Tetanus

Reviewed and revised 9 February 2014

OVERVIEW

• potentially lethal condition characterised by muscular rigidity and spasms, caused by the tetanospasmin toxin produced by Clostridium tetani, that may lead to life-threatening respiratory failure and autonomic dysregulation in severe cases
• rare in the developed world, but accounts 1 million deaths worldwide each year

TYPES

• cephalic
• local
• generalised
• neonatal (50% of tetanus deaths worldwide)

CAUSE

Clostridium tetani

• caused by toxin from Clostridium tetani -> able to survive in the environment as highly resistant spores
• anaerobic spore forming gram positive bacillus
• once in a suitable environment -> spores germinate -> bacteria multiply -> toxins released (tetanospasmin and tetanolysin)

Tetanospasmin

• taken up by motor nerves or haematogenous spread to CNS
• disrupts synaptic transmission by preventing release of neurotransmitters (zinc endopeptidase)
• preferentially prevents discharge from GABA inhibitory interneurons in spinal cord and brainstem
  -> unrestricted motor nerve activity and autonomic instability

CLINICAL FEATURES

Clinical triad of rigidity, muscle spasms and, if severe, autonomic dysfunction

• contaminated wound (may be trivial) or umbilical stump in neonates
• incubation period: 3-14d (1-60 at the extremes) = time to first symptom
• onset time: 1-7d = time from first symptom to first spasm
• rigidity (persists > 2 weeks)
  — trismus, dysphagia, increased tone in trunk muscles – greater on side of injury initially
• spasms (reduce after 2 weeks)
  — spontaneous or provoked by physical or emotional stimuli, laryngospasm, risus sardonicus, opisthotonos (severe spasm in which the back arches and the head bends back and heels flex toward the back)
• autonomic disturbance (onset after spasms, lasts 1-2 weeks)
  — tachycardia and hypertension may alternate with bradycardia and hypotension, dysrhythmia, cardiac arrest
  — salivation, bronchial secretions
  — gastric stasis, ileus, diarrhoea
• respiratory compromise
  — chest wall rigidity
  — laryngospasm
  — aspiration
  — retained secretions

DIFFERENTIAL DIAGNOSIS

Diagnosis of tetanus is made clinically

• strychnine poisoning
• trismus due to orofacial infection
• stiff person syndrome
• acute dystonic reaction
• seizure disorder
• hypocalcaemic tetany
• psychogenic
• meningism

Neonatal tetanus may resemble:

• Seizures
• meningitis
• sepsis

INVESTIGATIONS

• urinary strychnine to exclude this as a cause
• CK, UEC, CMP for rhabdomyolysis and to rule out low Ca
• ABG (respiratory failure)

MANAGEMENT

Resuscitation

A – intubate as requires large doses of sedatives to control muscle spasm and to overcome laryngospasm
B – at risk of aspiration and have copious bronchial secretions requiring frequent suctioning, often ventilated for 2-3 weeks until spasms subside
C – autonomic dysfunction necessitate monitoring in a critical care environment, fluctuant haemodynamics so use short acting agents; fluid loading
D – benzodiazepines in large doses (up to 100mg/h diazepam) -> non-depolarsing NMBD

Specific Therapy

• metronidazole (first choice); penicillin is used throughout most of the world but is a GABA antagonist
• anti-tetanus immunoglobulin: 100-300IU/kg of human Ig IM
• benzodiazepines; adjuncts include barbiturates, propofol, chlorpromazine
• Mg to 2-4mmol/L as useful in spasm treatment and limits autonomic instability
• consider dantrolene (unproven)
• consider intrathecal baclofen

Treat underlying cause and complications

• clean and debride wounds (source control)
• immunize (infection does not confer immunity) – Q10 yearly

Supportive care and monitoring – usual cares with emphasis on:

• calm environment
• cardiac monitoring
• nutrition e.g. enteral feeding
• often require tracheostomy
• prevention of pressure sores and GI stress ulcers

COMPLICATIONS

Respiratory

• Aspiration
• Laryngospasm/obstruction
• Sedative-associated obstruction
• Respiratory apnoea
• Type I (atelectasis, aspiration, pneumonia) and type II respiratory failure (laryngeal spasm, prolonged truncal spasm, excessive sedation)
• ARDS
• Complications of prolonged assisted ventilation (e.g. pneumonia)
• Tracheostomy complications (e.g. tracheal stenosis)

Cardiovascular

• Tachycardia, hypertension, ischaemia
• Hypotension, bradycardia, asystole
• Dysrhythmias
• Cardiac failure

Renal

• High output renal failure
• Oliguric renal failure
• Urinary stasis and infection

GI

• Gastric stasis
• Ileus
• Diarrhoea
• Haemorrhage

Other

• Dehydration
• Weight loss
• Thromboembolus
• Sepsis and multiple organ failure

Musculoskeletal

• Fractures of vertebrae during spasms
• Tendon avulsion during spasms
•  rhabdomyolysis

PROGNOSIS

Mortality

• untreated: >50% (usually due to respiratory failure)
• high level ICU care available: 10-25% (usually due to autonomic failure)

Survivors

• severe cases usually require 3-5 weeks in ICU
• often make full recovery

Indicators of poor prognosis

1. incubation of < 7 days
2. period of onset < 48 hours
3. portal of entry from umbilicus, uterus, burns, open fracture or IM injection
4. presence of spasms
5. temperature > 38.4
6. HR > 120 (adults), > 150 (neonates)

References and Links

LITFL

• Clinical Case – Stiff in the mouth

Journal

• Cook TM, Protheroe RT, Handel JM. Tetanus: a review of the literature. Br J Anaesth. 2001 Sep;87(3):477-87. Review. PubMed PMID: 11517134.
• Dingli K, Morgan R, Leen C. Acute dystonic reaction caused by metoclopramide, versus tetanus. BMJ. 2007 Apr 28;334(7599):899-900. PMC1857743.
• Farrar JJ, Yen LM, Cook T, Fairweather N, Binh N, Parry J, Parry CM. Tetanus. J Neurol Neurosurg Psychiatry. 2000 Sep;69(3):292-301. Review. PubMed PMID: 10945801; PubMed Central PMCID: PMC1737078.