Tetanus

Tetanus is a wound infection caused by the toxin of the anaerobic sporebearing rod Clostridium tetani, characterized by the defeat of the nervous system with attacks of tonic and tetanic seizures. Symptoms of tetanus include intermittent tonic spasms of the arboreal musculature. Diagnosis is based on the disease clinic. Treatment of tetanus is the appointment of immunoglobulin and intensive support.

ICD-10 codes

• АЗЗ. Tetanus of the newborn.
• A34. Obstetrical tetanus.
• A35. Other forms of tetanus.

There is no unified classification of tetanus. A working classification is generally accepted, which includes several items.

1. The entrance gates distinguish between wound, endometral (after abortion), infectious (when combined with purulent processes), injection (with the transition to disposable syringes in recent years does not occur), umbilical (tetanus of newborns), burn, traumatic and other rare forms, for example , urethral, rectal, vaginal (if damaged by mucous foreign bodies).
2. On the way of distribution divide into: local, ascending, descending (generalized) tetanus.
3. The severity of the flow is marked by a light, moderate, heavy and very severe form.

What causes tetanus?

Tetanus is caused by tetanus bacilli, which form long-lived spores and can be found in mud and feces of animals, where they remain viable for many years. Globally, about 500,000 people die of tetanus each year, the highest death rate among newborns and young children, but not all cases of tetanus can be identified, so these estimates can be considered rude. In the United States in 2001, only 37 cases of the disease were reported. 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 US, more than half of elderly patients have an inadequate level of antibodies. 33-50% of cases are registered in persons of this age group. The remaining cases of the disease are mostly registered in the age group of 20-59 years, in whom the immunization was inadequate. Morbidity in persons under 20 years of age is less than 10%. Patients with burns, surgical wounds, as well as persons with a history of indication of infected injection sites (drug addicts), are most likely to develop tetanus. Tetanus can be the result of trivial or even unnoticeable wounds. Infection can also develop after childbirth. This can occur in the uterus (maternal tetanus) or in the navel of the newborn (neonatal tetanus).

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

With a very small amount of toxin, it spreads along the muscles with defeat in them of nerve endings and regional nerve trunks. The process develops locally, most often causing no convulsive contraction, fibrillation. With a small amount of toxin, it spreads along the muscles and perineurally, including the nerve endings, the nerves to the synapses and roots of the spinal cord. The process is of the nature of an easy ascending form with the development of tonic and tetanic (clonic) seizures in the limb segment.

Rarely develop a moderate and severe ascending form of tetanus with a moderate and significant amount of toxin. Its distribution occurs peri- and endoneurally, as well as intraconsularly, affecting the anterior and posterior horns of the spinal cord, synapses and neurons, as well as motor nuclei of the spinal cord and cranial nerves. This is accompanied by the development of common tonic convulsions, against which there are tetanic ones.

When a toxin enters the blood and lymph, its spread occurs throughout the body, affecting all groups of muscles and nerve trunks and arriving from the neuron intra-axally to various motor centers. The rate of spread depends on the length of each neural path. The shortest neural path in the facial nerves, therefore, the convulsive process in them develops primarily, affecting the musculature of the face and chewing muscles. Then the centers of the muscles of the neck and back, later the limbs, are affected. Lastly, the respiratory muscles of the thorax and the diaphragm are involved in the process.

In a complex, this determines the development of the descending (generalized) form of tetanus.

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

What are the symptoms of tetanus?

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

Tetanus usually begins acutely, less often (up to a day), which is accompanied by a general malaise, traumatic pains in the wound or already formed scar, fibrillar twitchings of surrounding muscles, an increased reaction of the patient to external stimuli, especially sound and light, even slight touches to the wound or the surrounding muscles lead to a sharp increase in their tone and increased pain. Subsequently, this process extends to all muscles innervated by the affected nerve. Muscle pains are very strong due to their constant tonic tension and become literally unbearable under tetanic contractions - and this is the most characteristic sign of tetanus lesion.

Clinical manifestations are quite typical, but tetanus is rare and doctors, although they remember it, often do not assume that they met with him, and in most cases believe that there is an atypical form of some common disease.

