259R. Chawla and S. Todi (eds.), ICU Protocols: A stepwise approach, DOI 10.1007/978-81-322-0535-7_32, © Springer India 2012

A 40-year-old male patient was admitted to hospital with a 2-day history of fever, headache, and increasing confusional state. On examination, he was dis-oriented to time and place, was opening eyes on verbal command, had an incom-prehensible speech, and was moving all limbs appropriately. His neck was stiff and fundi were normal.

J. Shah , M.D., E.D.I.C. (*) Department of Intensive Care Unit , Bharti Vidyapeeth Medical College , Pune , India e-mail: drshahjignesh@rediffmail.com

S. Iyer , M.D., E.D.I.C. Department of Intensive Care Unit , Sahyadri Specialty Hospital , Pune , India

32 Acute Febrile Encephalopathy

Jignesh Shah and Shivakumar Iyer

A high index of suspicion should be maintained for a diagnosis of an infection involving the nervous system in any patient with fever and altered mental state. Time is essence in managing these patients as any delay could lead to irreversible brain damage (Fig. 32.1 ).

Step 1: Initiate resuscitation and assess neurological status In neurological problems, assessment of airway and need for intubation is of • paramount importance as these patients are at high risk of aspiration. Glasgow coma scale (GCS) below 8 usually requires airway protection (see • Chap. 78 ).

Step 2: Take history and perform focused examination Patients presenting with fever and altered mental status can be broadly divided • into three categories. 1. Primary central nervous system infection such as meningitis, encephalitis,

and brain abscess

260 J. Shah and S. Iyer

2. Systemic infection with confusional state 3. Noninfectious causes of fever and encephalopathy History and physical examination should be carried out systematically to identify • the category in which the patients belong.

Travel history (malaria, dengue, typhus, arbovirus infection) – Drug history (steroids, other immunosuppressive) – Trauma (splenectomy) – Symptoms of ENT infection – Neurosurgery –

Look for evidence of systemic infection,check WBCs, look for source of infection,

procalcitonin/CRP

Check Blood Sugar, ABG and serum electrolytes

Initial assessment and management of ABC

Approach to the patient with fever and encephalopathy

Focal neurological deficitNo focal neurological deficit

LP, if no raised ICP or mass effect, specificCSF studies according to clinical context

Treat accordingly

Prevention and treatment of raised ICP

Prevention of secondary injuries, e.g., aggressive control of fever and hyperglycemia

Consider endocrinopathies, malignant hyperthermia in relevant clinical context

Treat accordingly

If no infection, review drug chart for drugfever, NMS, serotonergic syndrome

CT imaging to rule out primary CNS structurallesion or evidence of infective etiology (contrastscan)

Evaluation for presence of focal neurological deficit

Appropriate investigations for search of sourceof sepsis, cultures

Fig. 32.1 Acute febrile encephalopathy management

26132 Acute Febrile Encephalopathy

Medical history of immunosuppressive disease, tuberculosis – History of tuberculosis in close family members –

Neurological examination should be performed.• Look for papilledema, airway re fl exes, focal or lateralizing neurological signs, –and neck stiffness.

Perform systemic examination to look for a source of sepsis. • Perform general examination for skin rash, eschar, injection marks (intravenous • drug abuse).

Step 3: Initiate empirical treatment (Table 32.1 ) In neurological infection, time is of essence, so empirical therapy should be started, • pending investigation especially in cases of suspected meningoencephalitis. Correct any obvious metabolic causes. •

Table 32.1 Therapy for meningoencephalitis

Herpes encephalitis Acyclovir 10 mg/kg IV 8 hourly (adjust for renal impairment) for 2 weeks

Bacterial meningitis Empirical (duration of therapy 14 days)

Ceftriaxone 2 g IV twice daily plus Vancomycin 10–15 mg/kg IV thrice daily Dexamethasone 0.15 mg/kg IV thrice daily for 4 days (prior to or concurrently with antibiotics) useful mainly in pneumococcal infection

Streptococcus pneumoniae (duration of therapy 14 days)

Ceftriaxone 2 g IV twice daily or Ceftriaxone 2 g IV twice daily plus Vancomycin 10–15 mg/kg IV thrice daily (if MIC of ceftriaxone >1 mcg/mL)

Neisseria meningitidis (duration of therapy 7 days)

Ampicillin 2 g IV 4 hourly or Ceftriaxone 2 g IV twice daily (if MIC to penicillin >0.1 mcg/mL)

Listeria monocytogenes (duration of therapy 21 days)

Ampicillin 2 g IV 4 hourly or Trimeth/sulpha 5 mg/kg 8 hourly (if allergic to penicillin)

Postneurosurgery ( Gram-negative bacilli and Staphylococcus aureus )

Carbapenem + vancomycin

Tubercular meningitis INH 5 mg/kg (300 mg in adults) Rifampicin (RIF) 10 mg/kg (600 mg in adults) Pyrazinamide (PZA) 15–20 mg/kg (maximum 2 g) Ethambutol (EMB) (15–25 mg/kg) Streptomycin (STM) (in selected cases) 15 mg/kg/day IM (maximum 1 g)

Duration A four-drug regimen that includes INH, RIF, PZA, and either EMB or STM for 2 months followed by INH and RIF alone if the isolate is fully susceptible, for an additional 10 months

262 J. Shah and S. Iyer

Step 4: Send basic investigations General investigation workup, such as Complete blood count (CBC), blood • culture, liver and renal pro fi le, coagulation parameters, electrolyte (e.g., calcium) panel, chest X-ray, echocardiogram (to exclude vegetation), should be performed in all patients. Exclude systemic infection.•

In endemic areas, look for malaria (peripheral smear and antigen), leptospira –(antibody), enteric fever (blood culture, antibody), dengue (antibody), typhus (antibody), and Japanese B encephalitis (antibody in serum and CSF). These will depend on geographic location of the patient.

