The method of stabilization of the perfusion pressure of the brain during induction of anaesthesia in patients with vnutricerepnae hypertension

 

(57) Abstract:

The invention relates to medicine, namely to anesthesiology, and can be used in anesthetic ensuring operations on the brain. The invention is aimed at reducing the complications associated with a decrease in perfusion pressure of the brain in patients with intracranial hypertension during induction of anaesthesia. To do this, at induction of anesthesia, intravenous mixture of fentanyl and clonidine.

The invention relates to medicine, namely to anesthesiology, and can be used for anesthetic management of surgical interventions on the brain.

The invention is directed to a method of stabilizing the perfusion pressure of the brain in patients with increased intracranial pressure during induction of anaesthesia.

One of the main mechanisms of compensation increase intracranial pressure is increasing and stabilizing the optimal level of perfusion pressure of the brain (VSD), which is determined by the formula: PWM GARDEN ICP, where the GARDEN mean arterial pressure and ICP, intracranial pressure. Correction PWM during induction of anesthesia based on objective data the greater the duration of induction of anesthesia, and the rapidity of development of ICP changes and GARDEN limits the application of pharmacological agents for the stabilization of these parameters. From the beginning of the induction of anesthesia prior to surgical decompression of the brain takes in average 20-90 minutes meanwhile, uncontrolled increase in ICP in the background of the original intracranial hypertension and exhaustion of the compensatory capacity of the organism is the cause of a sharp deterioration of the functional state of the brain, its viscosity-elastic qualities, leading to a significant complication of operative intervention open brain and unnecessary to neurological and psychological deficits in patients in the postoperative period. Usually the focus during induction of anesthesia in these patients is paid to the reduction of intracranial pressure. Preference is given intravenous anesthetics, reducing cerebral blood flow and metabolism: sodium oxybutyrate, propofol, and thiopental sodium. However, it is known that the action of sodium oxybutyrate accompanied by SOMATO-autonomic activation, and when it is used for induction of anaesthesia in pure form are manifested such negative aspects as prolonged sleep onset, the possibility of involuntary motor reactions and vomiting in the patient. This tends to complicate the technique of anesthesia by a combination of sodium oxybutyrate with Drury cases the occurrence of seizures after anesthesia with propofol in patients not having such seizures in history. While anesthesia on the electroencephalogram of these patients had signs of epileptiform activity.

The most dangerous period of induction of anaesthesia (because of the possibility of increasing ICP) is laryngoscopy and tracheal intubation. More attention is removed proper use of muscle relaxants, the main requirement is to prevent excessive muscle fibrillyatsy. Adequate blood oxygenation and prevention of increasing the tension of carbon dioxide in the blood is considered one of the basic security a period of induction of anaesthesia in patients with baseline intracranial hypertension.

Known method of stabilizing the perfusion pressure of the brain during induction of anaesthesia, which is based on the repeated administration of pentothal sodium before laryngoscopy and tracheal intubation, chosen as a prototype. While the induction of anesthesia is intravenous injection of thiopental sodium in a dose of 5 mg/kg for one minute, then entered the muscle (intravenous pancuronium 0.1 mg/kg) and, after a three-minute hyperventilation mask with a mixture of nitrous oxide and oxygen is 2:1, repeated doses of thiopental sodium 2.5 mg/Chania blood pressure by decreasing vascular tone, caused ganglioblokiruyuschimi effect of thiopental;

risk reduction in cardiac output due to cardiodepressive action of thiopental;

insufficient autonomic stability during laryngoscopy and intubation of the trachea due to violincello action of thiopental even in the face then, including m-cholinolytics in normal dosages.

All these risks are described in the literature and due to the strong direct depressive effect of this drug on the cardiovascular system.

Thus:

only considers the hypotensive effect of thiopental on intracranial pressure and is not taken into account the impact of this drug on systemic hemodynamics, which provides for the maintenance of adequate perfusion pressure of the brain;

it is impossible to predict the hemodynamic response to the introduction of additional doses of the drug before intubation;

the absence of physiological coherence between changes in ICP and GARDEN increases the probability of formation of inadequate perfusion pressure of the brain with all the ensuing consequences;

pronounced agathonissi effect of thiopental increases the risk of cancer of the rule, are the basis for the use of additional pharmacological correcting therapy, which greatly complicates and increases the number of unwanted reactions during induction of anesthesia.

