Key Points: CHAPTER 79: Tetanus

Universitas
Islam Bandung
Access Provided by:
Principles of Critical Care, 4e
CHAPTER 79: Tetanus
David L. Pitrak; Jason T. Poston; Jodi Galaydick
KEY POINTS
Tetanus is caused by Clostridium tetani and is a toxin-mediated disease.
Although rare in the USA, worldwide there are between 500,000 and 1 million cases a year, with over 200,000 deaths.
It characterized by trismus, dysphagia, and localized muscle rigidity near a site of injury, often progressing to severe generalized muscular spasms
complicated by respiratory failure and cardiovascular instability.
The diagnosis of tetanus is made on clinical grounds alone. A clinical diagnosis of presumed tetanus is sufficient to initiate treatment.
Patients with tetanus should be managed in an ICU. In severe cases, the first priority is control of the airway to ensure adequate ventilation and
correction of hypotension related to hypovolemia and/or autonomic instability.
Antitoxin therapy with human tetanus immune globulin is given intramuscularly (500-3000 IU) as early as possible.
Treatment to limit continued production and absorption of toxin includes surgical debridement of the site of injury and antimicrobial therapy
with intravenous metronidazole.
Traditionally muscle rigidity and spasms have been treated with high-dose benzodiazepines and narcotics. However, intravenous magnesium
therapy should also be considered.
Cardiovascular instability due to autonomic dysfunction is managed by ensuring normovolemia and using benzodiazepine, narcotic, and/or
magnesium sulfate infusions when needed.
Supportive measures include early provision of nutrition, correction of electrolyte disturbances, subcutaneous heparin administration for
prophylaxis of deep venous thrombosis, and prompt antimicrobial therapy for nosocomial infection.
With meticulous management of the manifestations of this disease and careful attention to prevention of its major complications, complete
recovery is possible in most cases.
Tetanus is often a disease of otherwise healthy active people. Fully developed tetanus is frequently rapidly fatal unless the patient is supported
through a lengthy period of painful muscle spasms complicated by respiratory failure, cardiovascular instability, and increased risk of pulmonary
embolism and nosocomial infection. In developed countries, this disease is likely to remain an uncommon but challenging problem that demands an
alert and aggressive approach to initial diagnosis and management. If this early management is coupled with attentive supportive care and avoidance
of complications over a period of prolonged critical illness, excellent outcomes are possible in most cases.
EPIDEMIOLOGY
Historically, tetanus was a feared complication of wound infections. This Clostridium tetani toxin-mediated disease is one of several toxin-mediated
diseases resulting from wound infections, along with staphylococcal and streptococcal toxic shock syndrome, wound botulism, and wound diphtheria.
Since the advent of routine vaccination after trauma injury and passive immunization for grossly contaminated wounds, tetanus has become
uncommon in the United States with an average of 43 cases annually from 1998 to 2000.1 Worldwide it is still a major cause of morbidity and mortality,
and remains one of the WHO targeted diseases. Overall, 500,000 to 1 million cases occur worldwide each year, with 213,000 deaths, the majority in
children less than 5 years of age. This is mainly due to inadequate vaccination, either because of access to care or neonatal infections before
Downloaded 2021524 7:32 A Your IP is 110.136.104.153
vaccination is given. The male:female ratio is approximately 3:2, representing a greater incidence of tetanus-prone wounds in males. If patients
CHAPTER 79: Tetanus, David L. Pitrak; Jason T. Poston; Jodi Galaydick Pagehave
1 / 12
©2021 McGraw Hill. All Rights Reserved. Terms of Use • Privacy Policy • Notice • Accessibility
access to supportive care for respiratory failure and cardiovascular instability, recovery is possible in most cases, although the road to recovery can be
quite long and fraught with complications of critical illness, most notably nosocomial infections and venous thrombosis.
Historically, tetanus was a feared complication of wound infections. This Clostridium tetani toxin-mediated disease is one of several toxin-mediated
diseases resulting from wound infections, along with staphylococcal and streptococcal toxic shock syndrome, wound botulism, Universitas Islam Bandung
and wound diphtheria.
Since the advent of routine vaccination after trauma injury and passive immunization for grossly contaminated wounds, tetanus has become
Access Provided by:
uncommon in the United States with an average of 43 cases annually from 1998 to 2000.1 Worldwide it is still a major cause of morbidity and mortality,
and remains one of the WHO targeted diseases. Overall, 500,000 to 1 million cases occur worldwide each year, with 213,000 deaths, the majority in
children less than 5 years of age. This is mainly due to inadequate vaccination, either because of access to care or neonatal infections before
vaccination is given. The male:female ratio is approximately 3:2, representing a greater incidence of tetanus-prone wounds in males. If patients have
access to supportive care for respiratory failure and cardiovascular instability, recovery is possible in most cases, although the road to recovery can be
quite long and fraught with complications of critical illness, most notably nosocomial infections and venous thrombosis.
PATHOGENESIS
Clostridium tetani spores are found in the soil and the gastrointestinal tract of humans and many nonhuman animals. Spores gain access to tissues
through trauma and may remain viable for months to years, but the incubation period is usually 7 to 10 days.2 The shorter the incubation period, the
more severe the symptoms, and this is most likely related to an inoculation effect.3 The spores are resistant to boiling and antiseptics, but are killed by
autoclaving at 121°C for 15 minutes.4 Usually spores get into tissues from a puncture wound, laceration, or abrasion, but inoculation can also occur
from tattoos, injections, burn wounds, frostbite, dental infections, and penetrating eye injuries.5 Neonatal cases can occur from umbilical stump
infections.
When the spores germinate the bacteria secrete tetanospasmin and tetanolysin. Tetanolysin is a virulence factor that causes local tissue necrosis.
Tetanospasmin is the toxin responsible for the clinical syndrome seen in tetanus. It is a very potent toxin, with an estimated minimum lethal dose being
2.5ng/kg of body weight.6 Inside the bacteria, the toxin is inactive, but when a bacterial cell dies, the toxin is released and activated by proteases. If
toxin is produced in larger amounts, it also accumulates in the lymphatic system of the invaded muscle, enters the bloodstream via the thoracic duct,
and is disseminated throughout the body. Toxin passing from blood to skeletal muscle then accumulates in the nerve endings of the motor fibers and
proceeds to the ventral horns or cranial nuclei or is taken up by the lymphatic system and recirculated in the blood. The rate of accumulation of toxin in
the ventral horns of the spinal cord depends on the length of the neural pathway and the activity of the muscles involved.7 Since jaw muscles and
spinal postural muscles have short neural pathways to the ventral horns and are continually active in the awake human, this is the likely explanation
for trismus and neck stiffness early in the course of the illness.
The toxin cleaves membrane proteins involved in neuroexocytosis and neurons that are involved become incapable of transmitter release.8
Tetanospasmin binds to gangliosides on the membranes of local nerve terminals at the myoneural junction. It then enters peripheral neurons and is
transported to neurons of the CNS via retrograde axonal transport. Tetanus appears when the toxin reaches spinal neurons. The neurons that are
affected secrete inhibitory neurotransmitters, that is, those that secrete GABA and glycine, are more sensitive to the toxin. Neurons that are involved
become incapable of transmitter release and as a result there is no inhibition of motor reflex responses. This leads to contractions of agonist and
antagonist muscles known as tetanic spasms. Once toxin is fixed to neurons, it cannot be neutralized, even with administration of antitoxin antibodies.
New nerve terminals and new synapses must form for resolution, on the order of 4 to 6 weeks.9 For this reason, therapy at the point of clinical tetanus
is only supportive.
The effect of tetanus toxin on the neuromuscular junction is presynaptic inhibition of acetylcholine release, which can result in paralysis of muscles.
Paralysis is less frequent and usually localized to areas of high toxin concentration because the neuromuscular junction is not as sensitive to tetanus
toxin as the inhibitory neurons. Autonomic dysfunction occurs later in the course of the disease because of the longer neuronal path. Sympathetic and
