Description

• Acute or subacute change in cognition, awareness, or arousal due to dysfunction of the reticular activating system, bilateral cerebral hemispheres, or both
• AMS accounts for 5–10% of all ED visits, with significantly higher rates in elderly patients (up to 40%)
• Common causes by age group:
  • Children: Seizures, metabolic disorders, toxic ingestions, infections (eg, meningitis).
  • Adults: Toxicologic, metabolic, and psychiatric causes predominate.
  • Elderly: Infections (UTIs, pneumonia, sepsis), metabolic disorders, polypharmacy, and neurodegenerative diseases.
• Classification of AMS:
  • Confusion: A behavioral state of reduced mental clarity, coherence, comprehension, and reasoning
  • Drowsiness: The patient cannot be easily aroused by touch or noise and cannot maintain alertness for prolonged periods of time
  • Lethargy: Depressed mental status in which the patient may appear wakeful but has depressed awareness of self and environment globally; cannot be aroused to full function
  • Stupor: The patient can be awakened only by vigorous stimuli, and an effort to avoid uncomfortable or aggravating stimulation is displayed
  • Coma: The patient cannot be aroused by stimulation and no purposeful attempt is made to avoid painful stimuli
  • Delirium: Acute onset of fluctuating cognition with impaired attention and consciousness, ranging from confusion to stupor

Etiology

Homeostatic 30%

• Hypoxic:
  • Severe pulmonary disease
  • Anemia
  • Shock
  • Intracardiac shunting (especially in pediatrics)
• Metabolic
  • Hypoglycemia; hyperglycemia
  • Diabetic ketoacidosis
  • Hyperosmolar hyperglycemic state (HHS)
  • Hyponatremia; hypernatremia
  • Hypocalcemia; hypercalcemia
  • Hypomagnesemia; hypermagnesemia
  • Hypophosphatemia
  • Acidosis; alkalosis
  • Dehydration
  • Deficiency: Thiamine, folic acid, B₁₂, niacin
  • Hyperammonemia (hepatic encephalopathy)
  • Uremia (renal failure)
  • CO₂ narcosis
• Endocrine
  • Myxedema coma
  • Thyrotoxicosis
  • Hypothyroidism
  • Addison disease
  • Cushing disease
  • Pheochromocytoma
• Hyperparathyroidism

Neurologic 25%

• Seizures, nonconvulsive status epilepticus, and postictal state
• Traumatic brain injury
• Concussion
• Diffuse axonal injury
• Hemorrhage (subdural, epidural, subarachnoid, intraparenchymal)
• Brain tumors
• Hydrocephalus
• Idiopathic intracranial hypertension
• Stroke
• Tumor
• Idiopathic intracranial hypertension (pseudotumor)
• HIV-related encephalopathy
• Autoimmune/inflammatory encephalitis
• Carcinoid meningitis
• Primary neuronal or glial disorders:
  • Creutzfeldt–Jakob disease
  • Marchiafava–Bignami disease
  • Adrenoleukodystrophy
  • Gliomatosis cerebri
  • Progressive multifocal leukoencephalopathy
• Porphyria

Infectious 20%:

• UTI (especially in elderly)
• Pneumonia
• Sepsis; bacteremia
• CNS infections
  • Meningitis
  • Encephalitis
  • Brain abscess
  • Fungal
  • Parasitic

Toxicologic 10%:

• Toxic alcohols
• Salicylates
• Sedatives and narcotics
• γ-Hydroxybutyrate (GHB)
• Anticonvulsants
• Psychotropics
• Isoniazid
• Heavy metals
• Carbon monoxide
• Cyanide
• Toxic plants (jimsonweed, mushrooms, etc.)
• Sympathomimetics
• Anticholinergic, cholinergic
• Antiemetics
• Antiparkinsonian medications
• Neuroleptic malignant syndrome
• Serotonin syndrome
• Malignant hyperthermia
• Withdrawal (especially alcohol, sedatives)

Cardiovascular and Hematologic Disorders 7%:

• Hypertensive encephalopathy
• Cerebral vasculitis
• Shock
• Myocardial Infarction
• Thrombotic thrombocytopenic purpura (TTP)
• Disseminated intravascular coagulation (DIC)
• Hyperviscosity syndrome
• MI

Environmental 5%:

• Hypothermia
• Heat stroke
• High-altitude cerebral edema

Psychiatric 3%:

• Primary psychiatric disorders:
  • Schizophrenia
  • Mania
  • Psychosis
  • Dissociative disorder
• Conversion disorder

