Tetanus

• Tetanus is a neurological disorder characterized by increased muscle tone and spasms, that is caused by tetanospasmin, a powerful protein toxin elaborated by Clostridium tetani.
• 1st described – Egypt 3000 years ago.
• 1st passive immunization - 1893.
• 800,000 - 1 million deaths/year.
• 400,000 - Neonatal.
• 80% of deaths occur in Africa & SE Asia.
• Remains endemic in 90 countries worldwide.

Clinical forms-

• Generalized
• Localized
• Cephalic
• Neonatal

• C. tetani
• Obligate anaerobe, motile, spore-forming, G +ve bacillus.
• Spores can withstand boiling for 20 min.
• Widely distributed in the environment.
• Found in the intestinal flora of domestic animals, horses, chickens, and humans.
• Toxins: tetanolysin & tetanospasmin.

• Worldwide
• Tetanus cases in the United States has declined significantly since 1947. This is likely due to the widespread use of tetanus vaccines.
• Sporadic
• Almost always affects non-immunized
• Partially immunized
• Fully immunized who fail to maintain adequate immunity with booster doses of vaccine
• Common in:
• Rural areas
• Warm climates
• Summer months
• Male

• C. tetani spores usually enter through contaminated wounds.
• Manifestations of tetanus are caused by an exotoxin (tetanospasmin) produced when bacteria lyse. The toxin enters peripheral nerve endings, binds there irreversibly, then travels retrograde along the axons and synapses, and ultimately enters the central nervous system (CNS).
• As a result:
  • Release of inhibitory transmitters from nerve terminals is blocked, causing unopposed muscle stimulation by acetylcholine and generalized tonic spasticity.
  • This typically leads to superimposed intermittent tonic seizures.
  • Disinhibition of autonomic neurons and loss of control of adrenal catecholamine release cause autonomic instability and a hypersympathetic state.
  • Once bound, the toxin cannot be neutralized.
• Most often, tetanus is generalized, affecting skeletal muscles throughout the body. However, tetanus is sometimes localized to muscles near an entry wound.

Symptoms of Tetanus

• The incubation period ranges from 2 to 50 days (average, 5 to 10 days).
• Symptoms of tetanus include:
• Jaw stiffness (most frequent)
• Difficulty swallowing
• Restlessness
• Irritability
• Stiff neck, arms, or legs
• Arching of the back (opisthotonos)
• Headache
• Sore throat
• Tonic spasms
• Later, patients have difficulty opening their jaw (trismus).

Spasms

• Facial muscle spasm produces a characteristic expression with a fixed smile and elevated eyebrows (risus sardonicus).
• Rigidity or spasm of abdominal, neck, and back muscles and sometimes opisthotonos (generalized rigidity of the body with arching of the back and neck) may occur.
• Sphincter spasm causes urinary retention or constipation.
• Dysphagia may interfere with nutrition.
• Characteristic painful, generalized tonic spasms with profuse sweating are precipitated by minor disturbances such as a draft, noise, or movement.
• Mental status is usually clear, but coma may follow repeated spasms.
• During generalized spasms, patients are unable to speak or cry out because of chest wall rigidity or glottal spasm.
• Rarely, fractures result from sustained spasms.
• Spasms also interfere with respiration, causing cyanosis or fatal asphyxia.

Autonomic Instability

• Temperature is only moderately elevated unless a complicating infection, such as pneumonia, is present.
• Respiratory and pulse rates are increased.
• Reflexes are often exaggerated.
• Protracted tetanus may manifest as a very labile and overactive sympathetic nervous system, including periods of:
• Hypertension
• Tachycardia
• Myocardial irritability

Causes of Death

• Respiratory failure is the most common cause of death. Laryngeal spasm and rigidity and spasms of the abdominal wall, diaphragm, and chest wall muscles cause asphyxiation.
• Hypoxemia can also induce cardiac arrest, and pharyngeal spasm leads to aspiration of oral secretions with subsequent pneumonia, contributing to a hypoxemic death.
• Pulmonary embolism is also possible.
• However, the immediate cause of death may not be apparent.

