The pathophysiology of delirium that is associated
with critical illness remains largely uncharacterized
and may vary depending on the cause.
The increased risk associated with the use of
GABAa agonists and anticholinergic drugs led to
the suggestion that the GABAergic and cholinergic
neurotransmitter systems play a contributory
role. In particular, central cholinergic deficiency
may be a final common pathway. Alternative
hypotheses include excess dopaminergic activity
and direct neurotoxic effects of inflammatory
cytokines. Currently, these hypotheses are unproven,
making pharmacologic management
strategies largely empirical.