Summary

Undifferentiated elevated temperature and altered mental status (AMS) is a medical emergency requiring immediate evaluation to prevent rapid clinical deterioration. Causes include infectious (e.g., bacterial meningitis, sepsis), drug-induced (e.g., serotonin syndrome), endocrine (e.g., thyroid storm), and neurological (e.g., intracranial hemorrhage) conditions. Clinical evaluation focuses on identifying the core features of fever and AMS, as well as distinguishing signs such as neuromuscular abnormalities (e.g., rigidity, clonus) and meningismus. Initial management involves an ABCDE survey and acute stabilization. Further diagnostics are based on suspected etiology and may include broad laboratory studies, blood cultures, and noncontrast CT head. Lumbar puncture is indicated for suspected CNS infection. Treatment is directed at the underlying cause and includes rapid active cooling for hyperthermia, empiric antibiotics for suspected infections, and benzodiazepines for agitation. Antidotes (e.g., dantrolene, cyproheptadine) may be required for certain toxidromes. Admission is almost always necessary, often to an intensive care unit, for continuous monitoring and supportive care.

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Etiology

Infectious ^[1]

Toxicological ^[3]

Endocrine ^[1]

Neurological ^[1]

Other

Heat stroke
Malignant catatonia ^[4]

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Clinical evaluation

Focused history

Duration and onset
Additional symptoms and/or prodrome (e.g., dyspnea, headache, clinical features of thyrotoxicosis)
Focused toxicological history
Exposures (e.g., high temperatures, travel history)

Focused physical examination

Focused neurological examination, including:
Focused toxicological physical examination
Signs of infection, e.g.:
- Signs of sepsis
- Clinical features of meningitis
Clinical features of thyrotoxicosis
Rashes, skin lesions, and/or mucosal involvement
Retained foreign body (e.g., tampons, wound packing)

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Initial management

Almost all causes of elevated temperature and altered mental status require emergency intervention. Perform diagnostics and management simultaneously, prioritizing the most likely cause.

Approach ^[5]

Safety
- Don PPE if appropriate (e.g., suspected meningitis or chemical contamination).
- For managing agitated patients, consider as indicated:
Stabilization
- Assess ABCDEs; if toxins are suspected, use the ABCDE approach for poisoning.
- Initiate urgent stabilization measures as needed, e.g.:
- Initiate cooling techniques.
Diagnostics
- Perform a clinical evaluation.
- Start a toxicological risk assessment as indicated.
- Obtain appropriate diagnostics.
Management
- Initiate condition-specific management.
- Consult specialists as needed (e.g., infectious disease, toxicology).
- Admit all patients; consider critical care admission for:
  - Vasoactive medications or medications that require frequent titration
  - Active cooling and/or core temperature monitoring
  - Mechanical ventilation and/or airway management

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Diagnostics

Perform diagnostic studies as indicated based on clinical suspicion in tandem with initial management.

Laboratory studies ^[5]

BMP
CBC
CPK
Liver chemistries
Serum drug levels (e.g., acetaminophen, salicylates, ethanol)
Blood gas analysis
Coagulation studies
Thyroid function tests
CSF analysis

Advanced studies ^[5]

ECG
Neuroimaging
- CT head without contrast: initial modality
- Additional imaging as indicated (see "Diagnostics for altered mental status" for details)
Chest x-ray
EEG

Targeted diagnostics

Targeted diagnostics are based on the clinical presentation and the suspected underlying etiology. For further information, see:

Diagnostics for the poisoned patient
Diagnostics for altered mental status
Diagnostics for sepsis
Toxicological risk assessment
Diagnostics in agitated or violent patients
Condition-specific diagnostics in "Common causes of elevated temperature and altered mental status"

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Common causes of elevated temperature and altered mental status

Substance-related causes

Common drug causes of elevated temperature and altered mental status ^[5]
	Distinguishing clinical features	Diagnostic tests	Initial management
Serotonin syndrome ^[6] ^[7]	Recent exposure (< 24 hours) to one or more serotonergic drugs Neuromuscular excitability (e.g., hyperreflexia, tremor, clonus, hypertonia) Autonomic dysfunction	Clinical diagnosis with evaluation for complications, e.g.: BMP CPK CBC Coagulation panel	Discontinue serotonergic drugs. Supportive care (e.g., benzodiazepines for agitation, active cooling) Cyproheptadine (moderate to severe or refractory symptoms) See also "Management of serotonin syndrome."
Neuroleptic malignant syndrome ^[6]^[8]	Recent exposure (days to weeks) to a causative agent (e.g., antipsychotics, dopamine antagonists) Autonomic dysfunction (e.g., hyperthermia, hypertension, tachycardia, tachypnea) Neuromuscular hypoactivity (e.g., hyporeflexia, lead-pipe rigidity)	Clinical diagnosis with evaluation for complications, e.g.: CPK (elevated) Urinalysis (myoglobinuria) CBC (leukocytosis) CMP	Discontinue causative drug. Supportive care (e.g., active cooling, VTE prophylaxis) Severe symptoms: pharmacotherapy (e.g., dantrolene, bromocriptine) See also "Treatment of neuroleptic malignant syndrome."
Malignant hyperthermia ^[6]^[9]	Recent exposure (minutes to 24 hours) to a causative agent (volatile anesthetics, succinylcholine) Rapid rise in temperature Autonomic dysfunction (e.g., hyperthermia, tachypnea, tachycardia) Generalized muscle rigidity and/or masseter rigidity Signs of end-organ damage	Clinical diagnosis Supportive features include: Increased end-tidal CO₂ Blood gas analysis showing mixed respiratory and metabolic acidosis BMP showing hyperkalemia	Discontinue causative drug. Administer dantrolene. Supportive care (e.g., active cooling) See also "Management of malignant hyperthermia."
Anticholinergic poisoning ^[5]^[6]	Exposure to causative agents (e.g., belladonna, anticholinergic agents) Autonomic dysfunction (e.g., arrhythmias, tachycardia, flushed skin, dry mouth, urinary retention, ileus) Normal reflexes and muscle tone	Clinical diagnosis Severe toxicity: Assess for features of end-organ damage (e.g., with CBC, CMP, CK, and blood gas). ECG if: Suspected tricyclic antidepressant or diphenhydramine toxicity Treatment with phytostigmine is planned	Supportive care (e.g., benzodiazepines for agitation, active cooling) Treatment of concurrent poisoning (e.g., tricyclic antidepressant poisoning, antipsychotic poisoning) Administer physostigmine (except in tricyclic overdose). If physostigmine is unavailable, consider rivastigmine. ^[5]^[10]
Salicylate poisoning ^[11]	Mild to moderate: tinnitus, lethargy, tachypnea Severe: coma, seizures, noncardiogenic pulmonary edema	Clinical diagnosis Serum salicylate level Blood gas analysis CMP, serum lactate Screening for coingestion	Avoid intubation and mechanical ventilation unless absolutely necessary. Serum and urine alkalinization As indicated GI decontamination Hemodialysis See also "Management of salicylate poisoning."
Delirium tremens ^[12]	History of heavy alcohol use with abstinence starting 72–96 hours prior Severe agitation, tremors Tactile and/or visual hallucinations	Clinical diagnosis	High-dose benzodiazepines (e.g., diazepam, lorazepam) Treatment of associated conditions (e.g., Wernicke encephalopathy, alcohol-associated hepatitis) See also "Management of alcohol withdrawal."

