Review
Tetanus
Tetanus remains a disease with a high mortality rate. It
still commonly occurs in developing countries where inade-
quate immunization programs exist. The incidence has been
dramatically reduced in the United States with the introduc-
tion of large-scale immunization programs. However, this
disease still occurs in people who are not adequately immu-
nized, especially the elderly. Managing patients with teta-
nus in the intensive care unit (ICU) has significantly reduced
the rate of mortality from this disease.2 However, crucial
therapy can be instituted in the emergency department. The
literature was reviewed. The present understanding of the
disease, its management, and prevention is discussed.
CASE REPORT
A 61-year-old woman accidentally punctured her left forearm with
a horseshoe pick, while cleaning the hoofs of her pet horse, 6 days
prior to admission. She developed right jaw pain 2 days prior to
admission, and her right jaw locked 1 day prior to admission,
which brought her to seek medical attention, Her private physician
gave her diptheria and tetanus toxoid vaccine and oral antibiotics for
a possible jaw infection. The following day, she presented to a local
emergency room unable to open her mouth. Tetanus was diagnosed
and she was transferred to our institution for admission and treat-
ment. There were no symptoms of dysphagia, respiratory difficulty,
or muscle spasm. The patient was uncertain if she had ever been
immunized for tetanus. She was allergic to penicillin. Physical ex-
amination was remarkable for trismus. The patient could not open
her mouth more than 1 cm between front incisors. There was a 5 mm
wound with eschar on the flexor surface of the left forearm. There
was no drainage or erythema. The patient was afebrile. There was
no evidence of muscular rigidity or spasms. Deep tendon reflexes
were normal. White blood cell count was 9,600/mm3 with a normal
differential. Other laboratory results, chest x-ray, and electrocar-
diogram (EKG) were noncontributory.
In the emergency department, the patient was given 3,000 IU of
tetanus immune globulin (TIG) intramuscularly (IM). An antitetanus
antibody level was drawn. Her wound was unroofed and cultures
sent. She was admitted to the ICU where diazepam and metronida-
zole were initiated and the surgeons debrided her wound. The anti-
tetanus antibody level was less than detectable. Wound cultures
grew a Clostridium species which was not further identified. Over
From the Department of Emergency Medicine, Medical Col-
lege of Wisconsin, Milwaukee, WI.
Manuscript received February 13, 1992; accepted April 6,
1992.
Address reprint reguests to Dr Kefer, Department of Emer-
gency Medidine, Medical College of Wisconsin, Milwaukee
County Medical Complex, 8700 W Wisconsin Ave, Milwaukee, WI
53226.
Key Words: Tetanus, tetanus toxoid, tetanus immune globulin.
Coovriaht 0 1992 bv W.B. Saunders Comoanv
07%6%7/92/l 005-O-011$5.00/O
MICHAEL P. KEFER, MD
the next 48 hours, the patient developed muscular spasms, con-
trolled with diazepam, and dysphagia with the inability to handle
secretions, which required intubation. Tachycardia and hyperten-
sion also developed and were controlled with calcium channel
blockers and sedation. Tracheostomy was eventually performed.
She had no other serious complications from the disease. She was
transferred to the medical floor on the 30th hospital day, was able to
tolerate oral intake by the 36th hospital day, and was discharged on
the 40th hospital day.
DISCUSSION
Tetanus is an exotoxin-mediated disease characterized by
increased rigidity and convulsive spasms of skeletal muscle.
It is caused by Clostridium tetani, an anaerobic, gram-
positive, spore-forming rod. The terminal endospore pro-
duces a characteristic tennis racket appearance of the bac-
teria when viewed microscopically. The organism produces
two exotoxins; hemolysin, which is clinically unimportant,
and tetanospasmin, the neurotoxin responsible for the clin-
ical manifestations of tetanus. Clostridium tetani is ubiqui-
tous, found in the soil and in the gastrointestinal tracts of
man and many domesticated animals.
Tetanus is a major problem in developing countries where
mandatory immunization programs are not enforced or re-
quired. It is often among the 10 most frequent causes of
death in such countries. There are an estimated 500,000
cases per year worldwide, with a mortality rate of 45%.
In the United States, in the biennium of 1987-88, 101 cases
of tetanus were reported to the Centers for Disease Control.
The incidence was 0.02 cases per 100,000. Tetanus in the
United States is typically a disease of older adults who are
not immunized or inadequately immunized. It most com-
monly follows an acute injury, but also results from chronic
wounds, such as skin ulcers, abscesses, or parenteral drug
abuse. In 4% of cases, there was neither a history of injury
nor an identifiable lesion. Many cases follow minor injury
not seen by a physician.
