Aneurysm treatment

Treatment for aneurysm rupture depends on the severity of the patient's condition upon admission and is due to the degree of involvement of the major pathogenetic mechanisms. The key moment in the complex of measures is the fact of an operative intervention with the turning off of the aneurysm from the blood stream, which prevents a repeated rupture (this feature is not completely fulfilled when enveloping the aneurysm - the possibility of a repeated rupture is preserved until 2-3 weeks - the time of formation of the collagen "outer framework" of an aneurysm based on the material , used for enveloping.

There are several periods of aneurysmal subarachnoid hemorrhage: acute (the first three days), acute (up to two weeks), subacute (2-4 weeks), and "cold" (more than a month after the development of hemorrhage). Each period has its own pathogenetic characteristics, depending on which the treatment tactics also change.

• So, the sharpest period is characterized by not yet sharply expressed angiospasm and moderate edema of the brain. Therefore, it is favorable for the operation. This applies only to patients I, II, III degrees of severity in HN. Patients with IV - V degrees are subject to surgery only if they have an intracerebral hematoma of a large volume (more than 60 ml) and the phenomena of acute occlusive hydrocephalus (the imposition of ventricular drainage). The remaining patients are subject to active conservative treatment before exiting the coma and complete regression of arteriopathy and cerebral edema.
• The acute period is characterized by an increase in the severity of arteriopathy, ischemia and cerebral edema. All patients are treated conservatively. Operative intervention is contraindicated except for cases of repeated rupture with the development of life indications. However, mortality after such operations exceeds 50%. The tactics for the progressing cerebrospinal fluid hypertension syndrome are similar to the previous period.
• Subacute period begins after two weeks and is characterized by normalization of all vital functions of the brain, regression of arteriopathy and edema, restoration of liquor circulation. In these terms operative treatment can be undertaken in patients with I, II, III degrees of severity for HH, and also with IV and V st., In which consciousness was restored, hemodynamics stabilized and the arteriopathy phenomena regressed according to transcranial Dopplerography. However, this is not the most favorable moment for the operation, since the normalization of all brain functions is not complete. But it is in these terms, according to statistical data, that the repeated ruptures of arterial aneurysms often occur. Therefore, it is necessary to strive to perform the operation without waiting for a "cold" period, thereby preventing a repeated rupture. Undoubtedly, a month after the break, the conditions for the operation are the most favorable. But it is more important to save those who have a repeated break up to a month, which is about 60% of all cases of rupture of an aneurysm.

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Emergency care and conservative treatment of aneurysm

Patients with subarachnoid hemorrhages should be transported to a specialized or neurological department (in the absence of a specialized hospital), for adequate diagnostic measures and rational choice of treatment tactics, taking into account objective data of the dynamic assessment of the patient's condition. Delayed transportation is possible with stabilization of arterial pressure, regression of headache and meningeal syndrome (for persons with I, I, III degrees of severity according to Н-Н), normalization of the state of vital functions, exit of the patient from coma (for persons with IV - V degrees of severity by H-H).

The therapeutic tactics in the SAC will be considered in connection with the pathogenetic mechanisms involved in the disease.

Therapy of constrictive-stenotic arteriopathy is formed from the following components:

• exposure to extravasal blood lysis products and their metabolites;
• maintenance of adequate regional cerebral blood flow in conditions of developed arteriopathy;
• Neuroprotective intervention with existing ischemia of the brain.

Any surgical intervention with an aneurysmal SAK is accompanied by a sanation of the subarachnoid spaces and, if necessary, ventricles of the brain, to evacuate blood clots that are a source of oxyhemoglobin and other biologically active substances that activate cyclooxygenase I and II types (COX-1, COG-2) triggering the metabolism of arachidonic acid with the formation of prostaglandins, thromboxane, prostacyclin.

Antagonist of this process are non-steroidal anti-inflammatory drugs (indomethacin IV bolus 50 mg / 20 min followed by 30 mg / hour for 3 days after rupture of aneurysm, tilpene 75-300 mg / day, aspirin and its injectable form acetylin-0, 5 - 3.0 g / day). At the end of the parenteral administration, the use of the drug per os is continued: movalis 7.5-30 mg / day, mesulide (nimesulide) 200-400 mg / day for 1 month. Caution should be observed in the presence of a patient with peptic ulcer disease or development of acute ulcers of the gastrointestinal tract; preference is given to selective inhibitors of COX 2 (celeprex, movalis, mesulide), in some cases - with rectal administration.

