Tetanus

Tetanus is a wound infection caused by the toxin of the anaerobic spore-forming bacillus Clostridium tetani, characterized by damage to the nervous system with attacks of tonic and tetanic convulsions. Symptoms of tetanus include intermittent tonic spasms of voluntary muscles. Diagnosis is based on the clinical picture of the disease. Treatment of tetanus consists of the administration of immunoglobulin and intensive support.

ICD-10 codes

• AZZ. Neonatal tetanus.
• A34. Obstetric tetanus.
• A35. Other forms of tetanus.

There is no single classification of tetanus. A working classification is generally accepted, which includes several positions.

1. According to the portal of entry, there are wound, endometrial (after abortions), infectious (in combination with purulent processes), injection (with the transition to disposable syringes, it has not been encountered in recent years), umbilical (tetanus of newborns), burn, traumatic and other rare forms, for example, urethral, rectal, vaginal (with damage to the mucous membrane by foreign bodies).
2. According to the route of spread, tetanus is divided into: local, ascending, descending (generalized) tetanus.
3. According to the severity of the disease, mild, moderate, severe and very severe forms are noted.

What causes tetanus?

Tetanus is caused by the tetanus bacillus, which forms long-lived spores and can be found in dirt and animal feces, where it remains viable for many years. Worldwide, tetanus kills about 500,000 people each year, with the highest mortality rate among newborns and young children, but not all cases of tetanus are detected, so these estimates can be considered rough. In the United States, only 37 cases of this disease were registered in 2001. The incidence of the disease is directly related to the level of immunization of the population, which indicates the effectiveness of preventive measures. In the United States, more than half of elderly patients have inadequate antibody levels. 33-50% of cases of the disease are registered in this age group. The remaining cases of the disease are mainly registered in people aged 20-59 years, whose immunization was inadequate. The incidence of the disease in people under 20 years is less than 10%. Patients with burns, surgical wounds, and those with a history of infected injection sites (drug addicts) are most likely to develop tetanus. Tetanus can result from trivial or even unnoticed wounds. The infection can also develop after childbirth. It can occur in the uterus (maternal tetanus) or in the navel of the newborn (neonatal tetanus).

When anaerobic conditions are created, the spores germinate, forming vegetative forms that secrete a specific tetanospasmin that acts on neurons. Depending on the amount of toxin, it can spread through local tissues, nerve trunks, lymphatic vessels, or with blood. The nature of the clinical manifestations of the disease depends on the route of spread.

With a very small amount of toxin, it spreads through the muscles with damage to their nerve endings and regional nerve trunks. The process develops locally, most often causing non-convulsive contraction, fibrillation. With a small amount of toxin, it spreads through the muscles and perineurally, including nerve endings, nerves to synapses and spinal cord roots. The process has the character of a mild ascending form with the development of tonic and tetanic (clonic) seizures in the limb segment.

Moderate and severe ascending forms of tetanus develop less frequently with moderate and significant amounts of toxin. Its spread occurs peri- and endoneurally, as well as intraxonally, affecting the anterior and posterior horns of the spinal cord, synapses and neurons, as well as the motor nuclei of the spinal cord and cranial nerves. This is accompanied by the development of general tonic seizures, against the background of which tetanic ones appear.

When the toxin enters the blood and lymph, it spreads throughout the body, affecting all muscle groups and nerve trunks and intra-axially from neuron to neuron, reaching various motor centers. The speed of spread depends on the length of each neural pathway. The shortest neural pathway is in the facial nerves, so the convulsive process develops in them first, affecting the facial muscles and chewing muscles. Then the centers of the muscles of the neck and back are affected, and later the limbs. The respiratory muscles of the chest and diaphragm are the last to be involved in the process.

Together, this determines the development of the descending (generalized) form of tetanus.

The brain is not affected by tetanus toxin, so patients remain conscious even in the most severe cases. There is a concept of so-called cephalic tetanus, when the brain is directly affected by clostridium tetani with penetrating head wounds with the development of general convulsions, but they have nothing in common with the convulsions characteristic of tetanus.

