eMedicine Specialties > Pediatrics: Cardiac Disease and Critical Care Medicine > Toxicology

Toxicity, Carbon Monoxide

Author: Samara Soghoian, MD, Medical Toxicology Fellow, Bellevue Hospital Center, New York University School of Medicine
Coauthor(s): Christopher I Doty, MD, FAAEM, Assistant Professor of Emergency Medicine, Residency Program Director, Department of Emergency Medicine, Kings County Hospital Center, State University of New York Downstate Medical Center; Michael Lucchesi, MD, Chair, Associate Professor, Department of Emergency Medicine, State University of New York at Brooklyn; Guy N Shochat, MD, Associate Clinical Professor of Emergency Medicine, University of California at San Francisco
Contributor Information and Disclosures

Updated: Nov 6, 2008

Introduction

Background

Carbon monoxide (CO) is colorless, odorless, tasteless, and highly poisonous. It is the most frequent agent of toxic exposure in North America.¹ In 2002, United States poison centers received carbon monoxide–related calls at a rate of 54.5 calls per million persons. Each year, approximately 40,000-50,000 visits to emergency departments involve documented exposure to carbon monoxide, and about 500 people per year die from unintentional exposure.

Carbon monoxide is produced from the incomplete combustion of organic matter, including fossil fuels. People who smoke cigarettes may have baseline levels of carboxyhemoglobin (HbCO or COHB) as high as 10%, and their susceptibility to toxic effects from inadvertent exposure to other sources of carbon monoxide may be heightened. Toxic exposures to carbon monoxide are most frequently the result of house fires or the use of fuel-burning heating appliances or poorly maintained generators. Intentional poisoning is far more often fatal than unintentional exposure. According to the Centers for Disease Control and Prevention (CDC), suicide involving exhaust pipes are responsible for 2000 deaths a year in the United States alone.²

Carbon monoxide intoxication may also result from inhaling methylene chloride, a volatile liquid found in degreasers, solvents, and paint removers. Most of the adsorbed vapors are exhaled unchanged, but up to one third is metabolized in the liver to carbon monoxide. Because tissues can store methylene chloride, its gradual release and metabolism elevates carbon monoxide levels more than twice as long as direct carbon monoxide inhalation does. Prolonged exposure to methylene chloride (up to 8 h) can produce carbon monoxide levels higher than 8%.

Acute carbon monoxide toxicity may cause asphyxia, myocardial dysfunction, and a full spectrum of peripheral and CNS effects. Symptoms are generally nonspecific and protean. Therefore, if a history of exposure is not given or suspected, this disease is extremely difficult to diagnose. In fact, carbon monoxide toxicity is frequently misdiagnosed as a simple headache or viral syndrome. A high index of suspicion must be maintained, particularly during the winter months, when faulty heating systems and enclosed spaces make carbon monoxide poisoning more common than it is at other times.

Pathophysiology

Carbon monoxide exerts its toxic effects by means of a combination of tissue asphyxia and inflammatory activity. Hypoxia occurs from 3 primary mechanisms: Carbon monoxide diminishes the oxygen carrying capability of hemoglobin, decreases the uptake of bound oxygen into tissues, and impairs the mechanisms of cellular respiration.

Carbon monoxide readily crosses capillary membranes in the lungs and binds the heme moiety on the erythrocyte hemoglobin complex with an affinity 200-300 times greater than that of oxygen. This binding drastically decreases binding spots available for oxygen transport. The amount of oxygen bound to hemoglobin in the setting of carbon monoxide exposure is proportional to the partial pressure of oxygen (PO₂) in respired air and can be increased by giving supplemental O₂.

Carbon monoxide also shifts the oxyhemoglobin dissociation curve to the left, inhibiting the release of bound oxygen to tissues. In addition, approximately 10-15% of absorbed carbon monoxide binds to extravascular proteins. Carbon monoxide dissolved in plasma is known to cross capillary membranes and bind myoglobin, reduced cytochromes, guanylate cyclase, and nitric oxide (NO) synthase. This process decreases the number of binding sites available for oxygen in select tissues, further contributing to hypoxia. The interplay of all these effects causes tissues exposed to carbon monoxide to have an oxygen tension lower than that due to simple hypoxia alone. Because of the high affinity of carbon monoxide for hemoglobin, even low ambient levels of CO can lead to clinically significant toxicity over long exposures.

Carbon monoxide directly impairs aerobic metabolism in tissues by poisoning the mitochondrial electron-transport chain. It does so by binding mitochondrial cytochromes, preventing the binding and subsequent reduction of oxygen at the end of the cycle. The process of oxidative phosphorylation cannot be completed, and, instead of making water and adenosine triphosphate (ATP), the mitochondria make destructive oxygen free radicals.

