SCCM Resource Library-Pro/Con: Bust the Clot or Suck It Out: Controversies in Pulmonary Embolism Management

Video Transcription

Welcome to SCCM 2022, Bust a Clot or Suck it Out, Controversies in PE Management. My name is Belinda Rivera-Lebron and I am the Director of the Acute and Chronic Thromboembolism  Program of the University of Pittsburgh and I'm going to be responsible for today's Pro Debate, Pharmacotherapy is Usually Appropriate.  For my disclosures, here is the clinical classification of PE. Notice the distinction between the American Heart Association and the European Society  of Cardiology terminology, using massives versus high, submassives versus intermediate and both use low.  And although sometimes the terminology is used interchangeably, the PE community is parting away from using massive and submassive as it has a connotation of size of clot burden  which has been shown not to correlate with mortality in multiple studies. Let's go through the different types of PE.  Massive or high risk are those who have hemodynamic instability. They're going to have a systolic blood pressure of less than 90 or requiring vasopressors  or have a drop in systolic blood pressure of over 40 for 15 minutes from what they're starting at. They're going to have a positive RV dysfunction on CT scan or echocardiogram.  They are going to have positive biomarkers although they're not needed to meet criteria. And they're going to have a positive PESI or PE Severity Index which includes patient  characteristics of age, history of cancer or cardiopulmonary disease, the systolic blood pressure, heart rate or O2 saturation that convey a higher morbidity and mortality.  And they're going to have a score of, if they're on the regular scale, three to five or in a simplified scale of one or more.  Low risk on the other hand are those who are not going to have any hemodynamic instability, who are not going to have any dysfunction on imaging and that they may not even have  a cardiac biomarker to go by. Now the conundrums really come for those who are in this intermediate risk category.  And as you can see for the European classification it hasn't been divided or further subdivided into intermediate highs and intermediate lows.  And the distinction is that both are going to be hemodynamically stable, notice here their blood pressure is going to be normal, however the intermediate high is going to  have both RV dysfunction by imaging plus an abnormal cardiac biomarker which may be a troponin or a BNP.  And the intermediate lows are going to have either one or none of them positive. Both are going to have an abnormal PESI score.  Most patients present with low risk PE, the majority of them. But however a big proportion of patients is going to present with intermediate and that's  why we need to pay attention to those patients. This is important because the mortality is different.  And as you can see here, mortality is very good in patients that have low risk PE but it increases as the severity of the PE changes.  So it can go from intermediate low to a 2-5%, to an intermediate high ranging from 5-20%, to high risk that can reach up to 50% or more if they have cardiac arrest.  For this talk we will focus on high risk and intermediate risk PE patients. So let's start with the systemic thrombolysis data in high risk PE. High risk PE has high mortality.  Here's data from the ICOPR, which is the International Cooperative PE Registry, one of the first  registries in reporting PE mortality, included almost 2,500 patients with 100 massive or high risk PE patients.  As you can see here, massive PE's mortality were reported as high as 52%. For the MAPIT registry, which is a German-based management strategy and prognosis of PE registry,  the mortality was reported as 8% in patients who were hemodynamically stable, 25% of those who were hemodynamically unstable, and as high as 65% for in-hospital mortality in those  that had cardiac arrest. This is the only randomized controlled trial to date of systemic thrombolysis in high risk PE. A total of eight patients were randomized.  Four patients were treated with unfractionated heparin and they died, and four patients were treated with streptokinase and they survived.  This trial was stopped early by the ethics committee, but 100% of the survival was seen in the lysis group.  Here's the meta-analysis published in 2004 by Wan and colleagues that included 11 randomized  controlled trials and close to 750 patients comparing lysis versus unfractionated heparin.  It showed a reduction in recurrent PE or death in those with massive PE, comparing 9% versus 19% with an odds ratio of .45 and significant confident intervals.  Another meta-analysis that included both intermediate and high risk PE patients showed a decrease  in all cost mortality in patients that were treated with thrombolytics, 2% versus 4%. Major bleeding and intracranial hemorrhage were higher in this group as well.  However, taking a closer look, it looks like patients that were 65 or younger did not have a significantly increased risk of bleeding.  Some of the limitations of this meta-analysis that there were varying definitions for hemodynamic instability as well as varying doses and types of lysis.  Now what about thrombolysis in patients that had in-hospital PE cardiac arrest? This was the PEPET study, which was the Pulseless Electrical Activity PE treated with thrombolysis,  a single center retrospective cohort of cardiac arrest patients with PEA due to massive PE. Of those, 16 had a preexistent PE diagnosis prior to their arrest and four, the diagnosis  was made after the lytics were given. A 50 milligram TPA bolus was pushed for one minute and the time from initiation of CPR to TPA was six minutes.  