Tetanus – 8 Interesting Facts

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Interesting Facts

  1. Tetanus is an acute, potentially fatal, noncommunicable, toxin-mediated disease caused by Clostridium tetani; it affects the central nervous system, causing painful muscle spasms and rigidity as well as autonomic dysfunction
  2. Clinical presentation includes fever, trismus, risus sardonicus, dysphagia, and muscular spasms descending from head to neck to trunk; autonomic instability is also common
    • Cephalic tetanus, an uncommon form associated with head wounds or ear infection, is confined to head and neck; it may present with cranial nerve palsies
    • Localized tetanus is uncommon but not rare; it is limited to the muscles surrounding the entry wound
    • Neonatal tetanus is common in resource-limited countries, occurring in infants of women who are unimmunized or underimmunized
  3. Diagnosis is made clinically; there is no diagnostic laboratory test
  4. Treatment includes tetanus antitoxin (ie, antibodies in any of various forms), antibiotics (metronidazole or penicillin), sedatives and muscle relaxants, and proper wound care (eg, debridement, cleaning, vaccination catch-up). Nutrition is an important component, owing to the high calorie demands of muscle spasms
    • Disease does not induce immunity. Immunization with tetanus toxoid series should be started as part of treatment regimen, and series should be completed during and after recovery
  5. Complications of tetanus may include laryngospasms, respiratory arrest, aspiration, cardiac arrhythmia, fractures, and nosocomial events due to long and complex illness; pulmonary embolism is a risk, especially in people who inject drugs and in older adults
  6. Even with optimal care, mortality rates are significant; survivors experience slow recovery and, in some cases (especially in neonates), permanent sequelae
  7. Immunization is the most effective means of prevention, and a primary series during childhood is universally recommended; periodic boosters maintain protective levels of immunity. Placental transfer of maternal antibody prevents neonatal tetanus
  8. Management of open wounds includes assessment of immunization status of patient and nature of wound to determine need for prophylactic tetanus toxoid and tetanus immunoglobulin

Pitfalls

  • Tetanus immunoglobulin can neutralize unbound toxin but does not affect toxin that is already bound to nerves 1

Urgent Action

  • Urgent intubation is necessary in patients with laryngospasm or excess salivation with dysphagia and aspiration

Terminology

Clinical Clarification

  • Tetanus is an acute, potentially fatal, noncommunicable, toxin-mediated disease affecting the central nervous system; it is characterized by painful muscle spasms and rigidity as well as autonomic dysfunction 2
  • Caused by Clostridium tetani, which exists in soil, dust, and excrement and which may contaminate surgical or traumatic wounds; in anaerobic conditions (eg, deep puncture wounds, devitalized tissue) it produces the neurotoxin that mediates disease 2
  • Although tetanus is a vaccine-preventable infection, it continues to occur in resource-limited countries (particularly in South Asia and sub-Saharan Africa), with high case fatality rates 3 4

Classification of tetanus

  • Based on clinical syndrome 5
    • Generalized tetanus
      • Most common (more than 80% of cases) and most severe presentation 1
      • Descending pattern of painful, involuntary muscle spasms and rigidity
        • Frequently begins with trismus (lockjaw) and risus sardonicus (rictus grin) followed by difficulty swallowing, rigidity of trunk muscles, and finally spasms of extremities
      • Neonatal tetanus, sometimes classified separately, is generalized tetanus occurring within the first few weeks of life, usually as a result of umbilical stump infection
    • Localized tetanus
      • Presents with muscle spasms proximal to entry site; may persist for many weeks
      • May progress to generalized tetanus when enough toxin gains access to central nervous system, or it may resolve spontaneously 6
    • Cephalic tetanus
      • Rare, localized disease limited to musculature of head and neck; may include flaccid cranial nerve palsies in addition to spasms of jaw muscles 1
      • Predominately associated with wounds of head and neck, otitis, or mastoiditis
      • May progress to generalized tetanus

Diagnosis

Clinical Presentation

History

  • History may include:
    • Injury accounting for portal of entry
      • Puncture, crush injury, burn, open fracture
      • Contamination may or may not have been recognized
    • Absent or incomplete immunization, including overdue adult boosters
  • Symptoms of generalized tetanus progress over 1 to 7 days, generally in a descending direction 2
    • Fever may be reported
    • Difficulty in chewing and swallowing may be noted early; in neonates, poor suck may be reported
    • Patients may experience difficulty speaking
    • As the disease progresses, painful tonic contractions and spasms may develop, causing neck stiffness and pain in back, abdomen, and extremities
    • Spasms may be triggered by loud noise, physical contact, or light
  • In cephalic or local tetanus, symptoms may be isolated to head or area of infection entry, respectively, or they may progress to generalized involvement

