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Literature review current through: Dec 2017. | This topic last updated: Nov 07, 2017.

INTRODUCTION — Tetanus is a nervous system disorder characterized by muscle spasms that is caused by the toxin-producing anaerobe Clostridium tetani, which is found in the soil. The clinical features of tetanus and its relationship to traumatic injuries were well known among the ancient Greeks and Egyptians and to many clinicians before the introduction of vaccination with tetanus toxoid in the 1940s. The term "lockjaw" (now called trismus) lives in modern parlance as a reminder of one of the cardinal features of tetanus: intense, painful spasms of the masseter muscles.

Tetanus can present in one of four clinical patterns:





Although tetanus is now rare in the developed world, the disease remains a threat to all unvaccinated people, particularly in developing countries. Since C. tetani spores cannot be eliminated from the environment, immunization and proper treatment of wounds and traumatic injuries are crucial for tetanus prevention. The epidemiology, pathogenesis, clinical features, diagnosis, and management of tetanus will be reviewed here. The principles of prevention of tetanus and management of tetanus-prone wounds are discussed separately. (See "Tetanus-diphtheria toxoid vaccination in adults" and "Diphtheria, tetanus, and pertussis immunization in infants and children 0 through 6 years of age" and "Diphtheria, tetanus, and pertussis immunization in children 7 through 18 years of age" and "Infectious complications of puncture wounds" and "Soft tissue infections due to dog and cat bites".)


Developed countries — Because of almost universal vaccination of children with tetanus toxoid in developed countries, the incidence of tetanus in these regions has dropped dramatically and steadily since 1940. During the period between 2001 and 2008, the United States Centers for Disease Control and Prevention (CDC) reported that there were 233 cases of tetanus in the United States, with an annual incidence of 0.10 cases/million population overall and 0.23 cases/million among individuals ≥65 years of age [1]. The case-fatality rate was 13.2 percent overall but was 31.3 percent among individuals ≥65 years of age. In 2009, 19 cases of tetanus and 2 deaths were reported in the United States through the national tetanus surveillance system [2].

Most patients with tetanus lack a history of receipt of a full series of tetanus toxoid immunization and receive inadequate prophylaxis following a wound [1,3,4]. Approximately three-fourths of patients who acquired tetanus in the United States between 2001 and 2008 recalled an acute injury prior to the onset of their symptoms, but approximately two-thirds of these individuals did not seek medical care [1]. Among 51 patients who sought care for an acute wound and had a sufficiently thorough surveillance report to allow evaluation, 49 (96 percent) did not receive adequate tetanus toxoid prophylaxis or tetanus toxoid prophylaxis plus tetanus immune globulin [1]. However, occasional patients with preexisting antitetanus antibodies (as measured by guinea pig or mouse protection assays) have developed tetanus [5]. (See "Tetanus-diphtheria toxoid vaccination in adults" and "Diphtheria, tetanus, and pertussis immunization in infants and children 0 through 6 years of age", section on 'Indications' and "Diphtheria, tetanus, and pertussis immunization in children 7 through 18 years of age", section on 'Indications'.)

Unlike in developing nations, neonatal tetanus is extremely rare in the United States. Only one case of neonatal tetanus was reported between 2001 and 2008; this case occurred in an infant whose mother had not been vaccinated [6]. Fifteen percent of patients with tetanus had diabetes mellitus, which is three times the estimated prevalence of diabetes in the United States. Another 15 percent of patients were injection drug users.

The annual incidence of tetanus in other developed countries is also low and declining due to vaccination programs. In England and Wales, for example, the annual incidence was 0.2 cases/million population, with the highest incidence in patients above the age of 64 years [7]. Italy reported the highest number of cases among the countries of Europe, but the annual incidence decreased from 0.5 to 0.2 per 100,000 from the 1970s to the 1990s [8]. The case-fatality ratio decreased from 68 to 39 percent over that same period; women >64 years of age were disproportionately affected.

Despite the low rate of clinical disease in developed countries, many adults are inadequately vaccinated against tetanus. In the serologic survey cited above in the United States between 1988 and 1994, protective levels of antitetanus antibody (>0.15 international units/mL) were present in 72 percent of individuals ≥6 years of age but only 31 percent of adults over the age of 70 [9]. Not surprisingly, protective antibody levels are more likely in adults with a history of military service, higher levels of education, and higher incomes [10].

