Fever with Altered Sensorium: Etiology, Evaluation, and Management

Definition and Framing

• Fever: core temperature >38°C (100.4°F)
• Altered sensorium: any deviation from normal consciousness - confusion, delirium, stupor, or coma (GCS <15)

ETIOLOGY

A. CNS Infections (Primary)

CNS infection should be considered in ALL patients presenting with headache, nuchal rigidity, fever, altered sensorium, or diffuse/focal neurologic findings. - Rosen's Emergency Medicine

B. Systemic Infections with CNS Involvement

C. Non-Infectious Causes

EVALUATION

Step 1: Rapid Primary Assessment (Immediate, <5 min)

• ABCDE: Airway, Breathing, Circulation, Disability (GCS), Exposure
• Vital signs: Temperature (core), BP, pulse, SpO2, RR
• Blood glucose - immediately (capillary glucometry)
• GCS scoring
• Pupillary responses

Step 2: Focused History

• Duration and pattern of fever (acute vs. subacute)
• Vaccination history (meningococcal, Hib, JE)
• Travel history (malaria-endemic zones, SE Asia for JE)
• Animal/tick/mosquito exposure
• Drug history (antipsychotics, serotonergic agents)
• Immunocompromise (HIV, transplant, steroids)
• Risk factors for bacterial meningitis: alcoholism, asplenia, crowded living
• Head trauma, neurosurgery, sinusitis, otitis media (source for meningitis/abscess)

Step 3: Targeted Physical Examination

• Meningeal signs: Neck stiffness, Kernig's (knee extension pain), Brudzinski's
• Skin: Petechiae/purpura (meningococcemia), eschar (scrub typhus), rash (dengue, rickettsial)
• Fundoscopy: Papilledema (raised ICP - contraindication for immediate LP)
• Focal neurologic deficit: Asymmetric pupils, cranial nerve palsies, hemiparesis
• Signs of systemic infection: RUQ tenderness, splenomegaly, jaundice, murmur
• Autonomic instability: Suggest NMS/serotonin syndrome

Step 4: Investigations

Bedside / Immediate

• Blood glucose (capillary)
• SpO2
• ECG

Blood

Imaging

CT or MRI should be done in patients with suspected brain abscess. MRI with gadolinium is the definitive test for spinal epidural abscess. - Rosen's Emergency Medicine

• Altered mental status or deteriorating consciousness
• Focal neurologic deficit
• New-onset seizure
• Papilledema
• Immunocompromised state
• Malignancy
• History of focal CNS disease (stroke, focal infection, tumor)
• Age >60 years - Tintinalli's Emergency Medicine

Lumbar Puncture (LP) - CSF Analysis

Sterilization of CSF can occur within 2-6 hours of antibiotics - never withhold empiric antibiotics to wait for LP. - Tintinalli's Emergency Medicine

MANAGEMENT

A. General Principles

1. Airway first: Intubate if GCS ≤8 or airway not protected
2. IV access x2, cardiac monitoring, SpO2 monitoring
3. Do NOT delay empirical treatment for investigations (except blood cultures drawn before antibiotics if possible in under 10 minutes)
4. Treat hypoglycemia immediately if present (50 mL of 50% dextrose IV)
5. Control seizures: Lorazepam/diazepam IV; phenytoin/levetiracetam for maintenance

B. Empirical Antimicrobial Treatment

After addressing airway, breathing, and circulation, immediately initiate empiric antibiotic therapy if bacterial meningitis is clinically suspected. Never delay administration of empiric antibiotic therapy for neuroimaging or LP. - Tintinalli's Emergency Medicine

First-line treatment for healthy adults with suspected bacterial meningitis is ceftriaxone or cefotaxime plus vancomycin. Aciclovir is recommended for patients with suspected encephalitis because HSV is a common pathogen. Clinical course and risk factors such as immunosuppression dictate the need to test and treat for fungal and TB meningoencephalitis. - Rosen's Emergency Medicine