Physical examination

  • Fever, with temperature ranging from 39 to 41 °C; instability of heart rate and blood pressure may be noted at presentation or may evolve during disease course 7
  • Presents a descending pattern over a week from onset, beginning with: 7
    • Trismus (lockjaw)
      • Inability to open mouth secondary to masseter muscle spasms; it is a hallmark sign, although not pathognomonic
    • Risus sardonicus (rictus grin)
      • Involuntary smile mimicking a sneer; it may be associated with furrowing of brow and accentuation of palpebral fissures
    • Nuchal rigidity
    • Abdominal rigidity with opisthotonic posturing (backward curvature), flexion of arms, and extension of legs
  • In cephalic tetanus, cranial nerve involvement may be seen as ptosis, facial droop, nystagmus, or dysarthria; these may occur before or after onset of trismus
  • In local tetanus, muscle spasms may be observed in area of entry wound

Causes and Risk Factors

Causes

  • Clostridium tetani spores are found ubiquitously in soil, especially in warmer climates 2
    • Manure or feces from animals (eg, horses, sheep, cattle, chicken, dogs, cats) may contain large numbers of spores
    • Spores are extremely resistant to heat and antiseptics, surviving years in adverse conditions
  • Clostridium tetani enters through nonintact skin or wound; anaerobic conditions allow germination of spores to produce tetanus toxin, which contains tetanospasmin (a neurotoxin) and tetanolysin (a hemolytic toxin) 2
    • Lacerations, punctures, chronic wounds, skin ulcers, animal bites, fissures of foot, burns, postsurgical sites
      • Acute injuries such as punctures or lacerations account for approximately 70% 5
      • Portal of entry is not evident in a significant percentage of patients (7% to 23%) 5
      • Neonatal tetanus develops when umbilical cord is cut with nonsterile instrument or is contaminated by unclean conditions 8
    • Tetanus toxin prevents release of certain inhibitory neurotransmitters, leading to unopposed muscle contractions; adrenal catecholamine release is also uninhibited, leading to autonomic instability 9
  • Incubation ranges from 3 to 21 days, with a mean of 10 days 1
    • In general, the greater the distance of the injury from the central nervous system, the longer the incubation period 1

Risk factors and/or associations

Age
  • In resource-limited countries, disease is common in neonates born in unsanitary conditions to women lacking current immunity 10
    • Placental transfer of maternal antibody to tetanus toxoid vaccine is generally protective for several months, but this possibility relies on the mother’s vaccination status being sufficient
  • In higher-income countries in which widespread immunization is practiced, infection occurs primarily in people older than 60 years, owing to waning immunity if booster doses are overlooked 5
Sex
  • Slight male to female predominance 11
Other risk factors/associations
  • Nature of entry site and surrounding tissues
    • Toxin production is fostered by anaerobic conditions in tetanus-prone wounds such as in deep puncture wounds, missile wounds, and wounds with devitalized tissue (eg, crush injury, burns, avulsions, frostbite, abortion) 12
      • People who inject drugs are at high risk and, for unknown reasons, may experience more severe disease 5
        • Most notable in injection of heroin (via IV, skin popping, or both) 13
    • Otitis media and dental infections may be a source of cephalic tetanus 12
  • Underimmunization against tetanus 11
    • A primary series of 3 to 4 doses induces protective immunity in nearly 100% of those vaccinated 2
      • Protective immunity lasts for 10 years, but it may wane thereafter unless booster doses are given
      • A single dose of tetanus toxoid does not generate sufficient immunity to prevent infection
    • Children without primary series of tetanus immunization
      • Over 90% of American children aged 6 to 11 years have fully protective levels of antitetanus antibody 14
    • Adults who are unimmunized or underimmunized, with waning immunity (eg, more than 10 years since toxoid booster vaccination)
      • In the United States, 50% of adults older than 60 years and 70% older than 70 years lack protective antibody levels 14
      • Public Health England recognizes the highest incidence of tetanus in persons older than 64 years as a result of underimmunization 15
    • Immunization is not universally administered or available in some resource-limited countries
  • Inadequate wound management 11
    • In addition to proper local care (eg, cleansing, debridement), tetanus immunoglobulin and/or tetanus toxoid may be indicated, based on nature of wound and immunization history
    • In a report of patients with tetanus in the United States who had sought medical care for acute wounds before onset of disease, 96% had not received appropriate tetanus prophylaxis 11
  • Diabetes, with or without extremity ulcers, appears to be a risk factor for tetanus 9

