Practice Essentials
Carbon monoxide (CO) is a colorless, odorless gas produced by incomplete combustion of carbonaceous material. Clinical presentation in patients with CO poisoning ranges from headache and dizziness to coma and death. Hyperbaric oxygen therapy (see the image below) can significantly reduce the morbidity of CO poisoning, but a portion of survivors still suffer significant long-term neurologic and affective sequelae. [1]
Monoplace hyperbaric chamber. Courtesy JG Benitez, MD, MPH.
CO is formed as a by-product of burning organic compounds. Many cases of CO exposure occur in private residences. [2] CO toxicity is especially common during power outages due to storms, as a result of the improper use of gasoline-powered portable generators to provide electricity and indoor use of charcoal briquettes for cooking and heating. [3, 4] Exhaust from generators and propulsion engines on houseboats has also been linked to CO poisoning. [5]
Most fatalities from CO toxicity result from fires, but 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 the following [6, 7] :
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Propane-fueled forklifts
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Gas-powered concrete saws
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Inhaling spray paint
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Indoor tractor pulls
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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. The 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.
Pathophysiology
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.
Cellular hypoxia from CO toxicity is 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 three 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 can produce direct cellular changes involving immunological or inflammatory damage by a variety of mechanisms, including the following [3] :
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Binding to intracellular proteins (myoglobin, cytochrome a,a 3)
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Nitric oxide generation leading to peroxynitrite production
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Lipid peroxidation by neutrophils
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Mitochondrial oxidative stress
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Apoptosis
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Immune-mediated injury
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Delayed inflammation
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. [8]
Studies have demonstrated release of nitric oxide free radicals (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. [9]
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. The 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.
Etiology
Most unintentional CO fatalities occur in stationary vehicles from preventable causes such as malfunctioning exhaust systems, inadequately ventilated passenger compartments, operation in an enclosed space, and utilization of auxiliary fuel-burning heaters inside a car or camper.
Most unintentional automobile-related CO deaths in garages have occurred despite open garage doors or windows, demonstrating the inadequacy of passive ventilation in such situations.
Colorado state data from 1986-1991 revealed that leading sources of 1149 unintentional nonfatal CO poisonings were residential furnaces (40%), automobile exhaust (24%), and fires (12%); however, furnaces were responsible for onlly 10% of fatal poisonings [10]
In the setting of structure fires, CO presents greater risk than thermal injury or oxygen deprivation, both for firefighters and victims. [11]
In most developing countries, cooking or heating is often done with unvented cookstoves, wood, charcoal, animal dung, or agricultural waste, which has been linked with elevated HbCO levels.
Boats and houseboats represent a significant and underappreciated source of exposure, with multiple case reports and studies. [5]
Epidemiology
Frequency
United States
Unintentional, non–fire-related CO poisoning is responsible for approximately 15,000 emergency department visits annually in the United States. In 2000-2009, the exposure site was reported as residence in 77.6% of cases and workplace in 12%. [12] The most common source of CO exposure in the home is furnaces (18.5%), followed by motor vehicles, stoves, gas lines, water heaters, and generators. [13] During 1999–2012, deaths from unintentional non–fire-related CO poisoning in the US totaled 6136, an average of 438 deaths per year. [14]
In 2021, the American Association of Poison Control Centers reported 12,728 single exposures to CO, 366 of which were intentional. Major outcomes occurred in 349 cases, and 124 deaths were reported. [15]
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. Nevertheless, the worldwide cumulative incidence of CO poisoning can be currently estimated at 137 cases per million population. The worldwide incidence has remained stable during the last 25 years, while the mortality rate has declined; annual mortality is currently estimated at 4.6 deaths per million population. [16]
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. [17]
Race
All ages, ethnic populations, and social groups are affected, yet particular groups may be at higher risk.
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Earlier data stated that, for unintentional fatalities, race-specific death rates were 20% higher for Blacks. More recent data reveal that non-Hispanic Whites and non-Hispanic Blacks to have equally high death rates, significantly above that of Hispanics and those classified as Other. [18]
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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, from the 1990s and 2005, 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. [19] However, a study of acute, severe CO poisoning from portable electric generators in the US from August 1, 2008 to July 31, 2011 found that 96% of patients spoke English. [4]
Sex
During 1999–2010, the average annual death rate from unintentional non–fire-related CO poisoning was more than three times higher for males than for females (0.22 versus 0.07 per 100,000 population, respectively). Males represented an overwhelming 74% of unintentional non–fire-related deaths. [18]
Age
Age-specific fatality rates increase with age and are highest in those older than 65 years. 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). [18, 13]
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.
Climate and weather
Age-adjusted fatality rates are higher in cold and mountainous Midwestern and Western states and peak in the winter months. In addition, hurricanes and other natural disasters that result in power outages can lead to a spike in CO poisonings, as those affected turn to alternative sources of fuel or electricity. [20] For example, multiple incidents of CO poisoning were reported in Southern states following the Katrina and Rita hurricanes of 2005, in Northeastern states following Hurricane Sandy in 2012, and in Florida following Hurricane Irma in 2017. [21, 22, 23] The Centers for Disease Control and Prevention has established a Web page providing clinical guidance for carbon monoxide (CO) poisoning after a disaster.
Prognosis
Considerations regarding prognosis include the following:
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Variability of clinical severity, laboratory values, and outcome limits prognostic accuracy
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Cardiac arrest, coma, metabolic acidosis, and high HbCO levels are associated with poor outcome
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Abnormal CT or MRI findings are associated with persistent neurologic impairment
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Neuropsychiatric testing may have prognostic efficacy in determining delayed sequelae
An analysis of 331 pediatric patients with CO poisoning seen at a single-site emergency department found risk factors associated with severe disease course were a low Glasgow Coma Scale score, high leukocyte count, and high troponin T levels at presentation. [24]
Survivors of intentional CO poisoning are at extreme risk for subsequent completion of suicide. [3]
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Monoplace hyperbaric chamber. Courtesy JG Benitez, MD, MPH.
