Delirium – a confusional syndrome or state – is characterized by changes in the level of consciousness, disorientation and behavioral problems.

It is common after surgery.

Do not confuse delirium (literally translated from Latin as outside the groove) and delirium, which is a disturbance of logical reasoning.

History of delirium

1881: Lasègue describes for the first time delirium tremens in alcoholics.

1892: Chaslin describes mental confusion and already notes clinical heterogeneity.

1911: Regis describes secondary post-dream delusions.

1935: Wolff and Curran describe it as a mental condition caused by malnutrition and poor blood supply in the brain.

Epidemiology of delirium

The highest incidence rates were observed in intensive care, postoperative and palliative care units. Since many of these studies excluded patients with cognitive impairment or dementia at baseline, these rates are likely underestimated.

In general medicine and geriatrics departments, the prevalence of delirium (present on admission) varies from 18 to 35%. More specifically, the prevalence of delirium in hospitalized elderly patients varies from 15 to 25% after major surgery and is estimated at 50% after high-risk surgery in the elderly, such as a hip fracture or heart surgery. Confusional state is therefore common after surgery.

The prevalence of delirium in the community setting is relatively low (1–2%), but its onset usually brings the patient to urgent care. It is present in 8 to 1% of elderly people admitted to the emergency room. Its prevalence at the end of life is around 85% in palliative care.

In intensive care units, delirium usually begins within the first few days of hospitalization and usually lasts 24 to 48 hours. The prevalence is 70%.

Delirium is consistently associated with an increased mortality rate in all non-surgical patient populations (e.g. medical, geriatric, and intensive care units). 15-18% of those who develop delirium in general or geriatric medicine wards are 1.5 times more likely to die within a year. In older patients with dementia, delirium is associated with increased rates of cognitive decline, institutionalization, and mortality.

The causes of delirium

While a single factor can lead to delirium, most often delirium is multifactorial. There are predisposing factors that are associated with etiological factors: advanced age, male sex, presence of dementia or psychiatric illness, consumption of drugs (eg benzodiazepines, sedatives, hypnotics) , alcohol dependence and decreased visual acuity.

In patients who are highly vulnerable to delirium, such as those with underlying dementia and several other disorders, a simple intake of medication – such as a single dose of sleeping pills – may be enough to precipitate delirium.

Conversely, in a healthy young patient, delirium will only develop after exposure to a series of major events, such as general anesthesia, major surgery, taking multiple psychotropic drugs, a stay in intensive care and sleep deprivation. 

Clinically, the implication of multiple causative factors is that treatment of a single risk factor is unlikely to resolve delirium, and that multiple approaches will be most effective in both preventing and treating delirium. .

The causes can be:

• metabolic disorders;
• infections (pneumonia, urinary tract infection, sepsis, etc.);
• neurological diseases or accidents (stroke, depression, epilepsy);
• surgical operations (operative shock, immobilization, general anesthesia );
• heart problems (heart failure, heart attack, heart rhythm disorder);
• trauma;
• autoimmune diseases (lupus);
• somatic ailments (retention of urine, fecal impaction);
• psychological causes;
• neoplasms;
• taking multiple medications or using psychoactive drugs (risk increased by 4.5 times).
• Withdrawal from a substance or medication (benzodiazepines, opiates, psychostimulants, alcohol).

Dementia is, along with mental confusion and depression, one of the etiological factors of delirium. Confusional episodes are common after an operation caused, for example, by postoperative hypoxia or hypotension. Tricyclic  antidepressants , antipsychotics and antiparkinsonens (which have anticholinergic properties), benzodiazepines and barbiturates, drug withdrawals (benzodiazepines, barbiturates) also cause delirium, as do morphine-type analgesics, some antihypertensives (beta-blockers, calcium channel blockers, etc.).

Pathophysiology

Delirium is undoubtedly the consequence of the involvement of several causal factors which, taken one by one, seem minor but which, when accumulated, trigger the disease.

It is likely that several sets of interacting biological factors lead to disruption of neural networks and decreased metabolism in certain regions of the brain, leading to cognitive dysfunction. Other causal mechanisms interfere more indirectly with neurotransmission. For example, the inflammatory response seen in sepsis can lead to a cascade of local neuroinflammation in the brain triggered by cytokines, leading to decreased blood flow and neuronal death. Neuroinflammation can lead to glial cell activation, which in turn leads to neuron death.