Signs And Symptoms

• Confusion:
  • Difficulty in maintaining a coherent stream of thinking and mental performance
  • Remember to consider level of education, primary language, and possible learning disabilities
• Inattention:
  • Inability to follow tasks, selectively focus on important pieces of information
• Memory deficit:
  • Inability to recall any of the following:
    • The date, inclusive of month, day, year, and day of week
    • The precise place
    • Items of universally known information
    • Why the patient is in the hospital
    • Address, telephone number, or Social Security number
• Impaired mental performance:
  • Difficulty retaining 7 digits forward and 4 backward
  • Difficulty naming ordinary objects
  • Serial calculations: serial 7 subtraction test
• Disorganized and rambling language:
  • May be mistaken for aphasia
• Fever
• Cushing reflex (hypertension/bradycardia)
• Hypotension
• Eye movements:
  • Ocular bobbing:
    • Cyclical, brisk, conjugate, caudal jerks of the globes, followed by a slow return to midposition
    • Seen in bilateral pontine damage, metabolic derangement, and brainstem compression
  • Ocular dipping:
    • Slow, cyclical, conjugate, downward movement of the eyes, followed by a rapid return to midposition
    • Seen in diffuse cortical anoxic damage
• Pupil exam:
  • Toxic and metabolic comas usually cause sluggish but intact pupils
• Focal findings (indicative of CNS process):
  • Hemiparesis
  • Hemianopsia
  • Aphasia
  • Myoclonus
  • Convulsions
  • Nuchal rigidity
• Asterixis:
  • Arrhythmic flapping tremor (almost always bilateral)
  • Seen in hepatic failure or severe renal failure
• Red flag signs and symptoms:
  • Severe hypoxia: SpO₂ <90% on room air.
  • Tachypnea: RR >30 breaths/min.
  • Tachycardia: HR >120 beats/min
  • Use of accessory muscles
  • Stridor
  • Altered mental status
• Diagnostic clues:
  • Diaphoretic/cool vs hot/dry skin
  • Pallor
  • Upright patient position
  • Ketotic breath odor

Essential Workup

• Assess ABCs, obtain vital signs, and perform rapid glucose test
• Conduct neurologic exam, including Glasgow Coma Scale
• Order metabolic panel, CBC, and toxicology screen
• Obtain brain imaging (CT/MRI) if focal deficits, trauma, or stroke suspected
• Consider lumbar puncture or EEG if infection or seizures are suspected

Diagnostic Tests And Interpretation

Differential Diagnosis

• Locked-in syndrome:
  • Communication may be established through eye movements (maintain vertical eye movements)
• Psychogenic unresponsiveness:
  • Conversion reactions
  • Catatonia
  • Malingering
  • Akinetic mutism (abulic state)
• Dementia:
  • Multiple progressive cognitive deficits
  • Attention is preserved in the early stages.

Prehospital

• Airway management if loss of airway patency or concern for inability to protect airway
• IV access, supplemental oxygen, cardiac monitor
• Spinal motion restriction if possibility of trauma
• Look for signs of an underlying cause:
  • Medications, medic alert bracelets
  • Document a basic neurologic exam, GCS, pupils, extremity movements
  • Gross signs of trauma
• Check blood glucose

Controversies

• Empirical dextrose should not be withheld or delayed if glucometry is not available
• Glucose can be safely administered before thiamine

Initial Stabilization/Therapy

• Early airway management if airway is compromised
• Identification of immediately reversible conditions (eg, hypoglycemia, opiate toxicity)

Ed Treatment/Procedures

• Consider empiric use of antibiotics for altered mental status of undetermined etiology, particularly if febrile:
  • Broad spectrum with good CSF fluid penetration, such as ceftriaxone and vancomycin
  • Consider coverage for herpes meningoencephalitis with acyclovir
  • If Listeria suspected (>50 y/o or immunocompromised), add ampicillin
• Empiric treatment if a toxic ingestion is suspected
• Specific therapy directed at underlying cause:
  • Correct body temperature
  • Blood pressure control
  • Electrolyte correction
  • Benzodiazepines for status epilepticus
  • Antipsychotics for agitation (cautious use to avoid oversedation)

Medication

• Acyclovir: 10 mg/kg/dose q8h
• Ceftriaxone: 2 g (peds: 100 mg/kg loading dose, followed by 100 mg/kg/d div q12–24h) IV q12h
• Dextrose: 1–2 mL/kg of D₅₀W (peds: 2–4 mL/kg D25W) IV
• Diazepam: 0.1–0.3 mg/kg slow IV (max 10 mg/dose) q10–q15min × 3 doses
• Lorazepam: 0.05–0.1 mg/kg IV (max 4 mg/dose q10–q15min)
• Mannitol: 0.5–1 g/kg IV
• Naloxone: 0.4–2 mg IV/IM/SC, 2–4 mg IN, 0.8–5 mg endotracheal (ET)
• Thiamine: 100 mg IM or in 1000 mL of IV fluid wide open
• Vancomycin: 15–20 mg/kg/dose q8–12h (max 2 g/dose)

Disposition

Follow-Up Recommendations

• Primary care follow-up to manage etiology that led to altered mental status (eg, adjust medication dosing, drug abuse treatment referral)