FRCA Notes

Tetanus

Tetanus isn't mentioned in the intermediate curriculum, making this topic eminently skippable.

'Toxins of the neuromuscular junction' is a Primary FRCA topic, thus making it technically fair game in the Final.

Resources

  • Tetanospasmin is a toxin produced by the spore-forming anaerobic bacterium Clostridium tetani, typically found in soil
    • It also releases a second toxin: exotoxin tetanolysin
  • The lethal dose is merely 1ng/kg
  • Globally still occurs frequently in neonates, often in developing nations
  • In the UK the majority of cases affect older adults, with no neonatal tetanus cases in decades

  • Routine vaccination occurs as part of the DPT (diphtheria, pertussis and tetanus) vaccine
  • Immunity is not necessarily lifelong and boosters may be required, especially if there has been exposure

  • Tetanus bacilli enter the body through broken skin, mucosal surfaces or (as in 20% of cases) the route of entry is not found
  • Tetanospasmin is released by the bacteria on entry into the body
  • There is an incubation period of ~7 days with symptoms 1-2 weeks after infection

  • Tetanospasmin binds the pre-synaptic membrane of the neuromuscular junction
  • Once bound, it is transported retrogradely to the axon's cell body
  • Further spread occurs trans-synaptically to adjacent motor and autonomic nerves

  • Tetanospasmin cleaves the protein synaptobrevin, responsible for neurotransmitter vesicle release
  • It thus inhibits GABA and glycine release from inhibitory spinal cord synapses involved in the regulation of muscle length and tension
  • This causes increased muscle tone and rigidity, interposed by paroxysmal muscle spasms

  • Sympathetic neurones are eventually affected, leading to autonomic irregularities
  • Neuronal binding of the toxin is irreversible

  • Clinical diagnosis based on:
  1. Muscle rigidity
    • Neck muscle stiffness
    • Trismus
    • Dysphagia

  2. Muscle spasms
    • Painful spasms of such strength they can break bones, which may be stimulated by light, sound or touch
    • Opisthotonus
    • Spasm of the facial muscles; risus sardonicus
    • Respiratory muscle spasm with severe hypoventilation and apnoea
    • Laryngeal spasm causing respiratory obstruction

  3. Autonomic dysfunction
    • Classic autonomic dysreflexic symptoms
    • Other symptoms such as salivation, sweating, increased bronchial secretions, hyperpyrexia, gastric stasis and ileus

  • Typically on ICU due to need for sedation/anaesthesia and airway control

Neutralise bacteria and unbound toxin

  • Antibiotics for C. tetani infection
    • Metronidazole the agent of choice
    • Erythromycin, tetracycline, chloramphenicol and clindamycin are alternatives
  • May need surgical washout or debridement of infected wounds/tissues

  • Use human tetanus immunoglobulin (HTIg) to neutralise toxin not yet bound to neurones
  • Does not remove alread-bound toxin

Control rigidity and spasm

  • First line: benzodiazepines e.g. high-dose midazolam infusion
  • Others:
    • Opioid infusion e.g. morphine, remifentanil
    • Propofol infusion
    • Clonidine infusion

  • Alternative agents to help control spasms:
    • Phenobarbital
    • Chlorpromazine
    • Baclofen
    • Dantrolene
  • NMBA infusion is an option in refractory cases

Control autonomic dysfunction

  • Sedation is also the first-line treatment for autonomic instability
    • Morphine
    • Clonidine
    • Magnesium infusion adjusted to achieve a plasma concentration of 2.5–4.0 mmol/L

  • High-dose atropine infusions may be required for refractory bradycardia

Supportive care

  • Standard ICU supportive care
    • Ventilator care bundles
    • Early enteral nutrition
    • Stress-ulcer prophylaxis
    • Monitor CK as risk of rhabdomyolysis from spasms
    • Adequate VTE prophylaxis

Outcomes

  • Disease process typically lasts 4-6 weeks
  • In the developed world, death from respiratory failure is still 10-20%, rising to close to 50% in developing nations