parasympathetic overactivity has been attributed to impaired neuronal inhibition of the adrenal glands.10
Because preformed circulating antibody to tetanospasmin can completely prevent development of the disease, tetanus occurs primarily in
nonimmunized or inadequately immunized patients, particularly the poor and elderly.11,12 Although vaccination results in antitoxoid antibodies that
neutralize the toxin, disease is still possible in those who have been properly vaccinated and receive appropriate booster doses of vaccine. Many
conditions may impair the immune response to vaccine, including advanced HIV infection. The course in these may be atypical and milder.13
CLINICAL MANIFESTATIONS
The majority of cases of tetanus follow some type of trauma or injury; however, in 15% to 25% of cases a portal of entry cannot be determined
(cryptogenic tetanus).14 Portal of entry can range from minor trauma producing a break in the skin, burn injuries, infected umbilical stumps,
postoperative sites, ischemic ulcers, the uterus after septic abortions, injection sites of narcotic addicts, and untreated otitis media.15 Cases of tetanus
have been seen in intravenous drug users associated with skin infections caused by use of inadequately sterilized needles.14,16 The incubation period
can range from 3 days to 3 weeks, but cases have occurred after several months. In general, the shorter the incubation period, the more severe the
CHAPTER 79: Tetanus, David L. Pitrak; Jason T. Poston; Jodi Galaydick Page 2 / 12
disease. However, a long incubation does not guarantee a mild course. A prodrome of malaise, irritability, and headache has been described but is
usually not seen.17
CLINICAL MANIFESTATIONS
Universitas Islam Bandung
The majority of cases of tetanus follow some type of trauma or injury; however, in 15% to 25% of cases a portal of entry cannot be determined
Access Provided by:
(cryptogenic tetanus).14 Portal of entry can range from minor trauma producing a break in the skin, burn injuries, infected umbilical stumps,
postoperative sites, ischemic ulcers, the uterus after septic abortions, injection sites of narcotic addicts, and untreated otitis media.15 Cases of tetanus
have been seen in intravenous drug users associated with skin infections caused by use of inadequately sterilized needles.14,16 The incubation period
can range from 3 days to 3 weeks, but cases have occurred after several months. In general, the shorter the incubation period, the more severe the
disease. However, a long incubation does not guarantee a mild course. A prodrome of malaise, irritability, and headache has been described but is
usually not seen.17
There are four basic forms of tetanus that can be distinguished clinically: generalized, local, cephalic, and neonatal. Only generalized, local, and
cephalic will be described in this chapter. In the adult intensive care unit setting, generalized tetanus is the most likely to be encountered.
GENERALIZED TETANUS
Generalized tetanus accounts for 80% of tetanus seen in clinical practice and is characterized by diffuse muscle rigidity affecting any voluntary muscle
group.4 As the disease progresses, more muscle groups become involved. A majority of patients (75%) will present with rigidity of the masseter muscle
(trismus), which results in difficulty with opening the mouth and chewing. It is not uncommon for these patients to present to a dentist first. Other
common manifestations include neck rigidity, stiffness, dysphagia, and reflex spasm. As the disease evolves the main manifestations are muscle
rigidity and reflex spasms. Muscle rigidity in the facial muscles results in risus sardonicus (sardonic smile), while opisthotonos is caused by rigidity of
the vertebral muscles and antigravity muscles. Vertebral fractures are not uncommon when these muscle groups are involved.17 Abdominal muscle
involvement may mimic peritonitis, while nuchal rigidity can simulate meningitis. Reflex spasms are present in 70% of patients and can be provoked by
external stimuli such as noise or manipulation of the patient. These spasms are tonic and clonic in nature and painful. Sustained spasms can lead to
exhaustion and hypoxia in patients. Laryngeal spasm may lead to asphyxia; early and aggressive airway management is indicated early in the disease
course because laryngeal spasm may occur at any time in the disease course.15 In the Edmondson and Flowers series of 100 patients, trismus and
dysphagia (described as sore throat) were the presenting symptoms in 75 cases and neck and back stiffness in 14 cases. However, in 88 cases, it was
possible to demonstrate trismus on initial physical examination.14,18
Spasms are initially tonic, followed first by high-frequency and then low-frequency clonic activity. In very severe tetanus, spasms may occur so
frequently that status epilepticus may be suspected, and may be forceful enough to cause fractures of long bones and of the spine. Spasm-induced
damage to muscles can also result in rhabdomyolysis complicated by acute renal failure.19 Spasms may be initiated by touch, noise, lights, and
swallowing, even in the sleeping patient. Spasms severe enough to require treatment may persist for up to 6 weeks.
In addition to being extremely painful, spasms can produce a variety of significant secondary effects. Apnea occurs when spasms involve the
respiratory muscles or larynx. Paralysis of skeletal muscles may occur following periods of sustained spasms due to presynaptic inhibition of
acetylcholine release at the neuromuscular junction. Similarly, paralysis of urinary bladder musculature together with spasm of perineal muscles has
been implicated in causing acute urinary retention. In pregnancy, spasms can cause abortion or miscarriage, although the fetus is not directly affected,
since the toxin does not cross the placenta. Inadequately treated spasms can also produce fever, although secondary infection and direct and indirect
actions of toxin on hypothalamic temperature regulation are often implicated.
The autonomic nervous system dysfunction of severe tetanus usually occurs 1 to 2 weeks after the onset of the disease but may occur earlier.20
Manifestations of impaired sympathetic inhibition include tachycardia, labile hypertension alternating with hypotension, peripheral vasoconstriction,
fever, and profuse sweating. Overactivity of the parasympathetic nervous system causes increased bronchial and salivary gland secretions,
bradycardia, and sinus arrest.21 These hemodynamic findings are similar to those seen in pheochromocytomas. Additional complications include
pulmonary edema, myocardial dysfunction, acute respiratory distress syndrome, pneumonia, sepsis, pulmonary embolism, gastrointestinal bleeding,
and poor nutritional status.1
LOCALIZED TETANUS
Localized tetanus is a less common presentation of tetanus and is characterized by rigidity of the group of muscles in close proximity to the site of
injury without systemic signs. The presence of circulating antitoxin prevents the systemic spread of the toxin, but there is not enough antitoxin to stop
local toxin uptake at a wound site. The toxin causes painful muscle contractions that can last for weeks. The disease may be mistaken for pain-induced
muscle spasms.17 Local tetanus may develop into generalized tetanus but is usually milder and less likely to be fatal, with mortality of approximately
1%.4
CEPHALIC TETANUS
Cephalic tetanus is a rare form of the disease, occurring with otitis media, following head trauma or chronic infection or the head and neck. Cephalic
tetanus after scalp or facial injury tends to occur earlier with an incubation period of 1 day to 2 weeks.22 It only involves the cranial nerves and is
injury without systemic signs. The presence of circulating antitoxin prevents the systemic spread of the toxin, but there is not enough antitoxin to stop
local toxin uptake at a wound site. The toxin causes painful muscle contractions that can last for weeks. The disease may be Universitas Islam Bandung
mistaken for pain-induced
Access Provided by:
muscle spasms.17 Local tetanus may develop into generalized tetanus but is usually milder and less likely to be fatal, with mortality of approximately
1%.4
CEPHALIC TETANUS
Cephalic tetanus is a rare form of the disease, occurring with otitis media, following head trauma or chronic infection or the head and neck. Cephalic
tetanus after scalp or facial injury tends to occur earlier with an incubation period of 1 day to 2 weeks.22 It only involves the cranial nerves and is
defined as trismus plus paralysis of one or more cranial nerves. Although the most common cranial nerve involved is VII, any cranial nerve can be
affected. Patients can present with a confusing clinical picture that may involve dysphagia, trismus, and focal cranial neuropathies.17 Isolated paralysis
of the facial nerve may be due to Bell palsy or an early manifestation of cephalic tetanus.23 In cephalic tetanus, cranial nerve palsies may precede
trismus.14,18 Progression to the generalized form can occur with cephalic tetanus and is associated with a poor prognosis.4,22,24
DIAGNOSIS AND LABORATORY TESTING