Clostridium tetani is a noninvasive organism. Wounds are
frequently contaminated with the spores of the organism, but
tetanus rarely develops because conditions of low oxygen
tension are not achieved. Spores may survive in the body
months to years and cause disease at a later time after minor
trauma that changes local conditions. This may account for
the cases in which no obvious injury is found. Toxin pro-
duction is favored by necrotic tissue, foreign bodies, or as-
sociated infection that establishes low oxidation-reduction
potentials. Infection by C tetani remains strictly localized.
The toxin produced is released upon lysis of the organism.
Tetanus toxin then enters the nervous system peripherally,
at the myoneural junction of alpha motor neurons, travels to
445
446 AMERICAN JOURNAL OF EMERGENCY
the cell body by retrograde axonal transport, then retrograde
transsynaptically to its site of action. Here, it blocks release
of y-aminobutyric acid and glycine, the transmitters of pre-
synaptic inhibitory neurons.4 Blockade of inhibitory im-
pulses results in muscle contraction, causing rigidity, and
permits reflex spasms to occur. As toxin production contin-
ues it also enters the circulation, spreading to myoneural
junctions throughout the body. Nerves with the shortest ax-
ons are affected first. Thus, symptoms begin in facial mus-
cles, typically with trismus, and progress to the neck, trunk,
and finally the extremities. Tetanospasmin has a disinhibi-
tory effect on the autonomic nervous system as well. Teta-
nospasmin has high affinity and specificity for anterior horn
inhibitory neurons. It is one of the most powerful poisons
known. The effects of the toxin appear to be permanent.
Recovery requires nerve terminal sprouting and formation of
new synapses.4
There are four forms of clinical tetanus: generalized, local,
cephalic, and tetanus neonatorum.3.6 Generalized tetanus
comprises the vast majority of cases. Invariably, this begins
with trismus and spreads throughout the body causing gen-
eralized muscle rigidity, spasms, and autonomic instability.
Local tetanus involves rigidity and spasms in the region of
the wound. This may occur when the amount of toxin pro-
duced is small. This form may progress to generalized teta-
nus.
Cephalic tetanus is rare, occurring in less than 1% of
cases. It is associated with head wounds and chronic otitis
media, and manifested by cranial nerve palsies, most often
VII. The involved musculature may be paretic until a spasm
intervenes. This form too can become generalized.
Tetanus neonatorum occurs mainly in developing coun-
tries which lack immunization programs and where poor ob-
stetrical conditions exist. Some primitive societies apply
cow dung to the cut umbilical cord as part of the birth ritual.
The disease occurs within 10 days of birth and is typically
manifested by irritability, grimacing, intense rigidity, and
opisthotonus. Characteristic spasms occur with minimal
stimulation. The mortality rate is extremely high.
The incubation time, defined as the time from injury to the
time of development of symptoms, ranges from 2 to 56 days,
but 80% of cases occur within 14 days. A short incubation
period is associated with severe disease. The most common
presenting complaints are pain and stiffness in the jaw, ab-
domen, or back, and dysphagia. With time, stiffness pro-
gresses to rigidity, and trismus, more commonly known as
lockjaw, occurs. Generalized rigidity of facial muscles
causes the characteristic expression called risus sardonicus.
Reflex spasms develop within 1 to 4 days of the first symp-
toms. The interval between the first symptoms and the first
reflex spasms is defined as the onset time. A shorter onset
time is also associated with severe disease. Spasms may be
precipitated by minimal stimuli such as noise, light, or touch,
and last seconds to minutes. They become more intense and
increase in frequency with disease progression. They can be
painful and dangerous causing apnea, fractures, or rhabdo-
myolysis. Before 1954, asphyxia from recurrent tetanic
spasms was the typical cause of death. The advent of neu-
romuscular blockade and mechanical ventilation made it
possible to prevent death from this cause. With control of
spasms, many patients with severe tetanus developed the
MEDICINE n Volume 10, Number 5 W September 1992
syndrome of overactivity of the sympathetic nervous system
first described by Kerr and coworkers in 1%8. It is char-
acterized by sustained labile hypertension and tachycardia,
cardiac arrhythmias, peripheral vasoconstriction, profuse
sweating, pyrexia, increased carbon dioxide output, in-
creased urinary catecholamines and hypotension. Sudden
cardiac death has since become a leading cause of death.2~7~8
Some attribute this cause to excess catecholamine produc-
tion from sympathetic nervous system overactivity based on
similarities between the myocarditis of tetanus and
pheochromocytoma. Others attribute sudden cardiac arrest
to the direct action of tetanospasmin on the myocardium.*
Recently, a group from Japan has suggested parasympa-
thetic overactivity may be the cause.