Diagnostic Procedures

Primary diagnostic tools

  • Diagnosis is based on clinical observation and patient history
    • Acute onset of hypertonia with trismus, muscular rigidity, and stimulus-induced tetany; history usually includes a recent wound or injury (although not invariably) 11
  • No specific laboratory tests exist to confirm or exclude diagnosis 5
  • Some authorities suggest testing for antitetanus antibody, on the grounds that protective levels argue against the diagnosis; this is controversial, 9 2 because tetanus has been reported in the presence of antibody levels above the defined threshold 4
  • Culture of wound may be indicated if wound appears clinically infected; however, attempts to recover Clostridium tetani specifically are not recommended because of poor sensitivity and specificity 5
    • Clostridium tetani is isolated from wounds in up to 30% of such cultures, and when it is present it may not definitively diagnose disease 12
      • Growth of Clostridium tetani does not always indicate tetanus toxin production
      • Growth of Clostridium tetani may be present without symptoms in adequately immunized persons
  • Electromyography may be helpful in some cases (eg, if no entry site is evident on physical examination or by history) 9
  • Tests for nonspecific biomarkers of infection (eg, WBC count, C-reactive protein level, procalcitonin level) may be indicated on the basis of fever or infected wound
  • Critical care management requires baseline chemistry panels, including renal function tests, creatine kinase level, and urine myoglobin level 5
  • In the United States, tetanus is a nationally notifiable condition 16

Laboratory

  • Antitetanus antibodies are undetectable in most patients presenting symptomatically 9
    • Currently accepted protective level of tetanus toxoid antibody is 0.01 units/mL 9
    • Presence of protective antibody level does not definitively exclude tetanus 2
  • WBC count, C-reactive protein level, and procalcitonin level may range from normal to elevated, depending on time of specimen collection relative to stage of disease 9
  • Elevated creatine kinase level reflects muscle damage; very high levels indicate risk for rhabdomyolysis and kidney injury

Functional testing

  • Electromyography 9
    • May show continuous discharge of motor subunits lacking the silent interval normally observed

Differential Diagnosis

Most common

  • Strychnine poisoning
    • Ingestion or inhalation of strychnine poison causes severe violent seizures in a conscious patient, usually appearing within 5 minutes to 1 hour after ingestion 17
    • Circumstances may suggest accidental exposure (eg, rodenticide) or suicide attempt
    • Serum biomarkers are nonspecific, but they may show lactic acidosis, hyperkalemia, elevated liver enzyme levels (ie, AST, lactate dehydrogenase, creatine kinase), and leukocytosis 17
    • Differentiated by reference laboratory assays for strychnine in blood and urine
  • Dental abscess
    • Severe abscess that extends into secondary spaces of mandible and neck may present with dysphagia and trismus
    • Generalized muscle spasms and rigidity are not seen
    • Physical examination may show fluctuant mass in gum surrounding affected tooth; there may be erythema, edema, and tenderness of overlying facial area or neck
    • Differentiated by history and clinical findings, and possibly also by imaging
  • Dystonic reaction
    • Reversible extrapyramidal effects occurring immediately or several hours after administration of a neuroleptic drug or central dopamine antagonist
    • Physical presentation includes muscle spasms of face, neck, and torso; it may also include fixed eye deviation, tongue protrusion, facial grimace, lateral head turning, trismus, and opisthotonos
    • Pronounced fixed eye deviation and lateral head turning is characteristic of dystonic reactions but uncommon in tetanus; these findings, a detailed medication history, and resolution upon administration of anticholinergic agents confirm diagnosis
  • Severe hypocalcemia
    • Insufficient calcium levels in blood or tissue causing tetany
    • Muscle stiffness and spasms may be local or generalized, and they may be associated with paresthesias
    • There may be a history suggesting causes of hypocalcemia (eg, thyroid or parathyroid surgery or radiotherapy, renal disease, vitamin D deficiency)
    • Physical findings include Chvostek sign (twitching of perioral, nasal, and eye muscles after percussion of facial nerve) or Trousseau sign (carpopedal spasm induced by inflation of a blood pressure cuff to exceed systolic pressure for 3 minutes) 18 19
    • Differentiate and confirm by serum calcium levels below reference range (eg, total level below 8.2 mg/dL or ionized level below 4.4 mg/dL) 18
  • Neuroleptic malignant syndrome
    • Caused by neuroleptic medications or atypical antipsychotic drugs used to treat schizophrenia, bipolar disorder, or other mental health conditions
    • Similar to tetanus, characterized by generalized muscular rigidity and autonomic instability
    • Fever may be present and temperature may be quite high
    • Unlike with tetanus, mental status change is usual
    • Differentiation is clinical; it may be supported by laboratory assays for implicated agents
  • Stiff person syndrome
    • Rare neurologic disorder characterized by severe muscle rigidity
    • As with tetanus, generalized spasms can be precipitated by movements, noise, touch, or emotional stimulation
    • Unlike tetanus, stiff person syndrome does not include trismus or facial spasms and responds quickly to diazepam 9