Changes in the sleep-wake cycle have been reported in patients with  sleep disturbances and sundowning syndrome. The cholinergic system is affected in delirium, a hypothesis supported by the fact that drugs with anticholinergic properties (ie, which cause a drop in acetylcholine levels) cause acute confusional episodes. Other neurotransmitters (GABA, dopamine) may also be involved.

The risk factors are:

• age
• Madness
• The male gender
• Previous history of delirium
• Vitamin deficiencies
• Depression, anxiety
• Pain, fractures. dehydration.

Diagnostic criteria  for delirium

Delirium is a clinical diagnosis, often misunderstood and easily overlooked. Recognition requires a brief cognitive screening and clinical observation.

Key diagnostic features include sudden and fluctuating onset of symptoms, inattention, altered level of consciousness, and impaired cognition (eg, disorientation, memory impairment, impaired language).

Perceptual disturbances (hallucinations or illusions), delusions, psychomotor disorders (hypo- or hyper-activity), inappropriate behaviors and emotional lability. The current reference standard diagnostic criteria are the American Psychiatric Association’s Diagnostic and Statistical Manual (DSM-IV) and the World Health Organization’s International Classification of Diseases (ICD-10).

The DSM-IV defines delirium as a mental disorder due to a general medical condition consisting of the combination of the following diagnostic criteria:

• disturbance of attention and consciousness;
• modification, impairment of cognitive performance (memory, orientation, language, perception disorders);
• alteration of sensory perceptions manifested by visual or auditory illusions or hallucinations that affect the patient’s behavior, with the possibility of panic reactions (fugue, aggression, etc.);
• the disturbance sets in in a short time (a few hours to a few days), with a fluctuating course throughout the day;
• evidence from the anamnesis, clinical and paraclinical examinations, that the disturbance is due to the direct physiological consequences of a general medical condition.

For the CIM-10 , the criteria are substantially the same, except that according to the CIM-10, the onset is usually sudden, the evolution is fluctuating during the day and the total duration of the episode is less than six month. In addition to these main criteria, there are:

• psychomotor disorders (hypo- or hyperactivity, prolonged reaction time, increased or decreased verbal flow, exaggerated startle reaction);
• a disturbance of the sleep-wake rhythm;
• emotional disturbances,  depression ,  anxiety , irritability,  apathy
• sometimes vegetative disorders (tachycardia, sweats, fever…);
• incoherent, logorrheic language.

More than 24 instruments have been used in scientific studies to identify delirium. The most widely used is the Confusion Assessment Method (CAM), with a sensitivity of 94% and a specificity of 89%. Cognitive testing is recommended for optimal use of the CAM. The CAM has been adapted for use in intensive care units, emergency rooms and nursing homes.

Clinical forms

Perceptual abnormalities include hallucinations, delusions, and misinterpretations. They are mostly visual and accompanied by emotional reactions. A sudden onset and a short and limited duration are necessary criteria for the diagnosis of the confusional episode, but the ICD-10 admits a maximum duration of the table over six months. The confusional episode can either reveal the presence of an undiagnosed dementia, or aggravate an already installed dementia.

Differential diagnosis

One `two-thirds of delirium diagnoses are missed due to the fluctuation of the clinical picture throughout the day.

Acute confusional state can be confused with the following diseases:

1. Dementia. Unlike delirium, the onset of  dementia  is insidious, vigilance is intact, hallucinations are rare, psychomotor activity is normal, mood is little altered, delusions are infrequent, speech is most often normal during early disease and neurological signs are often absent.

2. Wernicke’s aphasia. This disorder is marked by disorders of oral comprehension, verbal productions characterized by jargon or paraphasias. In some cases, the patient is difficult to channel, which can lead to a confusing diagnosis. A CT scan will help differentiate Wernicke’s aphasia from  delirium.

3. Amnesic stroke. The patient suffers from isolated amnesia, of sudden and transient installation (a few hours). The other cognitive functions are intact.

4. Gayet-Wernicke encephalopathy. This vitamin B1 deficiency results in a confusional syndrome with hypersomnia and hallucinations, and concerns people who are undernourished. Early treatment, before neurological signs appear, is critical.

Clinical evaluation of delirium

The most important step in the assessment is to learn the history from an informed observer (eg, a family member or caregiver) and perform a brief cognitive assessment.

