Merck Manual

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Larry M. Bush

, MD, FACP, Charles E. Schmidt College of Medicine, Florida Atlantic University;

Maria T. Vazquez-Pertejo

, MD, FACP, Wellington Regional Medical Center

Reviewed/Revised Jun 2023
Topic Resources

Tetanus is acute poisoning resulting 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 in 2019, tetanus was estimated to have caused 34,700 deaths, mostly in South Asia and Sub-Saharan Africa (1 General references Tetanus is acute poisoning resulting from a neurotoxin produced by Clostridium tetani. Symptoms are intermittent tonic spasms of voluntary muscles. Spasm of the masseters accounts for... read more General references ), but the disease is so rarely reported that this figure is only a rough estimate. According to the World Health Organization, in 2015 about 34,000 newborns died of neonatal tetanus, which was a 96% reduction since 1988 (2 General references Tetanus is acute poisoning resulting from a neurotoxin produced by Clostridium tetani. Symptoms are intermittent tonic spasms of voluntary muscles. Spasm of the masseters accounts for... read more General references ). This reduction was attributed to increased immunization.

In the United States since 1947, reported tetanus cases have declined more than 95%, and deaths resulting from tetanus have declined more than 99% (3 General references Tetanus is acute poisoning resulting from a neurotoxin produced by Clostridium tetani. Symptoms are intermittent tonic spasms of voluntary muscles. Spasm of the masseters accounts for... read more General references ). From 2009 to 2017, 264 cases of tetanus and 19 deaths resulting from tetanus were reported. Age distribution for cases was 23% in people ≥ 65 years, 64% in people aged 20 to 64 years, and 13% in people < 20 years, including 3 cases of tetanus neonatorum; all tetanus-related deaths occurred in people > 55 years (4 General references Tetanus is acute poisoning resulting from a neurotoxin produced by Clostridium tetani. Symptoms are intermittent tonic spasms of voluntary muscles. Spasm of the masseters accounts for... read more General references ).

Disease incidence is directly related to the immunization level in a population, attesting to the effectiveness of preventive efforts. In the United States, immunity levels tend to be lower in older age groups.

Patients with burns, surgical wounds, or a history of injection drug use 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) as a result of unsanitary delivery and umbilical cord care practices. Diabetes and a history of immunosuppression may be risk factors for tetanus.

General references

Pathophysiology of Tetanus

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, thereby causing unopposed muscle stimulation by acetylcholine and 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 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).


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, and myocardial irritability.

Causes of death

Respiratory failure Overview of Respiratory Failure Acute respiratory failure is a life-threatening impairment of oxygenation, carbon dioxide elimination, or both. Respiratory failure may occur because of impaired gas exchange, decreased ventilation... read more 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, and poor feeding. Bilateral deafness may occur in surviving children.

Diagnosis of Tetanus

  • Clinical evaluation

Tetanus should be considered when patients have sudden, unexplained muscle stiffness or spasms, particularly if they have a history of a recent wound or risk factors for tetanus.

Tetanus can be confused with meningoencephalitis of bacterial or viral origin, but the following combination suggests tetanus:

  • An intact sensorium

  • Normal cerebrospinal fluid

  • Muscle spasms

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.

Treatment of Tetanus

  • Supportive care, particularly respiratory support

  • Wound debridement

  • Tetanus antitoxin

  • Benzodiazepines for muscle spasms

  • Antibiotics

  • Sometimes medications for autonomic dysfunction

Treatment of tetanus requires maintaining adequate ventilation.

Additional interventions include early and adequate use of human tetanus immune globulin (TIG) to neutralize nonfixed toxin; prevention of further toxin production; sedation; control of muscle spasm, hypertonicity, fluid balance, and intercurrent infection; and continuous nursing care. IV immune globulin (IVIG), which contains tetanus antitoxin, may be used if TIG is not available.

General principles

The patient should be kept in a quiet room. Several principles should guide all therapeutic interventions:

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.

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 6000 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 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 Skin testing Skin testing .)

