Insulinocomatous therapy

Insulin therapy is the general name for insulin-based therapies; in psychiatry - a method of treating mentally ill patients with large doses of insulin, causing a coma or subcomatous condition, called insulin-shock or insulin-co-therapy (IT).

[1], [2], [3], [4]

Indications for insulin-co-therapy

In modern conditions, the typical and most frequent indication for carrying out IT is an acute attack of schizophrenia with a predominance of hallucinatory-paranoid symptoms and a short duration of the process. The closer the onset of the onset of the disease, the greater the chance of success. If the disease has a long chronic character, then IT is rarely used, mainly in a paroxysmal course of the process. Insulinocomatous therapy as an intensive method of treatment is used for recurrent schizophrenia with psychopathological syndromes (in particular, Kandinsky-Clerambo syndrome) and schizoaffective psychoses with pronounced resistance. Subcomatous and hypoglycemic doses of insulin can be prescribed for involuntary psychoses, prolonged reactive states, MDP. A special case when there is practically no alternative to IT is acute schizophrenic psychosis with complete intolerance to psychopharmacotherapy. Indications for forced IT do not differ from the indications for standard IT. Insulin-comatose therapy increases the duration of remission and improves their quality.

Preparation

Conduction of insulin-mediated therapy requires mandatory registration of the patient's informed consent (except for urgent cases). For incapacitated or underage patients, consent is given by their legal representative. Before the course of IT in the medical history, the conclusion of the clinical and expert commission is made.

To conduct IT, you need a separate room, equipped with the necessary tools and a set of medicines, a nurse trained in this technique, and a paramedic. Insulin-comatose therapy is a typical psycho-reanimation technique. The best place for it is the unit of psycho-reanimation.

Before carrying out the IT, the patient needs to conduct a study: a general blood and urine test, a biochemical blood test with the obligatory determination of sugar level and studying the sugar curve, lung radiography, electrocardiography. To resolve the issue of admission to IT appoint a consultation therapist. According to individual indications, you can also assign other studies. After dinner on the eve of the day of IT, the patient should not eat anything. The session is conducted in the morning on an empty stomach. For the period of the session, the patient is fixed in the lying position. Before the session, the patient is offered to empty the bladder. Then undress (for access to the veins, the possibility of a complete physical examination) and shelter. Limbs must be securely fixed (in case of hypoglycemia).

Methods of insulin-therapy therapy

There are several methods of insulin co-therapy. Zakel's method is classical. It is used up to the present time. During the first days, a coma dose is selected, which is administered in the following days. In a coma, patients are kept from a few minutes to 1-2 hours. Insulin coma is stopped by intravenous injection of 20-40 ml of 40% glucose solution. The patient quickly regains consciousness, begins to answer questions. The course of treatment can consist of a different number of sessions: from 8 to 35 and more. The number of participants in the treatment course is individual, depending on the tolerability of therapy and the dynamics of the condition.

There were also a sub-shock and a seamless method, long-course and prolonged-com methods, a method of repeated shocks, and intravenous insulin administration. IT was first used as a monotherapy, and with the advent of new methods began to be used in combination with psychotropic drugs, electroconvulsive therapy and other types of treatment.

The natural development of theory and practice of IT became the stage proposed by the Moscow Scientific Research Institute of Psychiatry of the RSFSR Ministry of Health in the 1980s. Modern modification of IT - forced insulin-comatose therapy. This method is developed on the basis of special studies of traditional IT and the dynamics of development of coma. The Moscow regional center of psycho-reanimation, carefully "sharpened" the methodology, included the theme of forced IT in the training program of psycho-reanimatologists.

Main differences and advantages boosted from standard IT:

• the introduction of insulin intravenously at a strictly prescribed rate, which has its own peculiarities of impact on the body, other than subcutaneous or intravenous fluid administration;
• rapid achievement of com due to forced depletion of the depot of glycogen, in connection with which there is a significant reduction in the duration of the course;
• a regular decrease in the insulin dose during the course, instead of increasing it with standard IT;
• The therapeutic effect can be manifested even before the development of coma;
• more perfect control of the patient's condition and management during the session, thereby reducing the number of complications.

When forced IT is important to meet the requirements for quality and purity of insulin because of the increased likelihood of development of phlebitis and allergies. For any type of insulin therapy, only short-acting insulin is suitable, and the use of any prolonged insulin is categorically unacceptable.

