Malignant neuroleptic syndrome: emergency care, prevention

People who are treated with neuroleptic, anticonvulsants or antidepressants have a high risk of developing a dangerous condition, such as neuroleptic syndrome. The syndrome can occur during the treatment course - for example, with an increase in the dosage of the drug, or with a sharp withdrawal of treatment - after a certain period of time.

The appearance of neuroleptic syndrome is difficult to predict. His treatment requires urgent medical intervention, because the lethal outcome of the syndrome is not uncommon.

[1], [2]

Epidemiology

The first mention of the neuroleptic syndrome was dated to the 60th years of the last century. Today, the doctors recognized this syndrome as one of the most adverse probable consequences of taking antipsychotics. The lethality of patients with the syndrome, according to different data, may be 3-38%, and in recent years, this percentage has been significantly reduced.

The incidence of neuroleptic syndrome, according to foreign periodical medical publications, is up to 3.23% of the total number of patients undergoing neuroleptic therapy. Over the past few years, the incidence of the syndrome has significantly decreased.

Most often, neuroleptic syndrome is diagnosed in middle-aged patients. Men are more likely to develop a syndrome, about 50%.

[3], [4], [5], [6], [7], [8],

Causes of the neuroleptic Syndrome

The most common development of neuroleptic syndrome is observed with the use of excessive doses of strong drugs of neuroleptic effect (eg, fluorophenazine), and in particular of medicines with prolonged (prolonged) properties.

However, this does not always happen: neuroleptic syndrome can develop with the use of any neuroleptic drug, however, somewhat less often.

The syndrome can be detected after a sharp increase in dosage, while taking two or three antipsychotics simultaneously, with a combination of neuroleptics with lithium-based medications.

Hereditary cases of neuroleptic syndrome development have not been fixed, therefore this theory is not considered.

The syndrome often occurs in patients with previously diagnosed disorders of the psyche: with schizophrenia, affects, neuroses, with mental underdevelopment, etc.

[9], [10], [11], [12], [13], [14]

Risk factors

To accelerate the onset of neuroleptic syndrome may:

• organic brain damage;
• dehydration of the body;
• anorexia, severe exhaustion of the body;
• long periods of starvation or malnutrition;
• anemia;
• period after childbirth.

Even an insignificant at first glance cerebral injury, received several years ago, can affect the sensitivity to neuroleptic treatment. For this reason, patients with perinatal trauma, craniocerebral trauma, cerebral infectious diseases, degenerative brain lesions, and alcohol abusers may be included in the risk group.

[15], [16], [17], [18], [19], [20], [21]

Pathogenesis

The pathogenetic features of the neuroleptic syndrome have not been fully understood. Many experts suggest that the syndrome arises from the blockade of dopaminergic structures in the hypothalamus and basal ganglia, and not as a result of intoxication with neuroleptics.

Some scientists explain that the increase in temperature - the main sign of the syndrome - appears because of the emerging rigidity of muscles and intramuscular hypermetabolism, which causes increased heat production.

At present, there is a common opinion among scientists that in the development of neuroleptic syndrome an important role is played by immunity disorders with further autoimmune failure in the central nervous system and visceral organs. Homeostatic disorders become the main causes of severe circulatory and consciousness disorders, which can lead to the death of the patient.

In addition, experts have found that the pathogenetic mechanism of the syndrome is associated with sympathoadrenal and serotonin hyperactivity.

[22], [23], [24]

Symptoms of the neuroleptic Syndrome

The neuroleptic syndrome is characterized by the following symptoms, which are referred to as the "tetrad" (four signs):

• increase in temperature (more than 37 ° C);
• general muscle weakness;
• blurred vision (possible development of coma);
• disorders in the work of the autonomic nervous system (excessive sweating, palpitations and arrhythmia, blood pressure jumps, skin blanching, increased salivation, respiratory and urinary disorders).

More than a quarter of patients show dystonic muscle contraction, and every second patient has a tremor in the fingers and / or limbs. Additionally, symptoms such as a or hypokinesia, nystagmus, speech disorders, dullness, tonic spasm of the masticatory muscles, swallowing disorders, opisthotonus may be observed.