Treatment

Goals

  • Prevent disease progression
    • Neutralize unbound toxin
    • Halt toxin production with antibiotics and source control (wound management)
  • Supportive and symptomatic care
    • Ensure intact, protected airway and appropriate ventilation
    • Control tetanic spasms and autonomic instability
    • Address metabolic issues
      • High caloric needs
      • Fluids to prevent kidney injury due to myoglobinuria

Disposition

Admission criteria

Admit all patients with suspected tetanus

Criteria for ICU admission
  • Patients with tetanus should be admitted to ICU for airway management and to monitor for autonomic complications
    • Quickly assess and treat patients presenting with airway obstruction (to prevent respiratory insufficiency)
    • Intubation or tracheostomy should be performed for severe laryngospasm; early tracheostomy is often expedient for control of secretions
    • Patients should be placed in a quiet, darkened part of the ICU, if possible

Recommendations for specialist referral

  • Consult advanced airway team to assess and manage airway and ventilation
  • Consult an infectious disease specialist to coordinate wound management, administration of antitoxin and antimicrobial therapy, and reporting
  • Consult a critical care specialist to aid in managing benzodiazepines, autonomic instability, nutrition, fluids, and electrolytes

Treatment Options

Bind circulating toxin and prohibit further toxin production

  • Administer antibodies
    • Various preparations
      • In the United States, human tetanus immune globulin (intramuscular) is first choice; if it is unavailable, use IV immunoglobulin 1 (which offers some tetanus-specific antibody activity because of vaccination in the donor population 20)
      • In some countries, equine tetanus immunoglobulin is more readily available and is recommended 2
    • Binds circulating toxin but not toxin that has already bound to nerves 1
  • Administer tetanus toxoid vaccine 5
    • Complete an age-appropriate series 21
    • Disease does not generate protective immunity
  • Begin antibiotic therapy with metronidazole or penicillin 2
  • Perform thorough wound cleaning and debridement

Pharmacotherapy of muscle spasms and autonomic instability

  • Administer sedatives (ie, benzodiazepines) to control muscle spasms, relieve anxiety, and induce sedation
    • Sedative hypnotics such as midazolam and propofol are alternative drugs effective at achieving moderate sedation, spasm control, and rigidity control; they may cause less respiratory depression, although high doses are often needed, dictating caution and monitoring 5
  • Administer labetalol (or esmolol) for hypertension; avoid diuretics and selective β-blockers (without α-blocking activity) 5
  • Administer atropine or isoproterenol for bradycardia 5
    • Vasopressors (eg, dopamine, norepinephrine) may be necessary if there is associated hypotension that does not respond adequately to fluids 5 21
  • Magnesium sulfate has been used for its effects on both muscle spasms and autonomic dysfunction; it has no clearly proven benefit over other agents, but some studies have shown a trend toward less need for mechanical ventilation and shorter hospital stay 4
  • Morphine has also been used, both for sedation and to reduce sympathetic tone 9

