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Abstract
To date the management of pulmonary thrombo-embolism is still largely limited to anticoagulation. Heparin and oral anticoagulation have been shown to be effective in reducing recurrence and death in venous thrombo-embolism. During the acute stage, systemic thrombolytic therapy has also been advocated for the rapid dissolution of the thrombus in patients with haemodynamic instability. We describe four patients with acute pulmonary thrombo-embolism who were managed with catheter-based thrombus manipulation with intrapulmonary thrombolysis. This management strategy should be considered in patients with pulmonary thrombo-embolism who continue to deteriorate despite conventional management with anticoagulation or systemic thrombolysis.
- pulmonary thrombo-embolism
- catheter manipulation
- thrombus
- thrombolytic therapy
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Pulmonary thrombo-embolism (PE) is a common cause and consequence of hospital admission, with a significant mortality and morbidity. Male sex, old age, serious medical or surgical diseases, immobilisation and trauma are important predisposing factors in patients dying of such disease.1 Untreated PE is associated with a mortality rate of approximately 30%, but can be decreased to 1–10% with the institution of appropriate diagnosis and treatment.2-5
PE usually results from acute obstruction by thrombus, at any location of the pulmonary vascular tree. If severe, it leads to haemodynamic deterioration, systemic acidosis, right heart failure, cardiogenic shock, and ultimately death. To date, the management of PE is still largely limited to anticoagulation. Unfractionated heparin, nicoumalone and warfarin have been shown to be effective in reducing recurrence and death in venous thrombo-embolism,4 5 and more recently, low-molecular-weight heparins are increasingly used with their relative ease of administration and lack of requirement for anticoagulation monitoring.6 During the acute stage, systemic thrombolytic therapy has been advocated for the rapid dissolution of the thrombus, with some acute reduction of pulmonary artery pressure; nevertheless more evidence is needed for its long-term prognostic benefit, although it may have a role in patients with haemodynamic instability, as such patients have a mortality rate of approximately 20%, despite the use of anticoagulants and other supportive measures.7 8
Besides systemic thrombolytic therapy, there have been isolated reports on the use of pulmonary angiography and catheter-based manipulation with intrapulmonary thrombolysis to achieve clot fragmentation and dissolution (table 1).9-13 We describe four patients who presented to our centre with massive PE who were managed with catheter manipulation and intrapulmonary thrombolysis.
Right heart catheterisation, pulmonary angiography and catheter manipulation for pulmonary embolus examples of studies in the literature
Summary of the four case histories
Case reports
Case 1
A 46-year-old Caucasian man was admitted after an assault resulting in a closed fracture of the neck of left humerus and left wrist. He had a medical history of mild asthma and was a non-smoker. Both arm fractures were reduced under general anaesthesia and a piece of autologous bone graft was used to seal the humoral fracture with a metal plate. He was mobilised and well for 3 days postoperatively, when he suddenly experienced acute onset dyspnoea, and became tachycardic (130 beats/min in sinus rhythm) and hypotensive (86/58 mmHg). His white cell count was 21.6 × 109/l and arterial blood gases showed pH 7.34, pCO2 3.7 kPa, pO2 9.9 kPa, bicarbonate 17.5 mmol/l and base excess of −8.6. Central venous pressure was elevated at +29 cm water. A bedside transthoracic echocardiogram showed a dilated right atrium and ventricle with impaired right ventricular contraction. Left ventricular contraction was normal.
A clinical diagnosis of PE, originating from an axillary vein thrombosis, was made and 95% oxygen was adminstered through a rebreathing mask with subsequent arterial gases showing pH 7.36, pCO2 4.1 kPa, pO2 11.2 kPa, bicarbonate 19.7 mmol/l and base excess −5.8. A bolus of 5000 units intravenous (iv) unfractionated heparin was given, followed by an infusion rate of 25 000 units over the next 24 hours. Colloid (haemacel) and dopamine at 2–5 μg/kg/min were given iv to optimise systemic and renal output. However, the condition of the patient continued to deteriorate, with persistent hypotension and increasing hypoxia, and heparin was substituted for a systemic infusion of iv streptokinase at 100 000 units/h. He was referred to the on-call cardiologists for pulmonary angiography and clot manipulation.
Via a right femoral venous puncture, a 6F Gensini catheter (Cordis) was manipulated into the heart. The mean right atrium (RA) pressure was 18 mmHg, right ventricle (RV) pressure 50/5 mmHg (mean 26) and pulmonary artery (PA) pressure 55/20 mmHg (mean 32). Pulmonary angiography confirmed a large thrombus obstructing the left main pulmonary artery. The Gensini catheter and a J guide wire (0.038”, USCI) were used under direct image intensifier control for attempted clot fragmentation, resulting in the clot successfully being dispersed to a more peripheral location. The catheter was then leftin situ, in close proximity to the residual thrombus for further streptokinase infusion. A repeat right heart catheter the following day revealed a mean RA pressure of 15 mmHg and PA pressure of 42/16 mmHg (mean 26) with some persistence of the clot, although smaller in size. A further attempt at clot fragmentation and clot dispersion was made with a 8F pigtail catheter (Cordis) with the clot displaced to an even more peripheral location.
