Tetanus

Author: Daniel J Sexton, MD

Section Editor: John G Bartlett, MD
Deputy Editor: Anna R Thorner, MD

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Jul 2017. | This topic last updated: Jun 21, 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:

● Generalized
● Local
● Cephalic
● Neonatal

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".)

EPIDEMIOLOGY

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 to 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, for example,
tetanus was the second most common cause (14 percent) after stroke [13].

Neonatal tetanus, which the World Health Organization targeted for elimination by 1995,
accounted for approximately 59,000 deaths in 2008 [14]. While this represents a decrease
in mortality of 92 percent compared with 1988 [14], as of 2014, 24 countries had still not
eliminated maternal and neonatal tetanus [15]. (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 [16,17] and
binding tightly and irreversibly to receptors at these sites [16,18], tetanus toxin blocks
neurotransmission by its cleaving action on membrane proteins involved in
neuroexocytosis [19,20]. The net effect is disinhibition of neurons that modulate
excitatory impulses from the motor cortex. 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 [16]. 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 is 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
[15,16,18,20]. 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 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 [21]
● Patients with dental infections
● Diabetic patients with infected extremity ulcers
● Patients who inject illicit and/or contaminated drugs

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.

CLINICAL FEATURES

Incubation period — The incubation period of tetanus can be as short as 2 days or as

long as 38 days, with most cases occurring a mean of 7 to 10 days following exposure
[15]. The incubation period is typically shorter in neonatal tetanus than in non-neonatal
tetanus [15]. (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) [22]. 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
● Opisthotonus
● 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
● Dysphagia

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 [23]. The facial nerve is most
commonly in cephalic tetanus [24], 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 [25]. 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) [15]. 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 [26].

Neonatal tetanus presents with refusal to feed and difficulty opening the mouth due to
trismus [15]. 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 [16]; 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 [27].

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 [28]. 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 [29]. 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 [30]. 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) [31]. However, in two
subsequent studies, there was no difference in mortality in patients treated with penicillin
and those treated with metronidazole [6,32]. 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 eight hours), cefuroxime (2 g IV every six 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 [11,33].
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 [34]. 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 [35]. 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) [36]. 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 [35].

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 [37-39]. 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 [38]. 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.

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 [40]. 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 [41]. 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) [42]. In some cases, baclofen has been used without the need for artificial
ventilation [43]. 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 [44] because
of its use in clinical series for the management of autonomic dysfunction and as
adjunctive treatment for controlling spasms [44-47].

Magnesium sulfate — Magnesium sulfate acts as a presynaptic neuromuscular

blocker, blocks catecholamine release from nerves, and reduces receptor responsiveness
to catecholamines [48]. 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 [44]. 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 [49].
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 [15]. 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 [15,26], whereas the majority of patients with tetanus recover when
modern supportive care is available [50].

Neonatal tetanus, once nearly always fatal, now has mortality rates of 3 to 88 percent
[15]. Patients with shorter incubation periods (eg, ≤7 days) have increased disease
severity and mortality [15,51].

Among neonatal infections, survivors may recover fully or have varying degrees of
neurologic damage ranging from minor intellectual deficits to cerebral palsy [52]. The
prognosis appears excellent (mortality 2 percent in a study from India) with infections not
associated with spasms [51].

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".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education

materials, “The Basics” and “Beyond the Basics.” The Basics patient education pieces are
written in plain language, at the 5th to 6th grade reading level, and they answer the four or
five key questions a patient might have about a given condition. These articles are best
for patients who want a general overview and who prefer short, easy-to-read materials.
Beyond the Basics patient education pieces are longer, more sophisticated, and more
detailed. These articles are written at the 10th to 12th grade reading level and are best for
patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to
print or e-mail these topics to your patients. (You can also locate patient education
articles on a variety of subjects by searching on “patient info” and the keyword(s) of
interest.)

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

SUMMARY

● 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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