Aneurysm treatment

Treatment for aneurysm rupture depends on the severity of the patient's condition upon admission and is determined by the degree of involvement of the main pathogenetic mechanisms. The key point in the complex of measures is the fact of performing surgical intervention with the exclusion of the aneurysm from the blood flow, preventing a repeated rupture (this feature is not fully met when wrapping the aneurysm - the possibility of a repeated rupture remains for up to 2-3 weeks - the period of formation of the collagen "external frame" of the aneurysm based on the material used for wrapping.

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

• Thus, the acute period is characterized by not yet sharply expressed angiospasm and moderate cerebral edema. Therefore, it is favorable for surgery. This applies only to patients with I, II, III degrees of severity according to H-H. Patients with IV-V degrees are subject to surgery only if they have a large intracerebral hematoma (more than 60 ml) and symptoms of acute occlusive hydrocephalus (imposition of ventricular drainage). Other patients are subject to active conservative treatment until recovery from the comatose state and complete regression of arteriopathy and cerebral edema.
• The acute period is characterized by increasing severity of arteriopathy, ischemia and cerebral edema. All patients are treated conservatively. Surgical intervention is contraindicated except in cases of repeated rupture with the development of vital indications. However, mortality after such operations exceeds 50%. Tactics in relation to progressive cerebrospinal fluid-hypertension syndrome are similar to the previous period.
• The 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 cerebrospinal fluid circulation. During these periods, surgical treatment can be undertaken in patients with I, II, III degrees of severity according to H-N, as well as with IV and V stages, in whom consciousness has been restored, hemodynamics have stabilized and arteriopathy phenomena have regressed according to transcranial Doppler data. However, this is not the most favorable moment for surgery, since the normalization of all brain functions is not complete. But it is precisely during these periods, according to statistical data, that repeated ruptures of arterial aneurysms most often occur. Therefore, it is necessary to strive to perform the operation without waiting for the “cold” period, thereby preventing a repeated rupture. Undoubtedly, a month after the rupture, the conditions for surgery are most favorable. But it is more important to save those in whom a repeated rupture occurs within a month, which is about 60% of all cases of aneurysm rupture.

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Emergency care and conservative treatment of aneurysm

Patients with subarachnoid hemorrhages should be transported to a specialized or neurological department (if there is no specialized hospital) to conduct adequate diagnostic measures and rationally select treatment tactics taking into account objective data from the dynamic assessment of the patient's condition. Delayed transportation is possible with stabilization of blood pressure, regression of headache and meningeal syndrome (for patients with I, I, III degrees of severity according to H-N), normalization of the state of vital functions, and the patient's recovery from a comatose state (for patients with IV-V degrees of severity according to H-N).

Treatment tactics for SAH will be considered in connection with the pathogenetic mechanisms involved in the disease.

Therapy for constrictive-stenotic arteriopathy consists of the following components:

• impact on the products of extravascular blood lysis and their metabolites;
• maintaining adequate regional cerebral blood flow in conditions of developed arteriopathy;
• neuroprotective intervention in existing cerebral ischemia.

Any surgical intervention for aneurysmal SAH is accompanied by sanitization of the subarachnoid spaces and, if necessary, the cerebral ventricles, in order to evacuate blood clots, which are a source of oxyhemoglobin and other biologically active substances that activate cyclooxygenase types I and II (COX-1, COX-2), which triggers the metabolism of arachidonic acid with the formation of prostaglandins, thromboxane, and prostacyclin.

Nonsteroidal anti-inflammatory drugs act as antagonists of this process (indomethacin intravenously by bolus of 50 mg/20 min followed by administration of 30 mg/hour for 3 days after aneurysm rupture; naklofen 75-300 mg/day; aspirin and its injectable form acelysin - 0.5-3.0 g/day). After completion of parenteral administration, the drug is continued to be used per os: movalis 7.5-30 mg/day, mesulide (nimesulide) 200-400 mg/day for 1 month. Caution should be exercised if the patient has a peptic ulcer or the development of acute ulcers of the gastrointestinal tract; preference is given to selective COX-2 inhibitors (celebrex, movalis, mesulide), in some cases - with their rectal administration.

