Carbon Monoxide poisoning: pathophysiology and treatment
Carbon monoxide (CO) is a common poison worldwide, effecting roughly160/100,000 individuals annually although incidence may be higher in some developing counties. Hospital visits in the USA for CO number ~50,000/year, with ~1,300 deaths. Accidental exposures account for the majority of non-fatal poisonings, and are estimated in the USA to cost over $1 billion annually for direct hospital care and lost earnings. CO-mediated biological effects are due to an interplay of responses arising from competition among CO, nitric oxide (.NO) and oxygen (O2). Health risks are related to cardiac and neurological injuries. CO kills via the well-recognized hypoxic stress due to carboxyhemoglobin (COHb). It also causes brain injuries in ~25-50% of survivors from severe poisoning. Neurotoxicity involves perivascular oxidative stress and inflammatory responses. Based on several lines of reasoning, hyperbaric oxygen therapy (HBOT) has been used to treat acute CO poisoning, although its acceptance worldwide is variable. Animal models indicate that some neurotoxicity results from perivascular oxidative stress, neutrophil adherence to endothelium and inflammatory responses in brain which involve modifications to myelin basic protein (MBP). Cerebral white matter changes identified by MRI are common in patients with neurological sequelae, MBP elevations in CSF are correlated with development of neurological sequelae, and elevations are diminished in those treated with HBOT. In addition to alterations of MBP, elevations in TNFα, interleukin (IL)-1β, IL-6, and NF-kB occur in cerebral cortex and hippocampus post-CO. CO patients suffering encephalopathy exhibit increases in plasma IL-1β and several other cytokines. Recent studies of common inflammatory responses have documented roles for so-called extracellular vesicles (EVs), but there are many questions pertaining to their actions. Animal models have demonstrated elevations of microparticles (MPs) in blood due to CO poisoning. When these MPs are harvested and injected into naïve animals, the recipients exhibit the same functional deficits and biochemical changes in brain as do animals directly exposed to CO. There are mechanistic links between formation of MPs and so-called inflammasomes that generate IL-1β, and in a number of disorders vascular damage due to MPs can be directly linked to IL-1β. Crucially, HBOT was recently shown to inhibit formation of MPs and production of mature IL-1β, which adds to the list of potential therapeutic mechanisms of action in CO poisoning. This presentation will summarize current clinical and research findings related to CO poisoning and its treatment.