Other causes

Common nondrug causes of elevated temperature and altered mental status
‎	Distinguishing clinical features	Diagnostic tests	Initial management
Bacterial meningitis ^[13]	Classic triad of meningitis Meningococcal meningitis Petechiae or purpura Possible features of Waterhouse-Friderichsen syndrome	CT head (based on criteria for imaging prior to LP) Lumbar puncture and CSF analysis Blood cultures	Empiric antibiotic therapy for bacterial meningitis Corticosteroids See also "Treatment of meningitis."
Sepsis or septic shock ^[5]^[14]	Clinical features of sepsis Features of the underlying infection	Sepsis screening tools (e.g., SIRS criteria) Blood and urine cultures Serum lactate	IV fluid resuscitation Broad-spectrum antibiotics Vasopressors as indicated See also "Management of sepsis."
Herpes simplex encephalitis ^[15]	Acute onset of behavioral changes, psychosis, or seizures Focal neurological signs	CSF PCR for HSV MRI brain	IV acyclovir See also "Management of HSV encephalitis."
Toxic shock syndrome ^[5]	Prodrome: flu-like symptoms, erythematous macular desquamating rash, mucosal involvement Signs of shock (e.g., hypotension) Signs of end-organ hypoperfusion	Workup for sepsis (e.g., BMP, CBC, blood cultures) Focused cultures from suspected sources (e.g., vagina, wounds) TSST-1 assay and/or TSST-1 antibody titers	IV fluid resuscitation and/or vasopressors Source control Empiric antibiotic therapy for TSS (e.g., vancomycin plus clindamycin) See also "Management of toxic shock syndrome."
Thyroid storm ^[16]^[17]	Hyperpyrexia Tachycardia (> 140 beats/minute) and possible arrhythmia Features of thyrotoxicosis-induced cardiac failure Agitation, seizures, coma	Clinical diagnosis confirmed with thyroid function tests (↓ TSH, ↑ free T₃ and/or T₄) Burch-Wartofsky Point Scale: to assess severity and guide treatment	Antithyroid drugs Beta blockers (e.g., propranolol) IV fluid resuscitation Supportive care (e.g., calming medication, electrolyte repletion, antipyretics) See also "Treatment of thyroid storm."
Heatstroke ^[5]^[18]^[19]	Body temperature usually > 40.0°C (> 104°F); hot to the touch Muscle flaccidity or rigidity Tachypnea, tachycardia, hypotension	Clinical diagnosis with evaluation for complications, e.g.: BMP CPK, myoglobin Coagulation panel	Active cooling; goal: < 39°C (< 102.2°F) within 30 minutes IV fluid resuscitation See also "Management of heatstroke."

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Mimics

Etiologies for individual clinical features

See the following for more information:

Elevated body temperature
Altered mental status

False positives

High temperature

Recent hot food, beverages, or smoking when measuring oral temperature
Increase in body temperature due to physiological factors (e.g., recent exercise)
Excess clothing, heavy blankets
Heating pads

Altered mental status

Impaired communication, e.g.:
- Hearing loss
- Vision loss
- Language barriers
- Neurodevelopmental disorders (e.g., autism spectrum disorder)
Sleep deprivation
Acute grief or emotional trauma
Baseline dementia
See also "Coma mimics."

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Elevated temperature and altered mental status

Summary

Etiology

Infectious [1]

Toxicological [3]

Endocrine [1]

Neurological [1]

Other

Clinical evaluation

Focused history

Focused physical examination

Initial management

Approach [5]

Diagnostics

Laboratory studies [5]

Advanced studies [5]

Targeted diagnostics

Common causes of elevated temperature and altered mental status

Substance-related causes

Other causes

Mimics

Etiologies for individual clinical features

False positives

High temperature

Altered mental status

Infectious ^[1]

Toxicological ^[3]

Endocrine ^[1]

Neurological ^[1]

Approach ^[5]

Laboratory studies ^[5]

Advanced studies ^[5]