Developing countries — In contrast with developed nations where tetanus is rare, tetanus remains endemic in the developing world, and the incidence often increases following natural disasters such as earthquakes and tsunamis [11]. Approximately one million cases of tetanus are estimated to occur worldwide each year, with 300,000 to 500,000 deaths [11]. In 2002, tetanus caused an estimated 180,000 deaths worldwide [12]. Among patients admitted for neurologic conditions to one hospital in Nigeria, tetanus was the second most common cause (14 percent) after stroke [13].

Case-fatality rates in developing countries remain high and have not changed significantly in the past several decades. The pooled fatality rate of 3043 adult African patients reported in 27 studies was 43 percent (95% CI 37 to 50 percent) [14]. The high fatality rate likely reflects the fact that mechanical ventilation is often not available in African medical facilities. Longer incubation periods were associated with lower fatality rates.

Neonatal tetanus, which the World Health Organization targeted for elimination by 1995, accounted for approximately 59,000 deaths in 2008 [15]. While this represents a decrease in mortality of 92 percent compared with 1988 [15], as of 2014, 24 countries had still not eliminated maternal and neonatal tetanus [16]. (See 'Neonatal tetanus' below.)

PATHOGENESIS — Tetanus occurs when spores of Clostridium tetani, an obligate anaerobe normally present in the gut of mammals and widely found in soil, gains access to damaged human tissue. After inoculation, C. tetani transforms into a vegetative rod-shaped bacterium and produces the metalloprotease tetanospasmin (also known as tetanus toxin).

After reaching the spinal cord and brainstem via retrograde axonal transport within the motor neuron, tetanus toxin is secreted and enters adjacent inhibitory interneurons, where it blocks neurotransmission by its cleaving action on the membrane proteins involved in neuroexocytosis [17-20]. The net effect is inactivation of inhibitory neurotransmission that normally modulates anterior horn cells and muscle contraction. This loss of inhibition (ie, disinhibition) of anterior horn cells and autonomic neurons results in increased muscle tone, painful spasms, and widespread autonomic instability.

Muscular rigidity in tetanus occurs though a complex mechanism that involves an increase in the resting firing rate of disinhibited motor neurons and lack of inhibition of reflex motor responses to afferent sensory stimuli [21]. Lack of neural control of adrenal release of catecholamines induced by tetanus toxin produces a hypersympathetic state that manifests as sweating, tachycardia, and hypertension. (See 'Generalized tetanus' below.)

Tetanus toxin-induced effects on anterior horns cells, the brainstem, and autonomic neurons are long lasting because recovery requires the growth of new axonal nerve terminals. (See 'Duration of illness' below.)

The mechanisms of binding to and inhibition of neural cells are related to specific portions of the tetanospasmin (tetanus toxin) molecule. Tetanus toxin is produced initially as an inactive polypeptide chain by actively growing organisms. This synthesis is controlled by genes located in an intracellular plasmid.

After death of the clostridial bacterium, the toxin is released and then activated by bacterial or tissue proteases into its active form, which contains a heavy chain necessary for binding and entry into neurons and a light chain responsible for its toxic properties [16,20-22]. Heavy chains are further cleaved by pepsins into specific fragments, which individually mediate binding to specific types of neural cells. Presynaptic inhibition of neurotransmitter release is mediated via light chains.

Tetanolysin is another toxin produced by C. tetani during its early growth phase. It has hemolytic properties and causes membrane damage in other cells, but its role in clinical tetanus is uncertain.

Predisposing factors — Because C. tetani will not grow in healthy tissues, a convergence of factors must be present in order for tetanus toxin to be elaborated in the human host. This combination of factors usually includes absence of antibodies (ie, from inadequate vaccination) plus two or more of the following:

A penetrating injury resulting in the inoculation of C. tetani spores

Coinfection with other bacteria

Devitalized tissue

A foreign body

Localized ischemia

The above factors explain why tetanus-prone injuries include splinters and other puncture wounds, gunshot wounds, compound fractures, burns, and unsterile intramuscular or subcutaneous injections (that often occur in injection drug users). These predisposing factors can also explain why tetanus can develop in unusual clinical settings such as in:

Neonates (due to infection of the umbilical stump)

