Delirium

Acute confusional state secondary to an organic brain disorder that is:

Delirium tremens is a subtype of delirium occurring 48-72 hours after alcohol withdrawal, and is covered elsewhere.

Epidemiology and Risk Factors

Delirium is exceedingly common in inpatients:

  • Occurring in:
    • ~70% of ventilated ICU patients
    • ~50% of surgical patients
    • ~30% of medical patients
  • Majority are hypoactive delirium

Despite this documented high prevalence, it is likely delirium is still under-diagnosed.

Risk Factors
Modifiable Non-Modifiable
  • Infection
  • Hypoxia
  • Hypercarbia
  • Acidosis
  • Hyponatraemia
  • Medications
    • Anticholinergic
    • Opioids
    • Sedatives
    • Polypharmacy
  • Physical
    • Restraints
    • IDC
    • Immobility
  • Supportive
    • Constipation
    • Dehydration
    • Pain
  • Age
  • Pre-existing cognitive impairment
  • Dementia
  • Depression
  • Hepatic impairment
  • Institutionalised prior to admission

Pathophysiology

Poorly understood; proposed mechanisms include:

  • TNF-α activation in microglia
  • Altered cerebral blood flow
  • Thalamic dysfunction
  • Relative dopamine excess

Aetiology

Clinical Manifestations

Diagnostic Approach and DDx

Screening for delirium is recommended:

  • By major intensive care societies
  • Regularly
    • Usually daily in appropriate patients.
    • Unclear how this should best be performed in practice
    • Sensitivity and specificity of screening tools varies widely between publications
      Likely affected substantially by implementation and local practice.
  • Using standardised tools
    • Confusion Assessment Model (CAM-ICU)
    • Intensive Care Delirium Screening Checklist (ICDSC)

Both scores are designed for binary prediction (present/absent) of delirium, although quantification of a spectrum of delirium is also possible.

Confusion Assessment Model

The CAM-ICU score is:

  • A point in time assessment
  • Specific but not sensitive for delirium
  • Relatively quick and straightforward to perform
  • Requires prior calculation of the RASS

The RASS is a 10-point scale that grades patient arousal from:

  • +4: Combative
    Violent, with immediate danger to staff.
  • +3: Very agitated
    Pulls or removes indwelling devices.
  • +2: Agitated
    Non-purposeful, fights ventilator.
  • +1: Restless
    Anxious but not aggressive.
  • 0: Alert and calm
  • -1: Drowsy
    Sustained (>10s) awakening to voice.
  • -2: Light sedation
    Brief awakening to voice.
  • -3: Moderate sedation
    Movement or eye opening to voice.
  • -4: Deep sedation
    Movement or eye opening to pain.
  • -5: Unarousable
    No response to pain.

Investigations

Bedside:

Laboratory:

Imaging:

Other:

Management

  • Maximise preventative interventions
    Predominantly non-pharmacological.
  • Correct cause
  • Minimise pharmacological intervention
  • Remember the family
    Emphasise delirium is common and transient.

Specific therapy:

  • Pharmacological
    • Antipsychotics
      • Typical antipsychotics
        • Haloperidol
          • 0.5-10mg, usually 1-2mg IV
          • Risk of QTc prolongation
      • Atypical antipsychotics
        Lower extrapyramidal side effects.
        • Olanzapine
          • 2.5-5mg PO BD
          • Can be given via sublingual wafers
        • Quetiapine
          • 12.5-50mg PO BD
        • Risperidone
          • 0.5-1mg PO BD
    • α2-agonists
      • Clonidine
      • Dexmedetomidine
  • Physical
    Non-pharmacological interventions are covered under preventative management, but remain a critical part of treating active delirium.

Extrapyramidal side effects are adverse drug-induced movement disorders secondary to dopamine-receptor antagonism, and include:

  • Dystonia
    Involuntary muscle contraction, with abnormal posturing and repetitive movements.
    • Oculogyric crisis
      Bilateral upward gaze.
    • Opisthotonus
      Severe spine/neck hyperextension.
    • Torticollis
    • Trismus
  • Akathisia
    Physical restlessness.
  • Tardive dyskinesia
    Tongue and facial choreoathetoid movements, which may impair swallowing.
  • Parkinsonism
  • Pharyngeal dystonia
    May precipitate airway crises.

Supportive care:

Disposition:

Preventative:

  • Orientation aids
    • Orientation clues
      • Windows with natural light
      • Clocks
      • Calendars with todays date
      • Verbal statements of the time, date, and location
    • Familiar individuals
      • Family
        • Greatest familiarity
        • Sense of control
        • Sense of safety
      • Nursing and medical staff
  • Minimise disorientation
    • Sensory impairments
      • Hearing aids
      • Glasses
  • Minimise agitation
    • Environmental noise
    • Sleep quality
    • Physical restraints
    • Medical restraints
      • IDC
      • IV lines
  • Address risk factors
    • Minimise sedation
      Avoid deep sedation without good reason.
    • Pain
    • Bowel care
    • Polypharmacy
    • Appropriate oxygenation and haemodynamic target
    • Electrolyte correction
  • Patient diaries
    • Fill gaps in memory after ICU discharge
    • Rationalise traumatic hallucinations

Balancing opioid related harm and pain management is a difficult balancing act. On balance, I am to ensure adequate analgesia (minimising opioid when able, and using lower-risk opioids) and accept some opioid related harm.

Marginal and Ineffective Therapies

  • Benzodiazepines
    Significant independent risk factor for delirium, and recommended only for:
    • Delirium tremens
    • Urgent control of dangerous hyperactive delirium
  • Prophylactic antipsychotics
    May ↓ duration or severity, but no improvement in mortality.
  • Anticholinesterases
    Worsen delirium.
  • Melatonin
    No change in rate of delirium, or quality and quantity of sleep.

Anaesthetic Considerations

Complications

Prognosis

Key Studies

  • Pro-MEDIC (2022)
    • ~850 Australian adults across 12 ICUs with expected ICU admission >72 hours
    • 4mg enteric melatonin nocte for 14 days vs. placebo
    • No change in delirium (by CAM-ICU) or sleep quality or quantity

References

  1. Bersten, A. D., & Handy, J. M. (2018). Oh’s Intensive Care Manual. Elsevier Gezondheidszorg.
  2. Krewulak, K.D., Rosgen, B.K., Ely, E.W., Stelfox, H.T., Fiest, K.M., 2020. The CAM-ICU-7 and ICDSC as measures of delirium severity in critically ill adult patients. PLoS One 15, e0242378.
  3. Wibrow B, Martinez FE, Myers E, et al. Prophylactic melatonin for delirium in intensive care (Pro-MEDIC): a randomized controlled trial. Intensive Care Med. 2022;48(4):414-425. doi:10.1007/s00134-022-06638-9