PNEUMOLOGY



MARCO ANTÔNIO FERREIRA ALMEIDA


Management of Both Stable and Unstable Acute Pulmonary Embolism


The management of patients with acute pulmonary embolism is difficult, but a rational approach is possible. A constant awareness of the potencial for sudden death long-term morbidity must be a guiding light for physicians whenever the condition is suspected.

Cor pulmonale can occur acutely as a result of a single large embolus or chronically from the cumulative effect of multiple small emboli. Most patients with massive pulmonary embolism and hemodynamic compromise from acute cor pulmonale die before they are able to obtain medical care.

Even when an initial pulmonary embolism is not massive, it has the potential for further embolization, which creates a life-threatening situation for the patient. In addition, a small pulmonary embolism that does not cause acute hypoxemia or overt hemodynamic instability still has the potential to produce long-term morbidity. Each clot that is trapped in the pulmonary circulation raises pulmonary vascular resistance in direct relation to the amount of pulmonary blood flow it impedes. The goals of therapy in this case are: (1) to prevent the formation of new thrombus, (2) to prevent further embolization of preformed thrombus, and (3) to reduce or prevent long-term morbidity associated with pulmonary vascular occlusion and cor pulmonale.

Small asymptomatic or minimally symptomatic pulmonary emboli are very common, and it makes sense to think that part of the lung's purpose is to act as a filter for small thrombi that otherwise would pass into the arterial circulation. Unfortunately, it is impossible to predict which patients with so- called stable pulmonary embolism will subsequently have massive embolus and acute cor pulmonale.

Patients in stable condition

Most patients who present with suspect acute pulmonary embolism are not hypotensive or hypoxemic. Nonetheless, all should have intravenous acess and should be given oxygen. An increase in alveolar oxygen decrease pulmonary vascular resistance and improves pulmonary hemodynamics.

Anticoagulation

The traditional mainstay of treatment for patients with deep venous thrombosis and pulmonary embolism is immediated anticoagulation with heparin, followed by t least 12 weeks of anticoagulation with heparin sodium. Heparin therapy lessens the mortality from pulmonary embolism by interfering with the production of news thrombus, thus reducing the likelihood of recurrent anticoagulation.

In the absence of specific contraindications, heparin therapy should be started as soon as the diagnosis of pulmonary embolism is seriously considered . The risk of recurrent acute pulmonary embolism is dramatically reduced for patients who receive adequate anticoagulant therapy within 48 hours of the initial event.

The effectiveness of heparin is strongly dependet on dose. For an average-sized adult, the initial bolus of heparin should be at least 1280U/hr. Heparin dosing for pulmonary embolsim is the same as that for deep vein thrombosis.

After full anticoagulation has been established with heparin ( a therapeutic activated partial thromboplastin time is often obtained within 6 hours ), orla warfarin may be initiated. It is not safe to start warfarin in a patient with thromboembolic disease without prior heparinization, because the drug actually causes a clinically significant hypercoagulable state during the early stages of use.

Vena Cava Filters

When a patient with deep venous thrombosis or pulmonary embolism cannot tolerate anticoagulant therapy, a filter device can be introduced through a catheter and positioned within the vena cava to trap the large emboli before they reach the pulmonary circulation. Filters do not provide absolute protection; they are not intended to trap small emboli, and there are many reported cases of m m masssive or fatal embolism as a result of emboli passing through or around a well positioned filter. Indications for placing a filter are: (1)Presence of contraindications to anticoagulant therapy, (2)anticoagulant resistance, (3)recurrent thromboembolism despite anticoagulantion, (4)Large, free-floating thrombus demonstrated in proximal deep veins, (5)Paradoxal embolization through patent forame ovale into arterial circulation, (6) Chronic pulmonary hypertension due to chronic embolization, (7)Cor pulmonale and no tolerance for additional pulmonary clot load.

Thrombolysis

The use of thrombolytic agents should be consideredin all cases of proven pulmonary embolism, even if patients initially are clinically in steble condition. Unlike heparin, thrombolytic agents can dissolve existing clot in both the deep venous system and the pulmonary circulation. Large prospective trials and follow-up studiea have demonstrated that in contrast to heparin therapy alone, thrombolysis can achieve improved pulmonary flow dynamics, normalization of gas exchange, decreased right ventricular failure and greater short-term exercise capacity.

Physicians often are reluctant to administter thrombolytic agents, even when the drugs are clearly indicated. Sometimes this is due to concern over contraindications(Table 1). heparin can often be used when thrombolytic agents cannot; heparin does not affect established clot after bleeding has stopped, whereasthrombolytic agents are able to dissolve established clot until it has become fully mature.

Full anticoagulation doses of heparin can be given immediately after major surgery, but thrombolytic therapy should be delayed until local vessel healing has occured( usually 10 to 14 days ). Most pos operative thrombus is fairly mature and resistant to lysis after 2 weeks, but in clinical settings where even a little bleeding would be catastrophic, thrombolysis should be avoided for up to 6 or even 8 weeks. Advanced age, menstruation, and controlled hypertension are not contraindications to heparin therapy or to thrombolysis.