Supportive care

  • Begin nutritional support early 5
    • Muscle spasms impose substantial catabolic demand; patients may lose up to 15% of body weight
  • Administer IV fluids to manage high levels of creatine kinase
  • Urinary catheterization alleviates urinary retention, which otherwise may provoke bladder spasms
  • Start physical therapy as soon as spasms have subsided
  • Other routine measures not specific to tetanus include prevention of pressure ulcers, stress-induced peptic ulcers, and thromboembolism

Drug therapy

  • Antitoxins for active tetanus
    • Tetanus immunoglobulin 1 2
      • Use for active tetanus to bind circulating toxin and prohibit further toxin production
      • Tetanus Immune Globulin (Human) Solution for injection; Neonates: Optimal dose not established. 500 units IM once. 22
      • Tetanus Immune Globulin (Human) Solution for injection; Infants 1 to 5 months: Optimal dose not established. 500 units IM once as effective as 3,000 to 6,000 units. May adjust dose based on infection severity.
      • Tetanus Immune Globulin (Human) Solution for injection; Infants, Children, and Adolescents 6 months to 17 years: Optimal dose not established. 500 units IM once as effective as 3,000 to 6,000 units. May adjust dose based on infection severity.
      • Tetanus Immune Globulin (Human) Solution for injection; Adults: Optimal dose not established. 500 units IM once as effective as 3,000 to 6,000 units. May adjust dose based on infection severity.
      • Some experts recommend infiltration of part of the dose locally around the wound, although efficacy has not been proven
    • IV immunoglobulin
      • Immune Globulin (Human) Solution for injection; Infants, Children, and Adolescents: 200 to 400 mg/kg IV once.
      • Immune Globulin (Human) Solution for injection; Adults: 200 to 400 mg/kg IV once.
  • Antitoxin is also used as part of prophylactic regimen for management of tetanus-prone wounds 1 2
    • Tetanus immunoglobulin
      • Use for patients with severe or contaminated wounds if immunization history is unknown or if fewer than 3 doses of a tetanus toxoid vaccine have previously been given
      • For infants younger than 6 months, consider maternal tetanus toxoid immunization history at time of delivery when determining the need for treatment of the infant
      • Tetanus Immune Globulin (Human) Solution for injection; Infants 1 to 5 months: 250 units IM once, or alternatively, 4 units/kg IM once.
      • Tetanus Immune Globulin (Human) Solution for injection; Infants and Children 6 months to 6 years: 250 units IM once, or alternatively, 4 units/kg IM once.
      • Tetanus Immune Globulin (Human) Solution for injection; Children and Adolescents 7 to 17 years: 250 units IM once.
      • Tetanus Immune Globulin (Human) Solution for injection; Adults: 250 units IM once.
  • Tetanus toxoid vaccines are administered as part of routine immunization, in the treatment of tetanus, and in prophylactic management of tetanus-prone wounds 2 12
    • Per CDC, the primary series consists of 5 doses for children or 3 doses for unimmunized adults, indicated routinely in all persons without a contraindication, and in treatment and follow-up of persons with tetanus (the disease itself does not confer immunity)
    • Wound management
      • If immunization history is unknown or if fewer than 3 doses of a tetanus toxoid–containing vaccine have previously been given, give vaccine for clean, minor wounds or other severe or contaminated wounds. If 3 or more doses of a tetanus toxoid–containing vaccine have been given, give vaccine for clean, minor wounds if 10 years or more have elapsed since the previous dose of tetanus toxoid–containing vaccine, or for other severe or contaminated wounds if 5 years or more have elapsed since the previous dose of tetanus toxoid–containing vaccine
        • Vaccines
          • Tdap (tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine)
          • Td (tetanus and diphtheria toxoids vaccine)
        • Tdap is preferred to Td in patients who have not previously received Tdap
    • Tdap (tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine)
      • Clostridium Tetani Toxoid antigen (Formaldehyde inactivated), Corynebacterium Diphtheriae Toxoid antigen (Formaldehyde inactivated), Bordetella Pertussis Toxoid antigen (Formaldehyde, Glutaraldehyde inactivated), Bordetella Pertussis Filamentous Hemagglutinin antigen (Formaldehyde inactivated), Bordetella Pertussis Pertactin antigen (Formaldehyde inactivated) Suspension for injection; Children 7 to 9 years†: 0.5 mL IM.
      • Clostridium Tetani Toxoid antigen (Formaldehyde inactivated), Corynebacterium Diphtheriae Toxoid antigen (Formaldehyde inactivated), Bordetella Pertussis Toxoid antigen (Formaldehyde, Glutaraldehyde inactivated), Bordetella Pertussis Filamentous Hemagglutinin antigen (Formaldehyde inactivated), Bordetella Pertussis Pertactin antigen (Formaldehyde inactivated) Suspension for injection; Children and Adolescents 10 to 17 years: 0.5 mL IM.
