Pathophysiology
Clinical meaning
Delirium is an acute, fluctuating disturbance in attention, awareness, and cognition that develops over hours to days and represents a medical emergency indicating underlying physiological derangement. It is NOT a psychiatric disorder but rather a manifestation of acute brain dysfunction caused by medical illness, medication effects, metabolic derangement, or physiological stress. Delirium affects 20-30% of general medical inpatients, 50-80% of ICU patients on mechanical ventilation, 15-53% of post-surgical patients (highest after hip fracture repair and cardiac surgery), and up to 87% of patients receiving palliative care at the end of life. Despite its high prevalence, delirium is underdiagnosed in 50-70% of cases, particularly the hypoactive subtype, because it is often mistaken for depression, fatigue, or dementia. The pathophysiology of delirium is multifactorial and incompletely understood, but several interconnected mechanisms have been identified. The neuroinflammatory hypothesis proposes that systemic inflammation (from infection, surgery, trauma, or critical illness) activates peripheral immune cells that release pro-inflammatory cytokines (IL-1beta, IL-6, TNF-alpha) into the systemic circulation. These cytokines cross the blood-brain barrier (BBB) -- either through circumventricular organs where the BBB is naturally fenestrated, through...