Agitation

Basics

Description

Agitation, a state of extreme restlessness:

Is characterized by increased verbal and motor activity
May be the presenting symptom of a variety of medical and psychiatric disorders
Has a broad spectrum of severity
- From excessive talkativeness to threatening or violent behavior
- Includes excited delirium syndrome:
  - Characterized by agitation, acidosis, hyperadrenergic autonomic dysfunction
  - Associated with sudden cardiac death, particularly after a violent struggle

Epidemiology

Incidence and Prevalence Estimates

6% of emergency visits are for behavioral disturbances
∼1.7 million emergency visits annually in U.S. involve agitated patients

Etiology

Medical etiologies:

Infectious:
- CNS infections:
  - Encephalitis
  - Meningitis
  - Neurosyphilis
  - Abscess
- Hyperactive or mixed delirium secondary to sepsis from non-CNS sources
Metabolic derangements:
- Electrolyte derangement:
  - Hyponatremia
  - Hypocalcemia
  - Hypoglycemia
- Renal failure
- Acid/base disturbances
- Hepatic encephalopathy
- Wernicke encephalopathy
- Wilsons disease
Endocrinopathies:
- Thyroid storm
- Hyperparathyroidism
Pulmonary etiologies:
- Hypoxemia
- Hypercarbia
Toxicologic causes:
- Toxidromes:
  - Sympathomimetic
  - Anticholinergic
  - Cholinergic
  - Alcohol intoxication
  - Alcohol withdrawal
- Neuroleptic malignant syndrome (NMS)
- Serotonin syndrome (SS)
Neurologic causes:
- Tumors
- CNS infections (see above)
- Huntington disease
- Ischemic cerebrovascular accident
- Traumatic intracranial hemorrhage
- Subarachnoid hemorrhage
- Postseizure

Psychiatric etiologies:

Mania/agitated depression
Psychotic illnesses such as schizophrenia
Anxiety disorders

Diagnosis

Signs and Symptoms

A detailed history and physical exam are critical in differentiating between medical and psychiatric causes of agitation

History

The HPI has a sensitivity of 94% in detecting medical illness in psychiatric patients.
- If a detailed HPI is unattainable from the patient seek collateral information from family, friends, and prehospital providers
Inquire about:
- Trauma
- Recent illness and fever
- Headache, loss of consciousness, neurologic deficits, or visual hallucinations
- Current medications
- History of:
  - Psychiatric illness
  - Substance abuse
  - HIV/immunosuppressed state
  - Cancer
  - Neurologic disorders, including epilepsy

Physical Exam
A thorough exam is critical to differentiate between medical and psychiatric causes

Vital sign abnormalities should prompt a full evaluation for a medical cause:
- Hyperthermia may indicate an infectious etiology, NMS, SS, or excited delirium syndrome
Perform a toxidrome-oriented exam, including:
- Pupillary assessment
- Skin evaluation for diaphoresis or absence of sweat
- Evaluation for urinary retention
A detailed neurologic exam is mandatory:
- Any neurologic deficit requires a full evaluation for an underlying medical illness
- Orientation, memory, and attention should be intact for patients with a psychiatric cause of agitation:
  - Alterations in orientation and memory are seen in delirium and dementia
  - Inattention, such as inability to recite the days of the week backward, should raise suspicion of delirium
- Muscle tone and reflexes should be assessed:
  - Muscle rigidity may indicate NMS
  - Hyperreflexia and clonus may indicate SS

Interpretation

The diagnostic work up is directed by the history, physical exam, and underlying suspicion of for a medical etiology of the agitation

Essential Workup

At minimum all patients should have:

A full set of vital signs
A complete physical exam, including a detailed neurologic exam and tests of cognition and attention
Blood glucose testing

Diagnostic Tests and Interpretation

Diagnostic tests should be directed on the basis of the suspicion of a medical etiology for the patient's agitation, and history and physical exam findings

Imaging
Head CT should be considered in trauma patients or those with neurologic deficits

Diagnostic Procedures/Other

Lumbar puncture should be considered in patients:
- With meningeal signs
- Where infection is suspected as etiology of agitation but no source is identified

Differential Diagnosis

Agitation may be the presenting symptom of an underlying medical illness, substance abuse or withdrawal, or a psychiatric illness

Treatment

Pre Hospital

Prehospital providers frequently encounter agitated or violent patients and should:

Follow regional protocols regarding physical restraints and chemical sedation
Provide prenotification when transporting an agitated or violent patient so that the receiving hospital can mobilize necessary resources
Obtain a fingerstick glucose if feasible

Initial Stabilization/Therapy

Airway, Breathing, Circulation, Disability, and Exposure (ABCDE)
Treat life-threatening medical/traumatic conditions as appropriate
Severely agitated patients may become violent:
- Patients should change into hospital gowns and be searched for weapons
- Physical restraints and parenteral chemical sedation should be used when necessary to ensure safety of patient(s) and staff

Ed Treatment/Procedures

When a medical etiology is suspected or diagnosed:

Treatment should be directed at underlying cause

When a psychiatric etiology is suspected or diagnosed:

Emergency psychiatric referral is indicated

Management of agitation:

