Method for postoperative anesthesia in thoracic surgery

FIELD: medicine, thoracic surgery, anesthesiology.

SUBSTANCE: as non-narcotic medicinal preparation one should apply heparin to be introduced intratracheally at the dosage of 300-500 IU/kg, moreover, heparin should be introduced during the first 30 min after the operation is over. The present innovation enables to create prolonged anesthetizing effect in combination with prophylaxis of postoperational thrombohemorrhagic complications due to heparin capacity to be kept in the body due to its accumulation by mast cells at blockade of their fermentative activity followed by its gradual release into the blood.

EFFECT: higher efficiency.

1 cl, 1 ex, 3 tbl


The invention relates to medicine, namely to surgery, anesthesiology and critical care medicine, and can be used for postoperative pain management of patients operated on his chest.

Adequate postoperative analgesia is the basic condition for the implementation of the program active postoperative rehabilitation of patients operated on the chest. Postoperative pain is the primary cause of the development of pathological postoperative complex of syndromes. Acute pain increases the rigidity of the muscles of the thorax and anterior abdominal wall, leading to decreased tidal volume, vital capacity of the lungs and alveolar ventilation. The consequence is the collapse of the alveoli, hypoxemia and decreased oxygenation of the blood. The difficulty of clearing amid pain syndrome violating the evacuation of bronchial secretions, which helps atelectasia with subsequent development of pulmonary infection. Therefore, there are manifestations of acute respiratory failure in the early postoperative period in these patients.

Related hyperactivity of the sympathetic nervous system, in addition to tachycardia, hypertension and increased peripheral vascular resistance, causing postoperative hypercoagulation and, therefore, increases the t risk of blood clots.

Activation of the autonomic nervous system on the background of the pain syndrome increases the tonus of the smooth muscles of the intestine with reduced peristaltic activity and the development of postoperative paresis. And finally, nociceptive stimulation polymodality systems of the spinal cord can lead to enhanced receptor fields and increased sensitivity bulbospinal neuronal structures of the spinal cord.

The result is the formation of chronic postoperative neuropathic pain syndromes, based on the above-mentioned plastic changes in the Central nervous system. In particular, it is known that one to two thirds of patients undergoing surgery on the chest, for a long time suffer from postthoracotomy pain. The frequency of their development depends on the intensity of pain in the early poslenarkoznogo period and the adequacy of analgesia during the first postoperative week.

At the present time there is no optimal method of postoperative pain management. The main place in the Arsenal of painkillers take narcotic analgesics used systemically or epidurally. However, it is known that opiates inhibit vital body functions such as breathing, they quickly develop a tolerance and addiction - drug addiction.

Current PR is the problem of anesthesiology is to develop new methods of anesthesia, based on the application neopytnyh pharmacological tools partially or completely abandon the use of narcotic analgesics. This has not only medical but also of great social importance, because drugs in modern society are a source of growing drug abuse and crime.

There is a method of pain relief in the postoperative period, including parenteral non-narcotic drugs (Nasibova, Waseleski and other Nonsteroidal anti-inflammatory drugs (aalisin) in the postoperative anesthesia and intensive care. //Anesth. and Reanimator. - 1994. No. 4. - P.41-45).

In the quality of medicines in this way is used aalisin, which is injected intravenously over 30-60 minutes 2-3 times per day, in combination with baralgin and tramadol. Introduction atselizina begins after 1-2 hours after the operation. The method allows to reduce the dose of opioid analgesics and related side effects and to get the full benefit of anesthesia.

However, non-steroidal anti-inflammatory drugs (NSAIDs) and, above all, derivatives of acetylsalicylic acid have quite severe side effects: lead to the development of thrombocytopathy, acute gastric ulcers and exacerbation of ulcerative bole is no, what increases the risk of postoperative bleeding. In addition, they are drugs with a high risk of allergic reactions and have a teratogenic effect.

The closest analogue is a method of postoperative pain management, including parenteral non-narcotic drugs (RF patent 2192859, IPC 7 a 61 K 31/41, And 61 R 25/04, And 61 M 19/00, 2002 - prototype).

