Description

• Carbon monoxide (CO) is an odorless, tasteless, colorless gas produced during the incomplete combustion of carbon-based compounds. If inhaled, CO may cause nonspecific symptoms and is potentially fatal.
  • CO inhalation leads to displacement of oxygen from binding sites on hemoglobin to form carboxy hemoglobin (COHb).
  • The formation of COHb leads to tissue hypoxia from decreased oxygen carrying capacity and a left shift of the oxyhemoglobin dissociation curve.
  • CO binds to mitochondrial cytochrome oxidase, impairing adenosine triphosphate (ATP) production. It also binds to myoglobin, affecting muscle function.
• System(s) affected: cardiovascular, pulmonary, musculoskeletal, nervous

Pregnancy Considerations
Tissue hypoxia due to CO poisoning may cause significant fetal abnormalities because CO has a stronger affinity and a longer half-life when bound to fetal hemoglobin. The fetus is therefore susceptible to adverse outcomes even if the mother is unaffected.

Epidemiology

Incidence

• CO poisoning is the third leading cause of poisoning death in the United States.
• Accounts for 50,000 ER visits annually (16 cases per 100,000 population); 1–3% are fatal.
• Approximately 15,000 intentional poisoning occur per year, accounting for 2/3 reported deaths (10-fold higher than unintentional poisonings).
• Results in approximately 1,200 to 1,600 deaths a year in the United States due to fire- and non–fire-related poisoning.
• Vague symptoms may cause patients to not seek care, leading to underdiagnosis.

Prevalence

• More prevalent during the winter months in areas with colder climate
• Occupational exposure to methylene chloride, an industrial solvent that is a component of paint remover, can also lead to CO poisoning.

Etiology and Pathophysiology

• CO is rapidly absorbed through the lungs, binding hemoglobin with 210 to 240 times the affinity of oxygen. This stabilizes hemoglobin in the relaxed high affinity state (R state), reducing oxygen-carrying capacity and delivery, leading to left shift of the oxyhemoglobin dissociation curve.
• CO inactivates cytochrome oxidase. This leads to decreased ATP production, especially in tissues with high metabolic demands (brain, heart). The electron transport chain continues, generating superoxide radicals, leading to further damage.
• Increased peroxynitrite production contributes to impaired mitochondrial function and hypoxia.
• CO displaces NO from platelets, leading to platelet activation and aggregation. Oxidative stress, lipid peroxidation, and apoptosis are additional effects.
• Mitochondrial dysfunction and hypoxia leads to myocardial stunning and injury.
• Proteases released from neutrophil degranulation interact with xanthine hydrogenase forming xanthine oxidase. This inhibits endogenous defense against oxidative stress.
• Brain hypoxia leads to excitatory amino acid production and increased nitrite levels, resulting in further ischemia.
• CO also initiates an inflammatory cascade that can lead to oxidative degradation of nervous system lipids and delayed neurologic damage.
• CO also promotes the release of NO which can lead to profound hypotension.

Risk Factors

• Alcohol and tobacco use
• Patients with severe COPD regardless of current tobacco smoke exposure
• Closed or improperly ventilated spaces
• Fires and fire-related injuries
• High-risk vocations: coal miners, auto mechanics, paint stripping, work in the solvent industry
• Exposure to exhaust from motor vehicles, faulty furnaces, stoves, generator use (power outages and storms), and other fuel burning devices
• If exposed, infants, elderly patients, and patients with comorbid conditions such as cardiovascular disease, anemia, and chronic respiratory conditions have increased risk for poor outcomes.
• Increased endogenous CO production occurs in patients with hemolytic anemia.

General Prevention

• Appropriate ventilation around fuel-burning devices
• Installation of in-home CO monitors or alarms
• Postexposure determination of CO source to limit future exposures, eliminate source, and initiate treatment
• Public policy to ensure building code safety
• Limiting occupational exposures for those who work with automobiles, paint, solvents, or mines

Commonly Associated Conditions

• CO and cyanide poisoning often occur simultaneously after smoke inhalation and have synergistic effects.
• Intentional poisoning often occurs in the context of coingestion of other substances (~40%).
• Up to 50–75% of fire-related injuries have a component of CO poisoning.