Patients in unstable condition

Patients with pulmonary embolism who have severe hypoxemia or any degree of hypotension are considered to be in unstable condition. In these patients, the intrinsic excess capacity and compensatory mechanism of the cardiopulmonary system have been completely overwhelmed, and the risk of sudden death from any additional pulmonary clot load is extremely high.

Routine and adjunticve therapy -

Heparin and oxygen administration should be started exactly as for a stable patient with suspected pulmonary embolism. Additional supportive therapy can buy time, but there are only two acceptable definitive treatment options for apatient with profund hypoxemia or hypotension: thrombolysis or emergency surgical embolectomy. Without agressive management, early death is likely.

Fluid and phamacologic management -

the presence of hypotension from acute cor pulmonale nearly always means that the right ventricule is dilated and overfilled and is working against an extremely high afterload and triscupid regurgitation, and any effort to increase flow is met with a dramatic rise in pulmonary arterial and right ventricular pressures. In most cases of acute cor pulmonale, gentle pharmacologic preload reduction unloads the congestedpulmonary circuit and reduces right ventricular pressures. Agents useful for preload reduction include Hydralazine hydrocloride, Nifedipine, Captopril, Prostaglandins and Aminophylline. If right ventricular end-diastolic pressures are extremely high, diuresis may be effective both for preload reduction and for removing extravascular lung water to improe pulmonary vascular compliance.

Clinically, acute cor pulmonale with hypotension looks a little like hypovolemic shock, but with respect to the Starling curve, it is just the opposite, and agressive fluid challenge often pushes a dilated right ventricule into complete collapse. Pulmonary artery catheterization is essential if potentially destabilizing pharmacologic agents are to be used or if there is any question whether the patient needs increased or decreased preload.

If vasopressors are need, both beta1 and beta2 effects are desirable. A beta1 effect increases myocardial contractility and a beta2 effect decreases pulmonary vascular resistance and lowers pulmonary arterial pressure. Isoproterenol hydrocloride has been traditionally recommended, but norepinephrine has been much more effective in some studies and epineprine should be equally effective at low "beta-agonist" doses.

Thrombolysis and embolectomy -

When a patient withproven pulmonary embolism is in a unstable condition, immediated clot removal by thrombolytic therapy or by emergency surgical embolectomy is the accepted standard of care.

Emergency surgical removal of freshly embolized thrombus is not as difficult as pulmonary thromboendarterectomy for chronic pulmonary arterial obstruction, but the procedure still is associated with a very high mortality rate, and it is reserved for instances when there is absolute containdication to thrombolysis or when the patient's condition has failure to improve after thrombolysis.

Thrombolytic agents do not prevent the reaccumulation of new thrombus, so anticoagulant therapy with full-dose heparin should always be started along with the infusion of any thrombolytic agent.

Thrombolytic therapy usually is indicated only when the diagnosis of deep venous thrombosis or pulmonary embolism has been proved beyond a reasonable doubt, but much depends on the clinical situation.

The choice of a thrombolytic agent for pulmonary embolism should be based on the drug's safety, efficacy, and speed of action.Mortality in patients with unstable pulmonary embolism is high, and death occurs rapidly. Cost concerns alone, even if substancial, can not justify the use of a slow-acting agent when a faster one is available. The fastest-acting thrombolytic agent available today is rTPA, or Alteplase recombinante. Faster-acting agents and faster administration regimens are expected to become available in the future.

The recommended dosage of Alteplase for thrombolysis in patients with pulmonary embolism, in total dose of 100 mg, is given over periods of 90 minutes, as follows:

  1. 15 mg initial bolus
  2. 50 mg infusion over first 30 minutes
  3. 35 mg infusion over next hour.

The dose of Altplase should always be adjust for patients who weigh less than 70 Kg. Dose adjustement is prorated; if the patients weighs 10% less than 70 Kg, each component of the dose is reduced by 10%.

Emergency thoracotomy -

Closed-chest cardiopulmonary ressuscitation can not force blood through an obstructed pulmonary circuit, so cardiac arrest from pulmonary embolism is a reconized indication for immediated thoracotomy. Massage of the pulmonary arteries may succeed indislodging proximal thrombus and may partially relieve acute obstruction of right ventricule outflow. If the patient is resuscitated, surgical embolectomy is necessary.

Cardiopulmonary bypass -

Femoral cardiopulmonary by-pass is ideal in cases of cardiopulmonary collapse due to pulmonary embolism, because it provides both perfusion and gas exchange while the patient is watting definitive therapy. The large-bore femoral vein and artery catheters used for bypass are not a contraindication to thrombolysis, but after successful clot lysis they must be left in place until the systemic lytic state has worn off.

Bibliography:

Handler J a , Feield C F Acute pulmonary embolism. Postgraduated Medicine 1995 ; 97(1) : 61-72.


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