In this way as a non-narcotic medicinal use clonidine, which is injected epidurally several times a day for two to three days after surgery. The lack of drugs in the postoperative period eliminates the symptoms of serious negative consequences of their side effects.

However, epidural anesthesia, being invasive method of pain relief, carries the risk is heavy enough iatrogenic complications, the most serious of which is a profound disorder of respiration and hemodynamics in patients with total spinal anaesthesia. Performing anesthesia may be accompanied by technical difficulties and does not guarantee to achieve complete pain relief.

Repeated introduction into the epidural space clonidine necessary to provide anesthesia (as hydrochloride does not result in prolonged anesthesia), bears the risk and who fitiavana tissues with subsequent infection of the Central nervous system.

In addition, hypotensive, clonidine has a strong sedative effect that in the postoperative period can lead to adynamia and thereby reduce the depth of breathing. Epidural injection of clonidine leads to the necessity of finding patients in the ward ICU for 2-3 days.

The objective of the invention is to create an effective and safe neopitnogo method of postoperative pain management of patients after thoracic operations in excluding or reducing the use of analgesic drugs.

The technical result - lasting analgesic effect, combined with the prevention of postoperative thrombohemorrhagic complications; simplification of the method, reducing the trauma and risk of infection; no oppression of consciousness; reduction of time of stay of the patient in the ward ORIT.

This technical result is achieved in that in the method of postoperative pain management, including parenteral non-narcotic drugs, the authors proposed as non-narcotic drugs to use heparin in a dose of 300-500 IU/kg, administered intratrahealno. Introduction heparin may be conducted within the first 30 minutes after the end of the operation.

It is known that heparins are a group negatively the charger, side buttons is different sulfated mucopolysaccharides, with direct anticoagulant effect on the blood, as well as a number of other biological effects. The anticoagulant effect of heparin is implemented indirectly by blocking the enzyme of the coagulation factors. Another important property is the ability to bind to endothelial cells of the vascular wall, which increases the negative charge and thromboresistant the past, which in turn leads to the improvement of microcirculation of tissues.

Thus, heparin, to a certain extent, can be attributed to substances that have vasoprotective action, which is implemented in two ways: a protective effect on the vascular endothelium and the blockade of thrombin. This reduces the selection vasoconstrictor enzymes and attenuated vasospasm and hyperplasia of smooth muscle cells. At the same time in the available sources of information, we did not find information about the analgesic properties of heparin and heparin as the sole analgesic when conducting post-operative analgesia.

Clinical studies conducted by the authors showed that intratracheal injection of heparin at a dose of 300-500 IU/kg in the early postoperative period after surgical interventions on the organs of the thorax has a pronounced analgesic on the op perate, comparable to the effect of narcotic analgesics: the absence of pain sensations, breathing, active cough, activation of patients in the first hours after surgery. This is confirmed by early normalization of hemodynamics, respiration, the hemostatic system.

These doses of heparin are effective and safe. The use of heparin in doses below 300 IU/kg is not possible to achieve a sufficient level of anesthesia, excessive doses above 500 IU/kg may lead to increased postoperative bleeding no significant changes in the quality of analgesia.

Unlike clonidine heparin can be entered intratrahealno that much easier method significantly reduces the invasiveness and risk iatrogenic damage and infection. The duration of analgesic effect (within days) and long-term moderate hypocoagulation, probably provided by the ability of heparin to persist in the body by the accumulation of fat cells by blockade of their enzymatic activity and with subsequent gradual release it into the blood (A.G. Orlova //Pharmacology and toxicology. - 1989. - C, No. 3. - P.55-59).

Preferably heparin in the first 30 minutes after the operation, which avoids recovery period pain sensitivity after stopping dei is the major drugs for anaesthesia, providing post-operative a feeling of comfort to the patient. The terms of stay of the patient in the ward ORIT can be reduced to 1 day.

In addition to analgesia, the method allows us to simultaneously solve other problems of early post-operative period due to the use of known properties of heparin. It is known that intratracheal injection of heparin significantly improves the drainage of sputum. Another important factor is the prevention of thromboembolic complications due to reduction under the action of heparin consumption of coagulation factors, anticoagulants and platelet count.