Tissue hypoxia and oxidative stress account for most of the pernicious effects of carbon monoxide in the body. Hypoxic stress in patients with carbon monoxide poisoning is increased because of its effects on mitochondrial electron transport and cellular respiration. Although the acutely toxic effects of carbon monoxide are primarily due to hypoxia, activation of inflammatory processes plays a major role in carbon monoxide poisoning, particularly in the development of neurologic damage.

Inflammatory and immune-mediated mechanisms contribute to the development of the systemic inflammatory response syndrome (SIRS) and delayed neurologic sequelae (DNS). Animal models demonstrated that carbon monoxide causes perivascular changes in the CNS that cause neutrophil sequestration and activation in the brain. Reactive oxygen species released by these cells then cause brain lipid peroxidation. Byproducts of peroxidation alter myelin basic protein (MBP) in the presence of carbon monoxide, altering immunologic recognition of MBP and starting a cascade of autoimmune activity against cerebral proteins.

Frequency

United States

Estimates of the frequency of carbon monoxide exposure widely vary. The scope of the problem is difficult to assess because patients with carbon monoxide mild exposures may not seek medical attention and because carbon monoxide poisoning is frequently misdiagnosed. The CDC estimates that 15,200 people per year were treated in US emergency rooms for unintentional, non–fire-related carbon monoxide exposures in 2001-2002.² Most exposures occur during the winter months.

Mortality/Morbidity

Approximately 480 unintentional deaths and 2000 suicides per year are due to carbon monoxide poisoning in the United States.

• Certain groups are more susceptible than others to the toxic effects of carbon monoxide. Morbidity and mortality risks are increased in fetuses; infants; young children; people older than 65 years; people who smoke; and patients with heart disease, pulmonary disease, or anemia.
• In one study, 37% of patients treated for moderate-to-severe carbon monoxide poisoning with hyperbaric oxygen therapy nonetheless had acute myocardial injury (ECG changes and/or elevated biomarkers). Patients were relatively young (mean age 47.2 y), and rates of previous cardiovascular disease were low (6.5% for previous myocardial infarction, 2.6% for previous revascularization procedure, and 3% for a history of congestive heart failure [CHF]). About 38% of patients with acute myocardial infarction after carbon monoxide poisoning died (24% overall) at a median follow-up of 7.6 years.
• Over one half of patients with severe carbon monoxide poisoning develop encephalopathy within a month of injury.

Race

All races are equally susceptible to the physiologic effects of carbon monoxide poisoning, but non–English-speaking immigrants and minority racial groups are at increased risk of exposure.

• For example, the unintentional death rate related to carbon monoxide is 20% higher among African Americans than Caucasians.
• The difference is primarily due to economic disparities among racial and ethnic groups in the United States. Members of economically disadvantaged social groups are most likely to be involved in house fires, to have malfunctioning or no carbon monoxide detectors in the home, to have faulty indoor heating systems, and to work in high-risk settings.

Sex

CDC analysis of data from the National Vital Statistics Program and National Electronic Injury Surveillance System All Injury Statistics for 2001-2003 showed that male individuals and female individuals were equally likely to seek care in the emergency department for non–fire-related carbon monoxide exposure and poisoning. However, male individuals were 2.7 times more likely than female individuals to die from carbon monoxide toxicity, with a case fatality rate increased by 2.3 times (where the rate was defined as the number of carbon monoxide deaths divided by the sum of carbon monoxide exposures X 100). Reasons for this discrepancy are not clear.

Age

The very young and very old are most susceptible to both exposure and the pernicious effects of carbon monoxide.

• The CDC reports that, in the United States in 2001-2003, children younger than 4 years had the highest incidence of unintentional carbon monoxide exposure but the lowest death rates from carbon monoxide poisoning.²
• In the CDC report (2005), the risk of death from CO poisoning increased with age. The case fatality rate for carbon monoxide was 0.6% for children younger than 4 years, increasing to 5.5% in adults aged 55-64 years. In 2001-2003, 23% of all deaths from carbon monoxide poisoning occurred in adults older than 65 years.
• Human and animal data suggest that carbon monoxide is both teratogenic and highly associated with fetal death. Neonates and in utero fetuses are most vulnerable to CO poisoning, for a number of reasons. Fetal hemoglobin binds carbon monoxide with greater affinity than does adult forms, resulting in increased tissue hypoxia at similar HbCO levels. The fetus also has a low baseline PO₂, and levels of HbCO at equilibration are 10-15% higher than maternal levels.

