Insulin coma therapy

Insulin therapy is a general name for treatment methods based on the use of insulin; in psychiatry, it is a method of treating mentally ill patients using large doses of insulin that cause a comatose or subcomatose state, called insulin shock or insulin comatose therapy (IT).

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Indications for insulin comatose therapy

In modern conditions, the typical and most frequent indication for IT is an acute attack of schizophrenia with a predominance of hallucinatory-paranoid symptoms and a short duration of the process. The closer in time the attack is to the onset of the disease, the greater the chances of success. If the disease is of a protracted chronic nature, then IT is rarely used, mainly in the case of an attack-like course of the process. Insulin comatose therapy as an intensive treatment method is used for recurrent schizophrenia with psychopathological syndromes (in particular, Kandinsky-Clerambault syndrome) and schizoaffective psychoses with pronounced resistance. Subcomatose and hypoglycemic doses of insulin can also be prescribed for involutional psychoses, protracted reactive states, and 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 indications for standard IT. Insulin comatose therapy helps to increase the duration of remissions and improve their quality.

Preparation

Insulin comatose therapy requires mandatory informed consent from the patient (except in urgent cases). For incapacitated or minor patients, consent is given by their legal representative. Before the course of IT, the conclusion of the clinical expert commission is entered into the medical history.

To perform IT, a separate room equipped with the necessary instruments and a set of drugs, a nurse trained in this method, and an orderly are needed. Insulin comatose therapy is a typical psychoreanimatology method. The best place to perform it is a psychoreanimatology unit.

Before performing IT, the patient must undergo a study: a general blood and urine test, a biochemical blood test with mandatory determination of sugar levels and study of the "sugar curve", chest X-ray, electrocardiography. To decide on admission to IT, a consultation with a therapist is prescribed. Other studies can be prescribed based on individual indications. The patient should not eat anything after dinner on the day before the day of IT. The session is performed in the morning on an empty stomach. For the duration of the session, the patient is fixed in a lying position. Before the session, the patient is asked to empty the bladder. Then they are undressed (to access the veins, to allow a full physical examination) and covered. The limbs must be securely fixed (in case of hypoglycemic excitations).

Methods of insulin comatose therapy

There are several methods of insulin coma therapy. The Zakel method is classical. It is still used today. During the first days, a coma dose is selected, which is administered in the following days. Patients are kept in a coma from several minutes to 1-2 hours. Insulin coma is stopped by intravenous administration of 20-40 ml of 40% glucose solution. The patient quickly regains consciousness and begins to answer questions. The course of treatment may consist of a different number of sessions: from 8 to 35 or more. The number of comas in the treatment course is individual, depending on the tolerability of the therapy and the dynamics of the condition.

There were also subshock and non-shock methods, extended course and prolonged coma methods, repeated shock methods and intravenous insulin administration. IT was initially used as monotherapy, and with the advent of new methods, it began to be used in combination with psychotropic drugs, electroconvulsive therapy and other types of treatment.

The stage of natural development of the theory and practice of IT was the modern modification of IT proposed by the Moscow Research Institute of Psychiatry of the Ministry of Health of the RSFSR in the 80s - forced insulin comatose therapy. This method was developed on the basis of special studies of traditional IT and the dynamics of the development of a comatose state. The Moscow Regional Center for Psychoreanimatology, having carefully "honed" the method, included the topic of forced IT in the training program for psychoreanimatologists.

The main differences and advantages of forced from standard IT:

• intravenous administration of insulin at a strictly specified rate, which has its own specific effects on the body, different from subcutaneous or intravenous jet administration;
• rapid achievement of coma due to forced depletion of glycogen depots, due to which there is a significant reduction in the duration of the course;
• a natural reduction in the insulin dose during the course instead of increasing it with standard IT;
• the therapeutic effect may manifest itself even before the development of comatose states;
• more advanced monitoring of the patient's condition and management during the session, thereby reducing the number of complications.