The course of the disease may be long, 1 to 2 months or
more. Spasms usually diminish after 14 days and resolve
over the following week or two. Residual stiffness may last
for prolonged periods, but complete recovery occurs in most
cases of uncomplicated tetanus.
Complications of tetanus and its management contribute
significantly to morbidity and mortality. Inadequate ventila-
tion is a constant threat with resultant hypoxia or atelectasis.
Other risks are aspiration from dysphagia; arrhythmias, hy-
pertension, or hypotension from autonomic instability or
myocarditis; fractures of the spine or long bones; gastroin-
testinal ulceration; secondary infection from the original
wound or intravenous or bladder catheters; and pneumonia,
thromboembolic disease, or decubiti from prolonged immo-
bilization.
The diagnosis is clinical, based on history and physical.
Clostridia is recovered from the wound in less than 30% of
cases.3 Moreover, recovery of the organism does not prove
the diagnosis, as the organism may be part of the wound
flora. A definite history of immunization, or a serum anti-
body level of greater than or equal to 0.01 IUlmL, makes the
diagnosis unlikely. Any detectable level of antitoxin anti-
body is thought to be partially protective and its presence
indicates previous immunization.
No disease resembles advanced tetanus. In the patient
presenting with trismus, the following should be considered:
orofacial infection (parotitis, tonsillar abscess, etc), dystonic
reaction, mandibular fracture, temporomandibular joint pa-
thology, hyperventilation, and hysterical reaction. In the pa-
tient presenting with muscle spasms, strychnine poisoning,
dystonic reaction, hyperventilation, and hypocalcemia
should be considered.
Treatment is based on four principles. The first is to pre-
pare for rapid deterioration of the patients condition. All
patients should be admitted to the ICU until it is clear that
the disease has stabilized at a level that can be managed on
the general ward. In 1987, Trujillo et al. reported that the
impact of ICU care resulted in a decrease in mortality, from
44% to 15%.2
The second principle is to prevent further absorption of
toxin. Immediate administration of TIG is indicated. The
antitoxin will neutralize any circulating toxin, but has no
effect on that already fixed to nerve tissue. It has little im-
pact on existing symptoms. However, the case fatality ratio
in mild to moderately severe disease is reduced significantly
when TIG is administered early. Although recommended
dosage has ranged from 500 to 10,000 IU, the exact effective
MICHAEL P. KEFER W TETANUS
dose has not been established. The median recommended
dose is 3,000 IU, given IM. 1*3*69**11 There is no proven value
of local infiltration of TIG at the wound site. The half-life is
25 days; therefore, only one dose is required.
The third principle is to eradicate the organism, the source
of toxin. Wounds should be debrided to remove foreign bod-
ies and devitalized tissue. The evidence on the effectiveness
of antibiotics on the treatment of tetanus remains unclear.
Penicillin remains the antibiotic most frequently used,
though one study found metronidazole more efficacious.*
The fourth principle is to provide supportive care until
recovery occurs by the formation of new synapses. To min-
imize the risk of precipitating spasms, the patients room
should be as quiet and dark as possible and manipulation
minimized, including elimination of unnecessary routine pro-
cedures. Benzodiazepines have a major role in the treatment
of tetanus due to their sedative and muscle relaxant proper-
ties. Diazepam has been used most often and is titrated to
effect. Dantrolene has been used as a muscle relaxant in less
severe cases.13 Severe spasms may be refractory to benzo-
diazepines, and neuromuscular blockade with paralytics will
be necessary.
Airway protection and maintenance of ventilation are of
major concern. Prophylactic intubation should be antici-
pated. Tracheostomy should be considered early when it is
apparent the patient will require mechanical ventilation or is
otherwise unable to protect the airway.
No single drug or combination of drugs has been consis-
tently effective in controlling the cardiovascular manifesta-
tions of autonomic instability.14 Drugs causing B-blockade
have been associated with increased risk of sudden death.
Ganglionic blockade has been used with variable results.
Satisfactory control is reported with the use of magnesium
sulfate. Magnesium infusion inhibits the release of catechol-
amines from peripheral nerves and the adrenal gland, and
reduces receptor sensitivity to these neurotransmitters.
