TETANUS

DEFINISI
Tetanus is an acute, often fatal, disease caused by an exotoxin produced by the bacterium
Clostridium tetani. It is characterized by generalized rigidity and convulsive spasms of skeletal
muscles. The muscle stiffness usually involves the jaw (lockjaw) and neck and then becomes
generalized. (cdc)
Tetanus is an acute, often fatal, disease caused by an exotoxin produced by the bacterium
Clostridium tetani. It is characterized by generalized rigidity and convulsive spasms of skeletal
muscles. The muscle stiffness usually involves the jaw (lockjaw) and neck and then becomes
generalized (WHO,2010)
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" (or trismus) lives in modern parlance as a reminder of one of the
cardinal features of tetanus: intense, painful spasms of the masseter muscles, and an inability to
open the mouth. (UPTODATE, 2021)
C. tetani is a slender, gram-positive, anaerobic rod that may develop a terminal spore, giving it a
drumstick appearance. The organism is sensitive to heat and cannot survive in the presence of
oxygen. The spores, in contrast, are very resistant to heat and the usual antiseptics. They can
survive autoclaving at 249.8°F (121°C) for 10–15 minutes. The spores are also relatively
resistant to phenol and other chemical agents.(cdc)
The spores are widely distributed in soil and in the intestines and feces of horses, sheep, cattle,
dogs, cats, rats, guinea pigs, and chickens. Manure-treated soil may contain large numbers of
spores. In agricultural areas, a significant number of human adults may harbor the organism. The
spores can also be found on skin surfaces and in contaminated heroin.(cdc)
C. tetani produces two exotoxins, tetanolysin and tetanospasmin. The function of tetanolysin is
not known with certainty. Tetanospasmin is a neurotoxin and causes the clinical manifestations
of tetanus. On the basis of weight, tetanospasmin is one of the most potent toxins known. The
estimated minimum human lethal dose is 2.5 nanograms per kilogram of body weight (a
nanogram is one billionth of a gram), or 175 nanograms for a 70-kg (154lb) human. (cdc)

Pathogenesis
C. tetani usually enters the body through a wound. In the presence of anaerobic (low oxygen)
conditions, the spores germinate. Toxins are produced and disseminated via blood and
lymphatics. Toxins act at several sites within the central nervous system, including peripheral
motor end plates, spinal cord, and brain, and in the sympathetic nervous system. The typical
clinical manifestations of tetanus are caused when tetanus toxin interferes with release of
neurotransmitters, blocking inhibitor impulses. This leads to unopposed muscle contraction and
spasm. Seizures may occur, and the autonomic nervous system may also be affected. (cdc)

This combination of factors usually includes absence of antibodies (ie, from inadequate
vaccination) plus two or more of the following: (uptodate)

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

●Coinfection with other bacteria

●Devitalized tissue

●A foreign body

●Localized ischemia

These predisposing factors can also explain why tetanus can develop in unusual clinical settings
such as in: (uptodate)

●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

●Patients with dental infections

●Diabetic patients with infected extremity ulcers

●Patients who inject illicit and/or contaminated drugs

Clinical Features
The incubation period ranges from 3 to 21 days, usually about 8 days. In general the further the
injury site is from the central nervous system, the longer is the incubation period. Shorter
incubation periods are associated with a higher chance of death. In neonatal tetanus, symptoms
usually appear from 4 to 14 days after birth, averaging about 7 days. (cdc)
Local tetanus is an uncommon form of the disease, in which patients have persistent contraction
of muscles in the same anatomic area as the injury. These contractions may persist for many
weeks before gradually subsiding. Local tetanus may precede the onset of generalized tetanus but
is generally milder. Only about 1% of cases are fatal. (cdc)
Cephalic tetanus is a rare form of the disease, occasionally occurring with otitis media (ear
infections) in which C. tetani is present in the flora of the middle ear, or following injuries to the
head. There is involvement of the cranial nerves, especially in the facial area. (cdc)
The most common type (about 80%) of reported tetanus is generalized tetanus. The disease
usually presents with a descending pattern. The first sign is trismus or lockjaw, followed by
stiffness of the neck, difficulty in swallowing, and rigidity of abdominal muscles. Other
symptoms include elevated temperature, sweating, elevated blood pressure, and episodic rapid
heart rate. Spasms may occur frequently and last for several minutes. Spasms continue for 3–4
weeks. Complete recovery may take months. (cdc)

Tonic and periodic spastic muscular contractions are responsible for most of the classic clinical
findings of tetanus such as: (uptodate)

