Tetanus in Emergency Medicine Medication

Drugs used to treat muscle spasm, rigidity, and tetanic seizures include sedative-hypnotic agents, general anesthetics, centrally acting muscle relaxants, and neuromuscular blocking agents. Antibiotics are used to prevent multiplication of C tetani, thus halting production and release of toxins.

Class Summary

Sedative-hypnotic agents are the mainstays of tetanus treatment. Benzodiazepines are the most effective primary agents for muscle spasm prevention and work by enhancing GABA inhibition. Diazepam is the most frequently studied and used drug. Diazepam reduces anxiety, produces sedation, and relaxes muscles. Lorazepam is an effective alternative. Large amounts of either may be required (up to 600 mg/d).

Phenobarbital is another anticonvulsant that may be used to prolong 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.

Magnesium sulphate can be used alone or in combination with benzodiazepines to control spasm and autonomic dysfunction: 5 g (or 75 mg/kg) intravenous loading dose, then 2-3 g/h until spasm control is achieved.^[3] Monitor patellar reflex, as areflexia (absence of patellar reflex) occurs at the upper end of the therapeutic range (4 mmol/L). If areflexia develops, dose should be decreased to avoid overdose. 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.^[4]

Diazepam (Valium)

Mainstay of treatment of tetanic spasms and tetanic seizures. Depresses all levels of CNS, including limbic and reticular formation, possibly by increasing activity of GABA, a major inhibitory neurotransmitter.

Phenobarbital (Barbita, Luminal)

Drug dose must be small enough so that respirations are not depressed. If patient is already on a ventilator, higher doses may provide desired sedation.

Class Summary

These agents can inhibit both monosynaptic and polysynaptic reflexes at spinal level, possibly by hyperpolarization of afferent terminals.

Baclofen (Lioresal)

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 PO baclofen. Repeated IT injections have been efficacious in limiting duration of artificial ventilation or preventing intubation.

May induce hyperpolarization of afferent terminals and inhibit both monosynaptic and polysynaptic reflexes at spinal level.

Entire dose of baclofen is administered as a bolus injection. Dose may be repeated after 12 h or more if spontaneous paroxysms return.

Continuous IT baclofen has been reported in a very small number of patients with tetanus. Refer to manufacturer's product information on Lioresal IT for further information.

Dantrolene (Dantrium)

Stimulates muscle relaxation by modulating skeletal muscle contractions at a site beyond the myoneural junction and by acting directly on the muscle. Not FDA approved for use in tetanus but has been described in a small number of case reports.

Class Summary

These agents are used to neutralize any toxin that has not reached the CNS.

Tetanus immune globulin (TIG)

Used as prophylaxis against tetanus and to treat patients with circulating tetanus toxin. TIG provides passive immunity. 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.

Class Summary

Administer to patients with clinical tetanus. However, efficacy is questioned. Theoretically, antibiotics may prevent multiplication of C tetani, thus halting production of toxin. Nevertheless, a study of 364 patients found no difference in fatality rates between patients who received antibiotics and those who did not. Penicillin G is the drug of choice. Metronidazole is considered by some to be a better drug. One study demonstrated a lower mortality for patients administered metronidazole compared with penicillin.^[5] Tetracycline is an alternative drug for patients who are allergic to penicillin or metronidazole. Large doses of antibiotics are recommended to favor diffusion into devitalized tissue.

Penicillin G (Pfizerpen)

Interferes with synthesis of cell wall mucopeptide during active multiplication, resulting in bactericidal activity against susceptible microorganisms.

A 10- to 14-d course of treatment is recommended. Large IV doses of penicillin may cause hemolytic anemia and neurotoxicity. Cardiac arrest has been reported in patients administered massive doses of penicillin G potassium. Patients with renal failure are particularly at risk.

Metronidazole (Flagyl)

Active against various anaerobic bacteria and protozoa. Appears to be absorbed into cells, and intermediate-metabolized compounds that are formed bind DNA and inhibit protein synthesis, causing cell death.

A 10- to 14-d course of treatment is recommended. Some consider this the DOC since penicillin G is also a GABA agonist, which may enhance effects of the toxin.

Doxycycline (Vibramycin, Doxychel)

Inhibits protein synthesis and thus bacterial growth by binding with 30S and possibly 50S ribosomal subunits of susceptible bacteria. A 10- to 14-d course of treatment is recommended.

Class Summary

These agents inhibit the transmission of nerve impulses at neuromuscular junctions of skeletal muscles and/or autonomic ganglia.

Vecuronium (Norcuron)

Prototypic, nondepolarizing neuromuscular blocking agent that reliably results in muscular paralysis. For maintenance of paralysis, a continuous infusion may be used.

Infants are more sensitive to neuromuscular blockade activity, and although the same dose is used, recovery is prolonged by 50%. Not recommended for use in neonates.