May 2019 By PsychDB.com

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.

Prevalence

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]

Risk Factors

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).

Delirium Risk Factors

Modifiable Essentials Modifiable Medical Non-modifiable
• Sensory impairment (hearing or vision)
• Immobilization (catheters or restraints)
• Environment (for example, admission to an intensive care unit)
Pain
• Emotional distress
• Sustained sleep deprivation
• Medications (e.g. - sedative hypnotics, narcotics, anticholinergic drugs, corticosteroids, polypharmacy, alcohol withdrawal or other drugs)
• Acute neurological diseases (e.g. - acute stroke [usually right parietal], intracranial hemorrhage, meningitis, encephalitis)
• Ongoing illness (e.g. - infection, iatrogenic complications, acute illness, anemia, dehydration, poor nutrition, trauma, fractures, HIV)
• Metabolic derangement
• Surgery
Dementia or cognitive impairment
• Advancing age (>65 years)
• History of delirium, stroke, neurological disease, falls or gait disorder
• Multiple comorbidities
• Male sex
• Chronic renal or hepatic disease
Criterion A

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

Criterion B

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.

Criterion C

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

Criterion D

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.

Criterion E

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.

Specifiers

Specifiers

Specify if:

  • Substance intoxication delirium: Criteria A and C predominate in the clinical picture and when they are sufficiently severe to warrant clinical attention
  • Substance withdrawal delirium: Criteria A and C predominate in the clinical picture and when they are sufficiently severe to warrant clinical attention
  • Medication-induced delirium: When criteria A and C arise as a side effect of a medication taken as prescribed.
  • Delirium due to another medical condition: There is evidence from the history, physical examination, or laboratory findings that the disturbance is attributable to the physiological consequences of another medical condition.
  • Delirium due to multiple etiologies: There is evidence from the history, physical examination, or laboratory findings that the delirium has more than one etiology (e.g., more than one etiological medical condition; another medical condition plus substance intoxication or medication side effect).

Severity Specifier

Specify if:

  • Acute: Lasting a few hours or days
  • Persistent: Lasting weeks or months

Hyperactive or Hypoactive Specifier

Specify if:

  • Hyperactive: The individual has a hyperactive level of psychomotor activity that may be accompanied by mood lability, agitation, and/or refusal to cooperate with medical care.
  • Hypoactive: The individual has a hypoactive level of psychomotor activity that may be accompanied by sluggishness and lethargy that approaches stupor.
  • Mixed level of activity: The individual has a normal level of psychomotor activity even though attention and awareness are disturbed. Also includes individuals whose activity level rapidly fluctuates.

Hypoactive/Hyperactive/Mixed

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]

Why Is It Important to Identify Delirium?

Delirium has a fluctuating course and can overlap with dementia, which makes it hard to detect. The lack of routine cognitive assessments also makes it hard to monitor changes in a patient's mental status. Delirium is also under appreciated in terms of its importance and consequences. Patients with ongoing delirium have a significantly higher risk of mortality, significant increases in length of stay, increased costs of hospitalization, and increased chance of nursing home placement.[5][6][7][8][9] One final reason includes ageism, the expectation of: “Aren't older people generally confused?”

Delirium is Often Missed!

Doctors and nurses do a poor job of identifying delirium.[10] Even if symptoms are identified, they may be misattributed to depression or dementia. It is particularly under-recognized in patients over age 80, those with hypoactive delirium, impaired vision, and dementia.

Delirium Screening Tools

Name Rater Description Download
Confusion Assessment Method (CAM) Clinician The Confusion Assessment Method (CAM) is a standardized evidence-based tool that allows clinicians to identify and recognize delirium quickly and accurately in both clinical and research settings. It has a sensitivity of 94‐100% and specificity of 90‐95%.[11][12] See the training guide for full instructions. Short Version
Critical Care Version

History

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:

  • Medical and Psychiatric History (acute and chronic)
    • Sensory impairments (hearing/vision)
    • Elimination patterns (urinary and bowel frequency)
  • Recent Surgeries
  • Medication History (Prescription, OTC)
  • Substance Use History (especially for alcohol)
  • Previous cognitive functioning, ADLs, and IADLs
  • History of Presenting Illness (HPI)
    • Onset and course of confusion
    • History previous episodes of delirium (and treatment response)
    • Sleep patterns
  • Social History

DIMS-R

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, or urinary retention. Then consider the medical etiologies below. In geriatric populations, also consider the geriatric giants.

