Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

INITIAL

clean and minor wound

1st line – wound debridement

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INITIAL
|
clean and minor wound
1st line – 

wound debridement

Prevention of tetanus is always preferable to management of the clinical syndrome.

All wounds should be thoroughly cleaned and debrided.[3][4][38]

Wound debridement removes spores and necrotic tissue, eradicating the anaerobic conditions that facilitate clostridial growth. Antibiotic penetration into devitalized tissue is likely to be poor, emphasizing the importance of adequate wound debridement.[50]

Consider – tetanus vaccine

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INITIAL
|
clean and minor wound
Consider – 

tetanus vaccine

Treatment recommended for SOME patients in selected patient group

The management of clean and minor wounds should take into account the patient's immunization status. Immunosuppressed patients may not be adequately protected and additional boosting and/or immune globulin may be required; in the US, immunosuppressed patients should be managed as if they were incompletely immunized.[3][4][38]

Clean and minor wounds do not require human tetanus immune globulin (TIG).[3][4][38]

US recommendations for vaccination in patients with clean and minor wounds are as follows:[3][38]

Patients who have only had up to 2 doses of tetanus toxoid-containing vaccine or an uncertain vaccination history should be given tetanus toxoid-containing vaccine; patients who have received ≥3 doses do not require tetanus toxoid-containing vaccine unless they have not received a dose in the last 10 years.

Tetanus toxoid is only available in combination with other antigens such as diphtheria and pertussis. The following vaccines are recommended for active vaccination in patients with tetanus-prone wounds: diphtheria/tetanus/acellular pertussis vaccine (DTaP); tetanus/diphtheria vaccine (Td for children ≥7 years of age and adults; or DT for children up to 7 years of age); and tetanus/low-dose diphtheria/acellular pertussis vaccine (Tdap). DTaP is recommended for children aged <7 years. DT is used when the pertussis vaccine component is contraindicated. Tdap can be given if the person is 11 years of age or older and has not yet received Tdap.[3][29][38]

If a tetanus booster is indicated for wound management during pregnancy, Tdap should be administered instead of Td if the woman has not received Tdap previously.[35]

tetanus-prone wound

1st line – wound debridement

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INITIAL
|
tetanus-prone wound
1st line – 

wound debridement

Prevention of tetanus is always preferable to management of the clinical syndrome.

Wounds or burns that are considered to be tetanus prone and high risk include the following: requiring surgical management but delay in intervention over 6 hours; puncture-type injury or a significant degree of devitalized tissue (especially in contact with soil or manure); certain animal bites and scratches; foreign body-containing wounds; open fractures; concomitant systemic sepsis.[3][4][38]

All wounds should be thoroughly cleaned and debrided.[3][4][38]

Wound debridement removes spores and necrotic tissue, eradicating the anaerobic conditions that facilitate clostridial growth. Antibiotic penetration into devitalized tissue is likely to be poor, emphasizing the importance of adequate wound debridement.[50]

Plus – tetanus vaccine ± tetanus immune globulin (TIG) or tetanus antitoxin or human normal immune globulin

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INITIAL
|
tetanus-prone wound
Plus – 

tetanus vaccine ± tetanus immune globulin (TIG) or tetanus antitoxin or human normal immune globulin

Treatment recommended for ALL patients in selected patient group

The management of tetanus-prone wounds should take into account the patient's immunization status. Immunosuppressed patients may not be adequately protected and additional boosting and/or immune globulin may be required; in the US, immunosuppressed patients should be managed as if they were incompletely immunized.[3][4][38]

US recommendations for vaccination in patients with tetanus-prone wounds are as follows:[3][38]

Patients who have only had up to 2 doses of tetanus toxoid-containing vaccine or an uncertain vaccination history should be given tetanus toxoid-containing vaccine and intramuscular TIG; patients who have received ≥3 doses do not require tetanus toxoid-containing vaccine unless they have not received a dose in the last 5 years. These patients do not require TIG.[3][38] 

