Tetanus: Treatment and Medication
Treatment
Emergency Department Care: Treatment of tetanus is directed toward the treatment of muscle spasm, prevention of respiratory and metabolic complications, neutralization of circulating toxin to prevent the continued spread, and elimination of the source.
- Admit patients to the ICU. Due to risk of reflex spasms, maintain a dark and quiet environment for the patient. Avoid unnecessary procedures and manipulations.
- Seriously consider prophylactic intubation 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; prepare for emergency surgical airway control. Rapid sequence intubation techniques (eg, with succinylcholine) are recommended to avoid this complication.
- Perform tracheostomy in patients requiring intubation for more than 10 days. Tracheostomy has also been recommended after onset of the first generalized seizure.
- Surgical therapy includes debridement of wounds to remove organisms and to create an aerobic environment.
- The current recommendation is to excise at least 2 cm of normal viable-appearing tissue around the wound margins.
- Incise and drain abscesses.
- Delay any wound manipulation until several hours after administration of antitoxin due to risk of releasing tetanospasmin into the bloodstream.
- Institute prevention measures for deep venous thrombosis, gastrointestinal ulcer, and decubitus ulcer.
- The maintenance of nutrition is extremely important and should be carried out in seriously ill patients via nasoduodenal tubes, gastrostomy tube feedings, or parenteral hyperalimentation.
Consultations:
- An intensive care medicine specialist should be the primary physician coordinating the patient's care.
- Consult a pulmonary medicine specialist after admission to the ICU for patients with severe respiratory symptoms or those requiring mechanical ventilation.
- Consult an anesthesiologist after admission to the ICU if intrathecal baclofen is to be administered.
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.Drug Category: Anticonvulsants -- 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.
Phenobarbital is another anticonvulsant that may be used to prolong effects of diazepam. Phenobarbital also is used to treat severe muscle spasms and provide sedation when neuromuscular blocking agents are used.
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. Adult Dose Mild spasms: 5-10 mg PO q4-6h prn
Moderate spasms: 5-10 mg IV prn
Severe spasms: Mix 50-100 mg in 500 mL D5W and infuse at 40 mg/hPediatric Dose Mild spasms: 0.1-0.8 mg/kg/d PO divided tid/qid
Moderate or severe spasms: 0.1-0.3 mg/kg IV q4-8hContraindications Documented hypersensitivity; narrow-angle glaucoma Interactions Toxicity of benzodiazepines in CNS is increased when used concurrently with alcohols, phenothiazines, barbiturates, and MAOIs; cisapride can increase diazepam levels significantly Pregnancy
D - Unsafe in pregnancy
Precautions Caution in patients receiving other CNS depressants; caution in patients with low albumin levels or hepatic failure because diazepam toxicity may increase
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. Adult Dose 1 mg/kg IM q4-6h; not to exceed 400 mg/d Pediatric Dose 5 mg/kg/d IV/IM divided tid/qid Contraindications Documented hypersensitivity; marked impairment of liver function; severe respiratory disease; nephritic patients Interactions May decrease effects of chloramphenicol, digitoxin, corticosteroids, carbamazepine, theophylline, verapamil, metronidazole, and anticoagulants (patients stabilized on anticoagulants may require dosage adjustments if added to or withdrawn from their regimen); coadministration with alcohol may produce additive CNS effects and death; chloramphenicol, valproic acid, and MAOIs may increase phenobarbital toxicity; rifampin may decrease phenobarbital effects; induction of microsomal enzymes may result in decreased effects of oral contraceptives in women (must use additional contraceptive methods to prevent unwanted pregnancy; menstrual irregularities also may occur) Pregnancy
D - Unsafe in pregnancy
Precautions In prolonged therapy, evaluate hematopoietic, renal, hepatic, and other organ systems; caution in fever, hyperthyroidism, diabetes mellitus, and severe anemia since adverse reactions can occur; caution in myasthenia gravis and myxedema
Drug Category: Skeletal muscle relaxants -- 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.Adult Dose <55 years: 1000 mcg IT
>55 years: 800 mcg ITPediatric Dose <16 years: 500 mcg IT
>16 years: Administer as in adultsContraindications Documented hypersensitivity Interactions Opiate analgesics, benzodiazepines, alcohol, TCAs, guanabenz, MAOIs, clindamycin, and hypertensive agents may increase baclofen effects Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions Caution in patients with history of autonomic dysreflexia and when spasticity is used to obtain increased function; autonomic dysreflexia can result from withdrawal of this medication
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. Adult Dose 1 mg/kg IV over 3 h; repeat q4-6h prn Pediatric Dose 0.5 mg/kg IV bid initial; increase to 0.5 mg/kg IV bid/qid, then by increments of 0.5-3 mg/kg bid/qid prn; not to exceed 100 mg qid Contraindications Documented hypersensitivity; active hepatic disease (hepatitis, cirrhosis) Interactions Toxicity may increase with coadministration of clofibrate and warfarin; coadministration with estrogen may increase hepatotoxicity in women >35 y Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions May cause hepatotoxicity (use only for recommended indications); caution in impaired pulmonary function and severe cardiac insufficiency; may cause photosensitivity with exposure to sunlight
Drug Category: Antitoxins -- These agents are used to neutralize any toxin that has not reached the CNS.
