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Severe Pulmonary Embolism - 12/3/2012

posted Dec 3, 2012, 7:54 AM by Rohit Das   [ updated Dec 27, 2012, 6:39 AM by Purnema Madahar ]

It’s that time again…to hopefully enlighten your minds with tantalizing, clinically applicable, information courtesy of our daily noon conference topics. Today, we talked about pulmonary embolism, but focused particularly around severe, or “massive,” PE and appropriate management. Yea…we’ve talked about PE in this daily quite a bit already, including its overdiagnosis (8/16/2012), prognostic factors and the PESI severity score (8/21/2012), and important aspects of the seminal PIOPED study (8/28/2012). Seems like August was pretty heavy on the PE front…nevertheless, I think it warrants further discussion. Let’s talk about the management of severe PE:

·         What are the management options for patients with severe pulmonary embolism?

·         What are the guidelines for thrombolysis? How substantial is the evidence behind it?

·         The ever enigmatic IVC filter – is there evidence for its utility in severe PE?

What are the management options for patients with severe pulmonary embolism?

·         Let’s not take anticoagulation for granted…it is still the mainstay therapy, severe PE or not-so-severe, overdiagnosed PE. There has only been one randomized trial ever published looking at anticoagulation versus no anticoagulation (Lancet, 1960…too old school to get my hands on), but that along with several other observational studies have confirmed its efficacy. In those days, mortality from PE decreased from 30% to 4-8% with anticoagulation, and recurrence risk (which is usually what kills patients with PE) without anticoagulation is about 25%. As we talked about on 8/16, current outcome data is probably skewed by overdiagnosis.

·         Besides anticoagulation, the other options we have are thrombolysis, IVC filters, and embolectomy….

What are the guidelines for thrombolysis? How substantial is the evidence behind it?

·         From the most recent CHEST 2012 guidelines (attached), the most widely accepted recommendation (though only Grade 2C) for systemic thrombolysis is persistent hypotension, which means systolic blood pressure ≤ 90 mmHg, or (very importantly) a decrease in systolic blood pressure of ≤ 40 mmHg from baseline despite adequate fluid resuscitation. The value of thrombolysis for other indications )in the absence of hypotension), like severe hypoxemia, RV dysfunction, is uncertain and considered on a case-by-case basis.

·         Regarding the evidence…pretty lacking, actually. Attached is a meta-analysis of nine randomized trials comparing tPA with subsequent anticoagulation versus anticoagulation alone. Of note, five of the trials excluded patients in shock, thus potentially limiting this paper’s applicability to the more “severe” PE population.

·         Overall, the trial showed a non-significant mortality reduction with tPA; the relative risk reduction was 0.63 (95% CI of 0.32-1.23). In a sensitivity analysis including patients in shock, the relative risk reduction was still not significant – RR of 0.51 (95% CI of 0.23-1.16). This non-significant mortality reduction came at the expense at a significantly higher risk of major hemorrhage – RR of 1.76 (95% CI of 1.04-2.98).

·         Though controlled trials have basically yielded uncertain results, observational data has been in support of thrombolysis. In a recently published retrospective cohort study, among unstable patients (defined as having an ICD-9 code of shock or ventilator dependence), mortality with thrombolytic therapy was 15%, versus 47% in patients who only received anticoagulation. Difficult what to make of this, given the potential confounders and such…but interesting…

·         There are several contraindications to tPA, all related to major bleeding risk. Some of these include the presence of an intracranial neoplasm, recent (<2 months) intracranial surgery/trauma, history of a hemorrhagic stroke and recent surgery (<10 days) just to name a few…

The ever enigmatic IVC filter – is there evidence for its utility in severe PE?

·         IVC filters have always had a theoretical backing behind them – given that PE-related mortality is usually related to a recurrent embolic event as opposed to the initial, presenting, event, it would make sense that sticking a filter between a clot and your lungs would be a good idea…

·         Unfortunately, there is an extreme paucity of literature and basically no controlled trials looking at the efficacy of IVC filters (along with anticoagulation) in unstable patients…in an observational study done by the same group as mentioned above, unstable patients who received an IVC filter had a significantly lower case mortality rate than those who didn’t – 6.4% versus 15%. In the CHEST 2012 guidelines, the only strong recommendation for IVC filter placement for PE is when there is a strong contraindication to anticoagulation.

·         In the PREPIC study – one of the largest and only studies looking at the efficacy of IVC filters in patients with proximal vein thromobosis – patients who had an IVC filter had a lower incidence of PE at 12 days (1.1% versus 4.8%), but a higher incidence of recurrent DVT at 2 years (20.8% versus 11.6%). There was no significant difference in survival at 2 or 8 years between the two groups.

Quick word on embolectomy – the procedure is generally done by IR in the context of a patient in whom thrombolysis is considered, but failed or contraindicated. Generally, the clot isn't "removed" per se, but rather fragmented as to improve blood flow through the pulmonary bed and alleviate the pressure burden on the right ventricle. Data supporting its efficacy is lacking (surprise!) and limited to case series…

Just to clarify – I don't want to discount the potential value of thrombolysis and IVC filters -- thrombolysis, especially, can be life-saving. Ultimately, it will always be difficult to get good data on the efficacy of such "last resort" measures, mainly because there aren't enough cases to work will encounter the “severe” PE eventually and its definitely worth knowing the evidence behind these therapeutic options…

Nice to get the daily back up again, more to come…KEEP READING!!