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Tetanus Author: Patrick B Hinfey, MD; Chief Editor: Burke A Cunha, MD

Background

Tetanus is an illness characterized by an acute onset of hypertonia, painful muscular contractions(usually of the muscles of the jaw and neck), and generalized muscle spasms without other apparentmedical causes. Despite widespread immunization of infants and children in the United States since the1940s, tetanus still occurs in the United States. Currently, tetanus is a severe disease primarily of older adults who are unvaccinated or inadequately vaccinated.

Tetanus may be categorized into the following 4 clinical types:

Generalized

Localized

Cephalic

Neonatal Approximately 50-75% of patients with generalized tetanus present with trismus (―lockjaw‖), which is the

inability to open the mouth secondary to masseter muscle spasm. Nuchal rigidity and dysphagia are alsoearly complaints that cause risus sardonicus, the scornful smile of tetanus, resulting from facial muscleinvolvement.[1] 

 As the disease progresses, patients have generalized muscle rigidity with intermittent reflex spasms inresponse to stimuli (e.g. noise, touch). Tonic contractions cause opisthotonos (ie, flexion and adduction of the arms, clenching of the fists, and extension of the lower extremities). During these episodes, patientshave an intact sensorium and feel severe pain. The spasms can cause fractures, tendon ruptures, andacute respiratory failure.

Patients with localized tetanus present with persistent rigidity in the muscle group close to the injury site.The muscular rigidity is caused by a dysfunction in the interneurons that inhibit the alpha motor neuronsof the affected muscles. No further central nervous system (CNS) involvement occurs in this form, andmortality is very low.

Cephalic tetanus is uncommon and usually occurs after head trauma or otitis media. Patients with thisform present with cranial nerve (CN) palsies. The infection may be localized or may become generalized.

Neonatal tetanus (tetanus neonatorum) is a major cause of infant mortality in underdeveloped countriesbut is rare in the United States. Infection results from umbilical cord contamination during unsanitarydelivery, coupled with a lack of maternal immunization. At the end of the first week of life, infected infantsbecome irritable, feed poorly, and develop rigidity with spasms. Neonatal tetanus has a very poor prognosis.[2, 3] 

 Although at present, tetanus is rare, it has not been eradicated, and early diagnosis and intervention arelifesaving. Prevention is the ultimate management strategy for tetanus.

Pathophysiology

Clostridium tetani, an obligate anaerobic gram-positive bacillus, is the pathogen responsible for tetanus.This bacterium is nonencapsulated and forms spores that are resistant to heat, desiccation, anddisinfectants. The spores are ubiquitous and are found in soil, house dust, animal intestines, and humanfeces. Spores that gain entry can persist in normal tissue for months to years.

To germinate, the spores need tissue with the proper anaerobic conditions.[4]Wounds with low oxidation-reduction potential, such as those with dead or devitalized tissue, a foreign body, or active infection, areideal for germination of the spores and release of toxin. Infection by C tetani results in a benign

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appearance at the portal of entry because of the inability of the organism to evoke an inflammatoryreaction (unless coinfection with other organisms develops).

When the proper anaerobic conditions are present, the spores germinate and produce the following 2toxins:

Tetanolysin – This substance is a hemolysin with no recognized pathologic activity

Tetanospasmin – This toxin is responsible for the clinical manifestations of tetanus[5] ; by weight, it is oneof the most potent toxins known, with an estimated minimum lethal dose of 2.5 ng/kg body weight

Tetanospasmin is synthesized as a 150-kd protein consisting of a 100-kd heavy chain and a 50-kd lightchain joined by a disulfide bond.[6] The heavy chain mediates binding of tetanospasmin to the presynapticmotor neuron and also creates a pore for the entry of the light chain into the cytosol. The light chain is azinc-dependent protease that cleaves synaptobrevin.[7] 

 After the light chain enters the motor neuron, it travels by retrograde axonal transport from thecontaminated site to the spinal cord in 2-14 days. When the toxin reaches the spinal cord, it enters centralinhibitory neurons. The light chain cleaves the protein synaptobrevin, which is integral to the binding of neurotransmitter containing vesicles to the cell membrane.

 As a result, gamma-aminobutyric acid (GABA)-containing and glycine-containing vesicles are notreleased, and there is a loss of inhibitory action on motor and autonomic neurons .[7] With this loss of central inhibition, there is autonomic hyperactivity as well as uncontrolled muscle contractions (spasms) inresponse to normal stimuli such as noises or lights.

Once the toxin becomes fixed to neurons, it cannot be neutralized with antitoxin. Recovery of nervefunction from tetanus toxins requires sprouting of new nerve terminals and formation of new synapses.

Localized tetanus develops when only the nerves supplying the affected muscle are involved.Generalized tetanus develops when the toxin released at the wound spreads through the lymphatics andblood to multiple nerve terminals. The blood-brain barrier prevents direct entry of toxin to the CNS.

Etiology

The etiologic agent of tetanus, C tetani, is an anaerobic, motile, gram-positive rod that forms an oval,colorless, terminal spore and assumes a shape that resembles a tennis racket or a drumstick. The spores

may survive for years in some environments and are resistant to disinfectants and to boiling for 20minutes. Vegetative cells are easily inactivated and are susceptible to several antibiotics.

Tetanus can be acquired outdoors as well as indoors. The source of infection usually is a wound(approximately 65% of cases), which often is minor (eg, from wood or metal splinters or thorns).Frequently, no initial medical treatment is sought. Chronic skin ulcers are the source in approximately 5%of cases, and in the remainder of cases, no obvious source is identified.

Tetanus can also develop as a complication of chronic conditions such as abscesses and gangrene, andit may complicate burns, frostbite, middle ear infections, dental or surgical procedures, abortion,childbirth, and intravenous (IV) or subcutaneous drug use. In addition, possible sources not usuallyassociated with tetanus include intranasal and other foreign bodies and corneal abrasions.

Underimmunization is an important cause of tetanus. Tetanus affects nonimmunized persons, partially

immunized persons, or fully immunized individuals who do not maintain adequate immunity with periodicbooster doses.

