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Tetanus

(Lockjaw)

by Joseph R. Lentino, MD, PhD

Tetanus is acute poisoning from a neurotoxin produced by Clostridium tetani. Symptoms are intermittent tonic spasms of voluntary muscles. Spasm of the masseters accounts for the name lockjaw. Diagnosis is clinical. Treatment is with human tetanus immune globulin and intensive support.

Tetanus bacilli form durable spores that occur in soil and animal feces and remain viable for years. Worldwide, tetanus is estimated to cause over half a million deaths annually, mostly in neonates and young children, but the disease is so rarely reported that all figures are only rough estimates. In the US, an average of 29 cases/yr were reported from 2001 through 2008. Disease incidence is directly related to the immunization level in a population, attesting to the effectiveness of preventive efforts. In the US, well over half of elderly patients have inadequate antibody levels and account for one third to one half of cases. Most of the rest occur in inadequately immunized patients aged 20 to 59. Patients < 20 account for < 10%. Patients with burns, surgical wounds, or a history of injection drug abuse are especially prone to developing tetanus. However, tetanus may follow trivial or even inapparent wounds. Infection may also develop postpartum in the uterus (maternal tetanus) and in a neonate's umbilicus (tetanus neonatorum).

Pathophysiology

C. tetani spores usually enter through contaminated wounds. Manifestations of tetanus are caused by an exotoxin (tetanospasmin) produced by the germinating spores. The toxin may enter the CNS along the peripheral motor nerves or may be bloodborne to nervous tissue. Tetanospasmin binds irreversibly to the ganglioside membranes of nerve synapses, blocking release of inhibitory transmitter from nerve terminals and thereby causing a generalized tonic spasticity, usually with 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.

Pearls & Pitfalls

  • Tetanus toxin binds irreversibly to nerve terminals, and once bound, it cannot be neutralized.

Symptoms and Signs

The incubation period ranges from 2 to 50 days (average, 5 to 10 days). Symptoms include

  • Jaw stiffness (most frequent)

  • Difficulty swallowing

  • Restlessness

  • Irritability

  • Stiff neck, arms, or legs

  • 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. Spasms also interfere with respiration, causing cyanosis or fatal asphyxia. The immediate cause of death may not be apparent.

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.


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, and myocardial irritability.


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

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 wk of life is characterized by rigidity, spasms, and poor feeding. Bilateral deafness may occur in surviving children.


Diagnosis

  • Clinical evaluation

A history of a recent wound in a patient with muscle stiffness or spasms is a clue. Tetanus can be confused with meningoencephalitis of bacterial or viral origin, but the combination of an intact sensorium, normal CSF, and muscle spasms suggests tetanus. Trismus must be distinguished from peritonsillar or retropharyngeal abscess or another local cause. Phenothiazines can induce tetanus-like rigidity (eg, dystonic reaction, neuroleptic malignant syndrome).

C. tetani can sometimes be cultured from the wound, but culture is not sensitive; only 30% of patients with tetanus have positive cultures. Also, false-positive cultures can occur in patients without tetanus.

Prognosis

Tetanus has a worldwide mortality rate of 50%, 15 to 60% in untreated adults, and 80 to 90% in neonates even if treated. Mortality is highest at the extremes of age and in drug abusers. The prognosis is poorer if the incubation period is short and symptoms progress rapidly or if treatment is delayed. The course tends to be milder when there is no demonstrable focus of infection.

Treatment

  • Supportive care, particularly respiratory support

  • Wound debridement

  • Tetanus antitoxin

  • Benzodiazepines for muscle spasms

  • Metronidazole or penicillin

  • Sometimes drugs for autonomic dysfunction

Therapy requires maintaining adequate ventilation. Additional interventions include early and adequate use of human immune globulin to neutralize nonfixed toxin; prevention of further toxin production; sedation; control of muscle spasm, hypertonicity, fluid balance, and intercurrent infection; and continuous nursing care.

General principles

The patient should be kept in a quiet room. Three principles should guide all therapeutic interventions: prevent further toxin release by debriding the wound and giving an antibiotic ( Antibiotics); neutralize unbound toxin outside the CNS with human tetanus immune globulin and tetanus toxoid, taking care to inject into different body sites and thus avoid neutralizing the antitoxin; and minimize the effect of toxin already in the CNS.


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.


