Chapter 156: Tetanus

Tetanus is uncommon in the United States but continues to have a substantial health impact in developing countries. The worldwide incidence of tetanus is approximately 1 million cases per year, with a mortality rate of 20% to 30%.¹

The Centers for Disease Control and Prevention defines tetanus as a syndrome of acute onset of hypertonia and/or painful muscular contractions (usually of the muscles of the jaw and neck) and generalized muscle spasms without other apparent medical cause as reported by a health professional.² In the United States, tetanus is a reportable disease, aggregated through the National Notifiable Diseases Surveillance System.

Improved childbirth practices, widespread immunization programs for children, decennial tetanus boosters for adults, mechanization of agriculture, and use of chemical fertilizers rather than animal manure have resulted in a >95% decline in the annual incidence of tetanus in the United States since 1947.² From 2001 to 2008, 233 tetanus cases were reported in the United States from 45 states, with the majority of cases reported from five states: California (n = 60), Florida (n = 25), Texas (n = 12), New York (n = 12), and Pennsylvania (n = 11).² Most patients who develop tetanus have inadequate immunity to the disease. Due to waning immunity and failure to receive routine boosters, only 31% of Americans >70 years old have adequate tetanus immunity.³ As a result, the average annual incidence of tetanus among those ≥65 years of age is higher (0.23 cases per 1 million population) than among those age 5 to 64 years (0.08 cases per 1 million population). Tetanus among children and neonatal tetanus are uncommon in the United States as well as in other developed countries. The case fatality rate is approximately 13%, with the elderly accounting for the majority of deaths.²

Most cases of tetanus in the United States are associated with an acute wound. Puncture, contaminated, infected, or devitalized wounds account for approximately 70% of tetanus cases. Although less common, chronic wounds, ulcers and other wounds in diabetics, and dental abscesses are also associated with the disease. Diabetics and injection drug users have an increased risk of contracting tetanus.^2,4

Most patients who develop tetanus do not seek medical care for their initial wound. In those who do seek initial treatment and later develop tetanus, up to 95% do not receive appropriate therapy.²

Clostridium tetani is a motile, nonencapsulated, anaerobic gram-positive rod, and its toxins cause tetanus. C. tetani exists in either a vegetative or a spore-forming state. The spores are ubiquitous in soil and in animal feces and are resistant to destruction, surviving on environmental surfaces for years. In agricultural areas, adults may harbor the organism, and spores have been found on skin or in contaminated heroin.^4,5 C. tetani is usually introduced into a wound in the spore-forming, noninvasive state but can germinate into a toxin-producing, vegetative form if tissue oxygen tension is reduced. Crushed or devitalized tissue, a foreign body, or the development of infection favors the growth of the toxin-producing form of C. tetani.^5,6

C. tetani produces two exotoxins: tetanolysin, which appears to favor the expansion of the bacterial population, and tetanospasmin, a powerful neurotoxin responsible for all of the clinical manifestations of tetanus. Tetanospasmin reaches the nervous system by hematogenous spread of the exotoxin to peripheral nerves and by retrograde intraneuronal transport. Tetanospasmin does not cross the blood–brain barrier, but retrograde intraneuronal transport of the exotoxin enables tetanospasmin to gain access to the CNS.⁶

Tetanospasmin prevents the release of the inhibitory neurotransmitters glycine and γ-aminobutyric acid from presynaptic nerve terminals, releasing the nervous system from its normal inhibitory control. Loss of inhibition may also affect the preganglionic sympathetic neurons, resulting in sympathetic overactivity and high circulating catecholamine levels.^5,6,7,8

Tetanus results in generalized muscular rigidity, violent muscular contractions, and autonomic nervous system instability.⁶ Wounds that become contaminated with toxin-producing C. tetani are often puncture wounds, but contaminated wounds range from deep lacerations to minor abrasions.² No wound is identified in up to 10% of patients with tetanus. Tetanus can also develop after surgical procedures, otitis media, or abortion and can develop in injection drug users from contaminated heroin and in neonates through infection of the umbilical stump.^4,9

