BMH Medical Journal

BMH Med. J. 2020; 7 (Suppl): Early Online. Geriatrics & Gerontology Initiative: International Workshop on Care of the Elderly

Abstract

Few conditions demonstrate the relationship between psychological states and medical illness as clearly as delirium. It is at once a frequent reason for referral to psychiatrists by medical practitioners, and a condition that is frequently missed among sick in-patients. This is important because up to half of post-operative patients and even up to 87% of ICU patients over the age of 65 have been diagnosed with delirium.

Keywords: Delirium, Elderly

What is delirium?

The word “delirium” refers to a global deficit in cognitive capacities. Other terms that have been used, include acute brain syndrome, acute cerebral insufficiency, encephalopathy, toxic psychosis, organic psychosis, or the organic mental syndrome. However, as these terms may be imprecise or suggest an etiology, delirium remains the standard term.

The diagnosis of delirium is clinical, and at its core involves identification of a pattern of signs and symptoms of clouding of consciousness, impaired attention, and altered states of arousal (hyper- or hypo- arousal).

Other manifestations might include alterations in the sleep-wake cycle, perceptual abnormalities (illusions or hallucinations), changes in mood, suspiciousness or delusions, speech articulation abnormalities, or other cognitive deficits.

These symptoms typically develop over hours or days and fluctuate in their intensity (although less overt symptoms persist even into periods of relative improvement). Delirium is a reliable indicator of physical disease, including the toxic effects of a number of poisons. Hence, delirium mostly runs an acute course, either deteriorating or resolving fairly rapidly in line with the underlying condition.

Apart from those specific to the causal agent(s), delirium itself presents a number of risks, primarily related to sufferers’ inability to care for themselves or dependence on outside assistance. Falls, injuries, infections, wandering, dehydration or starvation may supervene, complicating the clinical picture. A confused, agitated person may also pose a risk to themselves and others around them.

Clinical evaluation

At the bedside, the typical history is that of a deterioration or change in arousal levels that develops rapidly. The onset may be closely associated with an identifiable medical illness, which makes the diagnosis easier.

Along with fluctuations in arousal (manifested by alternating periods of agitation and lethargy), patients make errors in reporting their current place, time, or in recognizing people around them. Notably, the characteristic symptom is of misrecognition in all these domains, rather than a refusal to respond, or claims of ignorance - thus a son may be mistaken for a brother, or the hospital for the patient’s home. Orientation to time is usually lost first, followed by that to place and to person. The ability to recognize oneself is almost never lost except in the most profound cases, and should be interpreted cautiously.

Disorientation may also manifest as spatial confusion, with the patient getting lost within the home (example on the way to the bathroom) or wandering out of their homes. This is most clearly identifiable when present even in familiar spaces.

Attention may be impaired in a number of ways that can be observed by clinicians or carers:

- An inability to focus, with the patient instead appearing vacant, withdrawn or perplexed (often described as being “muddled”)
- Easy distraction by irrelevant stimuli, or a failure to be distracted by relevant stimuli (example voiding urges)
- Disproportionate responses to stimuli (example an easy startle)
- Failure to shift attention, or to sustain attention during a task (example stopping midway through eating or conversation)

This attentional disturbance may be an important factor in patients’ difficulty in retaining new information during a period of delirium, and for caregivers’ complaints about incomplete recall of events during this period.

As noted previously, symptoms fluctuate, but are usually worst at night, a phenomenon referred to as “sundowning”. Patients may have a reversal of the sleep-wake cycle, reduced or increased overall sleep, and/or vivid dreams.

Perceptual abnormalities such as hallucinations (typically visual or tactile) or illusions (mostly visual) may occur. Most often these are frightening, and contribute to patients’ agitation. An exception is the so-called “Lilliputian” hallucinations seen in complicated alcohol withdrawal syndrome, which are usually experienced as pleasant. Abnormal tactile experiences may be associated with characteristic behaviours, where patients apparently pick at imaginary insects crawling on their skin or bedclothes.

