Recently the importance of pulmonary embolism as a relatively common cause of death has become more widely appreciated, despite gross underestimation of this problem by the prevalent statistics. Pulmonary embolism is quite common, but often unrecognised clinically which suddenly presents without much warning.
Incidence:
The true incidence of pulmonary embolism is unknown and estimates of its frequency vary, depending on the diagnosis i.e. clinical, following investigation or postmortem studies. A mortality survey estimated 21,000 deaths in U.K. each year from pulmonary embolism. Recent survey shows that around 650,000 patients in U.S.A. are annually afflicted with symptomatic pulmonary embolism. No definite data is available in context to the incidence of pulmonary embolism in India.
Aetiopathogenesis:
Virchow in 1846 showed that pulmonary ’embolii’ were due to impaction of dislodged venous thrombi formed elsewhere. Thus, when considering the etiology of pulmonary embolism, we primarily consider the causes of peripheral venous thrombosis.
This involves the triad as postulated by Virchow, namely:
(1) Changes in blood flow (Stasis)
(2) Changes in vessel wall (Endothelial damage)
(3) Changes in blood (Hypercoagulability)
(1) Changes in Blood Flow:
Stasis may predispose to venous thrombosis, particularly in presence of other risk factors. Stasis can occur as a result of low cardiac output states (heart failure), prolonged bed rest or other causes of restriction of lower limb venous return e.g. in chronically hospitalised patients; it may also occur in passengers following long air flights.
(2) Changes in Vessel Wall:
The current concept is that an injured vessel wall/platelet interaction is probably the starting point of a thrombus. Electron microscopy demonstrates that under certain circumstances, platelets gain access to the subendothelial layers of blood vessels; ADP and other substances are released which helps platelets to stick together.
(3) Changes in Blood:
Attention has been focused on the interaction between blood platelets and coagulation mechanism in relation to vessel injury. Thrombosis begins by deposition on vascular endothelium of masses of platelets; platelets liberate thromboplastins which convert prothrombin to thrombin and thus result in clot formation. The coagulation mechanism is probably dominant in determining the ultimate size of thrombus.
High Risk Patients:
Clinical, latest diagnostic aids and post-mortem studies have led to the identification of certain risk factors in the development of venous thrombosis and subsequent pulmonary embolism.
Although lower extremities are usually considered the source of emboli, they may also arise from other sites like axillary, hepatic, portal or renal veins. Embolus may also arise from the right heart in certain conditions, like acute right ventricular myocardial infarction, cardiomyopathy and most important in our country, rheumatic carditis, particularly in presence of atrial fibrillation where there is dislodgement of thrombus from right atrial appendage. Besides, amniotic fluid, fat, air and bone-marrow particles have been implicated on occasions in the production of pulmonary embolism.
Clinical spectrum of pulmonary thrombo embolism:
Pulmonary embolism includes the following clinical syndromes:
(1) Acute minor embolism
(2) Acute massive embolism
(3) Subacute massive embolism
(4) Recurrent thrombo-embolic pulmonary artery hypertension (vide infra)
(1) Acute Minor Embolism:
This occurs due to impaction of small blood clot in a distal pulmonary artery. Hence, there is preservation of collaterals and no haemodynamic consequences. Clinically it may be silent, or there may be features suggestive of pulmonary infarction like pleuritic pain, haemoptysis, pleural rub and occasionally fine crepitations.
(2) Acute Massive Embolism:
The volume of embolic material in this case must be sufficient to obstruct 50%, or more of the pulmonary arterial tree. In contrast to minor embolism, haemodynamic disturbances, rather than pleural involvement are the mode of presentation. Acute massive embolism is the commonest cause of acute cor pulmonale.
The haemodynamic disturbances are categorized as follows:
a. Acute reduction in cardiac output
b. Acute disturbances of ventilation and perfusion.
c. Acute right ventricular failure
Acute Reduction in Cardiac Output:
The sudden reduction in cardiac output due to obstruction to right ventricular output is responsible for the common presenting symptom of massive embolism i.e. collapse in a patient who is severely dyspnoeic. The syncope and shock may be almost momentary or prolonged in severe cases.
Acute Disturbance of Ventilation and Perfusion:
This results in acute dyspnoea, tachypnoea and hyperventilation. The resultant characteristic finding of low arterial PO2 (average-50 mm Hg) and low arterial Pco2 (average-35 mm Hg) may be found in proportion of cases due to right to left shunting across a patent foramen ovale. In some cases due to shunt like effect due to mismatched ventilation-perfusion of lung.
