The neurotoxicology of carbon monoxide - Historical perspective and review.

Carbon monoxide (CO) has been recognized as a poison for centuries, and remains one of the most common causes of both accidental and deliberate poisoning worldwide. Despite this, there are widespread misconceptions with regards to the mechanisms, diagnosis and outcomes of CO induced poisoning such as the idea that CO poisoning is rare; that carboxyhaemoglobin levels above 20% and loss of consciousness are required before nervous system damage ensues; and that the binding of CO to haemoglobin is the only mechanism of toxicity. Prevention and diagnosis of CO poisoning is hampered by the lack of awareness of CO as a cause of illness, among both the general public and healthcare professionals. To complicate matters further there is no standardized definition of CO poisoning. Carboxyhaemoglobin levels are often used as a marker of CO poisoning, yet plasma levels rapidly reduce upon removal of the source and are therefore an unreliable biomarker of exposure and tissue damage. Adverse neuropsychiatric outcomes after CO poisoning are difficult to define, especially as they fluctuate, mimic other non-specific complaints, and are not present in all survivors. This paper challenges a number of misconceptions about CO poisoning which can result in misdiagnosis, and consequently in mismanagement. We illustrate how recent developments in the understanding of CO toxicology explain the particular susceptibility of the central nervous system to the effects of CO exposure. Crown