      • Clostridium Tetani Toxoid antigen (Formaldehyde inactivated), Corynebacterium Diphtheriae Toxoid antigen (Formaldehyde inactivated), Bordetella Pertussis Toxoid antigen (Formaldehyde, Glutaraldehyde inactivated), Bordetella Pertussis Filamentous Hemagglutinin antigen (Formaldehyde inactivated), Bordetella Pertussis Pertactin antigen (Formaldehyde inactivated) Suspension for injection; Adults: 0.5 mL IM.
    • Td (tetanus and diphtheria toxoids vaccine)
      • Corynebacterium Diphtheriae Toxoid antigen (Formaldehyde inactivated), Clostridium Tetani Toxoid antigen (Formaldehyde inactivated) Suspension for injection; Children and Adolescents 7 to 17 years: 0.5 mL IM.
      • Corynebacterium Diphtheriae Toxoid antigen (Formaldehyde inactivated), Clostridium Tetani Toxoid antigen (Formaldehyde inactivated) Suspension for injection; Adults: 0.5 mL IM.
  • Antibiotics
    • Metronidazole
      • Metronidazole Solution for injection; Neonates 34 weeks postmenstrual age and younger: 15 mg/kg IV loading dose, then 7.5 mg/kg/dose IV every 12 hours.
      • Metronidazole Solution for injection; Neonates 35 to 40 weeks postmenstrual age: 15 mg/kg IV loading dose, then 7.5 mg/kg/dose IV every 8 hours.
      • Metronidazole Solution for injection; Neonates older than 40 weeks postmenstrual age: 15 mg/kg IV loading dose, then 10 mg/kg/dose IV every 8 hours.
      • Metronidazole Solution for injection; Infants, Children, and Adolescents: 30 mg/kg/day (Max: 4 g/day) IV in divided doses every 6 hours for 7 to 10 days.
      • Metronidazole Solution for injection; Adults: 500 mg IV every 6 hours for 7 to 10 days.
    • Penicillin G (benzylpenicillin)
      • Penicillin G Sodium Solution for injection; Neonates 0 to 7 days†: 50,000 units/kg/dose IV/IM every 12 hours.
      • Penicillin G Sodium Solution for injection; Neonates older than 7 days†: 50,000 units/kg/dose IV/IM every 8 hours.
      • Penicillin G Potassium Solution for injection; Infants†, Children†, and Adolescents†: 100,000 units/kg/day (Max: 12 million units/day) IV/IM in divided doses every 4 to 6 hours for 7 to 10 days.
      • Penicillin G Potassium Solution for injection; Adults: 20 million units/day IV/IM in divided doses every 4 to 6 hours for 7 to 10 days.
  • Diazepam
    • Infusion may cause pain and thrombophlebitis
    • Diazepam Solution for injection; Neonates: 0.1 to 0.3 mg/kg/dose IV every 1 to 4 hours PRN. If spasms persist, consider 0.1 mg/kg/hour continuous IV infusion; titrate by 0.1 mg/kg/hour PRN up to Max: 0.8 mg/kg/hour. 22
    • Diazepam Solution for injection; Infants and Children 1 month to 4 years: 0.1 to 0.2 mg/kg/dose IV or 1 to 2 mg IV/IM every 3 to 6 hours PRN.
    • Diazepam Solution for injection; Children and Adolescents 5 to 17 years: 0.1 to 0.2 mg/kg/dose IV or 5 to 10 mg IV/IM every 3 to 6 hours PRN.
    • Diazepam Solution for injection; Adults: 0.1 to 0.2 mg/kg/dose IV or 5 to 10 mg IV/IM every 3 to 6 hours PRN. Larger doses and up to 600 mg/day IV may be required.
  • Midazolam 23
    • Midazolam Solution for injection; Adults: 5 to 15 mg/hour continuous IV infusion.
  • Labetalol
    • Labetalol Hydrochloride Solution for injection; Adults: 0.25 to 1 mg/minute continuous IV infusion.
  • Morphine
    • Morphine Sulfate Solution for injection; Infants, Children, and Adolescents: 0.02 to 0.05 mg/kg/hour continuous IV infusion.
    • Morphine Sulfate Solution for injection; Adults: 0.5 to 1 mg/kg/hour continuous IV infusion.
  • Magnesium sulfate
    • Magnesium Sulfate Solution for injection; Neonates: 50 mg/kg IV once, then 30 to 50 mg/kg/hour continuous IV infusion until spasm control and to maintain serum magnesium concentrations of 1 to 2.5 mmol/L. Monitor patellar reflex and decrease dose if areflexia occurs.
    • Magnesium Sulfate Solution for injection; Infants, Children, and Adolescents: 100 mg/kg IV once, then 40 mg/kg/hour continuous IV infusion; may titrate by 5 mg/kg/hour every 6 hours until spasm control and to maintain serum magnesium concentrations of 2.5 to 5 mmol/L. Max: 100 mg/kg/hour. Lower infusion rates of 4 to 17 mg/kg/hour also used. Monitor patellar reflex and decrease dose if areflexia occurs.
    • Magnesium Sulfate Solution for injection; Adults weighing 45 kg or less: 40 or 75 mg/kg IV once, then 1.5 to 3 g/hour continuous IV infusion until spasm control. Monitor patellar reflex and decrease dose if areflexia occurs.
    • Magnesium Sulfate Solution for injection; Adults weighing more than 45 kg: 40 or 75 mg/kg (Max: 5 g) IV once, then 2 to 3 g/hour continuous IV infusion until spasm control. Monitor patellar reflex and decrease dose if areflexia occurs.