For the first sessions of forced IT, the authors proposed an empirically established insulin delivery rate of 1.5 IU / min, which, with a standard initial dose of 300 IU, determines the duration of the session to be 3.5 hours. Nelson (2004), the sessions proceed slightly softer if the rate of insulin administration is 1.25 IU / min and the initial standard dose of 300 IU is administered for 4 hours. It is empirically accepted to maintain the rate of insulin delivery such that within 1 minute 1 patient enters the bloodstream / 240 part of the planned dose for this session. This provides an adequate rate of reduction in blood sugar.

The entire treatment course can be divided into three stages.

1. The glycogen depletion stage (usually the 1-3 st session), during which the administered insulin dose is constant and is 300 IU, and the depth of hypoglycemia before the standard session is increased.
2. The step of lowering insulin doses (usually 4-6th session), when coma occurs before the introduction of the full calculated dose of the drug.
3. The stage of the "comatose plateau" (usually starting from the 7th session until the end of the course), when the comatose dose is stable or its slight fluctuations are possible, the average coma dose is 50 IU.

Coping with hypoglycaemia

From the first session, hypoglycaemia is stopped in full (even if there were no signs of hypoglycemia during the session) 200 ml of 40% glucose solution was dripped intravenously at the fastest possible rate. Immediately after restoration of consciousness, 200 ml of warm sugar syrup (based on 100 g of sugar per 200 ml of water) are given orally. If the first session does not carry out full-fledged cupping, then there may be repeated hypoglycemic coma. Coping hypoglycemia should be started after 3 minutes of the patient's stay in a coma. Longer comatose conditions, previously recommended, contribute to the development of lingering coma and do not improve the effectiveness of treatment.

Sessions insulinokomatoznoy therapy should be conducted daily without breaks for the weekend. Organization of work provides for the constant availability of qualified personnel and all other conditions for conducting daily sessions.

[5], [6], [7]

Duration of the course of insulin-therapy

Approximate number of comatose sessions is 20, however individual fluctuations in the duration of the treatment course (5-30) are possible. The basis for the completion of the course is the persistent elimination of psychopathological symptoms. During the course of treatment, a qualified assessment of the patient's mental status is necessary.

During the course of IT, the risk of infectious diseases increases, and therefore it is necessary to conduct treatment in a dry warm room, change the patient's wet clothes in a timely manner, examine it daily for inflammatory diseases, and at least twice a day conduct thermometry.

Before the course of IT it is necessary to obtain the opinion of the clinical and expert commission and informed consent of the patient. An important measure is the careful documentation of each session, which increases the patient's safety and protects the staff from accusations of wrong actions.

The sections of the List of Insulin-Coat Therapy:

• surname, name and patronymic of the patient, body weight, age, unit of the hospital, attending physician;
• monitoring of sessions - every half hour noted hemodynamics, the state of consciousness, somatic signs of hypoglycemia, as well as complications and ongoing medical measures;
• the prescribed and administered dose of insulin, the rate of administration;
• a method of arresting hypoglycemia with indication of the doses of carbohydrates;
• premedication;
• blood sugar and other indicators;
• the signature of the doctor and the nurse.

The doctor at the end of each session appoints in the "IT sheet" the dose of insulin for the next session and introduces additional instructions for keeping the session. At the end of the course, the "Sheet of IT" is pasted into the medical history.

[8], [9], [10], [11], [12]

Factors affecting efficiency

In certain cases, IT gives the best in quality and much more persistent effect than treatment with psychotropic drugs. It is known that the effect of IT is much higher than the frequency of spontaneous remissions. In cases with a disease duration of up to six months, the effectiveness of IT is 4 times higher than the frequency of spontaneous remissions, with a prescription of 0.5-1 year - 2 times. At late terms of the beginning of treatment of distinction are less essential. The effect of IT in schizophrenia depends to a large extent on the syndrome that was formed at the beginning of treatment. The best results of insulin therapy are achieved with hallucinatory-paranoid and paranoid (but not paranoid) syndromes. The effectiveness of IT decreases with the presence in the clinical picture of the phenomena of depersonalization, mental automatisms and pseudo-hallucinations, apatoabulic and hebephrenic syndromes. In the onset of the Kandinsky-Clerambo syndrome, the likelihood of a prolonged remission after IT is high, but the longer this symptom complex keeps, the worse the therapeutic prognosis. In determining the indications for IT, attention is also drawn to the type of schizophrenia flow. The value of the type of flow is particularly large with a prescription for more than a year. The greatest effect is achieved with paroxysmal flow and recurrent schizophrenia. The faster in the course of IT are found the shift to the better, the more favorable the forecast.