The diagnosis of tetanus is based on clinical manifestations rather than laboratory tests. In areas where tetanus is endemic diagnosis is relatively easy,
but in developed countries where the disease is less prevalent diagnosis can be delayed. The spatula test is a simple test that can be helpful in
diagnosis. In the presence of tetanus, the posterior pharyngeal wall will contract due to a reflex contraction of the masseters when touched by a
spatula. In a study by Apte and Kanad used the test on 400 patients with suspected tetanus and was found to have sensitivity of 94% and a specificity of
100% for diagnosing tetanus.25 Although the clinical presentation for tetanus is usually characteristic, there is a differential diagnosis that includes
malignant hyperthermia, atropine poisoning or an adverse effect of metoclopramide, strychnine poisoning, and acute hypercalcemia. In some cases,
the diagnosis is difficult due to an atypical presentation. For instance, dysphagia may be the major symptom. The major clinical features on which the
diagnosis of tetanus is based are listed in Table 79-1 along with the features of other conditions with which it can be confused.
TABLE 79-1
Differential Diagnosis of Tetanus: Clinical Features
Tetanus Strychnine Neuroleptics SMSa Rabies Meningitis
Trismus + + + + − −
Nuchal rigidity + + + + − +
Risus sardonicus + + − − − −
Opisthotonus + + + − + −
Muscle rigidity (continuous) + + + − − −
Muscle rigidity (intermittent) − − − + + −
Encephalopathy − − − − + +
Rapid course − + + − − −
aStiff-man syndrome.
Tissue cultures are positive in less than 50% of patients.15 Since the organism is noninvasive, blood cultures are of little value except in diagnosing
secondary infection. The severity of disease is inversely related to the duration of the incubation period, which can be defined as the time of injury to
the first appearance of spasms. This can be useful to determine the timing and need for airway protection.
A complete blood count will usually show a leukocytosis with a left shift, and less frequently, a lymphocytosis. Examination of urine may reveal
proteinuria and leukocytes thought to result from accumulation of tetanus toxin in the kidneys.23 Other nonspecific laboratory abnormalities include
elevation of serum transaminases, increased catecholamine levels in serum and urine, and decreased serum cholinesterase level. Creatinine
phosphokinase (CPK) is usually normal initially but generally rises with the onset of muscular spasms. Idoko and colleagues reported elevated
cerebrospinal fluid (CSF) protein levels in 26 of 34 (76.5%) patients with tetanus.26 The elevation of CSF protein appeared to correlate with disease
severity. Nineteen patients with severe disease (10 ultimately fatal) had significantly higher CSF protein values (mean = 1582 mg/L) than mild cases
Tissue cultures are positive in less than 50% of patients.15 Since the organism is noninvasive, blood cultures are of little value except in diagnosing
secondary infection. The severity of disease is inversely related to the duration of the incubation period, which can be defined as the time of injury to
Access Provided by:
the first appearance of spasms. This can be useful to determine the timing and need for airway protection.
A complete blood count will usually show a leukocytosis with a left shift, and less frequently, a lymphocytosis. Examination of urine may reveal
proteinuria and leukocytes thought to result from accumulation of tetanus toxin in the kidneys.23 Other nonspecific laboratory abnormalities include
elevation of serum transaminases, increased catecholamine levels in serum and urine, and decreased serum cholinesterase level. Creatinine
phosphokinase (CPK) is usually normal initially but generally rises with the onset of muscular spasms. Idoko and colleagues reported elevated
cerebrospinal fluid (CSF) protein levels in 26 of 34 (76.5%) patients with tetanus.26 The elevation of CSF protein appeared to correlate with disease
severity. Nineteen patients with severe disease (10 ultimately fatal) had significantly higher CSF protein values (mean = 1582 mg/L) than mild cases
(mean =400 mg/L).26
TREATMENT
The goals of tetanus treatment are to reduce the production and deposition of tetanospasmin, to prevent painful and potentially harmful muscle
spasm, and to provide supportive care.10,14,15 Limiting the reach of tetanospasmin is accomplished by successful management of the responsible
wound, antibiotic therapy, and administration of antitoxin. Muscle tetany is controlled by minimizing muscle stimulation and providing
pharmacotherapy to prevent the muscle spasm. Supportive care often begins with an assessment of airway patency and the ability of the patient to
ventilate, later shifts focus to stabilizing the circulation impacted by autonomic instability, and throughout requires vigilance to prevent complications
of what is commonly a prolonged critical illness.
For this reason, patients with a presumptive diagnosis of tetanus should be admitted to the intensive care unit with consultation with a critical care
specialist to help with management and complications of the disease.14,15,27 Because the onset of the disease ranges from less than 1 to 12 days, even
patients with mild tetanus should be observed in a high acuity setting for at least 1 week, or 2 weeks if symptom resolution is slow. Patients with
incubation periods of greater than 20 days who have only localized rigidity can be safely discharged to a lower acuity setting after a few days of
