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Cardiologic society (2000)

— Aspirin per os 250-500 mg (the first dose is masticated), later, in absence of apparent contraindications, by 75-325 mg/day;

— Nitrates up to a disappearance of symptoms or appearance of side effects (head-aches or hypotension);

— Blockers under AP control and HR to 50-60 per min.;

— Heparin. Non-fractionated heparin (NFH with molecular weight of
12000-15000 dalton) applied for these purposes for a long time has a number
of drawbacks. Its application requires a systematic control of activated partial
thromboplastin time (APTT) in order to avoid bleeding from the overdosage.
NFH is being bound with blood plasma proteins unpredictably that interferes
with its maintenance therapeutic concentration in blood. NFH has a poor
influence on thrombin being a part of the thrombus itself. Low-molecular
heparins (LMH) with the weight of 400-500 dalton are deprived of all these
drawbacks. They have persistent and predictable antithrombotic effect with
minimal danger of hemorrhage complications that excludes a need in
systematic homeostasis control and allows to carry out prevention and

treatment of thromboses even in the course of surgeries. Clinical application of LMH started since the end of the 80-ties, and one of them is a widely known enoxiparin (clexane). It is manufactured in ready to use syringes by 20, 40 and 80 mg. For treatment of instable angina pectoris and acute phase of myocardial infarction without Q wave clexane is used in combination with aspirin. It is introduced subcutaneously (do not introduce intramuscularly!) in the dose of lmg/kg every 12 hours. Treatment is continued up to patient's clinical stabilization (2-8 days), it is accompanied by per os intake of aspirin by 100-325 mg once a day.

LMHs are contraindicated in thrombocytopenia, acute uncontrollable bleeding, recently endured hemorrhagic insult. It is not recommended to combine them with higher (analgetic and antipyretic) doses of aspirin, nonsteroid analgetics, glucocorticoids. When complications arise clexane is neutralized by protamine sulfate (i/v 1 mg per every 1 mg of clexane).

If a determination of troponins is impossible, in high degree of AMI risk by clinical findings and ECG, administration of heparin — NFH intravenously or LMH (clexane) subcutaneously, is continued. When signs of ischemia are maintained, a coronaroangiography is recommended in institutions having a potential and experience to determine the degree of atherosclerotic injury of coronary arteries and to take a decision of invasive intervention (percutaneous balloon stenting of the artery or aortocoronary bypass).

In low degree of risk a symptomatic therapy is continued, a loading test (veloergometry or treadmill) is carried out before patient's discharge.

A thrombolytic therapy for the patients with ACS without STsegment elevation is not recommended.

A transitory segment elevation may be noted in Prinzmetal's angina (vasospastic) requiring nitrites application.

If a stable elevation of ST segment is determined on the ECG, it is the evidence of complete acute coronary artery occlusion, developing macrofocal transmural AMI and an immediate carrying out of thrombolysis or angioplasty is required.

A therapy directed to prevention of complications and decrease of probability of unfavorable outcomes of the disease is carried on for all patients with AMI having no contraindications for this.

The most important measure is an urgent restoration of blood flow through infarct-associated artery. In so doing, no more than 90 minutes must elapse from the appearance of symptoms of disease to the start of thrombolytic therapy (from the bell to the needle), and the time from the moment of admission to the hospital to the start of treatment (from the door to the needle) should be 20-30 min. This period is the most significant index of the work of medical institution. A decision of necessity to apply thrombolytic therapy must be taken in the shortest time possible, however, it is not always feasible to establish a

correct diagnosis for this period of time. Therefore, from practical point of view in presence of acute coronary syndrome with ST segment elevation on the ECG, an immediate thrombolytic therapy is needed, and when ST is on the isoline — ECG monitoring.

Thrombolytic therapy (TUP in the first 6 hours since the onset of the disease exceeds all the rest medicamentous methods of treatment.

Indications for carrying out TLT: on the ECG there is an elevation of ST segment more than 0.1 mV or bundle branch block in the first 12 hours after an admission to the in-patient department. A change of ST segment must be noted no less than in two adjacent ECG leads.

Contraindications for thrombolytic therapy:

1. Absolute:

— gastrointestinal hemorrhage for the last month;

— insult endured for the last 6 months;

— hemorrhagic diathesis in anamnesis;

— dissecting aortic aneurysm;

— surgical operation or head injury for the last three months;

— severe trauma;

— metastatic tumors of the brain.

2. Relative:

— transitory disorders of cerebral blood circulation for the last 6 months;

— application of indirect anticoagulants;

— pregnancy;

— hypertension (AP>180 mm Hg);

— recent laser treatment of the retina;

— puncture of vessels, uncontrollable by compression;

— traumatic CPCR.