Most often, in practice, there is a descending (generalized) tetanus of the medium-severe course (68%). The prodromal period is short (6-8 days). It is accompanied by an increase in body temperature to 38-39 degrees, abundant, often pouring sweat. Pain in the throat, neck, face. The first thought of the doctor - is it sore throat? For differential diagnosis, it is sufficient to examine the pharynx. But if you carefully look at the patient's face, it clearly shows up with a pathognomonic symptom. Trism caused by tonic contraction of the chewing muscles, as a result of which the patient can not open his mouth.

Sardonic (mocking, snide) smile, caused by convulsions of facial muscles (forehead in wrinkles, eye cracks narrowed, lips stretched and corners of mouth lowered downwards). Dysphagia due to spasm of muscles involved in the swallowing act. By the second day, cramps of the occipital and long muscles of the back join, as a result of which the head throws back, the back bends in the lumbar region so that you can bring your arm under the waist. By the end of the second day, muscles of the limbs are involved in the process. At the same time, tonic convulsions also join tonic convulsions. They can develop on their own from a few within a day to hourly and are accompanied by sharp spasms of the musculature. This develops a typical picture of opisthotonus. The patient arches at the expense of a sharp contraction of the muscles, arching the back of the head, heels and elbows. Unlike hysteria and catalepsy, muscular spasm increases with sound (enough to clap hands) or light (turn on the light) irritation. In addition, in tetanus, only large muscles are involved in the process, the brushes and feet retain mobility, which is never the case with hysteria and catalepsy, on the contrary, the hands are clenched into a fist, the feet are stretched out. With a tetanic contraction of the face and neck, the tongue moves forward and the patient bites it, as a rule, bites, which does not happen with epilepsy, meningitis and craniocerebral trauma, which is characterized by tongue twisting. From the 3rd-4th day a convulsive syndrome in the muscles of the abdomen, chest, joins, which acquire a "rocky" consistency. In the last place, the muscles of the diaphragm are involved in the process. The patient is constantly conscious, screaming for pain. Due to spasm of the pelvic floor muscles, urination and defecation are impaired.

Characteristic changes in internal organs. The first week is characterized by tachycardia, hypertension, loud heart sounds. Breathing is superficial, frequent, stagnant changes in the lungs due to cough suppressed. From the 7th to the 8th day signs of decompensation are formed: deafness of cardiac tones, hypotension, arrhythmias; in the lungs inflammatory and severe stagnant changes are formed. Increases respiratory and heart failure, acidosis and hypoxia, which can lead to paralysis of the heart or respiration. Complications, of course, develop, but with a moderate form do not have a fatal character.

In severe form, the prodromal period is 24-48 hours, after which the entire above-described symptom complex develops rapidly. Aetanic convulsions are pronounced, their duration increases to 1-5 minutes, hourly, and even 3-5 times per hour occur. Complications from the lungs and heart develop quickly and heavier than with the medium-heavy form. Lethality increases due to asphyxia, the development of atelectasis, paralysis of the heart and respiration.

With a very severe form of the prodromal period from a few hours to a day, sometimes tetanus develops lightning fast, without a prodrome. Cardiac and pulmonary insufficiency develops within a day. Aetanic cramps are almost constant, very powerful, which often leads to the development of fractures of bones and muscle ruptures. The lethality is almost 100%.

The clinic of the ascending form of tetanus differs by the initial lesion of the peripheral muscles of the limbs with a gradual extension of the zone of excitability and convulsions until it reaches the roots of the spinal cord and motor centers. Then the clinic of a typical descending form is formed. It should be noted that the prodromal period is more prolonged, up to 2-4 weeks, it proceeds more favorably, the convulsive syndrome is not so pronounced, they are rare, short-lived, there is almost no opisthotonus and lesion of the respiratory musculature.

Light (local) tetanus is rare, the prodromal period is long, the wound has time to heal. But suddenly there are convulsive twitchings (fibrillation) in the area of the former wound, and then also tonic convulsions with raspiruyuschimi pains, tetanic seizures are not noted. The process captures: usually one segment of the limb. Symptoms resemble myositis, but unlike it, tetanus and cramps intensify with tetanus when exposed to external stimuli (light, sound) without touching the site of the lesion, which does not happen with myositis. In neurological practice, facial paralytic tetanus of Rosa may occur. Along with trismus on the affected side develops paralysis of the muscles of the face, and sometimes the eyeball, and on the opposite side muscle tension of the face and narrowing of the eye gap. In fact, a one-sided sardonic smile is formed. It somewhat resembles the manifestation of the neuritis of the facial nerve, but it is not characterized by trismus and muscle tension on the opposite side.