In a smaller number of patients, myoclonic spasms, hyperkinesis, epileptic seizures are observed.

The first signs can sometimes appear in the form of dehydration - a decrease in turgor, dry skin, dryness of the oral mucosa.

The clinical picture is growing, reaching its limit for 1-3 days, but in some cases the process is more intense - for several hours.

Due to the considerable weakness of the muscles - including the respiratory ones - dyspnea develops. The expressed spasm of skeletal musculature is capable to provoke rhabdomyolysis, proceeding with the increase of the content of creatine phosphokinase in the bloodstream. Further, myoglobinuria, acute renal failure, metabolic acidosis, and lack of oxygen in the tissues are observed. As complications can act aspiration pneumonia, heart attack, septicemia, thromboembolism, shock, pulmonary edema, necrosis of the intestine, paralysis.

Stages

Neuroleptic syndrome proceeds through stages, which in different patients may be more or less pronounced:

1. The stage of neuroleptic parkinsonism is characterized by trembling of the limbs, the head. The movements of the patient are constrained, the muscle tone rises: the muscles evenly resist at all stages of passive movement.
2. An acute dystonic stage is one of extrapyramidal complications after taking antipsychotic drugs. The stage is manifested by involuntary movements in the form of contractile spasms of individual muscle groups throughout the trunk.
3. The stage of akathisia is accompanied by a temporary or incessant inner sensation of motor tension: the patient feels the need to constantly make any movements, or change the position of his body.
4. The stage of belated dyskinesia is characterized by hyperkinesis, sometimes involving the facial muscles. There is a violent involuntary motor activity (more often in elderly patients).
5. Stage directly neuroleptic syndrome.

[25], [26], [27]

Forms

• Malignant neuroleptic syndrome.

Most experts are of the opinion that the malignant neuroleptic syndrome has mainly a central etiology. It follows that most of the disorders occur in the subcortex of the brain.

Nevertheless, an important role in the process is played by the effect of antipsychotic drugs on skeletal muscles, which can lead to the disintegration of myocytes (the so-called rhabdomyolysis) and the blocking of peripheral dopamine receptors.

Neuroleptics potentiate blockade of central dopamine receptors, which leads to significant disorders of motor activity, with such an important feature as muscle rigidity.

The change in the metabolism of dopamine, in turn, is a trigger mechanism in the violation of the autonomic nervous system and cardiac activity.

Simultaneously, almost all metabolic processes are violated, the permeability of the blood-brain membrane changes. The reactions of intoxication are started, the cerebral edema begins. As a result - the emergence of mental disorders and failures at a conscious level.

• Extrapyramidal neuroleptic syndrome.

Extrapyramidal neuroleptic syndrome is a combination of neurologic symptoms, which are manifested primarily by motor disorders, due to the use of neuroleptic drugs. This term also includes disorders that are provoked by treatment with other drugs that interfere with dopaminergic activity: antidepressants, antiarrhythmics, cholinomimetics, lithium-based drugs, anticonvulsant and anti-Parkinsonics are included in such drugs.

The syndrome can be accompanied by all extrapyramidal disorders: parkinsonism, trembling of limbs, dystonia, chorea, tics, myoclonic cramps, etc. Such symptoms are combined with any mental abnormalities.

• Neuroleptic deficiency syndrome.

This syndrome has many other names - in particular, it is often called a neuroleptic defect, or neuroleptic-induced deficiency syndrome. The development of the syndrome is often mistaken for schizophrenia, because of similar signs:

• apathy;
• general retardation;
• slow speech reproduction;
• weakness;
• abulic syndrome;
• lack of motivational and proactive factors;
• isolation, withdrawal into oneself;
• inattention and memory impairment;
• decreased emotionality;
• indifference, absolute composure.

Often this state is complicated by psychotic reactions in the form of depersonalization and derealization. At the same time there are extrapyramidal disorders, a depressed state (depression, bad mood), irritability, sleep disturbances, phobias.

