Tetanus

Introduction and Etiology

• Tetanus is a life-threatening, vaccine-preventable disease. It is caused by the aerobic, gram-positive, spore-forming bacteria Clostridium tetani, which produces the neurotoxin tetanospasmin.¹ Tetanospasmin blocks the release of inhibitory neurotransmitters GABA and glycine from neurons, resulting in the classic presentation of muscle rigidity, painful muscle spasms, and trismus.²
• C. tetani forms spores that are found in soil, dust, and human and animal feces. These spores can withstand harsh environmental conditions, including cold, heat, and common disinfectants. Thus, C. tetani is widespread in the environment and is not thought to be fully eradicable.^1,2
• Tetanus is highly lethal, with 100% mortality without treatment, though it remains 10–20% even with treatment.³
• Incidence and mortality from tetanus have decreased significantly, but it persists in low-income areas with lower vaccination compliance. In these areas, neonates and pregnant women are disproportionately affected groups.² In high-income countries, tetanus cases occur more commonly in elderly adults (older than 60 years) due to waning immunity, and in intravenous (IV) drug users.¹

Pathophysiology

• Infection occurs when spores enter the body through breaks in the skin barrier, especially deep or necrotic wounds. Once inoculated, the spores germinate under anaerobic conditions and produce two toxins: tetanospasmin (TeNT), the primary neurotoxin, and tetanolysin, whose role is not fully understood.
• Under normal conditions, inhibitory interneurons in the spinal cord release vesicles containing the neurotransmitters GABA and glycine, and this process is regulated by the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex.²
• Once tetanospasmin enters the wound, it binds to peripheral motor neurons and is retrogradely transported to the central nervous system (CNS). TeNT then acts as a protease, cleaving SNARE proteins and preventing the release of GABA and glycine from vesicles. This loss of inhibitory control leads to unopposed excitatory signaling, resulting in rigidity, hyperreflexia, and painful spasms, as seen in tetanus.²
• In addition to affecting motor neurons, tetanospasmin can also impair inhibitory control in autonomic neurons, leading to unregulated catecholamine release. The resulting autonomic dysfunction is a major contributor to mortality and necessitates intensive monitoring.²
  • For example, cardiovascular instability due to autonomic dysfunction occurs in approximately 10–30% of patients with tetanus and is characterized by rapid and unpredictable swings between hypertension/tachycardia and bradycardia/hypotension.²

Clinical Presentation

• The clinical presentation of tetanus typically begins 3–21 days after exposure. Earlier symptom onset is associated with more severe disease and a poorer prognosis.³
• Trismus is often the first presenting symptom, followed by progressive muscle stiffness and painful spasms.¹
• Tetanus is classified into four forms: generalized, neonatal, localized, and cephalic, each with distinguishing features (Table 1).

• Opisthotonus, the severe hyperextension of the back that produces the characteristic arched posture, is a late clinical sign. It is less frequently seen in recent years, which is thought to be associated with patients receiving earlier treatment.²
• Autonomic nervous system dysfunction is a dangerous complication that is challenging to manage and associated with a poor prognosis. In neonates, autonomic dysfunction occurs at the onset of symptoms, whereas in adults it develops within a few days.²
• Loss of autonomic control leads to hemodynamic lability, characterized by rapid swings between episodes of hypertension/tachycardia and bradycardia/hypotension. Other manifestations include excessive sweating, cardiac arrhythmias, acute urinary retention, and fecal incontinence.⁶

Diagnosis and Treatment

• Tetanus is diagnosed clinically based on clinical presentation. Cultures for Clostridium tetani are supportive of the diagnosis but not definitive, as they may yield positive results even in the absence of clinical disease.1
• Management of tetanus includes antitoxin administration, wound debridement, antibiotics, control of muscle spasms, management of autonomic dysfunction, possible use of other adjuncts, possible airway management, and supportive care (Table 2).
• Wound debridement
  • The wound should be thoroughly cleaned and debrided to eliminate the source of ongoing toxin production.1
• Antitoxin and antibiotics
  • Two forms of tetanus antitoxin are available: human tetanus immunoglobulin equine antitoxin.
  • Both are effective at neutralizing unbound toxins, with no significant differences in efficacy or side-effect profiles.¹
  • Metronidazole should be administered enteral or IV for 7–10 days.
  • Metronidazole is the antibiotic of choice over penicillin G due to improved outcomes and a better side-effect profile, but penicillin G is an acceptable alternative.⁴
• Control of muscle spasms
  • Benzodiazepines are first-line agents, most commonly diazepam or midazolam. Severe cases may require neuromuscular blocking agents followed by mechanical ventilation and sedation.⁴
• Management of autonomic dysfunction
  • Pharmacologic management of the hemodynamic instability associated with autonomic dysregulation depends on the presentation.
  • Beta blockers like esmolol are first-line for tachycardia and hypertension, while atropine, glycopyrrolate, and other vasoactive and chronotropic agents are used for bradycardia and hypotension.
• Pharmacologic adjuncts discussed in the literature
  • IV magnesium sulfate has been used to assist with autonomic regulation.
  • Opioids are thought to help minimize autonomic stimulation due to pain.
  • Dexmedetomidine or clonidine has been used for anxiolysis.
• Supportive care and future vaccination
  • Because natural infection does not produce immunity, all patients are recommended to receive a full course of the vaccine after recovery.²

Anesthetic Considerations

• In patients with tetanus, anesthetic considerations center on airway management, prevention and mitigation of muscle spasms, and vigilant management of autonomic dysfunction and resulting hemodynamic instability.
• Since benzodiazepines are the first-line treatment for spasms, there is a dual risk of respiratory depression from both the tetanus-associated muscle spasms and the sedation from benzodiazepines (a risk compounded by concurrent opioid administration).²
  • Patients with severe tetanus-associated muscle spasms can deteriorate to respiratory failure. Early airway protection is recommended by endotracheal intubation or, in severe cases, tracheostomy.²
  • If intubation is required, muscle relaxation with a nondepolarizing neuromuscular blocking agent is recommended.⁴ Depolarizing neuromuscular blockers such as succinylcholine are contraindicated due to the risk of hyperkalemia and potentially fatal cardiac arrest.⁸
• Airway management carries a high risk due to the possibilities of severe trismus that can render oral intubation impossible, neck rigidity, and pharyngeal muscle spasms.²
  • Trismus is caused by unopposed excitatory CNS signaling and is often mechanically rigid, making it unlikely to be reliably overcome by neuromuscular blocking agents such as rocuronium.
  • If severe trismus prohibits oral access, attempts to use a muscle relaxant and intubate could lead to a potentially fatal “cannot intubate, cannot ventilate” situation, necessitating tracheostomy.
  • Pharyngeal and laryngeal spasms pose a significant risk of acute airway obstruction and should be anticipated during periods of patient stimulation, such as intubation.
  • Although there are no society-wide standards or guidelines for the anesthetic management of tetanus, the high risk of trismus and airway spasms suggests that video laryngoscopy should be considered a primary approach, given its success in difficult airway scenarios.
• Autonomic dysfunction may result in rapid swings between hypertension/tachycardia and bradycardia/hypotension.
  • Due to the rapid, unpredictable swings in hemodynamics, continuous electrocardiogram monitoring is standard. Arterial line placement is also commonly used for tighter, real-time hemodynamic control.^2,7