For those who work in the ICU like me, this is very difficult to accomplish. They did show a ROSC of two to 15 minutes post-TPA with a 91% survival to discharge  and 87% survival at two years without any significant major bleeding. Now let's move on to the data of systemic thrombolysis in intermediate risk PE patients.  The first thing to recognize in the intermediate risk population is that a large proportion of these patients may be in cardiogenic shock despite having a normal blood pressure.  This was shown in a study that we did after combining patients from the University of Pittsburgh and the University of Pennsylvania, including 92 patients that were already referred  for catheter directed thrombolysis in which baseline hemodynamics were obtained. And as you can see here, 40% of those patients had a cardiac index of less than 1.8, which  most will agree that meet criteria for cardiogenic shock. Now here notice how the admission systolic blood pressure was normal in both groups.  And another thing to point out is that in this study that their shock index was less than 1. Shock index, as you know, heart rate divided by systolic blood pressure, which has been  extensively studied in sepsis, is a very useful marker of mortality. Now we have incorporated using shock index in our intermediate risk population sometimes  when we want to decide on whether the patient needs advanced therapies. Now what's the data of systemic thrombolysis in intermediate risk PE?  This study, largest study to date, randomized control trial called the PATHO trial, included over 1,000 patients with intermediate high risk PE.  So as they needed to have both RV dysfunction by imaging and a positive troponin. The primary outcome was all-cause mortality or hemodynamic collapse within seven days  of randomization, which was defined by the need for CPR, the systolic blood pressure  drop of less than 90 for 15 minutes or more, or a drop of over 40 with an end-organ hypoperfusion or presser initiation.  You can see here that the primary outcome was met and thrombolysis was deemed superior. However, a closer look at the results will show that the death from any cause in both  groups was low and not significantly different, but the primary impone was actually driven  by a reduction in escalation to emergent therapy or hemodynamic decompensation, which was significantly different among both groups.  The other important finding is that the major bleeding was 6% versus 1%, so a five times higher risk of bleeding, and the stroke risk was 2% versus 0.2%, with a 12 time higher  risk of stroke, including intracranial hemorrhage. Therefore, the key here is to identify those patients that are highest risk of decompensation  in which reperfusion may be justified, but the routine use of systemic lysis in this population is not recommended.  A recently published meta-analysis only including patients with intermediate risk PE patients  had 12 studies, did favor the use of thrombolysis in this population with almost a 40% decreased  mortality, did confirm the increased risk of bleeding compared to anacoagulation, though. So after reviewing this data, what do major guidelines recommend regarding the use of  systemic thrombolysis in both high risk and intermediate risk patients? Let's take a look. So the guidelines say that the use of systemic thrombolysis in PE is recommended for those  with high risk PE and low bleeding risk by the American Heart, European Society of Cardiology, ACCP, the PERT, which is a PE response team consortium.  It's recommended in those with a confirmed PE that had a cardiac arrest by the PERT, American Heart, ACLS, and the European Resuscitation Council, and for cardiac arrest with highly  suspected PE as well. Now with intermediate risk PE on patients who deteriorate but have yet to develop hypotension  and have low bleeding risk, systemic thrombolysis can be considered, again, recommended by a AHA, ESC, the ACCP, and PERT, but it's not recommended for everyone else that has an  intermediate risk PE without a clinical deterioration or definitely not with low risk PE.  So here's a practical approach to management of PE from the 2019 European Respiratory Society and European Society of Cardiology.  The first step is to assess for hemodynamic instability. If the patient's hypotensive, automatically, or in shock, or automatically they're considered  high risk, and reperfusion therapy is highly recommended as first line. If patient is not hemodynamically unstable, then there's really time for risk stratification,  and here's where we're going to introduce using the PESI score, PE Severity Index, or the Simplified PESI score, and RV imaging using ECHO or CTA.  If both are absent, the patient's low risk. If one or both are present, then the patient's in that intermediate risk category.  For patients who have intermediate low risk PE, anticoagulation alone is sufficient, but for those who have intermediate high risk, again, having both biomarkers and cardiac  dysfunction by imaging, starting anticoagulation with readily available rescue reperfusion if clinical deterioration is seen, is recommended.  