Tetanus

Aka: Tetanus, Tetanic opisthotonus, Clostridium tetani, Risus Sardonicus, Sardonic Grinning, Rictus Grin, Tetanus Prophylaxis, Cephalic Tetanus

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II. Epidemiology

  1. Incidence (2008 U.S.): 0.06 per million persons

III. Pathophysiology

  1. Clostridium tetani
    1. Motile, spore forming Gram Positive Rod
    2. Obligate Anaerobe
    3. Organism lives in soil as well as the stool of domestic animals and people
  2. Tetanus spores enter patient via wounds (even minor, superficial wounds, umbilical stump of newborn)
    1. Incubation Period 3 to 21 days after wound exposure
    2. Tetanus spores germinate in anaerobic environments (e.g. devitalized or necrotic tissue)
    3. No person to person transmission
  3. Germinated spores produce Tetanus toxin (exotoxin)
    1. Tetanus toxin spreads to nerves
    2. Either hematogenous spread or retrograde transmission via nerves
  4. Tetanus Toxin (Tetanospasmin) irreversibly binds nerves
    1. Toxin is composed of 2 subunits
      1. H-Heavy subunit binds Neuronal gangliosides
      2. L-Light subunit blocks release of inhibitory Neurotransmitters (Glycine, GABA)
    2. Mechanism
      1. Prolonged motor Neuron discharge in the absence of inhibitory Neuron activity
        1. Allows for high frequency Muscle impulses, resulting in Tetany
      2. Tetanus toxin blocks presynaptic release of inhibitory Neurotransmitters
        1. Blocks Glycine and GABA release from Renshaw inhibitory interneurons

IV. Risk Factors

  1. Contaminated wounds or Puncture Wounds (e.g. Open Fractures, ocular injuries)
    1. However up to 30% of Tetanus cases occur in clean wounds (e.g. surgical wounds)
    2. Contamination of the neonatal umbilical stump occurs in developing countries (esp. unimmunized mother)
  2. Inadequate tetanus Vaccination (or large pathogen burden)
  3. Advanced age (waning Immunity)
  4. HIV Infection
  5. Diabetes Mellitus
  6. Corticosteroids or other Immunosuppressants

V. Signs

  1. General
    1. Muscle spasms are initially intermittent (each lasting seconds to minutes)
    2. With progression, spasms increase in frequency and duration
    3. Spasms may be triggered by even minor stimuli (light touch or noise)
  2. Opisthotonos (arching of back)
    1. Diffuse Muscle firing of both the stronger extensor and weaker flexor back Muscles
  3. Lockjaw (Trismus)
    1. Painful, contractions of the masseter and neck Muscles
  4. Facial Muscle spasms
    1. Risus Sardonicus (Sardonic Grinning)
  5. Abdominal rigidity
    1. Seen in older children and adults
  6. Other regions of Muscle spasm
    1. Oropharyngeal Muscle spasm (Dysphagia)
    2. Neck Muscle spasms (Torticollis)
    3. Laryngeal Muscle spasm (airway compromise)
    4. Respiratory Muscle spasm (apnea)
  7. Autonomic instability associated with Catecholamine release (onset 1 week after motor symptoms)
    1. Fever
    2. Irritability and motor restlessness
    3. Sweating
    4. Tachycardia
    5. Labile Blood Pressure including Hypertension
    6. Dysrhythmias

VI. Types

  1. Neonatal Tetanus (accounts for 50% of worldwide deaths)
    1. Associated with contamination of the neonatal umbilical stump
    2. Presents in the first week of life with poor feeding, decreased movement, irritability, Muscle rigidity and spasms
  2. Localized Tetanus to one body region (rare)
    1. Typically progresses to Generalized Tetanus
    2. Lower mortality if Tetanus remains localized
  3. Cephalic Tetanus
    1. Localized Tetanus from a head, ears, nose or neck wound
    2. Involves Muscles of eyes, face, Tongue and pharynx
    3. Affects Cranial Nerves and may result in a secondary Bell's Palsy
    4. Lower mortality than in generalized Tetanus
      1. However Cephalic Tetanus often progresses to generalized Tetanus
  4. Splanchnic Tetanus
    1. Swallowing and respiratory Muscles affected
  5. Generalized Tetanus (80% of cases)
    1. Associated with rigidity, spasm and Autonomic Dysfunction
    2. Onset at 3 to 21 days after infection
    3. Associated with higher mortality rates
    4. Cephalocaudal spread of Muscle spasms
      1. Lockjaw
      2. Opisthotonos
      3. Death due to diaphragmatic spasm or laryngospasm

VII. Diagnosis

  1. Tetanus is a clinical diagnosis
  2. Specific testing identifies Clostridium tetani in only 30% of Tetanus cases

VIII. Differential Diagnosis

  1. Local Trismus
    1. See Trismus
    2. Alveolar abscess or other local soft tissue infection
    3. Mandibular Trauma
  2. Tetany (generalized increased tone)
    1. Hypocalcemia
    2. Hypoparathyroidism
    3. Hypomagnesemia
    4. Strychnine Poisoning
    5. Dystonic Reaction
  3. Opisthotonos (arched back)
    1. Strychnine Poisoning
  4. Risus Sardonicus (Sardonic Grin)
    1. Strychnine Poisoning
    2. Wilson's Disease
    3. Water dropwort (Oenanthe crocata) Poisoning
      1. Appendino (2009) J Nat Prod 72(5):962-5 +PMID:19245244 [PubMed]
  5. Other conditions
    1. Meningitis
    2. Encephalitis
    3. Rabies
    4. Neuroleptic Malignant Syndrome