Tetanus toxoid is only available in combination with other antigens such as diphtheria and pertussis. The following vaccines are recommended for active vaccination in patients with tetanus-prone wounds: diphtheria/tetanus/acellular pertussis vaccine (DTaP); tetanus/diphtheria vaccine (Td for children ≥7 years of age and adults; or DT for children up to 7 years of age); and tetanus/low-dose diphtheria/acellular pertussis vaccine (Tdap). DTaP is recommended for children aged <7 years. DT is used when the pertussis vaccine component is contraindicated. Tdap can be given if the person is 11 years of age or older and has not yet received Tdap.[3][29][38]

If a tetanus booster is indicated for wound management during pregnancy, Tdap should be administered instead of Td if the woman has not received Tdap previously.[35]

Passive immunization with TIG:

TIG neutralizes toxin, reducing the duration and severity of tetanus. Toxin binds irreversibly to tissues; therefore, only circulating and unbound toxin can be neutralized.

Toxoid should be injected at a different site from TIG so that it is not "neutralized" by the passive immunization.[3]

When indicated, intramuscular TIG is the treatment of choice and should be used if it is available.[1][38]​ Tetanus antitoxin (equine) is more widely available in the developing world (it may not be available or may be difficult to access in some countries), but has a higher incidence of anaphylaxis (20% of cases) and a much shorter half-life (2 days).[19] Tetanus antitoxin (human) may also be available in some countries. If intramuscular TIG cannot be sourced, in the UK, guidelines recommend that the subcutaneous or intramuscular formulation of human normal immune globulin may be given as an alternative.[39]

Primary options

tetanus immune globulin (human): children and adults: see local specialist protocol for dosing guidelines

Secondary options

immune globulin (human): children and adults: see local specialist protocol for dosing guidelines

ACUTE

with clinical tetanus

1st line – supportive care

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ACUTE
|
with clinical tetanus
1st line – 

supportive care

Patients should be stabilized and an airway secured to ensure adequate ventilation (which can be compromised by the muscle spasms) and prevention of aspiration. Patients should be transferred to an intensive care unit. External stimulation, which can precipitate muscle spasms, should be minimized.

Airway management: there is a high risk of aspiration; therefore, establishing a secure airway early is paramount before laryngeal obstruction and/or aspiration occurs.

Prolonged mechanical ventilation is often required, sometimes for weeks, and early percutaneous tracheostomy is appropriate.[49] Patients with tetanus have increased salivation and bronchial secretions; mouth care, regular tracheal suction, and chest physical therapy are crucial to prevent secondary pulmonary infection and atelectasis. Boluses of sedation and neuromuscular blocking agents are required for these procedures to avoid stimulation.

Management should include prevention of decubitus ulcers. Limb physical therapy can be started as soon as spasms have abated.

Compression stockings, subcutaneous heparin, and calf pumps are indicated as prophylaxis for venous thromboembolism.

A proton-pump inhibitor may be prescribed to reduce stress ulceration.

Primary options

esomeprazole: children: consult specialist for guidance on dose; adults: 20-40 mg intravenously once daily

Plus – benzodiazepine

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ACUTE
|
with clinical tetanus
Plus – 

benzodiazepine

Treatment recommended for ALL patients in selected patient group

Muscle spasms are both painful and potentially life-threatening if they cause airway compromise or respiratory failure.

Benzodiazepines have been the mainstay of controlling muscle spasms, and in addition have anticonvulsant, sedative, and anxiolytic effects. Diazepam is often used.[1] Diazepam metabolites are active with long half-lives (desmethyldiazepam has a half-life of >100 hours), and for this reason midazolam infusions may be preferred.[54][55] In children, diazepam may cause significant respiratory depression; therefore, midazolam or lorazepam may be preferred.