And the key word here is rescue, which means that most patients will do just fine with anticoagulation alone, but you want to be vigilant if there is any decompensation to  rapidly be able to mobilize the patient for advanced reperfusion. This is a more detailed algorithm by the PER Consortium, an association of hospitals with  PE response teams with the goal to standardize PE care and improve outcomes. This was developed using both evidence-based and real-world data and expert opinion.  Decisions for treatment should be individualized based on patient characteristics, comorbidities, and risk of bleeding.  The PER concept lays on sharing decision-making, especially when data is not readily available. So let's take a closer look at the high-risk PE algorithm.  So for patients who are already diagnosed with a high-risk PE who are hemodynamically  unstable, the first thing to do, in addition to consulting PERT, would be assessing contraindications for thrombolytics.  If the patient does not have a contraindication, then a full-dose lytics should be recommended.  If the patient has a relative contraindication, then either reduced-dose systemic lytic or  consideration for advanced therapies such as catheter-directed intervention is recommended.  And a patient is an absolute risk for thrombolysis, such as intracranial hemorrhage or active bleeding, then considering catheter or surgical embolectomy is recommended.  If the patient has refractory shock even after the first therapy has been introduced or there is any clinical decompensation or cardiac arrest, we consider using mechanical support.  Some experts may even say to consider mechanical support earlier in this population. Now this is a closer look at the intermediate-risk algorithm.  As you can see here, it's recommended to involve PERT for those patients, especially if they have an intermediate high-risk after you've diagnosed them.  Starting an coagulation is ultimately the most important thing, and then monitoring for any signs of clinical decompensation.  If that's the case, then assessing for contraindications to thrombolytics is the next step.  If there's no contraindications, then consideration for catheter-directed intervention such as catheter-directed thrombolysis or reduced-dose systemic lytic may be recommended.  Now if there is a contraindication to thrombolysis, then considering the use of catheter or surgical thrombectomy is recommended.  So in summary, in PE patients, pharmacotherapy with systemic lytics is usually appropriate. Why?  Because it's readily available, TPA is available in both large academic centers and community hospitals, fast administration, it may be pushed over one minute or takes two hours  at most in an infusion, rapid onset of action, it's half-life, it's 4-10 seconds for TPA or 15-25 seconds for tenecteplase, and its effects may be seen as fast as right after  completing the infusion. Like I showed you, it has mortality benefit, best shown in high-risk, but also different  meta-analysis have definitely demonstrated an intermediate risk as well, and its use is supported by major guidelines. Now how does it compare to catheter-directed therapy?  You can see here that systemic thrombolysis meets most of the advantages when compared to catheter-directed therapies.  Okay, again, readily available, it doesn't depend on operator experience, it's a one-job  person and you don't need to activate a cath lab or an OR, fast administration as I mentioned,  rapid onset of action, it doesn't take hours to get this set up, mortality benefit, like I told you, maybe there's some mortality benefit for catheter-directed therapy, but that's  yet to be seen in randomized prospective trials.  Decision-making risk definitely is a downside, and we're in which the catheter-directed therapies have an advantage.  Data on patients with cardiac arrest, and supported by major guidelines, both of them depending on which guidelines are used.  Now the reality is that this is all easier said than done. Decision-making is challenging. Why?  Well, first, advanced treatments vary by institution, specialty, and operator experience, two, variation  and ambiguity in clinical guidelines exist, and three, there is lack of robust, large clinical trials. And this is why PERT is so important.  So again, what is the PERT PE response team? A multidisciplinary team with expertise in the diagnosis, medical, surgical, and interventional  management of PE who collaborate to improve patient care. We discuss patients in real time, individualized decision-making for each patient.  Its use has been adopted nationally and internationally. It's been shown to work in academic and non-academic settings.  So in summary, if we reformulate the question to, is systemic thrombolysis the treatment of choice for high-risk PE?  The answer, yes, for patients without contraindication stethetics, no, for patients with contraindication stethetics. This is simple.  However, is systemic thrombolysis a treatment of choice for intermediate-risk PE? The answer is no for most patients, but yes for those with signs of clinical decompensation.  But the bottom line is that a combination of systemic lysis, catheter-directed therapies, and surgical thrombectomy offers balance in safety and efficacy and should be discussed  in a multidisciplinary fashion in a PERT team to better have a recommendation individualized for each patient.  And here I thank you for the opportunity, and here's my email, and I'm happy to take any questions. Hello. My name is Michael Shishady.  I'd like to thank the Society of Critical Care Medicine for inviting me to speak at this PROCON session.  