At a glance......
- 1 Pathophysiology
- 2 Types of Delirium
- 3 Causes of Delirium
- 4 Symptoms of Delirium
- 5 Diagnosis of Delirium
- 6 Treatment of Delirium
Delirium is a common neuropsychiatric syndrome in the elderly. The DSM-IV-TR defines delirium as a “disturbance of consciousness and a change in cognition that develop over a short period of time. The syndrome includes fluctuations in consciousness over the course of the day, a reduced ability to focus, sustain and shift attention, and evidence that the disturbance is caused by the direct physiological consequence of a medical condition [rx].
In general, the prevalence of delirium is dependent on several factors, including the patient population, care setting, the method of study and diversity of antecedent events. The prevalence of delirium in the community is 1–2%, but increases in the setting of general hospital admissions to 6–56% [rx], with the higher prevalence associated with increased age [rx] and increased severity of medical illness [rx].
Alcohol acts as central nervous system depressant. It enhances the effect of inhibitory neurotransmitters while down-regulating excitatory neurotransmitters. Alcohol interacts with GABA receptors, chloride ion receptor acting as an inhibitory neurotransmitter, via several mechanisms to enhance its activity. Over time, through prolonged alcohol exposure, there is a decrease in GABA activity and alteration in the type of GABA receptor and function. Abrupt cessation of alcohol causes a decrease in the inhibitory actions of GABA neurotransmitter resulting in overactivity of the central nervous system.
Alcohol also inhibits the action of NMDA receptor by acting as a receptor antagonist. It inhibits the action of glutamate, which is an excitatory amino acid. Prolonged alcohol abuse results in receptor up-regulation. Abrupt discontinuation of alcohol causes an increase in the action of glutamate, resulting in profound excitatory action. This may have a clinical manifestation of sympathetic overdrive, such as agitation, tremors, tachycardia, and hypertension.
Certain individuals are more vulnerable to suffer from withdrawal symptoms than others. Though the etiology remains unclear, there is a correlation between the duration of alcohol exposure and withdrawal symptoms.[rx][rx]
Types of Delirium
There are three types of delirium
- Hypoactive – meaning that the person acts sleepy or withdrawn
- Hyperactive – meaning that a person is agitated
- Mixed – meaning that a person alternates between these two types
- Delirium subtypes have been defined based on the presence (hyperactive) or absence (hypoactive) of psychomotor agitation, perceptual disturbances, and/or changes in level of consciousness.[rx] Often both subtypes are present concurrently (mixed).[rx–rx]
Causes of Delirium
Mental confusion can result from chronic organic brain pathologies, such as dementia, as well.
- Neuroinflammation – Patients who develop delirium have shown an elevated PCR and Cortisol, although IL-8 is prevalent among patients in and out of ICU. The cytokines activate the endothelium and the coagulation cascade, which predisposes to microvascular thrombosis and blood flow dysfunction. The neuroinflammation leads to infiltrate cytokines and leukocytes to the hematoencephalic barrier and then in the central nervous system in which produce ischemia and neuronal apoptosis.
- Cholinergic Deficiency Hypothesis – Acetylcholine is a very important neurotransmitter in attention and consciousness. It is known, acetylcholine acts as a modulator in sensory and cognitive input so, an impairment in the route leads to develop symptoms of hypoactive or hyperactive delirium, including inattention, disorganized thinking, and perceptual disturbances. Cholinergic pathways project from basal forebrain and pontomesencephalon to interneurons in the striatum and finally targets throughout the cortex.
- Neurotransmitter Imbalance – The dopamine excess contributes to hyperactive delirium and is related to decreased acetylcholine. The dopaminergic and cholinergic pathways overlap in the brain, this explains why dopamine receptors impact acetylcholine levels and explain the clinical manifestations of delirium, including hyperactive and hypoactive forms. The imbalance between neurotransmitter and cholinergic pathway may result in delirium.
- Chronic Stress – Activates the sympathetic nervous system and de hypothalamus-hypophysis-suprarenal glands axis, which elevate the cytokines levels and results in chronic hypercortisolism that can cause an alteration in the hippocampus function. Cortisol is the main hormone in response to stress and has deleterious effects among 5HT 1A receptors. The association between this receptors and delirium is not conclusive. High cortisol levels produce a reduction in GABA release and impairment in neuronal energy bombs.
