Oxygen is the proverbial 'double-edged sword' in that it is a necessity for life in moderation and toxic and detrimental to life in excess. This too is the dilemma in hyperbaric oxygen (HBO) treatment in cerebral ischemic-anoxic insults such as stroke, head injury, near drowning, asphyxia, cardiac arrest, etc., i.e. the brain at risk, where regions of ischemia are beside regions of marked hyperemia. The natural heterogeneity of normal brain tissue oxygenation compounds the problem with different microvascular brain regions living at various levels of oxygenation from 0 to arterial PO(2) as an added complication. The application of HBO, whether normobaric or hyperbaric, will result in brain tissue oxygenation ranging from normoxic to highly hyperoxic with the latter possibly exacerbating the injury sustained. On this basis, the application of multiple therapeutic interventions may be considered, for example, HBO in combination with free radical scavengers or inhibitors of free radical generating enzymes. Despite these difficulties in moderating oxygen delivery to treat cerebral ischemic-anoxic insults, overwhelming preclinical evidence indicates that HBO administered during or within 2 hours post-insult effectively attenuates the severity of brain damage sustained. The primary disconnection between pre-clinical and clinical efficacy of HBO then appears to be the time of application. Clinically, HBO therapy is applied at the earliest 6 hours post-insult but usually between 12 hours or longer post-insult. Pre-hospital application of HBO may be required for clear-cut demonstration of clinical efficacy.

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