Delirium medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Pratik Bahekar, MBBS [2] ; Vishal Khurana, M.B.B.S., M.D. [3]

Overview

Treatment of delirium involves two main strategies: first, treatment of the underlying presumed acute cause or causes; secondly, optimizing conditions of the brain. This involves ensuring that the patient with delirium has adequate oxygenation, hydration, nutrition, and normal levels of metabolites, so that drug effects are minimized, constipation treated, pain treated, and so on. Detection and management of mental stress are also very important. Therefore, the traditional concept that the treatment of delirium is 'treat the cause' is not adequate; patients with delirium actually require a highly detailed and expert analysis of all the factors which might be disrupting brain function. This involves ensuring that the patient with delirium has adequate oxygenation, hydration, nutrition, and normal levels of metabolites, that drug effects are minimized, constipation treated, pain treated, and so on. Detection and management of mental stress is also very important.

Non-Pharmacological Treatments

• Delirium is not a disease, but a syndrome (collection of symptoms) indicating dysfunction of the brain.
• Treatment of delirium is achieved by treating the underlying dysfunction cause.
• Non-pharmacological methods are the first measure in delirium unless there is severe agitation that places the person at risk of harming oneself or others.
• Avoiding unnecessary movement
• Avoidance of inter-and intra‑ward transfers
• Continuity of care from caring staff
• Avoidance of physical restraints
• Involving family members
• Having recognizable faces at the bedside
• Sensory aids should be available and working where necessary
• Maintenance or restoration of normal sleep patterns
• Approach and handle gently
• Avoid sudden and irritating noise (Pump alarms)
• Careful management of bowel and bladder elimination
• Having a means of orientation available (such as a clock and a calendar) may be sufficient in stabilizing the situation
• Reassurance and explanation to the patient and carer of any procedures or treatment, using short simple sentences
• If this is insufficient, verbal and non-verbal de-escalation techniques may be required to offer reassurances and calm the person experiencing delirium.

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The T-A-DA Method (Tolerate, Anticipate, Don't Agitate)

• T-A-DA is an effective management technique for people with delirium.
• All unnecessary attachments are removed (IVs, catheters, NG tubes) which allows for greater mobility.
• Patient behavior is tolerated, even if it is not considered normal as long as it does not put the patient or other people in danger.
• This technique requires that patients have close supervision to ensure that they remain safe.
• Patient behavior is anticipated so care givers can plan required care.
• Patients are treated to reduce agitation.
• Reducing agitation may mean that patients are not reoriented if reorientation causes agitation.

Wandering and Rambling Speech

• Wandering patients needs close observation insecure and closed surroundings.
• Distract agitated wandering [[patient], relatives can prove helpful in curtailing agitation.
• If the patient is agitated, rule out common stressors such as pain, thirst, need for toilet.
• It is not advisable to agree with rambling talk, instead one may follow the following strategies:

1. Acknowledge the feelings expressed ‑ ignore the content
2. Change the subject
3. Tactfully disagree (if the topic is not sensitive)

Restrains

• Physical restraints are often used as a last resort with patients in a severe delirium.
• Restraint use should be avoided as it can increase agitation and risk of injury.
• In order to avoid the use of restraints some patients may require constant supervision.
• Local laws on restrains must be well known to care providers.
• If non-pharmacological techniques fail, or if de-escalation techniques are inappropriate, only then pharmacological treatment is indicated.

Medical Therapy

• Physostigmine a cholinergic drug can useful if delirium is caused by anticholinergic medications.
• In hypercatabolic conditions and extremely agitated patients recommendation is paralysis, sedation, and mechanical ventilation.
• Palliative treatment with opiates may be needed for patients with delirium for whom pain is an aggravating factor.
• Multivitamin replacement is required if B vitamin deficiencies are suspected.(alcoholic or malnourished).

Pharmacotherapy

• Antipsychotics
• Sedative
• Cholinergic
• Morphine and Paralysis
• Antidepressant

• For patients who have agitation, comparative randomized controlled trials have found that midazolam combined with droperidol may be better than droperidol or olanzapine alone.