What are the symptoms of tetanus?

The incubation period for tetanus is on average 6-14 days, with fluctuations from 1 hour to a month, rarely more. The shorter the incubation period, the more severe the process. The severity of the disease is determined by the severity of the convulsive syndrome, the frequency and speed of the onset of convulsions from the onset of the disease, their duration, the body's temperature reaction, the state of the cardiovascular system, respiration, the presence and severity of complications.

Tetanus usually begins acutely, less often a short (up to a day) prodrome, which is accompanied by general malaise, nagging pain in the wound or already formed scar, fibrillary twitching of the surrounding muscles, increased patient reaction to external stimuli, especially sound and light, even light touches to the wound or surrounding muscles lead to a sharp increase in their tone and increased pain. Subsequently, this process spreads to all muscles innervated by the affected nerve. Muscle pain is very strong due to their constant tonic tension and becomes literally unbearable with tetanic contractions - and this is the most characteristic sign of tetanus damage.

The clinical manifestations are quite characteristic, but tetanus is rare and doctors, although they remember about it, often do not assume that they have encountered it, and in most cases they believe that it is an atypical form of some common disease.

The most common in practice is descending (generalized) tetanus of moderate severity (68%). The prodromal period is short (6-8 days). It is accompanied by an increase in body temperature to 38-39 degrees, profuse, often profuse sweating. Pain in the throat, neck, face. The doctor's first thought is - is it angina? For differential diagnosis, it is enough to examine the pharynx. But if you look closely at the patient's face, then pathognomonic symptoms are clearly revealed. Trismus, caused by tonic contraction of the masticatory muscles, as a result of which the patient cannot open his mouth.

A sardonic (mocking, malicious) smile caused by spasms of the facial muscles (the forehead is wrinkled, the eye slits are narrowed, the lips are stretched and the corners of the mouth are lowered). Dysphagia caused by spasms of the muscles involved in the act of swallowing. By the second day, spasms of the occipital and long back muscles join in, as a result of which the head is thrown back, the back is curved in the lumbar region so that a hand can be placed under the lower back. By the end of the second day, the muscles of the limbs are involved in the process. At the same time, tetanic spasms join the tonic spasms. They can develop on their own from several during the day to hourly and are accompanied by sharp spasms of the muscles. In this case, a typical picture of opisthotonus develops. Due to a sharp contraction of the muscles, the patient bends in an arc, leaning on the back of the head, heels and elbows. Unlike hysteria and catalepsy, muscle spasm intensifies with sound (it is enough to clap your hands) or light (turn on the light) stimulation. In addition, with tetanus, only large muscles are involved in the process, the hands and feet remain mobile, which never happens with hysteria and catalepsy, on the contrary, the hands are clenched into a fist, the feet are extended. With tetanic contraction of the face and neck, the tongue moves forward and the patient usually bites it, which does not happen with epilepsy, meningitis and craniocerebral trauma, which are characterized by the tongue sinking. From the 3rd-4th day, convulsive syndrome joins in the muscles of the abdomen and chest, which acquire a "rocky" consistency. The diaphragm muscles are the last to be involved in the process. The patient is constantly conscious, screaming from pain. Due to spasm of the pelvic floor muscles, urination and defecation are impaired.

Changes in the internal organs are characteristic. In the first week, tachycardia, hypertension, and loud heart tones are characteristic. Breathing is shallow and rapid, congestive changes in the lungs increase due to suppressed coughing. From the 7th-8th day, signs of decompensation are formed: muffled heart tones, hypotension, arrhythmia; inflammatory and severe congestive changes are formed in the lungs. Respiratory and cardiac insufficiency, acidosis, and hypoxia increase, which can lead to cardiac or respiratory paralysis. Complications, of course, develop, but in moderate cases they are not fatal.

