RU2627289C1 - Method for anesthetic maintenance during radical surgery for cancer patients - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: after patient admission to the operating room dexmedetomidine administration starts at a dose of 0.6-0.8 mcg/kg/h. Then epidural space catheterization is perform lying on the side. Analgesic mixture administration starts at a rate of 5 ml/hour and continued throughout the operation. During denitrogenation, intravenous dexmedetomidine sedation is performed at an dose of 0.6-0.8 mcg/kg/hr, after repeated denitrogenation and transition to closed circuit, oxygen supply is stopped. The breathing bag is completely emptied, then Xe is fed rapidly, once filling the breathing bag, ventilation by pure Xe flow of 150-300 ml per minute is begun under the control of FiO₂ to reduce the oxygen concentration in the breathing circuit to 40% and Xe concentration to 60%, and then oxygen is supplied at a dose of 4 ml/kg, maintaining the balance in the ratio of Xe:O₂ 60:40. Xe flow is reduced to 0-100 ml/min intravenous administering of dexmedetomidine is continued throughout the operation at a dose of 0.3-0.6 mcg/kg/hr. Prior to surgical wound suturing Xe supply is stopped. After surgery, anesthesia machine is converted to a semi-open circuit, oxygen flow is increased to 5 l/min, sodium sugammadex is introduced at the rate of used bromide rocuronium. The patient extubated, in the early postoperative period analgesic mixture administration is continued at a rate of 5 ml/hr and intravenous dexmedetomidine administration is continued at a dose of 0.3-0.6 mcg/kg/h under the control of sedation level and hemodynamics.

EFFECT: method allows to obtain an efficient multimodal anesthetic protection, reduce xenon and narcotic analgesics consumption during extended and highly-traumatic cancer surgery.

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Description

The invention relates to the field of medicine, anesthesiology, and specifically to methods of anesthetic management of radical operations in cancer patients.

The questions of choosing an adequate and at the same time sparing method of anesthesia and analgesia in cancer patients, often of advanced age with pronounced concomitant pathology, remain complex and not completely resolved. A set of aggression factors in the form of the influence of a malignant process on the body, which is accompanied by a violation of the function of the affected organ, leads to general disorders of homeostasis, with the development of tumor intoxication and a violation of various types of metabolism. Chemotherapy methods with high toxicity can also adversely affect the course of the perioperative period. Radical surgical treatment, as a rule, is an extended, and often simultaneous operation. All this requires effective anesthetic management and postoperative management of cancer patients. The use of xenon as an anesthetic in various fields of surgery, including oncology, has shown significant advantages of the latter over other inhalation and non-inhalation anesthetics. Its use is limited by high cost.

A known method of anesthesia in cancer patients using xenon (RF patent No. 2319515, publ. March 20, 2006), including: premedication, intubation of the trachea with subsequent denitrogenation, the supply of xenon-oxygen mixture in the ratio of 70:30 to a closed respiratory circuit, the flow is set to volume ratio: O ₂ - 0.3 l / min, Xe - 1.0 l / min under the control of FiO ₂ , and, after reaching the surgical stage of anesthesia, the supply of xenon-oxygen mixture is carried out in a ratio of Xe and oxygen of 60:40 flow to 1 l / min The main disadvantage of this method is the conduct of general anesthesia in mononarcosis mode, which does not allow to achieve a reliable level of anesthetic protection, in addition, with a flow of xenon-oxygen mixture of 1 l / min there is a very large consumption of expensive xenon anesthetic.