[13], [14], [15], [16], [17], [18],

Alternative therapies

With the advent of psychotropic drugs, psychopharmacotherapy virtually supplanted insulin-comatose therapy. From comatose methods of treatment, an alternative to IT is electroconvulsive therapy and atropine-comatose therapy. In recent years non-pharmacological methods have been widely used, used in combination with comatose to treat patients with therapeutic resistance to psychotropic drugs. Such methods include hemosorption, plasmapheresis, ultraviolet and laser irradiation of blood, magnetotherapy, acupuncture, hyperbaric oxygenation and adaptation to periodic hypoxia, unloading diet therapy, etc. Alternative methods of treatment also include transcranial electromagnetic stimulation, biological feedback, sleep deprivation, phototherapy, psychotherapy. The differentiated use of these methods allows for successful treatment and high results in patients with endogenous psychoses resistant to psychopharmacotherapy.

[19], [20], [21], [22], [23]

Contraindications

There are temporary and constant contraindications. The latter are divided into relative and absolute. Temporary contraindications include inflammatory processes and acute infectious diseases, exacerbation of chronic infections and chronic inflammatory processes, as well as drug intoxication. Constant absolute contraindications include severe diseases of the cardiovascular and respiratory systems, peptic ulcer disease, hepatitis, cholecystitis with frequent exacerbations, nephro-nephritis with impaired renal function, malignant tumors, all endocrinopathies, pregnancy. Constant relative contraindications include mitral defects with stable compensation, hypertension I-II degree, compensated pulmonary tuberculosis, kidney disease in remission. Contraindication for IT is the poor development of superficial veins, which hinders the introduction of insulin and the relief of hypoglycemia.

[24], [25], [26], [27]

Possible complications

During the IT period, the following complications are possible:

• psychomotor agitation;
• repeated hypoglycemia;
• protracted coma;
• convulsive twitching and epileptiform seizures;
• vegetative disorders;
• phlebitis.

Psychomotor agitation in forced IT arises much more rarely and is much less pronounced than with traditional IT. More often excitation arises against the background of the sopor. It is usually short-lived and does not require special procedures.

Repeated hypoglycemia in forced IT are less common than with traditional IT. Usually they occur in the second half of the day. For cupping, glucose is administered.

One of the most dangerous complications is a protracted coma, which is extremely rare with forced IT. Who is stopped by the administration of glucose * under the control of blood sugar. In some cases, special resuscitation is needed. Further treatment with insulin should be discontinued.

In the hypoglycemic state, convulsive twitchings of certain muscle groups can occur, which do not require special treatment. When generalizing seizures, prescribe additional symptomatic therapy and reduce the comatose dose of insulin. Epileptiform seizures may occur. A single fit will not add up to a contraindication to insulin therapy, but requires symptomatic treatment. A series of seizures or the development of EC is a serious contraindication to IT.

Vegetative disorders that occur with hypoglycemia are manifested by excessive sweating, drooling, increased pulse, falling or rising blood pressure, etc. These disorders do not serve as a basis for interrupting treatment. If the patient's condition worsens sharply, in addition to introducing glucose, additional medication is prescribed according to the indications.

Phlebitis are relatively rare and do not serve as a contraindication for IT. To treat this complication, anti-inflammatory therapy is recommended.

Historical reference

The use of shock methods began with the opening of the Viennese psychiatrist Manfred Sakel. As far back as 1930, he noticed that morphine addicts have a much easier abstinence syndrome if they inject hypoglycemia with insulin and starvation. In 1933, the scientist investigated the effect of severe unconscious conditions that occur after the administration of insulin on an empty stomach. Later, Sakel applied insulin-co-therapy for the treatment of schizophrenia.

In 1935, his monograph, summarizing the first experiments, was published.

Since that time, a triumphal procession of insulin-co-therapy has begun in psychiatric hospitals all over the world. In our country this method was first used in 1936. A.E. Kronfeld and E.Ya. Sternberg, who in 1939 published the Instruction on insulin shock therapy, a collection of "Methods and techniques of active therapy of mental illnesses" edited by V.A. Gilyarovsky and P.B. Posvyanskogo and many other works on this topic. The rapid recognition and success of insulin shocks was associated with its effectiveness.