In severe form, the prodromal period is 24-48 hours, after which the entire symptom complex described above quickly develops. Tetanic convulsions are pronounced, their duration increases to 1-5 minutes, they occur every hour, and even 3-5 times per hour. Complications from the lungs and heart develop quickly and are more severe than in moderate form. Mortality increases due to asphyxia, development of atelectasis, paralysis of the heart and breathing.

In a very severe form, the prodromal period lasts from several hours to a day, sometimes tetanus develops lightning fast, without a prodrome. Cardiac and pulmonary failure develop within 24 hours. Tetanic convulsions are almost constant, very powerful, which often leads to the development of bone fractures and muscle ruptures. Mortality is almost 100%.

The clinical picture of ascending tetanus is characterized by the initial lesion of the peripheral muscles of the extremities with a gradual expansion of the zone of excitability and convulsions until it reaches the roots of the spinal cord and motor centers. After that, the clinical picture of the typical descending form is formed. It should be noted that the prodromal period is longer, up to 2-4 weeks, proceeds more favorably, the convulsive syndrome is not expressed so sharply, they are rare, short-lived, there is almost no opisthotonus and damage to the respiratory muscles.

Mild (local) tetanus is rare, the prodromal period is long, the wound has time to heal. But suddenly convulsive twitching (fibrillation) appears in the area of the former wound, and then tonic convulsions with bursting pains, tetanic convulsions are not observed. The process usually affects one segment of the limb. Symptoms resemble myositis, but unlike it, with tetanus, convulsions and pain increase when exposed to external stimuli (light, sound) without touching the affected area, which does not happen with myositis. In neurological practice, Rose's facial paralytic tetanus may be encountered. Along with trismus, paralysis of the facial muscles, sometimes of the eyeball, develops on the affected side, and on the opposite side, tension of the facial muscles and narrowing of the eye slit. In fact, a one-sided sardonic smile is formed. Somewhat reminiscent of the manifestations of facial nerve neuritis, but trismus and muscle tension on the opposite side are not characteristic of it.

Recovery and reverse development of the process occurs slowly, usually within 2-4 weeks. From the 10th-14th day, tetanic convulsions weaken in frequency and intensity, and by the 17th-18th day they stop completely. From this moment, the period of convalescence begins and manifestations of tetanus complications come to the fore. Tonic convulsions last until the 22nd-27th day, mainly remaining in the abdominal muscles, calf muscles and back. Trismus usually lasts until the 30th day, and can be longer. Restoration of cardiac activity occurs only by the end of the second month from the onset of the disease, tachycardia and hypotension persist throughout the convalescence period. Complications of tetanus

There are no specific complications characteristic only of tetanus. All of them are determined by the intensity and duration of the convulsive syndrome and damage to the respiratory muscles. Impaired respiratory function and cough reflex leads, first of all, to the development of a patient number of pulmonary complications: bronchopneumonia, congestive pneumonitis, pulmonary edema and atelectasis with airway obstruction. Against this background, purulent complications can also develop, up to the generalization of infection in the form of sepsis, which is one of the causes of death. Disturbances in ventilation and gas exchange form the development of hypoxia, first respiratory, and then metabolic acidosis with disruption of metabolic processes in all organs and tissues, primarily the brain, heart, liver and kidneys. Hypoxic encephalopathy is formed with disruption of the central regulation of the function of internal organs. The development of hepatorenal syndrome is caused not only by metabolic disorders, but also by difficult urination due to pelvic floor spasm. All this leads to disruption of cardiac activity. The cardiac conduction system itself does not suffer, but hypoxic carditis and congestive heart failure are formed.

Severe tetanic convulsions may result in muscle ruptures, most often of the iliopsoas and abdominal wall muscles, dislocations, and rarely bone fractures. Opisthotonus may lead to compression deformation of the thoracic spine (tetanokyphosis), especially in children. The structure of the vertebrae is restored within 1-2 years, or various forms of osteochondropathy are formed (in children, Scheuermann-Mau and Kohler diseases are more common). After recovery, muscle hypotrophy, muscle and joint contractures, paralysis of the III, VI, and VII pairs of cranial nerves often form, which significantly complicates the patient's rehabilitation.