The incubation period for tetanus ranges from <24 hours to >1 month. Short incubation periods are associated with severe disease and a poor prognosis for recovery. Clinical tetanus can be categorized into three forms: generalized, cephalic, and local. Generalized tetanus accounts for about 80% of cases. The most frequent presenting complaints of patients with generalized tetanus are pain and stiffness in the masseter muscles (lockjaw). Nerves with short axons are affected initially, so symptoms appear first in the facial muscles, with descending progression to the muscles of the neck, trunk, and extremities. The transition from muscle stiffness to rigidity leads to the development of trismus and the characteristic facial expression: risus sardonicus (sardonic smile). Reflex convulsive spasms and tonic muscle contractions are responsible for the development of dysphagia, opisthotonos flexing of the arms, clenching of the fists, and extension of the lower extremities. Spasms can last for 3 to 4 weeks, and recovery depends on regrowth of axonal nerve terminals and may take months.⁶ Complications of tetanus include rhabdomyolysis and long-bone fractures secondary to violent muscle contractions. The mental status is normal, an important consideration in differentiating tetanus from other disorders (Table 156–1). Patients remain conscious and alert unless laryngospasm or contraction of respiratory muscles results in respiratory compromise. Other complications of prolonged hospitalization include pulmonary embolus, pneumonia, and sepsis. Aspiration pneumonia is present in 50% to 70% of autopsied cases.^5,6

Autonomic changes are generally a hypersympathetic state, occurring during the second week of clinical tetanus and including tachycardia, labile hypertension, profuse sweating, hyperpyrexia, and increased urinary excretion of catecholamines.^6,7,8 Neonatal tetanus, a form of generalized tetanus, develops in infants born to inadequately immunized mothers, frequently after unsterile treatment of the umbilical cord stump.⁹ Infants with neonatal tetanus are weak, irritable, and have an inability to suck. Symptoms are evident by the second week of life.⁹

Cephalic tetanus follows injuries to the head or occasionally otitis media and results in dysfunction of the cranial nerves, most commonly the seventh. It has a poor prognosis.

Local tetanus is manifested by rigidity of muscles in proximity to the site of injury and usually resolves completely after weeks to months. Local tetanus may progress to the generalized form of the disease. Approximately 1% of the cases are fatal.^5,6

Tetanus is diagnosed clinically. In the United States, 96% of tetanus cases occur in those with unknown or inadequate immunization history.² Certain populations, especially the elderly, those requiring hemodialysis, and the immunocompromised, are more likely to have inadequate immunity.^10,11 There are no laboratory tests to diagnose tetanus, although serum antitoxin titers of >0.01 IU/mL (by mouse neutralization assay) are usually protective. An immunochromatographic dipstick test offers the advantage of rapid assessment of immunity, with an 88% sensitivity and 98% specificity, and may be useful in regions with high disease incidence.¹² However, tetanus has developed in patients with protective levels of antitetanus antibodies.¹³ Wound culture is of limited value, because C. tetani may be cultured from wounds in the absence of clinical disease and may not be recovered in patients with documented tetanus.

Table 156–1 provides the differential diagnosis of tetanus. Strychnine poisoning most closely mimics the clinical picture of generalized tetanus.

Treatment is summarized in Table 156–2. Admit patients with tetanus to the intensive care unit. Respiratory compromise requires immediate neuromuscular blockade and intubation. Minimize environmental stimuli to prevent the precipitation of reflex convulsive spasms.

TETANUS IMMUNOGLOBULIN

Human tetanus immunoglobulin neutralizes circulating tetanospasmin and toxin in the wound but not toxin that is already fixed in the nervous system. Even though tetanus immunoglobulin does not ameliorate the clinical symptoms of tetanus, early reports suggest it reduces mortality.¹⁴ The dose varies depending on the purpose. For postexposure prophylaxis, a single dose of 250 units (4 units/kg in children) IM given in the anterolateral thigh or deltoid is recommended. For the treatment of actual tetanus, the optimal dose of tetanus immunoglobulin is unknown, but 3000 to 6000 units IM is the usual recommended dose, administered in a separate syringe and opposite the site of tetanus toxoid administration. At least a portion of the dose should be administered around the wound itself.⁵ Tetanus immunoglobulin should be given before wound debridement, because exotoxin may be released during wound manipulation. Repeated doses of tetanus immunoglobulin are unnecessary because of its long half-life of 28 days.

WOUND MANAGEMENT

Identify and debride the wound to improve the oxidation-reduction potential of infected tissue and to prevent further toxin production.