observation provided no progression of the disease has occurred. As a general rule, the peak severity of tetanus can be roughly estimated by the time
of injury to the first appearance of spasms; the earlier the spasms, the more severe the disease is likely to be. This information can be useful to predict
the timing and need for supportive care.17 Medications commonly used in the management of tetanus are listed in Table 79-2 together with their
indications and usual doses.
TABLE 79-2
Drugs Used in Medical Management of Tetanus
Medication Indication Dose (Usual)
HTIGa Generalized tetanus 500-3000 IU intramuscular
Metronidazole Toxin production (given in all cases) 500 mg IV/PO q6h
Midazolam Spasms, sedation, and cardiovascular instability 0.3-30.0 mg/h IV (mean =9.0 mg/h), titrate to effect
Magnesium sulfate Spasms and cardiovascular instability 40 mg/kg IV load over 30 minutes, then 1-3 g IV/h
Titrate to serum concentrations of 2-4 mmol/L
Cisatracurium Neuromuscular blockade for severe muscle spasms 1-2µg/kg/min IV, titrate to effect
Dantrolene Rigidity and spasms 0.5-1.0 mg/kg IV q4-6h
Clonidine Cardiovascular instability 300µg q8h via nasogastric tube
aHuman tetanus immune globulin.
WOUND MANAGEMENT
Aggressive surgical treatment of tetanus-producing wounds is believed to result in improved survival via the removal of spores and necrotic tissue
necessary for toxin formation. Foreign bodies should be removed and wounds should be aggressively debrided and left open.17 The wound should be
Clonidine Cardiovascular instability 300µg q8h via nasogastric tube
Access Provided by:
aHuman tetanus immune globulin.
WOUND MANAGEMENT
Aggressive surgical treatment of tetanus-producing wounds is believed to result in improved survival via the removal of spores and necrotic tissue
necessary for toxin formation. Foreign bodies should be removed and wounds should be aggressively debrided and left open.17 The wound should be
excised with a several centimeter margin of viable tissue, and amputation should be considered if gangrene is present on an extremity wound.28 The
decision to perform a hysterectomy on a patient who develops tetanus in the postpartum period should be based on the presence of associated
invasive bacterial sepsis, gangrene of the uterus, or uterine injury. Tetanus is not itself an indication for hysterectomy.23
After debridement of necrotic tissue, the wound should be cared for as any other wound that has not been complicated by clinical tetanus. This
includes vigilant observation of the wound for progression or secondary infection, as well as the application of a topical dressing. Local antibiotic
therapy targeted at Clostridium tetani or direct tetanus immunoglobulin instillation to the area has not been well studied and its role has not been well
established.17
ANTITOXIN THERAPY
The administration of antitoxin to inactivate toxin already bound to the central nervous system has been shown to be of no benefit.17 Since only
unbound toxin can be neutralized, therapy is aimed at giving intramuscular human tetanus immune globulin (HTIG). In general, HTIG is given as soon
as possible.10,11,15 However, controversy persists regarding the preferred route and dosage of antitoxin. The recommended dosage of HTIG ranges
from 500 to 3000 units. In areas where HTIG is not readily available, equine antitoxin can be administered in doses 1500 to 3000 units intramuscularly.17
The administration on pooled immunoglobulin has also been proposed as an alternative to HTIG. Patients also need to receive active immunization
with three doses of tetanus toxoid, spaced at least 2 weeks apart following recovery from the acute infection. Booster doses should then be given every
10 years throughout life.17
ANTIMICROBIAL THERAPY
Antibiotics are generally given both to treat infection at the injury site and to eliminate continued toxin production. They likely play a minor role in
management of the disease. Metronidazole 500 mg intravenously every 6 hours for 10 days is the antibiotic of choice for C tetani.29 Penicillin G,
tetracycline, erythromycin, clindamycin, and chloramphenicol are also effective, and penicillin has traditionally been the antibiotic of choice.10,29
However, penicillin can aggravate spasms because it is a GABA antagonist and limited evidence has shown patients treated with intravenous penicillin
have prolonged infection with positive cultures lasting up to 16 days. It is also likely that most wounds associated with tetanus are polymicrobial and
harboring β-lactamase–producing bacteria which penicillin would be inactivated. In a study by Ahmadsyah and Salim metronidazole was compared to
procaine penicillin. The patients in the metronidazole group had a lower mortality rate, shorter length of stay, and better response to treatment.29 A
second study by Yen et al compared penicillin and metronidazole showed no difference in mortality.30 For these reasons, penicillin is no longer
recommended for tetanus.17,31
Complications of tetanus are numerous and frequent. The need for long-term endotracheal intubation and ventilatory support coupled with increased
risk of aspiration may result in bacterial pneumonia. Other nosocomial infections also occur, as many patients require a long-term stay in an ICU.
These may include infections of vascular access catheters, catheter-related urosepsis, and infected decubitus ulcers. Protracted immobilization places
the patient at risk for deep venous thrombosis and pulmonary thromboembolism, which is commonly reported as a cause of death.
MINIMIZING MUSCLE SPASM