If necessary, IVIG or antitoxin can be injected directly into the wound, but this injection is not as important as good wound care.

Tetanus infection does not confer immunity, so unless their vaccination history indicates completion of a full primary series, patients should receive a full primary tetanus vaccination series using an age-appropriate preparation (see Prevention Prevention Tetanus is acute poisoning resulting from a neurotoxin produced by Clostridium tetani. Symptoms are intermittent tonic spasms of voluntary muscles. Spasm of the masseters accounts for... read more Prevention below). Antitoxin and vaccine should be injected into different body sites to avoid neutralizing the vaccine.

Management of muscle spasms

Medications are used to manage spasms.

Benzodiazepines are the standard of care to control rigidity and spasms. They 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.

Diazepam has been used most extensively, but midazolam 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 or other paralytic medications 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 medications (eg, pipecuronium, rocuronium) also work, but no randomized clinical comparative trials have been done.

Intrathecal baclofen (a GABAA agonist) is effective in treating reflex spasms but has no clear advantage over benzodiazepines. Coma and respiratory depression requiring ventilatory support are potential adverse effects.

Dantrolene can be given initially by infusion and thereafter for up to 60 days. Hepatotoxicity and expense limit its use.

Management of autonomic dysfunction

Morphine may be given every 4 to 6 hours to control autonomic dysfunction, especially cardiovascular; total daily dose is 20 to 180 mg.

Beta-blockade is used to control episodes of hypertension and tachycardia, but use of long-acting medications such as propranolol is not recommended. Sudden cardiac death is a feature of tetanus, and beta-blockade can increase risk; however, esmolol, a short-acting beta-blocker, has been used successfully. IV atropine has been used at high doses; 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.

Magnesium sulfate given by IV continuous infusion at doses that maintain serum levels between 4 to 8 mEq/L has a stabilizing effect, eliminating catecholamine stimulation (1 Treatment references Toxins produced by Clostridioides difficile strains in the gastrointestinal tract cause pseudomembranous colitis, typically after antibiotic use. Symptoms are diarrhea, sometimes bloody... read more ). Patellar tendon reflex is used to assess overdosage. Tidal volume may be impaired, so ventilatory support must be available. Serum magnesium levels and electrical cardiac activity need to be closely monitored throughout the infusion period.

Other medications that may prove useful include

  • Pyridoxine, which lowers mortality in neonates

  • Valproic acid, which blocks GABA-aminotransferase, inhibiting GABA catabolism

  • Angiotensin-converting enzyme inhibitors, which inhibit angiotensin II and reduce norepinephrine release from nerve endings

  • Dexmedetomidine (a potent alpha-2 adrenergic agonist)

  • 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.

Metronidazole is the recommended antibiotic.

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.

Treatment reference

  • 1. Thwaites CL, Yen LM, Cordon SM, et al: Effect of magnesium sulphate on urinary catecholamine excretion in severe tetanus. Anaesthesia 63(7):719–725, 2008. doi: 10.1111/j.1365-2044.2008.05476.x

Prognosis for Tetanus

The case fatality rate of patients with tetanus varies widely between resource-rich and resource-poor nations. With use of modern supportive care, including mechanical ventilation, most patients recover.

Mortality is highest at the extremes of age and in injection drug users.

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.

Prognosis reference

Prevention of Tetanus

Tetanus vaccination is required for all infants, children, adolescents, and adults.

Children are given diphtheria/tetanus toxoids/pertussis vaccine (DTaP Diphtheria-Tetanus-Pertussis Vaccine Vaccines that contain diphtheria toxoid, tetanus toxoid, and acellular pertussis help protect against diphtheria, tetanus, and pertussis, but they do not prevent all cases. For more information... read more ) at ages 2 months, 4 months, 6 months, 15 to 18 months, and 4 to 6 years; they should get a tetanus-diphtheria-pertussis (Tdap Indications Vaccines that contain diphtheria toxoid, tetanus toxoid, and acellular pertussis help protect against diphtheria, tetanus, and pertussis, but they do not prevent all cases. For more information... read more ) booster at age 11 to 12 years, and tetanus toxoid with diphtheria toxoid (Td Tetanus-Diphtheria Vaccine A vaccine for tetanus alone is available, but the tetanus vaccine is typically combined with those for diphtheria and/or pertussis. The vaccine for diphtheria is available only in combination... read more ) every 10 years thereafter. Those 7 through 18 years who have not been fully vaccinated should receive one dose of Tdap with additional doses according to an individualized catch-up scheduled based on CDC recommendations.