I will be taking the topic of pulmonary embolism, intervention is a better choice, although you can see that I have entitled it, When Intervention is a Better Choice.  My disclosures include funding from NIDDK and NIGMS that are not related to pulmonary embolism research, and I will also note that I do not perform catheter-based or surgical  procedures for pulmonary embolism. Let's start with a case, a 75-year-old female with a remote history of ischemic CVA with  no residual deficits who presents with acute shortness of breath and pleuritic chest pain six weeks following a presumed curative resection of colonic adenocarcinoma.  She has a CT of the chest showing an acute pulmonary embolism located in the right main PA, non-occlusive in the right lower lobar pulmonary artery.  Her vital signs are notable for a heart rate of 95, blood pressure 105 over 75, slight desaturation on room air, which is corrected with 2 liters nasal cannula, and her TTE shows  an RV to LV ratio of 1.3 with moderately reduced RV function. She has an elevated troponin. So to the point of this session, bust the clot or suck it out or perhaps something else.  So that's the framing, but here's the overview of what I'd like to talk about in my part,  PE risk stratification and outcomes, thrombolysis limitations, embolectomy options and evidence, and weighing competing risks and moving forward.  So let's start for a sec with PE risk stratifications and outcomes, and I think it's important to  understand what the risks are so that we can balance what kind of therapies we want to use and what are the risks that are associated with those therapies because I don't want  to take extra risks if I think I have a very low risk patient in front of me and that patient can simply be managed by heparin or low molecular weight heparin alone.  And so there are a couple of different methods of risk stratifying patients with pulmonary embolism.  These are not the only ways to do this, but the AHA criteria of risk stratification divide patients into low, submassive, and massive pulmonary embolism, whereas the European risk  stratification schema divides patients into low, intermediate low, intermediate high, and high.  And these categories are based on whether there is right ventricular dysfunction, either  on CT scan or an echo, whether there are abnormal biomarkers, biomarkers of myocardial injuries such as troponin, and also whether or not there's hemodynamic instability.  And hemodynamic stability, of course, is associated with the highest mortality, a 30% mortality around the one month mark, both due to the acute PE itself and then the  underlying diseases that patients have, and that's deemed the massive category. But it's also the smallest category, about 5% of patients present with that,  whereas among the patients who are hospitalized for PE, about 35 to 55% of them fit into this intermediate risk or submassive category, whereas around half  of the patients who have a very low risk of mortality fit into the low risk category. I'll note that this middle risk category, the submassive or intermediate  risk PE, has an estimated mortality of between 3 and 15%, usually measured around 30 to 90 days, and while a portion of that is related to underlying illness,  there's no question that a chunk of that mortality comes specifically from the pulmonary embolism itself, and I think this is a useful framework for us to  just think through as we're then evaluating the therapies we may want to apply to these patients. Looking at long-term outcomes, this is two-year  follow-up in the PATHO study, which included patients randomized to systemic thrombolytics and heparin alone. Mild exertional dyspnea was seen still in 33%  with New York Heart Association functional class 3 to 4 in about 11%. There were persistent echocardiographic findings of RV dysfunction in 7 to 19% of  patients and chronic thromboembolic pulmonary hypertension in about 2 to 3% of patients. We would, of course, like to improve these outcomes, and  thrombolytics have been proposed as a therapy that could do just that, but I want to take a few minutes to talk about what the limitations of thrombolytic  therapy are. I'll first make mention of thrombolysis for patients with high-risk PE, specifically shock. Most of you will be familiar with this study from Mexico  City of thrombolytics plus heparin versus heparin alone. The good thing about this study is that it was a randomized control trial. The not as good is that it  was a tad small, eight patients total. It was terminated when four out of four heparin alone patients died within the first one to three hours, whereas zero  out of the four patients who received streptokinase died. They were all alive at two years. Clearly, this is limited data. It's only eight patients. Based on  this, systemic thrombolysis has become the standard of care for high-risk PE patients. Intermediate-risk PE, on the other hand, has much richer data. These  are data from the PATHO study, the largest of the studies to compare systemic thrombolytics to anticoagulation alone. You can see PATHO,  the goddess of persuasion, up there in the right-hand corner. From an efficacy standpoint, the PATHO investigators found that their composite outcome, which  was death from any cause or hemodynamic compensation within the first seven days, was significantly reduced among those who received thrombolytics, driven  principally by a reduction in hemodynamic decompensation. But from a safety standpoint, major bleeding was clearly higher in the thrombolytic group, almost  12% versus 2.5% among those who received anticoagulation alone. Hemorrhagic stroke was seen in 2% of those receiving thrombolytics versus 0.2% of those who  received anticoagulation alone. Of course, PATHO also conducted a long-term outcome study, which was extremely helpful and in some ways unfortunate, I  think, if you want to be in the camp of giving thrombolytics to these patients.  