Etiology
Tetanus is a specific infection often associated with trauma. In addition to occurring following various injuries, it can also develop in postpartum women and newborns under unsanitary delivery conditions. The causative agent is Clostridium tetani, an obligate anaerobic gram-positive bacillus. This bacterium is normally found in the intestines of humans and animals and is excreted into the surrounding environment through feces. It exists in spore form in nature, particularly in soil. Clostridium tetani demonstrates strong environmental adaptability, including resistance to boiling. The contamination rate of wounds by Clostridium tetani is high, with contamination rates on battlefields reaching as much as 25%–80%. However, tetanus develops in only 10%–20% of those contaminated, suggesting that additional factors are required for the disease to develop. The primary contributing factor is a hypoxic (oxygen-deprived) environment. Deep wounds with small external openings, necrotic tissue, blood clots, tight packing of wounds, ischemia, or concurrent infections with aerobic bacteria that consume residual oxygen in the wound may create conditions suitable for the growth and proliferation of Clostridium tetani.
Pathophysiology
In an oxygen-deprived environment, Clostridium tetani spores germinate and proliferate, producing large quantities of exotoxins, primarily tetanospasmin. Tetanospasmin is absorbed into the spinal cord, brainstem, and other areas, where it binds to synapses of interneurons, inhibiting the release of inhibitory neurotransmitters. This leads to heightened excitability of motor neurons due to the loss of central inhibition, causing sustained muscle tension and spasms. Additionally, tetanospasmin blocks the spinal cord's inhibition of the sympathetic nervous system, resulting in excessive sympathetic stimulation, causing elevated blood pressure, tachycardia, hyperthermia, and profuse sweating.
Clinical Manifestations
The incubation period for tetanus is commonly 7–8 days but can range from as short as 24 hours to as long as several months or even years. A shorter incubation period typically correlates with a poorer prognosis. Approximately 90% of cases occur within two weeks of injury.
Prodromal Symptoms
During the early stages, symptoms include general fatigue, dizziness, headache, difficulty chewing, local muscle tightness or pulling pain, and hyperactive reflexes.
Classic Symptoms
The hallmark presentation is paroxysmal intense muscle spasms superimposed on sustained muscle tension (rigidity and stiffness). The muscles most commonly affected first are the masseter muscles (jaw muscles), followed by facial muscles, neck muscles, back and abdominal muscles, limb muscles, and eventually the diaphragm. Common clinical signs include:
- Trismus (lockjaw): Difficulty opening the mouth.
- Facial Expression Changes: Furrowed brows, drooping corners of the mouth, and a characteristic "sardonic grin."
- Neck Rigidity and Opisthotonos: Stiffness of the neck and hyperextension of the head. When the back and abdominal muscles contract simultaneously, the more powerful back muscles cause the body to arch into a "opisthotonos" or "lateral opisthotonos" posture.
- Respiratory Impairment: Diaphragm involvement during spasms can result in cyanosis of the face and lips, difficulty breathing, or even respiratory arrest.
Minor stimuli such as light, sound, touch, or swallowing can provoke episodes of spasms. Intervals between spasms vary, with frequent episodes indicating more severe disease.
Patients typically remain conscious during spasms but exhibit painful facial expressions. Each spasm lasts from a few seconds to several minutes. Severe spasms can lead to muscle tears or even fractures. Bladder sphincter spasms may result in urinary retention, and persistent diaphragm or respiratory muscle spasms can cause respiratory arrest. The leading causes of death in tetanus are asphyxia, heart failure, or pulmonary complications.
The course of the disease usually lasts 3–4 weeks. With aggressive treatment and no complications, the frequency and severity of spasms may gradually diminish, and the recovery phase typically spans approximately one week. Muscle tension and hyperactive reflexes may persist for some time. During recovery, some patients may experience psychiatric symptoms, such as hallucinations or disorganized speech and behavior, although these typically resolve spontaneously.
In some cases, symptoms are limited to persistent localized muscle rigidity at the wound site, which may last for weeks or months, with a better prognosis. In neonates, clinical manifestations tend to be atypical due to weaker muscle strength. These include inability to cry, feed, or move, and signs of weak or labored breathing.
Diagnosis and Differential Diagnosis
Laboratory tests are rarely useful for diagnosing tetanus, and the diagnosis primarily relies on clinical findings. A suspicion for tetanus should arise in patients with a history of trauma and symptoms such as muscle rigidity, trismus, neck stiffness, and hyperactive reflexes.
Differential diagnoses include:
Purulent Meningitis
Although "opisthotonos" and neck stiffness might be present, paroxysmal spasms are absent. Purulent meningitis is characterized by severe headache, high fever, projectile vomiting, and occasional altered consciousness. Cerebrospinal fluid (CSF) analysis typically shows increased pressure and elevated white blood cell counts.
Rabies
A history of being bitten by a rabid animal is often evident, and spasms primarily involve the swallowing muscles. Symptoms include inability to swallow water, excessive salivation, and spasms triggered by water sounds or visual stimuli.