Neonatal tetanus

Tetanus infection of newborns occurs mainly during births outside of a medical facility, when they are delivered by people who do not have medical training, in unsanitary conditions, and the umbilical cord is tied with non-sterile objects (cut with dirty scissors, a knife, and tied with ordinary untreated threads).

The incubation period is short, 3-8 days, in all cases a generalized severe or very severe form develops. Prodromal period is very short, up to 24 hours. The child refuses to suckle due to trismus and dysphagia, cries. Soon powerful tonic and tetanic convulsions join in, which are accompanied by a piercing cry, involuntary passage of urine and feces, tremor of the lower lip, chin, tongue. Trismus may not be expressed due to muscle weakness, but a mandatory symptom is blepharospasm (eyes tightly squeezed shut). During convulsions, laryngospasm with asphyxia is often noted, which most often causes death.

The child's appearance is characteristic: he is cyanotic, all the muscles of the body are tense, the head is thrown back, the face is frozen, with a wrinkled forehead and clenched eyes, the mouth is closed, the lips are stretched, their corners are lowered, the nasolabial folds are sharply outlined. The arms are bent at the elbows and pressed to the body, the hands are clenched into fists, the legs are bent at the knee joints, crossed. The body temperature is often elevated, but hypothermia may also occur.

Mortality is very high - from 80 to 100%, only timely and high-quality treatment can reduce mortality in children to 50%. Rigidity lasts 2-4 weeks and subsequent convalescence lasts 1-2 months. A rapid decrease in muscle rigidity is a very unfavorable prognostic sign and indicates increasing hypoxia.

Tetanus of the brain, tetanus infection of the brain and cranial nerves is a form of localized tetanus. The latter most often occurs in children and can manifest as chronic otitis media. This disease is most often found in Africa and India. All cranial nerves, especially the 7th pair, can be involved in the pathological process. Tetanus of the brain can become generalized.

Acute respiratory failure is the most common cause of death. Spasm of the glottis, as well as rigidity and spasm of the muscles of the anterior abdominal wall, chest, and diaphragm, lead to asphyxia. Hypoxemia can also cause cardiac arrest, and pharyngeal spasm leads to aspiration of oral contents, which subsequently causes pneumonia, which contributes to the development of hypoxemic death.

How is tetanus diagnosed?

Tetanus is diagnosed clinically based on the characteristic clinical picture. There is no delay in starting treatment, as laboratory test results will arrive in at least 2 weeks. But the diagnosis must be confirmed legally. Material is collected from wounds, inflammation sites, and blood, observing all anaerobic rules. The material is placed in nutrient media (Martin broth or Legru-Ramon broth) under a layer of vegetable oil. Cultivation is performed, and on the 2nd, 4th, 6th, and 10th days, microscopy of the cultures is performed. Detection of gram-positive rods with round terminal spores does not yet confirm their belonging to tetanus; it is necessary to identify the toxin. To do this, 1 part of the culture is taken from the culture under sterile conditions and diluted with 3 parts of saline solution, left for 1 hour to precipitate large particles. The supernatant in a volume of 1-2 ml is introduced into 50 ml of a medium containing mycerin sulfate and polymyxin to suppress gram-negative microflora. Then it is administered intramuscularly either to mice (0.5 ml) or guinea pigs (3 ml). The appearance of signs of tetanus in animals 5 days after the injection indicates the presence of tetanospasmin.

How is tetanus treated?