Activators of fibrinolysis recommended for carrying out thrombolytic therapy in AMI are given in Table 17.

Estimation of effectiveness of thrombolytic therapy in clinic may be carried out by invasive and noninvasive methods.

The invasive method of estimation lies in the determination of coroniry artery perfusion by the findings of coronarography (absence of perfusion, penetration without perfusion, partial perfusion and complete perfusion).

The noninvasive method of estimation of effectiveness of thrombolytic therapy is less precise and carried out by indirect signs of reperfusion:

1. arresting or significant decrease of painful syndrome in 30-60 minutes after beginning of thrombolytics administration;

2. a normalization or significant diminution of ST segment elevation;

3. a sharp increase of CPK (by 20^0%);

4. Appearance of reperfusion arrhythmias:

— accelerated idioventricular rhythm;

— ventricular extrasystolic arrhythmia;

Table 17 Activators of fibrinolysis for carrying out thrombolytic therapy

— ventricular tachycardia; „

— ventricular fibrillation.

The most effective preparation is alteplase, the least effective — strepto­kinase.

The time of carrying out a thrombolytic therapy, from the start of development of AMI symptomatology, exerts substantial influence on the efficiency of treatment. Therefore, fibrinolytics must be applied in the first 2-6 hours from the onset of myocardial infarction, but still their application is permissible and 6-20 hours later.

When a pain syndrome and ST elevation are maintained, we may suppose that these patients have a protracted development of AMI in developed collateral blood circulation.

To the shortcomings of thrombolytic therapy we may refer:

1) absence of reperfusion in some patients;

2) reocclusion — reinfarction conditioned by atherosclerotic plaque and incompletely lyzed thrombus, that becomes a substrate for reocclusion development, besides, a mechanism of thrombogenesis may be triggered again on the "fresh" wound surface. Vasoconstriction caused by thrombolytics contributes to this.

Complications of thrombolytic therapy:

1) hemorrhages, primarily, from the places of punctures;

2) hemorrhagic insult in 0.5-1.5% cases;

3) allergic reaction, in application of streptokinase in particular;

4) hypotension associated with dilatation in response to the action of bradykinins and other BAS, as well as associated with vagal reflexes in the reperfusion of the left ventricular posterior wall;

5) reperfusion arrhythmias in 60-80%) cases that, because of their high rate, serve as noninvasive markers of reperfusion.

Just after a lysis, clexane (40 mg) is introduced intravenously with further subcutaneous administration by 40 mg every 8 hours for 4 days.

^-blockers are indicated for all patients with AMI after thrombolysis for additional diminution of the infarction area, decrease of the rate of primary ventricular fibrillation, prevention of renewal of angina and reinfarction. One has to use blockers without internal sympathomimetic activity (propranolol, timolol, atenolol, metoprolol). In the terms less than 6 hours after AMI development a drop-by-drop administration of ^-blockers is indicated with subsequent changeover to peroral intake under HR and AP control. Duration of blockers' application is extended for a year, and, sometimes, for the whole life. Contraindications for their use are bradycardia (HR less than 60 per min), hypotension (AP< 100 mm Hg), 3-rd - 4-th degree A-V block, grave obstructive diseases of the lungs, bronchial asthma and insulin-dependent diabetes mellitus.

Nitrates after thrombolytic therapy are indicated in presence of cardiac failure, hypertension and anginal pain. Method of nitrates' administration is intravenous drop-by-drop in the first 24-48 hours. It is important not to permit AP decrease lower than 80 mm Hg, since it may lead to the increase of MI dimensions.

Antagonists of angiotensin-converting enzyme (ACE) are indicated for all patients with left ventricular dysfunction that disappears in the course of 24 hours. Here, an adequate dose selection is necessary in order not to allow a hypotension. In initial AP _t lower than 100 mm Hg one cannot apply ACE.

The dosage of ACE inhibitors starts from small single doses with their continuous increase up to a complete recommended dose in the course of 24-48 hours (captopril, lisinopril).

Antiarrhythmic preparations. Lidocaine, with preventive purpose now, is not recommended, since decreasing the risk of fibrillation development, lidocaine increases the risk of asystole development.

At present, Ca⁺⁺ antagonists are not recommended since they exert no effect on the size of infarction focus, reinfarction rate and lethality. Some authors note a tendency to a growth of unfavorable outcomes when C⁺⁺ antagonists are applied. In the late terms of AMI they are used only by indications.

Mg⁺⁺ is not used in this period.

There are some data of positive results in application of non-hemoglobin carrier of gases — perftoran in the dose of 6 mg/kg as a single dose in the first 6 hours after AMI development.

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