RU2126667C1 - Method of common controlled hyperthermia of human organism - Google Patents

Abstract

FIELD: oncology. SUBSTANCE: patient's body is immersed in hot water. In this case, use is made of common anesthesia and high-frequency ventilation of lungs. Method includes introduction of urotropine before warming-up at intensive warming-up and after recovery of normothermia. EFFECT: enhanced efficiency of treatment, improved safety.

Description

 The invention relates to medicine and can be used in oncology, resuscitation, neurology, narcology, virology and dermatology.

 Known methods for reproducing artificial hyperthermia by general physical warming up of the patient’s body against the background of anesthesia and mechanical ventilation (IVL), which are used in the treatment of cancer (Alexandrov N.N., Savchenko N.E. et al. The use of hyperthermia and hyperglycemia in the treatment of malignant tumors. - M .: Medicine, 1980, S. 53-72).

 A known method of general warming up of the body (application 94031924/14 (032069), priority from 09/02/94, decision to grant a patent from 11/06/97. Author - G. Gleim). According to this method, the patient’s organism is heated with hot water against the background of barbituric anesthesia and mechanical ventilation after preliminary administration of pyridoxine, hexamethylenetetramine, alpha-tocopherol, sodium oxybutyrate, 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 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.

The objective of the invention is the ability to manage and increase the safety of artificial general hyperthermia in the range of 42.5 - 44 ^o C.

 On the eve of the hyperthermia procedure (for example, the day before it is carried out), the patient will be examined generally accepted clinical and biochemical parameters: blood hemoglobin and its formula, the level of protein and its fractions, sugar and basic blood electrolytes. On the night before the procedure, premedication using diazepam (10 mg) is carried out, and for drug addicts - in individual doses. Immediately before the procedure (for 2 to 3 hours), 20 ml of a 20% solution of urotropin are given enterally, by mouth, and 200 ml of a 40% solution of glucose are injected intravenously at a rate of 0.5 - 1 g / kg / h, with insulin (0.1 units / g glucose). Then pour reopoliglukin (5 ml / kg) and Ringer's solution (10 ml / kg) with potassium chloride (7.5% - 20 ml), ascorbic acid (5% - 10 ml), pyridoxine (5% - 10).

 Induction in anesthesia is carried out using rexenal (2.5% - 250 - 300 mg) or calypsol in a dose that turns off consciousness (250 - 300 mg). After administration of a depolarizing type muscle relaxant, for example, listenone, at a dose of 3–5 mg / kg, the trachea is intubated and high-frequency mechanical ventilation (high-frequency artificial lung ventilation) is started, for example, with the “Assistant-1” apparatus.

HF ventilation mode: P inspiration (inspiratory pressure) 18 - 20 cm H ₂ O, BH (respiration rate) 105 cycles per minute. The adequacy of HF mechanical ventilation is controlled by pulse oximetry, while the level of saturation should be in the range of 97 - 100%. Basic muscle relaxation is provided by arduan (0.03 - 0.05 mg / kg). An electrothermometer sensor is placed in the middle third of the esophagus. After that, fentanyl (0.05% - 2 ml) is injected intravenously and they begin active physical heating of the patient's body. For this patient is immersed in a bath with hot water of constant temperature (45 - 47 ^o C), with the exception of the head. In the process of active heating, water convection is forcedly carried out, maintaining the rate of increase in patient temperature not lower than 1 ^o C for 5 minutes. This is facilitated not only by "mixing" the water in the bath, but also by the periodic (after 5 - 7 min) infusion of fentanyl, pronounced hyperemia of the skin of the patient's body. At a heating height, urotropin (0.2 ml / kg of a 40% solution) is intravenously administered and the half dose of this drug is repeated at the stage of passive cooling of the patient. After increasing the body temperature (in the esophagus) to 43 - 44 ^o With the patient is removed from the bath. Continue HF mechanical ventilation and infuse intravenously with 200 ml of freshly thawed single-group plasma.

The process of raising the temperature stops and due to the effects of air temperature in the operating room, ice bubbles on the head and the mode of high-frequency mechanical ventilation, a slow, passive restoration of normothermia occurs. After lowering body temperature to 37 ^o C (in the esophagus), the patient is covered with blankets.