Only 12-14% of patients with tetanus in the United States have received a primary series of tetanustoxoid. During 1998-2000, only 6% of all patients with tetanus were known to be current with tetanusimmunization, with no fatal cases reported among this group.[8] Surveillance data from this period revealedthe following:

In 73% of patients with tetanus in the United States, tetanus occurred after an acute injury, includingpuncture wounds (50%), lacerations (33%), and abrasions (9%)

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Stepping on a nail accounted for 32% of the puncture wounds

Tetanus was found to occur in burn victims; in patients receiving intramuscular injections; in personsobtaining a tattoo; and in persons with frostbite, dental infections (eg, periodontal abscesses),penetrating eye injuries, and umbilical stump infections

Other reported risk factors included diabetes, chronic wounds (eg, skin ulcers, abscesses, or gangrene),parenteral drug abuse, and recent surgery (4% of US cases)

During 1998-2000, 12% of patients with tetanus in the United States had diabetes (with mortality, 31%),compared with 2% during 1995-1997; of these patients, 69% had acute injuries and 25% had gangreneor a diabetic ulcer 

The median time interval between surgery and onset of tetanus was 7 days

Tetanus was reported after tooth extractions, root canal therapy, and intraoral soft tissue traumaWorldwide risk factors for neonatal tetanus include the following:

Unvaccinated mother, home delivery, and unhygienic cutting of the umbilical cord increase susceptibilityto tetanus

A history of neonatal tetanus in a previous child is a risk factor for subsequent neonatal tetanus

Potentially infectious substances applied to the umbilical stump (eg, animal dung, mud, or clarifiedbutter) are risk factors for neonates

Immunity from tetanus decreases with advancing age. Serologic testing for immunity has revealed a lowlevel among elderly individuals in the United States. Approximately 50% of adults older than 50 years arenonimmune because they never were vaccinated or do not receive appropriate booster doses. Theprevalence of immunity to tetanus in the United States exceeds 80% for persons aged 6-39 years but isonly 28% for those older than 70 years.

Epidemiology

United States statistics

Because of the widespread use of tetanus immunizations, the reported incidence of tetanus in the UnitedStates has declined substantially since the mid 1940s (see the first image below). The lowest averageannual number of cases for a 3-year period in the United States was 41 cases per year during 1995-1997.

Tetanus Cases in US from 1947-2005. From Tetanus and Tetanus Toxoid:Epidemiology and Prevention of Vaccine-Preventable Diseases. National Immunization Program, Centers for DiseaseControl and Prevention. January 2006. The reported number of tetanus cases and average annual incidence rates in the United States from1998 to 2000, by state, are shown in the image below. An average of 43 cases was reported annually.

Some suggest that only 40% of tetanus cases are reported to the Centers for Disease Control andPrevention (CDC).

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Image from "Number of Tetanus Cases Reported and Average Annual IncidenceRates, by State." Pascual FB, McGinley EL, Zanardi LR, et al: Tetanus surveillance—United States, 1998−2000. MMWRSurveill Summ. 2003 Jun 20;52(3):1-8. The number of tetanus cases reported, the average annual incidence rates, and the survival status of patients, by age group, for the period 1998-2000 are shown in the image below.

Image from "Number of Tetanus Cases Reported, Average Annual Incidence Rates,and Survival Status of Patients, by Age Group." Pascual FB, McGinley EL, Zanardi LR, et al: Tetanus surveillance —UnitedStates, 1998−2000. MMWR Surveill Summ. 2003 Jun 20;52(3):1-8. Of the 130 cases of tetanus reported in the United States from 1998 to 2000, California and Texas hadthe highest reported numbers. All 50 states require that children be vaccinated before being admitted topublic schools. More than 96% of children have received 3 or more diphtheria and tetanus toxoids pluspertussis (DTP) vaccinations by the time they begin school.

Heroin users, particularly those who inject themselves subcutaneously, appear to be at high risk for tetanus. Quinine is used to dilute heroin and may support the growth of  C tetani . The incidence of tetanusin people who use injection drugs increased 7.4% between 1991 and 1997, from 3.6% of all cases in1991-1994 to 11% in 1995-1997. Injection drug users accounted for 15% of US tetanus cases from 1998to 2000 (see the image below). Of the 19 people who used injection drugs and contracted tetanus in

1998-2000, only 1 reported an acute injury.

Image from "Number of Tetanus Cases Reported Among Persons With Diabetes or Injection-Drug Use (IDU), by Age Group." Pascual FB, McGinley EL, Zanardi LR, et al: Tetanus surveillance—United States,1998−2000. MMWR Surveill Summ. 2003 Jun 20;52(3):1-8. From 1995-2000, 81% of cases in the United States were generalized tetanus, 15% were localized, and3% were cephalic; 1 case of neonatal tetanus was reported.

International statistics

C tetani is found worldwide in soil, on inanimate objects, in animal feces, and, occasionally, in humanfeces. Tetanus is predominantly a disease of underdeveloped countries. It is common in areas where soilis cultivated, in rural areas, in warm climates, during summer months, and among males. In countrieswithout a comprehensive immunization program, tetanus predominantly develops in neonates and youngchildren.[9, 10] 

Developed nations have incidences of tetanus similar to those observed in the United States. For instance, only 126 cases of tetanus were reported in England and Wales in 1984-1992.

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 Although tetanus affects all ages, the highest prevalence is in newborns and young people. [11] In 1992, anestimated 578,000 infant deaths were attributed to neonatal tetanus. In 1998, 215,000 deaths occurred,more than 50% of them in Africa. Tetanus is a target disease of the World Health Organization (WHO)Expanded Program on Immunization. Overall, the annual incidence of tetanus is 0.5-1 million cases.WHO estimated that in 2002, there were 213,000 tetanus deaths, 198,000 of them in children younger than 5 years.

Age-related demographics

Neonatal tetanus is rare, occurring most frequently in countries without comprehensive vaccinationprograms.

The risk for development of tetanus and for the most severe form of the disease is highest in the elderlypopulation. In the United States, 59% of cases and 75% of deaths occur in persons aged 60 years or older. From 1980 through 2000, 70% of reported cases of tetanus in the United States were amongpersons aged 40 years or older. Of all these patients, 36% are older than 59 years and only 9% areyounger than 20 years.

Sex-related demographics

Tetanus affects both sexes. No overall gender predilection has been reported, except to the extent that

males may have more soil exposure in some cultures. In the United States from 1998 to 2000, theincidence of tetanus was 2.8 times higher in males aged 59 years and younger than in females in thesame age range.

 A difference in the levels of tetanus immunity exists between the sexes. Overall, men are believed to bebetter protected than women, perhaps because of additional vaccinations administered during militaryservice or professional activities. In developing countries, women have an increased immunity wheretetanus toxoid is administered to women of childbearing age to prevent neonatal tetanus.