Mnemonic

The mnemonic DIMS-R can be used to remember the common causes of delirium and provide a structured approach:

  • D - Drugs: Is there a drug intoxication, or conversely, a drug withdrawal? Look for sedating medications, anticholinergic medications, and never forget alcohol withdrawal)
  • I - Infections: Is the genitourinary system, chest, skin/soft-issue, or blood infected? If so, consider CXRs or further infectious work up if needed.
  • M - Metabolic: Are there any changes to glucose, electrolytes, extended electrolytes, creatinine, liver enzymes, VBG CO2, TSH, or B12 that would reflect endocrinopathies, renal failure, or liver failure?
  • S - Structural: Think about serious intracranial pathologies like stroke, hemorrhage, seizures, or neoplasms. Neuroimaging may be required.
  • R - Retention: Is there fecal impaction or urinary retention? If so, consider abdominal X-rays, palpation, DRE, disimpaction.

Depression, Delirium, or Dementia?

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-occuring conditions include accelerated and long-term cognitive, functional decline, institutionalization, re-hospitalization, and increased mortality.[16]

A Comparison of Delirium, Dementia, and Depression

Delirium Dementia Depression
Cardinal feature Confusion and Inattention Memory loss Sadness, anhedonia
Onset Acute or subacute Insidious Slow
Course Fluctuating, often worse at night Chronic, progressive (but stable over the course of a day) Single or recurrent episodes; can be chronic
Duration Hours to months Months to years Weeks to years
Level of Conciousness (LOC) Impaired, fluctuates Normal in early stages Normal
Attention (i.e. - able to focus on tasks) Poor Normal (except in
late stages)
May be impaired
Orientation (i.e. - date, location) Fluctuates Poor Normal
Memory (i.e. - short-term memory) Poor Poor May be impaired
Hallucinations Common (visual) Rare, except in
late stages (and depends on type of dementia)
Not usually (only if psychotic depression)
Delusions Fleeting, non-systematized Often absent Not usually (only if psychotic depression)
Psychomotor Increased (hyperactive) or reduced (hypoactive) No Yes
Reversibility Yes Rarely Yes
EEG Findings Moderate to severe background slowing Normal or mild diffuse slowing Normal (usually)
Delirium should be thought of as a symptom, not a diagnosis. That is, you must recognize it and treat the underlying condition causing the delirium! Also don't forget that delirium is often multifactorial in etiology and therefore requires a multifactorial approach.

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]

Baseline

Routine investigations include: CBC, electrolytes, BUN/Cr, Ca, Mg, phosphate, LFTs, glucose, TSH, oxygen saturation or ABGs, urinalysis, CXR, and ECG.

Neuroimaging

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.

EEG

In some settings, EEGs may be used to identify delirium. EEG features such as posterior dominant rhythm and visual analysis of EEG features have approximately 80% accuracy in differentiating delirious from non‐delirious patients[21][22][23] EEGs may also be useful in identifying occult seizures and differentiate delirium from psychiatric disorders.

Non-pharmacological

In non-ICU setting patients, always start with non-pharmacological interventions first, both in the prevention and management of delirium.[24][25][26] Multiple risk factors should be mitigated as suggested by the table below:

Non-pharmacological Delirium Prevention

Risk Factor Intervention
Cognitive impairment Orient the patient by having a clock, watch, or calendar. Have a board with team member names, a schedule, ongoing communication to reorient them (e.g. - remind the patient where they are, get a sitter, asking family members to stay, asking family to bring items that can keep patient occupied). Do therapeutic activities including: cognitively stimulating activities TID (e.g. - current events, word games, structured reminiscence [get them to recall events in the past]).
Sleep deprivation Warm drinks, relaxation tapes, back massages at night. Enhance sleep by implementing unit‐wide noise reduction and schedule adjustments to allow sleep. Coordinate schedules (drugs, vitals, procedures) to allow uninterrupted sleep at night (low noise and lighting). Encourage normal sleep–wake cycles (open blinds, encourage wakefulness and mobility during daytime)
Immobility Implement early mobilization including ambulation or active range of motion exercises TID. Minimize use of catheters, IVs, and restraints.
Visual impairment Make sure they have visual aids such as glasses, and other adaptive equipment. Reinforce use of aids daily.
Hearing impairment Make sure they have hearing aids, portable amplifying devices, earwax disimpaction if needed, and special communication techniques. Reinforce use of aids daily.
Volume depletion Early recognition and repletion with fluids
Enivronment Avoid putting delirious patients in the same room together, and minimize room changes

