Ia.ble.2 lists the many possible causes of delirium, using the well-known I WATCH DEATH mnemonic. (i5) However, the links between these insults and the neuropathogenesis of delirium are poorly understood. Electrophysiological, brain imaging, and neurotransmitter studies all show a generalized disturbance of cortical and subcortical function. It is unclear whether there are subtypes associated with different mechanisms, though delirium tremens is said to have a different electroencephalographic pattern of fast activity, from the slow activity seen in other forms of delirium. (4) There is limited evidenced regarding mechanisms after cardiac surgery (the possible role of microemboli) and some other types of disorder, including renal failure, and following trauma.

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Table 2 Causes of delirium

There is evidence of increased susceptibility to delirium with increasing age. This is generally ascribed to reduced 'cerebral reserve', which may be related to reduced acetylcholinesterase activity, and to cerebrovascular changes. Pre-existing brain pathology of any kind (e.g. degenerative conditions such as Parkinson's disease, cerebrovascular disease, dementia, chronic infections such as HIV) is likewise a risk factor. The more severe the precipitating illness and the more acute its onset, the more likely it is to be followed by delirium.(!5) A reduced serum albumin level is an important contributory factor in many cases of chronic disease. Decreased protein binding of psychoactive and other drugs leads to higher concentrations of the free drug, and hence to greater toxicity at a given dose level.

Psychoactive drugs of all types are especially prone to cause, or contribute to, delirium. This includes antipsychotics (especially those with anticholinergic actions, notably thioridazine), antidepressants, and hypnotics.

There has been considerable research on some neuropsychiatric consequences (including delirium) of some disorders (such as liver and renal failure) and treatments. An example of the latter is the now considerable evidence of the acute neuropsychological deficits following cardiac surgery, some of which are transient but which may also be permanent. Clinical and psychometric features have been related to perfusion procedures, the relationship to postoperative microembolic damage, and the role of various protective procedures.(6)

A further particularly important example is intoxication by alcohol, which may cause delirium. This also applies to other psychoactive substances, licit or otherwise, such as LSD (lysergic acid diethylamide) and MDMA ('ecstasy', methylenedioxymethamphetamine). Most such episodes occur in the community, however, and do not present to doctors. Delirium tremens (delirium due to sudden withdrawal of alcohol in a person chemically dependent on alcohol) is a common cause of referral in liaison psychiatric practice. It is important because it carries a significant morbidity and mortality, yet it is largely preventable and treatable. (See also Ch§2t§I,4.2,..2...,3.)

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