The post-procedure course was complicated by acute renal failure which was treated with haemofiltration for 7 days. The patient recovered fully and was discharged home on Day 30.
Case 2
A 18-year-old woman was transferred to our unit from a local orthopaedic hospital after developing a persistent sinus tachycardia, hypotension and poor arterial oxygen saturation in the immediate postoperative period. She had undergone an endoprosthetic replacement of the left tibia after excision of an osteosarcoma. She had been treated with subcutaneous heparin. On arrival in our hospital, 22 hours after her initial deterioration, her temperature was 38°C, pulse 150 beats/min, blood pressure 85/60 mmHg, and central venous pressure +16 cm water. Mechanical ventilation was in situand arterial blood gases showed a pH 7.2, pCO2 6.8 kPa, pO2 20 kPa, bicarbonate 18.4 mmol/l and base excess of −7.6. An electrocardiogram (ECG) confirmed sinus tachycardia, with a frontal axis + 800, right bundle branch block and a S1Q3T3 pattern.
As a result of her critical condition, right heart catheterisation and pulmonary angiography was performed immediately upon arrival (figures 1and 2). Mean RA pressure was 14 mmHg, RV 50/0 mmHg (mean 25), and PA 42/20 mmHg (mean 32). Bilateral thrombi were visualised to obstruct all intermediate pulmonary branches during pulmonary angiography. An attempt to disperse some of the clots to a peripheral location was made, and the cardiac catheter was left in situ for a continuous streptokinase infusion at 100 000 units/h. The patient was transferred to the Intensive Care Unit for continued ventilation, but remained in cardiogenic shock, with a blood pressure of 40/20 mmHg, despite ionotropic support (iv adrenaline boluses in addition to background infusion of 800 μg/kg/min) and died later that day with no reponse to therapeutic measures.
Pulmonary angiograms demonstrating thrombus within the right pulmonary artery (case 2)
Pulmonary angiograms demonstrating thrombus within the left pumonary artery (case 2)
Case 3
A 30-year-old woman was admitted with a history of dyspnoea and collapse following a recent in-patient stay for a minor superficial leg injury. She was a smoker and was previously in good health. On examination she had a tachycardia of 138 beats/min, with a blood pressure 90/50 mmHg. The ECG showed sinus tachycardia with widespread ST segment depression. A chest X-ray was unremarkable. PE was suspected on clinical grounds and confirmed with a pulmonary angiogram, which demonstrated the presence of blocked pulmonary arterial branches in the right upper and middle intermediate branches. The mean RA pressure was 12 mmHg, and PA pressure was 45/16 mmHg (mean 28). A 8F pigtail catheter (Cordis) was used to disperse the thrombi and the catheter left in the right main pulmonary artery for continuous streptokinase infusion. A repeat pulmonary angiogram performed 2 days later showed complete dissolution of thrombus and patient was discharged on warfarin after 8 days of hospitalisation.
Case 4
A 36-year-old male smoker presented with left-sided pleuritic chest pain, dyspnoea and a productive cough. An initial diagnosis of left lower lobe pneumonia was made and treatment with antibiotics initiated. On day 2, he experienced a sudden onset of increasing dyspnoea. arterial blood gases revealed severe hypoxaemia with pH 7.4, pCO2 3.9 kPa, pO2 5.3 kPa, bicarbonate 22.6 and a base excess of −1.6. Chest X-ray confirmed pneumonic consolidation in the left lower zone whilst the rest of the lung fields was clear. An ECG showed sinus tachycardia without evidence of myocardial ischaemia.
In view of the mismatch between the degree of hypoxaemia and consolidation, and deteriorating clinical state (increasing dyspnoea, hypotension and hypoxia), a PE was suspected. Pulmonary angiography using a size 6 Gensini catheter (Cordis) revealed a major obstruction of the right main pulmonary artery with thrombus, and clot dispersion was attempted using the catheter and J guide wire (0.038”, USCI). Streptokinase was then infused via the catheter into the pulmonary artery. A repeat pulmonary angiogram 2 days later showed satisfactory perfusion to all areas of the right lung. The patient was subsequently discharged on Day 15. Subsequent clinic follow-up investigations revealed the presence of nephrotic syndrome secondary to membraneous glomerulonephritis.