Closest to the proposed is a method of combined xenon anesthesia in cancer patients (RF patent No. 2444380, publ. 10.03 2012), including premedication with atropine, denitrogenation with pure oxygen, induction, myoplegia, intubation, re-denitrogenation by means of mechanical ventilation, followed by transition to closed circuit, the introduction of short-acting narcotic analgesics at the traumatic stages, while propofol is administered intravenously during denitrogenation at a dose of 4 mg / kg / h, also simultaneously after entering the operating room, the epidural space is punctured at the level of T4-T11 and 40 mg of lidocaine is administered, then the epidural catheter is catheterized, after which the analgesic mixture is infused: 47 ml 0.2% ropivacaine; 2 ml of 0.005% fentanyl; 0.1 ml of 0.1% adrenaline at a speed of 15 ml / h for 20 minutes, after which the rate of administration is reduced to 7-10 ml / h, 20-25 minutes after the start of epidural administration of the mixture in the operating room, 2 ml of 0.005% fentanyl, 0.5-0.6 ml of 0.1% atropine, induction is carried out with propofol 2-2.5 mg / kg, intubation, denitrogenation for 8-10 minutes with 100% oxygen on a half-open circuit, after switching to a closed circuit, no more than 500 ml of oxygen is left in the breathing bag, the flow is reduced to zero, then the phase of rapid saturation of Xe 1 is carried out , 3-1.5 VEL of a patient under FiO ₂ control until the oxygen concentration in the respiratory circuit is 40%, when Xe reaches 60%, a flow of 250-400 ml / min is established until a stable equilibrium is reached, after which, when a stable equilibrium is reached in the ratio Xe: O ₂ 60:40, the Xe stream is reduced to 0-160 ml / min, and oxygen is supplied to the circuit at a dose of 4 ml / kg, at traumatic stages fentanyl is administered in a fractional bolus intravenous dose of 0.1 mg.

The known method has the following disadvantages - at the stage of denitrogenation sedation with propofol at a dose of 4 mg / kg / hour and simultaneous epidural infusion of the analgesic mixture in a sufficiently large amount consisting of 47 ml of 0.2% ropivacaine, 2 ml of 0.005% fentanyl and 0.1 ml 0.1% adrenaline can cause hypotension, which requires correction with vasoactive drugs, which is especially undesirable in depleted cancer patients with concomitant pathology of the cardiovascular system. In addition, during extended operations on the abdominal organs, the number of bolus injections of fentanyl can be quite frequent, since these surgical interventions are highly traumatic. The stage of awakening during xenon anesthesia may be accompanied by episodes of excitement, which is associated with a quick exit from anesthesia and the occurrence of postoperative nausea and vomiting. The analgesic effect of epidural block in the early postoperative period, as a rule, is insufficient during traumatic operations and there is a need for the use of opioids and / or sedatives.

Anesthesia for oncological interventions should be proactive and multimodal, with an emphasis on the preventive blockade of pathological afferent impulses from the surgical wound. The use of alpha-2 adrenergic agonists can be one of the ways to increase the effectiveness of anesthetic benefits. Alpha-2 adrenergic receptors are distributed in all organs and systems of the body, including receptor subtypes (A, B, C), and are activated by non-selective endogenous adrenergic agonists. The physiological aspects of the anesthetic combination, including the NMDA Xe antagonist and the alpha-2 adrenergic dexmedetomidine agonist, are described by Frank Nicholas Peter. Alpha-2 adrenergic agonists have analgesic and anesthetic effects. However, the method of application in clinical practice with advanced operations in cancer patients has not been developed.

A new technical result is obtaining an effective multimodal anesthetic protection, reducing the consumption of xenon and narcotic analgesics during advanced and highly traumatic oncological operations.

To achieve a new technical result in the method of anesthetic management of radical operations in cancer patients, including puncture and catheterization of the epidural space at the level of T4-T11, premedication of 0.5-1.0 ml of 0.1% atropine and 2 ml of 0.005% fentanyl, denitrogenation pure oxygen, induction with propofol 2-2.5 mg / kg, intubation, xenon supply to the anesthesia system and anesthesia followed by oxygen supply, injection of an analgesic mixture into the epidural catheter: 47 ml of 0.2% ropivacaine; 2 ml of 0.005% fentanyl; 0.1 ml of 0.1% adrenaline, when a patient enters the operating room, intravenous administration of dexmedetomidine at a dose of 0.6-0.8 μg / kg / h is started, then epidural space is catheterized while the patient is lying on his side, inserted into an epidural catheter throughout the operation, an analgesic mixture at a rate of 5 ml / hour, then premedication and induction are performed, muscle relaxation is carried out with rocuronium bromide at a dose of 0.6 mg / kg, intubation and denitrogenation are performed for 8-10 minutes with 100% oxygen in a half-open circuit to obtain on gas the analyzer 99% oxygen in the respiratory circuit, after switching to the closed circuit, the oxygen supply is temporarily stopped, and the breathing bag is completely emptied, then Xe is quickly fed into the closed circuit of the anesthesia apparatus, while filling the breathing bag, ventilation begins with a clean Xe flow of 150-300 ml per min under the control of FiO ₂ until the oxygen concentration in the respiratory circuit is equal to 40% and Xe concentration is 60%, when a stable equilibrium is reached in the Xe: O ₂ ratio _of 60:40, the Xe flow is reduced to 0-100 ml / min, and serving ki Loroda at a dose of 4 ml / kg, the introduction of dexmedetomidine is continued throughout the operation at a dose of 0.3-0.6 μg / kg / h, before the closure of the surgical wound, the supply of Xe is stopped, after the operation the anesthesia machine is transferred to a half-open circuit, oxygen is increased to 5 l / min, sodium sugammadex is administered based on the used rocuronium bromide, the patient is extubated, administration of the analgesic mixture at a rate of 5 ml / h is continued in the early postoperative period, and intravenous administration of dexmedetomidine at a dosage of 0.3-0.6 μg / kg / h od controlled level of sedation and hemodynamics.