Tetanus immune globulins (Hyper-Tet, Bay-Tet) -- 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. Adult Dose Prophylaxis: 250-500 U IM in opposite extremity to tetanus toxoid
Clinical tetanus: 3,000-10,000 U IMPediatric Dose Prophylaxis: 250 U IM in opposite extremity to tetanus toxoid
Clinical tetanus: Administer as in adultsContraindications Patients with hypersensitivity to horse or cow proteins should not receive the equine or bovine antitoxins; do not inject in same site or with same syringe as tetanus toxoid; not to be administered intravenously Interactions Live-virus vaccines may not replicate successfully, and antibody response could be reduced when vaccine is administered after tetanus immune globulin because of presence of antibodies in the immune globulin; live-virus vaccines should ideally be administered at least 3 mo after therapy with tetanus immune globulin; if administration of an immune globulin preparation becomes necessary because of exposure to disease, live-virus vaccines can be given simultaneously with immune globulin at site remote from that chosen for immune globulin; vaccine virus replication and stimulation of immunity occurs 1-2 wk after vaccination, therefore, if interval between administration of vaccine and immune globulin is <14 d or if they were administered simultaneously, vaccination should be repeated at least 3 mo after immune globulin preparation was given, unless serologic testing indicates that adequate antibodies were formed Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions Caution in patients with prior systemic allergic reactions following administration human immunoglobulin preparations; caution in severe thrombocytopenia or any coagulation disorder that would contraindicate IM injections
Drug Category: Antibiotics -- 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 to penicillin. 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.Adult Dose 10-24 million U/d IV/IM divided qid Pediatric Dose 100,000-250,000 U/kg/d IV/IM divided qid Contraindications Documented hypersensitivity Interactions Probenecid can increase effects of penicillin; coadministration of tetracyclines can decrease effects of penicillin Pregnancy
B - Usually safe but benefits must outweigh the risks.
Precautions Caution in impaired renal function
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.Adult Dose 500 mg PO q6h or 1 g IV q12h; not to exceed 4 g/d Pediatric Dose 15-30 mg/kg/d IV divided q8-12h; not to exceed 2 g/d Contraindications Documented hypersensitivity; first trimester of pregnancy Interactions Cimetidine may increase toxicity of metronidazole; may increase effects of anticoagulants; may increase toxicity of lithium and phenytoin; disulfiramlike reaction may occur with orally ingested ethanol Pregnancy
B - Usually safe but benefits must outweigh the risks.
Precautions Adjust dose in hepatic disease; monitor for seizures and development of peripheral neuropathy
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. Adult Dose 100 mg PO/IV q12h Pediatric Dose <8 years: Not recommended
<100 lb (45 kg): 2 mg/lb/d (4.4 mg/kg/d) PO/IV divided bid
>100 lb (45 kg): Administer as in adultsContraindications Documented hypersensitivity; severe hepatic dysfunction Interactions Bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; tetracyclines can increase hypoprothrombinemic effects of anticoagulants; tetracyclines can decrease effects of oral contraceptives, causing breakthrough bleeding and increased risk of pregnancy Pregnancy
D - Unsafe in pregnancy
Precautions Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider drug serum level determinations in prolonged therapy; tetracycline use during tooth development (last half of pregnancy through age 8 y) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines
Drug Category: Neuromuscular blocking agents -- 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.Adult Dose 0.08-0.1 mg/kg IV; may reduce to 0.05 mg/kg if patient has been treated with succinylcholine
Maintenance of paralysis: 0.025-0.1 mg/kg/h IV; may titrate to desired train-of-4 response (commonly 2 of 4 twitches)Pediatric Dose 7 weeks to 1 year: 0.08-0.1 mg/kg/dose followed by maintenance dose of 0.05-0.1 mg/kg q1h prn
1-10 years: May require higher initial dose and more frequent supplementation
>10 years: Administer as in adultsContraindications Documented hypersensitivity; myasthenia gravis or related syndromes Interactions When vecuronium is used concurrently with inhalational anesthetics, neuromuscular blockade is enhanced; renal or hepatic failure as well as concomitant administration of steroids may result in prolonged blockade despite withdrawal of the agent Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions In myasthenia gravis or myasthenic syndrome, small doses of vecuronium may have profound effects
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Synonyms And Related Keywords
Clostridium tetani, C tetani, tetanus immunization, tetanus vaccination, tetanus toxoid, diphtheria and tetanus toxoids plus pertussis vaccinations, DPT vaccination, lockjaw, stiffness of the jaw, risus sardonicus, hypertonia, tetanus, muscle spasms, lacerations, puncture wounds, burns, abrasions