Recovery and reverse development of the process occurs slowly, often within 2-4 weeks. From the 10th to the 14th day, tetanic convulsions are weakened by the frequency of occurrence and intensity, and by the 17-18th day they cease completely. From this moment the period of convalescence begins and the manifestations of complications of tetanus come out on the first place. Tonic convulsions last until 22-27 days, mainly retained in the abdominal muscles, gastrocnemius muscles and back. Trismus usually lasts until the 30th day, and maybe longer. Restoration of cardiac activity occurs only towards the end of the second month from the onset of the disease, the entire period of convalescence remains tachycardia and hypotension. Complications of tetanus

Specific complications, characteristic only for tetanus, no. All of them are determined by the intensity and duration of the convulsive syndrome and the defeat of the respiratory muscles. Violation of the function of respiration and cough reflex results, first of all, in the development of a sick number of pulmonary complications: bronchopneumonia, congestive pneumonitis, pulmonary edema and atelectasis in the obstruction of the respiratory tract. Against this background, purulent complications can develop, up to the generalization of infection in the form of sepsis, which is one of the causes of deaths. Disturbances in ventilation and gas exchange form the development of hypoxia, at first respiratory, and then metabolic acidosis with impaired metabolic processes in all organs and tissues, primarily the brain, heart, liver and kidneys. Hypoxic encephalopathy is formed with a violation of the central regulation of the function of internal organs. The development of hepatorenal syndrome is caused not only by metabolic disturbances, but also by difficulty urinating due to pelvic floor spasm. All this leads to a violation of cardiac activity. The very conductor system of the heart does not suffer, but hypoxic carditis and congestive heart failure are formed.

The consequence of severe tetanic seizures may be muscle ruptures, more often ileo-lumbar and abdominal wall muscles, dislocations, rarely fractures of bones. The histone can lead to compression deformity of the thoracic spine (tetanokiphos), especially in children. Restoration of the structure of the vertebrae occurs within 1-2 years, or various forms of osteochondropathies are formed (in children, the Sheyermann-Mau, Kehler disease is more common). After recovery, muscle hypotrophy, contracture of muscles and joints, paralysis of III, VI, VII pairs of cranial nerves are often formed, which greatly complicate the rehabilitation of the patient.

Tetanus newborn

Infection of newborns with tetanus occurs mainly during childbirths outside a medical institution when they are taken by people who do not have medical education under unhygienic conditions, and the cord is bandaged with non-sterile objects (cut with dirty scissors, a knife, and bandaged with normal untreated threads).

The incubation period is short, 3-8 days, in all cases a generalized severe or very severe form develops. The prodromal period is very short, up to 24 hours. The child refuses to suck breast because of trismus and dysphagia, crying. Soon, powerful tonic and tetanic convulsions join in, which are accompanied by a shrill cry, involuntary discharge of urine and feces, tremor of the lower lip, chin, and tongue. Trismus may not be expressed due to the weakness of the musculature, but a mandatory symptom is blepharospasm (eyes tightly squeezed). In the period of seizures, laryngospasm with asphyxia is often noted, which often leads to death.

The appearance of the child is characteristic, it 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, and the nasolabial folds are sharply outlined. The handles are bent at the elbows and are pressed to the trunk, the hands are clenched into fists, the legs are bent at the knee joints, crossed. Body temperature is often increased, but there may be hypothermia.

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

Tetanus of the brain, tetanus infection of the brain and cranial nerves is a form of localized tetanus. Most often, the latter occurs in children and can manifest as chronic otitis media. The most common disease occurs in Africa and India. In the pathological process, all cranial nerves, especially the 7th pair, can be involved. Tetanus of the brain can pass into 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?