With forced IT, it is important to comply with the requirements for the quality and purity of insulin due to the increased likelihood of developing phlebitis and allergies. With any type of insulin therapy, only short-acting insulins are suitable, and the use of any prolonged insulins is strictly unacceptable.

For the first sessions of forced IT, the authors of the method proposed an empirically established rate of insulin administration of 1.5 IU/min, which, with a standard initial dose of 300 IU, results in a session duration of 3.5 hours. According to A.I. Nelson (2004), sessions proceed somewhat more gently if the rate of insulin administration is 1.25 IU/min and the initial standard dose of 300 IU is administered over 4 hours. It is empirically accepted to maintain the rate of insulin administration such that 1/240 of the dose planned for a given session enters the patient's blood within a minute. This ensures an adequate rate of blood sugar reduction.

The entire course of treatment can be divided into three stages.

1. The glycogen depletion stage (usually 1-3 sessions), during which the administered insulin dose is constant and amounts to 300 IU, and the depth of hypoglycemia before stopping the standard session increases.
2. The stage of reducing insulin doses (usually 4-6th session), when coma occurs before the full calculated dose of the drug is administered.
3. The “comatose plateau” stage (usually from the 7th session until the end of the course), when the comatose dose is stable or its minor fluctuations are possible, the average comatose dose is 50 IU.

Relief of hypoglycemia

From the very first session, hypoglycemia is completely stopped (even if there were no signs of hypoglycemia during the session) by administering 200 ml of a 40% glucose solution intravenously by drip at the maximum possible rate. Immediately after consciousness is restored, 200 ml of warm sugar syrup is given orally (at the rate of 100 g of sugar per 200 ml of water). If complete stopping is not carried out from the very first session, repeated hypoglycemic comas may occur. Stopping hypoglycemia should begin after 3 minutes of the patient's stay in a coma. Longer comatose states, recommended earlier, contribute to the development of a protracted coma and do not increase the effectiveness of treatment.

Insulin comatose therapy sessions should be conducted daily without breaks on weekends. The organization of work provides for the constant presence of qualified personnel and all other conditions for conducting daily sessions.

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Duration of the course of insulin comatose therapy

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

During the IT procedure, the risk of infectious diseases increases, therefore it is necessary to carry out treatment in a dry, warm room, promptly change the patient's wet clothes, examine him daily for inflammatory diseases, and take temperature measurements at least twice a day.

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

Sections of the "Insulin comatose therapy sheet":

• patient's last name, first name and patronymic, body weight, age, hospital department, attending physician;
• monitoring of sessions - every half hour, hemodynamic parameters, state of consciousness, somatic signs of hypoglycemia, as well as complications and ongoing treatment measures are noted;
• prescribed and administered dose of insulin, rate of administration;
• method for stopping hypoglycemia with indication of carbohydrate doses;
• premedication;
• blood sugar and other tests;
• signature of the doctor and nurse.

At the end of each session, the doctor prescribes the insulin dose for the next session in the "IT Sheet" and enters additional instructions for conducting the session. At the end of the course, the "IT Sheet" is pasted into the medical record.

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Factors Affecting Efficiency

In certain cases, IT provides a better and much more stable effect than treatment with psychotropic drugs. It is known that the effect of IT is significantly higher than the frequency of spontaneous remissions. In cases with a disease history of up to six months, the effectiveness of IT is 4 times higher than the frequency of spontaneous remissions, with a disease history of 0.5-1 year - 2 times. At late stages of treatment initiation, the differences are less significant. The effect of IT in schizophrenia largely depends on the syndrome that has formed by 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 is reduced in the presence of depersonalization phenomena, mental automatisms and pseudohallucinations, apatoabulic and hebephrenic syndromes in the clinical picture. At the onset of Kandinsky-Clerambault syndrome, the probability of prolonged remission after IT is high, but the longer this symptom complex persists, the worse the therapeutic prognosis. When determining indications for IT, attention is also paid to the type of schizophrenia. The significance of the type of course is especially great if the disease has been going on for more than a year. The greatest effect is achieved with paroxysmal course and recurrent schizophrenia. The faster a shift for the better is detected during IT, the more favorable the prognosis.