Acute Right Ventricular Failure:
This occurs as a result of sudden obstruction of right ventricular outflow tract leading to acute dilatation and poor contractibility of right ventricle. This resultant chest pain due to low cardiac output and coronary insufficiency erroneous diagnosis of myocardial infarction, however, while a patient of myocardial infarction is orthopnoeic a patient of pulmonary embolism prefers to lie flat. Clinically there is raised jugular venous pressure and appearance of summation gallop. Haemodynamically, there is moderate elevation of pulmonary arterial and right ventricular pressures.
(3) Subacute Massive Embolism:
In these cases, patients have a long history extending for days or weeks. Unlike in acute embolism, patients with subacute embolism frequently give history suggestive of deep vein thrombosis, along with episodic pleuritic pain, haemoptysis and gradually progressive dyspnoea. The longer duration results in higher pulmonary arterial pressure as compared to massive embolism.
Aids to Diagnosis:
Diagnosis of pulmonary embolism is aided by the index of clinical suspicion, particularly in presence of high risk factors e.g. sudden appearance of chest pain or syncope or shock in a patient with congestive cardiac failure.
Confirmation of diagnosis requires a number of preliminary as well as sophisticated investigations like of following:
Diagnosis of Deep Vein Thrombosis:
Since it is deep venous thrombosis which leads to pulmonary embolism, hence a discussion on the diagnosis of pulmonary embolism must include recent advances in the diagnosis of deep venous thrombosis.
This involves:
1. Clinical examination which must progress from foot end upwards. Homan’s sign is often unrewarding.
2. Investigations likely to be valuable:
(a) Venography.
(b) Labelled fibrinogen technique- This involves the incorporation of 131I (131 Iodine) labelled fibrinogen into the thrombus.
(c) Ultrasonic flow detector.
Electrocardiogram:
Electrocardiographic abnormalities are seen in 85% of patients with proven acute pulmonary embolism. A normal E.C.G. does in no way exclude the diagnosis of pulmonary embolism since E.C.G. changes may be transient or delayed, serial E.C.G. recordings are particularly useful in the diagnosis of pulmonary embolism.
The electrocardiographic abnormalities are due to diminished coronary perfusion.
The common abnormalities are as follows:
1. Sinus tachycardia is very common. S1 Q3 T3 pattern which simulates acute inferior wall infarction. The absence of current of injury pattern in III, absence of Q in avF and presence of ‘T’ wave inversion in right precordial leads differentiates pulmonary embolism from acute inferior infarction.
2. Incomplete RBBB pattern is more common than complete RBBB pattern which may be transient.
3. Right ventricular strain pattern as characterised by T-inversion in right precordial leads.
4. Clockwise rotation due to acute dilatation of R.V.
5. On rare occasions left sided ECG abnormalities (e.g. ST-T wave changes over V4-V6) may be present due to coexistent coronary artery disease or due to development of coronary insufficiency.
Thus electrocardiography in a case of acute pulmonary embolism not only differentiates it from myocardial infarction, but also excludes coexistent ischaemic or valvular heart disease.
Plain Chest X-Ray:
Radiography of chest is also useful in the differentiation of acute pulmonary embolism from other causes of collapse and shock. Besides, it helps in the identification of preexisting heart or lung disease.
The common radiological abnormalities are:
1. Loss of lung volume as manifested by raised dome of diaphragm.
2. Patchy oligaemia.
3. Abnormalities of pulmonary artery perfusion: due to rapid cut off pulmonary artery there may be ‘plump’ or ‘pear’ shaped hilar shadows.
4. Infarct shadows which are initially wedge shaped but later on may leave linear scars.
5. Changes in the size and configuration of heart.
Biochemical Investigations and other laboratory investigations:
The triad of high LDH, normal SGOT and elevated serum bilirubin though helpful for the diagnosis of massive pulmonary embolism is rarely obtainable.
Serum fibrinogen-fibrin degradation products are usually elevated following an attack of massive pulmonary embolism.
Lung Function Studies:
Very few studies have been performed on the mechanical lung functions close in time to an embolic episode. Sasahara and his colleagues (1967) reported reduction in vital capacity and FEV in 80% or more of a large group of patients, 2/3rd of whom were studied within a week of suspected embolism.
Alveolar gas exchange studies in acute embolic period reveals:
(i) Mismatched VA/Q ratio.
(ii) Reduced diffusing capacity.
(iii) Widened arteriolar alveolar gradients for CO2.
Central Venous Pressure:
It is characteristically elevated due to acute right sided congestive cardiac failure.
Haemodynamic Responses:
Previously there were relatively few data on the hemodynamic studies in acute pulmonary embolism. It is only recently, that the National Co-operative study (Urokinase – Pulmonary Embolism Trial (1973) has recorded haemodynamic measurements in 143 patients with angiographically proved thromboembolism.