Morphine sulfate has also been shown to be effective by
blocking sympathetically mediated vasoconstriction through
histamine release mechanisms. Continuous epidural anes-
thesia has been used in severe tetanus, felt by the investiga-
tors to have three beneficial effects: sympathetic blockade,
muscle relaxation, and analgesia. Recently, the use of con-
tinuous spinal anesthesia has been used to induce complete
blockade of the autonomic nervous system. The hemody-
namics are then regulated artificially with catecholamine in-
fusions. An example of dramatic cardiovascular instability,
with systolic blood pressure changing from 300 mm Hg to 0
mm Hg within seconds, is described.
General therapeutic measures are also important and in-
clude deep venous thrombosis (DVT) prophylaxis, gastroin-
testinal ulcer prophylaxis, decubitus ulcer prevention, and
close attention to nutritional status. In the more severe cases
of tetanus, an intense catabolic state exists. Tube feedings or
hyperalimentation are usually required. All patients with tet-
anus require primary immunization because the amount of
toxin causing disease is insufficient to confer immunity.
Tetanus is a preventable disease when appropriate immu-
nization guidelines are followed. Active immunization is re-
sponsible for the dramatic reduction in the incidence of tet-
anus. This uses tetanus toxoid which is tetanus toxin inac-
tivated by formaldehyde.
447
Current recommendations for primary immunization in
children less than 7 years old are to administer tetanus and
diptheria toxoids with pertussis vaccine (DPT) at age 6-8
weeks, with the second and third dose at 4-8 week intervals,
the fourth dose 1 year after the third, and a booster at age 4-6
years. Primary immunization for individuals 7 years or older
consists of three doses of adult-type diptheria and tetanus
toxoids (dT). The first and second doses are given 4-8 weeks
apart, followed by the third dose 6-12 months later. Inter-
ruption of the recommended schedule, regardless of the de-
lay between doses, does not interfere with the final immunity
achieved, nor does it require starting the series over again. A
booster dose of dT is given at IO-year intervals after com-
pletion of the primary series. Side effects are uncommon,
but are more frequent and severe in persons who receive an
excess number of boosters. These include local swelling and
erythema, and hypersensitivity reactions. Association with
seizure, encephalopathy, or neuropathy has been reported
rarely. l6
In patients presenting with acute injury, including those
who are pregnant, the need for active immunization with
tetanus toxoid, with or without passive immunization with
TIG, depends on the nature of the wound and the patients
immunization status.16* If the wound is clean and minor,
and primary immunization has been completed, a booster is
required if 10 years has elapsed since the last vaccination.
For all other wounds, a booster is appropriate if 5 years has
since elapsed. In patients who have an incomplete or uncer-
tain primary immunization status, dT should be given for any
type of wound. In addition, if the wound is tetanus-prone,
TIG, 250 IU IM, should be administered. Tetanus-prone
wounds include those contaminated with dirt or saliva, punc-
ture wounds, avulsions, gunshot wounds, bums, and frost-
bite. If the wound is considered highly tetanus-prone, the
recommended dose of TIG is 500 IU IM. High-risk wounds
include those over 24 hours old, those containing devitalized
tissue that cannot be fully debrided, and those exposed to
high levels of bacterial contamination such as barnyards,
sewers, or bowel contents. Passive immunization with TIG
ensures protective levels of antitoxin greater than 0.01 IU/
mL for about 4 weeks. Administration of TIG may be done
simultaneously with dT and will not interfere with the im-
mune response, but it must be given in a separate syringe, at
a separate site, and with the adsorbed (not fluid) form of dT.
If a contraindication to tetanus toxoid exists, only passive
immunization with TIG should be given accordingly.
SUMMARY
Tetanus is a preventable disease with proper immuniza-
tion. The marked decline in the incidence over the past sev-
eral decades has resulted from widespread use of tetanus
prophylaxis and improved wound management in the emer-
gency department. Emergency physicians are among the
most frequent providers of tetanus vaccination. We can
stress the importance of proper immunization and encourage
patients to keep accurate immunization records. This can
maximize protection of patients from tetanus, and minimize
adverse reactions from excessive administration of booster.
Tetanus can be fatal even with proper treatment. Vital treat-
ment measures can easily be completed in the emergency
department.
448 AMERICAN JOURNAL OF EMERGENCY MEDICINE n Volume 10, Number 5 n September 1992
The author thanks Laura Sohn for assistance in manuscript
preparation.
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