Inhalation (intratracheal) the route of administration of heparin is known in the treatment of patients with disorders of the respiratory tract accompanied by disorders of hemostasis and thrombosis prophylaxis (N. Molino, Belluardo C. //Minerva cordioangiol. -1973. - Vol.21 - R-142; R.L. Bick, T.S. Ross //Semin. Trombos. Res. - 1985. - Vol.11, No. 2. - P.213-217.). While the introduction of heparin at a dose of 350 to 400 IU/kg leads to long-term moderate gipokoagulyatsii without any adverse reactions.

The method is as follows. Preferably within 30 minutes after the end of the operation directly into the lumen of the trachea through the catheter conducted through an endotracheal tube, introduce a solution of heparin in a dose of 300-500 IU/kg Entered thus heparin within the next day is to provide the level of anesthesia, does not require the use of drugs.

Study of the analgesic action of heparin administered intratrahealno conducted in two randomized groups of patients, in 10 people in each, operated on for limited forms of pulmonary tuberculosis. The quality of postoperative analgesia was studied by subjective perception of pain on a 3-point scale (1 point - the presence alone of pain, difficult breathing and cough and requiring supplemental analgesics; 2 points - the presence of pain only when moving or coughing; 3 credits the state of comfort, no pain when moving or coughing), integral indices of Central hemodynamics, external respiration, changes in the hemostatic system. Patients studied groups after conducting thoracic surgery just before extubating was administered once intratrahealno heparin at a dose of 300-500 IU/kg; patients of the control group during the first days after the operation has received narcotic analgesics (morphine 20 mg intramuscularly 3 times a day) in combination with NSAIDs (aspirin, Ketanov).

As a result of the research showed that the subjective assessment of the severity of postoperative pain and quality of analgesia in the treatment group, which received intratrahealno heparin was more blah is opryatnoy, than patients of the control group who received narcotic analgesics (table 1).

Table 1

Assessment of pain patients in points
The group of patientsThe stages of the research
After surgeryAfter 3 hoursAfter 6 hoursAfter 12 hoursAfter 24 hours

Monitoring data the main parameters of gas exchange and hemodynamics in both groups revealed no significant differences in the immediate postoperative period. Studies of the reaction of blood on the operating injury showed that patients receiving heparin, the postoperative period was characterized by a less pronounced response to the operating injury (table 2, 3).

Table 2

The blood counts in the treatment group
IndicatorsThe stages of the survey
Source After surgeryAfter 3 hoursAfter 24 hoursAfter 72 hours
Leukocytes, X109/l5,33±0,90  9,48±0,647,25±1,07
Platelets, X109%218,0±16,5209,0±13,9205,5±18,9209,0±21,3242,5±16,0
AFT, %50,7+10,332,5+3,619,8+5,633,2+4,344,0+12,7
Thrombin time with.12,0±0,612,3±0,511,8±1,311,7±0,512,2±0,8
Fibrinogen, g/l2,72±0,382,30±0,382,13+0,293,38±0,65to 4.38±0,48
Table 3

Blood counts are sick the control group
IndicatorsThe stages of the survey
SourceAfter surgeryAfter 3 hoursAfter 24 hoursAfter 72 hours
Leukocytes, x109%5,28±0,45  11,0±1,38,95±1,2
Platelets, X109/l189,3±9,0182,7±2,1214,0±74,0to $ 179.7±7,8220,0±29,4
AFT, %53,7±6,640,3±1,943,0±12,238,3±4,949,0±12,8
Thrombin time with.12,2±0,911,0+1,613,0±010,7±0,510,7±0,9
Fibrinogen, g/l2,33+0,122,07±0,172,47±0,964,10±0,79of 5.40±0,29
AT-III,%of 87.3±9,086,3±9,4 65,7±14,675,0±2,483,3±11,8

Patients of the studied group noted a moderate lengthening of thrombin time, and less pronounced in comparison with the control group the decrease of anti-thrombin III (AT III), indicating a lesser likelihood of postoperative thrombotic complications. In addition, this group of patients in the first hours after surgery was significantly reduced adhesion-aggregation activity of platelets (AAFT)that, apparently, evidenced by a decrease in consumption of platelets in the reactions of blood coagulation. Therefore, in these patients the level of platelets in the postoperative period practically did not change, while patients in the control group the level of platelets was significantly reduced in the first day after surgery. Elevated numbers of blood leukocytes in patients of the control group shows a more pronounced stress response on the operating injury (table 2, 3).

