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, substance induced, and psychiatric conditions
  • Has a broad spectrum of severity:
    • From excessive talkativeness to threatening or violent behavior
  • Requires prompt stabilization and search for an underlying etiology

Epidemiology

Incidence And Prevalence Estimates

  • 7% of emergency visits are for behavioral disturbances
  • ∼1.7 million emergency visits annually in US 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
    • Wilson 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)
  • Environmental exposures:
    • Carbon monoxide
    • Hyperthermia
  • Neurologic causes:
    • Tumors
    • CNS infections (see above)
    • Head Injury
    • Ischemic cerebrovascular accident
    • Intracranial hemorrhage
    • Postseizure
    • Dementia and chronic cognitive disorders

Psychiatric etiologies:

  • Mania or 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 and recent changes to medications
    • History of:
      • Psychiatric illness
      • Substance use
      • 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 infection, NMS, SS, or thyrotoxicosis
  • Assess for external signs of trauma
  • 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 imperative:
    • 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

Diagnostic Tests And Interpretation

The diagnostic workup is directed by the history, physical exam, and underlying suspicion 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

Labs

  • Consider based on presentation:
    • Basic metabolic panel
    • Liver function tests
    • Thyroid function tests
    • Creatine kinase
    • Serum or urine toxicology screen
    • Pregnancy test

Imaging

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

Diagnostic Procedures/Surgery

  • ECG if concerned for electrolyte abnormalities or toxic ingestion
  • Lumbar puncture should be considered:
    • With meningeal signs
    • When 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 use, or withdrawal, or a psychiatric illness

Treatment

Prehospital

  • 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 medication 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
  • Pharmacologic intervention:
    • 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 older adults
    • Antipsychotics:
      • First line for patients with psychosis, alcohol intoxication
      • 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
      • Geriatric consideration: Low dose can be used when verbal de-escalation is unsuccessful
    • Ketamine:
      • May consider in severely agitated patients when antipsychotics and benzodiazepines have failed
      • 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
      • Due to risk of worsening agitation/psychosis, not recommended in patients with schizophrenia
    • Combination therapy:
      • May produce more rapid sedation than monotherapy
      • Should be considered in highly agitated/violent patient
      • Eg, Midazolam and droperidol, lorazepam and haloperidol
  • Physical restraint use:
    • Should coincide with administration of medication to calm the patient
    • Associated with risk of harm to patients and staff:
      • Rhabdomyolysis, nerve injury
    • Should be discontinued for less restrictive measures as soon as able
    • Must be documented appropriately by physician and nurse

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

Follow-Up

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) 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

Assume agitation has a medical etiology until proven otherwise.

  • 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
    • Presentation that is inconsistent with prior psychiatric illness
  • The term “Excited Delirium Syndrome” is no longer preferred by numerous physician societies
    • Hyperactive Delirium with Severe Agitation is the recommended clinical term

Pitfalls:

  • Incomplete evaluation for a medical etiology
  • Foregoing less invasive measures including verbal de-escalation and oral medication
  • Improper dosing of sedatives/antipsychotics leading to oversedation or need for repeat dosing
  • Failure to apply restraints appropriately, leading to risk of harm to staff and patient

Additional Readings

  1. Gottlieb M, Long B, Koyfman A. Approach to the agitated emergency department patient. J Emerg Med. 2018;54:447–457.  [PMID:29395692]
  2. Kennedy M, Koehl J, Shenvi C, et al. The agitated older adult in the emergency department: a narrative review of common causes and management strategies. J Am Coll Emerg Physicians Open. 2020;1:812–823.  [PMID:33145525]
  3. 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;13:3–10.  [PMID:22461915]
  4. Roppolo LP, Morris DW, Khan F. Improving the management of acutely agitated patients in the emergency department through implementation of Project BETA (Best Practices in the Evaluation and Treatment of Agitation). J Am Coll Emerg Physicians Open. 2020;1:898–907.  [PMID:33145538]
  5. Springer B. Hyperactive delirium with severe agitation. Emerg Med Clin N Am. 2024;42:41–52.

See Also (Topic, Algorithm, Electronic Media Element)

Authors

Katherine Dowdell