We now have way too many treatment options for sub-massive and massive pulmonary embolism (PE) patients who aren't coding in front of you. How do you decide which one is right for your patient? To help answer this question, I am joined today by Oren Friedman, pulmonary critical care doc and one of the members of the Cornell PEAC team.
Cornell Pulmonary Embolism (PE) Advanced Care Team (PEAC), aka the CLOT Team
Oren Friedman MD, Pulm Crit Care; James Horowitz MD, Cardiology; Arash Salemi MD, Cardiac Surgery; Akhilesh Sista MD, Interventional Radiology
You can shoot the team an email: peadvancedcare at gmail dot com
Who Should We Treat?
30% normotensive patients have RVD; 10% progressed to shock; 5% in hospital mortality[cite]10859287[/cite]
The Better Risk Categories for Pulmonary Embolism
- Well and Stable Sub-Massive
- High-Risk Sub-Massive
- Massive
PEITHO Trial
Full dose tenecteplase with concurrent heparin
- Death or hemodynamic decompensation occurred in 2.6% of the tenecteplase group as compared with 5.6% of the placebo group
- Extracranial bleeding occurred in 32 patients (6.3%) in the tenecteplase group and 6 patients (1.2%) in the placebo group (P<0.001)
- Intracranial Bleed 10 patients (2%) in the tenecteplase group and 1 patient (0.2%) in the placebo group (P=0.003)
Also see my bud, Salim Rezaie's post on PEITHO and Konstantinides' prior study [cite]12374874[/cite]
Ryan Radecki made some great observations in his post on PEITHO
- The criteria for myocardial injury was a troponin I >0.06 ?g/L or troponin T >0.01 ?g/L. These may be relatively inclusive thresholds.
- Not all placebo patients developing hemodynamic collapse received subsequent thrombolysis; likewise, almost half of those who received open-label thrombolysis had no hemodynamic collapse.
- Half the deaths in the placebo arm were “sudden unexplained” or “other”, compared with bleeding or stroke complications in the thromboysis arm.
TOPCOAT Trial
Jeff Kline's trial was stopped midway through due to an institution change. Complicated primary endpoint with promising, but unusable results [cite]24484241[/cite]
For the scoop on this one see the Bottom Line Review post on TOPCOAT
MOPETT Trial
Half-dose alteplase led to a marked reduction in pulmonary hypertension without sig. complications
Sharifi M et al. Moderate pulmonary embolism treated with thrombolysis (from the “MOPETT trial). (J Cardiol 2013; 111: 273)
See this prior EMCrit Wee as well on MOPPETT
Update: This meta-analysis states that the half-dose may be appropriate, effective, and safe [cite source='pubmed']24412030[/cite]
Meta-Analysis
Chatterjee et al. have the most current meta-analysis on this topic (JAMA. 2014;311(23):2414-2421)
See the Bottom Line Review post on this study
Nakamura just published another MA this week; see Rory Spiegel's take on the two here
Is it just in the Oldies?
Markedly lower risk in <75 y/o in PEITHO and <65 in the Meta-Analysis
The Treatment Options
Heparin Alone
tried and true. but even if some degree of resolution of presenting severe symptoms, there is the question of long-term consequences of leaving a large clot burden–namely, loss of exercise tolerance due to chronic pulmonary hypertension
Systemic Thrombolysis
With either full or half-dose alteplase or full-dose tenecteplase
Catheter-Based Intra-Arterial Thombolytic Infusion
Angiography guided placement of pulmonary artery catheters allowing a 24-hour infusion of low dose tPA. [cite]19875060[/cite]
A newer therapy is the EKOS catheter. This uses ultrasound to continuously break up the clot during the IA Thrombolysis. Many of us wonder if this is any better than standard catheter-based therapy. [cite]24226805[/cite], [cite]23601295[/cite] See the PulmCCM Post on the Circulation RCT of EKOS
Interventional Mechanical Clot Disruption
AngioJet-a catheter that breaks up the clot with a high speed jet of saline, heparin, or tPA that then sucks up clot using Bernoulli physics. Very little systemic drug is delivered. Oren's center doesn't like the device; other centers use it. This letter is by an adovcate.
AngioVac-This device uses an ECMO-like system to suck up clot and then return the declotted blood to the venous circulation. It requires huge introducer sheaths. Oren alluded to its main benefit being intra-cavitary or vena cavae clots. Some are billing this as a replacement for embolectomy in many cases.
Surgical Embolectomy
Requires the patient to go on cardiopulmonary bypass and have a sternotomy. Recent experience with surgical embolectomy has had much
better results , much lower mortality than historical, [cite]15867775[/cite]
Temporary VA ECMO as a bridge to one of these other therapies
See the EDECMO site for more on this therapy
Oren's Algorithm
Oren's Slide Set
We discussed this topic with Jeff Kline a few years ago in Podcast 51
Fibrinolysis in PE with Jeff Kline
Want to know what to do for the rest of resuscitation for these patients?
We'll have a podcast soon regarding the management of right ventricular failure, until then see this excellent post by Josh Farkas.
