Management of Acute Agitation and Delirium in Adults
Full update July 2023
The following charts provide information to help guide pharmacotherapy for acute agitation and/or delirium, when necessary. Mild to moderate agitation may respond to verbal de-escalation or calm surroundings.5,7 Assess oxygen saturation, glucose level, and electrolytes.5 Consider infection as a possible cause.5 Treat the patient with meds if the patient is a danger to themselves or others, or is not calm enough to be medically evaluated.7 Consider oral options if the patient can cooperate and quick onset is not imperative, and intramuscular over intravenous (unless the patient already has IV access).18,20 A toolbox offering strategies and resources for preventing and treating delirium is also provided.
Management of Acute Agitation in Adults by Clinical Scenario
Clinical Scenario |
Suggested Options or Resources |
Alcohol intoxication |
Consider an antipsychotic.7 Try to avoid benzodiazepines due to risk of respiratory depression.7 Ketamine is an emerging option.21 Consider it second-line.4 Consider alcohol withdrawal (below) instead of intoxication if a patient with a history of alcohol use has a low or undetectable alcohol level or withdrawal symptoms such as delirium, sweating, tachycardia, or tremors.7 |
Alcohol withdrawal |
Use a benzodiazepine first-line to control symptoms and prevent seizures from withdrawal.28 If the patient is cooperative, use an oral benzodiazepine (e.g., chlordiazepoxide, diazepam, lorazepam); otherwise, use a parenteral benzodiazepine (e.g., lorazepam or midazolam [faster onset]).4,7,24
|
Delirium |
Treat/address underlying causes (e.g., hypoxia, hypoglycemia, infection, medications, electrolyte disturbances).7
If neither alcohol nor benzodiazepine withdrawal is suspected, an antipsychotic is usually the drug of choice.7
Dexmedetomidine is suggested for delirium in ventilated patients if agitation is interfering with weaning and extubation [Evidence level B-1]37,54 Ketamine is an emerging option.21 Consider it second-line.4 See our toolbox below, Preventing and Treating Delirium in Inpatients, for more information. |
Dementia |
Assess for pain or other treatable causes.8 Lean toward an antipsychotic vs a benzodiazepine in the elderly, due to fall risk.10
Warnings about excess mortality associated with the use of antipsychotics in patients with dementia are based on studies of several weeks’ duration.8 Harm may come to the patient or others from withholding antipsychotics in an acute situation.8 |
Psychosis or Mania |
If the patient is cooperative, use an oral antipsychotic (e.g., risperidone, olanzapine).4,7
Parenteral antipsychotic options include droperidol, olanzapine, aripiprazole, or haloperidol.6,30,42 Consider adding a benzodiazepine (e.g., lorazepam 1 to 2 mg, midazolam [faster onset]):4,7,26
Dexmedetomidine sublingual film is an emerging option for patients with agitation due to schizophrenia or bipolar disorder. See “Dexmedetomidine” row below for additional information. |
Stimulant intoxication (e.g., methamphetamine) |
Generally use a benzodiazepine first-line.7
Ketamine is an emerging option.21 Consider it second-line.4 |
Traumatic brain injury |
Evidence is limited.41 Consider olanzapine,
Benzodiazepines are commonly used, except in cases of alcohol or benzodiazepine withdrawal, but some evidence suggests that they might impede neurologic recovery, and increase length of stay and duration of amnesia.41 |
Unknown cause |
With psychotic symptoms (see above):
Without psychotic symptoms:
Ketamine is an emerging option.13 Consider it second-line.4 |
-Continue to the next section for a Comparison of Therapeutic Options for Acute Agitation in Adults-
Comparison of Therapeutic Options for Acute Agitation in Adults
Drug |
Administration Tips/Comments |
Dexmedetomidine, sublingual |
Consider a sublingual or buccal dose of 120 mcg (film) for mild or moderate agitation, or 180 mcg (film) for severe agitation, in adults with schizophrenia or bipolar disorder.11 Two additional half doses may be given, 2 hours apart.11 Max total dose in 24 hours is 240 mcg (mild to moderate agitation) or 360 mcg (severe agitation).11 Only use the 120 mcg dose for patients 65 years or older. Dose should be reduced in liver impairment.36 Efficacy:
Safety:
|
Droperidol |
Efficacy:
Safety:
|
Haloperidol |
If the patient is cooperative, use PO haloperidol 5 mg.7 May repeat in 15 minutes.7 If parenteral dosing is needed, consider starting with 5 mg IM.7 Single doses higher than 7.5 mg to 10 mg are not more effective for most patients and may have more side effects.6 May repeat in 15 minutes.7 Can give IV(off-label) if access is available and benefits of rapid sedation outweigh risks. If given IV, start with 1 to 2 mg. May repeat in 15 minutes.11 Push over several minutes to decrease the risk of side effects (e.g., hypotension, arrhythmias, movement disorders).11 Continuous ECG monitoring recommended.11 Most patients respond to one to three doses.3 Maximum total dose in 24 hours is 20 mg PO/IM (5 to 10 mg IV).7 Efficacy:
Safety:
|
Ketamine |
Ketamine (e.g., 4 to 5 mg/kg IM [maximum 500 mg/dose] or 1 mg/kg IV) is emerging as an option:13,21
Efficacy:
Safety:
|
Midazolam |
Consider midazolam 2.5 to 5 mg IM or IV, alone or with droperidol, to get agitated adult patients under control quickly (e.g., <10 minutes).14,17,18,22 Efficacy:
Safety:
|
Olanzapine |
If patient is cooperative, use PO olanzapine 5 to 10 mg. May repeat in 2 hours. Maximum total dose in 24 hours is 20 mg.7 An orally disintegrating tablet is available. IM dose is 10 mg. May repeat in 20 minutes. Maximum total dose in 24 hours is 30 mg.7 Do NOT use the extended-release IM injection (Zyprexa Relprevv). Can give IV (off-label) if access is available and benefits of rapid sedation outweigh risks. May be as effective as droperidol.23 Consider a conservative starting dose of 2.5 to 5 mg IV. May repeat in five minutes [Evidence level B-3 and B-1].2,14 A dose of 10 mg, followed by a dose of 5 mg after five minutes if needed, has been studied.14 Requires reconstitution.12 Efficacy: Time to sedation similar to droperidol (i.e., median time to sedation <15 minutes) [Evidence level B-1].14 More effective than haloperidol [Evidence level B-3].19 Safety: Some experts recommend monitoring for respiratory depression for at least an hour after use, especially in cases of alcohol intoxication.2 Use of parenteral olanzapine with parenteral benzodiazepines is not recommended in the product labeling due to risk of excessive sedation and cardiorespiratory depression based on post-marketing reports.12,33 However, other data suggests that olanzapine may not be riskier than other antipsychotics in regard to respiratory depression.22,31,33 Do NOT use the extended-release IM injection (Zyprexa Relprevv [US]).12 |
Quetiapine |
Often used for ICU delirium and preferred for patients with Parkinson’s disease or Lewy body dementia.18,53 For patients with Parkinson’s disease or Lewy body dementia, consider a dose of 12.5 mg to 25 mg.18 Consider starting with 50 mg twice daily (12.5 to 50 mg per day in elderly).44 |
Risperidone |
Initial dose is 2 mg (oral; 0.5 to 1 mg in elderly).7,18 May repeat in 2 hours. Maximum total dose in 24 hours is 6 mg.7 An orally disintegrating tablet is available. |
Ziprasidone |
No advantage over other options. Initial dose is 10 to 20 mg IM. May repeat every two hours (10 mg) or four hours (20 mg). Maximum total dose in 24 hours is 40 mg.15 Appears to pose a relatively high risk of QT prolongation.15 Avoid in patients at risk of torsades de pointes.1 May take three to five minutes to reconstutite.27 Can store reconstituted solution for up to seven days in the refrigerator, or 24 hours at room temperature if protected from light.15 A hazardous drug (i.e., requires special handling in people of childbearing potential due to reproductive risk).12,34 Relatively expensive. |
-Continue to the next section for a toolbox for Preventing and Treating Delirium in Adults-
Preventing and Treating Delirium in Inpatients
Goal |
Suggested Strategies or Resources |
Identify patients at high risk of delirium. |
Risk factors can be categorized as predisposing factors or precipitating factors.9 The more predisposing factors a patient has, the more susceptible they are to precipitating factors.9
Precipitating risk factors include:9
Risk factors with the strongest association for delirium in ICU patients are:37
|
Review medications and make recommendations to reduce the risk of delirium. |
