infectious diseases
Tetanus
Treatment of Tetanus
Supportive care, particularly respiratory support Wound debridement Tetanus antitoxin Benzodiazepines for muscle spasms Antibiotics Sometimes medications for autonomic dysfunction Treatment of tetanus requires maintaining adequate ventilation. Additional interventions include early and adequate use of human tetanusimmune globulin(TIG) to neutralize nonfixed toxin; prevention of further toxin production; sedation; control of muscle spasm, hypertonicity, fluid balance, and intercurrent infection; and continuous nursing care. IV immune globulin (IVIG), which contains tetanus antitoxin, may be used if TIG is not available. The patient should be kept in a quiet room. Several principles should guide all therapeutic interventions: Prevent further toxin release by debriding the wound and giving an Antibiotics . Neutralize unbound toxin outside the CNS with TIG. Immunize using tetanus toxoid, taking care to inject it into a different body site than the antitoxin. Minimize the effect of toxin already in the CNS. Because dirt and dead tissue promoteC. tetanigrowth, prompt, thorough debridement, especially of deep puncture wounds, is essential. Antibiotics are not substitutes for adequate debridement and immunization but typically are given. The benefit of human-derived antitoxin depends on how much tetanospasmin is already bound to the synaptic membranes—only free toxin is neutralized. For adults, TIG 500 units IM once appears as effective as higher doses ranging from 3000 to 6000 units and causes less discomfort. Some medical experts recommend infiltration of part of the dose locally around the wound, but its efficacy has not been proved. Antitoxin of animal origin is far less preferable because it does not maintain the patient’s serum antitoxin level well and risk of serum sickness is considerable. If horse serum must be used, the usual dose is 50,000 units IM or IV. (CAUTION: See Skin testing .) If necessary, IVIG or antitoxin can be injected directly into the wound, but this injection is not as important as good wound care. Tetanus infection does not confer immunity, so unless their vaccination history indicates completion of a full primary series, patients should receive a full primary tetanus vaccination series using an age-appropriate preparation (see Prevention below). Antitoxin and vaccine should be injected into different body sites to avoid neutralizing the vaccine. Medications are used to manage spasms. Benzodiazepinesare the standard of care to control rigidity and spasms. They block reuptake of an endogenous inhibiting neurotransmitter, gamma-aminobutyric acid (GABA), at the GABAAreceptor. Diazepamcan help control seizures, counter muscle rigidity, and induce sedation. Dosage varies and requires meticulous titration and close observation. Diazepamhas been used most extensively, butmidazolamis water soluble and preferred for prolonged therapy.Midazolamreduces risk of lactic acidosis due to propylene glycol solvent, which is required fordiazepamandlorazepam, and reduces risk of long-acting metabolites accumulating and causing coma. Benzodiazepines may not prevent reflex spasms, and effective respiration may require neuromuscular blockade withvecuroniumor other paralytic medications and mechanical ventilation.Pancuroniumhas been used but may worsen autonomic instability.Vecuroniumis free of adverse cardiovascular effects but is short-acting. Longer-acting medications (eg, pipecuronium,rocuronium) also work, but no randomized clinical comparative trials have been done. Intrathecalbaclofen(a GABAAagonist) is effective in treating reflex spasms but has no clear advantage over benzodiazepines. Coma and respiratory depression requiring ventilatory support are potential adverse effects. Dantrolenecan be given initially by infusion and thereafter for up to 60 days. Hepatotoxicity and expense limit its use. Morphinemay be given every 4 to 6 hours to control autonomic dysfunction, especially cardiovascular; total daily dose is 20 to 180 mg. Beta-blockade is used to control episodes of hypertension and tachycardia, but use of long-acting medications such aspropranololis not recommended. Sudden cardiac death is a feature of tetanus, and beta-blockade can increase risk; however,esmolol, a short-acting beta-blocker, has been used successfully. IVatropinehas been used at high doses; blockade of the parasympathetic nervous system markedly reduces excessive sweating and secretions. Lower mortality has been reported inclonidine-treated patients than in those treated with conventional therapy. Magnesium sulfate given by IV continuous infusion at doses that maintain serum levels between 4 to 8 mEq/L has a stabilizing effect, eliminating catecholamine stimulation ( Treatment references ). Patellar tendon reflex is used to assess overdosage. Tidal volume may be impaired, so ventilatory support must be available. Serum magnesium levels and electrical cardiac activity need to be closely monitored throughout the infusion period. Other medications that may prove useful include Pyridoxine, which lowers mortality in neonates Valproic acid, which blocks GABA-aminotransferase, inhibiting GABA catabolism Angiotensin-converting enzyme inhibitors, which inhibitangiotensin IIand reducenorepinephrinerelease from nerve endings Dexmedetomidine(a potent alpha-2 adrenergic agonist) Adenosine, which reduces presynapticnorepinephrinerelease and antagonizes the inotropic effect of catecholamines Corticosteroids are of unproven benefit; their use is not recommended. The role of antibiotic therapy is minor compared with wound debridement and general support. Metronidazoleis the recommended antibiotic. In moderate or severe cases, patients should be intubated. Mechanical ventilation is essential when neuromuscular blockade is required to control muscle spasms that impair respirations. IV hyperalimentation avoids the hazard of aspiration secondary to gastric tube feeding. Because constipation is usual, stools should be kept soft. A rectal tube may control distention. Bladder catheterization is required if urinary retention occurs. Chest physiotherapy, frequent turning, and forced coughing are essential to prevent pneumonia. Analgesia with opioids is often needed. 1.Thwaites CL, Yen LM, Cordon SM, et al: Effect of magnesium sulphate on urinary catecholamine excretion in severe tetanus.Anaesthesia63(7):719–725, 2008. doi: 10.1111/j.1365-2044.2008.05476.x 