Unimmunized adults > 19 years are given one dose of Tdap as soon as possible followed by Td or Tdap every 10 years.

Pregnant women should be given Tdap Indications Vaccines that contain diphtheria toxoid, tetanus toxoid, and acellular pertussis help protect against diphtheria, tetanus, and pertussis, but they do not prevent all cases. For more information... read more during each pregnancy, preferably at 27 to 36 weeks gestation, regardless of when they were last vaccinated; the fetus can develop passive immunity from vaccines given at this time.

Because tetanus infection does not confer immunity, patients who have recovered from clinical tetanus should be vaccinated unless they have completed a full primary series.

Patients who have a wound that poses an increased risk of tetanus should be given prophylaxis depending on wound type and vaccination history; tetanus immune globulin also may be indicated (see table ).


Tetanus Prophylaxis in Routine Wound Management

History of Adsorbed Tetanus Toxoid

Clean, Minor Wounds

All Other Wounds*

DTaP, Tdap, or Td†


DTaP, Tdap, or Td†


Unknown or < 3 doses





3 doses

Yes if > 10 years since last dose


Yes if 5 years since last dose


* 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.

† DTaP is recommended for children < 7 years of age. For patients ≥ 11 years of age who have not previously received a dose of Tdap, a single dose of Tdap should be given. Patients ≥ 7 years of age who are not fully immunized against pertussis, tetanus, or diphtheria should receive one dose of Tdap for wound management and as part of the catch-up series.

‡ For adults, TIG 500 units IM once. People with HIV infection or severe immunodeficiency who have contaminated wounds (including minor wounds) should also receive TIG, regardless of their tetanus immunization history.

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

Adapted from Centers for Disease Control and Prevention: Wound management for tetanus prevention. Accessed June 5, 2023.

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.

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

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

  • Mortality is high in untreated neonates and adults.

  • Prevent tetanus by following routine immunization recommendations.

Drugs Mentioned In This Article

Drug Name Select Trade
Diastat, Dizac, Valium, VALTOCO
Nayzilam, Versed, Versed Syrup
Ativan, Loreev XR
No brand name available
ED Baclofen, FLEQSUVY, Gablofen, Lioresal, Lioresal Intrathecal, LYVISPAH, OZOBAX, OZOBAX DS
Dantrium, Revonto , RYANODEX
ARYMO ER, Astramorph PF, Avinza, DepoDur, Duramorph PF, Infumorph, Kadian, MITIGO, MORPHABOND, MS Contin, MSIR, Opium Tincture, Oramorph SR, RMS, Roxanol, Roxanol-T
HEMANGEOL, Inderal, Inderal LA, Inderal XL, InnoPran XL
Atreza, Atropine Care , Atropisol , Isopto Atropine, Ocu-Tropine, Sal-Tropine
Catapres, Catapres-TTS, Duraclon, Kapvay, NEXICLON XR
B-Natal, Neuro-K-500
Depacon, Depakene, Depakote, Depakote ER, Stavzor
IGALMI, Precedex
Adenocard, Adenoscan
Flagyl, Flagyl ER, Flagyl RTU, LIKMEZ, MetroCream, MetroGel, MetroGel Vaginal, MetroLotion, Noritate, NUVESSA, Nydamax, Rosadan, Rozex, Vandazole, Vitazol
Adacel, Boostrix, Certiva, Daptacel, Infanrix, Tri-Immunol, Tripedia
NOTE: This is the Professional Version. CONSUMERS: View Consumer Version
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