Considering the high protease activity of plasma and CSF, the use of nonspecific inhibitors is recommended (countered up to 50,000 units / day, trasilol, gordox in equivalent doses). Similar properties are also found in the aminocaproic and trinexamic acids previously used in the treatment of CAA, as inhibitors of thrombolysis. But at the present time, their use is significantly limited due to the high risk of developing secondary ischemic disorders in the background of hypercoagulability, despite attempts to correct this process by adjuvant administration of heparin.

Mandatory in the therapy of argeiopathy in SAK is the concept of ZN therapy (Hypertension, Hypervolemia, Hyperhydration), especially shown in the development of the clinic of arteriopathy and delayed ischemic deficiency. Hypertension is maintained at the level of blood pressure. 160-180 mm Hg, AD diast. 80-100 mm Hg (increase in the figures of blood pressure by 20-100 mm Hg from the initial). Controlled arterial hypertension is achieved using vasopressors (dopamine), glucocorticoids, parasympatopoic blockers (nonselective holinoblockers - atropine sulfate, etc.). Hypervolaemia and hemodilution are mandatory accompanied by measures aimed at improving the rheological properties of blood (albumin 10 - 20%, native plasma, reopolyglucin 200-400 ml / day). The total volume of injected solutions is 50-60 ml / kg / day with hematocrit control (up to 0.40). It is permissible to administer a solution of dextrose (glucose) 5% 500 ml / day. Hypertensive glucose solutions are not recommended because of the possible development of hyperglycemia followed by acidosis of brain tissue, aggravating ischemic damage.

It is recommended to use mediotherapeutic doses of nonfractional heparin (up to 10,000 units per day), which has antiaggregant activity. In addition, he neutralizes thrombin, weakens its stimulating effect on the synthesis of prostaglandins, prevents introducted indomethacin from inactivation by thrombin. More preferable is the use of low molecular weight heparin (Fraxiparin - 0.6-0.9 ml s / c in the peripodal region twice a day for 14-18 days). As a prophylaxis for the formation of erythrocyte thrombi, pentoxifylline is shown at a dosage of 400-1200 mg / day IV for 2-3 injections.

This therapy is optimal for use in the postoperative period with AA out of the bloodstream. Otherwise, it significantly increases the risk of re-hemorrhage. Accordingly, from controlled hypertension, it is preferable to abstain, resorting to it when the clinic of ischemic injury increases. A similar tactic is desirable with regard to direct anticoagulants. Complications of ZN therapy are myocardial infarction and pulmonary edema. Thus, monitoring of ECG and central venous pressure is required.

Concerning the effect of developing arteriopathy on the myogenic component of developing arteriopathy, the dihydropyridine blocking agent Ca2 + of the potential-dependent channels of nicardipine (0.075 mg / kg / hr iv for 14 days after rupture of the aneurysm) proved to be the most effective (according to dynamic angiographic control) for regression of the degree of narrowing of the arterial lumen. Complications in its use are pulmonary edema and hyperaemia (the relevant indicators should be monitored).

A promising drug is a peptide associated with the calcitonin gene, which possesses vasodilator properties, which are realized in the phase of the unfolded phenomena of arteriopathy. Its dosage form in the form of long-acting tablets undergoes clinical trials.

In the acute period of hemorrhage, when the narrowing of the arteries is caused only by myogenic mechanisms and adrenergic stimulation, administration of adrenoblockers (metoprolol 200 mg / day iv, labetalol 5-25 mg bolus followed by a daily dosage of 10-15 mg, propranolol), lidocaine is shown.

The third link in the therapy of arteriopathy is neuroprotective measures.

Another dihydropyridine derivative with Ca2 + blocking activity is nimodipine (nimotope). The drug does not affect the degree of narrowing the lumen of the arteries, but blocks the Ca ²⁺ potential-dependent channels of neurocytes, reducing the massiveness of the extracellular entry and release from the Ca ²⁺ depot into the cytoplasm (injected intravenously at 1 mg / h for the first 2 hours, then 2 mg / 5-7 days with the subsequent transition to oral administration 2 table 6 times a day - 7-10, up to 20 days), it is necessary to take into account the expressed hypotensive effect of the drug, which determines the pharmacological antagonism of the administered controlled AG.

Expressed dose-dependent inhibitory activity against lipoperoxidase with restriction of the formation of free radicals have glucocorticoids. In particular, methylprednisolone is recommended for use intraoperatively 1 mg / ml in physiological saline solution for subarachnoidal tanks, followed by intracisternal injection through the catheter 5 ml of the solution per day for 14 days. Parenteral administration to 20-30 mg / kg / day accounts for the expected effect, but exceeding the dose leads to the elimination of antioxidant effects and even the opposite result.