The diagnosis of tetanus is clinically based on a characteristic clinical picture. Since the beginning of treatment, they do not hesitate, as laboratory research data will arrive at least 2 weeks later. But it is necessary to confirm the diagnosis legally. The fence of the material is made from wounds, foci of inflammation and blood, observing all the rules of anaerobic activity. The material is placed in nutrient media (open hearth broth or Legra-Ramona broth) under a layer of vegetable oil. Cultures are made and on the 2nd, 4th, 6th, 10th days, microscopy of the crops is produced. The 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, under sterile conditions, one part of the culture is taken from the planting and 3 diluted with parts of saline solution, left for 1 hour to precipitate large particles. The supernatant in a volume of 1-2 ml is added to 50 ml of medium containing the mycelin sulfate and polymyxin to inhibit the gram-negative microflora. Then, intramuscularly injected or mice (0.5 ml), or guinea pigs (3 ml). The appearance of tetanus signs in animals 5 days after injection indicates the presence of tetanospasmin.

How is tetanus treated?

The mortality from tetanus in the world is 50%. 15-60% in adults and 80-90% in children, even with treatment. The highest mortality occurs in extreme age groups, as well as among intravenous drug users. The prognosis worsens with a short incubation period and a rapid progression of symptoms, as well as with delayed initiation of treatment. The course of the disease has the tendency to be moderate in those cases when there is no obvious focus of infection. Treatment for tetanus requires adequate ventilation. Additional therapeutic effects include the appointment of a human immunoglobulin to neutralize the unbound toxin, prevent further toxin formation, sedation, control of muscle spasms and hypertension, fluid balance and intercurrent infection, and sustained support.

Treatment of tetanus: basic principles

The patient should stay in a quiet room. All therapeutic effects must comply with 3 basic principles:

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

Treatment of a wound

Because contaminated and dead tissue contributes to the growth of C. Tetani, it is necessary to perform a thorough surgical cleaning of the wound, especially for deep stab wounds. Antibiotics can not serve as a substitute for thorough surgical treatment and passive immunization.

Antitoxin

The effectiveness of using human antitoxin depends on the amount of toxin already associated with synaptic membranes, since only a free fraction of toxin can be neutralized. Human immunoglobulin for adults is prescribed at a dose of 3000 units IM / m 1 time. A large volume can be divided and assigned 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 significantly less preferred. The latter is explained by the fact that it is difficult to achieve an adequate concentration of antitoxin in the serum of the patient, as well as a risk of developing serum sickness. When using horse serum, the dose of antitoxin should be 50,000 units intramuscularly or intravenously. If necessary, it is possible to inject an immunoglobulin into the wound site, but this injection is not as effective as the correct surgical purging.

[1], [2], [3], [4], [5], [6], [7], [8], [9], [10]

Treatment of muscular spasm

To control rigidity and spasms, benzodiazepines are a standard prescription. These drugs block the inverse capture of the endogenous inhibitory neurotransmitter alpha-aminobutyric acid (AABK) on the AABK receptor. Diazepam can help control spasms, reduce stiffness and lead to the desired sedation. The dose of diazepam varies and requires careful titration and monitoring of the patient's response. The most acute cases may require a dose of 10-20 mg intravenously every 3 hours (not exceed 5 mg / kg). For the prevention of seizures in less acute cases of disease, 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 repeated administration, if necessary, after 3-4 hours. Young 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. Children older than 5 years, the drug is prescribed in a dose of 5-10 mg / kg intravenously every 3-4 hours. Adults receive from 5-10 mg orally every 4-6 hours to 40 mg per hour intravenously drip. Despite the fact that diazepam is the most widely used, water-soluble midazolam (dose for adults is 0.1-0.3 mg / kg / hour in infusions, the dose for children is 0.06-0.15 mg / kg / hour in infusions) is more preferable for long-term therapy. Using midazolam eliminates the risk of developing lactic acidosis from propylene glycol (a solvent necessary for the preparation of diazepam and lorazepam). Also, when it is used, there is no cumulation of long-acting metabolites and, accordingly, coma.

When using benzodiazepines, reflex spasms may not be eliminated. In this case, neuromuscular blockade may be required for effective respiration. To achieve the latter, vecuronium bromide is used at a dose of 0.1 mg / kg intravenously and other paralytic preparations and mechanical ventilation of the lungs. Pancuronium bromide can also be used, but this drug may worsen autonomic instability. Vecuronium bromide does not have a side effect on the cardiovascular system, but is a short-acting drug. Longer acting drugs (for example, pipecuronium and rocuronium) are also used, however, no comparative randomized clinical trials have been performed with these drugs.