Race-related demographics

Tetanus affects all races. From 1998 to 2000, the incidence of tetanus in the United States was highestamong Hispanics (0.38 cases per million population), followed by whites (0.13 cases per millionpopulation) and then by African Americans (0.12 cases per million population).[8] 

Prognosis

The prognosis is dependent on incubation period, the time from spore inoculation to first symptom, andthe time from first symptom to first tetanic spasm. The following statements typically hold true:

In general, shorter intervals indicate more severe tetanus and a poorer prognosis

Patients usually survive tetanus and return to their predisease state of health

Recovery is slow and usually occurs over 2-4 months

Some patients remain hypotonic

Clinical tetanus does not produce a state of immunity; therefore, patients who survive the diseaserequire active immunization with tetanus toxoid to prevent a recurrence

 A rating scale has been developed for assessing the severity of tetanus and determining theprognosis.[12] On this scale, 1 point is given for each of the following:

Incubation period shorter than 7 days

Period of onset shorter than 48 hours

Tetanus acquired from burns, surgical wounds, compound fractures, septic abortion, umbilical stump, or intramuscular injection

Narcotic addiction

Generalized tetanus

Temperature higher than 104°F (40°C)

Tachycardia exceeding 120 beats/min (150 beats/min in neonates)

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The total score indicates disease severity and prognosis as follows:

0 or 1 – Mild tetanus; mortality below 10%

2 or 3 – Moderate tetanus; mortality of 10-20%

4 – Severe tetanus; mortality of 20-40%

5 or 6 – Very severe tetanus; mortality above 50%Cephalic tetanus is always severe or very severe. Neonatal tetanus is always very severe.

The case-fatality ratio in the United States was 91% in 1947,[8] 21-31% from 1982 to 1990, 11% from 1995to 1997, and 18% from 1998 to 2000. Current statistics indicate that mortality in mild and moderatetetanus is approximately 6%; for severe tetanus, it may be as high as 60%. Mortality in the United Statesresulting from generalized tetanus is 30% overall, 52% in patients older than 60 years, and 13% inpatients younger than 60 years.

Mortality is substantially higher for people older than 60 years (40%) than for those aged 20-59 years(8%). From 1998 to 2000, 75% of the deaths in the United States were in patients older than 60 years . [8] Inaddition, mortality is notably higher for people who require mechanical ventilation (30%) than for thosewho do not (4%).

High mortalities are associated with the following:

Short incubation period

Early onset of convulsions

Delay in treatment

Contaminated lesions of the head and the face

Neonatal tetanusClinical tetanus is less severe among patients who have received a primary series of tetanus toxoidsometime during their life than among patients who are inadequately vaccinated or unvaccinated.Mortality in the United States is 6% for individuals who had previously received 1-2 doses of tetanustoxoid, compared with 15% for individuals who were unvaccinated.

Residual neurologic sequelae are uncommon. Mortality usually results from autonomic dysfunction (eg,extremes in blood pressure, dysrhythmias, or cardiac arrest).

Patient EducationThe importance of childhood immunizations and boosters must be stressed. Midwives and birthattendants in developing and underdeveloped countries should be given training in aseptic birthingprocedures. The basics of wound care and first aid should be widely taught. Early recognition of symptoms and signs of localized tetanus and timely access to medical care are essential.

For patient education resources, see the Infections Center , Public Health Center , and Children’s HealthCenter , as well as Tetanus ,Immunization Schedule, Adults,and Immunization Schedule, Children. 

History

Most cases of tetanus in the United States occur in patients with a history of underimmunization, either because they were never vaccinated or because they completed a primary series but have not had abooster in the preceding 10 years. From 1995 to 1997, 54% of the reported cases in the United Stateshad an unknown tetanus vaccination history, 22% had no known previous tetanus vaccination, 9% had 1previous dose, 3% had 2, 3% had 3, and 9% had 4 or more. Persons who inject drugs also constitute ahigh-risk group.

The median incubation period is 7 days, and for most cases (73%), incubation ranges from 4 to 14 days.The incubation period is shorter than 4 days in 15% of cases and longer than 14 days in 12% of cases.Patients with clinical manifestations occurring within 1 week of an injury have more severe clinicalcourses.

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Patients sometimes remember an injury, but often, the injury goes unnoticed. Patients may report a sorethroat with dysphagia (early sign). The initial manifestation may be local tetanus, in which the rigidityaffects only 1 limb or area of the body where the clostridium-containing wound is located. Patients withgeneralized tetanus present with trismus (ie, lockjaw) in 75% of cases. Other presenting complaintsinclude stiffness, neck rigidity, restlessness, and reflex spasms.

Subsequently, muscle rigidity becomes the major manifestation. Muscle rigidity spreads in a descending

pattern from the jaw and facial muscles over the next 24-48 hours to the extensor muscles of the limbs.

Dysphagia occurs in moderately severe tetanus as a consequence of pharyngeal muscle spasms, andonset is usually insidious over several days. Reflex spasms develop in most patients and can be triggeredby minimal external stimuli such as noise, light, or touch. The spasms last seconds to minutes; becomemore intense; increase in frequency with disease progression; and can cause apnea, fractures,dislocations, and rhabdomyolysis. Laryngeal spasms can occur at any time and can result in asphyxia.

Other symptoms include elevated temperature, sweating, elevated blood pressure, and episodic rapidheart rate.

Sustained contraction of facial musculature produces a sneering grin expression known as risussardonicus.

Generalized tetanus

Generalized tetanus is the most commonly found form of tetanus in the United States, accounting for 85-90% of cases. The extent of the trauma varies from trivial injury to contaminated crush injury. Theincubation period is 7-21 days, largely depending on the distance of the injury site from the centralnervous system (CNS).

Trismus is the presenting symptom in 75% of cases; a dentist or an oral surgeon often initially sees thepatient. Other early features include irritability, restlessness, diaphoresis, and dysphagia withhydrophobia, drooling, and spasm of the back muscles. These early manifestations reflect involvement of bulbar and paraspinal muscles, possibly because these structures are innervated by the shortest axons.The condition may progress for 2 weeks despite antitoxin therapy because of the time needed for intra-axonal antitoxin transport.

Localized tetanus

Localized tetanus involves an extremity with a contaminated wound and is of highly variable severity. It isan unusual form of tetanus, and the prognosis for survival is excellent.

Cephalic tetanus

Cephalic tetanus generally follows head injury or develops with infection of the middle ear. Symptomsconsist of isolated or combined dysfunction of the cranial motor nerves (most frequently CN VII). Cephalictetanus may remain localized or may progress to generalized tetanus. It is an unusual form of tetanuswith an incubation period of 1-2 days. The prognosis for survival is usually poor.

Neonatal tetanus

Neonatal tetanus (tetanus neonatorum) is generalized tetanus that results from infection of a neonate. It

primarily occurs in underdeveloped countries and accounts for as many as one half of all neonataldeaths. The usual cause is the use of contaminated materials to sever or dress the umbilical cord innewborns of unimmunized mothers.

The usual incubation period after birth is 3-10 days, which explains why this form of tetanus is sometimesreferred to as the disease of the seventh day. The newborn usually exhibits irritability, poor feeding,rigidity, facial grimacing, and severe spasms with touch. Mortality exceeds 70%.

