eMedicine Specialties > Emergency Medicine > Toxicology

Toxicity, Carbon Monoxide

Author: Guy N Shochat, MD, Associate Clinical Professor of Emergency Medicine, University of California at San Francisco
Coauthor(s): Michael Lucchesi, MD, Chair, Associate Professor, Department of Emergency Medicine, State University of New York at Brooklyn
Contributor Information and Disclosures

Updated: Feb 17, 2009

Introduction

Background

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.

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.

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. A recent 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. During 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.

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.³

Race

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

• For unintentional fatalities, race-specific death rates were 20% higher for blacks.
• 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 recent 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 are non-English speaking.⁴

Age

Age-specific fatality rates are equivalent for individuals aged 15-74 years; rates increase for persons older than 75 years and decline for persons younger than 15 years.

• Age-adjusted fatality rates are higher in cold and mountainous locations.
• 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.

Clinical

History

Misdiagnosis commonly occurs because of the vagueness and broad spectrum of complaints; symptoms often are attributed to a viral illness. Specifically inquiring about possible exposures when considering the diagnosis is important. Any of the following should alert suspicion in the winter months, especially in relation to the previously named sources and when more than one patient in a group or household presents with similar complaints. Symptoms may not correlate well with HbCO levels.

• Acute poisoning
  • Malaise, flulike symptoms, fatigue
  • Dyspnea on exertion
  • Chest pain, palpitations
  • Lethargy
  • Confusion
  • Depression
  • Impulsiveness
  • Distractibility
  • Hallucination, confabulation
  • Agitation
  • Nausea, vomiting, diarrhea
  • Abdominal pain
  • Headache, drowsiness
  • Dizziness, weakness, confusion
  • Visual disturbance, syncope, seizure
  • Fecal and urinary incontinence
  • Memory and gait disturbances
  • Bizarre neurologic symptoms, coma
• Chronic exposures also present with the above symptoms; however, they may present with loss of dentition, gradual-onset neuropsychiatric symptoms, or, simply, recent impairment of cognitive ability.

Physical

Physical examination is of limited value. Inhalation injury or burns should always alert the clinician to the possibility of CO exposure.

• Vital signs
  • Tachycardia
  • Hypertension or hypotension
  • Hyperthermia
  • Marked tachypnea (rare; severe intoxication often associated with mild or no tachypnea)
• Skin: Classic cherry red skin is rare (ie, "When you're cherry red, you're dead"); pallor is present more often.
• Ophthalmologic
  • Flame-shaped retinal hemorrhages
  • Bright red retinal veins (a sensitive early sign)
  • Papilledema
  • Homonymous hemianopsia
• Noncardiogenic pulmonary edema
• Neurologic and/or neuropsychiatric
  • Patients display memory disturbance (most common), including retrograde and anterograde amnesia with amnestic confabulatory states.
  • Patients may experience emotional lability, impaired judgment, and decreased cognitive ability.
  • Other signs include stupor, coma, gait disturbance, movement disorders, and rigidity.
  • Patients display brisk reflexes, apraxia, agnosia, tic disorders, hearing and vestibular dysfunction, blindness, and psychosis.
  • Long-term exposures or severe acute exposures frequently result in long-term neuropsychiatric sequelae. Additionally, some individuals develop delayed neuropsychiatric symptoms, often after severe intoxications associated with coma.
  • After recovery from the initial incident, patients present several days to weeks later with neuropsychiatric symptoms such as those just described. Two thirds of patients eventually recover completely.
  • MRI changes may remain long after clinical recovery. Predicting and preventing long-term complications and delayed encephalopathy have been the object of recent studies, many of which focus on the role of hyperbaric oxygen therapy.

Causes

• Most unintentional 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 revealed that sources of 1149 poisonings were residential furnaces (40%), automobile exhaust (24%), and fires (12%).
• Furnaces were determined to be the source in 46% of nonfatal CO poisonings but in only 10% of fatal poisonings. This suggests that the role of home heating appliances is prominent in the large group of underreported nonfatal exposures.
• In the setting of structure fires, CO presents greater risk to firefighters and victims than thermal injury or oxygen deprivation.⁵
• Most developing countries utilize unvented cookstoves, burning wood, charcoal, animal dung, or agricultural waste. Studies have shown a concurrent rise in HbCO with these types of exposure in developing countries.

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