The drug of choice is dexamethasone, administered at a dosage of 16-20 mg / day for 7-14 days.

There are schemes of combined use of glucocorticoids and blockers of Ca ²⁺ channels: UN-diltiazem (O) 5 μg / kg / min IV for 2 weeks, 5% dextrose (O) 500 ml / day, hydrocortisone (H) 1600 mg in the first day after the hemorrhage, followed by a gradual decrease in the dose. Complication of this type of therapy in a number of cases is the development of atrioventricular blockade, regressing independently with a decrease in the dose of diltiazem.

Currently, the focus of antioxidant therapy aimed at inhibiting the activity of lipid peroxidation (LPO) processes has shifted from corticosteroids to 21-aminosteroids (substitution of the 21st hydroxyl group for the amino group in the non-glucocorticoid part of the molecule with a significant increase in antioxidant activity-the binding of hydroxyl and peroxy radicals) - Tyrilazate mesylate. In phase III clinical trials, he demonstrated a fairly high efficacy in combination with nimodipine, especially in males.

Endogenous antioxidants deficient in secondary ischemia are superoxide dismutase (SOD) (the preparation of polyethylene glycolconjugated SOD Dismuktee passed the III phase of clinical trials), tocopherols (alpha-tocopherol, beta-carotene - their effectiveness can be traced only in prophylactic applications, since active LPO prophylaxis directly is associated with the concentration of alpha-tocopherol on cell membranes at the time of occurrence of ischemia - up to 800-1000 mg / day in / m or orally). Donators of hydroxyl groups to neutralize free radicals are ascorbic (vitamin C - up to 2000 mg / day) and retinoic (vitamin A - up to 200,000 IU / day) acid. Inhibition of free radical formation can be effected by blocking the activity of xanthine oxidase (folic acid-calcium folinate-32.4 mg 2-3 times / day IM), chelation of iron and copper (deferroxamine, EDTA, kurenenil).

Another aspect of the damaging effect of ischemia on brain cells is the process of excitotoxicity (the release of excitatory mediator amino acids: glutamate and aspartate with activation of IMEA, AMPA receptors and active entry into the calcium cell), which is uncompetitively inhibited by ketamine, lidocaine, which is reflected in the following regimens: nimodipine - in / in the drip (the dosage is indicated above) to 5-7 days with continuation in tablets 6 days; ketamine - 1 μg / kg bolus followed by 3 μg / kg / min for 5-7 days; lidocaine - 1.5 mg / kg bolus and further 1.2 mg / kg / min. The scheme justifies itself when used in patients with III-V degrees of severity for H-H, while with a mild degree of SAK, the effect is absent.

The following combination can be used for pharmacological protection of the brain during the perioperative period or in the case of pronounced negative dynamics during delayed ischemic brain damage: thiopental sodium -1-1.5 mg IV (250-350 μg w / a), nimodipine-15 -20 mg IV (2-4 mg w / a), ketamine 400-500 mg IV (100-150 mg w / a). The way of administration is more optimal in / a, because it leads to a lesser degree of depression of hemodynamics, which negatively affects the overall outcome and requires complementation of the complex with vasopressors.

Under physiological conditions, the magnesium ions serve as the endogenous modulator of the IMB receptor and the hypomagnesemia formed during ischemia is corrected by the administration of magnesium sulfate in dosages of the order of 3.5-5 mg / kg, which ensures their blockade. Presynaptic inhibitors of glutamate release are riluzole (rilutec), lubeluzole.

As additional methods of neuroprotection should be mentioned sodium oxybutyrate (up to 80 ml / day), sodium thiopental or hexenal (monotherapy up to 2 g / day), tranquilizers of benzodiazepine series (diazepam 2-6 ml / day). A non-medicamentous means of increasing the resistance of the brain to hypoxia and ischemia is craniocerebral hypothermia with a decrease in body temperature by 1-2 ° C.

In a significant number of cases, SAK is accompanied by a spontaneous rise in BP in its absence before the disease. If the severity of the patient (IV-V, in some cases III H-H) makes it impossible to clone an aneurysm, this condition becomes pathological and increases the risk of repeated rupture of the aneurysm, requiring the appointment of antihypertensive drugs.

The standard first-line therapy in this situation is alpha and beta-adrenoblockers, which display pathogenetic activity (elimination of sympathicotonia, which has caused hypertension, but their use is inexpedient in the hypokinetic type of central hemodynamics that develops during severe CAA.