Primary options

diazepam: children and adults: consult specialist for guidance on dose

OR

lorazepam: children and adults: consult specialist for guidance on dose

OR

midazolam: children and adults: consult specialist for guidance on dose

Plus – wound debridement

Back
ACUTE
|
with clinical tetanus
Plus – 

wound debridement

Treatment recommended for ALL patients in selected patient group

All wounds should be thoroughly cleaned and debrided.[4][38]

Wound debridement removes spores and necrotic tissue, eradicating the anaerobic conditions that facilitate clostridial growth. Antibiotic penetration into devitalized tissue is likely to be poor, emphasizing the importance of adequate wound debridement.[50]

Plus – antibiotics

Back
ACUTE
|
with clinical tetanus
Plus – 

antibiotics

Treatment recommended for ALL patients in selected patient group

Antibiotics halt bacterial replication and thereby reduce the production of new toxins. Metronidazole has superseded penicillin G as the antimicrobial of choice for the treatment of tetanus.

Evidence suggests that, compared with penicillin G, metronidazole was associated with reduced mortality.[51] Other evidence indicates no difference in mortality, but that metronidazole is associated with a lower requirement for muscle relaxants and sedatives.[52]

Although penicillin G has traditionally been used,[19] it is structurally similar to gamma-aminobutyric acid (GABA) and competitively antagonizes this neurotransmitter, an action that could potentiate the effects of tetanus toxin in inhibiting release of GABA into the synaptic cleft and enhancing central nervous system excitability.[19]

Alternative antibiotics include clindamycin, tetracycline, and vancomycin;[1] however, an infectious disease specialist should be consulted for doses and regimens for this indication.

Primary options

metronidazole: children: consult specialist for guidance on dose; adults: 500 mg intravenously every 6 hours for 7-10 days

Secondary options

penicillin G potassium: children: consult specialist for guidance on dose; adults: 100,000 to 200,000 units/kg/day intravenously/intramuscularly given in divided doses every 4-6 hours for 7-10 days

Tertiary options

clindamycin: children and adults: consult specialist for guidance on dose

OR

tetracycline: children and adults: consult specialist for guidance on dose

OR

vancomycin: children and adults: consult specialist for guidance on dose

Plus – tetanus immune globulin (TIG) or tetanus antitoxin or human normal immune globulin + intramuscular tetanus vaccine

Back
ACUTE
|
with clinical tetanus
Plus – 

tetanus immune globulin (TIG) or tetanus antitoxin or human normal immune globulin + intramuscular tetanus vaccine

Treatment recommended for ALL patients in selected patient group

Passive immunization with TIG:

Intramuscular TIG should be administered to patients with clinical tetanus.[1][38] It should be administered as soon as possible after the injury.[1] Passive immunization neutralizes toxin, reducing the duration and severity of tetanus.

Intramuscular TIG (half-life 24.5 to 31.5 days) is the treatment of choice.[1][38]​​ If intramuscular TIG is unavailable, intravenous human normal immune globulin may be used.[38] Tetanus antitoxin (equine) is more widely available in the developing world (it may not be available or may be difficult to access in some countries), but has a higher incidence of anaphylaxis (20% of cases) and a much shorter half-life (2 days).[19]​ Tetanus antitoxin (human) may also be available in some countries.

Active immunization with tetanus vaccine:

All patients with clinical tetanus should receive immunization with tetanus toxoid-containing vaccine to stimulate long-term humoral and cellular immunity. In addition, it is thought that tetanus toxoid saturates ganglioside receptors, blocking the binding of wild-type toxin.[19]

Primary options

tetanus immune globulin (human): children and adults: see local specialist protocol for dosing guidelines

Secondary options

immune globulin (human): children and adults: see local specialist protocol for dosing guidelines

Plus – nondepolarizing neuromuscular blocking agents or intrathecal baclofen

Back
ACUTE
|
with clinical tetanus
|
with severe muscle spasms
Plus – 

nondepolarizing neuromuscular blocking agents or intrathecal baclofen

Treatment recommended for ALL patients in selected patient group

Some patients require paralysis with nondepolarizing neuromuscular blocking agents in addition to sedation. Traditionally pancuronium was used, although this was known to potentially aggravate autonomic instability.[57] Vecuronium and rocuronium are associated with less autonomic disturbance, and are preferred.

