====== Delirium prevention ======

===== 🛡️ Core Strategies for 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

===== 🏥 Hospital Protocols and Bundles =====

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

===== Systematic review and meta-analysis =====

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.
((de Oliveira HM, Gallo Ruelas M, Zamora FV, Oliveira de Paula G, Oliveira Fonseca PE, Luiz L, Fruett da Costa PR. Efficacy of Ramelteon, Suvorexant, and Lemborexant for Delirium Prevention in Hospitalized Patients: A Systematic Review and Meta-Analysis. Crit Care Med. 2025 Jun 13. doi: 10.1097/CCM.0000000000006737. Epub ahead of print. PMID: 40511987.)).
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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.