Mood symptoms fluctuate, with the patient appearing by turns perplexed, fearful, euphoric or depressed.

History-taking should also establish a baseline, and clues towards more longstanding cognitive or functional limitations. Very often, retirement or a medical illness may cover up serious cognitive impairments, which families may rationalize away. Normal ageing itself is associated with reduced cognitive flexibility, slower processing of information and reduced sleep.

The method of assessment

The assessment of the mental state in delirium is of vital importance. Due to fluctuations in mental state, typical features these should be clearly noted when they are present.

Setting: If feasible, the assessment should reduce distractions that the patient may be sensitive to. Moreover, as these patients are easily agitated, the presence of familiar persons may be helpful. Thus, assessments are best done in a quiet room with good lighting, preferably with a carer present.

Clear communication: stand or sit in a position comfortably within the person’s field of vision. Speak in a loud, clear voice with simple sentences. Make sure the patient is wearing spectacles and hearing aids.

Getting the best possible performance: Due to patients’ limited attention spans, they may falter on simple testing, and may require instructions to be repeated. This may itself be a sign of delirium, but may also be due to pre-existing cognitive deficits. In such cases, instructions may need to be repeated to make sure they are understood. Similarly, performance may be influenced by variations in severity, or agitation levels, and may need to be repeated to get an idea of the person’s actual capabilities.

Structured Instruments: Symptom checklists such as the Confusion Assessment Method (CAM) or CAM-ICU are useful to screen for and monitor delirium. They are not specific enough to be used as diagnostic instruments, especially when pre-existing cognitive deficits are present. However, they are useful for screening; as an aid to comprehensive assessment; and as a simple measure to chart severity over the course of treatment.

Causative factors

Delirium has a multi-factorial origin, except in selected situations with a single well-defined causal agent (example post-concussion or due to certain drug intoxications). A large differential diagnosis needs to be considered for causation, for reasons that are elaborated later.

Risk factors

Apart from the immediate causal agents, certain static factors may predispose an individual to developing delirium due to any cause - these include a poor general physical condition, pre-existing cognitive deficits, chronic pain, visual or hearing impairments, and reduced mobility. Many of these factors share one common attribute - they make it harder for the affected individual to perceive and use environmental cues to orient themselves. As many of these factors may affect the elderly more than other groups, this contributes to the higher risk in this age group. Moreover, the elderly have a brittle homeostasis for most metabolic parameters. Thus even relatively minor biochemical alterations may not be corrected, and this may predispose to delirium.

Pathophysiology

There is no unified pathogenesis of delirium. One final common pathway for delirium is probably a relative “cholinergic deficiency”, which may be responsible for the cognitive difficulties. Acetylcholine is a key neurotransmitter involved in the sleep-wake cycle, arousal and attention.

Conditions that may be mistaken for delirium

At a syndromal level, certain disorders may need to be differentiated from delirium. Here, primary psychiatric or neurocognitive disorders are considered in detail.

Dementia

Spatial confusion, misrecognitions, confabulation, short-term memory deficits and impairments in attention may all occur along the course of dementing illnesses. However, even when these symptoms are present together, they are usually not considered to be delirium, as the pathophysiology is probably different. Moreover, dementia has certain features that are not present in delirium:

a. Arousal levels are unaffected, and symptoms usually occur on the background of clear consciousness
b. These symptoms typically occur late in the course of dementia
c. The onset is usually gradual, with various symptoms being separated by extended periods of time
d. Patterns of cognitive deficit persist even in the presence of relatively normal attention and concentration

Depression

This is common in the differential diagnosis, particularly in connection with so-called depressive “pseudo-dementia”. Most often, this diagnosis is entertained when a hypoactive delirium occurs and the patient’s withdrawal and lack of motivation are attributed to the emotional state. As with dementia, depression does not usually lead to a primary change in arousal levels, and the pattern of cognitive deficits are most commonly a reflection of reduced processing speed and interference from psychological factors, leading to slowed performance that improves variably with encouragement.