Baclofen stimulates postsynaptic GABAB receptors and has been found to improve muscle spasms when given by intrathecal bolus or infusion, but only in a few small studies.[58][59][60][61] In a retrospective outcome study from a single centre in Portugal during 1998 to 2003, intrathecal baclofen was given as an initial bolus, followed by a continuous infusion.[62] This controlled spasms and rigidity in 21 of 22 patients with grade 3 tetanus. Most patients required therapy for at least 3 weeks (range 8 to 30 days). One patient developed meningitis secondary to infection of the intrathecal catheter. Intrathecal baclofen has a narrow therapeutic range and considerable inter-individual pharmacodynamic variability.[58]

Treatment with intrathecal baclofen should only be considered under specialist guidance and administration.

Primary options

vecuronium: children and adults: see local specialist protocol for dosing guidelines

OR

rocuronium: children and adults: see local specialist protocol for dosing guidelines

Secondary options

pancuronium: children and adults: see local specialist protocol for dosing guidelines

OR

baclofen intrathecal: children and adults: see local specialist protocol for dosing guidelines

Plus – magnesium sulfate + sedation + beta-blockade

Back
ACUTE
|
with clinical tetanus
|
with autonomic dysfunction
Plus – 

magnesium sulfate + sedation + beta-blockade

Treatment recommended for ALL patients in selected patient group

Autonomic dysfunction is extremely difficult to control. It arises in patients with severe disease, usually in the second week of illness.

Magnesium sulfate has previously been reported to be both an effective adjunct in controlling autonomic disturbance in heavily sedated patients with severe tetanus and successful in relieving spasms in nonventilated patients.[64][65]​​[66] One randomized controlled trial found that magnesium sulfate significantly reduced the requirement for other drugs (e.g., midazolam) for the control of muscle spasms and showed that patients are less likely to need verapamil for cardiovascular instability, when compared with placebo.[67] There was no difference in the need for mechanical ventilation.[67] An earlier, small prospective observational study suggested that magnesium sulfate reduced not only the use of neuromuscular blocking agents to control severe spasms but also the requirement for mechanical ventilation when compared with historical controls.[68] Conflicting results may reflect differences in study design and magnesium administration.[67] The aim is not to completely abolish muscle rigidity, but to reduce it to a level that is acceptable to the patient and allows swallowing of saliva, mouth care, and limb physical therapy. One meta-analysis of 3 controlled trials found no reduction in mortality for patients treated with magnesium sulfate compared with placebo or diazepam therapy. Conclusions about the effects of magnesium on duration of intensive care stay, duration of hospital stay, and requirement for ventilatory support could not be drawn, due to large methodological differences between the studies included.[69]

Sedation helps to reduce autonomic instability, and both benzodiazepines and morphine sulfate are useful in this regard. If patients are already on a benzodiazepine, treatment should be rationalized. Morphine sulfate reduces sympathetic tone in the heart and the vascular system, improving cardiovascular stability without compromising cardiac performance.[1][70]

Beta-blockade may be required in further management of the autonomic instability. Use, choice, and dosing of a beta-blocker should be decided in consultation with a specialist. Pure beta-blockade, with propranolol, has been associated with sudden death.[71] Labetalol has been used to provide combined alpha- and beta-blockade in a small number of patients.[78] Esmolol is an extremely short-acting beta-blocker and has been reported to be effective in controlling autonomic instability in case reports.[79][80]

Primary options

magnesium sulfate: children: consult specialist for guidance on dose; adults: 5 g intravenously as a loading dose, followed by 2-5 g/hour infusion, consult specialist for further guidance on dose

and

morphine sulfate: children and adults: see local specialist protocol for dosing guidelines

Secondary options

magnesium sulfate: children: consult specialist for guidance on dose; adults: 5 g intravenously as a loading dose, followed by 2-5 g/hour infusion, consult specialist for further guidance on dose

and

morphine sulfate: children and adults: see local specialist protocol for dosing guidelines

-- AND --

labetalol: children and adults: see local specialist protocol for dosing guidelines

or

esmolol: children and adults: see local specialist protocol for dosing guidelines

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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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