Blockers of potential calcium channels are used: phenylalkylamine derivatives (isoptin, finaptin, lekoptin 40-120 mg IV, slow, IM 3 times / day, 120-140 mg / 2 r / day orally as retard forms - isoptin, calanum BC), dihydropyridine (adalate, procardium - 30-120 mg / day for 1 dose, nicardipine 20-40 mg / day for 3 doses, amlodipine (norvask) 2.5-10 mg / day for 1 dose, felodipine captive) - 2.5-20 mg / day for 1 reception), benzodiazepine (diltiazem, dilren - 90 180-360 mg / day for 1 reception).

This group of drugs can be combined with blockers of the angiotensin-converting enzyme, especially in persons with an anamnesis of hypertension, incl. Renal - captopril (kapoten, tensiomin, alopresin) - 12,5 - 75 mg / day for 3 doses, enalapril (enap, enam, renitek, vasotek) - 5-20 mg / day for 1-2 doses, moexipril (moex) - 7,5-30 mg / day for 1 intake (especially recommended for women in the climacteric period), trandolapril (gopten, odric) - 2-4 mg / day for 1 dose, lisinopril (zestril, priniivil, sinopril) - 5-40 mg / day for 1 reception.

The group of ATII receptor blockers is used as an auxiliary therapy due to the lack of a rapidly advancing effect.

In case of GH resistance to standard therapy, ganglion blockers (pentamine, hygronium, benzohexonium) administered by physiological titration are used: dissolving the ampule in 10 ml of physiological solution and then bolus administration of 2-3 ml of the obtained solution with control of blood pressure in 15-20 minutes ( on the onset of the effect of the previous dose). The duration of the drug is 15-30 minutes.

With severe hypertension and lack of response to ganglion blockers, direct vasodilators are used: sodium nitroprusside (0.5-1.5 mg / kg / min), prostaglandin E2 (drip 90-110 ng / kg / min / dr), nitroglycerin (perlingant, nitro-poppy, nitro-pol-the content of the ampoule is diluted in 10 ml of distilled water and then added to a bottle with 5% glucose solution (200-400 ml), injected in droplets / drip under the monitoring of blood pressure. Min restores the initial BP figures.

Within the hypothalamic disorders, there is a syndrome of increased secretion of the atrial natriuretic peptide, manifested by hypovolemic hyponatremia and corrected using fludrocortisone. This situation should not be mistakenly assessed as a syndrome of inadequate secretion of an antidiuretic hormone with hypervolemic hyponatremia, which requires restriction of fluid administration.

Quite often there is cerebro-cardial syndrome, which consists in the violation of the central regulation of the heart (prolongation of QT, sharpening of T and P teeth, shortening of PK interval, wide teeth of V-associated with unfavorable outcome). In this case, correction with sympatholytic drugs (beta-blockers, Ca ²⁺ channel blockers), introduction of metabolic drugs (riboxin 10-20 ml / day, mildronate up to 20 ml / day), ECG monitoring, central hemodynamics with correction of developed disorders .

The central character is also worn by respiratory disorders with neurogenic pulmonary edema, the course of which is aggravated by the suppression of cough and pharyngeal reflexes (in patients IV to V of HH) with aspiration of oral contents and, in some cases, the development of Mendelssohn syndrome. This complex of pathological processes forms a violation of the function of external respiration with the development of purulent tracheobronchitis and pneumonia. Such patients are subject to intubation. If there is no recovery of normal breathing for 10-12 days, the tracheostomy is superimposed. Prevention of inflammatory processes is carried out by prescribing antibacterial drugs, incl. Inhalation (ultrasonic spraying of a mixture consisting of 500 ml of physiological saline, 200,000 units of penicillin, 250 units of monomycin, 10 ml of a 5% solution of kanamycin, 10 ml of 5% of ascorbic acid and chymotrypsin (20 mg) with hydrocortisone (250 mg) 2 -4 r / day). A bronchoscopic sanation of the tracheobronchial tree is carried out with the introduction of solutions of soda, antibiotics, hydrocortisone, proteolytic enzymes intrabronchially. With ventilation, an increased exhalation pressure is created, sufficient oxygen saturation is maintained.

Development of central hyperthermia requires neurovegetative blockade with the help of aminazine, pipolfen, droperidol, hypothermia by the introduction of cooled infusion solutions, hypothermia of the main vessels.

The manifestation of a stress reaction in SAK is the development of acute gastrointestinal ulcers with bleeding that significantly complicates the course of the disease. Preventive measures in this situation are the appointment of H2 blockers (cimetidine, ranitidine), the use of sedative therapy.

