Delirium

Delirium is a serious neuropsychiatric syndrome characterized by an acute confusional state with global impairments in attention and cognition.^[1] Delirium is often associated with a disturbance in the sleep-wake cycle, including daytime sleepiness, nighttime agitation, insomnia, excessive sleepiness, or wakefulness throughout the night. In some cases, complete reversal of the night-day sleep-wake cycle can occur.

• The community prevalence of delirium is low, between 1 to 2%, but increases with age, rising to 14% in individuals older than 85 years.
• The prevalence is 10% to 30% in older individuals presenting to emergency departments, where the delirium is a result of a medical illness. Rates are highest in post-surgical (hip surgery), palliative care for advanced cancer (up to 80%), ICU (up to 70%) and dementia populations.^[2]

• The development delirium can be due to multiple risk factors. Some of these risk factors are modifiable and thus a target in delirium prevention. Up to 40% of cases of delirium are preventable.^[3]
• In elderly patients, dementia is the most common risk factor (in up to two-thirds of all cases of delirium).

A disturbance in attention (i.e. - reduced ability to direct, focus, sustain, and shift attention) and awareness (reduced orientation to the environment).

The disturbance develops over a short period of time (usually hours to a few days), represents a change from baseline attention and awareness, and tends to fluctuate in severity during the course of a day.

An additional disturbance in cognition (e.g. - memory deficit, disorientation, language, visuospatial ability, or perception).

The disturbances in Criteria A and C are not better explained by another preexisting, established, or evolving neurocognitive disorder and do not occur in the context of a severely reduced level of arousal, such as coma.

There is evidence from the history, physical examination, or laboratory findings that the disturbance is a direct physiological consequence of another medical condition, substance intoxication or withdrawal (i.e. - due to a drug of abuse or to a medication), or exposure to a toxin, or is due to multiple etiologies.

• Patients can present with hypoactive delirium, where they appear lethargic, somnolent, and sluggish. This is often not recognized as they do not cause a “disturbance,” and may be mistakenly identified as depressed.
• In hyperactive delirium, patients are often agitated, hallucinating, and have inappropriate behaviour. Some patients can have a mixed delirium where they have a combination of both (fluctuations between agitation and lethargy).^[4]

Obtaining a good history is key and should be the first step when seeing a patient with delirium. Do not rely on just self-report by the patient. Use as many collateral sources as possible, including family, staff, and the chart.

The following items on history should always be obtained:

Before even considering pharmacologically managing delirium, always think about what could be causing delirium in the first place! First consider the non-medical issues that could cause an altered level of consciousness, including: pain, vision deficits, hearing deficits, hunger, constipation (i.e., fecal loading), or urinary retention. Then consider the medical etiologies below. In geriatric populations, also consider the geriatric giants.

A non-exhaustive list of potential causes for delirium include:

• In the geriatric population, it is important to differentiate between delirium, dementia, and depression, which can be difficult to distinguish.^[13][14][15] The prevalence of delirium superimposed on dementia ranges anywhere from 22% to 89% of hospitalized and community populations aged 65 and older with dementia.
• The negative outcomes of these co-occurring conditions include accelerated and long-term cognitive, functional decline, institutionalization, re-hospitalization, and increased mortality.^[16]

• One of the prevailing theories of the pathogenesis of delirium is acetylcholine deficiency.^[17]
• Acetylcholine plays an extensive role in attention and consciousness, and deficiencies are thought to result in the core symptoms of both hypoactive and hyperactive delirium. These symptoms include inattention, disorganized thinking, and hallucinations.^[18][19] Dopaminergic excess, inflammation (via interleukin-1, interleukin-2, interleukin-6, TNF-α, interferon), chronic stress (resulting in hypercortisolism), and diurnal changes are also thought to be factors that lead to the development of delirium.^[20]

• Routine investigations include:
  • Bloodwork
    • CBC, electrolytes, BUN/Cr, electrolytes (Na, Cl), extended electrolytes (Ca, Mg, phosphate), CK
    • LFTs, lipase, albumin, troponin
    • Random glucose, B12
    • TSH, free T3, free T4 (Hashimoto's)
    • Oxygen saturation or ABGs
  • Imaging
    • Chest X-Ray (CXR) (pneumonia)
    • Abdominal X-Ray (fecal loading or constipation, especially in patients with dementia or confusion who cannot report this accurately)
    • CT Head (acute stroke or intracranial abnormality)
    • ECG
  • Infectious etiology work up includes HIV, syphilis (EIA), lactate
  • Inflammatory work up, including CRP, lupus (ANA
, ESR, CRP)
  • Urinalysis (cultures), urine drug screen, urine/serum toxicology screen

• Neuroimaging generally has low yield in detecting delirium. Only consider this if there are new focal neurologic signs, a history of head trauma (suggesting a subdural hemorrhage), infections (encephalitis), or if there is no identifiable cause or improvement.

• EEGs may also be useful in identifying occult seizures and differentiate delirium from psychiatric disorders.
• Certain features on EEG have close to 80% accuracy in differentiating delirious from non‐delirious patients, including:^{[21][22][23][24]}
  • Slowing or dropout of the posterior dominant rhythm
  • Reduced alpha wave frequency^[25]
  • Generalized theta or delta slow-wave activity
  • Poor organization of the background rhythm and and diffuse slowing
  • Loss of reactivity of the EEG to eye opening and closing

In non-ICU setting patients, always start with non-pharmacological interventions first, both in the prevention and management of delirium.^[27][28][29] Multiple risk factors should be mitigated as suggested by the table below:

• Medications that might be contributing delirium should be withdrawn whenever possible. Psychoactive medications, including those with anticholinergic effects, and/or drugs recently initiated or with a dosage change are more likely to be precipitants of delirium.
• If the medication cannot be withdrawn, the lowest possible dose should be used, or substituted with a similar but lower risk medication.^[30]

• Antipsychotic medications should not be used as standard treatment for delirium, and should only be considered for patients with delirium experiencing severe agitation or distress.^[31]
• Most studies have shown that haloperidol (at doses < 3.5 mg daily), risperidone, and olanzapine are all equally effective in managing delirium.
• There is no evidence that prophylactic or preventative pharmacologic treatment works.^[32][33]
  • The adverse effects of antipsychotic medications include sedation, hypotension, falls, parkinsonism, QT interval prolongation and aspiration pneumonia.^[34]
  • If there are QTc prolongation concerns, then lower-risk antipsychotics such as aripiprazole can also be used.^[35]
• Antipsychotics if prescribed, should be at the lowest effective dose for the shortest possible duration and be reevaluated at or shortly after discharge.^[36]
• There is some emerging evidence that melatonin and melatonin agonists may be effective in the prevention and management of delirium.^[37][38]

• Proactive involvement with a specialist geriatrics consultation team may also play a role in reducing delirium in acute hospital settings.^[47]

• Delirium may serve as a marker for future cognitive decline and risk for future development of dementia.^[49] Incomplete recovery from delirium (even after discharge from hospital) can be common, and patients may need weeks or months to gradually recover.^[50] Some patients may have vivid recollections of their hospitaliation after an episode of delirium, and in some cases may develop posttraumatic stress disorder.^[51] Thus close post-discharge follow up and monitoring should be done for high-risk patients.