Reviewing Best Practices in the Treatment of Acute Agitation

Author: Tyler Frieda, PharmD, PGY-1 Pharmacy Resident, Mercy Hospital Springfield

Mentors: Hannah Norris, PharmD, BCPS; Amanda Troup, PharmD, BCPS, PGY-1 Pharmacy Residency Program Director

Program Number:  2021-12-06
Approved Dates:   February 1, 2022-August 1, 2022
Approved Contact Hours:  One Hour(s) (1) CE(s) per session

Objectives

• Explain the importance of appropriate management of acute agitation
• List conditions that contribute to acute agitation
• Explain the importance and role of de-escalation as primary agitation intervention
• Identify the role of pharmacological treatment in acute agitation
• Identify preferred pharmacological treatments of acute agitation based on associated conditions and treatment population

Background

Acute agitation is a symptom that can result from a variety of several different medical and psychiatric conditions. Agitation, especially if severe, can result in harm to the patient themselves, those trying to provide care, or both if not appropriately managed.¹ Several studies consistently show high rates of violence experienced by healthcare workers even in areas other than the emergency department. In a survey study by Li et al of 196 emergency medicine residents, 91% of residents reported experiencing some form of abuse, ranging from verbal abuse to physical attacks.² Similarly, a prospective study of 272 emergency medicine residents and attending physicians by Behnam et al found 78% of study respondents reported at least one act of violence in the last year,³ and a study of 101 emergency medicine physicians by Al-Sahwali et al reported 86% experiencing violence in the workplace with 7% experiencing physical assaults likely to have caused serious harm.⁴ These trends extend beyond the emergency room with 73% of psychiatry residents reported having been threatened with 36% having been physically assaulted based on a study by Schartz and Park,⁵ and a study of 364 workers at public infectious disease clinics by Schulte et al reported 38% experiencing a violent incident.⁶ Workplace violence is not only experienced by physicians as Kansagra et al study of 65 emergency departments found that nurses were least likely to report feeling safe among the healthcare workers interviewed.⁷ While these statistics are not strictly due to cases of agitation, they emphasize the prevalence of violence among healthcare workers, and highlight the importance of taking actions to prevent or minimize situations that place workers in harm. Appropriately managing agitation is one such action in which pharmacists can play an important role.

Etiology

As mentioned previously, agitation has several potential causes, and the pathophysiology, while not completely understood, is multifactorial in nature.^1,8 While psychiatric illnesses are often associated with agitation, they are by no means the only conditions associated with agitation. Table 1 lists conditions attributed to agitation. Differentiating the likely cause of a patient’s agitation is key in determining the treatment of agitation. Knowing the underlying condition will not only guide pharmacological therapy but non-pharmacological approaches as well. However, a thorough medical assessment may not be viable in an acutely agitated patient due to difficulties in acquiring clinical data in patients that may be uncooperative. A retrospective analysis of emergency psychological evaluations by Olshaker et al found that patient history as opposed to other clinical data studied (physical examination, vital signs, and laboratory testing) had the highest sensitivity (94%) for identifying underlying medical problems.⁹ This makes patient history the most important piece of data to collect when trying to assess an agitated patient. If an underlying medical condition that may be attributed to agitation is identified, treatment should focus on resolving the underlying condition.¹ Many of the medical conditions that contribute to agitation (noted in Table 1) are reversible such as metabolic abnormalities or infections. Reversing the contributing medical condition is likely to resolve the agitation as well. However, the time needed to resolve these conditions varies, and patients may require immediate action through one of the pathways discussed in this article.

Non-Pharmacological Treatment

As a pharmacist, it is important to understand the role these non-pharmacological treatment measures have in the treatment of acute agitation. The American Association for Emergency Psychiatry Project BETA expert consensus guidelines on the best practices in the treatment of agitation outline these approaches.^1,10,11 Historically, non-pharmacological approaches have included restraint and seclusion.¹¹ While these approaches are appropriate in select cases after other treatments have failed, de-escalation is regarded as the key approach to calming patients while maintaining the safety of coworkers.^1,10,11 Utilization of de-escalation strategies have been found to enhance a positive clinician-patient relationship, decrease the likelihood of restraints, seclusion, and hospital admissions, and decrease length of stay.¹⁰ Meanwhile, the use of restraints is associated with increased lengths of stay, increased likelihood of psychiatric hospitalization, increased likelihood to cause severe distress to patients harming the clinician-patient relationship, and more likely to result in harm to both patients and healthcare workers.¹¹ De-escalation contains key domains outlined by the Project BETA guidelines that were developed by a workgroup of emergency psychiatry practitioners experienced in behavioral emergencies. The key domains include: respect personal space, be concise and clear, listen to the patient, avoid further provocation, identify wants and needs, explain expectations and limits, establish verbal contact, agree or agree to disagree, offer choices and optimism, and debrief the patient and staff.¹⁰ The Project BETA workgroup consisted of emergency psychiatry practitioners experienced in behavioral emergencies who established these domains based on their collective experience and available evidence.¹⁰ For those interested in learning more about de-escalation, the website partnersincalm.com offers materials and updates for the treatment agitation including de-escalation.¹²