Historically, reduction of environmental stimuli that could induce muscular spasm (light, noise, touch) was the mainstay of therapy for patients with
tetanus. This remains true in locations where medical resources are limited. Stimulus reduction remains a goal for patients in resource rich
environments, but pharmacotherapy now plays the central role in reducing painful and potentially dangerous muscular spasms.
BENZODIAZEPINES
The most widely used medications for treatment of muscle spasms are the benzodiazepines. Benzodiazepines act indirectly as an agonist in the GABA
pathway by inhibiting an endogenous inhibitor at the GABA receptor.10 While diazepam has been used most extensively, shorter acting
benzodiazepines with more favorable pharmacokinetic profiles (such as midazolam) are also effective. These agents should be titrated to reduce
muscle rigidity, but also provide anxiolysis and an anesthetic effect that may be beneficial. As doses are escalated to achieve the desired effect, the
patient’s ability to protect his or her airway and ventilate may be compromised, and intubation and mechanical ventilation may be required if not
tetanus. This remains true in locations where medical resources are limited. Stimulus reduction remains a goal for patients in resource rich
environments, but pharmacotherapy now plays the central role in reducing painful and potentially dangerous muscular spasms.
Access Provided by:
BENZODIAZEPINES
The most widely used medications for treatment of muscle spasms are the benzodiazepines. Benzodiazepines act indirectly as an agonist in the GABA
pathway by inhibiting an endogenous inhibitor at the GABA receptor.10 While diazepam has been used most extensively, shorter acting
benzodiazepines with more favorable pharmacokinetic profiles (such as midazolam) are also effective. These agents should be titrated to reduce
muscle rigidity, but also provide anxiolysis and an anesthetic effect that may be beneficial. As doses are escalated to achieve the desired effect, the
patient’s ability to protect his or her airway and ventilate may be compromised, and intubation and mechanical ventilation may be required if not
already instituted based on the disease process (see “Supportive Care” below). Daily attempts to decrease the dose will prevent overtreatment and
minimize side effects, but care should be taken to avoid sudden discontinuation, which may precipitate withdrawal.
NEUROMUSCULAR BLOCKING AGENTS
When therapy with sedative medication fails to adequately control muscular spasms, neuromuscular blocking agents should be used. Nondepolarizing
agents such as pancuronium, vecuronium, and atracurium are most commonly administered; however, cisatracurium is preferred given it’s reliable
metabolism even in the setting of kidney or liver dysfunction.4,26,32 Patients treated with neuromuscular blockade must receive adequate sedation and
must be supported with mechanical ventilation. These medications should be stopped daily to assess the patient and whether continued
neuromuscular blockade is necessary. Baclofen has also been utilized and demonstrated to be effective in several studies.33,34 It is most commonly
used via an intrathecal route, and common adverse events include respiratory suppression, coma, and meningitis.
OTHER MEDICATIONS
Propofol has been reported to prevent muscular spasms, and may be used as adjunctive therapy. Magnesium sulfate, which has also been
demonstrated to improve autonomic instability (see “Supportive Care” below), may reduce the requirement for benzodiazepines and neuromuscular
blocking agents.35 Dantrolene has also been described in the treatment of tetanus.32,35,36 Historically, barbiturates and phenothiazines were also
given, but their use has decreased significantly given the widespread availability of the alternative agents described above.
SUPPORTIVE CARE
The high mortality associated with tetanus is attributable to the high acuity but also the prolonged duration of illness. Supportive care begins with the
ABCs: Airway, Breathing, and Circulatory support. However, the potential for prolonged critical illness makes avoidance of complications an essential
goal of therapy.
AIRWAY MANAGEMENT
Intensive care unit management significantly reduces the mortality from tetanus largely by providing airway protection and ventilatory support early in
the disease course.27 Patients with trismus and localized rigidity with no evidence of respiratory compromise do not require prophylactic endotracheal
intubation. However, patients with stridor from laryngospasm, diffuse rigidity, a generalized spasm, severe dysphagia, or any evidence of respiratory
compromise should be intubated. While many patients require intubation for the symptoms of disease, others will require intubation and ventilation
due to escalating doses of benzodiazepines or the initiation of neuromuscular blockade.
The preferred route (nasotracheal vs orotracheal) and method (awake vs anesthetized) of intubation depend on the clinical situation. However, a
clinician with extensive experience in airway management, such as an anesthesiologist, should perform intubation if possible. An emergency
cricothyrotomy tray should also be available at the bedside prior to attempted intubation. If paralysis is required to facilitate intubation, a
nondepolarizing agent may be preferred given the increased risk of hyperkalemia and cardiac arrest associated with depolarizing agents in patients
with tetanus.37 Early tracheostomy may be beneficial given that prolonged airway protection is common and tracheostomy may minimize stimulation
and consequent muscle spasm.
MANAGING AUTONOMIC INSTABILITY
Late presenting autonomic instability characterized by hypertension, hypotension, and arrhythmias has become the most common cause of death in
