Tetanus

Author: Daniel J Sexton, MD

Section Editor: John G Bartlett, MD
Deputy Editor: Meg Sullivan, MD

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is
complete.

Literature review current through: Nov 2019. | This topic last updated: Aug 03, 2018.

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 resource-rich settings, the disease remains a

threat to all unvaccinated people, particularly in resource-limited 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 children 6 weeks 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 "Animal bites
(dogs, cats, and other animals): Evaluation and management".)

EPIDEMIOLOGY

Resource-rich countries — Because of almost universal vaccination of children

with tetanus toxoid in resource-rich 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
children 6 weeks through 6 years of age", section on 'Schedules' and "Diphtheria,
tetanus, and pertussis immunization in children 7 through 18 years of age",
section on 'Indications'.)

Unlike in resource-limited 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 resource-rich 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 resource-rich 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].
Resource-limited countries — In contrast with resource-rich nations where
tetanus is rare, tetanus remains endemic in resource-limited settings, 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 resource-limited settings 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].

CLINICAL FEATURES

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
● 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 [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 in
adults" 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 full series (eg, three doses in
adults and children >7 years old) of tetanus and diphtheria toxoid-containing
vaccines, commencing immediately upon diagnosis. Such vaccines should be
administered at a different site than tetanus immune globulin. Specific
recommendations on vaccine formulations and vaccination schedules are
discussed in detail separately:

● (See "Tetanus-diphtheria toxoid vaccination in adults", section on 'Routine

adult immunization'.)
● (See "Immunizations during pregnancy", section on 'Tetanus, diphtheria, and
pertussis vaccination'.)
● (See "Diphtheria, tetanus, and pertussis immunization in children 6 weeks
through 6 years of age", section on 'Schedules'.)
● (See "Diphtheria, tetanus, and pertussis immunization in children 7 through
18 years of age", section on 'Schedule'.)

Subsequent tetanus doses, in the form of Td, are recommended at 10-year

intervals throughout adulthood [42]. 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 [43]. 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. 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].

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 [44]. 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)
[45]. In some cases, baclofen has been used without the need for artificial
ventilation [46]. 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 [47] because of its use in clinical series for the management of
autonomic dysfunction and as adjunctive treatment for controlling spasms [47-
50].

Magnesium sulfate — Magnesium sulfate acts as a presynaptic

neuromuscular blocker, blocks catecholamine release from nerves, and reduces
receptor responsiveness to catecholamines [51]. 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 [47]. 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 [52]. 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 resource-limited settings — Critical care services are often

unavailable or rudimentary in many resource-limited 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 resource-limited settings is also likely to play an important
role in preventing neonatal tetanus.
PROGNOSIS

Case-fatality rates for non-neonatal tetanus in resource-limited countries range

from 8 to 50 percent [16,31], whereas the majority of patients with tetanus
recover when modern supportive care is available [53].

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 [16,54].

Among neonatal infections, survivors may recover fully or have varying degrees
of neurologic damage ranging from minor intellectual deficits to cerebral palsy
[55]. The prognosis appears excellent (mortality 2 percent in a study from India)
with infections not associated with spasms [54].

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 AND RECOMMENDATIONS

● Although tetanus is now rare in resource-rich settings, the disease remains

a threat to all unvaccinated people, particularly in resource-limited 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 resource-limited settings is also likely to play an important
role in preventing neonatal tetanus. (See 'Prophylaxis' above.)

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