Obstetric patients (after septic abortions)

Postsurgical patients (with necrotic infections involving bowel flora)

Adolescents and adults undergoing male circumcision in sub-Saharan Africa [23]

Patients with dental infections

Diabetic patients with infected extremity ulcers

Patients who inject illicit and/or contaminated drugs [24]

Tetanus in patients without an identifiable cause — An identifiable antecedent cause for tetanus is obvious in more than 90 percent of patients presenting with tetanus, but no cause can be identified in a small percentage of patients with classic signs and symptoms of tetanus. Presumably, minor unnoticed abrasions or skin injuries are responsible for most or all of these "cryptogenic" cases. Tetanus has occurred rarely in patients who have received a timely and correct series of tetanus immunizations [25].


Incubation period — The incubation period of tetanus is approximately 8 days but ranges from 3 to 21 days [26]. The incubation period is typically shorter in neonatal tetanus than in non-neonatal tetanus [16]. (See 'Neonatal tetanus' below.)

Inoculation of spores in body locations distant from the central nervous system (eg, the hands or feet) results in a longer incubation period than inoculation close to the central nervous system (eg, the head or neck).

Generalized tetanus — The most common and severe clinical form of tetanus is generalized tetanus. The presenting symptom in more than half of such patients is trismus (lockjaw), although patients with generalized tetanus sometimes present with cephalic or localized tetanus. Patients with generalized tetanus typically have symptoms of autonomic overactivity that may manifest in the early phases as irritability, restlessness, sweating, and tachycardia. In later phases of illness, profuse sweating, cardiac arrhythmias, labile hypertension or hypotension, and fever are often present.

Patients with tetanus may develop reflex spasms of their masseter muscles rather than a (normal) gag response when their posterior pharynx is touched with a tongue blade or spatula (the spatula test). In one study of 400 consecutive patients with suspected tetanus, the sensitivity and specificity of this maneuver were high (94 and 100 percent, respectively) [27]. This test may even be useful in infants, but it is not useful when patients have severe trismus.

Patients with generalized tetanus characteristically have tonic contraction of their skeletal muscles and intermittent intense muscular spasms. Since patients with tetanus have no impairment of consciousness or awareness, both the tonic contractions and spasms are intensely painful. Tetanic spasms may be triggered by loud noises or other sensory stimuli such as physical contact or light. Tonic and periodic spastic muscular contractions are responsible for most of the classic clinical findings of tetanus such as:

Stiff neck


Risus sardonicus (sardonic smile)

A board-like rigid abdomen

Periods of apnea and/or upper airway obstruction due to vise-like contraction of the thoracic muscles and/or glottal or pharyngeal muscle contraction, respectively


During generalized tetanic spasms, patients characteristically clench their fists, arch their back, and flex and abduct their arms while extending their legs, often becoming apneic during these dramatic postures.

Local tetanus — Rarely, tetanus presents with tonic and spastic muscle contractions in one extremity or body region. Local tetanus often but not invariably evolves into generalized tetanus. Diagnosis in local tetanus can be difficult. For example, rarely patients with early tetanus may develop board-like abdominal rigidity that mimics an acute surgical abdomen.

Cephalic tetanus — Patients with injuries to the head or neck may present with cephalic tetanus, involving initially only cranial nerves. Like other forms of local tetanus, patients with cephalic tetanus often subsequently develop generalized tetanus. Prior to the appearance of the typical features of generalized tetanus, patients with cephalic tetanus may manifest confusing clinical findings including dysphagia, trismus, and focal cranial neuropathies that can lead to a misdiagnosis of stroke [28]. The facial nerve is most commonly in cephalic tetanus [29], but involvement of cranial nerves VI, III, IV, and XII may also occur either alone or in combination with others.

Neonatal tetanus — Neonatal tetanus occurs as a result of the failure to use aseptic techniques in managing the umbilical stump in offspring of mothers who are poorly immunized. The application of unconventional substances to the umbilical stump (eg, ghee or clarified butter, juices, and cow dung) have been implicated as common cultural practices that contribute to neonatal tetanus [30]. Neonatal tetanus can also result from unclean hands and instruments or contamination by dirt, straw, or other nonsterile materials in the delivery field.