• Acute neuroleptic syndrome.

At the heart of the neuroleptic syndrome lies an acute dopamine deficiency - the course of this state is always increasing and rapid. The clinical picture is growing, reaching its limit for 1-3 days, but in some cases the process is more intense - for several hours.

That's why help with neuroleptic syndrome should be provided as soon as possible and faster - because it depends not only on health, but also on the patient's life.

The so-called chronic neuroleptic syndrome refers to the period of late dyskinesia, which happens in about 20% of patients who regularly undergo treatment with neuroleptics, as well as in 5% of patients who take these drugs throughout the year. In other words, the chronic course of the syndrome includes those disorders that do not have a tendency to regress during six months after the end of treatment with neuroleptics.

[28], [29]

Complications and consequences

Late signs of neuroleptic syndrome can make themselves felt after a long period of time - such belated manifestations are usually "fixed" for the patient for a long time, and sometimes for life.

Such manifestations are quite typical. Most often it is:

• slowing down movements, gestures;
• inhibition of natural reactions;
• gait of the robot;
• uncertain, unsteady movements;
• slowing of mimic reactions;
• slowing down mental processes;
• deterioration of cognitive processes.

The degree of socialization of a person is sharply reduced. Often observed hyperkinetic obsessive movements, which is due to a change in muscle tone.

In the most unfavorable cases, neuroleptic syndrome is complicated:

• swelling of the brain;
• swelling of the lungs;
• insufficient function of the cardiovascular system;
• acute renal and hepatic dysfunction.

These complications can provoke a fatal outcome.

[30], [31], [32], [33], [34], [35]

Diagnostics of the neuroleptic Syndrome

Diagnosis is often overdue, since in many cases the possibility of neuroleptic syndrome development is not taken into account. A correct diagnosis can be made based on clinical signs of the disease, and additional laboratory tests will help to establish the severity of the condition and monitor the dynamics of the pathology.

Blood tests indicate an elevated white blood cell count (10-40 tons / μl), in some cases - a shift of the leukocyte formula to the left, an increase in the activity of creatine phosphokinase, lactate dehydrogenase and other muscle enzymes. There are signs of increased blood clotting and the presence of nitrogen in the blood, less often - increased activity of liver enzymes, increased calcium content in the blood, symptoms of metabolic disorders.

Analysis of cerebrospinal fluid is not informative.

Urinalysis indicates myoglobinuria.

Instrumental diagnostics in neuroleptic syndrome in the vast majority of cases is not carried out, since it has no clinically important significance. Only in extremely difficult situations, when the diagnosis is difficult due to external reasons, as well as with suspicion of brain damage, the doctor may resort to magnetic resonance imaging or computed tomography.

[36], [37], [38], [39], [40],

Differential diagnosis

Differential diagnosis is carried out:

• with benign neuroleptic extrapyramidal syndrome (proceeds without a consciousness disorder, without a rise in temperature);
• with a febrile form of catatonia (develops without prior treatment with antipsychotics);
• with meningitis, meningoencephalitis, hemorrhage into the subarachnoid space (a change in the analysis of cerebrospinal fluid is detected);
• with a thermal shock (proceeds without increased sweating and muscle hypertonia);
• with malignant hyperthermia (pathology precedes anesthesia with gaseous substance or injection of succinylcholine);
• with a feverish state with infection or intoxication;
• with alcoholic delirium.

Treatment of the neuroleptic Syndrome

Neuroleptic syndrome requires urgent treatment with placement of the patient in the intensive care unit of the hospital. Therapeutic actions consist in the urgent cancellation of antipsychotic or other provoking means, in the elimination of hypovolemia and dehydration, in preventing the development of insufficiency of the respiratory function, in preventing the development of acute renal failure, and in the immediate correction of body temperature.

For elimination of muscular weakness appoint Amantadine, Bromocriptine, medicines based on Levodopa.

It is also appropriate to use drugs benzodiazepine series - in particular, Relanium.

If the patient develops acute kidney failure, hemodialysis can be indicated.

