Delirium prevention

1. Identify and Modify Risk Factors Cognitive impairment: screen using tools like the Mini-Cog or MMSE

Sensory deficits: ensure access to glasses and hearing aids

Polypharmacy: review and minimize high-risk medications (e.g., benzodiazepines, anticholinergics, opioids)

Infection/sepsis, dehydration, metabolic disturbances: monitor labs and vitals closely

2. Promote Sleep and Circadian Rhythm Avoid nighttime disturbances

Limit noise and light

Use non-pharmacologic sleep aids (warm drinks, massage, relaxation techniques)

3. Enhance Orientation and Cognition Reorient frequently: clocks, calendars, family photos

Encourage familiar routines

Provide cognitive stimulation (conversation, reading)

4. Early Mobilization Assist with ambulation and physical therapy

Avoid physical restraints

5. Hydration and Nutrition Maintain adequate oral intake

Monitor for constipation or urinary retention

6. Vision and Hearing Optimization Ensure assistive devices are working and available

Address earwax or poor lighting

HELP (Hospital Elder Life Program)

ABCDEF Bundle in ICU (Assess pain, Both awakening and breathing trials, Choice of sedation, Delirium monitoring, Early mobility, Family engagement)

⚠️ High-Risk Settings Post-operative (especially orthopedic and cardiac surgery)

ICU

Palliative care

Nursing homes

de Oliveira et al. systematically searched PubMed, Embase, Cochrane Central Register of Controlled Trials, clinical trial registries, and gray literature databases through November 2024.

Study selection: Randomized controlled trials or observational studies involving hospitalized adults assessing the use of suvorexant, lemborexant, or ramelteon for delirium prevention were included.

Data extraction: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Cochrane guidelines, two reviewers extracted data independently. Quality was assessed using the Grading of Recommendations Assessment, Development, and Evaluation; Risk of Bias in Randomized Studies; and Risk of Bias in Nonrandomized Studies-of Interventions tools. Random-effects meta-analysis pooled risk ratios (RRs) and median differences with 95% CIs.

Data synthesis: Twenty-four studies involving 4489 patients were analyzed, of whom 1752 (39%) received one of the evaluated pharmacotherapies. Pooled analyses showed a significant reduction in delirium prevalence in both randomized trials (RR, 0.60; 95% CI, 0.38-0.97; low certainty) and observational studies (RR, 0.54; 95% CI, 0.43-0.68; low certainty). Exploratory analyses by individual agent did not identify credible subgroup effects (interaction p > 0.1), and medication-specific findings should be interpreted with caution. No significant effects were observed for ventilator days, mortality, or length of hospital or ICU stay (very low certainty).

Conclusions: Sleep-wake regulating pharmacologic agents were associated with 40%-46% relative risk reductions in delirium prevalence, based on low-certainty evidence. Although these findings are promising, the absence of credible subgroup effects limits conclusions about the comparative efficacy of individual agents. Further, high-quality, prospective trials are needed to confirm these results and to clarify the role of specific pharmacologic strategies in delirium prevention. ¹⁾.

This meta-analysis is a classic case of “garbage in, garbage out.” The authors use sophisticated methods to massage underwhelming data into a publishable form. They cloak uncertainty in terms like “promising” and “needs further research,” while the practical takeaway is clear: there is no solid evidence that any of these drugs prevent clinically significant delirium outcomes.

Until we have large-scale, high-quality, head-to-head trials, this meta-analysis should be filed under speculative pharmacology, not evidence-based practice.