Description

• 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

Etiology

• 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

• 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

• 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
• CONTROVERSIES:
  • 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

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 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)

Disposition

• 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)