The complexity of this method is obvious even now. In the early years of IT, when the technique was not yet worked out, the mortality rate reached 7% (according to Sakel, 3%). However, the method was met sympathetically and quickly spread. The atmosphere of the thirties contributed to this. The incurable, fatalities of schizophrenia became the main problem of psychiatry. An active method of treatment was eagerly awaited. Hypoglycemic shock did not inspire fears of its brutality, because the methods of fighting it were known.

A.E. Licko (1962, 1970). Author of the first and best monograph on this subject in the Soviet Union, based on his own observations, described the clinical manifestations of insulin hypoglycemia in terms of the syndromic principle, investigated the mechanism of insulin action on the central nervous system, and gave practical recommendations on the method of insulin-shock treatment of psychoses.

The mechanism of therapeutic action of insulin shocks in schizophrenia and other psychoses became very clear. Insulin shocks are still an empirical means of treatment, despite the large number of theories proposed over the past decades. All hypotheses can be divided into two groups: one based on clinical observations of the dynamics of the psychopathology pattern during treatment, others on the physiological, biochemical and immunological shifts detected by insulin shocks.

The most common are two theories that describe the mechanism of hypoglycemia. According to the "hepatic" theory, insulin, acting on the hepatocyte, enhances the formation of glycogen in it from glucose, which reduces the release of glucose by the liver into the blood. According to the "muscular" theory, the cause of hypoglycemia is that under the influence of insulin, muscle cells are intensively consuming glucose from the blood. There is an opinion that both mechanisms play a role in the development of hypoglycemia.

In contrast to the "peripheral" theories, theories of the action of insulin on the central nervous system were put forward, on the basis of which investigations of the conditioned reflex nature of insulin hypoglycemia appeared. In the first hypotheses describing the action of insulin on the central nervous system, the mechanism of development of coma, convulsions and other neurological phenomena was assessed as a consequence of sugar starvation of nerve cells. But this position was contradicted by many facts. It was suggested that insulin in large doses exerts a toxic effect on nerve cells, which is based on the development of tissue hypoxia of the brain. Hypoxic and toxic theories did not provide a sufficient understanding of the mechanism of insulin coma. The study of the effect of hydration and dehydration on the occurrence of insulin convulsions and coma, the presence of intracellular edema of brain cells and other organs led to the emergence of a hypo-glycemic hypothesis of insulin coma that answered a number of questions.

Theories explaining the mechanism of the therapeutic effect of insulin-co-therapy with psychoses, still do not exist. The therapeutic effect of IT was associated with the influence on the emotional sphere, correlations of the indices of higher nervous activity and the vegetative system of the patient, a favorable combination of protective inhibition and vegetative mobilization, an increase in the immune reactivity of the organism, etc. There was an interpretation of the therapeutic effect from G. Selye's theory of stress and adaptive syndrome . There were hypotheses explaining the therapeutic effect not by the action of the shock itself, but by chemical changes in the brain in the post-shock period. Many authors support the hypothesis of "hypoglycemic washing of neurons". Normally, using a sodium-calcium pump, the cell maintains a constant gradient of sodium and potassium concentrations on both sides of the membrane. With hypoglycemia, the source of energy (glucose) disappears for the functioning of the sodium-potassium pump, and it ceases to work. This hypothesis raises a number of questions and does not fully disclose the mechanism of therapeutic action. To date, it is believed that insulin-comatose therapy, like other shock treatments, has an undifferentiated global antipsychotic effect.

Insulin-comatose therapy of schizophrenia and other psychoses has received almost universal recognition. Indications for the insulin-shock method were all cases of schizophrenia, not yet treated with insulin. IT was recommended for the treatment of psychoses caused by organic (postencephalic) lesions of the central nervous system, prolonged infectious psychoses with a hallucinatory-paranoid syndrome. Insulinocomatous therapy was shown in involutional and alcoholic paranoid, chronic alcoholic hallucinosis, severe cases of morphine abstinence, hallucinatory-paranoid form of progressive paralysis, etc. There is experience of IT application in schizophrenia in children.

Despite obvious success, IT had active opponents, who considered this method to be ineffective and even harmful. In Western Europe in the 50's. Insulin-comatose therapy was consigned to oblivion after incorrectly conducted scientific works proving its "inefficiency". In our country, IT continues to be used and is considered one of the most effective methods of active biological therapy of psychoses.

With the advent and spread of psychotropic drugs, the status of IT psychoses has changed. In recent decades, this method has been used much less often. By the amount of accumulated knowledge and experience in the field of IT application, Russia has a great advantage over other countries. Nowadays, IT is used infrequently because of the high cost of insulin, the complexity of the treatment course and the long duration of treatment.