●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

Neonatal tetanus (NT) is a form of generalized tetanus that occurs in newborn infants. Neonatal
tetanus occurs in infants born without protective passive immunity, because the mother is not
immune. It usually occurs through infection of the unhealed umbilical stump, particularly when
the stump is cut with an unsterile instrument. Neonatal tetanus is common in some developing
countries but very rare in the United States. World Health Organization (WHO) estimates that in
2010, 58,000 newborns died from NT, a 93% reduction from the situation in the late 1980s.(cdc)
Tetanus is characterized by muscle rigidity and painful muscle spasms. In generalized tetanus
(the most common form), stiffness and pain often begin in the jaw muscles (trismus or “lock
jaw”) and/or neck, shoulder and abdominal muscles. Early in the disease course, spasms are
triggered by sensory stimuli such as touch, loud noises and bright lights. As the disease
progresses, muscle groups throughout the body are affected and spontaneous generalized seizure-
like tetanospasms develop. In the absence of the ability to provide ventilatory support, death is
usually due to respiratory failure. Autonomic dysfunction, including hypertension and
tachycardia alternating with bradycardia and hypotension can be present in more severe tetanus
cases and is associated with a poorer prognosis. (who)
Diagnosis
Tetanus diagnosis is strictly clinical; there are no confirmatory laboratory tests. The WHO
definition of adult tetanus requires at least one of the following signs: trismus (inability to open
the mouth) or risus sardonicus (sustained spasm of the facial muscles); or painful muscular
contractions. Although this definition requires a history of injury or wound, tetanus may also
occur in patients who are unable to recall a specific wound or injury. (who)

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. (uptodate)

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".)
(uptodate)

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".) (uptodate)

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".) (uptodate)

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 [34]. In addition, SPS is associated with autoantibodies against glutamic
acid decarboxylase. (See "Stiff-person syndrome".) (uptodate)
Medical Management
General measures

– Ensure intensive nursing care.

– The patient should be in a dark, quiet room. Blindfold neonates with a cloth bandage.
– Handle the patient carefully, while sedated and as little as possible; change position every 3 to
4 hours to avoid bedsores.
– Teach family the danger signs and instruct them to call the nurse for the slightest respiratory
symptom (cough, difficulty breathing, apnoea, excessive secretions, cyanosis, etc.).
– Establish IV access for hydration, IV injections.
– Gentle suction of secretions (mouth, oropharynx).
– Insert a nasogastric tube for hydration, feeding and administration of oral medications.
– Provide hydration and nutrition in feeds divided over 24 hours. In neonates, give expressed
breast milk every 3 hours (risk of hypoglycaemia).

General measures: if possible a separate ward/location should be designated for tetanus patients.
Patients should be placed in a quiet shaded area and protected from tactile and auditory
stimulation as much as possible. All wounds should be cleaned and debrided as indicated. (who)
All wounds should be cleaned. Necrotic tissue and foreign material should be removed. If tetanic
spasms are occurring, supportive therapy and maintenance of an adequate airway are critical.
(cdc)

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

Tetanus immune globulin (TIG) is recommended for persons with tetanus. TIG can only help
remove unbound tetanus toxin. It cannot affect toxin bound to nerve endings. A single
intramuscular dose of 500 units is generally recommended for children and adults, with part of
the dose infiltrated● Death around the wound if it can be identified. Intravenous immune
globulin (IVIG) contains tetanus antitoxin and may be used if TIG is not available. (cdc)

Immunotherapy: if available, administer human TIG 500 units by intramuscular injection or

intravenously (depending on the available preparation) as soon as possible; in addition,
administer age-appropriate TT-containing vaccine, 0.5 cc by intramuscular injection at a separate
site. [Tetanus disease does not induce immunity; patients without a history of primary TT
vaccination should receive a second dose 1–2 months after the first dose and a third dose 6–12
months later.] (who)

Since tetanus toxin is irreversibly bound to tissues, only unbound toxin is available for
neutralization. The use of passive immunization to neutralize unbound toxin is associated with
improved survival and it is considered to be standard treatment. (uptodate)

Because of the extreme potency of the toxin, tetanus disease does not result in tetanus immunity.
Active immunization with tetanus toxoid should begin or continue as soon as the person’s
condition has stabilized. (cdc)

Antibiotic treatment: metronidazole is preferred (500 mg every six hours intravenously or by

mouth); Penicillin G (100,000–200,000 IU/kg/day intravenously, given in 2–4 divided doses).
Tetracyclines, macrolides, clindamycin, cephalosporins and chloramphenicol are also effective.
(who)

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 [36]. 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.
(uptodate)

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 [13]. We suggest a treatment duration of 7 to 10 days. (uptodate)

The first study to compare penicillin and metronidazole found a greater reduction in mortality in
the metronidazole group (7 versus 24 percent) [37]. However, in three subsequent studies, there
was no difference in mortality in patients treated with penicillin and those treated with
metronidazole [38-40]. In one of the former studies, patients receiving metronidazole required
fewer muscle relaxants and sedatives [38]. 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. (uptodate)

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. (uptodate)

An alternative agent is doxycycline (100 mg every 12 hours); other agents with activity against
C. tetani are macrolides, clindamycin, vancomycin, and chloramphenicol [13,41]. The efficacy
of these agents has not been evaluated but, based upon in vitro susceptibility data, it is likely that
they are effective. (Uptodate)

Muscle spasm control: benzodiazepines are preferred. For adults, intravenous diazepam can be
given in increments of 5 mg, or lorazepam in 2 mg increments, titrating to achieve spasm control
without excessive sedation and hypoventilation (for children, start with doses of 0.1–0.2 mg/kg
every 2–6 hours, titrating upward as needed). Large amounts may be required (up to 600
mg/day). Oral preparations could be used but must be accompanied by careful monitoring to
avoid respiratory depression or arrest. (who)

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. 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 [47]. 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. 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 [27]. (uptodate)

Since these drugs may be required for a prolonged period of time (often weeks), they should be
tapered gradually to avoid withdrawal reactions.