The technical result of the proposed method is achieved by the combined effects on opioid and adrenergic antinociceptive system with simultaneous administration of narcotic analgesic (fentanyl) and alpha-2-adrenoagonists (clonidine).

It is known that opioid and adrenergic antinociceptive systems are an integral part of neuroregulatory system of the brain, which plays a leading role in ensuring optimal conditions for the functioning of the brain in extreme situations. This system provides physiological coherence systemic and cerebral compensatory processes in conditions of extreme effects on the body. The primary implementation mechanism of the pharmacological effects of fentanyl and clonidine are the structures of the brain stem. This ensures consistency between the changes of intracranial pressure and indicators of systemic hemodynamics, which is the basic condition for the formation and stabilizati is 2">

The inventive method differs from the prototype in that during the induction of anaesthesia intravenous mixture of fentanyl and clonidine. These drugs act on the system, forming an optimal correlation between intracranial pressure and systemic hemodynamics, as anti-stress drugs, they provide sufficient depth of anesthesia and at the same time retain the integrative mechanisms of the systemic and local (brain) processes. This significantly reduces the risk of complications associated with hypoperfusion of the brain during induction of anesthesia.

The method is as follows.

30-40 min before the operation the patient intramuscularly injected atropia 0.5-1 mg, morphine 10-20 mg, diphenhydramine 10-20 mg, and operating intramuscularly 10-20 mg Relanium. Induction of anesthesia and the stabilization of the perfusion pressure of the brain carry out intravenous mixture of fentanyl and clonidine. The mixture is prepared immediately before induction of anaesthesia, drugs are chemically compatible. The syringe is typed in 10 ml of a 0.005% solution of fentanyl and 2.0 ml of 0.01% solution of clonidine. The mixture is injected intravenously at the rate of: 3,5-7,1 mg/kg of body weight of fentanyl and 14.5-29,0 µg/kg body weight of clonidine. Applied miralax what I drugs: fentanyl and clopinel (half the estimated dose), Arduan (half the estimated dose, fentanyl and clopinel (half the estimated dose), Arduan (half the estimated dose). The introduction of each fraction preparations for 1 min. Adequate mask ventilation is possible after the introduction of the half of the calculated dose. The final dose of the medication depends on the patient and is determined by the signs of the first level of the 3rd stage of anesthesia.

The invention was developed and passed clinical trials in the United Spbggi them. Professor A. L. Polenov. Our clinical experience is more than 500 observations.

A comparative study of the proposed method and the prototype was performed in 39 patients with various brain tumors. The results of these studies are shown in table.

The table shows that the introduction during the induction of a mixture of fentanyl and clonidine level indicators that emerged after the introduction of half the estimated dose, remains almost unchanged until the end of the induction of anaesthesia. No changes in CVP and signs of hypoventilation during mask ventilation is associated with concurrent depression of the respiratory centre narcotic analgesics and off activity of the respiratory musculature the second ventilation after the introduction of the half of the calculated dose. The stability of the ICP and PDM during laryngoscopy and intubation of the trachea also shows greater efficiency neuro-vegetative stabilization in the second group of patients. Relative contraindications to the use of a combination of fentanyl and clonidine in anesthesiology emergency are marked hypovolemia and hypotension. When the primary injury of the brain stem, causing loss of Central regulation of vascular tone, the use of clonidine is impractical.

Here is an example extract from the history.