Central focal neurological syndromes

While certain localized lesions in the brain can produce a true delirium-like picture, others may produce some of the typical symptoms – example spatial confusion arising from a lesion in the non-dominant parietal lobe. The absence of other deficits, and differences in the evolution of symptoms, are helpful in this situation. Another neurological deficit that is frequently misdiagnosed as delirium is one of fluent aphasia, where clinicians misattribute the “irrelevant talk” to a confusional state. The careful exclusion of other symptoms is usually sufficient to differentiate these from delirium.

Psychotic illnesses

Primary psychotic illnesses cause agitation and disorders of thought form that may make assessment difficult. Moreover, the hallucinations and delusions that occur in both conditions may be misattributed to delirium. Moreover, these conditions may also cause a reduction in sleep, mimicking delirium. Catatonic stupor may resemble hypo-arousal. However, this difference can usually be effectively made at least with a period of observation.

Barriers to correct recognition

When a previously well patient presents with agitation, misrecognition and disorientation in the context of a discrete episode of illness, a diagnosis of delirium is easily made. However, quite often the presentation is more muted, leading to delays in identification.

- An impaired baseline – in patients with pre-existing cognitive dysfunction, it may be difficult to distinguish a supervening confusional episode.
- Debilitation – in many patients with delirium, the precipitating illness may itself affect a person’s ability to ambulate. In such situations, markers of delirium such as spatial confusion or disorientation may not be identified, or may be rationalized by carers
- Hypo-aroused delirium – in some patients, hypo-arousal rather than hyper-arousal may predominate within the clinical picture. In such patients, reductions in responsiveness may be attributed to being sick, unless the patient is asked specific questions related to orientation and attention.
- Fluctuations - mild attentional symptoms may not be apparent on one-to-one interviews, as the deficits may be overridden by novelty, the absence of distractions, or motivational factors. As many of these factors arise when a doctor assesses a patient, the true extent of deficits may not be identified.

Equally important are factors that lead to delirium being misdiagnosed. Agitation and uncooperativeness arising from any source may complicate any medical or psychiatric illness. In such situations, patients may refuse to answer the usual screening questions for orientation, or may consciously fabricate answers. In these situations, information from the mental state examination must be correlated with historical information, for inconsistencies within the self-report, observations and information from carers or other clinicians.

Establishing the etiology

A clinical evaluation may be sufficient in many cases to find a proximate cause for delirium. The history should look into the patient’s functioning prior to the onset, the evolution of symptoms, and exposure to toxins (including herbal preparations or over-the-counter medication). A comprehensive physical examination is indicated in all cases. This examination also includes the evaluation of the patient’s current cognitive abilities (at least orientation to time, place and person, and attention).

This examination should also assess for impairments in sight or hearing, for chronic pain and dehydration which may be factors in the persistence or worsening of agitation or delirium.

Specific patterns of onset and duration of the current episode may point towards a cause:

- Brief spells with abrupt onset with relatively intact cognitive function may be markers of a seizure disorder.
- A resting tremor, autonomic overactivity and insomnia may suggest alcohol withdrawal delirium (delirium tremens).
- Ophthalmoplegias and nystagmus may be indicative of Wernicke’s encephalopathy.

Investigations may be indicated by the examination findings. However, a minimum routine panel should include blood counts, inflammatory markers, electrolytes (including calcium, magnesium and phosphates) and liver function testing, and testing for asymptomatic infections using blood cultures, a chest radiograph and urinalysis. Where intoxications or poisonings are suspected, toxicology screens may be helpful. As has been stressed, the origin of delirium may be multi-factorial, and subtle alterations in these parameters may interact with other illnesses or pre-existing deficits in the clinical presentation.

While there is no recommendation for routine brain imaging investigations or CSF examinations, these tests should be done promptly if there are pointers towards a neurological cause, if there are signs of raised intracranial pressure, and when initial clinical evaluation does not suggest a cause. Electroencephalography (EEG) has a limited role in the specific diagnosis (especially to rule out non-convulsive status epilepticus) but is likely to show a generalized slowing of electrical activity.