The mortality rate of tetanus worldwide is 50%. 15-60% in adults and 80-90% in children, even with treatment. The highest mortality occurs at the extremes of age and among intravenous drug users. The prognosis is worse with a short incubation period and rapid progression of symptoms, as well as with delayed initiation of treatment. The course of the disease tends to be mild in cases where there is no obvious focus of infection. Treatment of tetanus requires maintenance of adequate ventilation. Additional therapeutic measures include administration of human immune globulin to neutralize unbound toxin, prevention of further toxin formation, sedation, control of muscle spasms and hypertension, fluid balance and intercurrent infection, and long-term support.

Treatment of tetanus: basic principles

The patient should be in a quiet room. All therapeutic interventions should comply with 3 basic principles:

• prevention of further release of the toxin. The latter is achieved by surgical cleaning of the wound and the administration of metronidazole at a dose of 500 mg intravenously every 6-8 hours;
• neutralize the toxin located outside the central nervous system. For this purpose, human tetanus immunoglobulin and tetanus toxoid are prescribed. Injections should be given in different parts of the body, which avoids neutralization of the antitoxin;
• minimize the effects of the toxin that has already entered the central nervous system.

Wound treatment

Because contaminated and dead tissue supports the growth of C. tetani, careful surgical debridement is essential, especially for deep puncture wounds. Antibiotics are not a substitute for careful debridement and passive immunization.

Antitoxin

The effectiveness of human antitoxin depends on the amount of toxin already bound to the synaptic membranes, since only the free fraction of the toxin can be neutralized. Human immunoglobulin for adults is given at a dose of 3,000 units intramuscularly once. A larger volume can be divided and administered to different parts of the body. The dose of immunoglobulin can vary from 1,500 to 10,000 units, depending on the severity of the wound. Antitoxin of animal origin is much less preferable. The latter is explained by the difficulty of achieving an adequate concentration of antitoxin in the patient's serum and the risk of developing serum sickness. When using horse serum, the dose of antitoxin should be 50,000 units intramuscularly or intravenously. If necessary, immunoglobulin can be injected into the wound site, but this injection is not as effective as proper surgical debridement.

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Treatment of muscle spasm

For the control of rigidity and spasms, benzodiazepines are the standard of care. These drugs block the reuptake of the endogenous inhibitory neurotransmitter alpha-aminobutyric acid (AABA) at the AABA receptor. Diazepam may help control spasms, reduce rigidity, and produce the desired sedation. The dose of diazepam is variable and requires careful titration and observation of the patient's response. The most acute cases may require a dose of 10-20 mg intravenously every 3 hours (not to exceed 5 mg/kg). For seizure prophylaxis in less acute cases, the dose of diazepam is 5-10 mg orally every 2-4 hours. The dose for infants over 30 days is 1-2 mg intravenously slowly, with repeat doses, if necessary, after 3-4 hours. Small children receive diazepine at a dose of 0.1-0.8 mg/kg/day to 0.1-0.3 mg/kg every 4-8 hours. For children over 5 years old, the drug is prescribed at a dose of 5-10 mg/kg intravenously every 3-4 hours. Adults receive 5-10 mg orally every 4-6 hours to 40 mg per hour intravenously by drip. Although diazepam is the most widely used, water-soluble midazolam (adult dose 0.1-0.3 mg/kg/hour infusions; child dose 0.06-0.15 mg/kg/hour infusions) is preferable for long-term therapy. The use of midazolam eliminates the risk of lactic acidosis from propylene glycol (a solvent required to prepare diazepam and lorazepam). Also, when using it, there is no accumulation of long-acting metabolites and, accordingly, no coma.

Benzodiazepines may not eliminate reflex spasms. In this case, neuromuscular blockade may be required for effective respiration. This is achieved by vecuronium bromide at a dose of 0.1 mg/kg intravenously and other paralytic drugs and mechanical ventilation. Pancuronium bromide can also be used, but this drug may worsen autonomic instability. Vecuronium bromide has no cardiovascular side effects, but it is a short-acting drug. Longer-acting drugs (eg, pipecuronium and rocuronium) are also used, but no comparative randomized clinical trials have been conducted on these drugs.