P R I m m e R. the Patient M, 46 years old, was treated in Spbggi with a diagnosis of neuroma VIII nerve right at the stage of Frank clinical changes. The patient was dominated by hypertensive symptoms headaches, objectively-congestive nipples optic nerves. It was decided to perform the operation, the destruction of neurinomas of the VIII nerve. For 30 min before the operation the patient was injected intramuscularly 0.8 mg of atropine 20 mg Dimedrol, 20 mg of morphine, operating 20 mg Relanium. The original ICP, measured by means of a catheter introduced into a lateral ventricle under local anesthesia, was 19 mm RT.article GARDEN 103 mm RT.article PDM 84 mm RT.article Heart rate 88 beats per minutes During a range of complete 4 mg ardoyne scheme: 6 ml of the mixture, 2 mg ardoin, 6 ml of a mixture of 2 mg of ardoyne. At the time of the introduction of half of the total dose of a mixture of ICP was 14 mm RT.article GARDEN 95 mm RT.article PDM 81 mm RT.article Heart rate 84 beats per minutes After administration of full dose ICP 13 mm RT.article GARDEN 85 mm RT.article PDM 72 mm RT.article Heart rate of 75 beats per minutes At the time of intubation ICP 13 mm RT.article GARDEN 89 mm RT.article PDM 76 mm RT.article Heart rate 72 beats per minutes So at all major stages of induction of anaesthesia, the patient remained stable parameters of systemic hemodynamics and adequate perfusion of the brain. Further surgery was uneventful postoperative period was uneventful.

The inventive method has the following advantages over the prototype: reduces complications associated with hypoperfusion of the brain during induction of anaesthesia, forming an optimal correlation between intracranial pressure and systemic hemodynamics. It provides sufficient depth of anaesthesia with preservation of the integrative mechanisms of systemic and local (brain) compensatory processes.

The METHOD of STABILIZATION of the PERFUSION PRESSURE of the BRAIN DURING INDUCTION of ANAESTHESIA IN PATIENTS WITH VNUTRICEREPNAE GENERALIA, including the introduction of drugs, characterized in that the injected mixture generally is

 

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The invention relates to compounds of the formula I

(I) or pharmaceutically acceptable salt accession acids him or stereoisomeric form of the compound, where

-A1= AND2- A3= AND4- bivalent radical having the formula

-CH=CH-CH=CH- (a-1)

-N=CH-CH=CH- (a-2)

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L is hydrogen, C1-C6alkyl, C1-C6allyloxycarbonyl, or a radical of the formula

-Alk - R5(b-1),

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Gwhere G2- CH=CH-CH=CH-, -S-(CH2)3,- -S-(CH2)/2-, -S-CH=CH - or-CH=C(CH3)-O-;

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R8- halophenol;

Y is O or NH;

Z1or Z2each independently NH or a direct link X-O

each Аlk independently - C1-C6alcander

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BANwhere In - perederina, piperidinyl or pyrrolidinyl group, each of which may be substituted by a lower alkyl group, lower alkylcarboxylic group, carbobenzoxy, afterburner (lower) accelgroup, phenylketone (lower) alkyl group, phenylcarbamoyl (lower) alkyl group or phenyl (lower) alkyl group, each of which may be substituted by a halogen atom or a lower alkoxygroup; p is 1 or 2; And -- is a bond, or two-, or trivalent aliphatic C1-6hydrocarbon residue which may be substituted by a lower alkyl group, oxo, hydroximino or hydroxy-group;means either simple or double bond, provided that when a represents a bond, thenmeans of a simple bond; R2and R3independent means ATO condition, both R2and R3are not hydrogen atoms, or R2and R3together with the adjacent nitrogen atom form piperidino, hexamethyleneimino, morpholino, pyrolidine, pieperazinove or 1-imidazolidinyl group, each of which may be substituted by a lower alkyl group, a phenyl (lower) alkyl group, a lower alkylcarboxylic group or diphenyl (lower) alkyl group or a physiologically acceptable salt additive acid

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R1-(CH2)n-Z,

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N-(CH2)mR2(A) or -(CH2)p, dioxolane, furan, tetrahydrofuran, methylfuran or thiophene, m is an integer from 1 to 3; R3is lower alkyl; R4is phenyl or a radical of dioxolane, furan or thiophene, p = 1, provided that when R1radical 1,2,3,4-tetrahydrobenzo-2-or 1,2,3,4-tetrahydroquinazoline-2,4-dione, R2and R4are not phenyl or substituted by a halogen phenyl, or their pharmacologically acceptable salts with antiacetylcholinesterase activity

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R2is methylene;

n is an integer 1 or 2, which have a high and strictly selective antiacetylcholinesterase activity and can find application in medicine
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