settings where respiratory support is available. The most rigorously studied medication is magnesium sulfate, which was studied in a randomized
control trial of 256 patients. Treatment with magnesium sulfate intravenously for 7 days led not only to a significant reduction in benzodiazepine and
neuromuscular blocking agent administration, but also to a reduction in mean heart rate and use of verapamil for autonomic instability (14% vs 3%).35
In addition to magnesium sulfate, labetalol is also widely reported as an effective treatment for autonomic hyperactivity. It is preferred overPage
CHAPTER 79: Tetanus, David L. Pitrak; Jason T. Poston; Jodi Galaydick β-blockade
7 / 12
38
alone, which has been associated with sudden cardiac death. Morphine sulfate and other opioid preparations, which are commonly used for
analgesia in critically ill patients, also help treat autonomic dysfunction. Additionally, atropine, clonidine, and an epidural with bupivacaine and
sufentanil have also been used successfully.39-41
MANAGING AUTONOMIC INSTABILITY
Late presenting autonomic instability characterized by hypertension, hypotension, and arrhythmias has become the most common cause of death in
Access Provided by:
settings where respiratory support is available. The most rigorously studied medication is magnesium sulfate, which was studied in a randomized
control trial of 256 patients. Treatment with magnesium sulfate intravenously for 7 days led not only to a significant reduction in benzodiazepine and
neuromuscular blocking agent administration, but also to a reduction in mean heart rate and use of verapamil for autonomic instability (14% vs 3%).35
In addition to magnesium sulfate, labetalol is also widely reported as an effective treatment for autonomic hyperactivity. It is preferred over β-blockade
alone, which has been associated with sudden cardiac death.38 Morphine sulfate and other opioid preparations, which are commonly used for
analgesia in critically ill patients, also help treat autonomic dysfunction. Additionally, atropine, clonidine, and an epidural with bupivacaine and
sufentanil have also been used successfully.39-41
OTHER CONSIDERATIONS
General critical care supportive measures should be implemented in patients with tetanus. These include establishing intravenous access and
insertion of a urinary catheter to monitor urine production and prevent urinary retention. Stress ulcer and venothromboembolic prophylaxis are
indicated in critically ill tetanus patients. Enteral feeding should be provided assuming a normal basal metabolic rate.42
PROGNOSIS
In the developing world mortality due to tetanus exceeds 50%, with most deaths due to acute respiratory failure and mortality is often higher in the
elderly.10,11,14,43 In areas with modern intensive care management, mortality ranges from 10% to 15%.10,44 The leading causes of death in this setting
are cardiovascular collapse and pneumonia. The general quality of critical care support is likely a key determinant of prognosis. In a recent study
tracking mortality from severe tetanus in Brazil over two decades, mortality fell from 36.5% in the early time frame to 18.0% in the later period, likely
related to general advances in ICU management.45
Predicting the severity of tetanus can be based on several factors. An incubation period of <5 days and onset of symptoms in less than 48 hours are
both indicators of poor prognosis. Extremes of age, lack of previous immunity, infections of the uterus, head and neck involvement, and early
autonomic instability are also associated with more severe disease. There has also been a higher mortality associated with intramuscular quinine
injection and intravenous heroin use.1,17,30
Finally, it is important to remember that recovery from tetanus does not guarantee natural immunity.11 Patients should begin their primary
immunization series prior to leaving the hospital; indeed, since passive immunization with HTIG does not interfere with successful active
immunization, the series can begin even before the patient leaves the ICU.
KEY REFERENCES
Ahmadsyah I, Salim A. Treatment of tetanus: an open study to compare the efficacy of procaine penicillin and metronidazole. Br Med J (Clin Res
Ed). September 7, 1985 291(6496):648-650.
Apte NM, Karnad DR. Short report: the spatula test: a simple bedside test to diagnose tetanus. Am J Trop Med Hyg. October 1995;53(4):386-387.
Bleck TP. Tetanus: pathophysiology, management, and prophylaxis. Dis Mon. September 1991;37(9):545-603.
Brook I. Current concepts in the management of Clostridium tetani infection. Expert Rev Anti Infect Ther. June 2008;6(3):327-336.
Buchanan N, Smit L, Cane RD, De Andrade M. Sympathetic overactivity in tetanus: fatality associated with propranolol. Br Med J. July 22
1978;2(6132):254-255.
Farrar JJ, Yen LM, Cook T, et al. Tetanus. J Neurol Neurosurg Psychiatry. September 2000;69(3):292-301.
Gergen PJ, McQuillan GM, Kiely M, Ezzati-Rice TM, Sutter RW, Virella G. A population-based serologic survey of immunity to tetanus in the United
States. N Engl J Med. March 23, 1995;332(12):761-766.
Gibson K, Bonaventure Uwineza J, Kiviri W, Parlow J. Tetanus in developing countries: a case series and review. Can J Anaesth. April
2009;56(4):307-315.
Thwaites CL, Yen LM, Loan HT, et al. Magnesium sulphate for treatment of severe tetanus: a randomised controlled trial. Lancet. October 21,
2006;368(9545):1436-1443.
Trujillo MH, Castillo A, Espana J, Manzo A, Zerpa R. Impact of intensive care management on the prognosis of tetanus. Analysis of 641 cases.
Chest. July 1987;92(1):63-65.
Finally, it is important to remember that recovery from tetanus does not guarantee natural immunity.11 Patients should begin their primary
