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Acute agitation (a “Code White”) in the medical setting can present as a challenge for both patients and health care providers. When using medications to manage acute agitation, there are several key concepts to consider, including the route of administration, onset of action, absorption, half-life, and the risk of adverse events.
What to Give?
Current practices for acutely agitated patients includes the combined use of an antipsychotic and a benzodiazepine. The reason for this combination is because it results in a rapid onset of action, with a short total duration of action and high sedation. Certain types of antipsychotics are also chosen to lower the risk of extrapyramidal symptoms (EPS). Anticholinergics may be given in combination as well to reduce the risk of extrapyramidal symptoms.
Don't Forget About Verbal De-escalation!
Before doing any kind of pharmacological intervention for agitation, always think about non-pharmacological ways to de-escalate the situation. In any Code White situation, understand that a patient is usually feeling threatened or scared, often due to their psychiatric symptoms or the stressful environment that they are in. In these cases, it is helpful to consider triggers that may be leading to these behaviours. For example, is there some way to bring the patient to a calmer environment and avoid the need for medications?
If security or additional staff are called to a Code White, it is important to outline to an agitated patient why there are additional people. If the patient doesn't understand why so many people are near them, this may worsen agitation or cause fear! Reassure the patient. For example, it can be helpful to tell the patient: “You may be wondering why there are security guards here. We work as a team and the staff are here for everyone's safety, including yours.”
Haloperidol or loxapine are the most commonly used medications in management of acute agitation.
Haloperidol versus Loxapine
Adapted from Procyshyn, Ric M., Kalyna Z. Bezchlibnyk-Butler, and J. Joel Jeffries. Clinical Handbook of Psychotropic Drugs. Hogrefe, 2017.
| Description | Haloperidol | Loxapine |
Potency | The amount of medication that needs to be given | High | Intermediate |
D2 Antagonism | Amount of antipsychotic effect, and EPS risk | +++++ | ++++ |
H1 Antagonism | Amount of sedation, drowsiness, postural hypertension | + | +++ |
5-HT2 Antagonism | Amount of anxiolytic effect/sedation | +/+++ | +++/++++ |
ACh M1 Antagonism | Mitigation of EPS, sedation | + | ++ |
TYPICAL ANTIPSYCHOTICS ARE CONTRAINDICATED in LBD
A severe sensitivity reaction occurs in an estimated 25-50% of
Dementia with Lewy Bodies (DLB) patients administered typical antipsychotic drugs (especially haloperidol). This results in cognitive impairment, sedation, increased/irreversible acute onset of parkinsonism, or symptoms resembling
neuroleptic malignant syndrome. If an antipsychotic must be used, then low potency atypical antipsychotics like clozapine or quetiapine should be used.
Emergency Benzodiazepine Use
| Onset of Action | Half-life |
Lorazepam | Rapid | 12 hours |
Clonazepam (PO) | Rapid | 12-48 hours |
Diazepam | Rapid | 24-100 hours |
Midazolam | Intermediate | 2-3 hours |
Alprazolam (PO) | Intermediate | 12 hours |
Antipsychotics
Loxapine 25 PO/IM q1h PRN for agitation (max 100mg/24hrs) |
Haldol 2.5-5mg PO/IM q1h PRN for agitation (max 20mg/24hrs) |
Olanzapine 5-10mg PO q2h PRN for agitation (max 20mg/24hrs) |
Lorazepam 1-2mg PO/SL/IM q1h PRN for agitation (max 8mg/24hrs) |
EPS Prevention
Benztropine 2mg PO q4h PRN for symptoms of EPS (max 6mg/24hrs) |
Pearls
IM Tip
Lorazepam and haloperidol can be delivered in the same syringe, whereas lorazepam and loxapine will require 2 separate injections.
For Providers