When the frequency and severity of the spasms have decreased, start weaning the diazepam
(gradually decrease the rate of infusion):
(https://medicalguidelines.msf.org/viewport/CG/english/tetanus-16689919.html)
– Calculate the total daily dose of IV diazepam and administer it orally in 4 divided doses, 6
hours apart, via nasogastric (NG)3 tube.
– Give first NG dose and decrease rate of IV infusion by 50%.
– Give second NG dose and stop IV diazepam infusion.
– If withdrawal signs4 appear, wean more slowly.
– Once on diazepam PO, wean by 10 to 20% of the original dose daily, until at a dose of 0.05
mg/kg every 6 hours.
– Then increase the interval from every 6 hours to every 8 hours for 24 hours as tolerated (wean
more slowly if withdrawal signs appear).
– Continue to increase the interval between the doses from every 8 hours to every 12 hours and
then to every 24 hours before stopping the diazepam.
– Each step should be for 24 hours or more if withdrawal signs appear.

Magnesium sulphate can be used alone or in combination with benzodiazepines to control spasm
and autonomic dysfunction: 5 gm (or 75mg/kg) intravenous loading dose, then 2–3 grams per
hour until spasm control is achieved. To avoid overdose, monitor patellar reflex as areflexia
(absence of patellar reflex) occurs at the upper end of the therapeutic range (4mmol/L). If
areflexia develops, dose should be decreased. (who)
Other agents used for spasm control include baclofen, dantrolene (1–2 mg/kg intravenous or by
mouth every 4 hours), barbiturates, preferably short-acting (100–150 mg every 1–4 hours in
adults; 6–10 mg/kg in children; by any route), and chlorpromazine (50–150 mg by intramuscular
injection every 4–8 hours in adults; 4–12 mg every by intramuscular injection every 4–8 hours in
children). (who)
Autonomic dysfunction control: magnesium sulphate as above; or morphine. Note: β-blockers
such as propranolol were used in the past but can cause hypotension and sudden death; only
esmalol is currently recommended. (who)
Airway / respiratory control: drugs used to control spasm and provide sedation can result in
respiratory depression. If mechanical ventilation is available, this is less of a problem; if not,
patients must be carefully monitored and medication doses adjusted to provide maximal spasm
and autonomic dysfunction control while avoiding respiratory failure. If spasm, including
laryngeal spasm, is impeding or threatening adequate ventilation, mechanical ventilation is
recommended when possible. Early tracheostomy is preferred as endotracheal tubes can provoke
spasm and exacerbate airway compromise. (who)
Adequate fluids and nutrition should be provided, as tetanus spasms result in high metabolic
demands and a catabolic state. Nutritional support will enhance chances of survival. (who)

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. (uptodate)

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. (uptodate)

Energy demands in tetanus may be extremely high, so early nutritional support is mandatory.
Enteral feeding is preferred. Placement of percutaneous endoscopic gastrostomy 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. (uptodate)
Prophylaxis of thromboembolism with heparin, low molecular weight heparin, or other
anticoagulants should be administered early. (uptodate)

Physical therapy should be started as soon as spasms have ceased, since tetanus patients often are
left with disability from prolonged muscle wasting and contractures [59]. (uptodate)

Considerations in resource-limited settings — Critical care services are often unavailable or

rudimentary in many resource-limited countries [13]. 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, ideally 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 [13]. Other options include eye shades and ear plugs to reduce stimuli.
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 and as an adjunctive for muscle spasm. (See 'Control
of muscle spasms' above and 'Magnesium sulfate' above.) (uptodate)

Complications
Laryngospasm (spasm of the vocal cords) and/or spasm of the muscles of respiration leads to
interference with breathing. Fractures of the spine or long bones may result from sustained
contractions and convulsions. Hyperactivity of the autonomic nervous system may lead to
hypertension and/or an abnormal heart rhythm. (cdc)
Nosocomial infections are common because of prolonged hospitalization. Secondary infections
may include sepsis from indwelling catheters, hospital-acquired pneumonias, and decubitus
ulcers. Pulmonary embolism is particularly a problem in drug users and elderly patients.
Aspiration pneumonia is a common late complication of tetanus, found in 50%–70% of
autopsied cases. In recent years, tetanus has been fatal in approximately 11% of reported cases.
Cases most likely to be fatal are those occurring in persons 60 years of age and older (18%) and
unvaccinated persons (22%). In about 20% of tetanus deaths, no obvious pathology is identified
and death is attributed to the direct effects of tetanus toxin. (cdc)