Neonatal tetanus typically occurs in infants 5 to 7 days following birth (range 3 to 24 days) [16]. The onset of illness is typically more rapid in neonatal tetanus than in older individuals and may progress over hours rather than days, probably because axonal length is proportionately shorter in infants [31].

Neonatal tetanus presents with refusal to feed and difficulty opening the mouth due to trismus [16]. Sucking then stops and facial muscles spasm, which may result in risus sardonicus (sardonic smile). The hands are often clenched, the feet become dorsiflexed, and muscle tone increases. As the disease progresses, neonates become rigid and opisthotonus (spasm of spinal extensors) develops.

Severity of illness — The severity and frequency of the clinical features of tetanus may vary from case to case, depending upon the amount of tetanus toxin that reaches the central nervous system. Symptoms and signs may progress for up to two weeks after the disease onset. The severity is related to the incubation period of the illness and the interval from the onset of symptoms to the appearance of spasms [21]; the longer the interval, the milder the clinical features of tetanus. In addition, illness may be milder in patients with preexisting but nonprotective levels of antitetanus antibodies. In one study of 64 patients with tetanus, serum obtained prior to the institution of treatment contained detectable levels of antibody in 35 percent of patients, and the severity of tetanus in these patients appeared to be inversely related to the level of pretreatment antitetanus toxin antibody [32].

Duration of illness — Tetanus toxin-induced effects are long lasting because recovery requires the growth of new axonal nerve terminals. The usual duration of clinical tetanus is four to six weeks.

DIAGNOSIS — The diagnosis of tetanus is usually obvious and can generally be made based upon typical clinical findings outlined above. Tetanus should especially be suspected when there is a history of an antecedent tetanus-prone injury and a history of inadequate immunization for tetanus. However, tetanus can sometimes be confused with other processes, as discussed in the following section.

DIFFERENTIAL DIAGNOSIS — Tetanus can sometimes be confused with the following mimics.

Drug-induced dystonias such as those due to phenothiazines — Drug-induced dystonias often produce pronounced deviation of the eyes, writhing movements of the head and neck, and an absence of tonic muscular contraction between spasms. By contrast, tetanus does not produce eye deviations, and the muscles are characteristic tonically contracted between spasms. Finally, administration of an anticholinergic agent such as benztropine mesylate will usually immediately reverse the spasms seen in drug-induced dystonias. Such therapy has no effect on patients with tetanus.

Trismus due to dental infection — Dental infections may produce trismus that may rarely be confused with cephalic forms of tetanus. However, the presence of an obvious dental abscess and the lack of progression or superimposed spasms usually make the distinction between the two diseases apparent after initial evaluation and/or a period of observation. (See "Deep neck space infections" and "Complications, diagnosis, and treatment of odontogenic infections".)

Strychnine poisoning due to ingestion of rat poison — Accidental or intentional strychnine poisoning may produce a clinical syndrome similar to tetanus. Supportive care for both conditions is critical; thus, the initial treatment of both conditions is identical. Assays of blood, urine, and tissue for strychnine can be performed in special reference laboratories. Such tests should be obtained when there is any suspicion of accidental or intentional poisoning or when a typical history of an antecedent injury or infection for tetanus is lacking or the patient has been adequately immunized for tetanus. (See "Strychnine poisoning".)

Malignant neuroleptic syndrome — Patients with malignant neuroleptic syndrome can present with striking symptoms of autonomic instability and muscular rigidity. However, the presence of fever, altered mental status, and recent receipt of an agent with a propensity to cause this complication usually makes the distinction from tetanus relatively easy. (See "Neuroleptic malignant syndrome".)

Stiff-person syndrome — Stiff-person syndrome (SPS) is a rare neurologic disorder characterized by severe muscle rigidity. Spasms of the trunk and limbs may be precipitated by voluntary movements or auditory, tactile, or emotional stimulation, all of which can also occur in tetanus. The absence of trismus or facial spasms and rapid response to diazepam distinguish SPS from true tetanic spasms [33]. In addition, SPS is associated with autoantibodies against glutamic acid decarboxylase. (See "Stiff-person syndrome".)