Physical Examination

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Common first signs of tetanus are headache and muscular stiffness in the jaw (ie, lockjaw), followed byneck stiffness, difficulty swallowing, rigidity of abdominal muscles, spasms, and sweating. Patients oftenare afebrile. Stimulation of the posterior pharyngeal wall may elicit reflex spasms of the masseter musclesthat cause patients to bite down as opposed to gag (spatula test) .[13] 

Severe tetanus results in opisthotonos, flexion of the arms, extension of the legs, periods of apnearesulting from spasm of the intercostal muscles and diaphragm, and rigidity of the abdominal wall. Late in

the disease, autonomic dysfunction develops, with hypertension and tachycardia alternating withhypotension and bradycardia; cardiac arrest may occur.

The lower extremity is the site of antecedent acute injury in 52% of patients, the upper extremity is thesite of antecedent injury in 34% of patients, and the head or the trunk is the site of antecedent injury in5% of patients.

Tetanic seizures may occur. Their presence portends a poor prognosis, and their frequency and severityare related to the severity of the disease. These seizures resemble epileptic seizures, with the presenceof a sudden burst of tonic contractions. However, the patient does not lose consciousness and usuallyexperiences severe pain. Seizures frequently occur in the muscle groups causing opisthotonos, flexionand abduction of the arms, clenching of the fists against the thorax, and extension of the lower extremities.

Patients with tetanus may present with abdominal tenderness and guarding, mimicking an acuteabdomen. Exploratory laparotomies have been performed before the correct diagnosis was apparent.

Tetanospasmin has a disinhibitory effect on the autonomic nervous system (ANS). ANS dysfunctionbecomes progressively evident as the level of toxin in the CNS increases. ANS disturbances (eg,sweating, fluctuating blood pressure, episodic tachydysrhythmia, and increased catecholamine release)are observed. Drugs with beta-blocker effects have been used to control the cardiovascular manifestations of ANS instability, but they also have been associated with increased risk of sudden death.

Generalized tetanus

Sustained trismus may result in the characteristic sardonic smile (risus sardonicus) and persistent spasmof the back musculature may cause opisthotonos. Waves of opisthotonos are highly characteristic of thedisease. With progression, the extremities become involved in episodes of painful flexion and adduction

of the arms, clenched fists, and extension of the legs.

Noise or tactile stimuli may precipitate spasms and generalized convulsions. Involvement of the ANS mayresult in severe arrhythmias, oscillation of blood pressure, profound diaphoresis,hyperthermia, rhabdomyolysis, laryngeal spasm, and urinary retention. In most cases, the patient remainslucid.

Localized tetanus

In mild cases of localized tetanus, patients may have weakness of the involved extremity, presumablydue to partial immunity; in more severe cases, they may have intense, painful spasms of the group of muscles in close proximity to the site of injury. This disorder may persist for several weeks but is usuallyself-limiting; however, more severe cases tend to progress to generalized tetanus.

Cephalic tetanus

Cephalic tetanus is a rare form of the disease that is usually secondary to chronic otitis media or headtrauma. It is characterized by variable CN palsies, most frequently involving CN VII. Ophthalmoplegictetanus is a variant that develops after penetrating eye injuries and results in CN III palsies and ptosis.

Rapid progression is typical. Cephalic tetanus may remain localized or, especially if left untreated,progress to generalized tetanus.

Neonatal tetanus

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Neonatal tetanus presents with an inability to suck 3-10 days after birth. Presenting symptoms includeirritability, excessive crying, grimaces, intense rigidity, and opisthotonos. In general, the physicalexamination findings are similar to those of generalized tetanus.

Complications

Complications include spasm of the vocal cords and spasm of the respiratory muscles that cause

interference with breathing.[14]

Patients experience severe pain during each spasm. During the spasm, theupper airway can be obstructed, or the diaphragm may participate in the general muscular contraction.

Sympathetic overactivity is the major cause of tetanus-related death in the intensive care unit (ICU).Sympathetic hyperactivity usually is treated with labetalol at 0.25-1 mg/min as needed for blood pressurecontrol or with morphine at 0.5-1 mg/kg/h by continuous infusion.

Neonatal tetanus follows infection of the umbilical stump, most commonly resulting from a failed aseptictechnique in a mother who is inadequately immunized. Mortality for neonatal tetanus exceeds 90%, anddevelopmental delays are common among survivors.

Before 1954, asphyxia from tetanic spasms was the usual cause of death in patients with tetanus.However, with the advent of neuromuscular blockers, mechanical ventilation, and pharmacologic controlof spasms, sudden cardiac death has become the leading cause of death. Sudden cardiac death has

been attributed to excessive catecholamine productions or the direct action of tetanospasmin or tetanolysin on the myocardium.

Nosocomial infections are common when hospitalization is prolonged. Secondary infections may includesepsis from decubitus ulcers, hospital-acquired pneumonia, and catheter-related infections. Pulmonaryembolism is a particular problem in drug users and elderly patients.

Further complications include the following:

Long bone fractures

Glenohumeral joint and temporomandibular joint dislocations

Hypoxic injury and aspiration pneumonia

Clotting in the blood vessels of the lung

Adverse effects of autonomic instability,[15] including hypertension and cardiac dysrhythmias

Paralytic ileus, pressure sores, and urinary retention

Malnutrition and stress ulcers

Coma, nerve palsies, neuropathies, psychological aftereffects, and flexion contractures

Diagnostic ConsiderationsStrychnine poisoning is the only condition that truly mimics tetanus. However, a number of conditions (eg,dental or other local infections, hysteria, neoplasms, and encephalitis) may cause trismus, and thesemust be differentiated these conditions from tetanus. The following conditions listed do not causemanifestations of tetanus other than trismus:

Strychnine poisoning

Dental infections Local infections

Hysteria

Neoplasms

Malignant hyperthermia

Stimulant use

Intraoral disease

Odontogenic infections

Globus hystericus

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Hepatic encephalopathy

Acute abdomen

Intracranial hemorrhage

Dystonic drug reactions (eg, phenothiazines, metoclopramide)

Acute abdominal emergencies

Seizure disorder (partial or generalized)

Serotonin syndrome Stroke, ischemic (cephalic tetanus)

Differential Diagnoses   Arthrogryposis 

  Conversion Disorder in Emergency Medicine 

  Dystonia, Tardive 

  Emergency Treatment of Rabies 

  Emergent Management of Subarachnoid Hemorrhage 

  Encephalitis 

Hemorrhagic Stroke

  Mandible Dislocation 

  Medication-Induced Dystonic Reactions 

  Neuroleptic Malignant Syndrome in Emergency Medicine   Pediatric Aseptic Meningitis 

  Pediatric Bacterial Meningitis 

  Peritonsillar Abscess in Emergency Medicine 

  Widow Spider Envenomation 

Laboratory Studies

No specific laboratory tests exist for determining the diagnosis of tetanus. The diagnosis is clinicallybased on the presence of trismus, dysphagia, generalized muscular rigidity, spasm, or combinationsthereof. Although the laboratory findings are not diagnostically valuable, they may help exclude strychninepoisoning.

