RU2594430C1 - Method of general controlled human body hyperthermia - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to anaesthesiology and resuscitation, and can be used for general controlled hyperthermia of human organism. This is ensured by planned infusion preparation. Before immersing the patient in hot water 1 mg/ml of Dalargin is administered intravenously. Then patient's body is totally heated up by immersion, except the head, in hot water with temperature of 42-47 °C at the rate of body heating equal to 0.5-1.5 °C for 5 minutes with saturation within normal limits up to temperature increase in esophagus till 42.5-44 °C. Temperature is measured in the middle one-third part of oesophagus. Additionally temperature is measured on the eardrum. Besides, anaesthesiology protection is provided by introducing relaxing agents, anesthetics and hypnotic drugs. Hyperthermia is carried out with monitoring of pulse frequency, heart, blood pressure values, saturation. BIS-monitoring is carried out. According to BIS-monitoring with simultaneous reduction of heating rate a biological critical point is determined. During hyperthermia Dalargin is introduced in the above dose at each degree starting from 40 °C being measured in esophagus, as well as at biological critical point. For 5-20 minutes effective warming is maintained not extending beyond the biological critical point. Pathogenetically substantiated drugs are administered depending on the available pathology. Then the patient is removed from the bath and normal temperature is restored.

EFFECT: method provides higher clinical effectiveness due to selection of reliable criteria reaching maximum heating, establishing exposure time and peak hyperthermia, as well as a result of administration of drug preventing possible development of thermal shock.

1 cl, 1 ex

Description

The invention relates to medicine, namely to anesthesiology and intensive care, and can be used in patients with oncological, neurological, orthopedic and infectious, immunological pathologies for the implementation of the therapeutic effect and prevention of complications.

A known method of general heating of the body (RF patent No. 2112471, IPC A61F 7/00, publ. 06/10/98). According to this method, the patient’s body is heated with hot water against the background of barbituric anesthesia and mechanical ventilation (mechanical ventilation) after the preliminary administration of pyridoxine, hexamethylenetetramine, alpha-tocopherol, sodium hydroxybutyrate, and hexamethylenetetramine is additionally added at the height of heating.

The disadvantages of this method are:

1. Sodium oxybutyrate (GHB) is used as one of the components of anesthesia, which is currently banned abroad due to its dangerous effects (transmineralization).

2. At the stage of warming up the patient’s body, mechanical ventilation is used in the mode of traditional (16-20 breaths per minute) volumetric ventilation of the lungs, which under conditions of hyperthermia may not provide the increased oxygen demand of the body.

3. The process of heating the body is "passive", its speed is not controlled, which in patients with different body weights can lead to dangerous complications.

4. The applied pharmacological protection measures (antioxidants, sodium hydroxybutyrate and two-time administration of hexamethylenetetramine) do not completely prevent the negative effects of thermal aggression, as evidenced by the need for mechanical ventilation in patients within 6 hours after a session of hyperthermia.

Closest to the proposed one is a method of general controlled hyperthermia of the human body (RF patent No. 2126667, IPC A61F 7/00, A61K 31/395, publ. 02.27.1999), including general heating of the patient's body by immersing it, except for the head, in hot water, using fentanyl anesthesia, high-frequency mechanical ventilation, providing saturation at the level of 97-100% and administering urotropine to the patient. The patient’s body is heated to a temperature in the esophagus of 42.5-44 ° C with hot water with a temperature in the range of 45-47 ° C, the body is heated at a rate of at least 1 ° C for 5 minutes by constant forced convection of the coolant. Before heating, urotropin (hexamethylenetetramine) is administered in an amount of 20 mg of a 20% solution enterally and additionally at a heating height of 0.2 ml / kg of a 40% solution intravenously, as well as 0.1 ml / kg of a 40% solution intravenously after restoration of normothermia.

The registration of the moment of manifestation of the “biological zero” phenomenon in the brain, called the biological turning point, is the most informative safety criterion for artificially reproduced OAG. Achieving a biological tipping point is manifested in a 80% reduction in brain biopotentials and is a signal to stop further active physical heating of the body.

Failure to achieve a biological tipping point does not allow the proper therapeutic effect of hyperthermia to be realized, and exceeding the temperature barrier can lead to dangerous complications. As a result, the therapeutic effect may not be achieved, since the high-temperature biological tipping point has an individually different temperature range.