Intrathecal baclofen (an AABK receptor agonist) is effective, but it is not significantly superior to benzodiazepines. It is given by continuous infusion. The effective dose ranges from 20-2000 mg/day. A 50 mg test dose is given first, and if the response is inadequate, 75 mg is given after 24 hours, and if there is still no response, 100 mg is given after another 24 hours. Individuals who do not respond to 100 mg are not candidates for continuous infusion. Potential side effects of the drug include coma and respiratory depression requiring mechanical ventilation.

Dantrolene (1-1.5 mg/kg IV loading dose followed by 0.5-1 mg/kg IV infusions every 4-6 hours for at least 25 days) relieves spasticity. Oral dantrolene can be used as a substitute for infusion for 60 days. Hepatotoxicity and high cost limit its use.

Morphine may be given every 4 to 6 hours to control autonomic dysfunction, especially cardiovascular dysfunction. The total daily dose is 20 to 180 mg. Beta-blockade with long-acting agents such as propranolol is not recommended. Sudden cardiac death is a feature of tetanus, and beta-blockers may increase its risk. However, esmolol, a short-acting blocker, has been used successfully. High doses of atropine have also been used; blockade of the parasympathetic nervous system significantly reduces sweating and secretion formation. Lower mortality rates have been reported with clonidine compared with conventional regimens.

Administration of magnesium sulfate in doses that achieve serum concentrations of 4-8 mEq/L (eg, 4 g bolus followed by 2-3 g/h) has a stabilizing effect and eliminates the effects of catecholamine stimulation. The knee jerk reflex is used to assess overdose. Respiratory volume may be affected, so treatment should be performed in wards where ventilator support is available.

Pyridoxine (100 mg once daily) reduces infant mortality. Newer agents that may be helpful include sodium valproate, which blocks AABK-transferase, thereby inhibiting AABK catabolism; ACE inhibitors, which inhibit angiotensin II and norepinephrine release from nerve terminals; dexmedetomidine, a potent alpha-2-adrenergic receptor agonist; and adenosine, which abolishes presynaptic norepinephrine release and antagonizes the inotropic effects of catecholamines. Glucocorticoids are of no proven benefit and are not recommended.

Treatment of tetanus: antibiotics

The role of antibiotics is minor compared with surgical debridement and general support. Typical antibiotics include benzylpenicillin 6 million units intravenously every 6 hours, doxycycline 100 mg orally twice daily, and metronidazole 500 mg orally every 8 hours.

Support

In cases of moderate or acute illness, the patient should be intubated. Mechanical ventilation is essential when neuromuscular block is required to control muscle spasms that interfere with spontaneous breathing. Intravenous feeding eliminates the risk of aspiration complications that may result from tube feeding. Since constipation is common in tetanus, the patient's stools should be kept soft. A rectal tube may be useful to control intestinal distension. If acute urinary retention develops, a urinary catheter should be placed. Chest physiotherapy, frequent turning, and forced coughing are necessary to prevent pneumonia. Narcotic analgesia is often required.

How to prevent tetanus?

Tetanus is prevented by a 4-dose primary immunization series, followed by booster doses every 10 years using adsorbed (primary) and liquid (booster) toxoid, which is a preferred method of prevention over antitoxin given in the event of injury. Tetanus toxoid may be given alone, in combination with diphtheria toxoid (in both children and adults), or in combination with diphtheria and pertussis (DPT). Adults require booster doses every 10 years to maintain immunity. Tetanus vaccination in unimmunized or inadequately immunized pregnant women creates both active and passive immunity in the fetus and should be given. It is given at 5–6 months of gestation, with a booster dose given at 8 months of gestation. Passive immunity develops when the mother is given a toxoid at a gestation period of less than 6 months.

After an injury, tetanus vaccination depends on the nature of the injury and the immunization history. Tetanus immunoglobulin may also be prescribed. Patients who have not been previously vaccinated receive 2 or 3 doses of the toxoid at 1-month intervals.