Dave administers the polite smack-down of neural intervention procedures. Also, he calls out some amazingly un-scientific conclusions by some neuro-interventionalists.
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Many thanks to Dr. Dave Newman for his superb Mini Journal Club on stroke interventions. However, as someone who trained in emergency medicine when the only thing we had to learn was whether to bleed or to purge and how much, I must take issue with his somewhat disparaging comments on bloodletting. I’m sure those negative trials on bloodletting that he mentions would have shown benefit if they had only used the newer and more effective instruments that we have for bloodletting today. Further, I have no doubt that many of the patients in those trials really were patients who should have been purged, so of course bloodletting could not be expected to work. Finally, I do not think it is fair to draw a parallel between bloodletting and neurovascular interventions for stroke. Bloodletting is obviously different, as it is orders of magnitude less expensive.
This was great. Thanks :) A few questions, What about intra-arterial tpa? It is not clot retrieval, and it allows a greater time window for treatment. More beneficial or less than traditional systemic tpa?
I am at a hospital that does some basic stroke care, such as tpa and following pts who received tpa. However, when a pt is beyond the 3 or 4.5 hr window but under the 6 -12 hour window or a 3 hour window pt who is not a candidate for tpa, we often transfer them to the university based hospital for further evaluation and possible neuro-intervention. In the studies discussed on emrap, these pt were better off getting tpa, but if you are out of the time window, (the italian study that compared tpa with interventions was in the time window) isn't a neuro-intervention better than nothing? We have nothing to offer our pts, where the university hospital has an option for them. Is this possibly where neuro-interventions are best used - when pts are out of the time window for tpa? I don't think most of our pts end up getting an intervention, but I do not know how the ones who get it, end up doing. Hopefullly, they do well.
In the podcast, we learn that time is not brain as no association between giving the drug earlier and better response to therapy. Then, why can't we go beyond 4.5 hrs with tpa?
Hello. I agree with the content of the MJC commentary. However, there is one consideration I would like to bring up that wasn't mentioned. Essentially, the studies reported essentially showed (overall) improved patency of the major artery but no significant improvement in overall patient outcomes. OK so if it doesn't help patients then it doesn't matter that the artery is open. I'm with you there. But the issue of the 'wishfullness' of neurointerventionalists in terms of new devices may deserve more consideration in the future... if there is a qualitative difference in the functionality of the new devices. And that consideration (in my mind) is that if the old devices did not do a good job of preventing distal embolization at the time of intervention, then they wouldn't be expected to due as much for actual brain perfusion. The theory behind at least some of the new devices is design change to prevent this distal embolization of clot fragments. I'm not saying they work and I have no data and we should believe that they do until we see data to prove it. I just wanted to bring up a point that a potential qualitative change in the intervention of question may warrant more consideration that was alluded to in the segment. There may (not there is but there may) be merit to different and not just 'new' devices. I'm a 2nd-year-out community EM provider with no industry or neurointerventionalist associations.
Mel & David, Absolutely wonderful segment. Having Mike politely interview the primary authors then having a polite rebuttal was extremely constructive. I liked your explanation of "wishful thinking" as a strong source of bias in addition to obvious financial incentives. I agree with you, Mel, in that this would have been even better had this been included in the same issue as Mike's interview, just as NEJM put all three articles in their same issue.
I would greatly enjoy hearing similar discussions between Jerry Hoffman and David on Perry's article regarding CT in SAH. I am like Al Sachetti in that I listen to EMA and EmRAP every month. When Jerry and David disagree on a given article, it would be interesting to hear them respond to eachother directly.
Lastly, I think this segment also shows that EmRAP would be the best forum to interview the ACEP leadership that decided to recommend TPA for stroke. Hold their feet to the fire. Keep up the great work, "what you do matters"!