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Alternative treatments

With the advent of psychotropic drugs, psychopharmacotherapy has practically replaced insulin coma therapy. Among coma treatment methods, electroconvulsive therapy and atropine coma therapy serve as an alternative to IT. In recent years, non-pharmacological methods used in combination with coma methods for the treatment of patients with therapeutic resistance to psychotropic drugs have become widespread. Such methods include hemosorption, plasmapheresis, ultraviolet and laser irradiation of blood, magnetic therapy, acupuncture, hyperbaric oxygenation and adaptation to periodic hypoxia, unloading dietary therapy, etc. Alternative treatment methods also include transcranial electromagnetic stimulation, biofeedback, sleep deprivation, phototherapy, and psychotherapy. Differentiated use of the listed methods allows for successful treatment and high results in patients with endogenous psychoses resistant to psychopharmacotherapy.

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Contraindications

There are temporary and permanent 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. Permanent absolute contraindications include severe diseases of the cardiovascular and respiratory systems, peptic ulcer, hepatitis, cholecystitis with frequent exacerbations, nephrosonephritis with impaired renal function, malignant tumors, all endocrinopathies, pregnancy. Permanent relative contraindications include mitral valve defects with persistent compensation, hypertension of I-II degree, compensated pulmonary tuberculosis, kidney diseases in the remission stage. Contraindication for IT is poor development of superficial veins, which complicates the administration of insulin and relief of hypoglycemia.

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Possible complications

During the period of IT the following complications are possible:

• psychomotor agitation;
• repeated hypoglycemia;
• prolonged comas;
• convulsive twitching and epileptiform seizures;
• vegetative disorders;
• phlebitis.

Psychomotor agitation during forced IT occurs much less frequently and is much less pronounced than during traditional IT. More often, agitation occurs against the background of stupor. It is usually short-lived and does not require special procedures.

Repeated hypoglycemia with forced IT is less frequent than with traditional IT. It usually occurs in the second half of the day. Glucose is administered to stop it.

One of the most dangerous complications is a prolonged coma, which is extremely rare with forced IT. It is treated with glucose* under blood sugar control. In some cases, special resuscitation measures are necessary. Further insulin treatment should be discontinued.

In a hypoglycemic state, convulsive twitching of individual muscle groups may occur, which do not require special treatment. In case of generalization of convulsions, additional symptomatic therapy is prescribed and the comatose dose of insulin is reduced. Epileptic seizures may occur. A single seizure is not a contraindication to insulin therapy, but requires symptomatic treatment. A series of seizures or the development of ES is a serious contraindication to IT.

Vegetative disorders that occur with hypoglycemia are manifested by increased sweating, salivation, increased heart rate, a drop or increase in blood pressure, etc. These disorders do not serve as grounds for interrupting treatment. If the patient's condition deteriorates sharply, then in addition to the introduction of glucose, additional drug therapy is prescribed as indicated.

Phlebitis is relatively rare and does not serve as a contraindication for IT. Anti-inflammatory therapy is recommended for the treatment of this complication.

Historical background

The use of shock methods began with the discovery of the Viennese psychiatrist Manfred Sakel. As early as 1930, he noted that the course of withdrawal symptoms in morphine addicts was significantly alleviated if hypoglycemia was induced by the administration of insulin and fasting. In 1933, the scientist studied the effect of severe unconscious states that occurred after the administration of insulin on an empty stomach. Later, Sakel used insulin comatose therapy to treat schizophrenia.

