Carbon Monoxide Poisoning: Pathogenesis, Management, and Future Directions of Therapy

Carbon monoxide (CO) poisoning affects 50,000 people a year in theUnited States. The clinical presentation runs a spectrum, ranging fromheadache and dizziness to coma and death, with a mortality rate rangingfrom 1 to 3%. A significant number of patients who survive COpoisoning sufferfrom long-term neurological and affective sequelae. Theneurologic deficits do not necessarily correlate with blood CO levels butlikely result from the pleiotropic effects of CO on cellular mitochondrialrespiration, cellular energy utilization, inflammation, and free radicalgeneration, especially in the brain and heart. Long-term neurocognitivedeficits occur in 15–40% of patients, whereas approximately one-third ofmoderate to severely poisoned patients exhibit cardiac dysfunction,including arrhythmia, left ventricular systolic dysfunction, andmyocardial infarction. Imaging studies reveal cerebral white matterhyperintensities, with delayed posthypoxic leukoencephalopathy ordiffuse brain atrophy. Management of these patients requires theidentification of accompanying drug ingestions, especially in the settingof intentional poisoning, fire-related toxic gas exposures, andinhalational injuries. Conventional therapy is limited to normobaricand hyperbaric oxygen, with no available antidotal therapy. Althoughhyperbaric oxygen significantly reduces the permanent neurologicaland affective effects of CO poisoning, a portion of survivors still havesubstantial morbidity. There has been some early success in therapiestargeting the downstream inflammatory and oxidative effects of COpoisoning. New methods to directly target the toxic effect of CO, suchas CO scavenging agents, are currently under development