Discussion
The diagnosis of PE is often made too late, at the patient's peril. When the thrombotic occlusion causes major haemodynamic compromise, as in our four cases, the diagnosis is seldom in doubt. The diagnosis is, however, less obvious in less severe cases, as symptoms are vague, non-specific or may even be absent initially. Simple investigations such as chest radiography and ECG are often inadequate.14 15 Bedside transthoracic echocardiography can provide some information to substantiate the diagnosis, as right ventricular dilatation with hypokinesis, abnormal septal position and paradoxical systolic motion, reduced left ventricular size, pulmonary artery dilatation, tricuspid and pulmonary regurgitation, and a lack of collapse of the inferior vena cava with inspiration are features suggestive of PE on the echocardiogram.16 17 The visualisation of thrombus in the right side of the heart or pulmonary artery is less common, but confirms the diagnosis.16 17More sophisticated investigations such as lung ventilation-perfusion scans, transoesophageal echocardiography and spiral computed tomography can add to the diagnostic accuracy in patients who are clinically stable enough to undergo these tests, which may add to the delay in making the diagnosis in more urgent situations.
Unfractionated heparin is no doubt the initial treatment of choice in the milder form of PE without haemodynamic instability or significant hypoxaemia. However, this form of treatment is associated with some uncertainity about the level of anticoagulation during the initial but crucial phase of PE. Systemic thrombolytic treatment has been advocated in some patients with PE associated with circulatory instability or hypoxaemia although larger studies with more outcome data are still needed. Although previous studies have demonstrated the short-term superiority of thrombolysis in terms of resolution of both radiographic and haemodynamic abnormalities when measurements were made within the first 24 hours, this does not appear to be sustained nor translated into a mortality benefit.7 8
In selected patients where anticoagulation or thrombolytic therapy are contraindicated, or fulminant PE is evident, pulmonary angiography and catheter-based manipulation can be life saving, although more evidence from randomised controlled trials is needed. Pulmonary angiography provides the gold standard for initially visualising the presence of thromboemboli in the pulmonary vasculature. Our usual practice is to perform this under local anaesthetic from the femoral vein, using a Seldinger technique; visualisation is performed in the postero-anterior position with injection of 35 ml of dye (Niopam 340) at 14 ml/s and a pressure of 900 psi via a pigtail or Gensini catheter. The risks of undertaking pulmonary angiography relate to bleeding at the groin (especially with concomitant anticoagulants), possible reactions to the contrast (allergy, renal impairment) and rarely, perforation of the right ventricle.
As illustrated with our cases, intravascular catheters or balloon angioplasty can be used to dislodge or fragment thrombus in a proximal segment of the pulmonary artery, to be dispersed to a more peripheral location. Such manoeuvres can lower the pulmonary vascular resistance, reduce strain on the right side of the heart, and improve perfusion to the affected lung segments. Concomitant use of thrombolytic therapy either via pulmonary artery catheter or peripheral venous catheter can be synergistic with catheter-based manipulation for the treatment of PE, in the absence of contraindications. Our usual practice is to administer streptokinase, initially 250 000 units over 30 minutes, followed by 100 000 units/h for 24–72 hours. The introduction of newer agents such as the glycoprotein IIb/IIIa receptor antagonists may provide alternative antithrombotic strategies in the future, but further trials are needed to confirm the value of these agents.
A large number of different catheters have been used in clinical reports (table 1) since Greenfield18 originally described the technique of transvenous catheter pulmonary embolectomy. The pigtail catheter is familiar to all cardiologists and because of its round coil design, could be regarded as one of the least trauma-inducing catheter. Moreover, the pigtail coil design can be utilised to a greater advantage by maximising the surface area with the ‘loop upon axial rotation’ ability of the catheter, which facilitates the dislodgement and fragmentation of the thrombus. This approach with the pigtail catheter was been used satisfactorily in two of our cases. In addition to the catheter shape, a larger size catheter with a bigger pigtail loop may be easier and more effective to manoeuvre than a smaller catheter of the same design; perhaps more purpose built catheters may be available in the future for this procedure.
At present, there are no data to support the routine use of pulmonary angiography and catheter-based manipulation in all cases of PE. This therapeutic measure should perhaps be reserved for cases whereby there are contraindications to anticoagulation or thrombolysis, or in patients with a rapidly deteriorating clinical course. Surgical embolectomy with or without inferior vena cava filter is another alternative to catheter-based manipulation in severe cases or in the presence of contraindications to thrombolysis, but its place in the management of PE remains controversial.19 20 Indeed, the operative mortality of surgical embolectomy in selected patients has been reported to be high, up to 40–70%,19 20 and the availability of an emergency cardiothoracic team would limit its widespread application.
In conclusion, we present four cases of acute PE where catheter-based thrombus manipulation with intrapulmonary thrombolysis were used, with a satisfactory outcome in three patients. We do accept that our patients had multiple interventions, including intravenous heparin, and intravenous and intrapulmonary thrombolysis, but we suggest that catheter-based thrombus manipulation with intrapulmonary thrombolysis could be considered in patients with PE who continue to deteriorate despite conventional management with anticoagulation or systemic thrombolysis, especially in centres with access to angiographic facilities.