Antitoxin

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, human tetanus immune globulin 3000 units IM is given once; this large volume may be split and given at separate sites. Dose can range from 1,500 to 10,000 units, depending on wound severity, although some authorities feel that 500 units are adequate. Antitoxin of animal origin 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 50,000 units IM or IV (C aution : See Allergic, Autoimmune, and Other Hypersensitivity Disorders:Skin testing). If necessary, immune globulin or antitoxin can be injected directly into the wound, but this injection is not as important as good wound care.


Management of muscle spasm

Drugs are used to manage spasms.

Benzodiazepines are the standard of care to control rigidity and spasms. They block reuptake of an endogenous inhibiting neurotransmitter, γ-aminobutyric acid (GABA), at the GABA A receptor.

Diazepam can help control seizures, counter muscle rigidity, and induce sedation. Dosage varies and requires meticulous titration and close observation. The most severe cases may require 10 to 20 mg IV q 3 h (not exceeding 5 mg/kg). Less severe cases can be controlled with 5 to 10 mg po q 2 to 4 h. Dosage varies by age:

  • Infants > 30 days: 1 to 2 mg IV given slowly, repeated q 3 to 4 h as necessary

  • Young children: 0.1 to 0.8 mg/kg/day up to 0.1 to 0.3 mg/kg IV q 4 to 8 h

  • Children > 5 yr: 5 to 10 mg IV q 3 to 4 h

  • Adults: 5 to 10 mg po q 4 to 6 h or up to 40 mg/h IV drip

Diazepam has been used most extensively, but midazolam (adults, 0.1 to 0.3 mg/kg/h IV infusion; children, 0.06 to 0.15 mg/kg/h IV infusion) is water soluble and preferred for prolonged therapy. Midazolam reduces risk of lactic acidosis due to propylene glycol solvent, which is required for diazepam and lorazepam, and reduces risk of long-acting metabolites accumulating and causing coma.

Benzodiazepines may not prevent reflex spasms, and effective respiration may require neuromuscular blockade with vecuronium 0.1 mg/kg IV or other paralytic drugs and mechanical ventilation. Pancuronium has been used but may worsen autonomic instability. Vecuronium is free of adverse cardiovascular effects but is short-acting. Longer-acting drugs (eg, pipecuronium, rocuronium) also work, but no randomized clinical comparative trials have been done.

Intrathecal baclofen (a GABA A agonist) is effective but has no clear advantage over benzodiazepines. It is given by continuous infusion; effective doses range between 20 and 2000 mcg/day. A test dose of 50 mcg is given first; if response is inadequate, 75 mcg may be given 24 h later, and 100 mcg 24 h after that. Patients who do not respond to 100 mcg are not candidates for chronic infusion. Coma and respiratory depression requiring ventilatory support are potential adverse effects.

Dantrolene (loading dose 1.0 to 1.5 mg/kg IV, followed by infusion of 0.5 to 1.0 mg/kg q 4 to 6 h for 25 days) relieves muscle spasticity. Dantrolene given orally can be used in place of infusion therapy for up to 60 days. Hepatotoxicity and expense limit its use.


Management of autonomic dysfunction

Morphine may be given q 4 to 6 h to control autonomic dysfunction, especially cardiovascular; total daily dose is 20 to 180 mg. β-Blockade with long-acting drugs such as propranolol is not recommended. Sudden cardiac death is a feature of tetanus, and β-blockade can increase risk; however, esmolol, a short-acting β-blocker, has been used successfully. Atropine at high doses has been used; blockade of the parasympathetic nervous system markedly reduces excessive sweating and secretions. Lower mortality has been reported in clonidine-treated patients than in those treated with conventional therapy.

Mg sulfate at doses that maintain serum levels between 4 to 8 mEq/L (eg, 4 g bolus followed by 2 to 3 g/h) has a stabilizing effect, eliminating catecholamine stimulation. Patellar tendon reflex is used to assess overdosage. Tidal volume may be impaired, so ventilatory support must be available.

Pyridoxine (100 mg once/day) lowers mortality in neonates. Other drugs that may prove useful include Na valproate (which blocks GABA-aminotransferase, inhibiting GABA catabolism), ACE inhibitors (which inhibit angiotensin II and reduce norepinephrine release from nerve endings), dexmedetomidine (a potent α-2 adrenergic agonist), and adenosine (which reduces presynaptic norepinephrine release and antagonizes the inotropic effect of catecholamines). Corticosteroids are of unproven benefit; their use is not recommended.