In cases where no cause is easily identified after this initial screening, certain other tests may be indicated, according to the clinical picture. These include serum levels of thiamine, folate and vitamin B12, thyroid stimulating hormone, cortisol, and ammonia; autoimmune serologies including ANA, complement levels, p-ANCA, c-ANCA, autoimmune encephalopathy serologies (standard panels look for antibodies to NMDA, GAD and VGKC); infectious serologies including VDRL/RPR, fungal or viral serologies (including HIV).

As subtle alterations in a number of parameters might lead to delirium, and levels might fluctuate it may be necessary to repeat any tests that are marginally altered, to spot changes in relative levels. While doing so, previous tests prior to the onset of delirium may be more appropriate for comparison, rather than relying on standard normal ranges.

Management

An important target for management of delirium is the distress and dysfunction to the patient as well as family. There are also findings to show that delirium is neurotoxic in itself, and that cognitive deficits (particularly in the domains of attention and memory) might persist beyond the period of overt confusion, and may be slow to resolve.

The primary management of delirium is the identification and treatment of the causative agent(s). Delirium-specific measures are supportive in their intent, but can make a marked difference by reducing symptoms and curtailing the duration of confusion. Due to the fluctuating nature of the illness, these management measures may need to be extended beyond the period of obvious confusion.

Non-pharmacological management

The most important parts of management are not medication-related. They are primarily modifications of the environment around the patient to (a) ensure the presence of overt cues and (b) to make sure that the patient does not get distressed/frustrated when unable to focus their attention.

The role of medication

The role of medication management is limited. If a decision to start such a medication is taken, it is usually with a clear and well-defined target, in order to make the patient more amenable to other measures, and prevent injuries due to falls or aggression.

The targets of this treatment may include psychotic symptoms such as hallucinations or delusions, behavioral symptoms like agitation or aggression, or alterations in the sleep-wake cycle.

Antipsychotic medications are the medication of choice for psychotic symptoms in delirium. For this indication, doses are generally lower than those used for the management of psychiatric illness—typical doses for haloperidol are in the range of 0.25 to 1mg, repeated twice or thrice every day. Repeated doses are preferred to avoid side effects that occur at peak plasma concentrations, and to allow for dose titration. Haloperidol and olanzapine are available for parenteral use as well.

Benzodiazepines are used less frequently, but are the preferred agents for management of alcohol or sedative-withdrawal delirium.

Melatonin and congeners such as ramelteon have also been used in the management of delirium, primarily to correct the sleep-wake cycle.

There is no strong evidence for disease-modifying effects for any of these medications. Therefore, routine prescription of medications to prevent delirium is not recommended. Moreover, the medications listed above should not be prescribed routinely for delirium, as they are likely to produce some degree of obtundation and could worsen cognitive functioning.

Antipsychotic medications can produce ECG changes including QTc prolongation. Benzodiazepines can cause respiratory depression. These must be monitored.

Specific conditions associated with delirium in the elderly

a) Large Bone fractures

Older populations are at risk of falls and fractures. Osteoporotic fractures, especially of the large bones, often require surgical intervention. This is a situation where delirium is frequently encountered.

Rates of delirium following fractures of the neck of femur have been reported to be as high as 53%. In just over half the cases, delirium occurs post-operatively, and lasts 2-3 days. The risks of delirium in this period are mostly related to the patient not participating in rehabilitation or post-op recovery; acquiring additional problems due to aspiration, bedsores, urinary tract infections or respiratory infections due to reduced mobility. Apart from the general measures suggested above, clinicians may focus on ensuring adequate pain relief, and should prioritize early mobilization.

b) Sedative dependence

Over the counter prescription of benzodiazepines are common in this population, and dependence may develop even without substantial tolerance. The withdrawal of these medications during the course of an unrelated illness, may be a frequent cause for delirium. For example, a patient who has been taking 10 mg of diazepam for 20 years, may be taken in to hospital after a fall.