Nondrug and supportive care

  • Wound management
    • Removal of necrotic tissue
    • Cleansing of vital tissue to reduce bacterial load and discourage spore germination
    • In neonatal tetanus, wide excision of umbilical stump is not indicated 2
  • Nutrition
    • Begin nasogastric feeding and/or parenteral nutrition to meet required nutritional needs during hyperactivity and muscle spasms 5

Monitoring

  • Immunization with tetanus toxoid series, which should be started as part of treatment regimen, should be completed during and after recovery
    • Counsel patient or caregiver on need for future doses to complete the series; arrange follow-up if possible

Complications and Prognosis

Complications

  • Cardiopulmonary complications
    • Respiratory arrest may occur in patients without mechanical ventilation
    • Aspiration pneumonia12
    • Autonomic derangements may result in cardiac arrhythmias, myocardial infarction, or asystole
    • Pulmonary embolism
      • Patients at high risk include those who inject drugs and older adults (aged 65 years or older) 12
    • Nosocomial events due to long and complex illness (eg, hospital-acquired pneumonia, ventilator-associated pneumonia)
  • Renal failure may occur as a result of rhabdomyolysis
  • Fractures and tendon ruptures are occasional complications
  • Survivors of neonatal tetanus may experience growth restriction and neurodevelopmental delay 4

Prognosis

  • Tetanus disease duration varies, averaging 4 to 6 weeks 9
  • Overall fatality rate for generalized tetanus is 10% to 20% with optimal care; 1 without access to ICU and mechanical ventilation, mortality rates in adults exceed 40% 3 24
    • Case fatality approaches 100% in the absence of medical intervention 8
    • Shorter incubation periods correlate with more severe disease, more complications, and higher risk of death 12
  • Neonatal mortality rates are generally higher
    • Poor outcome is portended in those with low birth weight, young age (younger than 6 days), or presence of fever, generalized rigidity, and risus sardonicus 10