Blood counts and blood chemical findings are unremarkable. Laboratory studies may demonstrate amoderate peripheral leukocytosis.

 A lumbar puncture is not necessary. Cerebrospinal fluid (CSF) is normal, except for an increased openingpressure, especially during spasms.

Serum muscle enzyme levels (eg, creatine kinase, aldolase) may be elevated.

 An assay for antitoxin levels is not readily available. However, a serum antitoxin level of 0.01 IU/mL or higher is generally considered protective, making the diagnosis of tetanus less likely (though rare caseshave been reported to occur despite the presence of protective antitoxin levels).

Wounds should be cultured in cases of suspected tetanus. It must be kept in mind, however, that C 

tetani sometimes can be cultured from the wounds of patients who do not have tetanus and frequentlycannot be cultured from the wounds of patients who do.

Spatula Test

The spatula test is a simple diagnostic bedside test that involves touching the oropharynx with a spatulaor tongue blade. In normal circumstances, it elicits a gag reflex, and the patient tries to expel the spatula(ie, a negative test result). If tetanus is present, patients develop a reflex spasm of the masseters and bitethe spatula (ie, a positive test result).

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In 400 patients, this test had a sensitivity of 94% and a specificity of 100% .[13] No adverse sequelae (eg,laryngeal spasm) were reported.

Other Studies

Electromyography (EMG) may show continuous discharge of motor subunits and shortening or absenceof the silent interval normally observed after an action potential.

Nonspecific changes may be evident on electrocardiography (ECG).

Imaging studies of the head and spine reveal no abnormalities.

 Approach Considerations

The goals of treatment in patients with tetanus include the following:

Initiating supportive therapy

Debriding the wound to eradicate spores and alter conditions for germination

Stopping the production of toxin within the wound

Neutralizing unbound toxin Controlling disease manifestations

Managing complicationsPatients should be admitted to an intensive care unit (ICU). If the facility does not have an ICU, thepatient should be transferred by critical care ambulance.

Passive immunization with human tetanus immune globulin (TIG) shortens the course of tetanus and maylessen its severity. A dose of 500 U may be as effective as larger doses. Therapeutic TIG (3,000-6,000units as 1 dose) has also been recommended for generalized tetanus.[16] Other treatment measuresinclude ventilatory support, high-calorie nutritional support, and pharmacologic agents that treat reflexmuscle spasms, rigidity, tetanic seizures and infections.

Initial Supportive Therapy and Wound Care

Patients should be admitted to the ICU. Because of the risk of reflex spasms, a dark and quietenvironment should be maintained. Unnecessary procedures and manipulations should be avoided.

Prophylactic intubation should be seriously considered in all patients with moderate-to-severe clinicalmanifestations. Intubation and ventilation are required in 67% of patients. Attempting endotrachealintubation may induce severe reflex laryngospasm; preparations must be made for emergency surgicalairway control.Rapid sequence intubation techniques (eg, with succinylcholine) are recommended toavoid this complication.

Tracheostomy should be performed in patients requiring intubation for more than 10 days. Tracheostomyhas also been recommended after onset of the first generalized seizure.

The possibility of developing tetanus directly correlates with the characteristics of the wound. Recentlyacquired wounds with sharp edges that are well vascularized and not contaminated are least likely to

develop tetanus. All other wounds are considered predisposed to tetanus. The most susceptible woundsare those that are grossly contaminated or that are caused by blunt trauma or bites. Wounds should beexplored, carefully cleansed, and properly debrided.

In many cases, the wound responsible for tetanus is clear at presentation, in which case surgicaldebridement offers no significant benefit. If debridement is indicated, it should be undertaken after thepatient has been stabilized. The current recommendation is to excise at least 2 cm of normal viable-appearing tissue around the wound margins. Abscesses should be incised and drained. Because of therisk of releasing tetanospasmin into the bloodstream, any wound manipulation should be delayed untilseveral hours after administration of antitoxin.

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Pharmacologic Therapy

Elimination of toxin production

 Antimicrobials are used to decrease the number of vegetative forms of C tetani (the toxin source) in thewound. For years, penicillin G was used widely for this purpose, but it is not the current drug of choice.Metronidazole (eg, 0.5 g every 6 hours) has comparable or better antimicrobial activity, and penicillin is a

known antagonist of gamma-aminobutyric acid (GABA), as is tetanus toxin. Metronidazole may also beassociated with lower mortality.[17] 

Other antimicrobials that have been used are clindamycin, erythromycin, tetracycline, and vancomycin.

Neutralization of unbound toxin

Tetanus immune globulin (TIG) is recommended for treatment of tetanus. It should be kept in mind thatTIG can only help remove unbound tetanus toxin; it cannot affect toxin bound to nerve endings. A singleintramuscular (IM) dose of 3000-5000 units is generally recommended for children and adults, with part of the dose infiltrated around the wound if it can be identified.

The World Health Organization recommends TIG 500 units by IM injection or intravenously (IV)—depending on the available preparation—as soon as possible; in addition, 0.5 mL of an age-appropriatetetanus toxoid−containing vaccine (Td, Tdap, DT, DPT, DTaP, or tetanus toxoid, depending on age or allergies), should be administered by IM injection at a separate site.

Tetanus disease does not induce immunity; patients without a history of primary tetanus toxoidvaccination should receive a second dose 1-2 months after the first dose and a third dose 6-12 monthslater.

Control of disease manifestations

Benzodiazepines have emerged as the mainstay of symptomatic therapy for tetanus. Diazepam is themost frequently studied and used drug; it reduces anxiety, produces sedation, and relaxes muscles.Lorazepam is an effective alternative. High dosages of either may be required (up to 600 mg/day).

To prevent spasms that last longer than 5-10 seconds, administer diazepam IV, typically 10-40 mg every1-8 hours. Vecuronium (by continuous infusion) or pancuronium (by intermittent injection) are adequate

alternatives. Midazolam 5-15 mg/hr IV has been used. If the spasms are not controlled withbenzodiazepines, long-term neuromuscular blockade is required.