TREATMENT — Treatment of tetanus is best performed in the intensive care unit in consultation with an anesthesiologist or critical care specialist trained in the management of the complications of this disease, including early and aggressive airway management. Unfortunately, little evidence exists to support any particular therapeutic intervention in tetanus. There are only nine randomized trials reported in the literature over the past 30 years [34]. The goals of treatment include:

Halting the toxin production

Neutralization of the unbound toxin

Airway management

Control of muscle spasms

Management of dysautonomia

General supportive management

Halting toxin production

Wound management — All patients with tetanus should undergo wound debridement to eradicate spores and necrotic tissue, which could lead to conditions ideal for germination.

Antimicrobial therapy — Although antibiotics probably play a relatively minor role in the management of tetanus, they are universally recommended. However, it is important to emphasize that appropriate antimicrobial therapy may fail to eradicate C. tetani unless adequate wound debridement is performed. This was illustrated by one study in which 45 isolates of C. tetani were obtained at the time of wound debridement from 84 Vietnamese patients with severe tetanus [35]. All 45 isolates were susceptible by disc diffusion and E-test to penicillin and metronidazole, and all were resistant to trimethoprim-sulfamethoxazole. However, C. tetani was isolated from the wounds of two patients who underwent debridement after more than two weeks of high doses of penicillin.

Metronidazole (500 mg intravenously [IV] every six to eight hours) is the preferred treatment for tetanus, but penicillin G (2 to 4 million units IV every four to six hours) is a safe and effective alternative [11]. We suggest a treatment duration of 7 to 10 days.

The first study to compare penicillin and metronidazole found a greater reduction in mortality in the metronidazole group (7 versus 24 percent) [36]. However, in two subsequent studies, there was no difference in mortality in patients treated with penicillin and those treated with metronidazole [6,37]. In one of the former studies, patients receiving metronidazole required fewer muscle relaxants and sedatives [6]. It is possible that the observed difference in outcomes may not be due to differences in the antimicrobial activity of the two agents but rather may be explained by the GABA antagonist effect of penicillins and third-generation cephalosporins, which may lead to central nervous system (CNS) excitability.

If a mixed infection is suspected, a first-, second-, or third-generation cephalosporin such as cefazolin (1 to 2 g IV every 8 hours), cefuroxime (2 g IV every 6 hours), or ceftriaxone (1 to 2 g IV every 24 hours) can be used.

An alternative agent is doxycycline (100 mg every 12 hours); other agents with activity against C. tetani are macrolides, clindamycin, vancomycin, and chloramphenicol [11,38]. The efficacy of these agents has not been evaluated but, based upon in vitro susceptibility data, it is likely that they are effective.

Neutralization of unbound toxin — Since tetanus toxin is irreversibly bound to tissues, only unbound toxin is available for neutralization. Unbound toxin has been demonstrated in 10 percent of serum samples and 4 percent of cerebrospinal fluid (CSF) samples of cases upon presentation [39]. The use of passive immunization to neutralize unbound toxin is associated with improved survival, and it is considered to be standard treatment.

In the United States, human tetanus immune globulin (HTIG) should be readily available and is the preparation of choice. A dose of 3000 to 6000 units intramuscularly should be given as soon as the diagnosis of tetanus is considered, with part of the dose infiltrated around the wound [40]. HTIG should be administered at different sites than tetanus toxoid.

Intrathecal administration of tetanus immune globulin is of unproven benefit. A randomized trial from Brazil compared intramuscular plus intrathecal administration of immunoglobulin (n = 58) with intramuscular therapy alone (n = 62) [41]. The patients receiving intrathecal therapy had a shorter duration of spasms, shorter hospital stay, and a decreased requirement for respiratory assistance. Mortality was not significantly affected.

However, a number of methodologic issues might have affected this study. The mortality rate for tetanus patients fell during the study period from 35 percent in historical controls to 12 percent among control patients in this study. While tetanus cases were graded upon admission, these grades were not reported, and the only note of more patients with grade III and IV disease among the controls compared with those receiving intrathecal immunoglobulin implies that these differences arose during the course of therapy. The investigators refer to tetanus hyperimmune globulin but merely list a lyophilized human immunoglobulin in the methods section.

In countries in which HTIG is not readily available, equine antitoxin is used intramuscularly or intravenously. When equine antitoxin is used, an intradermal test dose of 0.1 mL in a 1:10 dilution should be administered prior to giving the full dose in order to evaluate for hypersensitivity reactions [11]. In contrast, antecedent skin testing is not needed if a human preparation is to be used.