Antipsychotics

• Haloperidol is considered as a gold standard treatment for delirium.
• Typical antipsychotic drug is a preferred drug in delirium, because of its lower anticholinergic properties.
• Amongst atypical antipsychotics olanzapine is used along alone or adjuvant to haloperidol, others, such as risperidone, quetiapine, ziprasidone, and aripiprazole have shown promising results in the clinical studies.
• Use of haloperidol or ziprasidone in ICU admitted patients with acute respiratory failure or shock and hypoactive or hyperactive delirium, was not effective in reduction of delirium.
• Low dose of haloperidol and olanzapine have the same efficacy in treatment of delirium.
• Typically haloperidol dose differs with the severity of symptoms and co-morbidity of the patients.

Dose of Haloperidol

Geriatric population, and seriously ill patients	0.25 - 0.50mg four hourly
Healthier patients	2mg - 3mg per day
Very agitated patients	5mg - 10mg per hour iv

• Haloperidol can be administered orally, intramuscularly, or intravenously.
• IV route can reduce extrapyramidal side effects.
• Continuous IV infusions can be given instead of multiple IV bolus doses (haloperidol bolus, 10 mg i.v., followed by continuous intravenous infusion of 5–10 mg/hour).
• Droperidol has quick sedative effect in agitated patients with less respiratory or cardiac side effects.
• Antipsychotics are usually given for a short period of time approximately 1 week.
• Long-acting olanzapine injection, sometimes may cause delirium, this is known as a post-injection delirium sedation syndrome.
• The presentation is similar to antipsychotic overdose.
• Symptoms may range from confusion, sedation, dizziness, to extrapyramidal effects.
• Patients who require multiple bolus doses of antipsychotic medications, continuous intravenous infusions of antipsychotic medication may be useful ( haloperidol bolus, 10 mg i.v., followed by continuous intravenous infusion of 510 mg/hour; lower doses may be required for elderly patients).
• For patients who require a more rapid onset of action, droperidol, either alone or followed by haloperidol, can be considered.
• Patient needs to be observed for 3 to 4 hours after administrating the injection.

• Risperidol was found to be equivalent to haloperidol in terms of response rates and efficacy.

• Resperidone was effective in medically hospitalized delirium patients.
• The combination of haloperidol and chlorpromazine has also been tried in a few studies with positive outcomes.
• HIV-associated delirium has been effectively controlled by molindone- 40 to 140mg per day, however, more studies are required to validate this approach.

Sedatives

Indication for prescribing sedatives in delirium:

1. To conduct required diagnostic procedures or to deliver treatment
2. If the patient is a danger to others or themselves
3. Highly agitated or hallucinating patient

• Elderly patients and delirium with hypoactive features do not require sedation.
• All sedatives can cause delirium, especially if drugs like thioridazine, chlorpromazine which have anticholinergic effects.
• Sedatives must be used with caution with minimum possible dosage and should be discontinued if they are no longer required.
• Benzodiazepines can be beneficial in select cases of delirium, such as:
• Alcholol withdrawal
• Benzodiazepine withdrawal
• Contraindications of antipsychotics

1. Parkinson's disease
2. Neuroleptic malignant syndrome
3. Dementia with Lewy bodies

• Benzodiazepines can cause delirium or may worsen the condition.
• Contraindications of benzodiazepines may include hepatic encephalopathy, respiratory depression or compromised lung functions.
• Benzodiazepines must be used with caution if liver functions are compromised.

Cholinergics

• Physostygmine is used in delirium caused by anticholinergic medications.

Morphine and Paralysis

• Extremely agitated patients, unresponsive to other treatment, may need sedation and ventilatory support.
• It increases oxygenation and skeletal muscle exertion.
• Morphine is useful when pain is an important aggravating factor.
• Opiates, especially meperidine can exacerbate delirium because of their anticholinergic properties.

Antidepressants

• The antidepressant trazodone is occasionally used in the treatment of delirium, but it carries a risk of over-sedation, and its use has not been well studied.

List of Commonly Prescribed Medicines Attributing to Delirium

• Antiarrhythmic
• Antihistamine
• Antiparkinsonian drugs such as benzatropine
• Antispasmodic
• Benzodiazepine
• Diuretic e.g. Furosemide
• Incontinence medicines e.g. Oxybutynin
• Opioid Analgesics
• Tricyclic antidepressant.

