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 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, only 37 cases were reported in 2001. 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).
Manifestations of tetanus are caused by an exotoxin (tetanospasmin). 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.
Symptoms and Signs
The incubation period ranges from 2 to 50 days (average, 5 to 10 days). Symptoms include
Later, patients have difficulty opening their jaw (trismus).
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—even opisthotonos—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.
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.
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 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.
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.
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.
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.
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 (see see Anaerobic Bacteria: Antibiotics); neutralize 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.
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.
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 (Caution: See Drug Hypersensitivity on see Allergic, Autoimmune, and Other Hypersensitivity Disorders: Drug Hypersensitivity). 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 GABAA 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:
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 GABAA agonist) is effective but has no clear advantage over benzodiazepines. It is given by continuous infusion; effective doses range between 20 and 2000 μg/day. A test dose of 50 μg is given first; if response is inadequate, 75 μg may be given 24 h later, and 100 μg 24 h after that. Patients who do not respond to 100 μg 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.
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.
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.
A series of 4 primary immunizations against tetanus, followed by boosters every 10 yr, with the adsorbed (for primary immunization) or fluid (for boosters) toxoid is superior to giving antitoxin at the time of injury. Tetanus toxoid comes by itself, combined with diphtheria in both adult (Td) and child strengths (DT), and combined with diphtheria and pertussis (DTP). For routine diphtheria, tetanus, and pertussis immunization and booster recommendations, see discussed in Immunization. Adults need to maintain immunity with regular boosters q 10 yr. Immunization in an unimmunized or inadequately immunized pregnant woman produces both active and passive immunity in the fetus and should be given at a gestational age of 5 to 6 mo with a booster at 8 mo. Passive immunity develops when maternal toxoid is given before a gestational age of 6 mo.
After injury, tetanus vaccination is given depending on wound type and vaccination history; tetanus immune globulin may also be indicated (see Table 2: Anaerobic Bacteria: 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.
Last full review/revision August 2009 by Joseph R. Lentino, MD, PhD