C. Adjunctive Therapy: Steroids

• Give before or with the first dose of antibiotics - never after
• Reduces CSF inflammation, mortality, hearing loss and neurological sequelae
• Benefit best established for pneumococcal meningitis in adults; benefit in children for Hib meningitis
• One expert panel: can be given up to 4 hours after first antibiotic dose
• Less effective in settings of high HIV prevalence, malnutrition, or advanced disease

Early treatment with dexamethasone before or with the first dose of antibiotics has been shown to improve outcomes in patients with bacterial meningitis. - Bradley and Daroff's Neurology in Clinical Practice

D. Condition-Specific Management

• Parenteral artesunate (drug of choice) or quinine
• IV glucose correction
• Mechanical ventilation if needed
• Avoid corticosteroids (shown to be harmful in cerebral malaria)

• Acyclovir 10 mg/kg IV Q8h for 14-21 days
• Start empirically if encephalitis suspected (do NOT wait for PCR result)
• MRI: T2/FLAIR signal in medial temporal lobes and cingulate cortex
• EEG: temporal lobe periodic lateralizing epileptiform discharges (PLEDs)
• Early treatment is vital - outcomes far better before coma sets in

Early treatment of herpes simplex encephalitis yields the best results when administered before patients become comatose. - Plum and Posner's Diagnosis and Treatment of Stupor and Coma

• Rapid external cooling (target <39°C within 30 minutes)
• Cool IV fluids, ice packs to groin/axilla/neck
• No antipyretics (not effective - not true fever)
• Supportive care

• Identify and treat the source of sepsis
• Broad-spectrum antibiotics (Sepsis bundle)
• Organ support (fluid resuscitation, vasopressors if needed)

• Stop offending agent
• NMS: Dantrolene, bromocriptine; active cooling
• Serotonin syndrome: Cyproheptadine; benzodiazepines for agitation

• IV antibiotics covering biliary organisms
• Urgent endoscopic biliary decompression (ERCP)

E. Raised ICP Management

• Head of bed 30 degrees
• Mannitol 0.25-1 g/kg IV (or hypertonic saline)
• Hyperventilation (temporary, target pCO2 30-35 mmHg)
• Avoid fluid overload
• Urgent neurosurgery consult if abscess/hemorrhage

DIAGNOSTIC FLOWCHART

Fever + Altered Sensorium
         |
    Check ABCs → Stabilize → Blood glucose stat
         |
    ┌────────────┐
    Focal deficit  |  No focal deficit
    or papilledema?| No contraindication?
         |          |
     CT Head first  LP immediately
         |          |
    ─── Blood cultures → START ANTIBIOTICS + ACYCLOVIR + DEXAMETHASONE ───
         |
    Consider malaria smear, LFT, KFT, serology in endemic areas
         |
    CSF results → refine treatment

KEY CLINICAL PEARLS

1. Never delay antibiotics for CT or LP in a patient with suspected meningitis/encephalitis.
2. Always give empirical acyclovir if encephalitis (behavioral change + fever + seizure) is possible - HSV encephalitis is treatable and delays worsen outcomes.
3. Always give dexamethasone before or with the first antibiotic dose in suspected bacterial meningitis.
4. Papilledema or focal deficit = CT before LP (risk of herniation with LP).
5. In tropical settings, always exclude cerebral malaria in a febrile patient with altered consciousness before any other diagnosis.
6. In epidemic AES situations, consider JE - serology (CSF IgM ELISA) is the diagnostic method of choice.
7. Chemoprophylaxis for close contacts: Rifampicin or ciprofloxacin for N. meningitidis contacts; rifampicin for H. influenzae contacts with unvaccinated household members.

• Rosen's Emergency Medicine, Concepts and Clinical Practice - CNS Infections chapter
• Tintinalli's Emergency Medicine: A Comprehensive Study - Meningitis chapter
• Plum and Posner's Diagnosis and Treatment of Stupor and Coma - Herpes Simplex Encephalitis
• Bradley and Daroff's Neurology in Clinical Practice - Management of Bacterial Meningitis
• Park's Textbook of Preventive and Social Medicine - AES/JE chapter
• Harrison's Principles of Internal Medicine 22E (2025) - Adjunctive therapy in meningitis