Delirium

Definition and DSM-5 criteria. Delirium is an acute disorder of attention and cognition. DSM-5 requires: (i) disturbance of attention and awareness; (ii) acute onset with fluctuation over the day, a change from baseline; (iii) an additional cognitive disturbance; (iv) not better explained by a neurocognitive disorder and not occurring in coma; (v) evidence of a medical cause, substance, withdrawal or multiple aetiologies. DSM-5 and ICD-10 remain the gold standard.

Epidemiology and subtypes. Rates: ICU 30–80%, hospice 26–44%, general medical and oncology wards 18–35%, nursing home/post-acute care 16%; cardiac and vascular surgery 29–50%; hip fracture repair 12–48%. Subtypes are hyperactive, hypoactive and mixed; hypoactive is the commonest and the most frequently missed. Special phenotypes: delirium superimposed on dementia (DSD) — the hardest to diagnose and slowest to resolve, postoperative delirium (POD) versus postoperative cognitive dysfunction (POCD), ICU delirium, subsyndromal and persistent delirium.

Pathophysiology. The Systems Integration Failure Hypothesis (SIFH) unifies the competing theories: neuronal ageing, oxidative stress, neuroendocrine change, diurnal dysregulation and neuroinflammation together disrupt the neurotransmitter systems (cholinergic, dopaminergic, adrenergic, histaminic, serotonergic) and neuronal network connectivity. This explains both the heterogeneous presentation and why single-target drugs such as antipsychotics repeatedly fail in trials.

Predisposing and precipitating factors. The more predisposing factors present (age, cognitive impairment, frailty, sensory impairment, multimorbidity, polypharmacy), the smaller the precipitant needed. The full list is the DELIRIUM IS VERY PAINFUL mnemonic. Deliriogenic drugs to know: benzodiazepines (especially IV), antipsychotics, corticosteroids, H2-blockers in renal impairment, opioids (especially pethidine), muscle relaxants, antimuscarinics for overactive bladder, first-generation antihistamines, and zolpidem.

Diagnosis and evaluation. Screen all hospitalised older adults at least daily (weekly in post-acute care, monthly in long-term care) with CAM (sensitivity 94%, specificity 89%), 3D-CAM, 4AT or CAM-ICU. Never explain away a positive item. When in doubt, assume delirium until proven otherwise. Investigate in a targeted way; imaging, LP and EEG only on specific indication.

Management and prognosis. (i) Identify and treat every precipitant. (ii) Multicomponent non-pharmacologic care is the mainstay — reorientation, sensory aids, sleep protocol, early mobilisation, hydration, removal of tethers, family presence, interprofessional delivery. (iii) Behaviour is managed by T-A-DA (Tolerate, Anticipate, Don't Agitate), not restraints. (iv) No drug is FDA- or EMA-approved for delirium; benzodiazepines must not be used except in alcohol or benzodiazepine withdrawal; antipsychotics only for severe agitation posing danger, at the lowest dose for the shortest time, after non-pharmacologic measures fail. Prognosis: up to 45% are still delirious at discharge; persistence is 33% / 26% / 21% at 1, 3 and 6 months; delirium doubles the rate of cognitive decline for five years in Alzheimer's disease.

The SCCM PADIS Focused Update 2025 (Crit Care Med 2025) has hardened the drug position: it recommends against using haloperidol, atypical antipsychotics, dexmedetomidine, statins or ketamine to prevent delirium, and could issue no recommendation either for or against antipsychotics for treatment because their effect on outcomes is minimal. Its three positive conditional recommendations are dexmedetomidine over propofol when light sedation or delirium reduction is the priority, enhanced mobilisation/rehabilitation, and melatonin.