The use of a selective alpha-2 adrenergic agonist dexmedetomidine in the proposed mode helps to improve the effect of sedation, a more comfortable procedure for catheterization of the epidural space, since the infusion begins upon admission to the operating room. The period of repeated denitrogenation by means of artificial ventilation of the lungs against the background of sedation with dexmedetomidine is more favorable, does not require deepening anesthesia with propofol due to the anxiolytic properties of dexmedetomidine and proceeds against the background of stable hemodynamics. An increase in the effectiveness of xenon anesthesia is achieved through the synergistic mechanism of xenon and an alpha-2 adrenergic agonist, and the likelihood of adverse and undesirable side effects when using these drugs separately is also reduced. In addition, there is a decrease in the need during surgery for anesthetics and opioids, and after surgery, for sedatives and opioids. The extubation procedure does not create discomfort to the patient, since it takes place against the background of sedation of dexmedetomidine, which does not depress respiration. After extubation, dexmedetomidine enhances the analgesic effect of epidural blockade.

The xenon supply technology differs from the prototype, because after switching to a closed circuit, the breathing bag is completely empty, oxygen supply is temporarily stopped, and the breathing bag is quickly filled with Xe. Then start ventilation with a clean Xe stream of 150-300 ml / min under the control of FiO ₂ to decrease.

This allows you to reduce the time of onset of anesthesia and significantly reduce its consumption. The ratio of the components of the xenon-oxygen mixture 60:40 used in the proposed method is optimal for general anesthesia, since it can significantly increase the safety of xenon anesthesia, eliminating the possibility of intraoperative hypoxia and undesirable complications associated with it.

Epidural analgesia in this case provides antinociceptive protection due to the mutual potentiation of the analgesic effect. Fentanyl inhibits the transmission of pain impulses in the posterior horns of the spinal cord at the level of pre- and postsynaptic opioid receptors. Adrenaline suppresses the transmission of pain impulses in the posterior horns of the spinal cord at the level of pre- and postsynaptic α2 receptors. Ropivacaine in low concentrations blocks the sodium channels, disrupting the transmission of excitation in the synapses of the posterior horns of the spinal cord. However, in the proposed method do not carry out "saturation" for 20 minutes, and continue the introduction with a speed of 5 ml / hour at all stages of the operation.

The proposed method is based on the analysis of clinical trial data of 32 patients, monitoring results at all stages of central hemodynamics, determination of the concentration of hormones of the hypothalamic-pituitary-adrenal system, insulin, glycemia level and the concentration of inflammatory mediators IL-1, IL-6. The results of the studies confirmed that the developed method is an effective anesthetic aid.

The application of the developed scheme of anesthesia reduces the drug load on the body and enhances the analgesic effect of anesthesia, which allows to achieve a stable concentration of xenon in the gas mixture and significantly reduce the consumption of expensive Xe anesthetic. The use of xenon anesthesia, epidural analgesia and a selective alpha-2 adrenergic agonist, dexmedetomidine, provides maximum anesthetic protection with minimal side effects.