The controllability and higher safety of the claimed method of general hyperthermia is evidenced by the appearance of diuresis (150 - 250 ml / h), restoration of consciousness at a temperature of 37 ^o C and the possibility of termination of mechanical ventilation within 60 - 90 minutes after the heating procedure.

Thus, the clinically significant advantages of the invention are:
1. The ability, without signs of heat shock, to provide a manageable, fast (1 ^o C in 2 - 5 min) rate of implementation of general hyperthermia up to 43.5 - 44.0 ^o C.

 2 It is more effective to suppress thermal proteolysis in the blood by using the proposed sequence of triple use of urotropine.

 3 More reliably (due to the regime of high-frequency mechanical ventilation) to provide the organism's oxygen demand sharply increasing under conditions of hyperthermia.

 4 To achieve in patients after the hyperthermia procedure a sufficiently quick recovery of consciousness and adequate spontaneous breathing without the use of intensive care.

An illustration of the distinguishing features (rational 45 - 47 ^o C coolant temperature, forced constant convection of the coolant, optimal 1 ^o C for 2 - 5 min, the rate of heating of the patient’s body, the use of proteolysis suppression schemes in blood plasma, the use of the described regime of high-frequency mechanical ventilation and fentanyl anesthesia), as well as the positive effects of the invention can serve as an example.

 Example. Patient Sh., 43 years old. Case history 1389. Received in the intensive care unit of Novosibirsk LHB 1 in a planned manner. Diagnosis: Cancer of the right breast with metastasis in the right lung.

06/10/97. conducted general controlled hyperthermia (OUG) up to 43.6 ^o C. In this case, immediately before the start of the general warm-up, premedication with diazepam was carried out (10 mg), urotropine (20% - 20 ml) was administered enterically, 200 ml of a 40% glucose solution was transfused with insulin, 400 ml of reopoliglyukin, 500 ml of Ringer's solution with potassium chloride (7.5% - 20 ml), ascorbic acid and pyridoxine (10 ml of a 5% solution).

 Induction in anesthesia was performed by thiopental and calypsol. Relaxants, tracheal intubation, high-frequency mechanical ventilation in a mode providing saturation at the level of 99 - 100%. General anesthesia was maintained at a level of 111 by fractional administration of fentanyl intravenously.

The patient’s body was heated in a bath with water (46 ^o С) at a rate of 1 ^o С for 3 - 5 minutes. After reaching a temperature in the esophagus of 43.6 ^o With heating is stopped. The patient is removed from the bath. Bubbles with ice - to the head. 450 ml of thawed plasma and 150 ml of a 10% glucose solution with insulin (10 units) and potassium chloride (10 ml) were transfused intravenously. 60 minutes after normalization of the temperature, the patient is extubated.

 The next day, the patient is active, no complaints, self-serving. There is no need for intensive care. After 9 days, the patient underwent surgery: metastasectomy from the lower lobe of the right lung and sectoral resection of the right breast. Histological examination of samples of removed tissue revealed a pronounced, up to necrosis, pathomorphism of cancer cells.

The same patient after 4 months (10/17/97) was carried out without complications repeated general controlled hyperthermia (43.5 ^o C) as a method of anti-relapse therapy.

Thus, the rapid recovery of consciousness, diuresis and adequate spontaneous breathing in the patient and the uncomplicated course after the procedure of general, deep hyperthermia indicate the controllability and sufficient safety of the developed method of controlled hyperthermia (up to 44 ^o C) even in a patient with advanced form of breast cancer. 3P

Claims (1)

The method of general controlled hyperthermia of the human body, including general heating of the patient’s body by immersion of it, except for the head, in hot water, using fentanyl anesthesia, artificial ventilation of the lungs and administration of urotropin to the patient, characterized in that the patient’s body is heated to a temperature in the esophagus 42, 5 - 44 ^o C heated water with a temperature in the range of 45 - 47 ^o C, support the body heating rate not lower than 1 ^o C for 5 minutes by constant forced convection of the coolant, while using high-frequency artificial lung ventilation, providing a saturation level of 97 - 100%, and urotropin is administered enteral before the heating in an amount of 20 mg of a 20% aqueous solution and additionally at a heating height of 0.2 ml / kg of a 40% aqueous solution, and also - 0.1 ml / kg of a 40% solution intravenously after restoration of normothermia.