What you can see on the graph is just the cumulative risk of death, showing no real difference over time between placebo and systemic thrombolytics. But similarly,  what you can see in the table on the right is that looking at additional outcomes, such as functional limitation, frequency of pulmonary hypertension, frequency of  right ventricular dysfunction, frequency of chronic thromboembolic pulmonary hypertension, thrombolysis in these submassive PE patients did not affect those  outcomes, and this was going out to two years. So on the whole, the PATHO study showed some improvement in short-term outcomes, offset to some extent by an  increased risk of bleeding, including hemorrhagic stroke, and did not appear to impact long-term outcomes from pulmonary embolism.  Thrombolytic data are, of course, not limited to PATHO. There are a number of other studies done. This is a figure taken from a 2014 JAMA meta-analysis. You can  see PATHO at the bottom there, with an unclear benefit in terms of mortality, although the overall meta-analysis suggested that systemic thrombolysis may be  associated with a reduced rate of mortality compared with anticoagulants alone. But similar to the PATHO study, in the meta-analysis, major bleeding risks were  increased in patients who received thrombolysis. A major bleeding rate of 9% versus 3.5% in the anticoagulant group alone. Intracranial hemorrhage of 1.5% versus  0.2%. And then if you look in the higher age category, greater than 65 years, a 13%  major bleeding rate among those who received thrombolysis. So, non-trivial in terms of a potential adverse event related to systemic thrombolysis.  Catheter-directed thrombolysis represents something of a midpoint between the bust the clot and suck it out camps. When you're doing catheter-directed thrombolysis,  you mostly are busting the clot, sometimes aided by ulcerative colitis, which is a  ultrasound. And we would like to think that by using lower dose thrombolytics in these patients, we may reduce the rates of major bleeding. In this meta-analysis that was done  in 2019, I think although there's a lot of heterogeneity in these studies, one can see  the average rate of major bleeding is about 4%. And the average rate of intracranial hemorrhage with catheter-directed thrombolytics is on the order of 1%, maybe a little bit less.  These were not trials that were compared with other groups. It's difficult to tell exactly how representative they are, but it's hard to take away from this that catheter-directed  thrombolysis is associated with a very, very low risk of major bleeding.  And of course, these studies may not even capture the higher bleeding risk patients. Although  PATHO did allow some patients who had relative contraindications to systemic thrombolytics to  be enrolled, they did not exclude patients on the basis of gender or race. They were excluded  for being on vitamin K antagonist therapy. They were excluded if their blood pressure was high. And of course, you can see the list of major contraindications for people to systemic  thrombolytics in which this just may not represent a feasible approach.  And specifically in PATHO, I think it's useful to look. You can see when they did a subgroup  analysis, the patients who were older than 75 seemed to have a particularly higher risk when  it came to this is major extracranial bleeding. And similarly, with female patients, which suggests that there may be subgroups in whom thrombolysis represents added risk,  and perhaps we need another approach for these patients, at least another option.  Let's go through some of the embolectomy options and the evidence for those therapies.  Catheter-based embolectomy options. I have listed these without trade names. Those are things that  you can look up yourselves, but I listed them as a small-bore suction catheter, a large-bore  suction catheter with clot-engaging discs, and a large-bore suction catheter with a filter and a  re-infusion cannula. And it's really the first two that have a reasonable amount of evidence. I  will mention briefly the third one and the very limited evidence that exists for that. So this is an introduction to these and what kind of evidence we have for actually affecting  suction of clot. The small-bore, eight-french suction catheter was tested in a study called  ExtractPE. This was a single-arm study. Everybody received the intervention, 119 patients at 22  centers. They included patients with intermediate risk PE, as defined by a systolic blood pressure  greater than or equal to 90 and an RV to LV ratio greater than 0.9. Troponin positivity was not  required, but it was present in 71% of patients. I will note that 46% of the patients had a simplified  PE severity index of zero, which connotes a relatively low mortality, around 1% of 30 days.  