The method is as follows: after admission to the operating room, intravenous administration of dexmedetomidine at a dose of 0.6-0.8 μg / kg / h is started. Then, the epidural space is punctured lying on its side at the level of T4-T11 and a test dose of 40 mg of lidocaine is administered, then an epidural catheter is catheterized, after the installation of which the analgesic mixture is infused: 47 ml of 0.2% ropivacaine; 2 ml of 0.005% fentanyl; 0.1 ml 0.1% adrenaline at a rate of 5 ml / h. Then, 0.5-1.0 ml of 0.1% atropine and 2 ml of 0.005% fentanyl are intravenously administered, 2-2.5 mg / kg propofol is induced, rocuronium muscle relaxation is carried out with bromide (esmeron) 0.6 mg / kg, intubation is performed, denitrogenation for 8-10 minutes with 100% oxygen in a half-open circuit until 99% of the oxygen in the respiratory circuit is obtained on the gas analyzer, after switching to the closed circuit, the oxygen supply is temporarily stopped, and the breathing bag is completely empty, then xenon is quickly fed into the closed circuit of the anesthesia apparatus, once filling respiratory th bag begin ventilation pure Xe flow of 150-300 ml per minute under the control of FiO ₂ to reduce the oxygen concentration in the breathing circuit, equal to 40%, and the concentration of Xe is 60%. Upon reaching a stable equilibrium in the Xe: O ₂ ratio _of 60:40, the Xe flow is reduced to 0-100 ml / min, and oxygen is supplied to the circuit at a dose of 4 ml / kg. At all stages, iv administration of dexmedetomidine is carried out, including during denitrogenation. Under the control of hemodynamics, the dosage of dexmedetomidine can vary in the range of 0.3-0.6 μg / kg / h. Before the closure of the surgical wound, the supply of xenon is stopped. After the operation is completed, the anesthesia apparatus is transferred to a semi-open circuit, the oxygen flow is increased to 5 l / min, sodium sugammadex (Bridan) is administered based on the used rocuronium bromide (Esmeron), and the patient is extubated. In the early postoperative period, the administration of an analgesic mixture is continued at a rate of 5 ml / h and iv administration of dexmedetomidine in a dosage of 0.3-0.6 μg / kg / h under the control of sedation and hemodynamics

Example No. 1. Patient S., 80 l.

Diagnosis: Cancer of the proximal stomach, with the transition to the Z-line, Art. IIA, T2N1M0.

Concomitant diseases: IHD. Angina pectoris FC II. MCA with PCP, CABG autoarterial OA from 2003. PTC with stenting OA from 2007. Paroxysmal supraventricular tachycardia. CHF IIA Art. FC III. SD 2 type, Art. subcompensation. Hypertension stage III. Atherosclerosis of the aorta, AK, MK, BCA. Stenosis of OCA on the right 45%, the mouth of the NSA on the right 55%, OCA on the left 30% UIA. Risk 4. HIGM. CM vestibulopathy. ZhKB. Chr. calculous cholecystitis, without exacerbation. Kidney cysts. CRF-0. CKD 2 tbsp., Bilateral gonarthrosis, R-st III, Federal Tax Service II. Flexion-extensor contracture of the right knee joint. Focal thyroid formations. Euthyroidism. Polyp of the anal canal.

A gastrectomy with lymph node dissection D2 was performed under combined Xe anesthesia in combination with iv administration of dexmedetomidine using anesthetic aid according to the proposed method.

After performing the generally accepted preparation of the patient for surgery and anesthesia, upon admission to the operating room, the patient began iv administration of dexmedetomidine at a dose of 0.6 μg / kg / h. Then, lying on their side in the interspinous gap T6-T7, the epidural space was punctured with a Tuoha G18 needle, a test dose of 40 mg of lidocaine was administered, then catheterized with an epidural catheter (Portex). Then began the introduction of an analgesic mixture: ropivacaine 0.2% - 47 ml; fentanyl 0.005% - 2 ml; adrenaline 0.1% - 0.1 ml at a rate of 5 ml / h. Then, atropine 0.5 mg and fentanyl 0.1 mg were premedicated. Through the face mask of the anesthesia apparatus, 100% oxygen was inhaled along a half-open circuit at a gas flow of 6 l / min for 5 minutes. Then, introductory anesthesia was performed using propofol 2-2.5 mg / kg, esoperone myopelgia 0.6 μg / kg. After this, the patient was intubated. A mechanical ventilation was performed with 100% oxygen along a half-open circuit, with a gas flow of 8 l / min for 8 min, against a background of sedation with dexmedetomidine at a dose of 0.6 μg / kg / h. Then they switched to a closed circuit, the oxygen supply was temporarily stopped, the breathing bag was completely empty, then xenon was quickly supplied to the closed circuit of the anesthesia apparatus with a flow of 2 l / min for 40 seconds, filling the breathing bag once. The ventilation was started with pure Xe, reducing the flow to 150 ml / min, to reduce FiO ₂ 0.4 within 5 minutes, then the oxygen supply was opened into the circuit with a flow of 240 ml / min. Upon reaching a stable equilibrium in the Xe: O ₂ ratio _of 60:40, the Xe flow was reduced to 30 ml / min, and oxygen continued to flow into the circuit with a flow of 180-240 ml / min. Continued iv injection of dexmedetomidine at a dose of 0.3 μg / kg / h and the introduction of an analgesic mixture into the epidural catheter at a rate of 5 ml / h.