If they go into arrest, give tPA [cite source='doi']10.1371/journal.pone.0008323[/cite]
As to what dose, who knows? Here is a great post on it. I would give tenecteplase.
Expert Commentary on the Podcast
Provocative topic. Like it or not, these [PE Treatment Teams] are here to stay. I managed to get one going at Methodist. How? Well, maybe a little by perseverance, knowing the evidence, showing up for meetings, building alliances. Yeah, sure. But what sold it was when I found out for sure that the main competitor hospital, St. Vincents’ Hospital, was setting up the same program and had treated 18 patients with CDT [catheter-directed therapy] the month before. Then, suddenly attitudes changed. So what will be the main driver? The old ‘reducing practice variability’ line will be the party line. The real driver will be market share.
As Vic Tapson said in ATS two months ago “The practice is racing ahead of the evidence.” While I study lytics, and am a proponent of using them in massive and severe submassive, as your speaker advocates, I have to think like a contrarian for a minute. Funny thing is by reducing variability, we may all be doing the wrong thing instead of just some of us.
The standard lines from most pulmonologists is “All my submassive PE patients do fine with heparin and warfarin. You guys are putting them at risk because there is no mortality benefit.”
Then the JAMA SR [the Chatterjee one mentioned above] came out 3 weeks ago showing mortality benefit and a huge NNH:NNT ratio for age<65 for survival. A huge shift. Now they say “It still increases bleeding risk…and there is no improvement in quality of life.” So I show them TOPCOAT, and they don’t read it except to see that part of the outcome was a survey, and conclude that they don’t believe in surveys (despite similar surveys being the endpoint for many other lung treatments they use; besides, the SF36 was by far the minority driver of the composite endpoint in TOPCOAT). This is going to be like stroke: a substantial number of physicians with ambiguity intolerance syndrome will say the devil you know is better than the devil you don’t. They see the clot in the lungs as better than the bleed that might happen. There are outspoken emergency physicians who still think lytics are dead wrong for stroke, monkey-fisted that position, and in some sense have marginalized themselves from the mainstream. I suspect as we go forward, about 40% of the pulmonology community will be shaking their heads saying “what are you guys doing.” But, even if the evidence is mixed, market competition will drive this forward.
At this point, I agree with the speaker, who I believe is a pulmonologist. We should be giving systemic lytics to patients<70 years (more or less) with no contraindications, when the RV that is smashing the LV. Whether we should use catheter-directed therapy (CDT), is to me, the real question at this point. CDT offers the advantage of lower lytic dose, and Ekos just got FDA clearance to market, and has an army of cardiologists behind them. Curiously, IR guys think Ekos is bogus and prefer CDT. But no trial has compared Ekos or general CDT to systemic lytics, and I doubt any CDT advocates will try such an RCT.
Jeffrey Kline [aka the Man]
comments in brackets are EMCrit's
Update:
- Great Post on All of the Above from PulmCrit
- Newest SR
- Evidence to evaluate 24 hour peripheral IV thrombolysis
Additional New Information
More on EMCrit
- EMCrit 199 – Management of Massive Hemoptysis with Oren Friedman(Opens in a new browser tab)
- Podcast # 51: Fibrinolysis in Pulmonary Embolism(Opens in a new browser tab)
- Imaging in Pulmonary Embolism (PE) Algorithm(Opens in a new browser tab)
- EMCrit Wee – PERT Redux Panel Discussion
- EMCrit 308 – Risk Stratification and Treatment of Pulmonary Embolism (PE) 2021 – Is the PERT Wilted?
Additional Resources
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Professor
Nassau University Medical Center
No conflicts of interest (coi).
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Scott, Great podcast as always. Part of the problem is what do we mean by “submassive PE”? There is obviously a spectrum of disease. I’d be very hard pressed to lyse the patient who meets the definition by cardiac enzymes or BNP but otherwise looks great and has a slightly abnormal RV. Furthermore, three trials have now shown that thrombolysis does not reduce short term mortality. PEITHO, by far the largest trial ever done, clearly demonstrated that standard dose tenecteplase (100 mg), made people bleed. Hard to argue with a 10x increase in head bleeds in the treatment arm. There… Read more »
I watched Dr. Friedman’s lecture on emedhome.com and thought it was great. My question is the distinction between catheter directed thrombolysis and ultrasound assisted thrombolysis for acute PE. Do both require 15 hr infusions of tpa at his institution or does CDT mean squirting the TPA while macerating the clot as opposed to a prolonged infusion? I ask because it seems to me that if the PA pressure is very high, then a prolonged infusion would be less desirable versus opening up the clot ASAP to get the PA pressure down. Thanks so much for posting the neuroconference lectures online.… Read more »
both techniques use prolonged infusions. the doses delivered directly into the clot should provide same speed of resolution (at least) as the big systemic dose (especially when they give a bolus up front)
Great Podcast!
For your example of the young patient after 30+ hr plane trip and submissive PE with hypoxia, would you recommend transfer to a hospital with IR, if this patient comes to a community hospital without Interventional Radiology? If so, would you transfer him on a heparin drip?
In the well and stable sub-massive PE do you ever use lovenox instead of heparin? Why or why not?
Thanks for your help.