Phenobarbital is another anticonvulsant that may be used to prolong the effects of diazepam.Phenobarbital is also used to treat severe muscle spasms and provide sedation when neuromuscular blocking agents are used. Other agents used for spasm control include baclofen, dantrolene, short-actingbarbiturates, and chlorpromazine. Propofol has been suggested for sedation.[18] 

Intrathecal (IT) baclofen, a centrally acting muscle relaxant, has been used experimentally to weanpatients off the ventilator and to stop diazepam infusion. IT baclofen is 600 times more potent than oralbaclofen. Repeated IT injections have been efficacious in limiting duration of artificial ventilation or preventing intubation. Case reports and small case series have suggested that IT baclofen is effective incontrolling muscle rigidity,[19, 20] though others have questioned this.[21] 

The effects of baclofen begin within 1-2 hours and persist for 12-48 hours. The half-life elimination of baclofen in cerebrospinal fluid (CSF) ranges from 0.9 to 5 hours. After lumbar IT administration, thecervical-to-lumbar concentration ratio is 1:4. The major adverse effect is a depressed level of consciousness and respiratory compromise.

Management of complications

Specific therapy for autonomic system complications and control of spasms should beinitiated.[22] Magnesium sulfate can be used alone or in combination with benzodiazepines for this

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purpose. It should be given IV in a loading dose of 5 g (or 75 mg/kg), followed by continuous infusion at arate of 2-3 g/h until spasm control is achieved.[5] 

The patellar reflex should be monitored; areflexia (absence of the patellar reflex) occurs at the upper endof the therapeutic range (4 mmol/L). If areflexia develops, the dosage should be reduced. An infusion of magnesium sulfate does not reduce the need for mechanical ventilation in adults with severe tetanus, butit does reduce the requirement for other drugs to control muscle spasms and cardiovascular instability.[23] 

In a meta-analysis of 3 controlled trials that compared magnesium sulfate with placebo or diazepam for the treatment of patients with tetanus, magnesium sulfate did not reduce mortality or relative risk.[24] Theinvestigators concluded that further controlled trials were necessary to evaluate the potential effect of thistherapy on autonomic dysfunction, spasms, length of ICU and hospital stay, and requirement for mechanical ventilation.

Morphine is an option. In the past, beta blockers were used, but they can cause hypotension and suddendeath; only esmolol is currently recommended.

Hypotension requires fluid replacement and dopamine or norepinephrine administration. Parasympatheticoveractivity is rare, but if bradycardia is sustained, a pacemaker may be needed. Clinical tetanus doesnot induce immunity against future attacks; therefore, all patients should be fully immunized with tetanustoxoid during the convalescent period.

Diet and Activity

Maintenance of adequate nutrition is extremely important. Because of the risk of aspiration, patientsshould not be given any food by mouth. Nutrition should be provided to seriously ill patients vianasoduodenal tubes, gastrostomy tube feedings, or parenteral hyperalimentation. Consultation with anutritionist is helpful.

The patient should be on bed rest in a room that can be kept dark and quiet. Even the slightest physicalstimulus can cause a cycle of spasms.

Consultations

 An intensive care medicine specialist should be the primary physician coordinating the patient’s care.

Consultations with the following specialists may be appropriate as the clinical situation dictates:

Infectious diseases

Toxicology - To help confirm or exclude strychnine toxicity as the cause of symptoms

Neurology - To confirm or exclude seizures as a possible etiology of symptoms

Pulmonary medicine – To be consulted after admission to the ICU for patients with severe respiratorysymptoms or those requiring mechanical ventilation

Anesthesiology – To be consulted after admission to the ICU if intrathecal baclofen is to beadministered

Prevention

Prevention of tetanus is accomplished through vaccination with DTP or DTaP at the ages of 2 months, 4months, 6 months, 12-18 months, and 4-6 years. In 2006, the Advisory Committee on ImmunizationPractices (ACIP) issued recommendations for the use of Tdap.[25] 

For persons aged 7 years or older who have never been vaccinated against tetanus,  diphtheria, or  pertussis (ie, have never received any dose of DTP/DTaP/DT or Td), administer a series of 3vaccinations containing tetanus and diphtheria toxoids. The preferred schedule is a single dose of Tdap,followed by a dose of Td at least 4 weeks after Tdap and another dose of Td 6-12 months later. However,Tdap can be given once as a substitute for Td in the 3-dose primary series .[25] 

 Alternatively, in situations where the adult probably received vaccination against tetanus and diphtheriabut cannot produce a record, vaccine providers may consider serologic testing for antibodies to tetanusand diphtheria toxin with the aim of avoiding unnecessary vaccination. If tetanus and diphtheria antitoxin

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levels are each higher than 0.1 IU/mL, previous vaccination with tetanus and diphtheria toxoid vaccine ispresumed, and a single dose of Tdap is indicated.[25] 

 Adults who received other incomplete vaccination series against tetanus and diphtheria should bevaccinated with Td to complete a 3-dose primary series of tetanus and diphtheria toxoid-containingvaccines. One dose of Tdap should be used in place of Td if the patient has never received a dose of Tdap.

Pregnancy is not a contraindication to the use of Tdap in the second and third trimester.

Secondary prevention of tetanus is accomplished after exposure through appropriate wound cleansingand debridement and the administration of tetanus toxoid (Td, Tdap, DT, DPT, or DTaP, as indicated) andTIG, when indicated. Pediatric formulations (DT and DTaP) include about the same amount of tetanustoxoid as adult Td does but contain 3-4 times as much diphtheria toxoid.

The following wounds should be considered prone to tetanus:

Wounds that have been present for longer than 6 hours

Deep (>1 cm) wounds

Grossly contaminated wounds

Wounds that are exposed to saliva or feces, stellate, or ischemic or infected (including abscesses

Avulsions, punctures, or crush injuriesIt is not necessary to wait the typical 10 years to get the adult Tdap dose after the last Td dose. Aninterval as short as 2 years is suggested to reduce the likelihood of increased reactogenicity, and evenshorter intervals may be appropriate if the patient is at high risk for pertussis, has close contact withinfants, or may not be able to receive another vaccination. Providers should know that shorter intervalsare not contraindicated, that accumulating data reinforce safety of the vaccine, and that there are noconcerns about immunogenicity with the decreased interval.

Patients with tetanus-prone wounds should receive Td or DPT IM if they are younger than 7 years and if ithas been more than 5 years since their last dose of tetanus toxoid. Patients who have previously receivedfewer than 3 doses of tetanus toxoid and patients aged 60 years or older should receive TIG 250-500units IM, always in the opposite extremity to the toxoid.

 Adults without tetanus-prone wounds should be given Td or Tdap if they have previously have receivedfewer than 3 doses of tetanus toxoid or if more than 10 years have passed since their last dose. Tdap ispreferred to Td for adults vaccinated more than 5 years earlier who require tetanus toxoid as part of wound management and who have not previously received Tdap. Tdap is indicated only once; therefore,for adults previously vaccinated with Tdap (after age 7 years), Td should be used if a tetanustoxoid−containing vaccine is indicated for wound care.  