Others Causes of Delirium
- Mapping Fuhrerreich’s China
- Aluminium Toxicity
- Brain Damage
- Brain Tumor
- Brief Psychotic Disorder
- Brain Injury
- Heat Stroke
- Kidney Failure
- Kidney Infection (Pyelonephritis)
- Lassa Fever
- Lewy Body Dementia
- Lyme Disease
- Postpartum Depression
- Reye’s Syndrome
- Rocky Mountain Spotted Fever (RMSF)
- Seizure (Epilepsy)
- Shock (Medical)
- Sick Building Syndrome
- Sleep Apnea
- Yellow Fever
- STDs in Men
- Streptococcal Infections
- Toxic Shock Syndrome (TSS)
- Transient Ischemic Attack (TIA, Mini-Stroke)
- Acute Porphyria
- West Nile Virus
- Medication side effects (recovery may take time after drug discontinuation)
- Seizure disorders
- Severe dehydration
- Severe trauma
- Sleep deprivation or disturbances
- Vitamin deficiencies such as niacin, thiamine, vitamin B12, or vitamin C deficiency
Potentially modifiable risk factors
- Sensory impairment (hearing or vision)
- Immobilization (catheters or restraints)
- Medications (for example, sedative hypnotics, narcotics, anticholinergic drugs, corticosteroids, polypharmacy, withdrawal of alcohol or other drugs)
- Acute neurological diseases (for example, acute stroke [usually right parietal], intracranial hemorrhage, meningitis, enkephalitis)
- Intercurrent illness (for example, infections, iatrogenic complications, severe acute illness, anemia, dehydration, poor nutritional status, fracture or trauma, HIV infection)
- Metabolic derangement
- Environment (for example, admission to an intensive care unit)
- Emotional distress
- Sustained sleep deprivation
Nonmodifiable risk factors
- 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
The most important predisposing factors are listed below:[rx]
- Older age (> 65yo)
- Male sex
- Cognitive impairment / dementia
- Physical comorbidity (biventricular failure, cancer, cerebrovascular disease)
- Psychiatric comorbidity (e.g., depression)
- Sensory impairment (vision, hearing)
- Functional dependence (e.g., requiring assistance for self-care or mobility)
- Drugs and drug-dependence
- Alcohol dependence
Prolonged sleep deprivation, Environmental, physical/psychological stress
- Inadequately controlled pain
- Admission to an intensive care unit
- Immobilization, use of physical restraints
- Urinary retention, use of bladder catheter,
- Emotional stress
- Severe constipation/fecal impaction
- Sedatives (benzodiazepines, opioids), anticholinergics, dopaminergics, steroids, Polypharmacy
- General anesthetic
- Substance intoxication or withdrawal
Primary Neurologic Diseases
- Severe drop in blood pressure, relative to the patient’s normal blood pressure (orthostatic hypotension) resulting in inadequate blood flow to the brain (cerebral hypoperfusion)
- Stroke/transient ischemic attack
- Intracranial bleeding
- Meningitis, encephalitis
- Infections – especially respiratory (e.g. pneumonia) and urinary tract infections
- Iatrogenic complications
- Hypoxia, hypercapnea, anemia
- Poor nutritional status, dehydration, electrolyte imbalances, hypoglycemia
- Shock, heart attacks, heart failure
- Metabolic derangements (e.g. SIADH, Addison’s disease, hyperthyroidism, )
- Chronic/terminal illness (e.g. cancer)
- Post-traumatic event (e.g. fall, fracture)
- In surgery of cardiac, orthopedic, prolonged cardiopulmonary bypass, thoracic surgeries
Symptoms of Delirium
- Inattention – As a required symptom to diagnose delirium, this is characterized by distractibility and an inability to shift and/or sustain attention.[rx]
- Memory impairment – Memory impairment is linked to inattention, especially reduced formation of new long-term memory where higher degrees of attention is more necessary than for short-term memory. Since older memories are retained without need of concentration, previously formed long-term memories (i.e. those formed before the onset of delirium) are usually preserved in all but the most severe cases of delirium.
- Disorientation – As another symptom of confusion, and usually a more severe one, this describes the loss of awareness of the surroundings, environment and context in which the person exists. One may be disoriented to time, place, or self.
- Disorganized thinking – Disorganized thinking is usually noticed with speech that makes limited sense with apparent irrelevancies, and can involve poverty of speech, loose associations, perseveration, tangentiality, and other signs of a formal thought disorder.
- Language disturbances – Anomic aphasia, paraphasia, impaired comprehension, agraphia, and word-finding difficulties all involve impairment of linguistic information processing.