The main disadvantage of the method according to the patent of the Russian Federation No. 21266667 is that the maximum warming level is selected subjectively, since the choice of the biological tipping point is not quantified: according to the "classical" electroencephalogram (EEG), it is impossible to quickly judge in digital terms the approach and the onset of the biological tipping point.

In addition, this method has the following disadvantages:

- the drug Hexamethylenetetramine used can cause irritation of the renal parenchyma and, in some cases, contribute to the spread of the disease process with pyelitis and in many countries it is prohibited for use;

- the time interval for the patient to be at the height of hyperthermia is set arbitrarily.

The objective of the invention is to increase the effectiveness of treatment by determining the objective most simple and reliable criterion for achieving the maximum possible heating, setting the exposure time for the peak of hyperthermia, choosing a drug that prevents the possible development of trypsinemia, which can lead to the development of heat shock.

The problem is solved due to the fact that in the method of carrying out general controlled hyperthermia of the human body, which includes scheduled infusion preparation and general heating of the patient’s body by immersing him, except the head, in hot water with a temperature of 42-47 ° C with a body heating rate of 1 ° C per 5 min, ensuring saturation within normal limits, until the temperature in the esophagus rises to 42.5-44 ° C, monitoring of heart rate, heart rate, blood pressure, saturation, according to the invention, during ertermii administered dalargin. Temperature is measured in the middle third of the esophagus and on the eardrum. Bispectral monitoring (BIS monitoring) is carried out; according to BIS monitoring, at the same time a decrease in the heating rate, a biological tipping point is determined. For 5-20 minutes, effective warming is maintained, which does not go beyond the limits of the biological turning point, and pathogenetically substantiated drugs are administered depending on the existing pathology. Then the patient is removed from the bath and restore normothermia.

A positive therapeutic effect is achieved due to the fact that artificial hyperthermia is objectively established at the time of registration of a critical biological point, which indicates the onset of the therapeutic effect of hyperthermia. In this case, the limiting level of hyperthermia is determined, the duration of the biological tipping point is controlled, pharmacological preparations for maintaining hyperthermia within the selected regimen are stopped, and the drug is administered depending on the existing pathology.

When using real-time BIS monitoring, the spontaneous bioelectric activity of the brain is recorded, automatically processed and converted to a bispectral index. On the monitor screen, the value of the BIS index is displayed as a graphical trend and a number in the range from 0 (complete absence of bioelectric activity) to 100 (clear consciousness), which is the result of the analysis of EEG data for the previous 15 s and is updated every second. This signal processing technique eliminates excessive fluctuations in the index values and reduces the likelihood of errors associated with signal interruption or external influences. The bispectral index value linearly corresponds to the patient's sedation level at this value.

Temperature control not only in the middle third of the esophagus, but also on the tympanic membrane provides more reliable control of the body’s warming, since the transfer of heat in patients occurs at different speeds. The temperature difference for a certain point in time in the middle third of the esophagus and on the tympanic membrane should be the same.

The drug Dalargin belongs to the pharmacological group of regenerants and reparants, therefore its use in the process of carrying out hyperthermia provides an increase in the effectiveness of the procedure and treatment by increasing the speed and intensity of recovery processes in the body, as well as by stimulating DNA reduplication and cell division.

An example of a specific implementation of the method

After establishing indications for artificial hyperthermia, identifying (using traditional approaches) deviations in the indicators of homeostasis, a planned infusion preparation of the patient is carried out. For this, for example, correction of volemic and rheological disorders is carried out by intravenous infusion of sterofundin (5 ml / kg) and 10% glucose solution (10 ml / kg) with insulin (4-8 units) and potassium preparations (4% - 60-80 ml). 1 mg / ml Dalargin (Dalargin) is administered intravenously. Subsequently, it is administered in the indicated dosage for every degree, starting at 40 ° C in the esophagus and at the biological turning point. Induction in anesthesia is carried out with propofol in a dose that turns off consciousness. Electrothermometer sensors are installed in the middle third of the esophagus and on the tympanic membrane. A laryngeal mask is established (or tracheal intubation is performed) and after myoplegia (listenone), mechanical ventilation is started, which supports saturation of 95-100%. The patient (except the head) is immersed in a bath of water with a temperature of 46 ° C. An increase in temperature in the esophagus and on the tympanic membrane is carried out at a pace of not more than 0.5-1.5 ° C in 5 minutes. Next, they monitor the appearance of the effect of reducing the heating rate. This effect can be recorded in the range of 42.5-43.8 ° C. From this moment, depending on the clinical situation (the nature of the pathology, the stability of hemodynamics, etc.), the achieved effect of hyperthermia is maintained for 5-20 minutes, pathogenetically based drugs are administered, after which the patient is removed from the bath and the restoration of normothermia is started.