Infiltration of antitoxin, either human or equine, into the wound has sometimes been advocated but is of unproven value. The use of pooled intravenous immune globulin (IVIG) has been proposed as a possible alternative to HTIG [40].

Active immunization — Since tetanus is one of the few bacterial diseases that does not confer immunity following recovery from acute illness, all patients with tetanus should receive active immunization with a total of three doses of tetanus and diphtheria toxoid spaced at least two weeks apart, commencing immediately upon diagnosis. Tetanus toxoid should be administered at a different site than tetanus immune globulin. It should be assumed that anyone who is not adequately vaccinated or protected against tetanus is also inadequately protected against diphtheria [9]. The tetanus-diphtheria-acellular pertussis vaccine (Tdap) may be used instead of Td but, if used, recommendations are for this formulation to be used only once in adults, except in pregnant women, who should receive Tdap during each pregnancy [42-44]. Specific recommendations for the use of vaccines to protect against tetanus, diphtheria, and pertussis in adults, pregnant women, and children are discussed in detail separately. (See "Tetanus-diphtheria toxoid vaccination in adults", section on 'Indications for Td or Tdap vaccination' and "Pertussis infection in adolescents and adults: Treatment and prevention", section on 'Prevention' and "Immunizations during pregnancy", section on 'Tetanus, diphtheria, and pertussis vaccination' and "Diphtheria, tetanus, and pertussis immunization in infants and children 0 through 6 years of age" and "Diphtheria, tetanus, and pertussis immunization in children 7 through 18 years of age".)

Subsequent tetanus doses, in the form of Td, are recommended at 10-year intervals throughout adulthood [43]. Tetanus toxoid alone should be given only to those patients with documented allergy or untoward reactions to diphtheria toxoid. (See "Tetanus-diphtheria toxoid vaccination in adults".)

Control of muscle spasms — Generalized muscle spasms are life threatening since they can cause respiratory failure, lead to aspiration, and induce generalized exhaustion in the patient. Several drugs may be used to control these spasms. Attention to placement of the patient and control of light or noise in the room in an effort to avoid provoking muscle spasms was an important component of care for patients with tetanus in the past before the availability of drugs to prevent spasms. These measures are still vital in regions where the availability of neuromuscular blocking agents may be limited [11].

Benzodiazepines and other sedatives — Benzodiazepines have been used traditionally and are generally effective in controlling the rigidity and spasms associated with tetanus [11]. They also provide a sedative effect. Diazepam has been used most frequently, but other benzodiazepines are as effective as diazepam. Patients with tetanus often show tolerance to the sedating effects of benzodiazepines and may remain awake and alert after receiving doses that would sedate or cause anesthesia in other patients [25].

For tetanus, the usual starting dose of diazepam for an adult is 10 to 30 mg IV and repeated as needed every 1 to 4 hours; total daily doses as high as 500 mg may be required for an adult. Ventilatory assistance is imperative at these higher doses. When higher doses of the IV formulation of diazepam are used, the vehicle, propylene glycol, may produce hyperosmolarity and an anion gap metabolic (lactic) acidosis [45]. These abnormalities are often accompanied by acute kidney injury and can progress to multisystem organ failure. To avoid these problems when high doses of a benzodiazepine are required, a continuous infusion of IV midazolam can be given as it does not contain propylene glycol. For patients who are absorbing drugs well by the enteral route, diazepam can be given enterally via a feeding tube. Since these drugs may be required for a prolonged period of time (often weeks), they should be tapered gradually to avoid withdrawal reactions.

The properties, usual dosing regimens for sedation, and adverse effects of benzodiazepines are discussed in greater detail separately. (See "Sedative-analgesic medications in critically ill adults: Properties, dosage regimens, and adverse effects", section on 'Benzodiazepines' and "Sedative-analgesic medications in critically ill adults: Properties, dosage regimens, and adverse effects", section on 'Dosage regimens' and "Sedative-analgesic medications in critically ill adults: Properties, dosage regimens, and adverse effects", section on 'Propylene glycol toxicity'.)

Infusion of the anesthetic propofol may also control spasms and rigidity. Its prolonged use has been associated with lactic acidosis, hypertriglyceridemia, and pancreatic dysfunction.

