Carbon monoxide (CO) is a colorless, odorless, tasteless, and nonirritating gas produced by the incomplete combustion of any carbon-containing material. Common sources of human exposure include smoke inhalation in fires; automobile exhaust fumes; faulty or poorly ventilated charcoal, kerosene, or gas stoves; and, to a lesser extent, cigarette smoke and methylene chloride (See Methylene Chloride). CO poisoning accounts for approximately 50,000 emergency department visits every year in the United States.
Mechanism of toxicity. Toxicity is a consequence of cellular hypoxia and ischemia.
CO binds to hemoglobin with an affinity 250 times that of oxygen, resulting in reduced oxyhemoglobin saturation and decreased blood oxygen-carrying capacity. In addition, the oxyhemoglobin dissociation curve is displaced to the left, impairing oxygen delivery at the tissues.
CO may also directly inhibit cytochrome oxidase, further disrupting cellular function, and it is known to bind to myoglobin, possibly contributing to impaired myocardial contractility.
In animal models of intoxication, damage is most severe in areas of the brain that are highly sensitive to ischemia and often correlates with the severity of systemic hypotension. Postanoxic injury appears to be complicated by lipid peroxidation, excessive release of reactive oxygen species and excitatory neurotransmitters, and inflammatory changes.
Fetal hemoglobin is more sensitive to binding by CO, and fetal or neonatal levels may be higher than maternal levels.
Pharmacokinetics. The carboxyhemoglobin (CO-Hgb) complex gradually dissociates after removal from exposure. The approximate half-life of elimination of CO-Hgb during treatment with high-flow oxygen by tight-fitting mask or endotracheal tube is 74 minutes (range, 24–148 minutes). In room air the approximate half-life is as much as 200 minutes, and during hyperbaric oxygen therapy it is as short as 12–20 minutes.
Toxic dose. The recommended workplace limit (ACGIH TLV-TWA) for carbon monoxide is 25 ppm as an 8-hour time-weighted average. The level considered immediately dangerous to life or health (IDLH) is 1200 ppm (0.12%). However, the duration of exposure is very important. Whereas exposure to 1000 ppm (0.1%) eventually will result in 50% saturation of CO-Hgb, it may take several hours to reach that level. In 1895, Haldane experimented on himself by breathing CO at 2100 ppm for over an hour, and it was only after 34 minutes, when his level would have been approximately 25%, that he described a throbbing headache. Brief exposure to much higher levels may produce a more rapid rise in CO-Hgb.
Clinical presentation. Symptoms of intoxication are predominantly in organs with high oxygen consumption, such as the brain and heart.
The majority of patients describe headache, dizziness, and nausea. Patients with coronary disease may experience angina or myocardial infarction. With more severe exposures, impaired thinking, syncope, coma, convulsions, cardiac arrhythmias, hypotension, and death may occur. Although blood CO-Hgb levels may not correlate reliably with the severity of intoxication, levels greater than 25% are considered significant, and levels greater than 40–50% usually are associated with obvious intoxication.
Survivors of serious poisoning may experience numerous overt neurologic sequelae consistent with a hypoxic-ischemic insult, ranging from gross ...