Other Conditions
These may include temporomandibular joint arthritis, eclampsia, and conversion disorders.
Prevention
Clostridium tetani is an anaerobic bacterium that requires a hypoxic environment for growth and reproduction. Early thorough debridement of wounds and improvement of local circulation are important measures for preventing tetanus. Achieving stable immunity through artificial immunization is another key preventive approach. Active immunization involves the injection of tetanus toxoid antigens to stimulate the production of antibodies in the body for long-term immunity. Passive immunization is intended for injured individuals who have not received prior active immunization. Subcutaneous injection of tetanus antitoxin (TAT) at a dose of 1,500–3,000 IU should be administered as early as possible. Since tetanus has an incubation period, early antitoxin administration can provide preventive effects, but its protection is short-lived, lasting approximately 10 days. For patients with deep wounds that could be infected by anaerobic bacteria, an additional injection may be given after one week. TAT is prone to causing allergic reactions, so intradermal skin testing for allergy is essential before administration. For allergic patients, desensitization protocols should be followed. The optimal method of passive immunization currently available is intramuscular injection of 250–500 IU tetanus immune globulin (TIG).
Treatment
Tetanus is an extremely serious condition with high mortality rates, particularly in neonates and intravenous drug users. Comprehensive and aggressive treatment is essential, including the removal of toxin sources, neutralization of free toxin, control and alleviation of spasms, maintenance of airway patency, and prevention or management of complications.
Wound Management
For identifiable wounds, those with necrotic tissue retention or inadequate drainage should undergo debridement under anesthesia and spasm control, following treatment with antitoxin. Wounds should be flushed with 3% hydrogen peroxide solution, and appropriate drainage devices should be placed for sufficient drainage. If the wound appears healed while sub-crustal tracts or dead spaces are suspected, a careful inspection is necessary.
Use of Antitoxins
Tetanus antitoxin (TAT) is commonly used to neutralize free toxin. Typical doses range from 10,000–60,000 IU, administered via intramuscular injection and intravenous infusion. For intravenous administration, the antitoxin should be diluted in 5% glucose solution and infused slowly. Intradermal allergy testing must be conducted before treatment. Continuous use or dose escalation is not beneficial and may lead to allergic reactions or serum sickness. Tetanus immune globulin (TIG) is typically administered at a dose of 3,000–6,000 IU, usually in a single intramuscular injection.
It is important to note that tetanus infection does not confer lifelong immunity. Within one month after the confirmed diagnosis of tetanus, patients should receive a 0.5 mL dose of tetanus toxoid and complete the basic immunization series.
Antibiotic Therapy
Penicillin is the first-choice antibiotic and is administered via intramuscular injection at a dose of 800,000–1,000,000 U every 4–6 hours or in large doses intravenously at 2,000,000–10,000,000 U per day, divided into 2–4 doses, to inhibit Clostridium tetani. Alternatively, metronidazole may be given at 2.5 g per day in divided oral or intravenous doses for 7–10 days. If the wound shows signs of mixed bacterial infections, appropriate antibiotics should be selected.
Supportive and Symptomatic Treatments
Patients should be hospitalized in an isolation ward to minimize exposure to light, noise, and other potential triggers while avoiding unnecessary disturbances. Alternating sedative and antispasmodic medications may reduce spasms and alleviate discomfort. Options include 10% chloral hydrate, sodium phenobarbital, and diazepam. For severe cases, a combination sedative-hypnotic solution (containing 50 mg each of chlorpromazine and promethazine, 100 mg meperidine, and 250 mL of 5% glucose solution) may be administered as a slow intravenous infusion, though this is contraindicated under hypovolemic conditions. Midazolam and propofol may also be used for critically ill patients. For frequent and poorly controlled spasms, 2.5% thiopental sodium can be administered via slow intravenous injection at 0.25–0.5 g per dose, with caution for risks of laryngospasm and respiratory suppression. This approach is safer in patients who have undergone tracheostomy.
In neonatal tetanus, sedative and antispasmodic medications should be used judiciously, and alternatives such as lobeline or nikethamide may be considered. Given the high metabolic costs and significant water and electrolyte loss due to repeated spasms and sweating, attention should be paid to providing adequate nutrition (high-calorie, high-protein, and high-vitamin diets) as well as maintaining water-electrolyte balance.
Prevention and Management of Complications
Major complications include asphyxia, lung collapse, and pulmonary infections. Early tracheostomy is recommended for critically ill patients to improve ventilation and clear airway secretions. Mechanical ventilation or assisted respiration may be required, and hyperbaric oxygen therapy can be utilized as adjunct treatment. Regular turning and percussion of the back are necessary for sputum clearance and for the prevention of pressure ulcers. Strict aseptic techniques should be followed to prevent cross-infection. For patients with pulmonary infections, antibiotics should be selected based on the causative organism. Dedicated nursing care is advisable to minimize potential accidents, such as tongue biting or falls during spasms that could result in fractures or other injuries.