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732 PART 5: Infectious Disorders

of HTIG ranges from 500 to 3000 units. In areas where HTIG is not Nondepolarizing agents such as pancuronium, vecuronium, and atracu-
readily available, equine antitoxin can be administered in doses 1500 to rium are most commonly administered; however, cisatracurium is pre-
3000 units intramuscularly. The administration on pooled immuno- ferred given it’s reliable metabolism even in the setting of kidney or liver
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globulin has also been proposed as an alternative to HTIG. Patients also dysfunction. 4,26,32 Patients treated with neuromuscular blockade must
need to receive active immunization with three doses of tetanus toxoid, receive adequate sedation and must be supported with mechanical ven-
spaced at least 2 weeks apart following recovery from the acute infection. tilation. These medications should be stopped daily to assess the patient
Booster doses should then be given every 10 years throughout life. 17 and whether continued neuromuscular blockade is necessary. Baclofen
has also been utilized and demonstrated to be effective in several
ANTIMICROBIAL THERAPY studies. 33,34 It is most commonly used via an intrathecal route, and com-
mon adverse events include respiratory suppression, coma, and meningitis.
Antibiotics are generally given both to treat infection at the injury site ■
and to eliminate continued toxin production. They likely play a minor OTHER MEDICATIONS
role in management of the disease. Metronidazole 500 mg intravenously Propofol has been reported to prevent muscular spasms, and may be
every 6 hours for 10 days is the antibiotic of choice for C tetani. used as adjunctive therapy. Magnesium sulfate, which has also been
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Penicillin G, tetracycline, erythromycin, clindamycin, and chloram- demonstrated to improve autonomic instability (see “Supportive Care”
phenicol are also effective, and penicillin has traditionally been the anti- below), may reduce the requirement for benzodiazepines and neuro-
biotic of choice. 10,29 However, penicillin can aggravate spasms because it muscular blocking agents. Dantrolene has also been described in the
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is a GABA antagonist and limited evidence has shown patients treated treatment of tetanus. 32,35,36 Historically, barbiturates and phenothiazines
with intravenous penicillin have prolonged infection with positive cul- were also given, but their use has decreased significantly given the wide-
tures lasting up to 16 days. It is also likely that most wounds associated spread availability of the alternative agents described above.
with tetanus are polymicrobial and harboring β-lactamase–producing
bacteria which penicillin would be inactivated. In a study by Ahmadsyah SUPPORTIVE CARE
and Salim metronidazole was compared to procaine penicillin. The
patients in the metronidazole group had a lower mortality rate, shorter The high mortality associated with tetanus is attributable to the high
length of stay, and better response to treatment. A second study by Yen acuity but also the prolonged duration of illness. Supportive care begins
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et al compared penicillin and metronidazole showed no difference in with the ABCs: Airway, Breathing, and Circulatory support. However,
mortality. For these reasons, penicillin is no longer recommended for the potential for prolonged critical illness makes avoidance of complica-
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tetanus. 17,31 tions an essential goal of therapy.
Complications of tetanus are numerous and frequent. The need for
long-term endotracheal intubation and ventilatory support coupled with ■ AIRWAY MANAGEMENT
increased risk of aspiration may result in bacterial pneumonia. Other Intensive care unit management significantly reduces the mortality
nosocomial infections also occur, as many patients require a long-term from tetanus largely by providing airway protection and ventila-
stay in an ICU. These may include infections of vascular access catheters, tory support early in the disease course. Patients with trismus and
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catheter-related urosepsis, and infected decubitus ulcers. Protracted localized rigidity with no evidence of respiratory compromise do
immobilization places the patient at risk for deep venous thrombosis not require prophylactic endotracheal intubation. However, patients
and pulmonary thromboembolism, which is commonly reported as a with stridor from laryngospasm, diffuse rigidity, a generalized spasm,
cause of death. severe dysphagia, or any evidence of respiratory compromise should
be intubated. While many patients require intubation for the symp-
MINIMIZING MUSCLE SPASM toms of disease, others will require intubation and ventilation due to
escalating doses of benzodiazepines or the initiation of neuromuscu-
Historically, reduction of environmental stimuli that could induce mus- lar blockade.
cular spasm (light, noise, touch) was the mainstay of therapy for patients The preferred route (nasotracheal vs orotracheal) and method (awake
with tetanus. This remains true in locations where medical resources are vs anesthetized) of intubation depend on the clinical situation. However,
limited. Stimulus reduction remains a goal for patients in resource rich a clinician with extensive experience in airway management, such as an
environments, but pharmacotherapy now plays the central role in reduc- anesthesiologist, should perform intubation if possible. An emergency
ing painful and potentially dangerous muscular spasms. cricothyrotomy tray should also be available at the bedside prior to
■ BENZODIAZEPINES attempted intubation. If paralysis is required to facilitate intubation,

The most widely used medications for treatment of muscle spasms are a nondepolarizing agent may be preferred given the increased risk of
hyperkalemia and cardiac arrest associated with depolarizing agents in
the benzodiazepines. Benzodiazepines act indirectly as an agonist in patients with tetanus. Early tracheostomy may be beneficial given that
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the GABA pathway by inhibiting an endogenous inhibitor at the GABA prolonged airway protection is common and tracheostomy may mini-
10
receptor. While diazepam has been used most extensively, shorter mize stimulation and consequent muscle spasm.
acting benzodiazepines with more favorable pharmacokinetic profiles
(such as midazolam) are also effective. These agents should be titrated ■ MANAGING AUTONOMIC INSTABILITY
to reduce muscle rigidity, but also provide anxiolysis and an anesthetic Late presenting autonomic instability characterized by hypertension,
effect that may be beneficial. As doses are escalated to achieve the desired hypotension, and arrhythmias has become the most common cause of
effect, the patient’s ability to protect his or her airway and ventilate death in settings where respiratory support is available. The most rigor-
may be compromised, and intubation and mechanical ventilation may ously studied medication is magnesium sulfate, which was studied in a
be required if not already instituted based on the disease process (see randomized control trial of 256 patients. Treatment with magnesium
“Supportive Care” below). Daily attempts to decrease the dose will pre- sulfate intravenously for 7 days led not only to a significant reduction
vent overtreatment and minimize side effects, but care should be taken to in benzodiazepine and neuromuscular blocking agent administration,
avoid sudden discontinuation, which may precipitate withdrawal. but also to a reduction in mean heart rate and use of verapamil for
■ NEUROMUSCULAR BLOCKING AGENTS autonomic instability (14% vs 3%). In addition to magnesium sulfate,
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labetalol is also widely reported as an effective treatment for autonomic
When therapy with sedative medication fails to adequately control hyperactivity. It is preferred over β-blockade alone, which has been
muscular spasms, neuromuscular blocking agents should be used. associated with sudden cardiac death. Morphine sulfate and other
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