Management of Small, Submassive and Massive Pulmonary Embolism
Dr John Griffiths DICM MRCP FRCA MA
Focus on pulmonary embolism
The incidence of pulmonary embolism (PE) is estimated at 60-70 cases per 100,000 in the general population. Half of these patients develop PE either in hospital or in long term care.
Recognising the clinical probability of PE is of major importance as it ensures early initiation of appropriate treatment. In the majority of patients, computed tomographic pulmonary angiography (CTPA) is the lung imaging modality of choice to confirm the diagnosis of PE or identify an alternative pathology. By assessing right ventricular function, echocardiography plays a pivotal role in risk stratification. In addition, echocardiography is often able to demonstrate an intracardiac or proximal intrapulmonary thrombus. Efficient risk stratification enables accurate classification of PE. Classification of PE is important because each class of PE (“small”, “submassive” and “massive”) has a different evidence base to its management.
Focus on anticoagulation – “small PE”
Small pulmonary emboli are defined as emboli that do not cause pulmonary hypertension and do not affect right ventricular function. If appropriate management is given, the prognosis of small PE is excellent. The treatment of choice is anticoagulation with standard- or low-molecular weight heparin until adequate maintenance anticoagulation with warfarin is achieved. There is no evidence to support the use of thrombolysis in small PE.
Focus on thrombolysis – “massive PE”
Massive PE results in acute right ventricular dysfunction and systemic hypotension or even cardiac arrest. If massive PE is suspected clinically, then immediate intravenous administration of a thrombolytic agent is recommended, followed by urgent echocardiography and/or CTPA. However, the conclusive evidence for a reduction in mortality by the use of thrombolytic agents is sparse. At the current time, there is only one randomised controlled trial of thrombolysis versus heparin in the face of massive PE. This trial was stopped prematurely after eight patients had been randomised; all four patients who had received thrombolysis survived, whereas all four who had been given heparin died. In patients with both right heart intraventricular or intra-atrial thrombus and PE, mortality with thrombolysis was found to be one-third of that with heparin administration alone.
The thrombolytic agent of choice for the treatment of massive PE is recombinant tissue plasminogen activator (rTPA). The argument for rTPA is that in the presence of hypotension and cardiovascular instability, it is less likely to have a further effect on the blood pressure than streptokinase.
In the setting of acute massive PE, it is recommended that rTPA is administered as a single 50 mg bolus followed by anticoagulation with unfractionated heparin.
Focus on thrombolysis – “submassive PE”
Submassive PE is characterised by right ventricular dysfunction in a patient that remains normotensive. It remains unclear whether thrombolysis has a role in the management of submassive PE. In a recent German multicentre study, 256 patients with submassive PE confirmed radiologically were randomised to receive either rTPA plus heparin or heparin plus placebo. All patients enrolled in this study had either right ventricular dysfunction and/or pulmonary artery hypertension on transthoracic echocardiography. Patients with systemic hypotension and/or left ventricular dysfunction were excluded. Bleeding complications were low, with only one fatal bleed reported. This occurred in the heparin plus placebo group. Interestingly, no reported haemorrhagic strokes were reported. The number of “clinical deteriorations” requiring escalation of treatment (defined as thrombolysis, inotropic support or endotracheal intubation) was significantly lower in the thrombolysis group than in the heparin group (11.0% versus 24.6%). However, 30-day mortality did not differ significantly between the two groups (approximately 2.7%).
At the present time, the British Thoracic Society guideline recommends that “thrombolysis should be reserved for patients with clinically massive PE”.
Focus on percutaneous and surgical thrombectomy – “massive PE”
Modern interventional radiology offers several treatment options in the management of massive PE. A percutaneous catheter can be placed in the pulmonary arterial tree, and thrombi can either be removed by suction, or mechanically fragmented or dissolved by locally administered thrombolytic agents. The anatomical result can be assessed immediately by pulmonary angiography using the same catheter. Several small case series suggest both a high efficacy in restoring pulmonary perfusion and a low rate of complications. Possible catheter-related complications include cardiac arrhythmias, pulmonary reperfusion injury and pulmonary haemorrhage.
Open, surgical embolectomy can only be offered in specialist centres, and is usually reserved as a last resort when other methods have failed. There are various case reports and case series where surgical embolectomy has been used early in patients with massive and submassive PE, and results have generally been encouraging.
Although there are no large randomized trials investigating percutaneous techniques and surgical embolectomy, these modalities should form part of the algorithm in the treatment of major PE, especially in patients where thrombolysis is either absolutely contraindicated or where it has failed.
Focus on inferior vena cava (IVC) filters
The percutaneous placement of an IVC filter is indicated when anticoagulation cannot be undertaken because of active bleeding or in face of recent surgery. Other indications for IVC filters are recurrent or persistent PE despite adequate anticoagulation, or as additional prophylaxis in high-risk patients at high risk of further PE.
Focus on the role of magnesium sulphate and nitric oxide
Both intravenous magnesium sulphate and inhaled nitric oxide have been shown to be efficacious in decreasing pulmonary artery pressure and increasing cardiac output in animal models of acute PE. However, clear evidence of any clinical benefits of these interventions is currently lacking.
Key learning points
- In small, uncomplicated PE anticoagulation remains the treatment of choice
- In suspected massive PE with associated hypotensive shock, thrombolysis should be given unless there is a significant risk of major bleeding complications
- Surgical- and catheter-based thrombectomy are alternative strategies in the management of massive PE and must be considered when thrombolysis is either contraindicated or has failed.
- It remains unclear whether thrombolysis has a role in the management of submassive PE.
British Thoracic Society Standards of Care Committee Pulmonary Embolism Guideline Development Group. British Thoracic Society guidelines for the management of suspected acute pulmonary embolism.
Thorax 2003; 58: 470-484.
Simonneau G, Sors H, Charbonnier B, et al.
A comparison of low molecular-weight-heparin with unfractionated heparin for acute pulmonary embolism. The THESEE Study Group.
N Engl J Med 1997; 337: 663-669.
Jerjes-Sanchez C, Ramirez-Rivera A et al.
Streptokinase and heparin versus heparin alone in massive pulmonary embolism: a randomised controlled trial.
J Thromb Thrombolysis 1995; 2: 227-229.
Konstantinides S, Geibel A, Heusel Get al.
Heparin plus alteplase compared with heparin alone in patients with submassive pulmonary embolism.
N Engl J Med 2002; 347: 1143-1150.
Suarez JA, Meyerrose GE, Phisistkul S et al.
Review of catheter thrombectomy devices.
Cardiology 2004; 102: 11-15.
Dauphine C, Omari B.
Pulmonary embolectomy for acute massive pulmonary embolism.
Ann Thorac Surg 2005; 79: 1240-1244.
Haas NA, Kemke J, Schulze-Neick I, Lange PE.
Effect of increasing doses of magnesium in experimental pulmonary embolism.
Intensive Care Med 2004; 30: 2102-2109.