Considering the high protease activity of plasma and cerebrospinal fluid, the use of non-specific inhibitors is recommended (contrycal up to 50,000 U/day, trasylol, gordox in equivalent doses). Aminocaproic and tranexamic acids, previously used in the treatment of SAH as thrombolysis inhibitors, also have similar properties. However, at present, their use is significantly limited due to the high risk of developing secondary ischemic disorders against the background of hypercoagulation, despite attempts to correct this process by adjuvant administration of heparin.

The concept of ZN therapy (Hypertension, Hypervolemia, Hyperhydratation) is mandatory in the therapy of arteriopathy in SAH, especially indicated in the development of clinical arteriopathy and delayed ischemic deficit. Hypertension is maintained at the level of systolic BP 160-180 mm Hg, diastolic BP 80-100 mm Hg (an increase in BP by 20-100 mm Hg from the initial). Controlled arterial hypertension is achieved by using vasopressors (dopamine), glucocorticoids, parasympathetic blockers (non-selective anticholinergics - atropine sulfate, etc.). Hypervolemia and hemodilution are necessarily accompanied by measures aimed at improving the rheological properties of the blood (albumin 10 - 20%, native plasma, rheopolyglucin 200-400 ml / day). The total volume of administered solutions is 50-60 ml/kg/day with hematocrit monitoring (up to 0.40). Administration of 5% dextrose (glucose) solution 500 ml/day is acceptable. Hypertonic glucose solutions are not recommended due to the possible development of hyperglycemia with subsequent acidosis of brain tissue, which aggravates ischemic damage.

It is recommended to use medium-therapeutic doses of unfractionated heparin (up to 10,000 U per 72 days), which has antiplatelet activity. In addition, by neutralizing thrombin, it weakens its stimulating effect on prostaglandin synthesis and protects the administered indomethacin from thrombin inactivation. It is more preferable to use low-molecular heparin (fraxiparin - 0.6-0.9 ml subcutaneously in the periumbilical region twice a day for 14-18 days). Pentoxifylline is indicated as a preventive measure against the formation of erythrocyte thrombi at a dosage of 400-1200 mg/day intravenously in 2-3 administrations.

This therapy is optimal for use in the postoperative period with AA excluded from the bloodstream. Otherwise, its implementation significantly increases the risk of recurrent hemorrhage. Accordingly, it is preferable to refrain from controlled hypertension, resorting to it when the clinical picture of ischemic damage increases. Similar tactics are desirable for direct anticoagulants. Complications of AN therapy include myocardial infarction and pulmonary edema. Thus, ECG and central venous pressure monitoring is required.

With respect to the effect on the myogenic component of developing arteriopathy, the most effective (according to dynamic angiographic monitoring) in terms of regression of the degree of narrowing of the arterial lumen was the dihydropyridine blocker of Ca2+ potential-dependent channels nicardipine (0.075 mg/kg/hour intravenously for 14 days after aneurysm rupture). Complications with its use include pulmonary edema and hyperazotemia (relevant parameters should be monitored).

A promising drug is a peptide associated with the calcitonin gene, which has vasodilator properties that are realized in the phase of advanced arteriopathy. Its dosage form in the form of prolonged-release tablets is undergoing clinical trials.

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

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

Another dihydropyridine derivative with Ca2+ blocking activity is nimodipine (nimotop). The drug does not affect the degree of narrowing of the arterial lumen, but blocks Ca2 ⁺ potential-dependent channels of neurocytes, reducing the massiveness of the entry of extracellular and release from the depot of Ca2 ⁺ into the cytoplasm (administered intravenously by drip 1 mg/hour for the first 2 hours, then 2 mg/hour for 5-7 days with subsequent transition to oral administration 2 tablets 6 times a day - 7-10, up to 20 days) it is necessary to take into account the pronounced hypotensive effect of the drug, determining the pharmacological antagonism of the undertaken controlled hypertension.

Glucocorticoids have a pronounced dose-dependent inhibitory activity against lipid peroxidase with limitation of free radical formation. In particular, methylprednisolone is recommended for use intraoperatively at 1 mg/ml in physiological solution for irrigation of subarachnoid cisterns with subsequent intracisternal administration through a catheter of 5 ml of the resulting solution per day for 14 days. Parenteral administration of up to 20-30 mg/kg/day causes the expected effect, but exceeding the dose leads to the elimination of the antioxidant effect and even the opposite result.