Access Provided by:
immunization series prior to leaving the hospital; indeed, since passive immunization with HTIG does not interfere with successful active
immunization, the series can begin even before the patient leaves the ICU.
KEY REFERENCES
Ahmadsyah I, Salim A. Treatment of tetanus: an open study to compare the efficacy of procaine penicillin and metronidazole. Br Med J (Clin Res
Ed). September 7, 1985 291(6496):648-650.
Apte NM, Karnad DR. Short report: the spatula test: a simple bedside test to diagnose tetanus. Am J Trop Med Hyg. October 1995;53(4):386-387.
Bleck TP. Tetanus: pathophysiology, management, and prophylaxis. Dis Mon. September 1991;37(9):545-603.
Brook I. Current concepts in the management of Clostridium tetani infection. Expert Rev Anti Infect Ther. June 2008;6(3):327-336.
Buchanan N, Smit L, Cane RD, De Andrade M. Sympathetic overactivity in tetanus: fatality associated with propranolol. Br Med J. July 22
1978;2(6132):254-255.
Farrar JJ, Yen LM, Cook T, et al. Tetanus. J Neurol Neurosurg Psychiatry. September 2000;69(3):292-301.
Gergen PJ, McQuillan GM, Kiely M, Ezzati-Rice TM, Sutter RW, Virella G. A population-based serologic survey of immunity to tetanus in the United
States. N Engl J Med. March 23, 1995;332(12):761-766.
Gibson K, Bonaventure Uwineza J, Kiviri W, Parlow J. Tetanus in developing countries: a case series and review. Can J Anaesth. April
2009;56(4):307-315.
Thwaites CL, Yen LM, Loan HT, et al. Magnesium sulphate for treatment of severe tetanus: a randomised controlled trial. Lancet. October 21,
2006;368(9545):1436-1443.
Trujillo MH, Castillo A, Espana J, Manzo A, Zerpa R. Impact of intensive care management on the prognosis of tetanus. Analysis of 641 cases.
Chest. July 1987;92(1):63-65.
REFERENCES
1. Gibson K, Bonaventure Uwineza J, Kiviri W, Parlow J. Tetanus in developing countries: a case series and review. Can J Anaesth . April
2009;56(4):307-–315.
CrossRef [PubMed: 19296192]
2. Vandelaer J, Birmingham M, Gasse F, Kurian M, Shaw C, Garnier S. Tetanus in developing countries: an update on the Maternal and Neonatal
Tetanus Elimination Initiative. Vaccine . July 28 , 2003;21(24):3442-–3445.
3. Farrar JJ, Yen LM, Cook T, et al. Tetanus. J Neurol Neurosurg Psychiatry . September 2000;69(3):292-–301.
4. Edlich RF, Hill LG, Mahler CA, et al. Management and prevention of tetanus. J Long Term Eff Med Implants . 2003;13(3): 139-–154.
5. Poudel P, Budhathoki S, Manandhar S. Tetanus. Kathmandu Univ Med J (KUMJ) . July-September 2009;7(27):315-–322. [PubMed: 20071883]
6. Gill DM. Bacterial toxins: a table of lethal amounts. Microbiol Rev . March 1982;46(1):86-–94. [PubMed: 6806598]
7. Kaeser HE, Saner A. The effect of tetanus toxin on neuromuscular transmission. Eur Neurol . 1970;3(4):193-–205.
8. Schiavo G, Benfenati F, Poulain B, et al. Tetanus and botulinum-B neurotoxins block neurotransmitter release by proteolytic cleavage of
synaptobrevin. Nature . October 29 1992;359(6398): 832-–835.
9. Bleck TP. Tetanus: pathophysiology, management, and prophylaxis. Dis Mon . September 1991;37(9):545-–603.
6. Gill DM. Bacterial toxins: a table of lethal amounts. Microbiol Rev . March 1982;46(1):86-–94. [PubMed: 6806598]
Access Provided by:
7. Kaeser HE, Saner A. The effect of tetanus toxin on neuromuscular transmission. Eur Neurol . 1970;3(4):193-–205.
8. Schiavo G, Benfenati F, Poulain B, et al. Tetanus and botulinum-B neurotoxins block neurotransmitter release by proteolytic cleavage of
synaptobrevin. Nature . October 29 1992;359(6398): 832-–835.
9. Bleck TP. Tetanus: pathophysiology, management, and prophylaxis. Dis Mon . September 1991;37(9):545-–603.
10. Cook TM, Protheroe RT, Handel JM. Tetanus: a review of the literature. Br J Anaesth . September 2001;87(3):477-–487.
11. Hsu SS, Groleau G. Tetanus in the emergency department: a current review. J Emerg Med . May 2001;20(4):357-–365.
12. Gergen PJ, McQuillan GM, Kiely M, Ezzati-Rice TM, Sutter RW, Virella G. A population-based serologic survey of immunity to tetanus in the United
States. N Engl J Med . March 23 , 1995;332(12):761-–766.
13. Luisto M, Iivanainen M. Tetanus of immunized children. Dev Med Child Neurol . April 1993;35(4):351-–355.
14. Edmondson RS, Flowers MW. Intensive care in tetanus: management, complications, and mortality in 100 cases. Br Med J . May 26 ,
1979;1(6175):1401-–1404.
15. Alfery DD, Rauscher LA. Tetanus: a review. Crit Care Med . April 1979;7(4):176-–181.
16. Cherubin CE. Epidemiology of tetanus in narcotic addicts. N Y State J Med . January 15 , 1970;70(2):267-–271. [PubMed: 5263724]
17. Brook I. Current concepts in the management of Clostridium tetani infection. Expert Rev Anti Infect Ther . June 2008;6(3):327-–336.
18. Schon F, O’Dowd L, White J, Begg N. Tetanus: delay in diagnosis in England and Wales. J Neurol Neurosurg Psychiatry . August 1994;57(8):1006-–
1007.
19. Raman GV, Lee HA. Tetanus and renal failure. Br J Clin Pract . July-August 1984;38(7-8):275-–277. [PubMed: 6477803]
20. Kerr JH, Corbett JL, Prys-Roberts C, Smith AC, Spalding JM. Involvement of the sympathetic nervous system in tetanus. Studies on 82 cases.
Lancet . August 3 , 1968;2(7562):236-–241.
21. Wright DK, Lalloo UG, Nayiager S, Govender P. Autonomic nervous system dysfunction in severe tetanus: current perspectives. Crit Care Med .
April 1989;17(4):371-–375.
22. Jagoda A, Riggio S, Burguieres T. Cephalic tetanus: a case report and review of the literature. Am J Emerg Med . March 1988;6(2):128-–130.
23. Veronesi R. Tetanus, important new concepts. Amsterdam: Excerpta Medica . 1981:1.
24. Ernst ME, Klepser ME, Fouts M, Marangos MN. Tetanus: pathophysiology and management. Ann Pharmacother . December 1997;31(12):1507-–
1513. [PubMed: 9416389]