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

From this time on, the triumphal march of insulin-comatose therapy began in psychiatric hospitals all over the world. In our country, this method was first used in 1936 by A.E. Kronfeld and E.Ya. Sternberg, who in 1939 published the Instructions for Insulin Shock Therapy, a collection of “Methodology and Technique of Active Therapy of Mental Illnesses” edited by V.A. Gilyarovsky and P.B. Posvyansky, and many other works on this topic. The rapid recognition and success of insulin shock therapy were associated with its effectiveness.

The complexity of this method is obvious even now. In the first years of IT application, when the method had not yet been worked out, the mortality rate reached 7% (according to Sakel himself, 3%). However, the method was met with sympathy and quickly spread. The atmosphere of the thirties contributed to this. The incurability, fatality of schizophrenia became the main problem of psychiatry. An active method of treatment was eagerly awaited. Hypoglycemic shock did not inspire fears with its brutality, since the methods of combating it were known.

A.E. Lichko (1962, 1970) the author of the first and best monograph on this topic in the Soviet Union, based on his own observations described the clinical manifestations of insulin hypoglycemia according to the syndromic principle, studied 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 the therapeutic effect of insulin shocks in schizophrenia and other psychoses was clarified very slowly. Insulin shocks still remain an empirical means of treatment, despite the large number of theories proposed over the past decades. All hypotheses can be divided into two groups: some are based on clinical observations of the dynamics of the psychopathological picture during treatment, others - on physiological, biochemical and immunological shifts discovered under the influence of insulin shock therapy.

There are two most common theories describing the mechanism of hypoglycemia. According to the "liver" theory, insulin, acting on the hepatocyte, increases the formation of glycogen from glucose, which reduces the release of glucose from the liver into the blood. According to the "muscle" theory, the cause of hypoglycemia is that, under the influence of insulin, muscle cells intensively consume glucose from the blood. There is an opinion that both mechanisms are important in the development of hypoglycemia.

In contrast to the "peripheral" theories, theories of insulin action on the central nervous system were put forward, on the basis of which studies 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, seizures 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 has a toxic effect on nerve cells, which is based on the development of tissue hypoxia of the brain. The hypoxic and toxic theories did not provide a sufficient understanding of the mechanism of development of insulin coma. The study of the effect of hydration and dehydration on the occurrence of insulin seizures and coma, the presence of intracellular edema of brain cells and other organs led to the emergence of the hydration-hypoglycemic hypothesis of insulin coma, which answered a number of questions.

There are still no theories explaining the mechanism of the therapeutic effect of insulin comatose therapy in psychoses. The therapeutic effect of IT was associated with the effect on the emotional sphere, correlations of indicators of higher nervous activity and the patient's autonomic system, a favorable combination of protective inhibition and autonomic mobilization, an increase in the body's immune reactivity, etc. There was an interpretation of the therapeutic effect from the standpoint of G. Selye's teaching on 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, with the help of the sodium-potassium pump, the cell maintains a constant gradient of sodium and potassium concentrations on both sides of the membrane. In hypoglycemia, the source of energy (glucose) for the functioning of the sodium-potassium pump disappears, and it stops working. This hypothesis raises a number of questions and does not fully reveal the mechanism of the therapeutic effect. Today, it is believed that insulin comatose therapy, like other shock treatment methods, 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, protracted infectious psychoses with hallucinatory-paranoid syndrome. Insulin comatose therapy was indicated for involutional and alcoholic paranoid, chronic alcoholic hallucinosis, severe cases of morphine withdrawal, hallucinatory-paranoid form of progressive paralysis, etc. There is experience in using IT for schizophrenia in children.

Despite its obvious success, IT had active opponents who considered this method ineffective and even harmful. In Western European countries in the 1950s, insulin comatose therapy was consigned to oblivion after incorrectly conducted scientific studies 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 situation with IT psychoses has changed. In recent decades, this method has been used much less frequently. In terms of the amount of accumulated knowledge and experience in the field of IT application, Russia has a great advantage over other countries. Nowadays, IT is rarely used due to the high cost of insulin, the complexity of the treatment course, and the long duration of treatment.