In this situation, delirium presents similar to that seen in alcohol withdrawal. Tachycardia, unsteadiness and fluctuations in blood pressure are present, as seen with delirium tremens. Apart from prolonged use, major risk factors include the use of shorter acting benzodiazepines at higher doses. Reduced clearance may be caused by impaired liver and kidney functions, leading to dose accumulations.

Treatment involves replacement with a long-acting benzodiazepine (frequently diazepam or chlordiazepoxide), with doses titrated to suppress the specific symptoms (ie tremors, delirium, tachycardia etc), but not causing sedation. Dose equivalence charts for benzodiazepines may be useful as a rough guide in this. This dose is then gradually reduced, watching carefully for symptom breakthrough. Lorazepam may be preferred in patients with liver disease, or when shorter durations of action are required.

c) Dementia with delirium

As discussed extensively above, dementia is a risk factor for development of delirium. Reasons suggested include a lower “cognitive reserve” and overlap in the pathophysiology. Other issues that should be borne in mind include:

- overshadowing, where delirium is missed because it is attributed to worsening dementia
- assessment problems where memory problems are attributed to delirium rather than dementia
- prognostic issues.

Certain conditions, example vascular dementia or Lewy body dementia, may have episodes of worsening cognition that may resemble delirium, and clear up leaving behind deficits. Frequently, these acute episodes resembling delirium may be the first presentation of these conditions, and only a thorough exploration of pre-existing cognitive deficits would reveal the pre-existing condition.

Conclusion

Delirium assessment is an essential part of medical care, especially for the elderly—in part, this is due to its value as a common marker of serious bodily pathology; other reasons include its distressing nature to the patient and to carers, and the risks due to decreased judgement and self-care as a result of this condition. Despite this importance, delirium assessment is a skill that is not stressed enough during physician training, and symptoms are frequently missed. Reasons for such missed diagnosis, and some ways of avoiding this, are detailed above.

Delirium is usually identified on the basis of a typical triad of impaired attention, disorientation, and fluctuations in sensorium; psychotic symptoms are alterations in mood and sleep-wake cycle may on occasion be more prominent. Partial presentations are common, and different symptoms may be present at different time points during the assessment.

Management of the underlying cause forms the mainstay of treatment. Non-pharmacological treatment aims to make reorientation easier, and limit distress due to confusion. Pharmacological treatment is usually reserved for the narrower objective of containing agitation, psychotic symptoms or self-endangerment, and has a limited role unless these risks exist. Delirium prevention strategies based on early identification and intervention, and suitable environmental modification may be more effective than prophylactic medication.

Further Reading

1. David AS. Basic Concepts in Neuropsychiatry. In: David AS, Fleminger S, Kopelman M, Lovestone S, Mellers J, editors. Lishman’s Organic Psychiatry: A Textbook of Neuropsychiatry. 4 edition. Chichester: Wiley-Blackwell; 2012.

2. Grover S, Avasthi A. Clinical Practice Guidelines for Management of Delirium in Elderly. Indian J Psychiatry. 2018 Feb;60(Suppl 3):S329–40.

3. Schildkrout B. Masquerading Symptoms: Uncovering Physical Illnesses That Present as Psychological Problems. John Wiley & Sons; 2014. 947 p.

4. Hshieh TT, Inouye SK, Oh ES. Delirium in the Elderly. Psychiatric Clinics of North America. 2018 Mar;41(1):1–17.

5. De J, Wand APF. Delirium Screening: A Systematic Review of Delirium Screening Tools in Hospitalized Patients. Gerontologist. 2015 Dec 1;55(6):1079–99.

6. Inouye SK, Bogardus ST, Charpentier PA, Leo-Summers L, Acampora D, Holford TR, et al. A Multicomponent Intervention to Prevent Delirium in Hospitalized Older Patients. New England Journal of Medicine. 1999 Mar 4;340(9):669–76.

7. Potter J, George J, Guideline Development Group. The prevention, diagnosis and management of delirium in older people: concise guidelines. Clin Med (Lond). 2006 Jun;6(3):303–8.