- Sleep changes – Sleep disturbances in delirium reflect disturbed circadian rhythm regulation, typically involving fragmented sleep or even sleep-wake cycle reversal (i.e. active at night, sleeping during the day) and often preceding the onset of a delirium episode
- Psychotic symptoms – Symptoms of psychosis include suspiciousness, overvalued ideation and frank delusions. Delusions are typically poorly formed and less stereotyped than in schizophrenia or Alzheimer’s disease. They usually relate to persecutory themes of impending danger or threat in the immediate environment (e.g. being poisoned by nurses).
- Mood lability – Distortions to perceived or communicated emotional states as well as fluctuating emotional states can manifest in a delirious person (e.g. rapid changes between terror, sadness and joking).[rx]
- Motor activity changes: Delirium has been commonly classified into psychomotor subtypes of hypoactive, hyperactive, and mixed,[rx] though studies are inconsistent as to the prevalence of these subtypes.[rx] Hypoactive cases are prone to non-detection or misdiagnosis as depression.
- Hyperactive symptoms include hyper-vigilance, restlessness, fast or loud speech, irritability, combativeness, impatience, swearing, singing, laughing, uncooperativeness, euphoria, anger, wandering, easy startling, fast motor responses, distractibility, tangentiality, nightmares, and persistent thoughts (hyperactive sub-typing is defined with at least three of the above).[rx]
- Hypoactive symptoms include unawareness, decreased alertness, sparse or slow speech, lethargy, slowed movements, staring, and apathy (hypoactive sub-typing is defined with at least four of the above).[rx]
- An altered level of consciousness or awareness.
- A shortened attention span.
- Memory problems.
- Disorganized thinking and speech.
- A reversal of day and night.
- Difficulty writing, drawing, or finding words.
- Personality changes.
- An altered level of consciousness or awareness
- A shortened attention span
- Memory problems
- Disorganized thinking and speech
- A reversal of day and night
- Difficulty writing, drawing, or finding words
- Personality changes
- Delusions or hallucinations
- Restlessness, anxiety, sleep disturbance, or irritability
- Having trouble solving problems or doing tasks that used to be easy for you.
- Not knowing where you are or not recognizing family members or familiar items.
- Firmly held but false beliefs (delusions).
- Seeing, hearing, feeling, smelling, or tasting things that are not really there (hallucinations or illusions).
- Unfounded suspicions that others are after you or want to harm you (paranoia).
Diagnosis of Delirium
Another symptom of confusion is an immense difficulty attempting to solve problems or accomplish tasks that were previously easy to perform. People suffering from confusion will also find it hard to recognize members of their own family, and even familiar objects.
Examination, particularly in patients who are not fully cooperative, should focus on the following
- Vital signs
- Hydration status
- Potential foci for infection
- Skin and head and neck
- Neurologic examination
Findings can suggest a cause, as with the following
- Fever, meningismus, or Kernig and Brudzinski signs suggest CNS infection.
- Tremor and myoclonus suggest uremia, liver failure, drug intoxication, or certain electrolyte disorders (eg, hypocalcemia, hypomagnesemia).
- Ophthalmoplegia and ataxia suggest Wernicke-Korsakoff syndrome.
- Focal neurologic abnormalities (eg, cranial nerve palsies, motor or sensory deficits) or papilledema suggests a structural CNS disorder.
- Scalp or facial lacerations, bruising, swelling, and other signs of head trauma suggest traumatic brain injury.
The Confusion Assessment Method (CAM) Diagnostic Algorithm.
General diagnostic criteria
(A) Disturbance of consciousness (that is, reduced clarity of awareness of the environment) with reduced ability to focus, sustain, or shift attention
(B) A change in cognition (such as memory deficit, disorientation, language disturbance) or the development of a perceptual disturbance that is not better accounted for by a pre-existing, established, or evolving dementia
(C) The disturbance develops over a short period of time (usually hours to days) and tends to fluctuate during the course of the day
For delirium due to a general medical condition
(D) Evidence from the history, physical examination, or laboratory findings indicates that the disturbance is caused by the direct physiological consequences of a general medical condition
For substance intoxication delirium
(D) Evidence from the history, physical examination, or laboratory findings indicates that of either (1) the symptoms in Criteria A and B developed during substance intoxication, or (2) medication use is etiologically related to the disturbance
For substance withdrawal delirium
(D) History, physical examination, or laboratory findings indicate that the symptoms in Criteria A and B developed during, or shortly after, a withdrawal syndrome
For delirium due to multiple etiologies
(D) History, physical examination, or laboratory findings indicate that the delirium has more than one etiology (for example, more than one etiological general medical condition, a general medical condition plus substance intoxication or medication side effect)
- Laboratory testing – Blood and/or urine tests may be performed to determine the cause of the person’s delirium. Delirium may be the first manifestation of a severe infection or sepsis, so additional tests to identify infection may be done. A chest x-ray is often required to exclude pneumonia.