Step 5: Send speci fi c investigations It should be done expeditiously as time is of essence in these conditions. • Empirical treatment should be started pending the investigation to prevent fur-• ther brain damage. Neuroimaging•

CT scan/MRI of the brain (with contrast if not contraindicated). – Care should be taken to transport these patients for neuroimaging, and judi- –cious use of sedation should be done to avoid oversedation while facilitating proper image acquisition. If necessary, the patient should be intubated prior to imaging. – Brain abscess is characterized by ring-enhancing lesion either single (frontal –sinus infection), temporal (middle ear infection), or multiple (systemic infec-tion). Herpes encephalitis will show bitemporal involvement. Decision for imaging should not delay starting the empirical therapy. –

Cerebrospinal fl uid (CSF) study (see Table • 32.2 ) (see Chap. 100 ) CSF examination is essential to diagnose meningoencephalitis. – Coagulopathic state and thrombocytopenia need to be corrected prior to lum- –bar puncture (keep international normalized ratio [INR] <1.4 and platelet count >50,000). Prior brain imaging is required in patients with papilledema, seizures, or focal –neurological signs. CSF should be examined immediately. –

Cell count and type • Protein • Glucose (simultaneous blood glucose estimation is important; CSF glucose • value is normally 60–70% of blood glucose)

Table 32.2 CSF analysis in untreated meningitis CSF parameters Bacterial Tubercular Viral Fungal White cell count 1,000–10,000 100–1,000 <300 50–200 Neutrophil (%) >80 <10 <20 <50 Protein (mg/dL) 100–500 >250 Normal Mild rise Glucose (mg/dL) <40 <10 >40 <40

26332 Acute Febrile Encephalopathy

Adenosine deaminase (ADA) (if tuberculosis is suspected) • Gram stain, culture, and sensitivity • Acid-fast bacilli (AFB) stain • India ink for cryptococcal infection • DNA PCR for herpes virus • Cryptococcal antigen • TB PCR and BACTEC TB culture • Pneumococcal antigen •

A sample of CSF should be preserved by the laboratory for further testing. – Classical CSF fi ndings may change in partially treated meningoencephalitis. –

Step 6: Take isolation precaution Proper respiratory isolation precaution should be taken in patients with suspected • bacterial meningitis (see Chap. 48 ). The patient should wear mask during transportation. •

Step 7: Look for noninfectious causes of fever and neurological features • Structural brain lesions

Intracerebral hemorrhage, pontine bleeding, and subarachnoid hemorrhage – • Drugs and toxins

Organophosphorus, atropine, tricyclic antidepressants, phenothiazines, –cocaine, and amphetamines

• Heat stroke Take history of exposure to extreme heat and exertion. Look for evidence of –rhabdomyolysis.

• Neuroleptic malignant syndrome It is caused by central dopamine antagonism. – Clinical features include hyperpyrexia with “lead-pipe” rigidity, extrapyrami- –dal effects, and seizures. Other effects include rhabdomyolysis, renal failure, hepatic failure, and dissemi- –nated intravascular coagulation. Metabolic acidosis and elevated transaminases are common. Typical agents involved are haloperidol, chlorpromazine, promethazine, and –prochlorperazine. A few atypical agents such as risperidone, olanzapine, and quetiapine are also –responsible. Onset of symptoms is usually days to weeks after the inciting agent is –started. Management includes withdrawal of inciting agents, cooling, dantrolene, and –bromocriptine.

• Serotonergic syndrome It occurs within minutes to hours of initiating an offending agent. – Symptoms are hyperre fl exia, myoclonus, and hyperthermia. – Inciting agents are selective serotonin receptor uptake inhibitors (SSRIs), – tricyclic antidepressants, and trazodone.

264 J. Shah and S. Iyer

• Malignant hyperthermia (MH) MH is a speci fi c inherited muscle membrane disorder. – It causes a dangerous hypermetabolic state after anesthesia with suxametho- –nium and/or volatile halogenated anesthetic agents. Dantrolene sodium is a speci fi c antidote and induces fl accidity of muscle due –to inhibition of excitation–contraction coupling in skeletal muscle.

• Endocrine abnormalities Thyrotoxic crisis –

Suggested Reading

1. Mace SE. Central nervous system infections as a cause of an altered mental status? What is the pathogen growing in your central nervous system? Emerg Med Clin North Am. 2010;28(3):535–70.

A practical review of managing CNS infections. 2. Honda H, Warren DK. Central nervous system infections: meningitis and brain abscess. Infect

Dis Clin North Am. 2009;23(3):609–23. This article reviews the common infectious etiologies of central nervous system infections,

especially bacterial meningitis and brain abscess, and their subsequent management in the intensive care unit.

3. Ziai WC, Lewin JJ III. Update in the diagnosis and management of central nervous system infections. Neurol Clin. 2008;26(2):427–68.

This review focuses on early aggressive management of common infections of the central ner-vous system that require monitoring in an ICU setting.

4. Zunt JR, Marra CM. Cerebrospinal fl uid testing for the diagnosis of central nervous system infection. Neurol Clin. 1999;17(4):675–89.

This article discusses how these CSF tests are performed and addresses the sensitivity and speci fi city of such tests for the diagnosis of selected CNS infections.