Instrumental diagnosis

Laboratory and instrumental methods of diagnosis of PE

Pulmonary embolism is diagnosed using varieties of techniques such as chest X-ray, blood gas analysis and an electrocardiogram, D-dimer, echocardiography, spiral computed tomography, contrast-enhanced (CT angiography) of the chest, ventilation-perfusion lung scintigraphy, angiography, and other methods of diagnosis of thrombosis of deep lower limbs (ultrasound, CT venography).

 Electrocardiography (ECG) is most widely used method of investigation for PE. The ECG investigation shows the present of arrhythmias, conduction disorders , voltage and complex ventricular repolarization process, signs of overload of the right heart.

• Acute pulmonary embolism leads to the sudden appearance of pulmonary hypertension and development of acute pulmonary heart disease . The following signs have been shown on ECG in patients with pulmonary embolism: 
• Q _III -S _I (QR _III -RS _{I)  pathology}
• Hoisting ST segment in leads III, aVF, V _1.2 and discordant reduction ST segment in leads I, aVL, V _5.6.
• Appearance of negative T waves in leads III, aVF, V _1.2.
• Complete or incomplete right bundle branch block.
• Signs of overload right atrial (P-pulmonale) in leads II, III, aVF.
• Rapid positive dynamics of these changes while improving the patient's condition.

These ECG changes occur only in 15-40% of cases and more common with occlusion of the lumen of the pulmonary artery by half or more, however ECG remained normal in more than 27% cases of pulmonary embolism.

One of the major signs of acute pulmonary heart disease is the electrocardiographic Mc Jin-White syndrome (S _I Q _III T _III ): sudden appearance of deep dents S _I and Q _III , negative T _III . 

Chest X-ray

Chest X-ray - method has low sensitivity and specificity for the diagnosis of pulmonary embolism.  The main aim of radiography without contrast is to exclude other conditions that are similar to the clinical picture of pulmonary embolism (pneumonia, cancer, pneumothorax, pulmonary edema, and others). 

Radiological signs that may be associated with PE: raise diaphragm on the affected side; infiltration of the lung tissue (after 12-36 hours from onset); bulging of pulmonary artery;  right ventricular hypertrophy; enlargement of the superior vena cava and others. These symptoms only with a certain degree of probability may be associated with the occurrence of pulmonary embolism, and only in cases where they are combined with the described clinical symptoms of embolism (shortness of breath, chest pain, etc.).

                                                        

Radiographic signs of pulmonary embolism (Scheme Heinrich F., 1981): 1 - high dome of diaphragm; 2 - pleural effusion; 3 - lung infarction; 4 - "open" vessels at the root of lung contours; 5 - contralateral lung congestion; 6 - dilatation of the right ventricle; 7 - dilatation unpaired veins and the superior vena

symptoms of pulmonary embolism:

• Symptoms of acute pulmonary heart disease.
• The symptoms of impaired blood flow in the pulmonary artery (changes roots, pulmonary drawing).
• Symptoms of pulmonary infarction.

 Laboratories indicators

 The D-dimer is the most important laboratory indicator for diagnosing pulmonary embolism . In the analysis of blood gasses,  most common symptom of pulmonary embolism is a drop in oxygen partial pressure in arterial blood, which is observed at 13% occlusion of the pulmonary vascular bed, hypocapnia and respiratory alkalosis due to compensatory hyperventilation. Hypercapnia (increased PaCO2) is possible in extremely severe cases, due to pulmonary edema. Note Normal blood gas levels do not exempt diagnosis of pulmonary embolism.