- Brain imaging tests – If the cause of a person’s delirium cannot be determined based upon the history, physical examination, and laboratory testing, a computed tomography (CT) scan or magnetic resonance imaging (MRI) scan of the head may be recommended. This test can help to determine if an abnormal growth, bleeding, infection, or inflammation is present in the brain.
- Lumbar puncture – During a lumbar puncture, or spinal tap, a clinician uses a needle to remove a sample of spinal fluid from the area around the spinal cord in the low back. Several tests are done on the fluid to determine if an infection (such as meningitis or encephalitis) could be causing delirium, and if so, which antibiotic treatment is best. Lumbar puncture is not recommended for every person with delirium. It may be performed if other tests are unable to determine the cause, or if there are other signs of central nervous system infection.
- EEG testing – Electroencephalography (EEG) measures the electrical activity in the brain. It may be performed in a person with delirium to search for abnormal electrical activity that is commonly associated with seizures and epilepsy. It is not recommended for all people with delirium, but it may be performed if other tests are unable to determine the cause.
The differential diagnosis for DT includes the following
Neuroleptic malignant syndrome
Drug toxicity such as with amphetamine, hallucinogen, cocaine, heroin, and PCP
Electrolyte abnormalities such as hypocalcemia and hypomagnesemia
Toxic ingestion or exposures (ethylene glycol)
Acute liver failure
Treatment of Delirium
Any confusion that follows a trauma to the head, or immediately succeeding unconsciousness is a cause for serious concern. Even if the symptoms of confusion appear gradually over time, a person should consult a specialist for appropriate diagnosis and treatment.
There is no specific treatment for delirium. Instead, treatment focuses on several basic principles:
- Avoid factors known to cause or aggravate delirium, such as certain medications
- Identify and treat the underlying illness
- Provide supportive and restorative care
- Control dangerous and disruptive behaviors to avoid harm to the patient or others
- In people with a first episode of delirium, the initial treatment is often provided in a hospital setting. This allows the health care provider to monitor the patient, begin treatment of the underlying problem, and develop a long-term care plan with the patient and/or family.
Supportive care –The goal of supportive care is to maintain the patient’s health, prevent additional complications, and avoid those factors that can aggravate delirium. This includes:
- Making sure – the person gets enough to eat and drink (or providing nutrition through an IV, if needed)
- Treating pain and avoiding discomfort – including avoiding constipation
- Minimizing the use of restraints and bladder catheters – which can be uncomfortable, particularly to confused patients
- Encouraging movement – (getting out of bed in order to walk) with necessary assistance to avoid falls
- Having someone – help during meals and having the person sit upright to minimize the risk of inhaling food, drinks, and or saliva, which can lead to pneumonia
- Maintaining – a regular night-day/sleep-wake cycle when possible and avoiding sleep deprivation, and maintaining a reassuring and familiar environment with one or two visiting family members or familiar objects pictures from home
- Avoiding overstimulation – (eg, multiple visitors, loud noise), which can worsen delirium, but also avoiding understimulation (darkened room, complete silence)
- Making hearing – aids and eyeglasses available at the hospital if the patient uses these at home
- Managing behaviors – Some people with delirium have disruptive behaviors, potentially causing them to harm themselves or others. The person may say or do things that are obscene or offensive, but such behaviors do not reflect the person’s true beliefs. The person may also be at risk for falling, wandering off, or inadvertently removing intravenous lines.
- Sitter – Allowing a family member or other caregiver to stay with the patient at the bedside may help to manage the patient’s behavior. This person can provide reassurance, answer questions, reorient the patient, and notify staff if the person needs assistance. In some cases, the hospital is able to provide a sitter if a family member is unavailable. However, a familiar and trusted family member or friend can provide additional reassurance to the patient.
- Restraints – The use of restraints (to tie a person to their bed or chair) is almost never appropriate, as restraints can increase agitation and create additional problems by preventing the person from moving around as needed. Preventing movement also potentially allows skin sores (called pressure ulcers) to develop from sitting or lying in the same position for long periods. The use of restraints has not been shown to prevent harmful falls among hospitalized patients.
- Medications — Medications to control difficult behavior are only to be considered as a last resort, if the patient’s agitation is so extreme as to be a potential source of harm. Some classes of drugs, especially sedatives such as lorazepam and diazepam, can build up in the bloodstream and cause the person to become more confused. Antipsychotic medications, such as haloperidol, may be considered, but only in small doses and for short periods of time. If necessary, these medications should be stopped frequently, with direction or approval by the physician, so that the patient can be reevaluated. Antipsychotic medications are not recommended for long-term treatment.