Medication Review

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.[27]

Pharmacological

ABC! Always Be Conservative

Pharmacologic management should only be used if the symptoms of delirium threaten the patient's own safety, the safety of others, or would result in the interruption of essential therapy. Always start low and go slow, even if other healthcare providers might insist on higher doses earlier. (Remember that no drug is currently approved by any regulatory agency for the treatment of hospital associated delirium).
Don't forget to order a baseline ECG for a QTc, especially if you are starting out with haloperidol.

Most studies have shown that haloperidol (at doses < 3.5 mg daily), risperidone, and olanzapine were all equally effective in treating delirium. There is no evidence that prophylactic pharmacologic treatment works.[28] There is some emerging evidence that melatonin and melatonin agonists may be effective in the prevention and management of delirium.[29][30]

Pharmacological Management of Delirium

Medication Use Recommended Dosing Side Effects Clinical Pearls
Haloperidol First-line 0.5‐1 mg PO/IM bid and q4h PRN Extrapyramidal Symptoms (EPS) at higher doses (> 3mg), QTc prolongation, and neuroleptic malignant syndrome, somnolence, falls. Both typical and atypical antipsychotics increase the risk of death and cerebrovascular events, compared with placebo in elderly patients (> 65 years) with dementia.[31] In the elderly with Parkinson's disease or Lewy Body Dementia, atypical antipsychotics are preferred.
Risperidone First-line 0.5 mg BID Extrapyramidal Symptoms (EPS) (less likely than typicals like haloperidol, but still a risk, especially at higher doses), QTc prolongation, neuroleptic malignant syndrome, somnolence, falls. Both typical and atypical antipsychotics increase the risk of death and cerebrovascular events, compared with placebo in elderly patients (> 65 years) with dementia.[32] In the elderly with Parkinson's disease or Lewy Body Dementia, atypical antipsychotics are preferred.
Olanzapine First-line 2.5‐5 mg PO daily Same as risperidone Both typical and atypical antipsychotics increase the risk of death and cerebrovascular events, compared with placebo in elderly patients (> 65 years) with dementia.[33] In the elderly with Parkinson's disease or Lewy Body Dementia, atypical antipsychotics are preferred.
Quetiapine First-line 25 mg BID Same as risperidone Both typical and atypical antipsychotics increase the risk of death and cerebrovascular events, compared with placebo in elderly patients (> 65 years) with dementia.[34] In the elderly with Parkinson's disease or Lewy Body Dementia, atypical antipsychotics are preferred.
Lorazepam Second-line 0.5‐1 mg PO q4h PRN Paradoxical reactions, respiratory depression, sedation/somnolence, falls. This may worsen or prolong delirium! Really should only be used for patients with alcohol withdrawal, or patients with antipsychotic sensitivity (i.e. - Parkinson's Disease (PD) or Lewy Body Dementia (LBD))

ICU vs. Non-ICU Patients

The management of delirium in ICU patients may be different compared to a general medical ward. Recent trials have shown that antipsychotics may have limited efficacy in ICU patients with hypoactive delirium.[35][36]

Specialist Involvement

Proactive involvement with a specialist geriatrics consultation team may also play a role in reducing delirium in acute hospital settings.[37]

Delirium may serve as a marker for future cognitive decline and risk for future development of dementia.[38] Incomplete recovery from delirium (even after discharge from hospital) can be common, and patients may need weeks or months to gradually recover.[39] Some patients may have vivid recollections of their hospitaliation after an episode of delirium, and in some cases may develop posttraumatic stress disorder.[40] Thus close post-discharge follow up and monitoring should be done for high-risk patients.

For Providers