Verbal de-escalation techniques are first line for mild or moderate agitation
- Consider the “Ten Steps” for verbal de-escalation:
  - Respect personal space
  - Do not be provocative
  - Establish verbal contact
  - Be concise
  - Identify wants and feelings
  - Listen closely to what the patient is saying
  - Agree or agree to disagree
  - Lay down the law and set clear limits
  - Offer choices and optimism
  - Debrief the patient and staff
Chemical sedation options include:
- Benzodiazepines:
  - First-line therapy for undifferentiated agitation, alcohol withdrawal
  - Lorazepam or midazolam (shorter half-life)
  - Side effects: Respiratory depression, excessive somnolence, paradoxical disinhibition (rare):
    - Geriatric consideration: May precipitate or worsen delirium in geriatric patients
- Antipsychotics:
  - First line for patients with psychiatric etiology of agitation/psychosis
  - First generation: Haloperidol or droperidol (shorter half-life)
  - Second generation: Olanzapine, risperidone or ziprasidone (less sedation and fewer instances of extrapyramidal symptoms)
  - Side effects: QTC prolongation and extrapyramidal symptoms:
    - Low dose can be used in delirious geriatric patient when verbal de-escalation is unsuccessful
- Ketamine:
  - May consider in severely agitated patients when:
    - Antipsychotics and benzodiazepines have failed
    - Excited delirium syndrome is suspected
  - Side effects: Increased oral secretions, vomiting, laryngospasm (rare), hypertension, tachycardia, respiratory depression, emergence phenomenon:
    - Vital signs, mental status, and respiratory status should be closely monitored
    - Lorazepam may be simultaneously administered to prevent emergence phenomenon from ketamine
    - Use in the prehospital setting for severe agitation may be associated with high rates of ED intubation
- Combination therapy:
  - May produce more rapid sedation than monotherapy
  - Should be considered in highly agitated/violent patient
Midazolam, droperidol, lorazepam, and haloperidol

Physical restraint use:

Chemical sedation should be used to facilitate early discontinuation of physical restraints
Physician and nurses must document use and rationale for usage
Prolonged use can result in:
- Hyperthermia
- Rhabdomyolysis
- Nerve injury if extremities are kept in same position for prolonged time
- Excited delirium syndrome

Medication

Droperidol 2.5–5 mg IV/IM q3h prn
Haloperidol 2–10 mg IV/IM q3h prn
Ketamine:
- IM: 2–4 mg/kg (max 400 mg). Consider starting dose of 2 mg/kg (max 200 mg), repeat prn × 1 in 5 min for a maximum of 4 mg/kg
- IV: 0.5–1 mg/kg. Consider starting dose of 0.5 mg/kg, repeat prn × 1 after 5 min for a maximum of 1 mg/kg
Lorazepam 0.5–2 mg IV/IM
Midazolam:
- 0.07 mg/kg IM or 1 mg IV slowly q3min up to 5 mg

Ongoing Care

Disposition

Admission Criteria

Disposition is ultimately determined by the underlying cause of the agitation, the method of sedation, and whether the condition resolves
Admission is warranted if there is an underlying medical or psychiatric condition that requires inpatient treatment

Discharge Criteria
Discharge should be limited to those individuals where the underlying cause resolves (e.g., substance use/abuse) or can be safely treated as an outpatient

Issues for Referral

Psychiatric referral as appropriate
Alcohol/drug treatment as appropriate

Follow-Up Recommendations

Follow-up is determined by the causative medical or psychiatric condition(s)

Pearls and Pitfalls

Search for potential medical illnesses causing the agitation

Factors suggestive of medical causes include:
- New onset at age >45
- Abnormal vital signs
- Focal neurologic abnormalities
- Acute onset
- Visual hallucinations
- Abnormalities of memory or attention on cognitive testing
- Trauma with evidence of head injury

Pitfalls:

Not assessing for underlying medical cause of agitation
Not undressing patients and searching for weapons
Inadequate dosing of sedatives/antipsychotics
Failure to adjust extremity position in restraints to prevent nerve complications
Inadequate documentation of the need for restraint
Overmedication of the patient requiring intubation or reversal

Additional Reading

Gonin P, Beysard N, Yersin B, et al. Excited delirium: A systematic review. Acad Emerg Med. 2018;25(5):552–565.
Lukens TW, Wolf SJ, Edlow JA; American College of Emergency Physicians Clinical Policies Subcommittee on Critical Issues in the Diagnosis and Management of the Adult Psychiatric Patient in the Emergency Department. Ann Emerg Med. 2006;47:79–99.
Nordstrom K, Zun LS, Wilson MP, et al. Medical evaluation and triage of the agitated patient: Consensus statement of the American Association for Emergency Psychiatry Project BETA Medical Evaluation Workgroup. West J Emerg Med. 2012;8:3–10.
Riddell J, Tran A, Bengiamin R, et al. Ketamine as a first-line treatment for severely agitated emergency department patients. Am J Emerg Med. 2017;35:1000–1004.
Vilke GM, DeBard ML, Chan TC, et al. Excited delirium syndrome (EXDS): Defining based on a review of the literature. J Emerg Med. 2012;43:897–905.