Intra-enveloped baclofen (AABA receptor agonist) is effective, but this drug has no marked superiority to benzodiazepines. It is prescribed by continuous infusion. The effective dose varies from 20 to 2000 mg / day. Initially, a trial dose of 50 mg is given, if the answer is inadequate, after 24 hours 75 mg are prescribed, if after that the desired reaction is not, after another 24 hours, 100 mg of the drug are prescribed. Persons who do not respond to a dose of 100 mg can not be candidates for continuous infusion of the drug. Potential side effects from the administration of the drug are coma and respiratory depression, requiring mechanical ventilation of the lungs.

Dantrolene (loading dose of 1-1.5 mg / kg intravenously, followed by intravenous infusion of 0.5-1 mg / kg every 4-6 hours for less than 25 days) removes muscle spasticity. Dantrolene, administered orally, can be used as a substitute for infusion of this drug for 60 days. Hepatotoxicity and high cost limit the possibility of using this drug.

Morphine can be prescribed every 4 to 6 hours to monitor autonomic dysfunction, especially cardiovascular. The total daily dose is 20-180 mg. Blockade of beta-adrenoreceptors with long-acting drugs, such as propranolol, is not recommended. Sudden cardiac death is one of the traits of tetanus, and therefore the appointment of beta-blockers may increase the risk of its occurrence. Whatever it was, Esmolol, which is a short-acting blocker, has been used successfully. Also use atropine in high doses; blockade of the parasympathetic nervous system significantly reduces perspiration and the formation of secrets. There have been reports of a lower mortality rate with clonidine compared to conventional schemes.

The administration of magnesium sulfate at doses at which a serum concentration of 4-8 meq / L is achieved (for example, 4 g of bolus followed by 2-3 g / h) has a stabilizing effect and eliminates the effect of catecholamine stimulation. To assess the overdose, the knee jerk is looked at. The respiratory volume may suffer, and therefore treatment should be carried out in wards where there is a possibility of holding fan support.

The administration of pyridoxine (100 mg once a day) reduces mortality among infants. Newer drugs that may be helpful include sodium valproate, which blocks AABA transferase, which inhibits AABA catabolism, ACE inhibitors that inhibit angiotensin 2 and release of norepinephrine from nerve endings, dexmedetomidine is a potent agonist-alpha-2-adrenergic receptor, and adenosine, which eliminates the presynaptic release of norepinephrine and antagonizes the inotropic effect of catecholamines. The benefits of using glucocorticoids have not been proven, and their use is not recommended.

Treatment of tetanus: antibiotics

The role of antibiotics is small, compared with surgical wound cleaning and general support. Typical antibiotics include benzylpenicillin 6 million ED intravenously every 6 hours, doxycycline 100 mg vagus 2 times a day, and metronidazole 500 mg orally every 8 hours.

Support

In cases of mild or severe illness, the patient should be intubated. Mechanical ventilation is absolutely necessary in cases where neuromuscular blockade is required to control muscular spasms that interfere with self-breathing. Intravenous nutrition eliminates the risk of aspiration complications that can result from feeding through the probe. Since tetanus often develops constipation, the patient's stool should be kept soft. A rectal probe can be helpful in controlling the swelling of the intestine. With the development of acute urinary retention, a urinary catheter is required. Physiotherapy on the chest, frequent patient turn and forced cough are needed to prevent pneumonia. It is often necessary to carry out narcotic analgesia.

How to prevent tetanus?

Tetanus is prevented by 4 series of primary immunizations against this disease, followed by booster doses every 10 years using adsorbed (for primary immunization) and liquid (for booster injections) toxoid, are a more preferred method of prevention than antitoxin administration in trauma. Anti-tetanus toxoid can be prescribed alone, in combination with diphtheria toxin (both in children and adults), as well as in combination with antidiphtheria and anti-pertussis components (DTP). To maintain immunity, adults need booster doses every 10 years. Vaccination against tetanus in unimunized or inadequately immunized pregnant women forms both active and passive immunity in the fetus, and therefore should be appointed. It is carried out at the gestational age of 5-6 months, and the booster dose is administered at the gestational age of 8 months. Passive immunity develops when the mother of the toxoid is appointed at the gestational age of less than 6 months.

After the trauma, tetanus vaccination depends on the nature of the injury and the history of immunization. An antitetanus immunoglobulin can also be prescribed. Patients previously unvaccinated receive 2 and 3 doses of the toxoid at a 1-month interval.