Page 998 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

CHAPTER 79: Tetanus 729

pulmonary embolism and nosocomial infection. In developed countries,
• Price L, Planche T, Rayner C, Krishna S. Acute respiratory distress
syndrome in Plasmodium vivax malaria: case report and review of this disease is likely to remain an uncommon but challenging problem
that demands an alert and aggressive approach to initial diagnosis and
the literature. Trans R Soc Trop Med Hyg. July 2007;101(7):655-659. management. If this early management is coupled with attentive sup-
• Riddle MS, Jackson JL, Sanders JW, Blazes DL. Exchange transfusion portive care and avoidance of complications over a period of prolonged
as an adjunct therapy in severe Plasmodium falciparum malaria: a critical illness, excellent outcomes are possible in most cases.
meta-analysis. Clin Infect Dis. May 1, 2002;34(9):1192-1198.
• Taylor TE, Fu WJ, Carr RA, et al. Differentiating the pathologies EPIDEMIOLOGY
of cerebral malaria by postmortem parasite counts. Nat Med.
February 2004;10(2):143-145. Historically, tetanus was a feared complication of wound infections.
This Clostridium tetani toxin-mediated disease is one of several
toxin- mediated diseases resulting from wound infections, along with
staphylococcal and streptococcal toxic shock syndrome, wound botu-
REFERENCES lism, and wound diphtheria. Since the advent of routine vaccination
Complete references available online at www.mhprofessional.com/hall after trauma injury and passive immunization for grossly contaminated
wounds, tetanus has become uncommon in the United States with an
average of 43 cases annually from 1998 to 2000. Worldwide it is still a
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major cause of morbidity and mortality, and remains one of the WHO
CHAPTER Tetanus targeted diseases. Overall, 500,000 to 1 million cases occur worldwide
each year, with 213,000 deaths, the majority in children less than 5 years
79 David L. Pitrak of age. This is mainly due to inadequate vaccination, either because of
access to care or neonatal infections before vaccination is given. The
Jason T. Poston
Jodi Galaydick male:female ratio is approximately 3 : 2, representing a greater incidence
of tetanus-prone wounds in males. If patients have access to supportive
care for respiratory failure and cardiovascular instability, recovery is
possible in most cases, although the road to recovery can be quite long
KEY POINTS and fraught with complications of critical illness, most notably nosoco-
• Tetanus is caused by Clostridium tetani and is a toxin-mediated disease. mial infections and venous thrombosis.
• Although rare in the USA, worldwide there are between 500,000
and 1 million cases a year, with over 200,000 deaths. PATHOGENESIS
• It characterized by trismus, dysphagia, and localized muscle rigid- Clostridium tetani spores are found in the soil and the gastrointestinal
ity near a site of injury, often progressing to severe generalized tract of humans and many nonhuman animals. Spores gain access to
muscular spasms complicated by respiratory failure and cardio- tissues through trauma and may remain viable for months to years, but
vascular instability. the incubation period is usually 7 to 10 days. The shorter the incubation
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• The diagnosis of tetanus is made on clinical grounds alone. A clini- period, the more severe the symptoms, and this is most likely related to
cal diagnosis of presumed tetanus is sufficient to initiate treatment. an inoculation effect. The spores are resistant to boiling and antiseptics,
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• Patients with tetanus should be managed in an ICU. In severe but are killed by autoclaving at 121°C for 15 minutes. Usually spores get
cases, the first priority is control of the airway to ensure adequate into tissues from a puncture wound, laceration, or abrasion, but inocu-
ventilation and correction of hypotension related to hypovolemia lation can also occur from tattoos, injections, burn wounds, frostbite,
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and/or autonomic instability. dental infections, and penetrating eye injuries. Neonatal cases can occur
• Antitoxin therapy with human tetanus immune globulin is given from umbilical stump infections.
When the spores germinate the bacteria secrete tetanospasmin
intramuscularly (500-3000 IU) as early as possible. and tetanolysin. Tetanolysin is a virulence factor that causes local
• Treatment to limit continued production and absorption of toxin tissue necrosis. Tetanospasmin is the toxin responsible for the clini-
includes surgical debridement of the site of injury and antimicro- cal syndrome seen in tetanus. It is a very potent toxin, with an esti-
bial therapy with intravenous metronidazole. mated minimum lethal dose being 2.5 ng/kg of body weight. Inside
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• Traditionally muscle rigidity and spasms have been treated with the bacteria, the toxin is inactive, but when a bacterial cell dies, the
high-dose benzodiazepines and narcotics. However, intravenous toxin is released and activated by proteases. If toxin is produced in
magnesium therapy should also be considered. larger amounts, it also accumulates in the lymphatic system of the
• Cardiovascular instability due to autonomic dysfunction is man- invaded muscle, enters the bloodstream via the thoracic duct, and
aged by ensuring normovolemia and using benzodiazepine, is disseminated throughout the body. Toxin passing from blood to
narcotic, and/or magnesium sulfate infusions when needed. skeletal muscle then accumulates in the nerve endings of the motor
• Supportive measures include early provision of nutrition, correc- fibers and proceeds to the ventral horns or cranial nuclei or is taken
up by the lymphatic system and recirculated in the blood. The rate of
tion of electrolyte disturbances, subcutaneous heparin adminis-
tration for prophylaxis of deep venous thrombosis, and prompt accumulation of toxin in the ventral horns of the spinal cord depends
on the length of the neural pathway and the activity of the muscles
antimicrobial therapy for nosocomial infection. involved. Since jaw muscles and spinal postural muscles have short
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• With meticulous management of the manifestations of this disease neural pathways to the ventral horns and are continually active in the
and careful attention to prevention of its major complications, awake human, this is the likely explanation for trismus and neck stiff-
complete recovery is possible in most cases. ness early in the course of the illness.
The toxin cleaves membrane proteins involved in neuroexocyto-
sis and neurons that are involved become incapable of transmitter
Tetanus is often a disease of otherwise healthy active people. Fully release. Tetanospasmin binds to gangliosides on the membranes
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developed tetanus is frequently rapidly fatal unless the patient is sup- of local nerve terminals at the myoneural junction. It then enters
ported through a lengthy period of painful muscle spasms complicated peripheral neurons and is transported to neurons of the CNS via
by respiratory failure, cardiovascular instability, and increased risk of retrograde axonal transport. Tetanus appears when the toxin reaches

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