Patients were about 60 years old. Almost everybody had a bilateral PE and everybody had it in the  main PA or lobe. The device time, which is not the entire procedure time, just while the device was in the patient, was 37 minutes median. And TPA was also given to two patients  intra-procedurally and an additional five within the first 48 hours for 6% total who did end up  receiving TPA. I list the ICU need simply to note that many of these patients do not need to go to  the intensive care unit. 40% in this study did not need the ICU. The main efficacy outcome was looking  at the change in the RV to LV ratio at 48 hours. And so that 0.43 is a reduction, meaning they  started out at 1.43 and the ratio dropped down to 1.0, for example, at 48 hours. Safety was measured  by major bleeding. There were two patients who had that about 2%. There was pulmonary vascular injury in about 2% of patients thought to be perforation of a small pulmonary artery.  And then there was one ruled device-related death. This was in a patient who had a pulmonary  vascular injury, then subsequently developed bleeding at the insertion site, and ultimately, about 12 hours later, developed sustained ventricular tachycardia and expired.  Overall mortality in 30 days was 2.5%. Two of the patients were from underlying disease, and the third was the device-related death as ruled above.  There's a large-bore, 20-french suction catheter with clot-engaging discs. And you can see a  picture over on the right-hand side, the catheter first, and then where it comes out at the end,  these are expandable discs. As the catheter goes in, they're not expanded, but they can be expanded by the operator to engage the clot, and then pull the clot into the catheter to  be sucked out. And then you can see some of the images in A, you can see that the entire right lower lobe is essentially not being perfused. Then you have a few images showing  at the intervention, and then following the intervention, the improved perfusion to the  entirety of the right lung. This study was called the FLARE study. It was a single-arm, again,  study of around 100 patients at multiple centers. Similar risk stratification to those who were in  the EXTRACT-PE study, and similar age as well, around 56 years old. 90% of patients had bilateral  PE. 44% of them had central PE. The device time was a little longer. This is a mean, 57 minutes.  Fewer patients in this study received TPA, about 2%, and a similar need for ICU, about 60%.  The change in RV to LV ratio at 48 hours was 0.38. Major bleeding was seen in one patient, 1%.  One patient had a pulmonary vascular injury and required a lobectomy, and emergency intubation on the table was required in 3% of patients.  There was one patient who died within 30 days. This was from underlying disease, specifically a previously unrecognized metastatic breast cancer diagnosis.  This last one I'll just briefly mention. It's a large-bore 18 to 22 French suction catheter  with a filter and a reinfusion cannula. You can see this suction catheter here up in the upper  right that has a flared tip. This is different from the other catheters. The way that it's used  in the patient is that there's access at two sites. This catheter goes in to the spot where  suction is desired, and then there's a reinfusion cannula so that blood can be sucked out,  clot can be filtered out, and then the blood that is extracted is reinfused to the patient  to reduce the blood loss that sometimes can be associated with the straight suction catheters.  This is really limited to case series data coming out of MGH. It was a 15-patient study,  but only three of the patients had pulmonary embolism aspiration done. I've listed some of  the other characteristics here, but ultimately, it's such limited data from this study that it's  really difficult to tell how this applies overall to patients who have pulmonary embolism. I will  specifically note in summary here that there are very minimal data for this catheter on PE  aspiration in particular. There were many more of these that were IVC thrombus or thrombus that was  in the right atrium or right ventricle. It can be difficult to maneuver this catheter into the pulmonary artery, and it, of course, requires a pump and a circuit.  This is a comparison of some of the major mechanical thrombectomy trials with a representative  catheter-directed lytic trial, the CL2 trial, and the lytic arm from the patho-study systemic  lytics. I note here that the comparison is limited. Obviously, we're comparing across trials, and just noting in the first row there, only one trial was a randomized control.  Just the patho trial. The rest were single-arm studies, and so let's just look through how the  rest of these categories compare across these studies. Patients generally were intermediate risk PE. That was true for the thrombectomy studies. Most were for the catheter-directed  lytic study, although 20% of patients had high-risk PE, and then the patho-study although 20% of patients had high-risk PE, and then the patho-study specifically looked for  intermediate high. They mandated that patients had myocardial injury markers elevated, which  was true for most of the patients in the mechanical studies, but was not true for 100% of those.  