Clinical example

Patient D., 36 years old, was admitted to the IOC clinic with a diagnosis of Cr ovarii, mts in the lymph nodes of the retroperitoneal space. 4 courses of chemotherapy. Concomitant pathology - anemia cf. Art. severity (Hb 112 g / l). 4 OUG procedures were completed, the last on December 8th.

Before the procedure, a scheduled infusion preparation was carried out: Sterofundin 500.0 + Heparin - 10000 Units. 1 mg / ml Dalargin, Glucose 5% - 400.0 + Potassium chloride 4% - 30.0.

Introductory anesthesia was carried out 160 mg of Propofol iv, Atropine 0.1% - 1.0. After the administration of 200 mg of Listenon, the trachea was intubated, thermal sensors and a BIS monitor sensor were installed.

The lungs were ventilated with a Paravent PAT apparatus using an air-oxygen mixture of 1: 1 standard MOD.

After the administration of 4 mg of Arduan and the addition of Diprivan infusion 200 g through a perfuser at a rate of 40 ml / h, Glucose infusion 10% - 400.0 was started.

The patient was immersed in a bath with a water temperature of 46 ° C.

Initial BP 136/81 Torr, pulse 82 beats / min. The initial temperature in the esophagus is 36.6 ° C. Within 28 minutes a gradual increase in the patient's temperature to 42.6 ° C was carried out. Blood pressure increased as much as possible to 175/70 Torr, tachycardia to 178 beats / min. During the procedure, 10 ml of 0.005% solution of Fentanyl and an additional 200 mg of Diprivan were fractionally administered. The infusion volume was 1200.0 Glucose 10% with Panangin 50.0 and Riboxin 2% 50.0, vitamin C 5% - 50.0, vitamin B 5% - 40.0.

At the time of reaching body temperature of 40 ° C, 41 ° C, 42 ° C and at a critical biological point, iv was administered at a dose of 1 mg / ml Dalargin. At a temperature of 42.6 ° C, the cytostatic Endoxan was administered in a dose of 200 mg, with an exposure of 7 minutes.

After extracting the patient from the bath, blood pressure stabilized at 124/49 Torr after 6 minutes.

After 44 minutes, the patient's body temperature decreased to 38 ° C, at which point 1 mg / ml Dalargin was re-administered to the patient, but intramuscularly.

After restoration of adequate consciousness and independent breathing (1.5 hours after removing the patient from the bath), the patient is extubated. After another 30 minutes, the patient stood up on her own.

Accurate data on the results of using the proposed method in the long term (up to 5 years) were obtained from 38 patients. A positive result is recorded in all cases.

In accordance with the classification of WHO experts, the results of treatment were distributed as follows: complete tumor regression - 10%; partial tumor regression - 70%; process stabilization - 20%; disease progress is 0%. There were no fatal outcomes associated with OSH.

Claims (1)

A method for carrying out general controlled hyperthermia of the human body, including scheduled infusion preparation and general heating of the patient's body by immersing him, except the head, in hot water with a temperature of 42-47 ° C with a body heating rate of 0.5-1.5 ° C for 5 min ensuring saturation within normal limits, until the temperature in the esophagus rises to 42.5-44 ° C, measuring the temperature in the middle third of the esophagus, providing anesthetic protection of the body by introducing relaxants, anesthetics and hypnotics, monitoring the heart rate, heart contractions, indicators of blood pressure, saturation, characterized in that before immersing the patient in hot water, 1 mg / ml Dalargin is administered intravenously, and during hyperthermia, Dalargin is administered in the indicated dosage for each degree starting from 40 ° C in the esophagus and at the biological fracture point, additionally measure the temperature on the tympanic membrane, carry out BIS monitoring, according to BIS monitoring while reducing the heating rate, determine the biological tipping point, within 5-20 minutes effective warming is maintained, which does not go beyond the limits of the biological turning point, and pathogenetically substantiated drugs are administered depending on the existing pathology, then the patient is removed from the bath and normothermia is restored.