The common abnormalities in decreasing order of frequency are:
1. Arterial hypoxaemia.
2. Right ventricular systolic pressure > 25 mm Hg.
3. Elevation in total pulmonary resistance
4. Right ventricular end diastolic pressured > 6 mm Hg
5. Mean pulmonary artery pressure > 20 mm Hg
6. Mean right atrial pressure > 6 mm Hg
7. Decrease in cardiac index (2.7L/min/m2)
Scinti-Scan:
The use of perfusion scan utilising I131 or Te-99m Labelled macroaggregated human albumin have been proved to be useful in the study of pulmonary embolsim.
This investigation was first described by Wagner in 1964 and allows the determination of pulmonary blood flow in vessels as small as 50 micro, m. It is a very sensitive investigation but lacks specificity.
However, combined ventilation-perfusion scan shows perfusion defects unaccompanied by defects of ventilation; a finding specific for pulmonary embolism.
Pulmonary Arteriography:
This established or excludes the diagnosis of pulmonary embolism beyond doubt and also accurately determines the severity and distribution of embolism. Besides, to some extent it helps in determining the age of emboli; a recent emboli producing a convex filling defect while a lysed emboli produces a concave filling defect. The hazards of this investigation are perhaps overestimated.
There are two major angiographic signs of massive pulmonary embolism, namely, intraluminal defects and cut-off an artery. Pulmonary angiography must be carried out via an arm vein in order to avoid dislodgement of thrombi from iliac veins or inferior vena cava that may happen when the femoral route is used.
Differential Diagnosis:
Acute minor embolism must be differentiated from other causes of pleuritic pain and haemoptysis e.g. pneumonia.
Acute massive and subacute massive pulmonary embolism must be differentiated from other causes of collapse and shock.
(4) Recurrent Thrombo-Embolic Pulmonary Artery Hypertension:
The haemodynamic disturbance in this clinical syndrome gives rise to elevated pulmonary artery pressure and resultant right ventricular hypertrophy.
Investigations include preliminary X-ray demonstration of patchy oligaemia, with marked enlargement of main pulmonary artery and the electrocardiographic identification of right ventricular hypertrophy.
Catheterisation studies reveal high right ventricular and pulmonary arterial pressure. Diagnosis is confirmed by the angiographic demonstration of enlarged pulmonary arteries with asymmetric occlusions.
Pulmonary hypertension from recurrent thrombo-embolism must be distinguished from other causes of pulmonary hypertension like mitral valve disease or primary pulmonary hypertension.
Pulmonary angiogram showing dilated pulmonary artery of recurrent thromboembolism.
Management of Pulmonary Embolism:
In minor embolism where there is no haemodynamic disturbance, no treatment is required, except for the relief of symptoms. However, in cases of minor embolism associated with deep vein thrombosis anticoagulant therapy is perhaps a wise precaution against massive embolism.
In contrast, acute massive embolism always heralds therapy:
This involves:
A. Immediate resuscitation
B. Definitive therapy.
Immediate Resuscitation:
The following measures are adopted for the immediate resuscitation of a patient suffering from massive pulmonary embolism:
(i) Oxygen mask or endotracheal intubation.
(ii) External cardiac massage which may also help in the propagation of emboli.
(iii) Use of vasopressor drugs e.g. Metaraminol, Dopamine.
(iv) Correction of metabolic acidosis by I.V. bicarbonate.
(v) Use of plasma expanders like 500 ml of 70% Dextran.
(vi) High dose heparin intravenously (15,000 units) to combat serotonins—mediated vasoconstrictor effect.
If the above mentioned measures fail to resuscitate the patient then one may try:
(i) Intrapulmonary urokinase infusion
(ii) Emergency pulmonary embolectomy using inflow occlusion (modified Trendelenburg operation).
(iii) Immediate establishment of partial cardiopulmonary bypass (femoro-femoral bypass); pulmonary angiography may then be confirmed and patient transferred for emergency embolectomy.
Definitive Treatment:
There exists much controversy about the correct treatment of massive pulmonary embolism. It must be remembered that the establishment of diagnosis is a must before performing definite treatment like pulmonary embolectomy, which will obviously be fatal in a case of shock due to any other cause.
The currently available forms of treatment are:
1. Anticoagulants.
2. Thrombolytics.
3. Pulmonary Embolectomy.
1. Anticoagulants:
This involves intravenous heparin therapy in the early stages, replaced later by oral anticoagulants as heparin is tapered off and patient begins ambulation. In the absence of contraindications, the current recommendation is 10,000 units of IV. heparin as a single dose followed by 5,000-7,500 units of IV heparin every 4 hrs after confirmation of diagnosis or 1,000 units/hr by constant infusion.