Localized Tetanus

• In localized tetanus, there is spasticity of muscles near the entry wound but no trismus; spasticity may persist for weeks.
• Cephalic tetanus is a form of localized tetanus that affects the cranial nerves. It is more common among children; in them, it may occur with chronic otitis media or may follow a head wound.
• Incidence is highest in Africa and India.
• All cranial nerves can be involved, especially the 7th.
• Cephalic tetanus may become generalized.

Tetanus Neonatorum (Neonatal Tetanus)

• Tetanus in neonates is usually generalized and frequently fatal. It often begins in an inadequately cleansed umbilical stump in children born of inadequately immunized mothers.
• Onset during the first 2 weeks of life is characterized by:
  • Rigidity
  • Spasms
  • Poor feeding
• Bilateral deafness may occur in surviving children.

Classification

• Ablett's Classification of Tetanus Severity
• APACHE II Score
• Bademosi/Oshuntokun

Mild - spasm

Moderate - contact/reflex spasm

Severe - spontaneous spasm

Very Severe - status spasm/laryngospasm/apnoeic spells

Rating Scale

1 point is given for each of the following:

• Incubation period shorter than 7 days
• Period of onset shorter than 48 hours
• Tetanus acquired from burns, surgical wounds, compound fractures, septic abortion, umbilical stump, or intramuscular injection
• Narcotic addiction
• Generalized tetanus
• Temperature higher than 104°F (40°C)
• Tachycardia exceeding 120 beats/min (150 beats/min in neonates)

Severity and Prognosis

The total score indicates disease severity and prognosis as follows:

• 0 or 1 – Mild tetanus; mortality below 10%
• 2 or 3 – Moderate tetanus; mortality of 10-20%
• 4 – Severe tetanus; mortality of 20-40%
• 5 or 6 – Very severe tetanus; mortality above 50%
• Cephalic tetanus is always severe or very severe. Neonatal tetanus is always very severe.

Score	Severity	Prognosis (mortality rate)
0-1	mild	< 10%
2-3	moderate	10-20%
4	severe	20-40
5-6	very severe	> 50%

Ablett Classification of Tetanus Severity
Grade	Clinical features
I	Mild: mild to moderate trismus; general spasticity; no respiratory embarrassment [respiratory distress]; no spasms; little or no dysphagia
II	Moderate: moderate trismus; well-marked rigidity; mild to moderate but short spasms; moderate respiratory embarrassment with an increased respiratory rate greater than 30 [breaths/min]; mild dysphagia
III	Severe: severe trismus; generalized spasticity; reflex prolonged spasms; increased respiratory rate greater than 40 [breaths/min]; apneic spells; severe dysphagia; tachycardia greater than 120 [beats/min]
IV	Very severe: grade III and violent autonomic disturbances involving the cardiovascular system; severe hypertension and tachycardia alternating with relative hypotension and bradycardia, either of which may be persistent

Prognostic scoring systems in tetanus Dakar score
Prognostic Factors	Score 1	Score 0
Incubation period	< 7 days	≥ 7 days
Period of onset	< 48 h	≥ 48 h
Portal of entry	Umbilicus, Burns, Uterine, Open fracture, Surgical wound, Intramuscular injection	All others
Spasms	Present	Absent
Fever	> 38,4°C (101.12 °F)	≤ 38,4°C (101.12 °F)
Tachycardia	Adult >120 beats/min	Adult < 120 beats/min
	Neonate > 150 beats/min	Neonate < 150 beats/min

• Diagnosis: The diagnosis of tetanus is often clinical, by recognition of a triad of trismus, ridus sardonicus, and opisthotonus.
• Principles of Management: Provide supportive care, particularly respiratory support until the Tetanospasmin that is fixed in tissue has been metabolized.
1. Neutralize circulating toxin: ATS (Antitoxin Serum)
2. Remove the source of toxin: antibiotics
3. Muscle relaxant: diazepam
4. Fluids and calories
5. Nursing care
6. Active immunization (stat, first month, 6th month)

