Tetanus Treatment & Management

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 complications

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

Passive immunization with human tetanus immune globulin (TIG) shortens the course of tetanus and may lessen its severity. A dose of 500 U may be as effective as larger doses. Therapeutic TIG (3,000-6,000 units as 1 dose) has also been recommended for generalized tetanus. ^[20] Other treatment measures include ventilatory support, high-calorie nutritional support, and pharmacologic agents that treat reflex muscle spasms, rigidity, tetanic seizures and infections.

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

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

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

The possibility of developing tetanus directly correlates with the characteristics of the wound. Recently acquired 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 wounds are those that are grossly contaminated or that are caused by blunt trauma or bites. Wounds should be explored, carefully cleansed, and properly debrided.

In many cases, the wound responsible for tetanus is clear at presentation, in which case surgical debridement offers no significant benefit. If debridement is indicated, it should be undertaken only after the patient 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 the risk of releasing tetanospasmin into the bloodstream, any wound manipulation should be delayed until several hours after administration of antitoxin.

Elimination of toxin production

Antimicrobials are used to decrease the number of vegetative forms of C tetani (the toxin source) in the wound. 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 is also associated with lower mortality. ^[21]

Other antimicrobials that have been used are clindamycin, erythromycin, tetracycline, and vancomycin. Their role is not well established.

Neutralization of unbound toxin

Tetanus immune globulin (TIG) is recommended for treatment of tetanus. It should be kept in mind that TIG can only help remove unbound tetanus toxin; it cannot affect toxin bound to nerve endings. A single intramuscular (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-appropriate tetanus 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 toxoid vaccination should receive a second dose 1-2 months after the first dose and a third dose 6-12 months later.

Control of disease manifestations

Benzodiazepines have emerged as the mainstay of symptomatic therapy for tetanus. Diazepam is the most 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 every 1-8 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 with benzodiazepines, 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-acting barbiturates, and chlorpromazine. Propofol has been suggested for sedation. ^[22]

Intrathecal (IT) baclofen, a centrally acting muscle relaxant, has been used experimentally to wean patients off the ventilator and to stop diazepam infusion. IT baclofen is 600 times more potent than oral baclofen. 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 in controlling muscle rigidity, ^{[23, 24]} though others have questioned this. ^[25]

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, the cervical-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 be initiated. ^[26] Magnesium sulfate can be used alone or in combination with benzodiazepines for this purpose. It should be given IV in a loading dose of 5 g (or 75 mg/kg), followed by continuous infusion at a rate of 2-3 g/h until spasm control is achieved. ^[7]

The patellar reflex should be monitored; areflexia (absence of the patellar reflex) occurs at the upper end of 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, but it does reduce the requirement for other drugs to control muscle spasms and cardiovascular instability. ^[27]

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. ^[28] The investigators concluded that further controlled trials were necessary to evaluate the potential effect of this therapy 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 sudden death; only esmolol is currently recommended.

Hypotension requires fluid replacement and dopamine or norepinephrine administration. Parasympathetic overactivity is rare, but if bradycardia is sustained, a pacemaker may be needed. Clinical tetanus does not induce immunity against future attacks; therefore, all patients should be fully immunized with tetanus toxoid during the convalescent period.

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

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

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 respiratory symptoms or those requiring mechanical ventilation

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

Prevention of tetanus is accomplished through vaccination with DTP or DTaP at the ages of 2 months, 4 months, 6 months, 12-18 months, and 4-6 years. For the latest vaccination recommendations, see CDC Immunization Schedules.

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 3-4 vaccinations 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. ^[29]

Alternatively, in situations where the adult probably received vaccination against tetanus and diphtheria but cannot produce a record, vaccine providers may consider serologic testing for antibodies to tetanus and diphtheria toxin with the aim of avoiding unnecessary vaccination. If tetanus and diphtheria antitoxin levels are each higher than 0.1 IU/mL, previous vaccination with tetanus and diphtheria toxoid vaccine is presumed, and a single dose of Tdap is indicated. ^[29]

Adults who received other incomplete vaccination series against tetanus and diphtheria should be vaccinated with Td to complete a 3-dose primary series of tetanus and diphtheria toxoid-containing vaccines. 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 cleansing and debridement and the administration of tetanus toxoid (Td, Tdap, DT, DPT, or DTaP, as indicated) and TIG, when indicated. Pediatric formulations (DT and DTaP) include about the same amount of tetanus toxoid 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 injuries

It is not necessary to wait the typical 10 years to get the adult Tdap dose after the last Td dose. An interval as short as 2 years is suggested to reduce the likelihood of increased reactogenicity, and even shorter intervals may be appropriate if the patient is at high risk for pertussis, has close contact with infants, or may not be able to receive another vaccination. Providers should know that shorter intervals are not contraindicated, that accumulating data reinforce safety of the vaccine, and that there are no concerns 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 it has been more than 5 years since their last dose of tetanus toxoid. Patients who have previously received fewer than 3 doses of tetanus toxoid and patients aged 60 years or older should receive TIG 250-500 units 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 received fewer than 3 doses of tetanus toxoid or if more than 10 years have passed since their last dose. Tdap is preferred 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 tetanus toxoid−containing vaccine is indicated for wound care.

It is important to review the immunization status of all patients who present to an emergency department for any care (regardless of chief complaint). Immunizations should be administered if a lapse of more than 10 years has occurred since the last tetanus booster. If a patient does not remember or cannot give a history of immunization, an immunochromatographic dipstick test may be appropriate and cost-effective for determining tetanus immunity in this setting, though further study is needed to determine the applicability of this approach. ^[30]

The ACIP recommends vaccination at primary care visits for adolescents aged 11-12 years and for adults aged 50 years, review of vaccination histories, and updating of tetanus vaccination status. This is in addition 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. ^{[31, 32, 33]} Key points included the following:

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

• Tdap use in adults – All adults aged 19 years and older who have not yet received a dose of Tdap should receive a single dose, regardless of the interval since the last tetanus- or diphtheria toxoid−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 last receipt 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 may be given a single dose of Tdap instead of Td if they have not previously received Tdap; Tdap can be administered 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 2 available vaccines administered to a person 65 years or older is immunogenic and would provide protection, and a dose of either may be considered valid

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

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

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

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