Clinical

History

Carbon monoxide (CO) has been called the great imitator because of the protean symptoms it produces. As a result, carbon monoxide poisoning is frequently misdiagnosed.

• Patients may complain of any number of vague symptoms. In one series, headache was the most frequent complaint (37.5%), followed by dizziness (18%), nausea (17.3%), loss of consciousness (7.7%), shortness of breath (6.7%), and loss of muscle control (3.5%).
• Symptoms may be attributed to a viral syndrome, migraine or tension headache, anxiety attack, hyperventilation syndrome, or a nonspecific illness.
• Unless the patient is brought in from the scene of a fire, a high index of suspicion must be maintained to make the diagnosis. An important clue is the finding of similar complaints among people who work or live together, particularly during the winter months, when heaters are on and when windows tend to be closed.
• Anyone working with combustion engines or combustible gasses indoors should be considered to be at high risk. Carbon monoxide poisoning should also be considered in patients presenting with vague somatic complaints after a natural disaster, when generator use is common.
• If carbon monoxide poisoning is suspected or diagnosed, attempt to determine the source, the duration of exposure, the amount of time elapsed since the patient was withdrawn from the source, and the occurrence of any neurologic symptoms (eg, syncope, seizure, altered mental status, vertigo, focal neurologic deficits).

Physical

Although burns, singed facial hair, and oropharyngeal soot clearly suggest carbon monoxide exposure, physical findings specific to carbon monoxide poisoning are few.

• The classic cherry-red skin and retinal discoloration is seen only with the most severe cases of carbon monoxide poisoning and is generally a postmortem finding. The skin is most likely to be pale, cyanotic, or mottled because of hypoxia and cardiac depression.
• Bright red retinal veins are a relatively sensitive and early but often overlooked finding in moderate-to-severe cases of carbon monoxide poisoning. Ophthalmic examination may reveal flame-shaped retinal hemorrhages or papilledema.
• Carbon monoxide causes myocardial depression and dysrhythmias. Animal models suggest that shock, if present, is more likely due to vasodilation.
• Vital signs may reflect tachypnea, hypoxia, tachycardia, hypotension or hypertension, and mild hyperthermia. Pulse oximetry may remain in the normal range despite cyanosis and tissue hypoxia because the wavelengths produced by carboxyhemoglobin (HbCO) and oxyhemoglobin are read similarly by these machines. Carbon monoxide poisoning typically produces a pulse oximetry gap (the difference between the pulse oximeter reading and the spectrophotometrically measured oxyhemoglobin saturation).
• Rales may be a sign of noncardiogenic pulmonary edema.
• Neurologic and neuropsychologic symptoms frequently occur in the setting of acute carbon monoxide toxicity and are the most frequent long-term consequence of poisoning. Severe cases of carbon monoxide poisoning are often characterized by serious neurologic abnormalities including low Glasgow Coma Scale (GCS) scores and seizures.
• Overall, memory disturbances, including both anterograde and retrograde amnesia, are the most common neurologic abnormalities. Other signs include lethargy, stupor, coma, gait disturbance, movement disorders, apraxia, agnosia, tics, vestibular dysfunction, hearing and visual loss, rigidity, brisk reflexes, emotional lability, frank psychosis, and impaired judgment and cognitive function.

Causes

Carbon monoxide is produced by the incomplete combustion of organic matter and fuels (gas, oil, wood, charcoal). Therefore, fires are the major sources of exposure and toxicity.

• In 2004, the Consumer Product Safety Commission reported that about 64% of deaths from unintentional carbon monoxide poisoning were due to exposures in the home.³
• The most common cause of unintentional, non–fire-related carbon monoxide exposure is malfunctioning household heating appliances used in poorly ventilated rooms.
• The incidence of carbon monoxide poisoning increases after environmental disasters in which heating and electrical systems are destroyed. For example, after hurricanes Katrina and Rita in 2005, 78 cases of nonfatal carbon monoxide poisoning and 10 deaths were reported in affected counties in Alabama and Texas. Nearly all cases were due to gasoline-powered back-up generators being run outside but near the home's air conditioner, through which carbon monoxide was drawn into the home.
• Workers with a high risk of exposure to carbon monoxide include forklift operators, attendants of underground parking garages, and mechanics.
• Open-air exposure leading to carbon monoxide toxicity is not uncommon among motor boat enthusiasts, and it has been reported in children riding in the back of pick-up trucks.
• Fatal carbon monoxide poisonings due to cooking fumes are reported among climbers and polar explorers. An experimental study in Norway showed that a kerosene camping stove used inside a closed tent for 2 hours raised ambient carbon monoxide levels enough to cause a mean HbCO level of 21.5% and clinically significant hypoxia in healthy volunteers.⁴

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