What are the first-line medications for agitation in the Intensive Care Unit (ICU)?

From the Guidelines

For agitation in the ICU, first-line medications include dexmedetomidine, propofol, and antipsychotics like haloperidol, with dexmedetomidine being preferred for its minimal respiratory depression and ability to maintain arousability. The choice of agent depends on the patient's hemodynamic stability, underlying cause of agitation, and whether the patient is mechanically ventilated 1. Before medication administration, non-pharmacological approaches should be attempted, including reorientation, ensuring day-night cycles, early mobility, and addressing pain, constipation, or urinary retention.

Some key considerations for medication selection include:

• Dexmedetomidine (0.2-0.7 mcg/kg/hr IV infusion) offers minimal respiratory depression and maintains arousability 1.
• Propofol (5-80 mcg/kg/min IV infusion) has a rapid onset and offset but may cause hypotension and respiratory depression.
• Antipsychotics like haloperidol (0.5-5 mg IV every 6 hours as needed) can be effective, but their use should be cautious due to potential side effects.
• Benzodiazepines like midazolam (1-2 mg IV every 2-4 hours as needed) should be used cautiously due to their association with delirium 1.

Regular reassessment using validated tools like the RASS (Richmond Agitation-Sedation Scale) is essential to titrate medication and prevent oversedation. Addressing reversible causes of anxiety, delirium, and agitation, such as hypoxia, urinary retention, and constipation, is also crucial 1. The most recent and highest quality study, from 2020, supports the use of haloperidol and benzodiazepines in specific situations, but also emphasizes the importance of non-pharmacological approaches and careful medication selection 1.

From the FDA Drug Label

Olanzapine for Injection is indicated for the treatment of acute agitation associated with schizophrenia and bipolar I mania The recommended dose in these patients is 10 mg. A lower dose of 5 or 7.5 mg may be considered when clinical factors warrant. Midazolam is used for sedation before diagnostic or surgical procedures, and for the treatment of seizures. Haloperidol injection is indicated for the treatment of schizophrenia and for the control of agitation and aggression in patients with schizophrenia.

First line medications for agitation in the ICU:

• Olanzapine (IV): 10 mg dose, with a lower dose of 5 or 7.5 mg considered when clinical factors warrant 2
• Midazolam (IV): used for sedation, with a dose that must be individualized and carefully titrated to the patient's underlying medical/surgical conditions 3
• Haloperidol (IV): used for the treatment of schizophrenia and for the control of agitation and aggression in patients with schizophrenia, with a dose that must be carefully selected and monitored 4

From the Research

First-Line Medications for Agitation in the ICU

The management of agitation in the ICU is crucial to prevent complications and ensure patient safety. According to the available evidence, the following medications are considered first-line treatments for agitation in the ICU:

• Haloperidol: a neuroleptic that can be used to treat agitation, especially in patients with delirium 5, 6
• Lorazepam: a benzodiazepine that can be used to treat agitation, especially in patients with terminal delirium or delirium tremens 7, 8
• α2 agonists: may be considered as an alternative to haloperidol and lorazepam in certain cases 9

Considerations for Medication Selection

When selecting a medication for agitation in the ICU, the following factors should be considered:

• Underlying cause of agitation: medication selection may vary depending on the underlying cause of agitation, such as delirium, pain, or withdrawal syndrome 9
• Patient population: elderly patients, brain-injured patients, and patients with sleep deprivation may require special consideration when selecting a medication for agitation 9
• Dosing and administration: the dose and administration route of the medication should be carefully considered to minimize the risk of adverse effects 5, 6

Potential Risks and Benefits

The use of medications for agitation in the ICU is associated with potential risks and benefits, including:

• Risks: sedation, oversedation, delirium, and other adverse effects 5, 7, 8
• Benefits: improved patient safety, reduced risk of complications, and improved management of agitation 9, 6