It is important to review the immunization status of all patients who present to an emergency departmentfor any care (regardless of chief complaint). Immunizations should be administered if a lapse of more than10 years has occurred since the last tetanus booster. If a patient does not remember or cannot give ahistory of immunization, an immunochromatographic dipstick test may be appropriate and cost-effectivefor determining tetanus immunity in this setting, though further study is needed to determine theapplicability of this approach.[26] 

The ACIP recommends vaccination at primary care visits for adolescents aged 11-12 years and for adultsaged 50 years, review of vaccination histories, and updating of tetanus vaccination status. This is inaddition to recommending booster doses of tetanus and diphtheria toxoid every 10 years.

In 2011 and 2012, the ACIP issued updated recommendations for the use of Tdap .[27, 28, 29] Key pointsincluded the following:

Timing of Tdap after Td – Pertussis vaccination, when indicated, should not be delayed; Tdap should beadministered regardless of the interval since the last tetanus- or diphtheria toxoid−containing vaccine 

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Tdap use in adults – All adults aged 19 years and older who have not yet received a dose of Tdapshould receive a single dose, regardless of the interval since the last tetanus- or diphtheriatoxoid−containing vaccine, then should continue to receive Td for routine booster immunization 

Wound management for adults – A tetanus toxoid –containing vaccine may be recommended as part of standard wound management in adults aged 19 years and older if it has been at least 5 years since lastreceipt of Td; if a tetanus booster is indicated, Tdap is preferred to Td for wound management in adults

aged 19 years and older who have not received Tdap previously Adults aged 65 years and older  – Those who have or anticipate having close contact with an infant

younger than 12 months and have not received Tdap should receive a single dose of Tdap; others maybe given a single dose of Tdap instead of Td if they have not previously received Tdap; Tdap can beadministered regardless of the interval since the last tetanus- or diphtheria toxoid−containing vaccine;Td is then given for routine booster immunization

When feasible, Boostrix should be used for adults aged 65 years and older; however, either of the 2available vaccines administered to a person 65 years or older is immunogenic and would provideprotection, and a dose of either may be considered valid

Pregnant women who have not previously received Tdap  – Tdap should be administered duringpregnancy, preferably during the third or late second trimester (after 20 weeks’ gestation); if not givenduring pregnancy, it should be given immediately post partum; if a booster vaccination is indicatedduring pregnancy, it should be given according to the same time frame

Pregnant women with unknown or incomplete tetanus vaccination – To ensure protection, 3vaccinations containing tetanus and reduced diphtheria toxoids should be given, ideally at 0 weeks, 4weeks, and 6-12 months; Tdap should replace 1 dose of Td, preferably during the third or late secondtrimester 

Undervaccinated children aged 7-10 years – If there is no contraindication to pertussis vaccine, a singledose of Tdap is indicated; if additional doses of tetanus and diphtheria toxoid--containing vaccines areneeded, vaccinated should proceed according to catch-up guidance, with Tdap preferred as the firstdose

Worldwide, neonatal tetanus may be eliminated by increasing immunizations in women of childbearingage, especially pregnant women, and by improving maternity care. Administration of tetanus toxoid twiceduring pregnancy (4-6 weeks apart, preferably in the last 2 trimesters) and again at least 4 weeks beforedelivery is recommended for previously unimmunized gravid women. Maternal antitetanus antibodies arepassed to the fetus, and this passive immunity is effective for many months.

Medication Summary

The goals of pharmacotherapy are to stop toxin production within the wound, to neutralize unbound toxin,and to control disease manifestations. Drugs used to treat muscle spasm, rigidity, and tetanic seizuresinclude sedative-hypnotic agents, general anesthetics, centrally acting muscle relaxants, andneuromuscular blocking agents. Antibiotics are used to prevent multiplication of Clostridium tetani, thushalting production and release of toxins. Antitoxins are given to neutralize unbound toxin.

 Antibiotics, Other 

Class Summary

These agents are used to eradicate clostridial organisms in the wound, which may produce tetanus toxin.They are administered to patients with clinical tetanus; however, their efficacy is questioned. Penicillin Gwas long considered the drug of choice, but some now consider metronidazole to be superior in thissetting. Tetracycline is an alternative for patients who are allergic to penicillin or metronidazole. Largedoses of antibiotics are recommended to favor diffusion into devitalized tissue.

Metronidazole (Flagyl) 

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Metronidazole is active against various anaerobic bacteria and protozoa. It appears to be absorbed intocells, and intermediate-metabolized compounds that are formed bind DNA and inhibit protein synthesis,causing cell death. A 10- to 14-day course of treatment is recommended. Some consider it the drug of choice in tetanus because of its safety profile, efficient penetration into wounds and abscesses, andnegligible central nervous system (CNS) excitation.

Penicillin G (Pfizerpen) 

Penicillin G is a bactericidal antibiotic that binds to and inhibits penicillin-binding proteins, which aretranspeptidases that cross-link peptidoglycans, the final step in bacterial cell wall synthesis. Inhibition of cell wall synthesis and autolytic enzyme activation are responsible for its bactericidal action on dividingbacteria.

 A 10- to 14-day course of treatment is recommended. Large intravenous (IV) doses of penicillin maycause hemolytic anemia and neurotoxicity. Cardiac arrest has been reported in patients receivingmassive doses of penicillin G potassium. Patients with renal failure are particularly at risk.

Doxycycline (Vibramycin, Doryx, Doxy 100, Adoxa, Monodox) 

Doxycycline inhibits protein synthesis and thus bacterial growth by binding to 30S and possibly 50Sribosomal subunits of susceptible bacteria. A 10- to 14-day course of treatment is recommended.

Erythromycin (E.E.S., EryPed, Erythrocin, Ery-Tab) 

Erythromycin is a bacteriostatic agent that inhibits protein synthesis by binding to the 50S subunit of bacterial ribosomes. It is not the drug of choice for tetanus but may be used when the drugs of choicecannot be administered for some reason.

Clindamycin (Cleocin) 

Clindamycin is a bacteriostatic agent that binds to the 50S ribosomal subunit. It is not the drug of choicefor tetanus and may be used only if the drugs of choice cannot be used.

Tetracycline 

Tetracycline is a bacteriostatic agent that inhibits protein synthesis. It is not the drug of choice for tetanusand may be used only if the drugs of choice cannot be used.

Vancomycin 

Vancomycin is a bactericidal agent that inhibits cell wall and RNA synthesis. It is not the drug of choice for tetanus and may be used only if the drugs of choice cannot be used.