Studies have shown that the proposed method is effective analgesia is not inferior to traditional (most effective) anesthesia narcotic analgesics, while not having its negative consequences.

Example. Patient K., 23 years. Diagnosis: fibrous-cavernous is tuberculosis of the upper lobe of the right lung. Under intravenous balanced anesthesia with mechanical ventilation operation performed in the volume: upper lobectomy right. The operation took place at stable parameters of the AD - 120-130-140/80-90-100 mm Hg, pulse rate is 96 to 100 beats per 1 minute After surgery the patient was transferred to ICU patients on mechanical ventilation through an endotracheal tube. Before extubating into the lumen of the tracheobronchial tree of the suction catheter through the endotracheal tube put 30 thousand IU of heparin (450 mg/kg).

Within 1 hour after admission to the ward ICU patient regained consciousness and spontaneous breathing. After 3 hours after the operation the patient was lifted to his feet and continued to serve themselves. Breathing disorders, expectoration of sputum were observed. In the postoperative period of the first pain came later, 8 hours after the operation when changing body position and cough. The pain was eliminated by the introduction of 1 g of aspirin. During the first days after the operation the HELL 120-100/80-70, HR 86-74-66 beats per minute, respiratory rate 20-16 min, São293-98. Control of hemostasis was carried out immediately after the operation, and after 3, 6, 12 and 72 hours. Revealed changes did not go beyond the average for the group of observations. After 20 hours after surgery the patient was transferred to the Department of thoracic surgery. Further analgesia - Ketanov 10 mg intramuscularly 3 times in the ducks. The effect of anesthesia during observation was 2-3 points. Further postoperative period was without complications. Discharged home under the supervision of a specialist.

Thus, the use of heparin administered intratrahealno directly after thoracic operations, led to a prolonged postoperative analgesia in patients without the use of narcotic analgesics. While heparin has also ensured the prevention of postoperative disseminated intravascular coagulation and thrombohemorrhagic complications. The way low-impact, easy to use, reduces the period of stay of the patient in the ward ORIT.

1. Method of analgesia in the postoperative period, including parenteral non-narcotic drugs, characterized in that as a non-narcotic drug use heparin administered intratrahealno dose of 300-500 IU/kg

2. The method according to claim 1, wherein the heparin is administered during the first 30 min after the end of the operation.


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3 tbl

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2 ex

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wherein R1 means hydrogen atom or hydroxy-group; R2 and R3 each means independently of one another hydrogen atom or (C1-C4)-alkyl; R4, R5, R6 and R7 each means independently of one another hydrogen atom, (C1-C4)-alkoxy-group, (C1-C4)-alkyl or (C1-C4)-alkyl substituted with (C1-C4)-alkoxy-group; or R5 and R6 in common with carbon atoms to which they are joined mean 6-membered cycloaliphatic ring or 6-membered heterocyclic ring comprising two oxygen atoms; R8 means -NHR13 wherein R13 means hydrogen atom, (C1-C4)-alkyl or -COR14 wherein R14 means hydrogen atom; or R13 means -SO2R17 wherein R17 means (C1-C4)-alkyl; R9 means hydrogen atom; or R8 means -NHR18 wherein -NHR18 and R9 in common with carbon atoms to which they are joined mean 6-membered heterocycle; R10 means -OH; X means (C1-C4)-alkyl; Y means carbon atom; n = 1 or 2; p = 1; q = 1; r = 0 or 1. Also, invention describes pharmaceutical composition based on compound of the formula (I), a method for preparing compound of the formula (I) and intermediate compound that is used in the method for preparing. Compounds elicit the positive stimulating effect of β2-adrenoceptor.

EFFECT: improved preparing method, valuable medicinal properties of compounds.

13 cl, 3 tbl, 35 ex

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2 cl, 3 dwg, 1 ex

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