Reversible Causes of Delirium

Identify reversible causes of delirium and treat them promptly: Hypoglycemia or is Suspected

• IV Thiamine
• IV glucose

Hypoxia or anoxia (secondary to pulmonary compromise, cardiac problems, hypotension, severe anemia, CO poisoning)

• Prompt treatment with oxygen

Hyperthermia

• Rapid cooling

Severe hypertension

• Urgent administration of antihypertensive medications

Alcohol or sedative withdrawal

• Thiamine, folate and other B vitamins
• Intravenous Glucose
• Magnesium
• Phosphate.

Wernicke’s encephalopathy:

• Thiamine hydrochloride i.v. and followed by daily oral or IM doses

Anticholinergic delirium:

• Withdrawal of offending agent
• physostigmine.

Individual and Family Psychological and Social Characteristics

Psychodynamic issues, personality variables, and sociocultural environment are helpful in the management of specific anxieties and reaction patterns.

Discharge

1. The patient should be discharged after consulting all relevant disciplines in the hospital and outpatient care providers.
2. Housing and living issues like washing, dressing, medication must be sorted out before the patient is relieved from the hospital.
3. Cognitive and functional status (e.g. using standardized tools such as AMT and Barthel Index) must be accessed before discharge
4. Discharge summaries must be complete and descriptive.

Follow up

• Delirium is an indication of serious illness, therefore delirium cases must be referred to a Geriatrician, Psychiatrist, Social Worker, etc. for further workup and management.

Unique Challenges in the Treatment of Delirium

Side effects of pharmacotherapy

Antipsychotics:ECG monitoring is required to calibrate QTc interval. Cardiology consult should be done if QTc interval is more than 450msec or it is greater than 25% baseline. Dose adjustment or discontinuation of antipsychotic medication may be warranted. Haloperidol has can cause sedation and hypotension. Lowering of the seizure threshold, galactorrhea, elevations in liver enzyme levels, inhibition of leukopoiesis, neuroleptic malignant syndrome, and withdrawal movement disorders are rare side effects of antipsychotic medication.

'Bezodiazepines': Can cause behavioral dis-inhibition, amnesia, ataxia, respiratory depression, physical dependence, rebound insomnia, withdrawal reactions, and delirium. Adolescents and pediatric may suffer from disinhibition reactions, emotional lability, increased anxiety, hallucinations, aggression, insomnia, euphoria, and in-coordination.

Anticholinergics Causes bradycardia, nausea, vomiting, salivation, and increased gastrointestinal acid. Physostigmine can cause seizures. Tacrine can cause liver function abnormalities.

Education and Reassurement

• It is important for psychiatrist help patient understand symptoms of delirium, by explaining transient nature of delirium can help patients and their families in coping.
• As delirium is accompanied by behavioral changes, sometimes physicians and nursing staff may overlook the underlying medical condition responsible for delirium, therefore it is an important task for a psychiatrist to educate medical care provider about delirium.

Post Delirium Psychiatric Management

• Post recovery patients may remember their experiences during delirium. This can cause significant distress in the patients. Symptoms may range from have vivid, frightening recollections.
• Reassurance and explanation of condition can ease some stress.
• Standard psychiatric interventions utilized following traumatic experiences should be used.
• Psychotherapy can be helpful relieving anxiety, guilt, anger, depression, or other emotional states.

Competency

Because of transient impairment in cognition, orientation and other higher functions, patient may not be able to provide consent or there can be impairment of competency. Delirium itself does not make patient incompetent by law. Emergency cases can be treated without obtaining consent however non emergency cases pose an ethical dilemmas.

Elderly

Antipsychotic drugs can cause serious side effects in the geriatric population. Even though antipsychotic medications are prescribed for shorter duration of time in delirium, it caution must me practiced. Serious side effect tends to occur within 30 days of initiation of the treatment, serious side effects include,

• Extra pyramidal side effects
• Falls
• Hip fracture, are few events which are severe enough to warrant an acute hospital admission. It may also cause death. Serious side effects are more frequent and likely in patients receiving conventional antipsychotic drugs than atypical antipsychotic medicines. Antipsychotics are 1 of the 3 offending medicines that require acute hospitalization in nursing group population.