Attempt to reduce the use of medications, especially psychoactive medications and others associated with delirium (e.g., anticholinergics, benzodiazepines, and opioids).1,9,43
If needed, use the lowest effective dose of medications that could cause delirium.44 Ensure sedatives are used for a specific indication, targeting a light level of sedation.37
Recommend regimens for pain control when needed, using a multi-modal approach incorporating nonpharmacological interventions, non-opioid analgesics, regional anesthesia if appropriate, and the lowest effective doses of opioids if they are necessary.37
Look for meds that may cause constipation or dehydration. Recommend an effective bowel regimen and hydration such as IV fluids as appropriate.1 Schedule medication administration to prevent disturbing a normal sleep-wake cycle, if possible.1 Avoid starting medications such as antipsychotics, melatonin, or ramelteon for prophylaxis of delirium due to a lack of evidence for the practice.37,47 Cholinesterase inhibitors may be harmful.53 |
Use non-drug measures to prevent delirium. |
Implement non-drug preventive measures, such as:37
Use of the ABCDEF bundle (e.g., optimizing pain control, minimizing sedative use, early mobility, etc) in ICU patients is associated with less delirium.37 |
Watch for symptoms and screen regularly using a validated tool. |
Symptoms of delirium include:48
There are three types of delirium:48
The onset of symptoms is typically acute (i.e., hours to days).48 Delirium has been described as “acute brain failure.”9 The course of symptoms is typically fluctuating.48 Use a validated tool regularly (e.g., once per shift) to assess for delirium.37
|
Recommend drug treatment for delirium when needed. |
For agitation, see our chart, Management of Acute Agitation in Adults by Clinical Scenario, above. Consider use of the Richmond-Agitation Sedation Scale to help guide treatment (https://www.mdcalc.com/richmond-agitation-sedation-scale-rass) to identify patients who are agitated or combative. |
Discontinue drug treatment for delirium as appropriate. |
Medications to treat delirium are typically needed for one week or less.1 Consider stopping drug treatment (tapering if necessary) once symptoms are controlled.44,51 Evaluate the need for continuing antipsychotics daily.51 About 20% of patients who start an antipsychotic medication for delirium during an ICU stay continue on the drug after discharge from the hospital.55 Continuing antipsychotics unnecessarily can increase the risk of drug side effects and increase costs.37 |
Consult resources for updated information on the prevention and treatment of delirium. |
American Delirium Society (https://www.americandeliriumsociety.org/) ICU Delirium and Cognitive Impairment Study Group (http://www.icudelirium.org) Canadian Coalition for Seniors’ Mental Health (https://ccsmh.ca/) American Geriatrics Society (https://www.americangeriatrics.org/) Society of Critical Care Medicine (https://www.sccm.org/Home) |
Abbreviations: ECG = electrocardiogram; ICU = intensive care unit; IM = intramuscular; IV = intravenous; PO = oral; SNRI = serotonin norepinephrine reuptake inhibitor; SSRI = selective serotonin reuptake inhibitor.
Levels of Evidence
In accordance with our goal of providing Evidence-Based information, we are citing the LEVEL OF EVIDENCE for the clinical recommendations we publish.
Level |
Definition |
Study Quality |
A |
Good-quality patient-oriented evidence.* |
|
B |
Inconsistent or limited-quality patient-oriented evidence.* |
|
C |
Consensus; usual practice; expert opinion; disease-oriented evidence (e.g., physiologic or surrogate endpoints); case series for studies of diagnosis, treatment, prevention, or screening. |
*Outcomes that matter to patients (e.g., morbidity, mortality, symptom improvement, quality of life).
[Adapted from Ebell MH, Siwek J, Weiss BD, et al. Strength of Recommendation Taxonomy (SORT): a patient-centered approach to grading evidence in the medical literature. Am Fam Physician 2004;69:548-56. https://www.aafp.org/pubs/afp/issues/2004/0201/p548.html.]
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Cite this document as follows: Clinical Resource, Management of Acute Agitation and Delirium in Adults. Pharmacist’s Letter/Pharmacy Technician’s Letter/Prescriber Insights. July 2023. [390722]