ANTIBIOTICS

Antibiotics are of limited value but are traditionally administered, and parenteral metronidazole is the antibiotic of choice.^15,16 Do not give penicillin because it may potentiate the effects of tetanospasmin.⁶

MUSCLE RELAXANTS

Tetanospasmin prevents neurotransmitter release at inhibitory interneurons, and therapy of tetanus is aimed at restoring normal inhibition. The benzodiazepines are centrally acting inhibitory agents that have been used extensively for this purpose. However, the large IV doses of benzodiazepines required in tetanus may result in metabolic acidosis secondary to the propylene glycol vehicle in IV lorazepam or diazepam. Thus, many prefer midazolam, a water-soluble agent, for muscle relaxation.⁶ The effects of baclofen, a specific γ-aminobutyric acid agonist, vary.⁶

NEUROMUSCULAR BLOCKADE

Prolonged neuromuscular blockade aids in control of ventilation, muscular spasms, secondary fractures, and rhabdomyolysis. Succinylcholine can be given early for emergency airway control, whereas vecuronium is a good option for prolonged blockade because of minimal cardiovascular side effects.¹⁵

TREATMENT OF AUTONOMIC DYSFUNCTION

One randomized controlled trial in 256 patients with severe tetanus demonstrated that magnesium sulfate reduced autonomic instability and muscle spasm in the disease.⁷ Furthermore, magnesium sulfate has been shown to reduce urinary catecholamine excretion in patients with severe tetanus.⁸ However, a meta-analysis failed to show a benefit of magnesium sulfate on tetanus mortality, and the effect of the drug on duration of intensive care unit and hospital stay and need for ventilatory support was unclear.¹⁷

Adrenergic blocking agents may treat the autonomic dysfunction of severe tetanus. Choose either a short-acting β-blocker, such as esmolol, or labetalol, a combined α- and β-adrenergic blocking agent, if treating this manifestation of tetanus.

Morphine sulfate reduces sympathetic α-adrenergic tone and central sympathetic efferent discharge and produces peripheral arteriolar and venous dilatation.⁶ Clonidine, a central α₂-receptor agonist, may act to reduce the sympathetic hyperactivity that causes autonomic dysfunction and thereby provide better control of crises.¹⁸

Patients who recover from tetanus must receive active immunization, because infection does not confer immunity and vaccination is the only means of disease prevention. Give adsorbed tetanus toxoid (0.5 mL) IM at the time of presentation and at 6 weeks and 6 months after injury.

In patients with tetanus-prone wounds or those with incomplete vaccinations or greater than 10 years from previous vaccination, use tetanus-diphtheria (Td) if ≥7 years old, and use diphtheria and tetanus toxoids and acellular pertussis vaccine (DTaP) for those under 7 years old.¹⁹ DTaP contains over three times the amount of diphtheria component as Tdap and must be used for primary vaccination series in children. Because of the recent increase in the incidence of pertussis, adolescents and adults should receive a single lifetime dose of Tdap to replace one Td booster.¹⁹ An inadvertent dose of DTaP in an adult would count as the single lifetime dose of Tdap.

The revised Advisory Committee on Immunization Practices guidelines recommend administering a dose of Tdap during each pregnancy, irrespective of the patient's prior history of receiving Tdap or interval since last injection, to maximize the maternal antibody response and passive antibody levels in the newborn.²⁰ Tdap may be given at any point during pregnancy, with optimal timing between 27 and 36 weeks of gestation unless treating a specific wound. For women who have never received Tdap, it should be given to the mother immediately postpartum and to any direct caregivers to reduce the risk of pertussis to the newborn.

Table 156–3 summarizes the guidelines for tetanus immunization and tetanus prophylaxis in wound management.¹⁹ Only about 60% of patients with an acute injury who seek medical care receive appropriate tetanus wound prophylaxis.² Table 156–2 summarizes the management of tetanus.

Adverse reactions following tetanus immunization include erythema, induration, and pain at the injection site. Local reactions are common and usually self-limited. Exaggerated local reactions (Arthus reactions) occur occasionally after tetanus toxoid and involve extensive pain and swelling of the entire extremity. Arthus reactions occur most often in adults with high serum tetanus antitoxin levels who have received frequent doses of tetanus toxoid, the reason this therapy is limited to 10-year intervals.

Contraindications to Td or Tdap include a history of serious allergic reaction (respiratory compromise or cardiovascular collapse) to vaccine components. History of encephalopathy (e.g., coma or prolonged seizures) not attributable to an identifiable cause within 7 days of administration of a pertussis vaccine is a contraindication to Tdap. Reasons to defer Td or Tdap include Guillain-Barré syndrome ≤6 weeks after a previous dose of tetanus toxoid-containing vaccine, moderate to severe acute illness, unstable neurologic condition, or history of an Arthus hypersensitivity reaction to a tetanus toxoid–containing vaccine administered <10 years previously.¹⁹ If tetanus toxoid is contraindicated, consider passive immunization with tetanus immunoglobulin.