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 Anticonvulsants

Class Summary

Sedative-hypnotic agents are the mainstays of tetanus treatment. Benzodiazepines are the most effectiveprimary agents for muscle spasm prevention and work by enhancing gamma-aminobutyric acid (GABA)inhibition. Diazepam is the most frequently studied and used drug. Lorazepam is an effective alternative.

Phenobarbital is another anticonvulsant that may be used to prolong the effects of diazepam. Other agents used for spasm control include baclofen, dantrolene, short-acting barbiturates, andchlorpromazine.

Diazepam (Valium, Diastat, Diazepam Intensol) 

Diazepam modulates the postsynaptic effects of GABA-A transmission, thereby increasing presynapticinhibition. It appears to act on part of the limbic system, the thalamus, and hypothalamus to induce acalming effect. It is also an effective adjunct for the relief of skeletal muscle spasm caused by upper motor neuron disorders. Diazepam rapidly distributes to other body fat stores. To avoid adverse effects,individualize dosage and increase it cautiously.

Rapidly distributes to other body fat stores. Twenty minutes after initial IV infusion, serum concentrationdrops to 20% of Cmax.

Individualize dosage and increase cautiously to avoid adverse effects.

Midazolam (Versed) 

Midazolam is a shorter-acting benzodiazepine sedative-hypnotic that is useful in patients requiring acuteor short-term sedation. It also has amnestic and antiepileptic effects.

Lorazepam (Ativan) 

Lorazepam is a sedative hypnotic with a short onset of effects and a relatively long half-life. By increasingthe action of gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain,lorazepam may depress all levels of the central nervous system, including the limbic and reticular formation. The drug is an excellent choice when the patient needs to be sedated for longer than 24 hours.

Phenobarbital 

The drug dosage must be small enough to ensure that respirations are not depressed. If the patient isalready on a ventilator, higher dosages may provide the desired sedation.

Skeletal Muscle Relaxants

Class Summary

Skeletal muscle relaxants can inhibit both monosynaptic and polysynaptic reflexes at spinal level,possibly by hyperpolarization of afferent terminals. Benzodiazepines are used to control muscle spasmsand to provide sedation. Dantrolene and baclofen may also be considered for severe spasticity and mayassist with shortening duration of artificial ventilation. The use of propofol has been proposed.

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Baclofen (Lioresal, Gablofen) 

Baclofen, a central muscle relaxant, is a presynaptic GABA-B receptor agonist that may inducehyperpolarization of afferent terminals and inhibit both monosynaptic and polysynaptic reflexes at spinal

level. It lessens flexor spasticity and hyperactive stretch reflexes of upper motor neuron origin.

Baclofen is well absorbed, with an average oral bioavailability of 60% and a mean elimination half-life of 12 hours. Steady state is reached within 5 days with multiple dose administration. Metabolism occurs inthe liver (through P450-dependent glucuronidation and hydroxylation); 6 major and a few minor metabolites are produced. Elimination is through renal excretion.

For intrathecal (IT) administration, a pump is implanted subcutaneously (SC), and a catheter is implantedin the subarachnoid space of the spinal canal (where the medication is administered). Less medication isneeded, and systemic effects are decreased. This agent is reported to be effective in about 20% of patients; it appears to be of dramatic benefit in as many as 30% of children with dystonia, though thebenefit not always sustained.

Dantrolene (Dantrium, Revonto) 

Dantrolene stimulates muscle relaxation by modulating skeletal muscle contractions at a site beyond themyoneural junction and by acting directly on the muscle. It may reduce painful cramping and detrimentalmuscle tightening. It is not approved by the US Food and Drug Administration (FDA) for use in tetanusbut has been described in a small number of case reports.

Dantrolene acts peripherally at muscle fiber rather than at the neural level; it reduces muscle actionpotential –induced release of calcium and also affects intrafusal and extrafusal fibers and spindlesensitivity. It has no action on smooth or cardiac muscle tissue. Dantrolene induces release of calciumions into the sarcoplasmic reticulum, subsequently decreasing the force of excitation coupling.

Dantrolene is preferred for the cerebral form of spasticity; it is less likely to cause lethargy or cognitivechanges, as baclofen and diazepam do. It can be administered either orally or IV. The IV form is muchmore expensive and should be reserved for patients unable to take oral medications. Most patientsrespond to dosages of 400 mg/day or less. The drug is eliminated in urine and bile.

General Anesthetics, Systemic

Class Summary

These agents stabilize the neuronal membrane so the neuron is less permeable to ions. This prevents theinitiation and transmission of nerve impulses, thereby producing the local anesthetic effects.

Propofol (Diprivan) 

Propofol is a phenolic compound that elicits a sedative-hypnotic effect. It is used for induction andmaintenance of anesthesia or sedation. It has also been shown to have anticonvulsant properties.

Immune Globulins

Class Summary

 Antitoxins are used to neutralize any toxin that has not reached the CNS. They are used for passiveimmunization of any person with a wound that might be contaminated with tetanus spores.

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Tetanus immune globulin (Hypertet S/D) 

TIG is used to prevent tetanus and to treat patients with circulating tetanus toxin. It provides passiveimmunity. TIG should be used to treat all patients with active tetanus, in combination with other supportive

and therapeutic treatments. Should also be used to prevent tetanus in patients with inadequate or unknown immunization status after an acute injury. Administration should begin as soon as the clinicaldiagnosis of tetanus is made.

Neuromuscular Blocking Agents

Class Summary

Neuromuscular blocking agents inhibit the transmission of nerve impulses at neuromuscular junctions of skeletal muscles or autonomic ganglia.

Vecuronium 

Vecuronium is a prototypical nondepolarizing neuromuscular blocking agent that reliably results inmuscular paralysis. For maintenance of paralysis, a continuous infusion may be used. Infants are moresensitive to neuromuscular blockade activity, and though the same dose is used, recovery is prolongedby 50%. This drug is not recommended for use in neonates.

Vaccines, Inactivated, Bacterial

Class Summary

 Active immunization increases resistance to infection. Vaccines consist of microorganisms or cellular components that act as antigens. Administration of the vaccine stimulates the production of antibodieswith specific protective properties. Administer tetanus toxoid vaccine for wound prophylaxis if the vaccinehistory is unknown or if fewer than 3 tetanus toxoid immunizations have been administered.

Diphtheria and tetanus toxoids, and acellular pertussis vaccine (Infanrix, Adacel, Boostrix) 

DTaP may be administered into the deltoid or midlateral thigh muscles in children and adults. In infants,the preferred site of administration is the midlateral thigh muscles.

This vaccine promotes active immunity to diphtheria, tetanus, and pertussis by inducing the production of specific neutralizing antibodies and antitoxins. It is indicated for active booster immunization for tetanus,diphtheria, and pertussis prevention for persons aged 10-64 years. It is the preferred vaccine for adolescents scheduled for booster.