Altered Mental Status



  • Dysfunction in either the reticular activating system in the upper brainstem or a large area of 1 or both cerebral hemispheres
  • Definitions:
    • 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


  • Hypoxic:
    • Severe pulmonary disease
    • Anemia
    • Shock
    • Intracardiac shunting (especially in pediatrics)
  • Metabolic:
    • Hypoglycemia; hyperglycemia
    • Diabetic ketoacidosis
    • Nonketotic hyperosmolar coma
    • Hyponatremia; hypernatremia
    • Hypocalcemia; hypercalcemia
    • Hypomagnesemia; hypermagnesemia
    • Hypophosphatemia
    • Acidosis; alkalosis
    • Dehydration
    • Deficiency: Thiamine, folic acid, B12, niacin
    • Hyperammonemia (hepatic encephalopathy)
    • Uremia (renal failure)
    • CO2 narcosis
  • Toxicologic:
    • 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)
  • Infectious:
    • UTI (especially in elderly)
    • Pneumonia
    • Sepsis; bacteremia
    • Meningitis, encephalitis, brain abscess
  • Endocrine:
    • Myxedema coma
    • Thyrotoxicosis
    • Hypothyroidism
    • Addison disease
    • Cushing disease
    • Pheochromocytoma
    • Hyperparathyroidism
  • Environmental:
    • Hypothermia
    • Hyperthermia; heat stroke
    • High-altitude cerebral edema
    • Neuroleptic malignant syndrome
  • Vascular:
    • Hypertensive encephalopathy
    • Cerebral vasculitis
    • TTP, DIC, hyperviscosity
    • MI
  • Primary neurologic:
    • Seizures, nonconvulsive status epilepticus, and postictal state
    • Head trauma, concussion
    • Diffuse axonal injury
    • Structural brain lesions:
      • Hemorrhage (subdural, epidural, subarachnoid, intraparenchymal)
      • Infarction
      • Tumors
      • Demyelinating disorders
    • 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
  • Trauma; burns
  • Porphyria
  • Psychiatric
  • Multifactorial (especially in elderly)


Signs and Symptoms

  • 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:
    • Infectious etiologies, drug toxicities, endocrine disorders, heat stroke
  • Severe hypertension and bradycardia
    • Cushing reflex suggests intracranial lesion
  • Hypotension:
    • Infectious, toxicologic etiologies, decreased cardiac output
  • 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:
    • Nearly all toxic and metabolic causes of coma leave the pupillary reflexes sluggish but bilaterally intact
  • 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

  • Ask witnesses, family, pre-hospital personnel
  • Baseline mental status
  • Medical history (immunosuppressed, liver failure, depression, or chronic conditions)
  • Recent events: Trauma, fever, illness
  • Detailed medication list
  • Substance abuse history

Physical Exam
  • Vital signs
  • Head: Signs of trauma, pupils
  • Fundoscopic exam: Hemorrhage, papilledema
  • Neck: Rigidity, bruits, thyroid enlargement
  • Heart and lungs
  • Abdomen: Organomegaly, ascites
  • Extremities: Cyanosis
  • Skin: Diaphoretic/dry, rash, petechiae, ecchymoses, splinter hemorrhages, needle tracks
  • Neurologic exam
  • Mental status exam

Diagnostic Tests and Interpretation

  • Dextrostix and glucose
  • CBC
  • Electrolytes (including Ca, Mg, P)
  • BUN, creatinine
  • Toxicologic screen (including toxic alcohols)
  • ECG
  • Urinalysis
  • Blood and urine cultures (suspected infection)
  • PT, PTT (anticoagulated, liver failure patients)
  • Consider LFTs, thyroid function tests, ammonia, serum osmolarity, arterial blood gas
  • Consider B12, folic acid, RPR, urine porphobilinogen, heavy metal screening

  • Head CT scan:
    • Noncontrast only to rule out hemorrhage and mass effect
  • Chest radiograph: To diagnose pneumonia
  • MRI (if available):
    • Indicated when suspicious of ischemic stroke or other CNS abnormality
    • May be deferred when admitting the patient as part of the inpatient workup

Diagnostic Procedures/Other
  • Lumbar puncture (LP):
    • Indicated when the etiology remains unclear after labs and CT scan
    • Empiric antibiotics should be given before LP in patients with suspected meningitis
  • EEG (inpatient): For suspected seizure, nonconvulsive status epilepticus
  • Caloric stimulation of the vestibular apparatus to assess unresponsive patients

Differential Diagnosis

  • Locked-in syndrome:
    • Rare disorder caused by damage to the corticospinal, corticopontine, and corticobulbar tracts resulting in quadriplegia and mutism with preservation of consciousness
    • 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.


Pre Hospital

  • Airway management if loss of airway patency or concern for inability to protect airway
  • IV access, supplemental oxygen, cardiac monitor
  • Spine immobilization if possibility of trauma
  • “Coma cocktail”:
    • Dextrose
    • Naloxone
    • Thiamine
  • Look for signs of an underlying cause:
    • Medications, medic alert bracelets
    • Document a basic neurologic exam, GCS, pupils, extremity movements
    • Gross signs of trauma
    • Empirical dextrose should not be withheld or delayed if Dextrostix is not available
      • Glucose can be safely administered before thiamine

Initial Stabilization/Therapy

  • IV D50
  • Naloxone
  • Thiamine

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 yo or immunocompromised), add ampicillin
  • Empiric treatment if a toxic ingestion is suspected
  • Correct body temperature
  • Specific therapy directed at underlying cause


  • 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 ET
  • Thiamine: 100 mg IM or in 1,000 mL of IV fluid wide open
  • Vancomycin: 15–20 mg/kg/dose q8–12h (max 2 g/dose)

Ongoing Care


Admission Criteria
All patients with acute and persistent changes in mental status require admission

Discharge Criteria
  • Treated hypoglycemia related to insulin therapy with resolved symptoms
  • Chronic altered mental status (e.g., dementia) without change from baseline
  • Acute drug intoxication with return of patient's mental status to baseline, and drug has no potential for delayed toxicity

Follow-Up Recommendations

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

Pearls and Pitfalls

  • Consider reversible causes:
    • Hypoglycemia (check glucose, give dextrose)
    • Opiate overdose (trial of naloxone)
    • Thiamine deficiency (trial of thiamine)
  • Consider head CT for any patient with unclear etiology or neurologic abnormality
  • Consider empiric antibiotics in patients with fever or unclear etiology

Additional Reading

  • Edlow JA, Rabinstein A, Traub SJ, et al. Diagnosis of reversible causes of coma. Lancet. 2014;384:2064–2076.
  • Stevens RD, Cadena RS, Pineda J. Emergency neurological life support: Approach to the patient with coma. Neurocritical Care. 2015;23(S2):S69–S75.
  • Zehtabchi S, Abdel Baki SG, Malhotra S, et al. Nonconvulsive seizures in patients presenting with altered mental status: An evidence-based review. Epilepsy Behav. 2011;22:139–143.


David W. Schoenfeld
Christopher J. Shestak

© Wolters Kluwer Health Lippincott Williams & Wilkins