The occurrence of pulmonary infarction will lead to mild hyperbilirubinemia, leukocytosis and increased ESR. Transaminase and creatine phosphokinase usually not changed, which is of great important in the differential diagnosis of PE with myocardial infarction, but the levels of LDH, alkaline phosphatase may increase. The appearance of proteinuria and microscopic haematuria may be caused by hypoxia and impaired renal hemodynamic 

D-Dimer

D-dimer is a fibrin degradation product. Its plasma level is increased by thrombus formation, since it is always simultaneously activated by fibrinolytic system. Thus, a normal level of D-dimer makes the diagnosis of pulmonary embolism or deep vein thrombosis (DVT) is unlikely. Alternatively, fibrin can be formed by a number of other pathological conditions such as malignant tumors, inflammation, necrosis, dissecting aortic aneurysm et al., I.e.  D-dimer is not specific for PE, and a positive result has a low predictive value in its diagnosis. In addition, increasing the specificity of D-dimer for PE decreased during pregnancy and with age, accounting for <10% of patients older than 80 years.

Diagnosis of deep vein thrombosis (DVT) (US deep venous with compression tests, CT venography, MR venography)

In 90% of cases of pulmonary embolism are the source of blood clots in the deep veins of the lower extremities.  

Treatment

General overview, aims and objectives of the treatment

The aim of therapeutic measures in PE is to normalize or improve lungs perfusion, preventing the development of severe chronic pulmonary hypertension.

This can be achieved by:

• Suppression of thrombosis.
• Activating lysis of thromboembolism.
• Preventing further thrombus formation.
• Post syndrome treatment.

 Tactical measures on the acute phase PE.

5.                   Strict bed rest for the prevention of recurrence of pulmonary embolism.

6.                   Catheterization of central vein for infusions and determining the central venous pressure CVP.

7.                   Immediate bolus heparin to prevent further thrombogenesis(thromb formation )

8.                   Inhalation of oxygen-air mixture.

9.                   The struggle with the shock (hemodynamic support).

10.               thrombolysis or embolectomy .

11.               When complications of a heart attack, pneumonia antibiotic therapy is prescribed.

treatment of embolisn also aims at:

• Normalizing hemodynamic parameters (including infusion therapy, administration of positive inotropic drugs).
• Restoring the permeability of pulmonary artery (thrombolysis or embolectomy).

Pain relief

• Intravenously:
• Fentanyl 1-2 ml of 0.005% solution with 2.1 ml of 0.25% solution of droperidol .
• Or 0.5-1 ml of a 1% solution of morphine with 0.4-0.7 ml of 0.1% solution of atropine .
• Or other analgesics

Note: These medications are only administered by an anesthesiologist.

Morphine 1% - 1 ml with diluted solution of 0.9% sodium chloride and 20 ml (1 ml of the resulting solution contains 0.5 mg of active substance) and administered intravenously by fractional 4-10 ml (2.5 mg or ) every 5-15 minutes to eliminate pain and shortness of breath or until there are side effects (hypotension, respiratory depression, vomiting).

 Note also that opioids are contraindicated in acute abdominal pain, convulsive disorders, heart failure due to chronic lung disease.

 Hemodynamic and respiratory support

Acute right ventricular failure, leading to a decrease in cardiac output, is the main cause of death from pulmonary embolism. Thus, maintenance therapy is essential component for the treatment of pulmonary embolism. 

In PE patients with decreased cardiac index, but with normal BP, moderate infusion of (500 mL rheopolyglucin and dextran) can improve hemodynamic. Note that massive fluid therapy can deteriorate the function of the right ventricle due to mechanical distension and also through reflex mechanisms.

If arterial hypotension develops, immediately administer  Dexamethasone (4-8 mg),  Rheopolyglucin 400 ml with introduction rate of 20-25 ml / min; this is important to correct the electrolytes balance. Positive inotropic preparates  ( dopamine , Korotrop); the rate of administration of dopamine depends on the degree of cardiovascular system insufficiency and ranges from 3 to 15 ug / kg / min.

Contraindications of the use of dopamine: pheochromocytoma, ventricular fibrillation. Dopamine should not be mixed with a solution of sodium hydrogen carbonate.

If hypotension remains persistent,  dopamine and noradrenaline can be administered (Risk: cardiac arrhythmias, renal and mesenteric vasoconstriction, decrease blood flow into the internal organs; kidneys and liver

Possible alternative to dopamine administration are the sympathomimetic preparats,  Angiotensin Amide . 

