Harrison's Manual of Medicine
Chapter 18: Confusion, Stupor, and Coma
Approach to the patient: Disorders of Consciousness
Approach to the patient: Disorders of Consciousness
Disorders of consciousness are common; these always signify a disorder of the nervous system. Assessment should determine the level of consciousness (drowsy, stuporous, comatose) and/or content of consciousness (confusion, perseveration, hallucinations). Confusion is a lack of clarity in thinking with inattentiveness; delirium is used to describe an acute confusional state; stupor, a state in which vigorous stimuli are needed to elicit a response; coma, a condition of unresponsiveness. Pts in such states are usually seriously ill, and etiologic factors must be assessed (Tables 18-1 and 18-2).
| Toxins |
|---|
| Prescription medications: especially those with anticholinergic properties, narcotics, and benzodiazepines |
| Drugs of abuse: alcohol intoxication and alcohol withdrawal, opiates, ecstasy, LSD, GHB, PCP, ketamine, cocaine, “bath salts,” marijuana and its synthetic forms |
| Poisons: inhalants, carbon monoxide, ethylene glycol, pesticides |
| Metabolic Conditions |
| Electrolyte disturbances: hypoglycemia, hyperglycemia, hyponatremia, hypernatremia, hypercalcemia, hypocalcemia, hypomagnesemia |
| Hypothermia and hyperthermia |
| Pulmonary failure: hypoxemia and hypercarbia |
| Liver failure/hepatic encephalopathy |
| Renal failure/uremia |
| Cardiac failure |
| Vitamin deficiencies: B12, thiamine, folate, niacin |
| Dehydration and malnutrition |
| Anemia |
| Infections |
| Systemic infections: urinary tract infections, pneumonia, skin and soft tissue infections, sepsis |
| CNS infections: meningitis, encephalitis, brain abscess |
| Endocrine Conditions |
| Hyperthyroidism, hypothyroidism |
| Hyperparathyroidism |
| Adrenal insufficiency |
| Cerebrovascular Disorders |
| Global hypoperfusion states |
| Hypertensive encephalopathy |
| Focal ischemic strokes and hemorrhages (rare): especially nondominant parietal and thalamic lesions |
| Autoimmune Disorders |
| CNS vasculitis |
| Cerebral lupus |
| Neurologic paraneoplastic and autoimmune encephalitis |
| Seizure-Related Disorders |
| Nonconvulsive status epilepticus |
| Intermittent seizures with prolonged postictal states |
| Neoplastic Disorders |
| Diffuse metastases to the brain |
| Gliomatosis cerebri |
| Carcinomatous meningitis |
| CNS lymphoma |
| Hospitalization |
| Terminal end-of-life delirium |
Abbreviations: CNS, central nervous system; GHB, γ-hydroxybutyrate; LSD, lysergic acid diethylamide; PCP, phencyclidine.
| Initial Evaluation |
|---|
| History with special attention to medications (including over-the-counter and herbals) |
| General physical examination and neurologic examination |
| Complete blood count |
| Electrolyte panel including calcium, magnesium, phosphorus |
| Liver function tests, including albumin |
| Renal function tests |
| First-Tier Further Evaluation Guided by Initial Evaluation |
| Systemic infection screen |
|
| Electrocardiogram |
| Arterial blood gas |
| Serum and/or urine toxicology screen (perform earlier in young persons) |
| Brain imaging with MRI with diffusion and gadolinium (preferred) or CT |
| Suspected CNS infection or other inflammatory disorder: lumbar puncture after brain imaging |
| Suspected seizure-related etiology: electroencephalogram (EEG) (if high suspicion, should be performed immediately) |
| Second-Tier Further Evaluation |
| Vitamin levels: B12, folate, thiamine |
| Endocrinologic laboratories: thyroid-stimulating hormone (TSH) and free T4; cortisol |
| Serum ammonia |
| Sedimentation rate |
| Autoimmune serologies: antinuclear antibodies (ANA), complement levels; p-ANCA, c-ANCA, consider paraneoplastic/autoimmune encephalitis serologies |
| Infectious serologies: rapid plasmin reagin (RPR); fungal and viral serologies if high suspicion; HIV antibody |
| Lumbar puncture (if not already performed) |
| Brain MRI with and without gadolinium (if not already performed) |
Abbreviations: c-ANCA, cytoplasmic antineutrophil cytoplasmic antibody; CNS, central nervous system; CT, computed tomography; MRI, magnetic resonance imaging; p-ANCA, perinuclear antineutrophil cytoplasmic antibody.
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Citation
Kasper, Dennis L., et al., editors. "Chapter 18: Confusion, Stupor, and Coma." Harrison's Manual of Medicine, 20th ed., McGraw Hill Inc., 2020. harrisons.unboundmedicine.com/harrisons/view/Harrisons-Manual-of-Medicine/623079/all/Chapter_18:_Confusion_Stupor_and_Coma.
Chapter 18: Confusion, Stupor, and Coma. In: Kasper DLD, Fauci ASA, Hauser SLS, et al, eds. Harrison's Manual of Medicine. McGraw Hill Inc.; 2020. https://harrisons.unboundmedicine.com/harrisons/view/Harrisons-Manual-of-Medicine/623079/all/Chapter_18:_Confusion_Stupor_and_Coma. Accessed October 24, 2025.
Chapter 18: Confusion, Stupor, and Coma. (2020). In Kasper, D. L., Fauci, A. S., Hauser, S. L., Longo, D. L., Jameson, J. L., & Loscalzo, J. (Eds.), Harrison's Manual of Medicine (20th ed.). McGraw Hill Inc.. https://harrisons.unboundmedicine.com/harrisons/view/Harrisons-Manual-of-Medicine/623079/all/Chapter_18:_Confusion_Stupor_and_Coma
Chapter 18: Confusion, Stupor, and Coma [Internet]. In: Kasper DLD, Fauci ASA, Hauser SLS, Longo DLD, Jameson JLJ, Loscalzo JJ, editors. Harrison's Manual of Medicine. McGraw Hill Inc.; 2020. [cited 2025 October 24]. Available from: https://harrisons.unboundmedicine.com/harrisons/view/Harrisons-Manual-of-Medicine/623079/all/Chapter_18:_Confusion_Stupor_and_Coma.
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