Antibiotics

The role of antibiotic therapy is minor compared with wound debridement and general support. Typical antibiotics include penicillin G 6 million units IV q 6 h, doxycycline 100 mg po bid, and metronidazole 500 mg po q 6 to 8 h.


Supportive care

In moderate or severe cases, patients should be intubated. Mechanical ventilation is essential when neuromuscular blockade is required to control muscle spasms that impair respirations.

IV hyperalimentation avoids the hazard of aspiration secondary to gastric tube feeding. Because constipation is usual, stools should be kept soft. A rectal tube may control distention. Bladder catheterization is required if urinary retention occurs.

Chest physiotherapy, frequent turning, and forced coughing are essential to prevent pneumonia. Analgesia with opioids is often needed.


Prevention

A primary series of vaccinations followed by regular boosters is required. Children < 7 yr require 5 primary vaccinations, and unimmunized patients > 7 yr require 3. The vaccine may be tetanus toxoid alone (TT), but toxoid is typically combined with diphtheria and/or pertussis. Children's vaccines have higher doses of the diphtheria and pertussis components (DTaP, DT) than adult's vaccines (Tdap, Td).

Children are given DTaP at ages 2 mo, 4 mo, 6 mo, 15 to 18 mo, and 4 to 6 yr; they should get a Tdap booster at age 11 to 12 yr, and Td every 10 yr thereafter.

Unimmunized adults are given Tdap initially, then Td 4 wk and 6 to 12 mo later, and Td every 10 yr thereafter. Adults who have not had a vaccine that contains pertussis should be given a single dose of Tdap instead of one of the Td boosters. Adults ≥ 65 who anticipate close contact with an infant < 12 mo and who have not previously received Tdap should be given a single dose of Tdap. Pregnant women should be given Tdap at 27 to 36 wk gestation regardless of when they were last vaccinated; the fetus can develop passive immunity from vaccines given at this time. For routine diphtheria, tetanus, and pertussis immunization and booster recommendations, see Immunization.

After injury, tetanus vaccination is given depending on wound type and vaccination history; tetanus immune globulin may also be indicated (see Tetanus Prophylaxis in Routine Wound Management). Patients not previously vaccinated are given a 2nd and 3rd dose of toxoid at monthly intervals.

Because tetanus infection does not confer immunity, patients who have recovered from clinical tetanus should be vaccinated.

Tetanus Prophylaxis in Routine Wound Management

History of Adsorbed Tetanus Toxoid

Clean, Minor Wounds

All Other Wounds*

Td

TIG

Td

TIG

Unknown or< 3 doses

Yes

No

Yes

Yes

3 doses

Yes if > 10 yr since last dose

No

Yes if > 5 yr since last dose

No

*Such as (but not limited to) wounds contaminated with dirt, feces, soil, or saliva; puncture wounds; crush injuries; avulsions; and wounds resulting from missiles, burns, or frostbite.

For patients ≥ 10 yr, a single dose of Tdap should be given instead of one Td booster.

TIG 250–500 units IM.

Td = tetanus and diphtheria toxoids adsorbed (for adults); Tdap = tetanus and diphtheria toxoids, acellular pertussis (for adults); TIG = tetanus immune globulin (human).

Key Points

  • Tetanus is caused by a toxin produced by Clostridium tetani in contaminated wounds.

  • Tetanus toxin blocks release of inhibitory neurotransmitters, causing generalized muscle stiffness with intermittent spasms; seizures and autonomic instability may occur.

  • Mortality is 15 to 60% in untreated adults and 80 to 90% in neonates even if treated.

  • Prevent further toxin release by debriding the wound and giving an antibiotic (eg, penicillin, doxycycline), and neutralize unbound toxin with human tetanus immune globulin.

  • Give IV benzodiazepines for muscle spasm, and neuromuscular blockade and mechanical ventilation as needed for respiratory insufficiency due to muscle spasm.

  • Prevent tetanus by following routine immunization recommendations.

Resources In This Article

Drugs Mentioned In This Article

  • Drug Name
    Select Trade
  • FLAGYL
  • LIORESAL
  • No US brand name
  • ZEMURON
  • VALIUM
  • ATIVAN
  • DANTRIUM
  • LEVOPHED
  • ATROPEN
  • ADENOCARD
  • INDERAL
  • CATAPRES
  • DURAMORPH PF, MS CONTIN
  • BREVIBLOC
  • PRECEDEX
  • PERIOSTAT, VIBRAMYCIN

* This is a professional Version *