Delirium medical therapy

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

Non-pharmacological treatments

Delirium is not a disease, but a syndrome (i.e. collection of symptoms) indicating dysfunction of the brain, in the same way shortness of breath describes dysfunction of the respiratory system, but does not identify the disorder. Treatment of delirium is achieved by treating the underlying dysfunction cause, or in many cases, the causes (plural), as delirium is often multi-factorial. Non pharmacological methords 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 (e.g. 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.

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 in secure and closed surroundings.
• Distract agitated wandering patient, relatives can prove helpful in curtailing agitation.
• If 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 follwing stratergies,

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. If non pharmacological techniques fail, or if de-escalation techniques are inappropriate, only then pharmacological treatment is indicated.

Medical Therapy

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, 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. conditions the brain. 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 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. Physostigmine a anticholinergic drug can useful if delirium is caused by anticholinergic medications. For hypercatabolic conditions and extreamly agitated patients may be managed with paralysis, sedation, and mechanical ventilation. Palliative treatment with opiates may be needed by patients with delirium for whom pain is an aggravating factor. Multivitamin replacement is required if B vitamin deficiencies is suspected.(e.g.alcoholic or malnourished).

Pharmacotherapy

• Antipsychotics
• Sedatives
• Antidepressants

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 adjuvalent to haloperidol, others, such as risperidone, quetiapine, Ziprasidone, and aripiprazole have shown promising results in the clinical studies. British professional guidelines of the National Institute for Health and Clinical Excellence advise haloperidol or olanzapine. Typically haloperidol dose differs wrt severity of symptoms and comorbidity of the patients.

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 (e.g., haloperidol bolus, 10 mg i.v., followed by continuous intravenous infusion of 5–10 mg/hour). Droperidol can be given alone or after haloperidol, if quicker results are desired. Always start with the lowest possible dose and titrate according to symptoms. 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. It's presentation is similar to antipsychotic overdose. Symptomology 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 (e.g., haloperidol bolus, 10 mg i.v., followed by continuousintravenous 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 at 0.75mg per day to 3.1mg per day has demonstrated moderate to marked improvement of in delirium on the Clinical Global Impressions Scale, Brief Psychiatric Rating Scale, and Trzepacz Delirium Rating Scale. Risperidol was found to be equivalent to haloperidol in terms of response rates and efficacy. 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 patient is 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 a select cases of delirium, such as:

• Alcholol withdrawal
• Benzodiazepine withdrawal
• When antipsychotics are contraindicated,

1. Parkinson's disease
2. neuroleptic malignant syndrome
3. dementia with Lewy bodies

Benzodiazepines can cause delirium or may worsen the condition.

Antidepressants

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

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
• if severe physostigmine

Discharge

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

Follow up

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

Unique Challenges in the Treatment of Delirium

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.

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.