IX. Management

  1. General
    1. Hospital admission (typically ICU) for all active Tetanus infections
    2. No person to person transmission (not contagious)
  2. Background: Goals of management
    1. Eliminate Tetanus infection
      1. Wound Debridement and removal of necrotic tissue
      2. Antibiotics (see below)
    2. Neutralize unbound peripheral Tetanus toxin
      1. Treat with human tetanus Immunoglobulin
    3. Decrease effects of CNS bound Tetanus toxin
  3. Anti-Tetanus agents
    1. Human Tetanus immune globulin (TIG)
      1. Administer 3000-6000 units in a site away from the Tetanus ToxoidVaccine
      2. Equine Tetanus immune globulin (TIG) may be used if human formulation is not available
      3. Equine Tetanus antitoxin may be used if immune globulin is not available (test Hypersensitivity first)
    2. Antibiotics
      1. Metronidazole (first-line)
      2. Penicillin
      3. Treat co-infection if suspected (with Third Generation Cephalosporin)
      4. Other Antibiotics with activity (Doxycycline, Macrolides, Clindamycin, Vancomycin, Chloramphenicol)
    3. Tetanus Toxoid booster
      1. Given on patient recovery
      2. Primary Tetanus infection does not confer Immunity
  4. Other measures
    1. Ensure adequate airway (Advanced Airway)
      1. Rapid Sequence Intubation with non-depolarizing paralytic (e.g. Rocuronium)
    2. Control Muscle spasm (sedation, Analgesics and Muscle relaxants)
      1. Intravenous Benzodiazepines
      2. Morphine or Hydromorphone
      3. Other agents may be considered
        1. Baclofen and/or Dantrolene (common use based on minimal evidence)
        2. Dexmedetomidine (Precedex)
        3. Phenobarbital
        4. Magnesium
      4. Patients on Mechanical Ventilation
        1. Propofol sedation
        2. May also consider neuromuscular blocking agents (e.g. Vecuronium)
    3. Wound care
      1. See Wound Debridement as above
    4. Autonomic instability
      1. Avoid Propranolol (association with Sudden Cardiac Death)
        1. Other Beta Blockers may be used (e.g. Metoprolol)
      2. Clonidine
        1. May decrease sympathetic drive

X. Complications: Acute

  1. Airway
    1. Trismus
    2. Laryngospasm or respiratory arrest
  2. Cardiopulmonary
    1. Decreased diaphragm excursion
    2. Aspiration
    3. Aspiration Pneumonia
    4. ARDS
    5. Pulmonary Embolism
  3. Miscellaneous
    1. Fractures
    2. Death

XI. Complications: Chronic

  1. Abnormal Gait
  2. Muscle rigidity
  3. Memory Loss
  4. Persistent vegetative state

XII. Course

  1. Incubation Period: 3 to 21 days (10 days on average)
  2. Earlier onset after exposure is associated with more aggressive infection and worse prognosis
  3. Tetanus duration is 6-8 weeks (to allow nerve regrowth)
  4. Expect a long, slow recovery if survived

XIII. Prognosis

  1. Mortality is reduced to as low as 15% in developed countries with Intensive Care
  2. Adult Mortality: 52%
  3. Neonatal mortality: 88%

XIV. Prevention: Tetanus Prophylaxis

  1. Clean wounds well
    1. Irrigate extensively with adequate pressure
    2. Debride necrotic tissue
  2. Tetanus Vaccine
    1. Routinely update Tetanus Vaccine (Tdap or Td) every 10 years after initial Primary Series (DTaP) in children
    2. Severe wounds, crush injuries, punctures or burns, or contaminated (dirt, feces)
      1. Update Tetanus Vaccine at 5 years with Tdap or Td (or DTaP if age <7 years)
      2. Give Tetanus Immunoglobulin if indicated as below (severe or dirty wounds and <3 Vaccine doses)
    3. Unvaccinated patients
      1. Give Tetanus Vaccine (Tdap or Td, or if age <7 years DTaP) at 0, 6 and 12 months
  3. Tetanus Immunoglobulin (TIG)
    1. Indicated in dirty wound with <3 doses of Tetanus Vaccine (including Primary Series) or unknown status
    2. May give Tetanus Immunoglobulin up to 3 weeks after injury
  4. References
    1. (2020) Presc Lett 27(8): 46

XV. Resources

  1. CDC Tetanus information
    1. http://www.cdc.gov/tetanus/
  2. CDC Tetanus surveillance
    1. http://www.cdc.gov/tetanus/surveillance.html

XVI. References

  1. Harrison and Ruttan (2019) Crit Dec Emerg Med 33(7): 3-12
  2. Harrison and Ruttan (2023) Crit Dec Emerg Med 38(2): 23-31
  3. Nordt, Swadron, Orman and Ran in Herbert (2015) EM:Rap 15(7):15-16

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