Timely diagnosis

Be vigilant for the possibility of delirium; remember that many symptoms may be confused with other psychiatric syndromes, particularly depression in cases of hypoactive delirium and agitation in cases of substance intoxication and withdrawal.

Obtain information on the patient's baseline level of cognitive functioning from all available accessory sources (e.g., spouse, family, or nursing staff).

Screen for the development of delirium in high-risk groups. Use objective delirium rating scales if possible [e.g., Delirium Rating Scale-98 (+73) or confusion assessment method (+74)].

Identify and treat underlying medical problems that may be causing or contributing to delirium in your particular patient (+Table 1). The ultimate treatment of choice is the timely discovery and correction of the underlying medical causes of delirium. That is, aggressively treat infectious processes and electrolyte imbalances, correct vital signs and end-organ functioning, restore a more physiological sleep-wake cycle, minimize fear, anxiety, and pain, and manage extrinsic/environmental factors, such as lighting and noise control.*

Institute non-pharmacological treatment strategies* (based on Inouye's multicomponent intervention method for prevention of delirium in elderly patients) (+58).

Correct malnutrition, dehydration, and electrolyte abnormalities as quickly and safely as possible.

Remove immobilizing lines and devices (i.e., intravenous lines, chest tubes, bladder catheters and physical restraints) as early as safely possible.

Correct any sensory deficits the patient may have (i.e., eyeglasses or hearing aids).

Promote as normal a circadian sleep pattern as possible. It is better if this can be achieved by environmental manipulations, such as light control (i.e., lights on and curtains drawn during the day and lights off at night) and noise control (i.e., provide ear plugs, turn off TVs, and minimize night staff chatter) rather than by the use of medications.

Provide adequate intellectual and environmental stimulation as early as possible (e.g., orient the patient to date, time, and circumstance regularly, provide a newspaper, or set the TV to a news broadcast rather than to reruns).

Minimize environmental isolation.

Consider pharmacological treatment strategies.

Conduct an inventory of all pharmacological agents being administered to the patient. Any medication or agent known to cause delirium or to have high anticholinergic potential should be discontinued, if possible, or a suitable alternative should be instituted.*

Avoid using GABA-ergic agents to control agitation, if possible.* Exception: In patients undergoing CNS depressant withdrawal (i.e., alcohol, benzodiazepines, or barbiturates) or when more appropriate agents have failed and sedation is needed to prevent patient's harming himself or herself.

Adequately assess and treat pain because uncontrolled pain has been found to be a contributor to the development and exacerbation of delirium.*

Avoid the use of opioids for behavioral control of agitation (i.e., use only for pain management), because opioid use has been associated with delirium.*

For the pharmacological target management of delirium (all types) consider using the following.

Acetylcholinesterase inhibitor (e.g., rivastigmine, donepezil, physostigmine, or rivastigmine) for correction of central anticholinergic syndrome.

Serotonin antagonist (e.g., ondansetron), to control toxic elevations of serotonin usually associated with hypoactive delirium, although some studies have suggested use of a serotonin antagonist may be indicated in all types of delirium.

Opioid agent rotation, such as switching from morphine and meperidine to fentanyl or hydromorphone.

Melatonin or melatonin agonists (e.g., ramelteon) to promote a more natural sleep.

Dopamine antagonists to manage the theorized abnormally elevated levels of dopamine and provide restoration of putative hippocampal functions (e.g., short-term memory) and reversal of other regional brain disturbances (e.g., agitation, psychosis, or primitive reflexes), as well as to protect neurons against hypoxic stress and injury (+2, +75). The dose of dopamine antagonist used may depend on the type of delirium being treated (+1, +76++—+79).

α₂ Adrenergic agonists (e.g., dexmedetomidine or clonidine) for protection against the acute release of norepinephrine due to hypoxia or ischemia, which leads to further neuronal injury and the development or worsening of delirium. The data to date are more robust for delirium prevention (+69, +80),* although data are emerging for treatment, especially delirium associated with massive norepinephrine discharges (i.e., alcohol withdrawal).

N-methyl-d-aspartate receptor blocking agents to minimize glutamine-induced neuronal injury (e.g., amantadine or memantine).

For hyperactive delirium:

Use low to moderate doses of haloperidol (e.g., <20 mg/24 hour), if the patient's cardiac condition allows it and there are no significant electrolyte abnormalities.*

Before using haloperidol, obtain a 12-lead electrocardiogram and measure the corrected Q-T interval (QTc) and electrolyte levels. Correct potassium and magnesium levels, if needed.

If possible, avoid the use of other medications known to increase QTc and/or inhibitors of CYP3A4.

Discontinue use of haloperidol if QTc increases to >25% of baseline or >500msec.

When the use of haloperidol is contraindicated or not desirable (i.e., prolonged QTc or history of severe extrapyramidal symptoms), atypical antipsychotics should be considered (+1, +81):

Evidence is better for risperidone and quetiapine.*

Limited data are available for olanzapine, aripiprazole, and perospirone.

Avoid clozapine and ziprasidone. Note: antipsychotics should be used with caution and only short term for the management of delirium or agitation in patients suffering from dementia. Data suggest a twofold increase in mortality for patients with dementia after long-term treatment with antipsychotic agents (+82).

For hypoactive delirium:

Evidence suggests that dopamine antagonists may still have a place, given the excess dopamine theory.

If haloperidol is used, recommended doses are in the very low range (i.e., 0.25—1 mg/24 h).*

If an atypical antipsychotic is preferred, consider an agent with low sedation (i.e., risperidone); unless a sedative agent is needed to restore the sleep-wake cycle if there is not response to E.4 (see above).

In patients with extreme psychomotor retardation or catatonic features, in the absence of agitation or psychosis, consider the use of psychostimulant agents (e.g., methylphenidate, dextroamphetamine, or modafinil) or conventional dopamine agonists (e.g., bromocriptine, amantadine, or memantine).