Tuberculosis

Devastating mycobacterial disease that causes substantial global morbidity and mortality. Tuberculosis manifestations that may draw attention of the intensivist include:

Epidemiology and Risk Factors

Risk factors:

  • Living conditions
    • Institutionalised
    • Poverty and crowding
  • Immunosuppression
    • HIV
    • Diabetes
    • Transplantation
    • Prolonged steroid use

Pathophysiology

Mycobacterial tubercule is a fastidious mycobacterium, inhalation of which leads to one of four outcomes:

  • Immediate clearance
    No lasting consequences.
  • Primary/progressive disease
    Results in pulmonary infection, with or without lymphohaematogenous seeding to distant sites.
    • Occasionally leads to:
      • Miliary TB
      • Cerebral TB
  • Chronic/latent infection
  • Secondary/Reactivation TB
    Occurs when dormant mycobacteria reactivate.
    • Secondary pulmonary disease develops apical lesions that undergo caseation necrosis
      Leads to cavitation with surrounding fibrosis.
      • Caseous soup drains into bronchi, stimulating coughing which facilitates spread to other:
        • Parts of the lung
        • People
    • Meningeal disease develops due to haematogenous spread
      Characterised histologically by gelatinous exudate around fissures.

Aetiology

Five members of the mycobacterium complex are responsible:

  • M. tuberculosis
  • M. bovis
  • M. africanum
  • M. microti
  • M. canetti

Clinical Manifestations

Non-specific systemic features include:

  • Fever
  • Sweating
    Night sweats.
  • Weight loss
  • Anorexia

Primary Pulmonary Tuberculosis

Primary disease is:

  • Asymptomatic in 90%
  • More common in children and the immunocompromised
    • HIV
  • Characterised by:
    • Hilar lymphadenopathy
    • Pulmonary consolidation

Secondary Pulmonary Tuberculosis

Most pulmonary TB and is generally:

  • Due to either reactivation or reinfection
  • Seen in adults
  • Characterised by:
    • Apical infiltrates
      • Apical crepitations
      • Persistent pnuemonias
    • Cavitation
      Localised wheezing.
    • Coughing

Advanced features include:

  • Dyspnoea
  • Haemoptysis
  • Pneumothorax
    Rupture of cavity into pleura.
  • Pleural effusions

Tuberculosis Meningitis

Meningitic infection secondary to haematogenous spread, characterised by:

  • Vague 2-8 week prodrome of generalised unwellness
  • Subacute meningitis
    Often without neck stiffness.
  • Cranial nerve palsies
    20-25%.
  • Focal neurological deficit
  • Global deficit
    Late signs.
    • Seizures
    • Coma

Diagnostic Approach and DDx

Investigations

Bedside:

  • Bronchoscopy:
    • BAL
    • Bronchial biopsy
      May be indicated if high clinical suspicion and negative smear.

Laboratory:

Acid-fast refers to bacilli that have waxy (classically mycolic acids) substances in their cell wall, which retain a carbol fuchsin stain after being washed in an acidic solution.

The classic acid-fast stain is the Ziehl-Neelsen stain.

Adenosine deaminase is an enzyme that degrades immunosuppressive signalling by adenosine, and is locally upregulated in the presence of ↑ lymphocytes.

  • Nucleic acid amplification
    Amplifies known sections of DNA:
    • Available for fluid samples, including sputum
    • Moderately sensitive and highly specific
    • Can rapidly confirm diagnosis and presence of rifampicin resistance
    • Can differentiate M. tuberculosis from other mycobacteria
  • Sputum
    • Exceedingly difficult to culture
    • Multiple samples should be collected across different days
    • Request:
      • Fluorescent microscopy for acid-fast bacilli
      • Culture
      • Adenosine deaminase
  • Pleural fluid
    • Culture
      Negative in >75% of cases.
    • Adenosine deaminase
      >70/L favours TB; and may justify commencing treatment with high enough clinical suspicion.
  • CSF
    • Culture ~70% positive in meningeal disease.
    • Adenosine deaminase

Imaging:

  • CXR
    Very sensitive and a normal CXR almost excludes TB, except in:
    • HIV +ve patients
    • Early apical disease
  • CT Chest
    More sensitive than plain film for identifying:
    • Cavities
    • Lymphadenopathy
    • Bronchiectasis
    • Bronchopleural fistulae
    • Effusions
  • CT Brain
    Sensitive and not specific, features include:
    • Meningeal thickening with contrast enhancement
    • Tuberculomas
    • Hydrocephalus

Management

Specific therapy:

  • Pharmacological
    Local guideline and advice should be sort, particularly for resistant disease. The classical treatment of sensitive TB is a combination of 4 antimicrobials:
    • Initial phase
      8 weeks of:
      • Rifampacin 450-600mg daily
      • Isoniazid 300mg
      • Pyrazinamide 1.5-2g daily
      • Ethambutol 15mg/kg daily
        May cause visual disturbances; should be restricted to patients with reasonable acuity and ability to report disturbances.
    • Continuation phase
      4 months of:
      • Rifampicin
      • Isoniazid
  • Physical
    • Infection control measures
      • Treat as contagious if:
        • Active coughing
        • Positive AFB smear
        • <2 weeks of treatment (of non-resistant strains)
      • Should be managed in negative-pressure isolation

Disposition:

  • ICU
    Patients admitted to ICU generally have either:
    • Pulmonary TB
      • Acute respiratory failure
    • Tuberculosis meningitis

Marginal and Ineffective Therapies

Anaesthetic Considerations

Complications

  • Death
    • 25% in those requiring ICU
    • 50% in those requiring mechanical ventilation
  • B
    • Pneumothorax
    • Pleural effusion
  • D
    • Hydrocephalus
    • Seizures
    • Coma

Prognosis

Depends on the primary manifestation:

  • Pulmonary disease
  • Meningitis
    ~50% mortality.

Key Studies

References

  1. Hagan G, Nathani N. Clinical review: Tuberculosis on the intensive care unit. Crit Care. 2013;17(5):240.