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

There are schemes of combined use of glucocorticoids and Ca ²⁺ channel blockers: UN - diltiazem (O) 5 mcg/kg/min intravenously for 2 weeks, 5% dextrose (O) 500 ml/day, hydrocortisone (H) - 1600 mg on the first day after hemorrhage with subsequent gradual reduction of the dose. A complication of this type of therapy in some cases is the development of atrioventricular block, which regresses on its own 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 with an amino group in the non-glucocorticoid part of the molecule with a significant increase in antioxidant activity - binding of hydroxyl and peroxyl radicals) - tirilazate mesylate. In phase III clinical trials, it demonstrated fairly high efficiency in combination with nimodipine, especially in males.

Endogenous antioxidants, the deficiency of which occurs during secondary ischemia, are superoxide dismutase (SOD) (the drug polyethyleneglycol-conjugated SOD Dismutek has passed phase III of clinical trials), tocopherols (alpha-tocopherol, beta-carotene - their effectiveness is observed only with prophylactic use, since active prevention of lipid peroxidation is directly related to the concentration of alpha-tocopherol on cell membranes at the time of ischemia - up to 800-1000 mg / day intramuscularly or orally). Donors of hydroxyl groups for neutralizing free radicals are ascorbic (vitamin C - up to 2000 mg / day) and retinoic (vitamin A - up to 200,000 IU / day) acids. Inhibition of free radical formation can be achieved by blocking the activity of xanthine oxidase (folic acid - calcium folinate - 32.4 mg 2-3 times/day intramuscularly), chelation of iron and copper (deferroxamine, EDTA, cuprenil).

Another aspect of the damaging effect of ischemia on brain cells is the process of excitotoxicity (release of excitatory mediator amino acids: glutamate and aspartate with activation of imEA, AMPA receptors and active entry of calcium into the cell), non-competitively inhibited by ketamine, lidocaine, which is reflected in the following regimens of use: nimodipine - intravenously by drip (the dosage is indicated above) up to 5-7 days with continuation in tablets for 6 days; ketamine - 1 mcg / kg bolus followed by the introduction of 3 mcg / kg / min 5-7 days; lidocaine - 1.5 mg / kg bolus and then 1.2 mg / kg / min. The scheme justifies itself when used in patients with grades III-V severity according to H-N, while with a mild degree of SAH there is no effect.

The following combination can be used for pharmacological protection of the brain in the perioperative period or in case of pronounced negative dynamics during delayed ischemic brain injury: sodium thiopental - 1-1.5 mg IV (250-350 mcg IV), nimodipine - 15-20 mg IV (2-4 mg IV), ketamine - 400-500 mg IV (100-150 mg IV). The IV route of administration is more optimal, since it causes less hemodynamic depression, which negatively affects the overall outcome and requires supplementation of the complex with vasopressors.

Under physiological conditions, magnesium ions serve as endogenous modulator of IMBA receptors, and hypomagnesemia formed during ischemia is corrected by administration of magnesium sulfate in doses of about 3.5-5 mg/kg, which provides their blockade. Presynaptic inhibitors of glutamate release are riluzole (rilutek), lubeluzole.

Additional methods of neuroprotection include sodium oxybutyrate (up to 80 ml/day), sodium thiopental or hexenal (monotherapy up to 2 g/day), benzodiazepine tranquilizers (diazepam 2-6 ml/day). A non-drug method of increasing the brain's resistance to hypoxia and ischemia is craniocerebral hypothermia with a decrease in body temperature by 1-2° C.

In a significant number of cases, SAH is accompanied by a spontaneous rise in blood pressure, which was absent before the disease. If the severity of the patient (IV - V, in some cases III H-H) makes it impossible to perform aneurysm clipping, this condition becomes pathological and increases the risk of repeated rupture of the aneurysm, requiring the administration of antihypertensive drugs.

The standard first-line therapy in this situation is alpha- and beta-adrenergic blockers, which exhibit pathogenetic activity (elimination of sympathicotonia, which caused hypertension). But their use is inappropriate in the hypokinetic type of central hemodynamics, which develops in severe SAH.