Screening and Prevention

Prevention

  • Preventive measures consist of immunization, prophylactic wound management, and hygienic practices during childbirth and neonatal care
    • Immunization
      • Tetanus can be prevented through immunization with tetanus toxoid–containing vaccines; efficacy approaches 100% 12
      • Universal vaccination is recommended in infancy and childhood; schedules vary regionally, but they usually consist of 3 doses during the first year of life plus 2 additional doses before school age 8
        • Often administered as combination vaccines that include 1 or more other components: diphtheria, pertussis, Haemophilus influenzae type b, hepatitis B, and poliomyelitis 8
        • CDC recommends a primary series of 5 doses, administered at ages 2, 4, 6, and 15 to 18 months and at 4 to 6 years; catch-up schedules are available 25
        • For unimmunized adults, CDC recommends a dose of Tdap followed by a dose of Td at 4 weeks and 4 to 6 months after the initial Tdap; the order may be altered if availability of formulation or other circumstances dictate 26
      • Booster doses are required to maintain immunity 26
        • WHO 8 recommends a booster dose of tetanus toxoid during adolescence; CDC 25 recommends tetanus boosters given as Tdap at age 11 to 12 years and with every pregnancy, and every 10 years during adulthood
          • 1 adult booster should be given as Tdap 25
          • CDC recommends that ongoing decennial booster doses may be either Td or Tdap to allow flexibility for provider at point of care 27
          • Pregnant patients should receive Tdap at 27 to 36 weeks of gestation 25
      • Absolute contraindication is severe allergic reaction to a component of a tetanus and diphtheria toxoid vaccine 12
        • Tetanus immune globulin may be administered instead of tetanus toxoid as prophylaxis for wounds that would otherwise require tetanus toxoid
      • Local reactions are common but are usually not severe 12
        • Erythema, induration, or tenderness at injection site
        • Palpable nodule at injection site lasting for several weeks
        • Abscess at injection site
      • Exaggerated local reactions occasionally occur in people with very high serum antitoxin levels or those who have received frequent booster doses 12
        • Characterized by extensive painful swelling from shoulder to elbow beginning 2 to 8 hours after injection
    • Wound management 1
      • Clean all wounds with soap and water
      • Debride necrotic tissue and remove foreign material, if present
      • Consider the following to be tetanus-prone wounds: 12
        • Wounds contaminated with dirt, soil, feces, or saliva
        • Wounds with presence of necrotizing or devitalized tissue
        • Penetrating or puncture injury
        • Frostbite
        • Burns
        • Crush injuries
        • Avulsions
      • Determine need for tetanus toxoid vaccine and tetanus immunoglobulin based on immunization history and nature of wound 12
        • For persons known to have received 3 or more doses of tetanus toxoid:
          • For clean, minor wounds, administer a booster if previous dose was more than 10 years ago
          • For all other wounds (ie, tetanus-prone wounds), administer a booster if previous dose was more than 5 years ago
          • In all such cases, the booster may be either Td or Tdap; Tdap is preferred for persons who have not previously received Tdap or whose Tdap history is unknown 27
          • Tetanus immunoglobulin is not indicated
        • For persons with unknown immunization history or known to have received fewer than 3 doses of tetanus toxoid:
          • For clean, minor wounds, administer either Td or Tdap
            • Tdap is preferred for persons who have not previously received Tdap or whose Tdap history is unknown 27
          • For all other wounds (ie, tetanus-prone wounds), administer either Td or Tdap and tetanus immunoglobulin
            • Tdap is preferred for persons who have not previously received Tdap or whose Tdap history is unknown 27
          • Administer further doses of tetanus toxoid at appropriate intervals to complete the series 8
History of adsorbed tetanus toxoid (doses)Clean, minor wound: Tdap or Td†Clean, minor wound: TIGAll other wounds*: Tdap or Td†All other wounds*: TIG
Unknown or less than 3YesNoYesYes
3 or moreNo§NoNo¶No

Citation: Adapted from Kretsinger K et al: Preventing tetanus, diphtheria, and pertussis among adults: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP) and recommendation of ACIP, supported by the Healthcare Infection Control Practices Advisory Committee (HICPAC), for use of Tdap among health-care personnel. MMWR Recomm Rep. 55(RR-17):1-37, 2006, Table 14.

Neonatal tetanus can be prevented by immunizing women of reproductive age either during or outside pregnancy, and by maintaining sanitary conditions of birth and umbilical cord care

  • Vaccination is recommended for pregnant patients who are not immune 8
  • A Cochrane review found that 2 to 3 doses provide greater protection than a single dose 28
  • Focused efforts to improve birthing hygiene should include the “6 cleans” of delivery: 29
    • Clean hands, clean perineum, clean delivery surfaces, clean cord cutting, clean cord tying, clean cord care
  • Application of topical antibiotic to umbilical stump reduces tetanus risk in neonates 5

Sources

CDC: Tetanus: For Clinicians. CDC website. Updated January 23, 2020. Reviewed January 23, 2020. Accessed March 2, 2020. https://www.cdc.gov/tetanus/clinicians.html

Cross Reference  

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