Question 5

College Answer

1.  Define the rationale for thrombolysis

Standard therapy for pulmonary embolism is anticoagulation, which prevents additional thrombus from forming, but does not directly dissolve the clot that already exists. Thrombolysis theoretically gives primary treatment as it dissolves fibrin

2.  Define massive PE

Massive PE has traditionally been used to describe clot burden on radiology, but this was of little use clinically. Massive PE is more conventionally defined as a cardiogenic shock or SBP <90mmHg due to PE, either confirmed or strongly suspected on clinical grounds.

3.  Discuss the evidence in massive PE

The evidence for thrombolysis to improve mortality in massive PE is not strong, but there is a trend towards improved mortality and resolution of shock with thrombolysis. Most guidelines advocate the use of thrombolysis unless absolutely contraindicated i.e. intracranial haemorrhage

4.  Discuss the other options if thrombolysis can’t be done in massive PE

If thrombolysis is not possible or contraindicated then the other options for massive PE are surgical embolectomy or catheter embolectomy and fragmentation.

5.  Statement of candidate’s approach to thrombolysis in massive PE

Discussion

This is one of those "critically evaluate" questions; a structured approach is favoured:

Introduction

Massive PE is defined as a pulmonary embolism of sufficient size to cause systemic arterial hypotension. A submassive PE, in contrast, is one which only causes right heart dysfunction, without obstructive shock.

Rationale for thrombolysis

• Thrombolysis may decrease clot burden, in addition to what anticoagulation alone can accomplish.
• This may lead to the improvement of pulmonary blood flow
• Systemic haemodynamics may improve
• A long-term benefor of thrombolysis is the prevention of severe pulmonary hypertension which inevitably develops in the wake of large scale pulmonary emboli.

Evidence for benefits

• As the college has mentioned, the evidence for this practice is dodgy.
• The first randomised trial for this thrombolysis in massive PE comes from 1995, and was performed in a group of only 8 patients.
• All 4 patients receiving thrombolysis had survived without pulmonary hypertension at 2 years follow-up; whereas all the heparin-treated patients had died.
• Ten years later, thrombolysis is seen as a mandatory first-line step in the treatment of massive PE. It appears to reduce mortality by 55% according to a 2004 meta-analysis (including data from 748 patients).

Evidence for risks

• In the same meta-analysis, it was found that in comparison to heparin alone thrombolysis doubles the risk of major bleeding from 12% to 22% (which makes some sort of perverse sense, as it tends to halve PE-associated mortality).
• Real-world registry data suggests that this risk of bleeding is probably underestimated by clinical trial data, given how spotlessly perfect their patient selection is (whereas at the coalface, in the ED and ICU, a fair few patients are retrospectively, posthumously, discovered to have had some contraindication to thrombolysis).
• In short, the risk of death from bleeding is significant, and should be presented to the patient and family as a real possibility.

Alternative treatments

• Surgical embolectomy is a possibility, but good outcomes are only seen when a strong and organised purpose-built team is looking after the process, rather than some ad-hoc on-call cardiothoracic surgeon. Furthermore, the patients need to be carefully selected, and the sort of patient most in need of embolectomy are also the patients least likely to be selected for surgery (i.e. they are in florid cardiogenic shock, or worse yet they failed thrombolysis and are now full of alteplase).
• Clot fragmentation,
• Catheter embolectomy
• Catheter-directed thrombolysis

Conclusion

Thrombolysis is an important and potentially lifesaving step in the management of massive PE. If the patient does not meet criteria for thrombolysis, urgent percutaneous or open surgical embolectomy should be considered.

Kucher, Nils, et al. "Massive pulmonary embolism." Circulation 113.4 (2006): 577-582.

Jerjes-Sanchez, Carlos, et al. "Streptokinase and heparin versus heparin alone in massive pulmonary embolism: a randomized controlled trial." Journal of thrombosis and thrombolysis 2.3 (1995): 227-229.

Kucher, Nils, and Samuel Z. Goldhaber. "Management of massive pulmonary embolism." Circulation 112.2 (2005): e28-e32.

Wan, Susan, et al. "Thrombolysis compared with heparin for the initial treatment of pulmonary embolism a meta-analysis of the randomized controlled trials." Circulation 110.6 (2004): 744-749.

Kasper, Wolfgang, et al. "Management strategies and determinants of outcome in acute major pulmonary embolism: results of a multicenter registry." Journal of the American College of Cardiology 30.5 (1997): 1165-1171.