Electroconvulsive treatment is of great importance for the elimination of neuroleptic syndrome. The procedures are carried out by a gentle method, with the simultaneous use of preparations of myorelaxing and sedative action. It is possible to use short-term anesthesia.

After the attack of the syndrome is completely stopped, and the body functions are restored in full, if necessary, resumption of treatment with neuroleptics is allowed - with a mandatory revision of the dosage.

Urgent care

At the first signs of neuroleptic syndrome development, gastric lavage is shown in the shortest possible time - the sooner, the better. Washing is used even in cases where the drug was used several hours ago.

When washing the stomach into water, add sodium chloride or saline. The patient is given a salt laxative preparation and a sorbent.

Oxygen therapy is mandatory.

With the development of a collapoid state, measures are taken to hydrate the body: intravenously injected fluids and Noradrenaline (such drugs as Adrenaline or Ephedrine in a neuroleptic syndrome are contraindicated, due to the danger of developing paradoxical vasodilation). To support cardiac activity and prevent arrhythmia, use of lidocaine and diphenin is used, and convulsions show Diazepam.

In addition to intensive therapy, intensive diuresis is performed without the use of blood alkalinization.

Medications that are used to relieve neuroleptic syndrome

	Dosing and Administration	Adverse symptoms	Special instructions
Midantan (Amantadine)	Take 0.1 g orally three times a day, or as an intravenous drip in the amount of 0.2 g to three times a day.	There may be motor excitement, headache, lowering of blood pressure, arrhythmia, indigestion, violation of urination.	Treatment with the drug can not be stopped abruptly. Amantadine is incompatible with ethyl alcohol.
Bromocriptine	Take 2.5-10 mg three times a day.	Possible violations of the liver, dyspepsia, dizziness, hallucinations, lowering blood pressure, skin rashes.	Treatment is carried out under regular control of blood pressure and the general condition of the patient.
Nakom (Levodopa, Carbidopa)	Take ½-1 tablet three times a day.	Sometimes there are dyskinesias, blepharospasm, depression, chest pain, unstable blood pressure.	It is not recommended to abruptly abolish the drug, since it is possible to develop a condition close to NSA.
Diazepam	Assign 10 mg in the form of intravenous injection, and then switch to oral administration in an amount of 5-10 mg three times a day.	Possible adverse reactions such as drowsiness, dry mouth, urinary incontinence, lowering of blood pressure.	The dose of the drug decreases gradually. You can not combine diazepam with ethanol.

Prevention

To prevent the development of neuroleptic syndrome is very important, since the treatment of this pathology is rather complicated. It is recommended to resort to the appointment of antipsychotics only when it is really justified. For example, persons suffering from affective disorders or a split personality should take neuroleptics only in extreme cases and for a short time. Also, do not take long-term treatment with such drugs for people with mental retardation or organic pathologies, as well as for the elderly.

Before any case of taking neuroleptics, the patient should be carefully examined - at least once every six months, throughout the entire period of such therapy. If the therapeutic course should be a priori long (at least a year), then it is necessary to carry out trial doses of neuroleptic doses, or even their gradual cancellation.

If the patient has suspicious symptoms indicating a possible rapid development of neuroleptic syndrome, then it is necessary to inform his family about possible consequences. This will make it possible to decide whether to continue the treatment.

[41], [42], [43], [44], [45], [46]

Forecast

Neuroleptic syndrome is completed by the patient's death in about 15% of cases. The most common causes of death are thrombosis of the pulmonary artery, acute heart failure, insufficient kidney function, complicated aspiration pneumonia, respiratory distress syndrome.

Over the past few years, the mortality rate has been reduced, thanks to early diagnosis of the syndrome and the improvement of emergency and intensive care.

In case the patient with neuroleptic syndrome remains alive, then during 7-14 days the symptoms gradually fade. Cognitive disorders, violations of balance and coordination of movements, parkinsonism remain for more than 1-2 months and more. A more severe rehabilitation period is observed after treatment with neuroleptic drugs prone to accumulation, as well as in patients who have previously been diagnosed with schizophrenia.

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