The following agents are used: potential-dependent calcium channel blockers: phenylalkylamine derivatives (isoptin, finoptin, lekoptin - 40-120 mg intravenously slowly, intramuscularly 3 times a day, orally 120-140 mg / 2 times a day in the form of retard forms - isoptin, calan BK), dihydropyridines (adalat, procardia - 30-120 mg / day in 1 dose, nicardipine - 20-40 mg / day in 3 doses, amlodipine (Norvasc) - 2.5-10 mg / day in 1 dose, felodipine (plendil) - 2.5-20 mg / day in 1 dose), benzodiazepines (diltiazem, dilren - 90-180-360 mg / day in 1 dose).

This group of drugs can be combined with angiotensin-converting enzyme blockers, especially in individuals with a history of hypertension, including renal hypertension - captopril (capoten, tenziomin, alopresin) - 12.5 - 75 mg / day in 3 doses, enalapril (enap, enam, renitek, vasotec) - 5-20 mg / day in 1-2 doses, moexipril (moex) - 7.5-30 mg / day in 1 dose (especially recommended for women in menopause), trandolapril (hopten, odric) - 2-4 mg / day in 1 dose, lisinopril (zestril, prinivil, sinopril) - 5-40 mg / day in 1 dose.

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

In case of resistance of hypertension to standard therapy, ganglionic blockers (pentamine, hygronium, benzohexonium) are used, administered by the method of physiological titration: dissolution of the ampoule in 10 ml of physiological solution and then bolus administration of 2-3 ml of the resulting solution with monitoring of blood pressure after 15-20 minutes (after the effect of the previous dose has occurred). The duration of action of the drug is 15-30 minutes.

In case of severe hypertension and lack of response to ganglion blockers, direct vasodilators are used: sodium nitroprusside (0.5-1.5 mg/kg/min), prostaglandin E2 (IV drip 90-110 ng/kg/min), nitroglycerin (perlinganit, nitro, nitro-mak, nitro-pol - the contents of the ampoule are diluted in 10 ml of distilled water, and then added to a bottle with 5% glucose solution (200-400 ml), administered by jet/drip under blood pressure monitoring. Stopping the administration after 2-3 minutes restores the original blood pressure figures.

In the context of hypothalamic disorders, a syndrome of increased secretion of atrial natriuretic peptide is observed, manifested by hypovolemic hyponatremia and corrected by the use of fludrocortisone. This situation should not be mistakenly assessed as a syndrome of inappropriate secretion of antidiuretic hormone with hypervolemic hyponatremia, requiring fluid restriction.

Quite often, cerebrocardial syndrome is observed, consisting in a violation of the central regulation of cardiac activity (lengthening of QT, sharpening of T and P waves, shortening of the PK interval, wide V waves - associated with an unfavorable outcome). In this case, correction with sympatholytic drugs (beta-blockers, Ca ²⁺ channel blockers), introduction of metabolic drugs into the complex (riboxin 10-20 ml / day, mildronate up to 20 ml / day), ECG monitoring, central hemodynamics with correction of the developed disorders is advisable.

Respiratory disorders with neurogenic pulmonary edema are also of a central nature, the course of which is aggravated by the suppression of the cough and pharyngeal reflexes (in patients with stage IV-V H-H) with aspiration of the contents of the oral cavity and, in some cases, the development of Mendelson's 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 normal breathing is not restored within 10-12 days, a tracheostomy is indicated. Prevention of inflammatory processes is carried out by prescribing antibacterial drugs, including inhalation (ultrasonic spraying of a mixture consisting of 500 ml of saline, 200,000 U of penicillin, 250 U of monomycin, 10 ml of 5% kanamycin solution, 10 ml of 5% ascorbic acid solution and chymotrypsin (20 mg) with hydrocortisone (250 mg) 2-4 times a day). Bronchoscopic sanitation of the tracheobronchial tree is carried out with the introduction of soda solutions, antibiotics, hydrocortisone, and proteolytic enzymes intrabronchially. During mechanical ventilation, increased exhalation pressure is created, and sufficient oxygen saturation is maintained.

The development of central hyperthermia requires neurovegetative blockade using aminazine, pipolfen, droperidol, hypothermia by administering cooled infusion solutions, and hypothermia of the main vessels.

The manifestation of the stress reaction in SAH is the development of acute gastrointestinal ulcers with bleeding, which significantly complicates the course of the disease. Preventive measures in this situation include the administration of H2 blockers (cimetidine, ranitidine), and the use of sedative therapy.