You can also see that the patho-study enrolled, on average, older age patients, 67, whereas  the interventional studies were closer to 55 to 60. Device time was a little bit longer in the  flare study compared to the extract PE study, whereas in the catheter-directed lytic study, Seattle 2, patients received 12 to 24-hour infusions via the catheter. In patho, there  was just a fraction of patients who were actually treated ultimately with a device. Thrombolytic use was very uncommon in the mechanical thrombectomy studies,  and then you can see a comparison of change of RV to LV ratio at 48 hours, fairly similar across the interventional studies, not reported in patho. Major bleeding is a big  difference here when you just look at the absolute numbers. In the studies that didn't use or  essentially used almost no thrombolytics, the major bleeding rates were to 1%, whereas the  lytic studies are towards the 10 to 12% range. Again, I will note that these patient populations  may not be 100% comparable, so it's difficult to say for sure what would happen if you put  these head-to-head, but it is not too surprising that the major bleeding rates appear to be lower  in these mechanical thrombectomy single-arm trials. Procedural safety is, of course, important to keep in mind, and those risks will ultimately need to be weighed against the risks  that are conferred by thrombolytic therapy. And then the 30-day mortality of these groups globally  was not too dissimilar in the 1% to 3% range. Briefly on surgical embolectomy, it's not done  very frequently. There's a large New York State database study looking at surgical embolectomy as a first-line therapy, which was done in 0.1% of patients hospitalized for PE.  They did an actuarial survival analysis versus patients who received thrombolysis as first-line  therapy. That survival was similar, and, of course, looking at the patients, one might imagine  they would be a little bit different. They were similar in age, but the embolectomy patients were  more likely to have undergone recent surgery. It's hard to take too much out of this retrospective  study in terms of directing therapy. So a couple of brief words on weighing the competing risks  and moving forward, which I think we need to do in the field. Systemic thrombolysis. I think that  we can say, based on the studies, that is likely to decrease hemodynamic decompensation in the early  going. And, of course, systemic thrombolysis is readily available without the need for high-level  expertise. But some downsides include pretty well-demonstrated increased major bleeding risk, increased risk of intracranial hemorrhage, and no clear long-term outcome benefit.  But I will highlight, we know that because it's actually been studied.  Considering embolectomy, there's a possible decreased major bleeding  risk, such that we may feel more comfortable using this in patients with thrombolysis  contraindications, as an example. Anybody who's at higher risk. We have not pitted these patients  head-to-head against those who have received thrombolytics. And, of course, we can see from  these studies that there's a rapid decrease in RV strain. Again, that's not compared to control  patients who have received heparin, but prior studies would suggest that heparin alone is not  likely to decrease the RV strain that rapidly. But decreased RV strain is a surrogate marker.  It's not necessarily a clinically relevant marker. And some downsides for embolectomy include the  need for procedural expertise and figuring out the logistics of actually enacting these therapies in  a hurry. Pulmonary vascular injury is a concern. And, of course, there are limited clinical comparative outcomes data with thrombolysis or with anticoagulation.  What about high-risk PE? Do we have any new options? I will concede that systemic thrombolysis  is the current standard of care, but I think we should be thinking about another possible route.  And I am not recommending this. I just think that it is worthwhile to think through whether  there may be other options that we could test in this scenario. So, one that has been proposed  is to take a patient, if you can rapidly do this, to the catheter lab, having mechanical circulatory  support on standby, and then performing catheter-directed lysis versus embolectomy.  My feeling on this would be that for a patient who has really strong contraindications to  systemic thrombolysis, I might consider taking this route if I think that we can perform embolectomy  and effect a rescue in a patient that otherwise would be either nearly impossible or extremely  high-risk from a systemic thrombolytic standpoint. Clearly, more data would be helpful here.  And I will note, lastly, that there are clear priorities for study. We don't know the answer,  I don't think, to this question. We need better patient risk stratification because we'd like to  be able to say, we're only going to give some of these more advanced therapies that may have  higher risk to patients who really are going to have a high risk for bad outcomes otherwise.  We'd like to be able to tailor the therapies to individual patients. Certainly, PE response teams  could be used as an infrastructure to permit better data capture on patients that we're managing.  And we need focus, as was done in PATHO, on patient-centered medium and long-term outcomes  as well. In summary, intermediate risk PE may result in substantial mortality and morbidity,  but better risk stratifications are clearly needed. I think that the literature shows that systemic  and catheter-directed thrombolysis confers an increased risk of major extra and intracranial  hemorrhage. Catheter-based embolectomy data are now emerging. These data are not conclusive,  but this approach may offer an option to improve outcomes, particularly in patients who have a  higher bleeding risk. And I want to offer my particular thanks to Jay Geary, Steve Pugliese, and Tai Kobayashi for helping to provide information, literature, and some slides for  this talk. They are members and directors of our PERT team here at the University of Pennsylvania. Thank you very much.