5 minutes after the start of xenon inhalation, surgery began, the duration of the operation was 120 minutes. All subsequent anesthesia was performed at low gas flow with a FiO ₂ control _of at least 40%. The concentration of Xe throughout the operation remained stable 58-63% with a constant flow of Xe 0-50 ml / min. Before the closure of the surgical wound, the supply of xenon was stopped. After the operation, the anesthesia machine was transferred to a semi-open circuit, the oxygen flow was increased to 5 l / min, and the bridy was administered based on the used esmeron. After restoration of muscle tone by TOF monitoring, the patient was extubated, iv administration of dexmedetomidine at a dose of 0.3 μg / kg / h was continued and 5 ml / h of an analgesic mixture was introduced into the epidural catheter under the control of hemodynamics and sedation level; the patient was awakened fully adequate, no complaints.

Hemodynamics during the operation is stable at all stages: blood pressure = 120 / 80-110 / 70, pulse 80-68, СО 2-4 vol.%.

The adequacy of anesthesia was evaluated based on the following data: clinical presentation, monitoring of central hemodynamics, determination of hormone concentration of the hypothalamic-pituitary-adrenal system, insulin, glycemia level and concentration of inflammatory mediators IL-1, IL-6.

Subjective sensations of the patient after exit from anesthesia are pleasant. There were no complaints.

Example No. 2. Patient K., 57 p.

Diagnosis: Cancer of the angle of the stomach. Art. II In T4aN0M0.

Concomitant diseases: Hypertension III tbsp., Risk 4. Art. AH achieved. Obesity 3 tbsp.

An operation was performed in the amount of subtotal distal gastrectomy according to Ru with lymph node dissection D2 using anesthetic aid according to the proposed method.

After admission to the operating room on the background of intravenous administration of dexmedetomidine at a dose of 0.8 μg / kg / h lying on its side, puncture and catheterization of the epidural space in the interspinous gap T6-T7 were performed, the analgesic mixture was introduced into the catheter: ropivacaine 0.2% - 47 ml; fentanyl 0.005% - 2 ml; adrenaline (epinephrine) 0.1% - 0.1 ml at a rate of 5 ml / h. Then, atropine 0.5 mg and fentanyl 0.1 mg were premedicated. Through the face mask of the anesthesia apparatus, 100% oxygen was inhaled along a half-open circuit at a gas flow of 6 l / min for 10 minutes. Then, introductory anesthesia was performed using propofol 2-2.5 mg / kg, esoperone myopelgia 0.6 μg / kg. After this, the patient was intubated. A mechanical ventilation was performed with 100% oxygen along a half-open circuit, at a gas flow of 8 l / min for 10 minutes, until 99% oxygen was obtained in the respiratory circuit on a gas analyzer, against a background of sedation with dexmedetomidine at a dose of 0.8 μg / kg / h. Then they switched to a closed circuit, the oxygen supply was temporarily stopped, the breathing bag was completely emptied, then xenon was quickly supplied to the closed circuit of the anesthesia apparatus with a flow of 2.5 l / min for 30 seconds, filling the breathing bag once. The ventilation was started with pure Xe, reducing the flow to 250 ml / min, to reduce FiO ₂ 0.4 within 7 minutes, then the oxygen supply was opened to the circuit with a flow of 300 ml / min. Upon reaching a stable equilibrium in the Xe: O ₂ ratio _of 60:40, the Xe flow was reduced to 50 ml / min, and oxygen continued to flow into the circuit with a flow of 250-300 ml / min. During anesthesia, intravenous administration of dexmedetomidine at a dose of 0.6 μg / kg / h was continued and an analgesic mixture was introduced into the epidural catheter at a rate of 5 ml / h.