A brief cognitive screening should be done using cognitive screening tests such as the short MMSE or the Montreal Cognitive Assessment. If time is extremely limited, orientation assessment with an attention task provides a baseline screening.

The electroencephalogram (EEG) has limited sensitivity and specificity in the diagnosis of delirium. However, delirium is characterized by increased theta and delta activity.

The tools for assessing the severity of delirium are the Delirium index  and the Confusional State Evaluation, while the main screening tool is the Confusion Assessment Method. Other neuropsychological tests are also useful:  the mini-mental exam,  the clock test, and the  tracing test.

Given the high mortality rates, any suspicious or uncertain cases (including those with lethargy or unable to complete an interview) should be treated as delirium until proven otherwise. Initial management focuses on three concurrent priorities: (1) maintaining patient safety; (2) investigate causes; and (3) management of symptoms of delirium.

To maintain patient safety, efforts should focus on protecting the airway, maintaining hydration and nutrition, preventing falls, and avoiding restraints that increase the risk and persistence of delirium.

A complete medical check-up is necessary: ​​blood sugar, drug dosage, vitamin B12, thyroid function test, albumin, sodium, potassium, magnesium, etc.

Treatments

Delirium must be treated because it increases morbidity and the risk of institutionalization and length of hospitalization.

1. Stimulation of the patient during the day, by encouraging him and facilitating references to his natural living environment. Avoid isolation which promotes sensory deprivation. Reassure the patient by speaking calmly. Avoid noise and commotion.

2. Pharmacological treatment with psychotropic drugs with sedative effects: Clometiazole, carbamates, antipsychotics without anticholinergic effects (haloperidol, risperidone, clozapine, quetiapine, benzamides). It is absolutely necessary to avoid barbiturates and benzodiazepines, drugs which are often the cause of delirium, except in the case of delirium due to withdrawal from alcohol or benzodiazepines.

It is preferable to prescribe psychotropic drugs in a single evening dose, in order to restore the sleep-wake cycle. Repeated treatment during the day can cause a paradoxical on-off phenomenon with sudden aggravation of symptoms.

3. Parental treatment with vitamins B1, B6 and PP in alcoholics.

4. Sleep a lot, stay well hydrated and eat well.

5. Ensure that the patient sees and hears well.

6. Make sure loved ones are present. They must be well informed about the disease.

7. Communicate succinctly.

Does delirium lead to dementia?

A major area of ​​controversy is whether delirium is simply a factor in dementia vulnerability, or whether delirium itself leads to dementia. It is likely that both hypotheses are true. There is little doubt that the occurrence of an episode of delirium may reflect brain vulnerability and an increased risk of future dementia. In some cases, delirium can cause previously undiagnosed cognitive disorders to be treated. Delirium and dementia usually coexist, with dementia being a major risk factor for delirium, i.e. increasing the risk of delirium by 2-5 times.

A meta-analysis involving two studies with a total of 241 patients demonstrated that delirium was associated with an increased rate of dementia (+457%). In a sample of 225 cardiac surgery patients, delirium caused a severe one-time decline in cognitive functioning, followed by recovery over 6 to 12 months in most patients. However, a significant proportion, particularly those with prolonged delirium, never return to their original functioning. In 263 patients with Alzheimer’s disease, delirium caused an accelerated rate of cognitive decline after hospitalization. The decline is estimated to occur three times faster.

In summary

The confusional state (or delirium) is easy to overlook without a formal cognitive assessment. A brief cognitive examination can help identify delirium, with appropriate management. Additionally, older adults often take multiple psychoactive medications that increase the risk of delirium. Falling and loss of appetite are often warning signs.

1. Assess delirium in all older hospitalized patients: using a simple cognitive screening and confusional state rating scale. Be sure to get the history from someone close to the patient.
2. Reduce psychoactive drugs.
3. Use non-pharmacological approaches to manage sleep, anxiety, and restlessness.
4. Have pharmacological approaches for patients with severe agitation, who are at risk for self-harm, or who have psychotic symptoms (eg, hallucinations, delusional states).
5. Invite family members to care, especially for redirection and prevention of self-harm.
6. Encourage mobility.
7. Make sure patients wear their glasses, hearing aids and dentures. Being able to see, hear and eat is important.
8. Let patients know their schedule and keep them involved in their care. Communicate regularly with patients and their families.

Source: Sharon K et al. Delirium in elderly people. Lancet. 2014 March 8; 383(9920): 911–922.