Treatment of Tetanus

• Treatment of tetanus requires maintaining adequate ventilation.
• Early and adequate use of human tetanus immune globulin (TIG) to neutralize nonfixed toxin.
• Prevention of further toxin production.
• Sedation.
• Control of muscle spasm and hypertonicity.
• Management of fluid balance and intercurrent infection.
• Continuous nursing care.
• IV immune globulin (IVIG), which contains tetanus antitoxin, may be used if TIG is not available.

Antitoxin and Toxoid

• The benefit of human-derived antitoxin depends on how much tetanospasmin is already bound to the synaptic membranes—only free toxin is neutralized.
• For adults, TIG 500 units IM once appears as effective as higher doses ranging from 3000 to 7000 units and causes less discomfort.
• Some medical experts recommend infiltration of part of the dose locally around the wound, but its efficacy has not been proved.
• Antitoxin of animal origin, e.g. equine, is far less preferable because it does not maintain the patient’s serum antitoxin level well and risk of serum sickness is considerable.
• If horse serum must be used, the usual dose is 10,000 units IM or IV.

Intrathecal or Intramuscular?

• RCT-120 Patients: Intrathecal shows better clinical progression than Intramuscular.

Wound Care

• Because dirt and dead tissue promote C. tetani growth, prompt, thorough debridement, especially of deep puncture wounds, is essential.
• Antibiotics are not substitutes for adequate debridement and immunization but typically are given.

Control of Muscle Spasm

1. Diazepam
   • Benzodiazepines block reuptake of an endogenous inhibiting neurotransmitter, gamma-aminobutyric acid (GABA), at the GABAA receptor.
   • Diazepam can help control seizures, counter muscle rigidity, and induce sedation.
   • Dosage varies and requires meticulous titration and close observation.
2. Baclofen - IM, IV, intrathecal - efficacious*
3. Propofol
4. Dantrolene
5. Magnesium sulphate
   • Sri Lanka – 8 patients - clearly demonstrated efficacy
   • No diazepam, muscle relaxant, or ventilatory support
   • Therapeutic range - 2-4 mmol
   • 4 mmol- areflexia
   • 6 mmol- paralysis
6. Chlorpromazine

You must check deep tendon reflexes - depressed = toxicity

Respiratory Care

• Intubation/Tracheostomy +/- Mechanical Ventilation

Autonomic Dysfunction

• Labetalol, esmolol- Beta-blockade is used to control episodes of hypertension and tachycardia.
• Magnesium sulphate, clonidine, lorazepam, morphine
• Magnesium sulfate has a stabilizing effect, eliminating catecholamine stimulation. Patellar tendon reflex is used to assess overdosage
• Hypotension - volume expanders, vasoconstrictors
• Bradycardia - pacemaker

Antibiotics

• Penicillin, Metronidazole, Erythromycin, Tetracycline, Vancomycin
• Metronidazole vs Penicillin Johnson and Walker - convulsion
• Structure of Penicillin Ahmadsya & Salim - reduction in Mortality in Metronidazole group (7% vs 24%)
• Yen et al - 1000 patients - No significant difference
• *Metronidazole group requires less sedative & muscle relaxant

Additional Measures

• IV fluid
• Nutrition
• Physiotherapy
• Anticoagulation, etc.

• 10-60% Outcome is poor in: elderly, neonate, short incubation period & period of onset.
• Prognostic scoring system in tetanus:
  1. Dakar score
  2. Philip score
  3. Bademosi

• Fracture
• Respiratory failure
• Myoglobinuria
• Renal failure
• Intercurrent infections
• DVT/PTE (Deep Vein Thrombosis/Pulmonary Thromboembolism)
• Contractures

• Strychnine poisoning
• Alveolar abscess
• Dystonic drug reaction
• Tetany
• Rabies
• Meningitis
• Stiff-person syndrome