Table 1 Summary of evidence base for treatment modalities used in tetanus

Relief of muscle spasms

Benzodiazepines

Advantages: combined sedative, anticonvulsant and muscle relaxant effects

Used as standard therapy

Expert opinion favors use; standard of care

Readily available

A meta-analysis comparing against less used options nowadays showed no benefit in using diazepam

Disadvantages: prolonged duration of action with long-acting drugs

Ethical issues may prevent designing of trials to test efficacy

Magnesium sulfate

Advantages: readily available in resource-limited settings

Meta-analysis shows no mortality benefit (level of evidence A)

Use may be reasonable and should be considered depending on clinician judgment

Has anticonvulsant, muscle relaxant properties

Inadequate evidence to decide on a positive impact on ICU/hospital stay

Disadvantages: needs close monitoring

Risk of hypocalcaemia

Less effective in severe disease

Intrathecal baclofen

Advantages: abolishes spasms promptly

Evidence is limited to a few case series (level of evidence C)

May be harmful in settings where sterility and proper monitoring cannot be maintained

Disadvantages: risk of central nervous system infections High cost

Dantrolene, ketamine, propofol, botulinum toxin

Benefit observed in some case reports only (level of evidence C)

Cannot be recommended without further evidence

Reducing autonomic instability

Clonidine, morphine, bupivacaine with sufentanil, labetolol

Advantages: reduces tachycardia and systolic blood pressure fluctuations. The sedative effect of morphine reduces anxiety and cardiovascular instability

Evidence limited to case reports and few case series (level of evidence C)

Use may be reasonable on a case by case basis

Disadvantages: beta blockers can worsen hypotension, bradycardia

Administration of immunoglobulins

Administration of immunoglobulins is beneficial. The best route of administration (intramuscular alone versus intrathecal plus intramuscular) is debated

Evidence from two meta-analyses are conflicting

Intrathecal administration of immunoglobulins (in addition to intramuscular administration) may be beneficial

Use of antibiotics

Metronidazole use has a theoretical advantage over penicillin use as the latter can potentially facilitate tetanospasmin activity

There are no trials to suggest that antibiotic use is beneficial in tetanus

Either penicillin or metronidazole may be used as the antibiotic of choice in treating tetanus (expert opinion)

Evidence from a randomized controlled trial shows no benefit of choosing metronidazole over penicillin (level of evidence B)