Pharmacological Treatment

When to Use Medications and Best Practices

Medication therapy may be used in moderate to severe forms of agitation after de-escalation has failed.^1,8 The goal of medication administration in agitation is to calm the patient without over sedation.^1,8 In patients who partially respond to de-escalation, oral medications may still be offered but parenteral medication should be reserved only for patients posing an immediate threat to themselves or others.⁸ Even if de-escalation failed to sufficiently calm the patient, it may encourage the patient to be more cooperative to medication if it is offered as a choice to the patient.^8,10 Oral medications should be offered over parenteral medications in patients that are cooperative as the use of oral medications has been shown to be just as effective as parenteral medications in acute agitation.^8,13,14 Two prospective studies comparing oral and parenteral administration found no difference in the level of agitation at all the time points measured.^13,14 Administration of parenteral medications without consent harm the clinician-patient relationship as it can be viewed as punishment rather than treatment by the patient and can potentially cause distress to the patient.⁸ Parenteral medications without patient consent should only be used if the patient displays a clear risk of harm to themselves or others due to their agitation.⁸ In most patients, one dose of medication is effective in calming the patient. In the event that a single dose is insufficient, subsequent doses should be administered after enough time has been given for the prior dose to take effect. This length of time varies by the agent and route of administration used as shown in Table 3. Along with this, these medications have a maximum recommended 24-hour dose. Exceeding these increases the risk for adverse effects, particularly oversedation.

Special Populations

Pediatric³⁰

Data for treatment of acute agitation in pediatric populations is poor with mostly retrospective studies. Diphenhydramine is commonly for its well-established safety profile and familiarity despite having poor data in pediatric agitation. It also has the potential to cause a paradoxical reaction by worsening agitation. Lorazepam has more evidence but also caries the same risk for paradoxical reaction. Risperidone, olanzapine, chlorpromazine and ziprasidone have some evidence in pediatric populations as well. In general, diphenhydramine (PO/IM), lorazepam (PO/IM), risperidone (PO) or olanzapine (PO) can be used for moderate agitation. Avoid diphenhydramine and lorazepam if the child has a history of paradoxical reactions or diagnosis of autism or developmental disability. For severe agitation, chlorpromazine (PO/IM), olanzapine (IM) and ziprasidone (IM) can be added to the available agents, but diphenhydramine is not recommended in severe agitation due to its poor efficacy data compared to other agents. Dosing can be found in Table 3.

Geriatric³¹

These patients should be treated depending on the cause in a similar manner to adult patients with a few key differences. Doses should be decreased as these patients tend to have slower metabolisms and increased risk for adverse effects. Benzodiazepines should be avoided in most cases unless they are specifically indicated (alcohol withdrawal). Similarly, anticholinergics should be avoided especially in delirium. Patients with Parkinson’s disease or Lewy Body dementia, antipsychotics should be avoided with the exception of low dose quetiapine. Benzodiazepines may be used in these patients at reduced doses if indicated.

Pregnancy³²

Benzodiazepines are associated with cleft lip/palate in the first trimester, and low birth weight/muscle tone and premature births when used in the third trimester. However, these are from studies with long term use. Effects of single doses is not yet fully understood. Antipsychotics used in agitation are not associated with any teratogenic effects but long-term use may cause neonatal withdrawal. Short term use or single doses of antipsychotics can be used safely in acutely agitation pregnant patients

ICU³³

Follow PADIS guidelines to treat ICU specific causes of agitation (pain, delirium, etc.). For acute agitation, one-time doses of antipsychotics can be used. However, in cases of delirium, routine use of antipsychotics does not improve delirium symptoms or duration and may lead to unnecessary prescriptions for antipsychotics at discharge. Dexmedetomidine can be used in mechanically ventilated patients weaning off ventilation.

Conclusion

Adhering to appropriate treatment for acute agitation is an area that in which pharmacists can make an impact. As displayed by the statistics discussed earlier, violence in healthcare work is widespread and appropriately managing agitation can potentially help.^1-7 As such, de-escalation should always be performed first prior to medication or restraints/seclusion.¹⁰ Unless the patient is severely agitated, an attempt to offer oral medication should be made. If the patient is severely agitated and posing a risk to themselves or others, then parenteral medications can be administered. Restraint and seclusion should be used only as a last resort and for the shortest duration possible¹¹ The medication used should be directed towards the suspected contributing condition and population being treated while keeping safety parameters in mind such as maximum dosing and dosing intervals.^1,8 These recommendations are based on the Project BETA guidelines, and these guidelines should be used as a reference when treating acute agitation.¹

CE Quiz

References

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