid peroxidation and leukocyte-mediated inflammatory changes in the brain, a process that may be inhibited by hyperbaric oxygen therapy. Following severe intoxication, patients display central nervous system (CNS) pathology, including white matter demyelination. This leads to edema and focal areas of necrosis, typically of the bilateral globus pallidus. Interestingly, the pallidus lesions, as well as the other lesions, are watershed area tissues with relatively low oxygen demand, suggesting elements of hypoperfusion and hypoxia.

Studies have demonstrated release of nitric oxide free radical (implicated in the pathophysiology of atherosclerosis) from platelet and vascular endothelium, following exposure to CO concentrations of 100 ppm. One study suggests a direct toxicity of CO on myocardium that is separate from the effect of hypoxia.^[1]

HbCO levels often do not reflect the clinical picture, yet symptoms typically begin with headaches at levels around 10%. Levels of 50-70% may result in seizure, coma, and fatality.

CO is eliminated through the lungs. Half-life of CO at room air temperature is 3-4 hours. One hundred percent oxygen reduces the half-life to 30-90 minutes; hyperbaric oxygen at 2.5 atm with 100% oxygen reduces it to 15-23 minutes.

Frequency

United States

Approximately 2 million death certificates are filed yearly in the United States. State-level estimates of CO-related deaths were reported in 1991 for the 10-year period from 1979-1988. Exactly 56,133 death certificates contained codes addressing CO as a contributing cause; 25,889 (46%) were suicides, 15,523 (28%) involved burns or fires, 210 were deemed homicides, and 11,547 (21%) were categorized as unintentional.^[2] Heroin, the second leading cause of poisoning fatality, followed CO with 5948 deaths. In the same period, all other unintentional poisonings resulted in 40,424 deaths.^[2]

Of unintentional fatalities, 57% were associated with automobile exhaust.^[2] The next leading identifiable causes are coal, wood, or kerosene stoves and fireplaces; combustion of natural gas from a pipeline; combustion of gasoline, acetylene, or utility gas; and industrial sources.

Despite population growth and an increased number of cars, the unintentional death rate has declined by 63 deaths per year during the 10-year period from 1979-1988.^[2] This was attributed in part to increased stringency of auto emissions standards, necessitating a longer time to accumulate a toxic level in a given space.

Updated reporting has been done for the years 1999-2004 revealing CO poisoning as a contributing cause of death in 16,400 deaths. Of these 2,631 (16%) were listed as unintentional and non – fire-related.^[3]

Reporting of nonfatal unintentional non – fire-related exposures from 2001-2003 reveals an average of 15,000 yearly cases treated in emergency departments with 64% occurring in homes. The most common source being furnaces (18.5%) followed by motor vehicles, stoves, gas lines, water heaters, and generators.^[4]

Increasing evidence implicates ambient urban CO levels in rates of angina, arrhythmias, and cardiac arrest. Presuming that the evidence is quantifiable and depending on the true extent, this implies a significant underreporting of CO-associated deaths.

International

Quantifying the global incidence of CO poisoning is impossible because of the transient duration of symptoms in mild intoxication, the ubiquitous and occult nature of exposure, and the tendency of misdiagnosis. In contrast to findings in the United States, one Australian study of suicidal poisonings indicated no decrease following significantly lowered CO emissions from 1970-1996 and revealed no difference between the HbCO levels of occupants in cars with and without catalytic converters.^[5]

Race

All ages, ethnic populations, and social groups are affected, yet particular groups may be at higher risk.

• Earlier data stated that, for unintentional fatalities, race-specific death rates were 20% higher for blacks. More recent data reveal non-Hispanic whites and non-Hispanic blacks to have equally high death rates, significantly above that of Hispanic and those classified as Other.^[3]
• Conversely, intentional fatalities demonstrate that race-specific rates for blacks and other minority racial groups are 87% lower than for whites, revealing a cultural partiality to this form of suicide.

Two North American studies examined the incidence of CO toxicity from indoor heating devices used during severe winter storms. Both studies identified a strong association between CO toxicity and US immigrants who were non-English speaking.^[6]

Sex

• Males represented an overwhelming 74% of unintentional non – fire-related deaths.^[3]

Age

Age-specific fatality rates increase with age and are highest in the older than 65 years group. However, nonfatal exposures are more common in older teens and young adults (aged 15-34 y) than in older adults and are most common in young children (aged 0-4 y).^[4]

• Individuals with pulmonary and cardiovascular disease tolerate CO intoxication poorly; this is particularly evident in those with chronic obstructive pulmonary disease (COPD) who have the additional concern of ventilation-perfusion abnormalities and possible respiratory depressive response to 100% oxygen therapy.
• Neonates and the in utero fetus are more vulnerable to CO toxicity because of the natural leftward shift of the dissociation curve of fetal hemoglobin, a lower baseline PaO₂, and levels of HbCO at equilibration that are 10-15% higher than maternal levels.

Geographical

• Age-adjusted fatality rates are higher in cold and mountainous Midwestern and Western states and peak in the winter months. However, multiple incidents were reported in Southern states following the Katrina and Rita hurricanes of 2005.^[7]