- For the first-line treatment of a potentially reversible, hyperactive delirium, evidence supports, and published guidelines recommend, the use of first-generation antipsychotics, e.g., haloperidol and chlorpromazine. (These guidelines do not distinguish potentially reversible from irreversible delirium, nor do they address the principal underlying diagnosis and comorbidities, prognosis, functional status, goals of care, or irreversible delirium.)[rx,rx,rx,rx]
- Alpha-2 agonist medication uses have been shown to be effective in decreasing the incidence of delirium in critically ill patients. These agents cause minimal respiratory depression and help in maintaining a low heart rate. Therefore, they facilitate minimal hemodynamic fluctuations and lower energy expenditure that might result in global cerebral insult.[rx] Further, alpha-2 agonists may inhibit the release and production of neurotoxic glutamate, thereby having a neuroprotective effect.[rx]
- Likewise, opioids have no role in the treatment of agitation or delirium. These are analgesics with no anti-agitation actions. Sedation is a side effect of opioids (not a therapeutic effect), and is not reliable from patient to patient or opioid to opioid. Care should be taken to differentiate pain-related behaviors from delirium-induced behaviors.
- These function as sedatives, anxiolytics – skeletal muscle relaxants, amnestics, and potent antiepileptics. Using the titration technique[rx] discussed above, the minimum benzodiazepine dose needed to rapidly and safely relieve symptoms can be established. The dose of a benzodiazepine typically needed to control the symptoms of delirium is far below their median lethal dosages.[rx,rx]
- Olanzapine an atypical antipsychotic – has also been tested as a prophylactic agent to prevent postoperative delirium. 495 elderly patients undergoing elective knee or hip replacement were either assigned to a placebo arm or a treatment arm of 10mg of oral olanzapine. The treatment group had a significantly decreased incidence of delirium, but those patients who did suffer delirium had a longer, more severe course [rx].
- Donepezil – a cholinesterase inhibitor FDA-approved for the treatment of Alzheimer’s disease, has also been tried as a prophylactic agent for delirium. Eighty patients were randomized to receive donepezil 14 days prior to and 14 days after surgery. There was no significant difference in the two groups [rx].
Following are example of environmental interventions
- Engage patients in mentally stimulating activities to help them with disordered thinking
- Provide orienting and familiar materials to help patients know the time and date, where they are, and which staff are working with them.
- Ensure all individuals identify themselves each time they encounter the patient, even if the encounters are minutes apart.
- Minimize the number of people interacting with the patient and the quantity of stimulation the patient receives, e.g., television or loud music
- Use family or volunteers as constant companions to help reassure and reorient a delirious patient. Encourage staff to sit with the patient while they do their documentation
- Provide adequate soft lighting so patients can see without being overstimulated by bright lights.
- Manage fall risks.
- Provide warm milk, massage, warm blankets, and use relaxation tapes to optimize sleep hygiene and minimize sleep disturbances.
- Ensure patients use their glasses, hearing aids, etc., to optimize orientation, decrease confusion, and promote better communication.
- Ensure patients have good nutrition and an effective bowel and bladder management strategy.
- Monitor fluid intake. Rehydrate with oral fluids containing salt, e.g., soups, sport drinks, red vegetable juices. When necessary, infuse fluids subcutaneously rather than intravenously.[rx–rx]
- Use physical restraints only as a last resort to temporarily ensure the safety of both staff and a severely agitated and not redirectable patient,[rx,rx] and only until less restrictive interventions are possible.
- Provide education and support to help family members cope with what they are witnessing.[rx]
Altered mental status
To prevent relapse, the patient should be referred to alcoholic anonymous and other support groups.
Cognitive behavior therapy may help some patients prevent relapse
A referral to a psychiatrist to assess for depression and anxiety may help abstain from alcohol.
These tips may help
- Provide a reassuring environment for the patient, such as a quiet, well-lit room with familiar people and objects. It may also help to place a clock and wall calendar where a patient can see it.
- Talk with the doctor, nurse, or another member of the health care team about a patient’s hallucinations or unusual behaviors. The health care team can help you learn what to expect and how to manage these symptoms.
- Ask about stopping or switching medications that may worsen a patient’s mental confusion. Also, ask if there are other, untreated medical conditions that may be the cause of delirium.
- In some cases, giving antipsychotic medications helps control the symptoms of delirium. Although these drugs can have side effects, most can be managed well.