25. Apte NM, Karnad DR. Short report: the spatula test: a simple bedside test to diagnose tetanus. Am J Trop Med Hyg . October 1995;53(4):386-–387.
[PubMed: 7485691]
22. Jagoda A, Riggio S, Burguieres T. Cephalic tetanus: a case report and review of the literature. Am J Emerg Med . March 1988;6(2):128-–130.
Access Provided by:
23. Veronesi R. Tetanus, important new concepts. Amsterdam: Excerpta Medica . 1981:1.
24. Ernst ME, Klepser ME, Fouts M, Marangos MN. Tetanus: pathophysiology and management. Ann Pharmacother . December 1997;31(12):1507-–
1513. [PubMed: 9416389]
25. Apte NM, Karnad DR. Short report: the spatula test: a simple bedside test to diagnose tetanus. Am J Trop Med Hyg . October 1995;53(4):386-–387.
[PubMed: 7485691]
26. Idoko JA, Amiobonomo AE, Anjorin FI, Oyeyinka GO, Elechi C. Cerebrospinal fluid changes in tetanus: raised proteins and immunoglobulins in
patients with severe disease. Trans R Soc Trop Med Hyg . July-August 1990;84(4):593-–594.
27. Trujillo MH, Castillo A, Espana J, Manzo A, Zerpa R. Impact of intensive care management on the prognosis of tetanus. Analysis of 641 cases.
Chest . July 1987;92(1):63-–65.
28. Percy AS, Kukora JS. The continuing problem of tetanus. Surg Gynecol Obstet . April 1985;160(4):307-–312. [PubMed: 3983794]
29. Ahmadsyah I, Salim A. Treatment of tetanus: an open study to compare the efficacy of procaine penicillin and metronidazole. Br Med J (Clin Res
Ed) . September 7 , 1985;291(6496):648-–650.
30. Yen LM, Dao LM, Day NP, et al. Role of quinine in the high mortality of intramuscular injection tetanus. Lancet . September 17 ,
1994;344(8925):786-–787.
31. Campbell JI, Lam TM, Huynh TL, et al. Microbiologic characterization and antimicrobial susceptibility of Clostridium tetani isolated from wounds
of patients with clinically diagnosed tetanus. Am J Trop Med Hyg . May 2009;80(5):827-–831. [PubMed: 19407132]
32. Checketts MR, White RJ. Avoidance of intermittent positive pressure ventilation in tetanus with dantrolene therapy. Anaesthesia . November
1993;48(11):969-–971.
33. Santos ML, Mota-Miranda A, Alves-Pereira A, Gomes A, Correia J, Marcal N. Intrathecal baclofen for the treatment of tetanus. Clin Infect Dis .
February 1 , 2004;38(3):321-–328.
34. Engrand N, Guerot E, Rouamba A, Vilain G. The efficacy of intrathecal baclofen in severe tetanus. Anesthesiology . June 1999;90(6):1773-–1776.
35. Thwaites CL, Yen LM, Loan HT, et al. Magnesium sulphate for treatment of severe tetanus: a randomised controlled trial. Lancet . October 21 ,
2006;368(9545):1436-–1443.
36. Sternlo JE, Andersen LW. Early treatment of mild tetanus with dantrolene. Intensive Care Med . 1990;16(5):345-–346.
37. Azar I. The response of patients with neuromuscular disorders to muscle relaxants: a review. Anesthesiology . August 1984;61(2):173-–187.
38. Buchanan N, Smit L, Cane RD, De Andrade M. Sympathetic overactivity in tetanus: fatality associated with propranolol. Br Med J . July 22 ,
1978;2(6132):254-–255.
39. Sutton DN, Tremlett MR, Woodcock TE, Nielsen MS. Management of autonomic dysfunction in severe tetanus: the use of magnesium Page
sulphate
11 / and
CHAPTER 79: Tetanus, David L. Pitrak; Jason T. Poston; Jodi Galaydick 12
clonidine. Intensive Care Med . 1990;16(2):75-–80.
38. Buchanan N, Smit L, Cane RD, De Andrade M. Sympathetic overactivity in tetanus: fatality associated with propranolol. Br Med J . July 22 ,
Access Provided by:
1978;2(6132):254-–255.
39. Sutton DN, Tremlett MR, Woodcock TE, Nielsen MS. Management of autonomic dysfunction in severe tetanus: the use of magnesium sulphate and
clonidine. Intensive Care Med . 1990;16(2):75-–80.
40. Bhagwanjee S, Bosenberg AT, Muckart DJ. Management of sympathetic overactivity in tetanus with epidural bupivacaine and sufentanil:
experience with 11 patients. Crit Care Med . September 1999;27(9):1721-–1725.
41. Peduto VA, Pisanu GM, Piga M. Midazolam, propofol, and clonidine for sedation and control of autonomic dysfunction in severe generalized
tetanus. Minerva Anestesiol . April 1993;59(4):171-–178. [PubMed: 8327169]
42. Linton DM, Wells Y, Potgieter PD. Metabolic requirements in tetanus. Crit Care Med . July 1992;20(7):950-–952.
43. Udwadia FE, Lall A, Udwadia ZF, Sekhar M, Vora A. Tetanus and its complications: intensive care and management experience in 150 Indian
patients. Epidemiol Infect . December 1987;99(3):675-–684.
44. Jolliet P, Magnenat JL, Kobel T, Chevrolet JC. Aggressive intensive care treatment of very elderly patients with tetanus is justified. Chest . March
1990;97(3):702-–705.
45. Brauner JS, Vieira SR, Bleck TP. Changes in severe accidental tetanus mortality in the ICU during two decades in Brazil. Intensive Care Med . July
2002;28(7):930-–935.

Key Points: CHAPTER 79: Tetanus

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Key Points: CHAPTER 79: Tetanus

Uploaded by

Copyright:

Available Formats

Universitas

Principles of Critical Care, 4e

CHAPTER 79: Tetanus

David L. Pitrak; Jason T. Poston; Jodi Galaydick

DIAGNOSIS AND LABORATORY TESTING

Differential Diagnosis of Tetanus: Clinical Features

Tetanus Strychnine Neuroleptics SMSa Rabies Meningitis

Muscle rigidity (continuous) + + + − − −

Muscle rigidity (intermittent) − − − + + −

Drugs Used in Medical Management of Tetanus

Medication Indication Dose (Usual)

HTIGa Generalized tetanus 500-3000 IU intramuscular

Metronidazole Toxin production (given in all cases) 500 mg IV/PO q6h

Titrate to serum concentrations of 2-4 mmol/L

Dantrolene Rigidity and spasms 0.5-1.0 mg/kg IV q4-6h

Clonidine Cardiovascular instability 300µg q8h via nasogastric tube

aHuman tetanus immune globulin.

MINIMIZING MUSCLE SPASM

NEUROMUSCULAR BLOCKING AGENTS

MANAGING AUTONOMIC INSTABILITY

You might also like