7 minutes after the start of xenon inhalation, surgery began, the duration of the operation was 140 minutes. All subsequent anesthesia was performed at low gas flow with a FiO ₂ control _of at least 40%. The concentration of Xe throughout the operation remained stable 55-60% with a constant flow of Xe 50-70 ml / min. Before the closure of the surgical wound, the supply of xenon was stopped. After the end of anesthesia, the anesthesia apparatus was transferred to a semi-open circuit, the oxygen flow was increased to 5 l / min, and the bridyan was introduced based on the calculation of the used esmeron. After the restoration of muscle tone by TOF monitoring, the patient was extubated, iv administration of dexmedetomidine at a dose of 0.5 μg / kg / h was continued, and an analgesic mixture was introduced into the epidural catheter at a rate of 5 ml / h under the control of hemodynamics and sedation level. Hemodynamics during the operation is stable at all stages: blood pressure = 130 / 80-110 / 70, pulse 70-68, СО 2-4 vol.%.

The adequacy of anesthesia was evaluated based on the following data: clinical presentation, monitoring of central hemodynamics, determination of hormone concentration of the hypothalamic-pituitary-adrenal system, insulin, glycemia level and concentration of inflammatory mediators IL-1, IL-6.

Subjective sensations of the patient after exit from anesthesia are pleasant. There were no complaints.

The proposed method was used in 32 patients with various types of surgical interventions, on the abdominal organs, regarding oncological diseases, complications associated with anesthesia in the postoperative period, were not observed.

Thus, the application of the proposed method makes it possible to reduce the drug load to provide adequate anesthesia during surgical interventions in cancer patients. There is no metabolic effect on the parenchymal organs, myocardium, endocrine system of the patient’s body, which is important in oncology.

Claims (1)

Method for anesthetic management of radical operations in cancer patients, including puncture and catheterization of the epidural space at the T4-T11 level, premedication of 0.5-1.0 ml of 0.1% atropine and 2 ml of 0.005% fentanyl, denitrogenation with pure oxygen, induction with propofol 2 -2.5 mg / kg, intubation, xenon supply to the anesthesia system and anesthesia followed by oxygen supply, injection of an analgesic mixture into the epidural catheter: 47 ml of 0.2% ropivacaine; 2 ml of 0.005% fentanyl; 0.1 ml of 0.1% adrenaline, characterized in that when the patient enters the operating room, intravenous administration of dexmedetomidine at a dose of 0.6-0.8 μg / kg / h is started, then the epidural space is catheterized while the patient is lying on his side, an analgesic mixture is introduced into the epidural catheter during the entire operation at a rate of 5 ml / h, then premedication and induction are performed, muscle relaxation is performed with rocuronium bromide at a dose of 0.6 mg / kg, intubation and denitrogenation are performed for 8-10 minutes with 100% oxygen half open circuit until 99% of the oxygen in the respiratory circuit is received on the gas analyzer, after switching to the closed circuit, the oxygen supply is temporarily stopped and the breathing bag is completely empty, then Xe is quickly fed into the closed circuit of the anesthesia apparatus, while filling the breathing bag, ventilation begins with a clean Xe stream of 150-300 ml per min under the control of FiO ₂ until the oxygen concentration in the respiratory circuit is 40% and the Xe concentration is 60%, when a stable equilibrium is reached in the Xe: O ₂ ratio _of 60:40, the Xe flow is reduced to 0-100 ml / min, and in cont p start supplying oxygen at a dose of 4 ml / kg, the introduction of dexmedetomidine is continued throughout the operation at a dose of 0.3-0.6 μg / kg / h, before the closure of the surgical wound, the supply of Xe is stopped, after the end of the operation the anesthesia machine is transferred to half circuit, oxygen flow is increased to 5 l / min, sodium sugammadex is administered based on the used rocuronium bromide, the patient is extubated, in the early postoperative period, the analgesic mixture is continued at a rate of 5 ml / h and intravenous administration of dexmedetomidine to irovke 0.3-0.6 ug / kg / h under the control of the level of sedation and hemodynamics.