Neuromuscular blocking agents — Neuromuscular blocking agents are used when sedation alone is inadequate. Pancuronium, a long-acting agent, has been traditionally used. However, it may worsen autonomic instability because it is an inhibitor of catecholamine reuptake. Vecuronium can also be administered and is less likely to cause autonomic problems, but since it is short acting, it must be given as continuous infusion to provide adequate effects. Monitoring of patients on these drugs is extremely important to avoid or recognize complications, and these drugs should be stopped at least once a day in order to assess the patient's status.

Baclofen, which stimulates postsynaptic GABA beta receptors, has been used in a few small studies. The preferred route is intrathecal, and it may be given either in a bolus of 1000 mcg or by continuous intrathecal infusion [46]. Intrathecal baclofen given as an initial bolus in a dose ranging from 40 to 200 mcg followed by a continuous infusion of 20 mcg/hour was found to control spasms and rigidity in 21 out of 22 patients with grade III tetanus in a retrospective outcome study from a single medical center in Portugal. One of 22 patients developed meningitis secondary to infection of the intrathecal catheter despite the fact that most patients required such therapy for at least three weeks (range 8 to 30 days) [47]. In some cases, baclofen has been used without the need for artificial ventilation [48]. Phenothiazines and barbiturates were used in the past to control spasms but have largely been displaced by neuromuscular blocking agents.

Management of autonomic dysfunction — Several drugs have been used to produce adrenergic blockade and suppress autonomic hyperactivity; only treatment with magnesium sulfate has been studied in a randomized clinical trial in tetanus [49] because of its use in clinical series for the management of autonomic dysfunction and as adjunctive treatment for controlling spasms [49-52].

Magnesium sulfate — Magnesium sulfate acts as a presynaptic neuromuscular blocker, blocks catecholamine release from nerves, and reduces receptor responsiveness to catecholamines [53]. It has the advantage of worldwide experience in the treatment of eclampsia.

In a randomized, double blind trial in 256 hospitalized patients with severe tetanus in Vietnam, magnesium sulfate infusion compared with placebo controlled autonomic dysfunction [49]. The patients were randomly assigned to magnesium sulfate (loading dose 40 mg/kg over 30 minutes, followed by continuous infusion of either 2 g per hour for patients over 45 kg or 1.5 g per hour for patients ≤45 kg) versus placebo (5 percent glucose in water) infusion. The primary outcomes were requirement for mechanical ventilation and drugs to control muscle spasms and autonomic dysfunction. Magnesium infusion significantly reduced the requirement for other drugs to control muscle spasms, and patients treated with magnesium were 4.7 times (95% CI 1.4-15.9) less likely to require verapamil to treat cardiovascular instability than those in the placebo group. Magnesium sulfate infusion did not reduce the need for mechanical ventilation.

Beta blockade — Labetalol (0.25 to 1.0 mg/min) has frequently been administered because of its dual alpha- and beta-blocking properties. Beta blockade alone with propranolol, for example, should be avoided because of reports of sudden death [54]. Morphine sulfate (0.5 to 1.0 mg/kg per hour by continuous intravenous infusion) is commonly used to control autonomic dysfunction as well as to induce sedation.

Other drugs — Other drugs for the treatment of various autonomic events, which have been reported to be useful, are atropine, clonidine, and epidural bupivacaine.

Airway management and other supportive measures — Since tetanus toxin cannot be displaced from the nervous system once bound to neurons, supportive care is the main treatment for tetanus. In patients with severe tetanus, prolonged immobility in the intensive care unit is common, much of which is on mechanical ventilation and may last for weeks. Such patients are predisposed to nosocomial infections, decubitus ulcers, tracheal stenosis, gastrointestinal hemorrhage, and thromboembolic disease.

Endotracheal intubation is justified initially, but early tracheostomy is frequently indicated because of the likelihood of prolonged mechanical ventilation. The latter allows better tracheal suctioning and pulmonary toilet.

Energy demands in tetanus may be extremely high, so early nutritional support is mandatory. Enteral feeding is preferred if enough calories can be administered by this route. Placement of percutaneous endoscopic gastrostomy (PEG) tubes is commonplace, since this route may prevent gastroesophageal reflux, which may be induced by nasogastric tubes. Prophylactic treatment with sucralfate or acid blockers may be used to prevent gastroesophageal hemorrhage from stress ulceration.

