Impact of sequenced pharmacological optimisation and multicomponent bundle on early delirium severity trajectories in general medical inpatients.

BACKGROUND

Delirium is common in older medical inpatients, associated with prolonged hospitalisation, falls and cognitive decline. Despite recommendations for multicomponent non-pharmacological interventions, the additional benefit of structured pharmacological guidance and the impact on early delirium trajectories remain unclear.

METHODS

This study used a two-phase before-after design in a prospective cohort of 203 inpatients in two university-affiliated acute medical wards. Sixty-four patients received interventions comprising structured pharmacological guidance, educational videos, cognitive activity boards and light therapy. Delirium severity was assessed with the K-4AT on Days 1, 3 and 7. Mixed-effects models estimated time-by-intervention interactions, and dose-response analyses examined cumulative effects. Secondary outcomes included incident delirium, length of stay, falls, ICU transfer and in-hospital mortality. Exploratory paired analyses assessed within-group changes.

FINDINGS: Delirium occurred in 24.1%, associated with older age, prior delirium, psychotropic exposure and illness-severity. The time-by-exposure interaction favoured intervention at Day 7 (exp(β) = 0.40; 95% CI = [0.24, 0.66]; P = .001), with earlier improvements for pharmacologic guidance (Day 3, exp(β) = 0.64 [0.43, 0.95]; P = .026; Day 7, exp(β) = 0.46 [0.28, 0.76]; P = .002). Educational videos were associated with improvement by Day 7 (exp(β) = 0.39 [0.22, 0.67]; P = .001), and cognitive activity boards showed the largest effect (exp(β) = 0.09 [0.04, 0.17]; P < .001) in a small subgroup. A time-by-dose interaction indicated additive benefits with multiple components (Day 7, exp(β) = 0.72 [0.6, 0.85] per component; P < .001). Secondary outcomes did not differ.

INTERPRETATION: Multicomponent bundles combining pharmacological guidance and cognitive stimulation may attenuate delirium trajectories. Pharmacological guidance showed earlier improvements, and combined exposure showed additive benefits. These findings support further development of protocols to reduce delirium burden.