Management

Depeyling on the clinical presentation the patient needs to be treated either in intensive care unit, hospitnl wards or advanced referral hospitals. Those patients of PE who present with marked symptoins or are hemoclynamically unstable (low blood pressure, cyanosis or shock) need to be treated in an intensive care unit. Patienls with minor PE can be trealed at home. In sick patients, the aim o l treatment is to provide symptomatic relief, maintain oxygenation, ventilation and provide inotl.opic support.Patients who are l-~ypoxic require oxygen and may need ventilatory support.Dobutnmine, a beta adrenergic agonist with positive inotropic and pulmonary vasodilating effects should be considered a first line agent to treat right sided heart failure and cardiogenic shock. The use of diuretics, intravenous fluids and dopamine should be individualized. Sedation should be avoided if patient is showing arleiial hypoxemia.

Anticoagulation

Anticoagulant therapy has been the mainstay of treatment for VTE. Treatment of patients with uncomplicated PE or DVT involves similar anticoagulant regimens, in part because asymptomatic PE occurs frequently in patients with symptomatic proximal DVT, and vice versa. Treatment of VTE involves initiation of anticoagulant therapy with either UFH or LMWH and considering long-term initiation of oral
anticoagulation (Warfarin therapy).The utility of UF'H or LMWH in treatment of VTE have been documented in large number of studies. Both these heparins are effective, safe, provide symptomatic benefit and reduce the mortality and morbidity due to this disease. The incidence of PE, its recurrence and the long term sequale of this illness are reduced by use of heparin. UFH has been in clinical use for over 100 years, is safe and comparatively cheap. LMWH has become popular during the last decade and is gradually replacing the UFH. The primary difference between these two heparins relates to their pharmacological properties and cost. The main side effects of both the heparins is minor or major bleeding. The nlinor bleeding which is frequent with LMWH is subcutaneous haematoma at the site of injection. The other side effects of hepains are rare and include thrombocytopenia or osteoporosis. l11e treatment by either heparin is usually given for 5 to 7 days. Oral anticoagulation is stasled either sin~ultaneously or soon after depending on patient profile. Before initiating anticoagulation therapy,proper history should be obtained to rule out any histo y of bleeding (piles, peptic ulcer, hemorrhagic stroke) or related disorders.

Coinnlercial UFH is a heterogeneous mixture of carbohydrate chains ranging in molecular weight from 3000 to 30, 000 daltons, yet only approximately one third of UFH molecules contain the unique pentasaccharide sequence required for binding to AT, and hence for anticoagulant activity. Due to molecular heterogeneity of UFH its bioavailability is unpredictable and can vary from patient to patient. For achieving clinically predictable results a blood test is required while administering UFH.Monitoring of the activated partial thromboplastin time (aPTT) is needed and therapeutic range of aPTT ratio (patientfcontrol) of 1.5 to 2.5 is generally recommended. The UFH can be adniinistered intravenously (IV) by infusion or by subcutaneous (SC) route. However, the bioavailability of S C UFH is l'ess than that of lV UFH and larger initial doses of SC hepain are needed to achieve a therapeutic anticoagulant effect.'Due to this, intravenous infusion is preferred. The dosage schedule of LFH according to aPTT is shown in Table .
 

LMWH products are produced by controlled enzymatic or chemical depolymerization of UFH. They have a mean molecular weight of 5000 daltons. The reduced molecular size of LMWH results in improved bioavailability, longer half life and a more predictable anticoagulant response, making unmonitored, weight based SC administration feasible.

The LMWH has a predictable anticoagulant response and has been used on out patient basis for treatment of DVT and in stable patients with PE. Due to its ease of administration (subcutaneous) and no need for aPTT monitoring, SC LMWH is currently the preferred treatment for the majority of patients with VTE. The potential advantages of LMWH over UFH ase su~nmaiized in Table 8. I11 those at high risk for bleeding complications, IV UFH inay be preferred, because of its shorter half life and the reversibility of the ailticoagulant effect by administration of protarnine sulfate.Commercially, there are many preparations of LMWH available in the market. They all seem to be effective for treatment of VTE. Different dosage regimens are used for the various LMWH preparations. Table  shows the dosage schedule of LMWH which have been extensively used.

Oral anticoagulation therapy using warfirin or any other agent is advocated in majoiity of patients for variable duration. The duration of long-term anticoagulation is to be individualized depending bn risk factors. For patienls with VTE associated with a major transient risk factor such as recent surgery,anticoagulation therapy is usually reconlmended for three months. For patients with unprovoked VTE, stopping a~lticoagulant therapy after six or more months of treatment is associated with a high risk of recuirent VTE and justifies long-term anticoagulation for such patients. The argument favoring long term therapy is stronger if the unprovoked episode was PE; if a second or subsequent episode of unprovoked VTE occurs; or any hypercoaguable state is diagnosed. Regular monitoring of blood test called as prothrombin time and Inleinational Normalized Ratio (INR) is mandatory while administering oral anticoagulation. An INR of 2 to 2.5 is generally recommended. Inferior Vena Cava (IVC) filters are advocated to prevent further episodes of VTE in selected patients and particularly in those with contraindication to long-term anticoagulation.There are newer direct thrombin inhibitors agents like himdin, hirulog or oral Ximelagatran which are investigational at present and may become available in near future as substitute to existing anticoagulants.

Thrombolysis

Systemic IV infusion of thrombolytic agents have been proven superior to anticoagulation for treatment of PE. Compared with heparin in hemodynanlically stable patients with large PE, systemic thrombolytic therapy ;.educed moi-tality ('J1 per cent versus 4.7 per cent) and recurrent PE (18.7 per cent versus 7.7 per cent, P =0.016) but was associated with higher rates of bleeding complications. In view of the higher incidence of bleeding thrombolysis is not indicated in all patients with large PE.

The use of thrombolysis should be reserved for following category of patients. a) Patients with massive PE presenting as a life threatening emergency. b) Patients with sub-massive PE and demonstration of right ventricular dysfunction on echocardiography. c) Patients who develop recurrent PE despite treatment with heparin. The thrombolytic agents and their dosage schedule are shown in Table.In some centers thrombolytic agents are directly injected into pulmonary arteries(catheter directed thrombolysis) to facilitate clot lysis.
 

Newer Interventional and Surgical Treatment
 

There are patients who fail to improve despite all available treatment. For these patients interventional (catheter directed thrombolysis, clot fragmentation or thrombus aspiration) techniques used in catheterization laboratories or surgical techniques such as embolectomy atme indicated. These techniques are available in some advanced tertiaiy care hospitals.The indications for use of these illterventioi~s are: 1) Persistent arterial hypotension(systolic blood pressure < 90 mm Hg or a rapid decrease of > 40 mm Hg),

2) Systemic hypopetfusion and hypoxemia, 3) Need for cmdiopulmonary resuscitalion, 4) Severe right ventricular failure, and 5 ) Contraindication to c ti coagulation or thrombolysis.