Prophylaxis of thromboembolism with heparin, low molecular weight heparin, or other anticoagulants should be administered early.

Physical therapy should be started as soon as spasms have ceased, since tetanus patients often are left with disability from prolonged drug-induced paralysis and immobilization.

Considerations in the developing world — Critical care services are often unavailable or rudimentary in many developing countries [11]. When intensive care units (ICUs) are not available, acute respiratory failure is a leading cause of death from tetanus. In the absence of an ICU, a separate ward or room should be designated for patients with tetanus, and sensory stimuli should be kept to a minimum since loud noises, physical contact, and light can trigger tetanic spasms [11]. Nondepolarizing paralytic agents, such as vecuronium and pancuronium, are not safe to use in the absence of ventilatory support. However, benzodiazepines and baclofen can be used in such situations if doses are carefully titrated to avoid respiratory depression. Magnesium sulfate may be used to manage autonomic dysfunction. (See 'Control of muscle spasms' above and 'Magnesium sulfate' above.)

PROPHYLAXIS — Tetanus prophylaxis following a puncture wound is discussed in detail separately. The following table summarizes the approach to tetanus prophylaxis (table 1). (See "Infectious complications of puncture wounds", section on 'Tetanus immunization'.)

Immunization of women who are pregnant or of childbearing age reduces neonatal tetanus mortality by approximately 94 percent [16]. Improving hygiene during home births in the developing world is also likely to play an important role in preventing neonatal tetanus.

PROGNOSIS — Case-fatality rates for non-neonatal tetanus in developing countries range from 8 to 50 percent [16,31], whereas the majority of patients with tetanus recover when modern supportive care is available [55].

Neonatal tetanus, once nearly always fatal, now has mortality rates of 3 to 88 percent [16]. Patients with shorter incubation periods (eg, ≤7 days) have increased disease severity and mortality [16,56].

Among neonatal infections, survivors may recover fully or have varying degrees of neurologic damage ranging from minor intellectual deficits to cerebral palsy [57]. The prognosis appears excellent (mortality 2 percent in a study from India) with infections not associated with spasms [56].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Tetanus infection".)

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Basics topic (see "Patient education: Tetanus (The Basics)")


Although tetanus is now rare in the developed world, the disease remains a threat to all unvaccinated people, particularly in developing countries. Since Clostridium tetani spores cannot be eliminated from the environment, immunization and proper treatment of wounds and traumatic injuries are crucial for tetanus prevention. (See 'Introduction' above.)

Tetanus is a clinical diagnosis and must be considered in patients with muscle spasms and an inadequate vaccination history. (See 'Clinical features' above and 'Diagnosis' above.)

Supportive care is the mainstay of management to avoid complications such as respiratory failure, nosocomial infections, and thromboembolism. (See 'Treatment' above.)

Since the disease is mediated by a toxin, a crucial aspect of therapy is to eliminate ongoing toxin production, neutralize unbound toxin usually with human tetanus immune globulin, and immunize against tetanus since natural disease does not confer immunity. (See 'Treatment' above.)

Antimicrobials play an adjunctive role in the therapy of tetanus. We recommend metronidazole (500 mg intravenously every six to eight hours) for the treatment of tetanus. We suggest a treatment duration of 7 to 10 days. (See 'Antimicrobial therapy' above.)

Muscle spasms are controlled with sedation (usually benzodiazepines) or neuromuscular blockade. (See 'Control of muscle spasms' above.)

Autonomic hyperactivity can be treated with labetalol or morphine sulfate. Beta blockade without concomitant alpha blockade should be avoided. The use of magnesium sulfate for both autonomic dysfunction and additional control of muscle spasms has generated considerable interest. This drug is readily available and is used worldwide for the treatment of eclampsia. (See 'Management of autonomic dysfunction' above.)

Patients with shorter incubation periods have increased disease severity and mortality. (See 'Prognosis' above.)

Tetanus prophylaxis following a puncture wound is discussed in detail separately. The following table summarizes the approach to tetanus prophylaxis (table 1). (See "Infectious complications of puncture wounds", section on 'Tetanus immunization'.)

Immunization of women who are pregnant or of childbearing age dramatically reduces neonatal tetanus mortality. Improving hygiene during home births in the developing world is also likely to play an important role in preventing neonatal tetanus. (See 'Prophylaxis' above.)

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