Clinical case #1

Mrs. M, 71 years old, was diagnosed with Alzheimer’s disease (mild stage) after a physical examination and a cognitive performance evaluation (her Mini-Mental State Examination score is 22). In addition to medication for high blood pressure, Ms. M has been taking lorazepam 1 mg, 3 times a day, for more than 15 years to treat anxiety.
Mrs. M has been getting more confused at home for a few days, and her daughter is taking her to her doctor for an evaluation. Recognizing that benzodiazepines can contribute to acute confusional state  (delirium), the doctor stops the lorazepam. Three days later, Mrs. M’s confusion worsens and she develops nausea and tremors.

She is taken to the emergency room where she is admitted for benzodiazepine withdrawal, to find out if the delirium is caused by Alzheimer’s disease or the medication.

Although delirium is caused by several factors, drugs are frequent predisposing and aggravating factors and contribute to approximately 12% to 39% of cases of delirium.

Benzodiazepines and opioids are the drugs most often associated with an increased risk of delirium, as are drugs with strong anticholinergic properties (i.e. lowering acetylcholine in the brain).

In general, there are no strict rules on how to reduce and discontinue potentially risky medications. The steps to consider are:

• Consider tapering and discontinuing benzodiazepines in a patient taking more than the minimum expected doses for at least two weeks, especially after eight weeks of treatment.
• In the case of opioids, consider reducing them in a patient taking more than the minimum expected dose for more than a few days. When trying to eliminate symptoms of delirium, reduce opioids as quickly and as safely as possible, with a recommended reduction of less than 20% per day to prevent withdrawal symptoms.
• The onset and duration of withdrawal symptoms depend on the half-life of a drug. Withdrawal occurs earlier when one stops taking drugs with short elimination half-lives (usually within 1-2 days), while it may not appear until 3-8 days after stopping drugs with a half-life greater than 24 hours.

Abruptly stopping a sedative – both hypnotic and opioid – can lead to intolerable withdrawal symptoms.

Benzodiazepine withdrawal should be avoided because of the risk of severe complications, such as seizures and delirium.

Withdrawal seizures are particularly common with alprazolam due to its short half-life.

Therefore, greater caution should be exercised when phasing out this drug.

In general, withdrawal from opioids or anticholinergics is not life-threatening, but should be done with caution.

Key points

• Medications strongly implicated in delirium should be withdrawn or changed.
• Consider the dosage and duration of treatment, the half-life of the drug, and the nature of withdrawal symptoms when determining how quickly the dose of a drug should be tapered.
• A gradual reduction in activity over 2 or 3 days may be considered in hospitalized patients.

Clinical case #2

An octogenarian woman arrives at the emergency room for behavioral problems (agitation and visual and auditory hallucinations) accompanied by falls.

She is being treated for high blood pressure and has no psychiatric history. She is being treated with Plavix .

She has no confusion during the examination because she is aware of her hallucinations, which is the source of her anxieties.

Two diagnostic hypotheses are proposed:

• A confusional state  that occurs during dementia;
• A confusional state with a transient organic cause.

The following additional examinations were requested:

• A scanner having reported neither signs of hemorrhage or cerebral ischemia, nor of cerebral atrophy.
• An electrocardiogram.
• An electroencephalogram, which revealed heart rhythm disorders, with fluctuation of alertness.
• A mini-mental exam score of 24 out of 30, suggesting cognitive decline.
• No chronic mental illness according to the psychiatrist.

1st diagnosis ^_

A diagnosis of confusional state with hallucinations is made. Treatment with seresta (benzodiazepine) is provided.

The low MMSE score suggests the presence of mild cognitive decline .

An anomaly on the ECG suggests a heart problem, a hypothesis supported by the observation of an irregular heartbeat on the electroencephalogram.

A second, more in-depth electrocardiogram is undertaken.

2nd diagnosis

Medical staff diagnose:

• Atrial fibrillation treated in particular with anti-vitamin K (anticoagulant) and an antiarrhythmic.
• An enlarged left ventricle, characteristic of heart disease (heart disease is present in 70% of cases of atrial fibrillation)

This so-called paroxysmal atrial fibrillation (that is to say that it manifests itself in the form of an acute crisis for about a week and then ends spontaneously) leads to an acute confusional syndrome with a decrease in cerebral blood flow.

• Onset of very moderate cognitive impairment with preserved autonomy.

Following the implementation of the treatments, no recurrence was observed.