If there is bronchospasm. 

Slowly administer 10 ml of 2.4% solution of aminophylline ( aminophylline ) intravenously; inhalation of salbutamol 2.5 mg (1 Nebula) through nebulizer for 5-10 min and repeat after 20 minutes if there is no positive effect in the first inhalation.  Aminophylline decreases total peripheral vascular resistance and pressure in the pulmonary circulation, increases the sensitivity of the respiratory centres to the stimulating influence of carbon dioxide. Common side effects include tachycardia, tremor, irritability, nausea and / or vomiting. There have been cases of hypotension and heart failure after rapid administration of aminophylline. Overdose can lead to death due to the development of cardiac arrhythmias or seizures. When to administer aminophylline?  When systolic blood pressure SBP> 100 mmHg, excluding myocardial infarction, absence epilepsy, severe hypertension and paroxysmal tachycardia.

Isoproterenol - inotropes. It also has vasodilatation effect on blood vessels of the lungs, but this is not advantageous as it also has effect on peripheral vasodilatation. A decrease in blood pressure of the right ventricle may lead to its ischemia.

Norepinephrine directly exerts a positive inotropic effect in the right ventricle. Increase in blood pressure due to the stimulation of peripheral alpha-adrenergic receptors also improve blood flow to the right ventricle. Don’t us norepinephrine in hypotensive patients.

Dobutamine has been effective in patients with pulmonary embolism requiring hospitalization in the intensive therapy, dobutamine increased cardiac output, improved tissue oxygenation, increase cardiac index without any significant changes in heart rate, systemic and pulmonary arterial pressure. NOTE -increase in cardiac index may cause ventilation-perfusion mismatch.
Adrenalin  combines the advantages of norepinephrine and dobutamine without expanding system vessels. In shock, in patients with pulmonary embolism, the use of adrenaline can give very good results.

Levosimendan could improve the function of the right ventricle by improving its contractility and pulmonary vasodilation.

 Thrombolysis

Thrombolytic therapy is of first-line treatment in patients with cardiogenic shock and constant arterial hypotension, i.e. patients with pulmonary embolism at high risk . Contraindications to the use of thrombolysis:  myocardial infarction, severe gastrointestinal bleeding

 (e.g., surgery within the last 3 weeks or gastrointestinal bleeding notice less than one month), in patients with life-threatening pulmonary embolism considered as relative.

Absolute contraindications to thrombolytic therapy are only two: severe internal bleeding or recent spontaneous intracranial haemorrhage.

Thrombolytic ( streptokinase or urokinase or recombinant tissue plasminogen activator) are administered intravenously. The method of administration through a catheter into the pulmonary artery has no advantages.

The thrombolytic treatment should be started within 48 hours of the onset of symptoms, but can also be given to patients who have showed symptoms of PE for 6-14 days.

Table below shows the standard use of thrombolytic therapy with streptokinase, urokinase and recombinant tissue plasminogen activator (alteplase).

Heparin should not be administered at the same time  with streptokinase or urokinase, however  alteplase infusion combination is possible.

Thrombolytic treatment is associated with a high risk of bleeding, especially in the presence of concomitant diseases predisposing. Pooled data from a number of randomized studies, the incidence of major bleeding - fatal intracranial hemorrhage and bleeding - 13% and 1.8%. When using non-invasive diagnostic methods PE thrombolytic frequency-associated bleeding is reduced. 

 Approved thrombolytic therapy regimes PE

A drug	mode of administration
streptokinase	250 thousand units’ dose within 30 minutes at a rate of 100 thousand Units / h for 12-24 hours. Fast mode of administration: 1.5 million units within 2 hours.
urokinase	4400 U / kg dose for 10 minutes, followed by administration of 4400 U / kg per hour for 12-24 hours. Fast mode of administration: 3 million units within 2 hours.
Recombinant tissue plasminogen activator	100 mg for 2 hours or 0.6 mg / kg for 15 minutes (maximum dose - 50 mg).