During heparin therapy, tests for clotting time should be performed regularly and the value should be 2.3 times the normal.
2. Thrombolytics:
Several studies have shown that thrombolytic therapy results in considerably accelerated resolution as compared to heparin therapy. Streptokinase 250,000 units in the first hour, followed by maintenance therapy of 100,000 units over 24 hrs by constant infusion, are the usual adopted regime under steroid cover.
Thrombolytic therapy is contraindicated in conditions like acute gastric bleeding, severe hypertension, and H/O cerebrovascular accident. During thrombolytic therapy the thrombin clotting time must be checked regularly and kept at 2-3 time normal value.
3. Pulmonary Embolectomy:
Pulmonary embolectomy is the treatment of choice in the patients in whom thrombolytics are contraindicated or in occasional patients in whom there is a rapid deterioration despite thrombolytic therapy. Lastly embolectomy is also indicated in these patients in whom thrombolytic therapy is unlikely to exert its effect soon enough to prevent imminent death.
Criteria of pulmonary embolectomy may be enumerated as follow:
(i) Persistent shock unresponsive to treatment with fluids and vasopressors.
(ii) Massive pulmonary embolism with having 60% obstruction of pulmonary vasculature as revealed by angiography.
(iii) Right sided heart failure with an elevated and diastolic right ventricular pressure and C.V.P. above 15 cm.
Follow-Up:
AH patients should be maintained on anticoagulants for atleast 3 to 6 months. Since patients having one episode of pulmonary embolism are at increased risk of subsequent embolism, hence they must receive anticoagulant coverage whenever they are exposed to risks of thrombosis (e.g., surgery, bed rest).
There are a few patients in whom there is repeated pulmonary emboli despite anticoagulants control or in whom anticoagulants are contraindicated. These patients are at a risk of developing thrombotic pulmonary hypertension and in them there may be a place for inserting a filter in inferior vena cava. Lastly, an attempt to discover occult neoplasia is justified in many patients with unexplained pulmonary embolism.
Prophylaxis:
On the basis of several autopsy studies conducted, it seems that an effective method of prophylaxis would prevent mortality and morbidity associated with the spectrum of pulmonary thrombo-embolic diseases.
The chief methods employed are classified as follows:
Elimination of Deep Vein Stasis in Lower Limbs:
This involves early ambulation, guided physical exercises and specific methods to increase venous return in lower limbs (e.g., pneumatic compression or electrical stimulation).
Counteracting Blood Coagulability:
a. Drugs Affecting Platelet Aggregation:
Evidence of antiplatelet agents in prophylaxis of deep vein thrombosis is unconvincing.
b. Drugs Affecting Coagulation:
This involves utilisation of low dose heparin therapy and long term therapy with oral anticoagulants.
Prognosis:
Acute massive pulmonary embolism is almost always fatal if left untreated. In those that are fatal, 75% of deaths occur within one hour of symptoms and remaining 25% within 48 hours.
In case of smaller embolism prognosis is much better and the patient can have one or more clinically unrecognised attacks.
A pulmonary embolus tends to resolve over a period of time. Complete resolution may occur as soon as two weeks but is usually delayed upto two months. The pulmonary artery pressure usually returns to normal by three weeks.
It is now clear that chronic thrombo-embolic pulmonary hypertension is seldom, if ever, a complication of acute massive embolism. It is probably due to numerous clinically unrecognised attacks of minor embolism.
Special types of pulmonary embolism:
Fat Embolism:
Acute cor pulmonale due to fat embolism can occur when globules of liquid £at enter the systemic veins and are carried to the lungs.
Common causes of fat embolism include severe fractures or crush injuries, amputations, osteomyelitis and burns.
Since fat globules are able to penetrate lung capillaries and enter general circulation they may become lodged in the vessels of brain. Therefore both pulmonary and cerebral symptoms and signs may develop usually within 72 hrs after an accident.
Air Embolism:
Acute cor pulmonale can also be produced by air embolism. Unlike fat, air does not penetrate pulmonary capillaries.” IV. infusion, angiography, vaginal insufflations, operations on neck veins, dural sinuses are the usual source of air embolism. The volume of air required to occlude the pulmonary circuit is atleast more than 10 cc/kg body wt.
Amniotic Fluid Embolism:
This is particularly seen in pregnant mothers in third trimester of pregnancy, in puerperium and as a hazard of amniocentesis. There are associated features of D.I.C.