Video Summary

The video transcript discusses the management of pulmonary embolism (PE), specifically focusing on controversies surrounding the use of systemic thrombolysis and embolectomy. The speaker highlights the distinction between high-risk and intermediate-risk PE patients and emphasizes the importance of risk stratification. The transcript discusses the limitations of thrombolysis, including increased risk of bleeding and lack of long-term benefit. It also explores the efficacy and safety of catheter-directed thrombolysis and mechanical embolectomy. The speaker presents data from various studies, including the PATHO trial, which showed the reduction in recurrent PE or death in patients with massive PE who received thrombolytics compared to heparin. The transcript also mentions other studies that support the use of thrombolytics in intermediate-risk PE patients. However, the speaker acknowledges the increased bleeding risk associated with thrombolysis. The transcript briefly discusses the use of embolectomy as an alternative option, noting its potential benefits, such as lower risk of bleeding. Overall, the transcript suggests the need for better risk stratification, more research on patient-centered outcomes, and individualized treatment decisions based on patient characteristics and risk profiles.

Asset Subtitle

Pulmonary, Pharmacology, Hematology, 2022

Asset Caption

Pulmonary embolism (PE) is an important cause of mortality. One-third of deaths are sudden, and 60% are undiagnosed before death. Recognition of PE can be challenging because symptoms and clinical signs may be nonspecific. Patients with massive PE and frank shock require urgent support. Patients with submassive PE present more of a dilemma. Patients with elevated cardiac troponin and/or right right ventricular strain on echocardiography are at higher risk of in-hospital mortality; most of them will improve with conservative therapy but some will not. Precisely how to treat these patients remains a clinical challenge. New interventional strategies with either catheter-directed therapy, mechanical fragmentation, thrombectomy, or a combination of these have been proposed, but firm data supporting a benefit in hard outcomes is currently lacking. A pro/con debate will contrast pharmacologic therapy with interventional strategies for PE. Learning Objectives: -Perform risk stratification in patients with pulmonary embolism (PE) -Select patients for anticoagulation and/or thrombolytic therapy based on risk stratification and the risks and benefits of pharmacotherapy -Select patients for mechanical therapies and choose among available options based on risks and benefits -Consider the merits of a PE response team as an institutional strategy

Meta Tag

Content Type Presentation

Knowledge Area Pulmonary

Knowledge Area Pharmacology

Knowledge Area Hematology

Knowledge Level Intermediate

Knowledge Level Advanced

Membership Level Select

Tag Pulmonary Embolism

Tag Pharmacology

Tag Coagulation

Tag Thrombolysis

Year 2022

Keywords

pulmonary embolism

thrombolysis

embolectomy

risk stratification

bleeding risk

catheter-directed thrombolysis

mechanical embolectomy

patient-centered outcomes

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