The third significant aspect of the pathology under consideration, requiring specific correction, is the increase in intracranial pressure. Cerebral edema is essentially a compensatory reaction in response to an increase in the content of toxic products in the brain tissue and, being compensated, does not require correction (I - III st. H-H). In case of edema decompensation and the development of dislocation syndrome, it is indicated to ensure a hyperventilation regime with the creation of respiratory alkalosis, the introduction of dexamethasone 8-20 mg / day, methylprednisolone 500-1000 mg / day, albumin, native plasma. Osmotic diuretics are used as a last resort up to 0.5-0.8 g / kg / day in case of a threat of developing clinical manifestations of brain wedging.

Another aspect of this problem is hydrocephalus. Acutely developing, it is a consequence of occlusion of the cerebrospinal fluid pathways and manifests itself as a disorder of consciousness and focal neurological deficit. Delayed (normal pressure hydrocephalus) manifests itself as progressive dementia, ataxia and pelvic disorders. Conservative therapy consists of the use of acetazolamide (diacarb, radicarb - 0.5-2.0 g / day), but, as a rule, is ineffective and requires the imposition of ventricular drainage (temporary or permanent). The effectiveness of such manipulation completely depends on the initial level of perfusion of the affected areas of the brain (with regional cerebral blood flow less than 25 ml / 100 g / min, there is no restoration of lost functions). To prevent such phenomena, a number of foreign clinics use endolumbar and intracisternal administration of tissue plasminogen activator (after preliminary endovascular thrombosis of the aneurysm), which ensures rapid lysis of blood clots followed by delayed clipping of the aneurysm neck.

In 25% of patients, convulsions are observed during the first day and, in some cases, in the late period. Although no reliable differences in mortality and recurrent hemorrhages were found, anticonvulsant therapy is recommended. First of all, it is necessary to assess the patient's condition to exclude recurrent hemorrhage (if seizures develop in the late period or after surgery). In case of status epilepticus: diphenin intravenously at a dosage of 20 mg/kg, at a rate of no faster than 50 mg/min for 20-40 minutes under ECG and blood pressure control, if ineffective - additionally diazepam 10-20 mg or lorazepam 4-8 mg, if further ineffective - phenobarbital 10 mg/kg at a rate of 100 mg/min, followed by intubation and putting the patient into anesthetic sleep. For isolated seizures - depakine chrono (250 mg/day and higher), lamotrigine, which is also an inhibitor of glutamate release (lamictal - 75-100 mg/day with titration of dosage according to effectiveness).

Neurotransmitter insufficiency is corrected by prescribing MAO 2 inhibitors (yumex 20-40 mg/day), drugs (sinemet nacom, madopar 500-1000 mg/day).

For patients with altered consciousness, respiratory disorders, infectious and inflammatory complications (pneumonia, urinary infection, development of bedsores) are typical, which form 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 begin with semi-synthetic penicillins with resistance to beta-lactamase strains (up to 6-8 g / day) with the addition of cephalosporins (4-8 g / day), quinolones, and in some cases imipenems.

If the patient is in a comatose or vegetative state for a long time, catabolic processes are activated with increasing cachexia, which requires the introduction of anabolic steroids (retabolil, nerobolil 2 ml subcutaneously once a day) and immunomodulators (decaris, splenin) into the treatment complex.

The features of the regime are as follows:

• strict bed rest;
• complete physical and mental rest;
• control of physiological functions (often repeated ruptures of aneurysms occur during the act of defecation);
• turning in bed with treatment of areas where pressure sores may form, vibration massage of the chest;
• high-calorie nutrition (in a comatose state through a nasogastric tube, changed at least once every 3-4 days to avoid bedsores on the mucous membrane) up to 7000 kcal/day.

The subacute period is carried out using nootropic (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 intravenously or intramuscularly with subsequent continuation orally, vinpocetine (cavinton intravenously drip 2-4 ml/day in 200 ml of isotonic solution with further continuation 30-60 mg/day in 3 doses) in the absence of contraindications (heart rhythm disturbances, valvular heart disease, chronic cardiac and respiratory failure, tendency to hypotension, severe atherosclerosis). Active physiotherapeutic, mechanical correction of the existing functional defect is carried out. Sanatorium and resort treatment in local sanatoriums after 1-1.5 months after the operation with good and satisfactory functional outcomes.

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