The third important aspect of the pathology in question, which requires specific correction, is an increase in intracranial pressure. The cerebral edema is essentially a compensatory reaction in response to an increase in the content of toxic products in brain tissue and, being compensated, does not require correction (I-III st. Н-Н). In the case of decompensation of the edema and the development of a dislocation syndrome, the provision of a hyperventilation regime with the creation of respiratory alkalosis, the administration of dexamethasone 8-20 mg / day, methylprednisolone 500-1000 mg / day, albumin, native plasma is shown. Osmodiuretics are used as a last resort to 0.5-0.8 g / kg / day with the threat of developing a brain wedging clinic.

Another aspect of this problem is hydrocephalus. It develops sharply, it is a consequence of the occlusion of the liquor-conducting pathways and is manifested by a disorder of consciousness and a focal neurological deficit. Delayed (hydrocephalus of normal pressure) manifests itself as progressive dementia, ataxia and pelvic disorders. Conservative therapy consists in the use of acetazolamide (diacarb, radicarb - 0.5-2.0 g / day), but, as a rule, ineffective and requires the imposition of ventricular drainage (temporary or permanent). The effectiveness of such manipulation depends entirely on the initial level of perfusion of the affected areas of the brain (in the regional cerebral blood flow less than 25 ml / 100 g / min, the recovery of the lost functions does not occur). For the prevention of such phenomena in a number of foreign clinics, endoluminal and intracisternal administration of the tissue plasminogen activator (after pre-endovascular AA thrombosis) is used, which ensures rapid lysis of blood clots followed by a delayed clipping operation of the aneurysm neck.

In 25% of patients there is a convulsive syndrome on the first day and, in some cases, in a remote period. Although there are no significant differences in mortality and repeat hemorrhages, anticonvulsant therapy is recommended. First of all, it is necessary to assess the patient's condition in order to avoid re-hemorrhage (with the development of seizures in the delayed period or after surgical treatment). With the epistatus: diphenin IV in a dose of 20 mg / kg, at a rate no faster than 50 mg / min for 20-40 minutes under ECG and AD control, if ineffective - additionally diazepam 10-20 mg or lorazepam 4-8 mg , with further inefficiency - phenobarbital 10 mg / kg at a rate of 100 mg / min, followed by intubation and introduction of the patient into anesthetic sleep. With single convulsive attacks - depakin chrono (250 mg / day and above), lamotrigine, which is also an inhibitor of the release of glutamate (lamiktal - 75-100 mg / day with titration of the dosage according to efficacy).

Neurotransmitter deficiency is corrected by the appointment of MAO 2 inhibitors (Umeks 20-40 mg / day), drugs (sinemet nakom, madopar 500-1000 mg / day).

For patients with altered consciousness, respiratory disorders, infectious and inflammatory complications (pneumonia, uroinfection, development of pressure sores) are characteristic, forming the need for antibiotic therapy. The latter should be carried out under the control of the sensitivity of the flora to the drugs used and start with semisynthetic penicillins with resistance to beta-lactamase strains (up to 6-8 g / day) with the addition of cephalosporins (4-8 g / day), quinolones, in some cases, and imipenems .

When the patient is in the comatose or vegetative state for a long time, the catabolism is activated with the increase in cachexia, which requires the introduction of anabolic steroids (retabolil, nerobolil 2 ml SC 1 times / 2 days) and immunomodulators (decaris, splenin) into the therapeutic complex.

The features of the regime are as follows:

• strict bed rest;
• full physical and mental rest;
• control of physiological dispatches (often repeated ruptures of aneurysms occur during the act of defecation);
• turns in bed with treatment of places of possible formation of decubitus, vibromassage of the thorax;
• high-calorie nutrition (in comatose state through the nasogastric tube, changing at least 3-4 times a day to avoid pressure ulcers on the mucous membrane) to 7000 kcal / day.

Subacute period is carried out using nootropics (nootropil 2,4-3,6 g / day, pantogam 2-3 g / day) drugs, neurometabolites (cerebrolysin 5- \ 10 ml / day), vasoactive (nicergoline (sermion) 4-8 mg / day IV or IM followed by oral continuation, vinpocetine (Cavinton IV infusion 2-4 ml / day for 200 ml isotonic r-ra followed by 30-60 mg / day for 3 doses) in the absence contraindications (heart rhythm disturbances, valvular heart pathology, chronic cardiac and respiratory insufficiency, propensity to hypotension, expressed as roskleroz). An active physiotherapy, manual correction of existing Gosia functional defect. Displaying a spa treatment in the local health centers after 1-1.5 months. After surgery with good and satisfactory functional outcomes.

[2], [3], [4], [5], [6], [7]