title: Carbon Monoxide Poisoning: Pathogenesis, Management, and Future Directions of Therapy.
abstract: Carbon monoxide (CO) poisoning affects 50,000 people a year in the United States. The clinical presentation runs a spectrum, ranging from headache and dizziness to coma and death, with a mortality rate ranging from 1 to 3%. A significant number of patients who survive CO poisoning suffer from long-term neurological and affective sequelae. The neurologic deficits do not necessarily correlate with blood CO levels but likely result from the pleiotropic effects of CO on cellular mitochondrial respiration, cellular energy utilization, inflammation, and free radical generation, especially in the brain and heart. Long-term neurocognitive deficits occur in 15-40% of patients, whereas approximately one-third of moderate to severely poisoned patients exhibit cardiac dysfunction, including arrhythmia, left ventricular systolic dysfunction, and myocardial infarction. Imaging studies reveal cerebral white matter hyperintensities, with delayed posthypoxic leukoencephalopathy or diffuse brain atrophy. Management of these patients requires the identification of accompanying drug ingestions, especially in the setting of intentional poisoning, fire-related toxic gas exposures, and inhalational injuries. Conventional therapy is limited to normobaric and hyperbaric oxygen, with no available antidotal therapy. Although hyperbaric oxygen significantly reduces the permanent neurological and affective effects of CO poisoning, a portion of survivors still have substantial morbidity. There has been some early success in therapies targeting the downstream inflammatory and oxidative effects of CO poisoning. New methods to directly target the toxic effect of CO, such as CO scavenging agents, are currently under development.
authors.affiliation: 1 Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute.|2 Division of Pulmonary, Allergy, and Critical Care Medicine, School of Medicine.
authors.forename: Jason J
authors.identifier: 0000-0003-1347-9148
authors.initials: JJ
authors.lastname: Rose
authors.affiliation: 1 Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute.|2 Division of Pulmonary, Allergy, and Critical Care Medicine, School of Medicine.
authors.forename: Ling
authors.identifier: 0000-0003-4333-3158
authors.initials: L
authors.lastname: Wang
authors.affiliation: 1 Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute.
authors.forename: Qinzi
authors.initials: Q
authors.lastname: Xu
authors.affiliation: 1 Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute.
authors.forename: Charles F
authors.identifier: 0000-0001-9057-4021
authors.initials: CF
authors.lastname: McTiernan
authors.affiliation: 1 Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute.|3 Department of Pharmacology and Chemical, and.|4 Center for Metabolism and Mitochondrial Medicine, University of Pittsburgh, Pennsylvania.
authors.forename: Sruti
authors.initials: S
authors.lastname: Shiva
authors.affiliation: 1 Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute.|2 Division of Pulmonary, Allergy, and Critical Care Medicine, School of Medicine.
authors.forename: Jesus
authors.identifier: 0000-0003-3245-9978
authors.initials: J
authors.lastname: Tejero
authors.affiliation: 1 Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute.|2 Division of Pulmonary, Allergy, and Critical Care Medicine, School of Medicine.
authors.forename: Mark T
authors.initials: MT
authors.lastname: Gladwin
mesh_terms: D002249:Carbon Monoxide Poisoning / Q000175:diagnosis / Q000473:pathology* / Q000628:therapy*; D006801:Humans; D006931:Hyperbaric Oxygenation
keywords: carbon monoxide; carbon monoxide poisoning; mitochondria