376.3 🏥 內科專科考前版

376.3.1 Mechanistic Deep Dive

376.3.1.1 Pathophysiology

  • Neurotransmitter imbalance:
    • ↓ Acetylcholine (key)
    • ↑ Dopamine
    • ↑ Norepinephrine
    • ↑ Glutamate
    • ↓ GABA (or ↑ in some)
    • Cytokines, inflammation
    • Cortisol stress response
  • Multifactorial vulnerability
  • Brain reserve concept

376.3.1.2 Why Anticholinergics?

  • Block central cholinergic transmission
  • Predisposed brain (dementia, age) more vulnerable

376.3.1.3 Inflammatory Hypothesis

  • Cytokines (IL-1, IL-6, TNF) → BBB → neuroinflammation
  • Sepsis, surgery, infection

376.3.2 Recent Trials & Updates

376.3.2.1 DEXmedetomidine to Reduce ICU Delirium (Multiple Trials)

  • Less delirium vs BZDs (MIDEX, PRODEX, SEDCOM, MENDS, DESIRE)
  • Improved outcomes

376.3.2.2 Melatonin / Ramelteon for Prevention

  • Mixed evidence
  • May help in some

376.3.2.3 MIND-USA (2018)

  • Antipsychotics (haloperidol, ziprasidone) did NOT change delirium duration or outcome
  • Reinforces non-pharm primary approach

376.3.2.4 HEMORICAL: COVID-19 Delirium

  • COVID-19 high delirium rates
  • Multifactorial

376.3.2.5 POCD (Postoperative Cognitive Dysfunction)

  • Distinct from delirium
  • Cognitive decline post-surgery
  • Especially after cardiac surgery
  • Long-term implications

376.3.3 High-Yield Specialist Points

376.3.3.1 Charcot-Bouchard Approach

  • Not strictly delirium but mention

376.3.3.2 Delirium Tremens (DTs)

  • 48-96 hr after last drink
  • Severe autonomic + confusion + hallucinations + seizures possible
  • Mortality 5-15% untreated
  • BZDs (lorazepam, diazepam) titrated
  • Thiamine + glucose + magnesium

376.3.3.3 Wernicke vs Delirium Tremens

  • Wernicke: ophthalmoplegia + ataxia + confusion (triad, often subtle)
  • DTs: severe autonomic + hallucinations
  • Often co-occur
  • Always give thiamine before glucose

376.3.3.4 Hospital-Acquired Delirium Prevention

  • HELP program (Hospital Elder Life Program)
  • Inouye 1999 NEJM paradigm-shifting trial
  • Reduces incidence ~ 40%

376.3.3.5 Specific Drug Issues

Meperidine: - AVOID in elderly - Normeperidine accumulates → seizures + delirium - Use morphine or hydromorphone instead

Diphenhydramine: - “PRN sleep” in hospital → delirium - Use melatonin or trazodone instead

H2 Blockers (Ranitidine, Famotidine): - Can cause confusion (especially elderly with renal) - Use PPI instead

Steroids: - High-dose pulse → “steroid psychosis” - Or just delirium

Levetiracetam: - Behavioral side effects (irritability, depression) - Can mimic delirium

376.3.3.6 Catatonia

  • Stupor or excitement
  • Posturing, waxy flexibility, mutism
  • Many causes (psychiatric, medical, drug)
  • May mimic delirium
  • Lorazepam challenge (1-2 mg IV) often diagnostic
  • ECT for refractory

376.3.3.7 Encephalopathy Types

Type Features
Hepatic Asterixis, fetor hepaticus, triphasic EEG
Uremic Asterixis, myoclonus, improve with HD
Hypertensive (PRES) HTN, edema, posterior
Septic Common in ICU, multifactorial
Hashimoto Steroid-responsive, anti-TPO
Post-anoxic After cardiac arrest
Wernicke Triad, thiamine deficient
Drug-induced Various
Autoimmune NMDA-R, others

376.3.3.8 Post-COVID Brain Fog

  • Cognitive symptoms persist
  • May overlap with delirium recovery
  • Multifactorial

376.3.3.9 Outcomes

  • Delirium → 2-3x mortality at 1 year
  • 30% with persistent delirium 6 months
  • Accelerated dementia trajectory
  • Long-term cognitive deficits

376.3.4 Pearls

  • Delirium = acute + fluctuating + inattention + cognitive + organic
  • Hypoactive most common + most missed
  • CAM for diagnosis
  • HELP program for prevention
  • Treat underlying + minimize culprit drugs
  • Pharm = last resort (low-dose antipsychotics if needed)
  • AVOID BZDs unless alcohol/BZD withdrawal
  • Dexmedetomidine preferred in ICU
  • Meperidine, diphenhydramine, anticholinergics common iatrogenic culprits
  • Delirium → ↑ mortality + accelerated cognitive decline
  • Catatonia mimics — lorazepam challenge