Fantastic! Three thumbs up (Don't ask) ! A roller coaster ride truly phenomenal! EmRap segment of the year IMO, maybe the decade! Listen to this, listen to it now! Bring the kids! Fun for the whole family! Honestly David I thank u from the bottom of my cortex, perfused or not it sees this as a truly insightful and necessary rebuttal. When I heard the original piece where the interventionalist made that comment about "not needing research....I've seen it with my own eyes" I had to stop my iPhone and double check I was on EmRap....hard to fathom one so far along in their career making such a foolish statement. Statements such as these are usually followed by an immediate interject from Mel..."wha wha wha what???????? Then a rational disclaimer for the foolishness. Its nice to know that even the Great Sheep Husband has his down days.... perhaps his local mini mart was out of Monster that day....Kudos to Mel for halting his waltz with Matilda to add your "retort". God I could listen to that all day. Love it!
Love the segment and commentary on how wishful thinking can override data! It happens all the time in medicine and in the real world! While listening to this discussion on my way home after a shift in the emergency department, I started pondering the ischemic penumbra. We routinely treat the" ischemic penumbra" with hyperbaric oxygen in patients who have various types of chronic wounds. We see a very significant response in diabetic foot ulcers and other types of injuries that involve an area of ischemia, with surrounding areas of variably ischemic tissue that may respond if it is re-oxygenated. We also know that even if a small artery is blocked, collateral circulation can provide oxygenation to the ischemic area if the plasma delivered by the collateral is hyper-oxygenated. Oxygen delivery extends 3x the distance with hyper oxygenated plasma than when delivered by red cells. If we placed the patient with an acute stroke in the hyperbaric chamber and we saw a dramatic improvement shortly after getting them to pressure, (approximately 2.5 atm to 3 atm absolute), would that not give us a good idea that permanent reperfusion of the affected areas by recanalization might result in a benefit? We know from previous studies in human stroke patients, that they did not benefit from hyperbaric oxygen, however these were performed at a timeframe outside of what we would consider an acceptable window for treatment. We do know that in animal studies where the carotid artery is tied off and blood flow is interrupted and the animal goes into the hyperbaric chamber, there is an improvement in outcome after the tie is released, compared to the no HBO group. The human studies have not been done in the acute phase of a stroke. I think this is unfortunate. Hyperbaric oxygen has very few complications when used in the appropriate patient population. We also know that despite creating very high levels of oxygen, there is a well-documented inhibition of reperfusion injury. Despite huge partial pressures of oxygen, the release of toxic oxygen radicals is substantially reduced when patients undergo hyperbaric therapy acutely for a compartment syndrome. Hyperbaric oxygen may be able to assist in preventing some of the reperfusion changes in CVA also. This would be a very interesting way to test the hypothesis that the ischemic penumbra reperfusion actually matters. Just saying'...
If doubling the patency rate did not result in any improvement in clinical outcome. How can we continue to believe that the "open vessel" theory is applicable to the brain (as applied.) In other words, "How can we continue to believe that TPA works?"
Fantastic! Three thumbs up (Don't ask) ! A roller coaster ride truly phenomenal! EmRap segment of the year IMO, maybe the decade! Listen to this, listen to it now! Bring the kids! Fun for the whole family! Honestly David I thank u from the bottom of my cortex, perfused or not it sees this as a truly insightful and necessary rebuttal. When I heard the original piece where the interventionalist made that comment about "not needing research....I've seen it with my own eyes" I had to stop my iPhone and double check I was on EmRap....hard to fathom one so far along in their career making such a foolish statement. Statements such as these are usually followed by an immediate interject from Mel..."wha wha wha what???????? Then a rational disclaimer for the foolishness. Its nice to know that even the Great Sheep Husband has his down days.... perhaps his local mini mart was out of Monster that day....Kudos to Mel for halting his waltz with Matilda to add your "retort". God I could listen to that all day. Love it! Had to repost this as it seemed stuck in the cloud....
I agree w prestwig1 above, certainly seems to suggest brain tissue and heart tissue can not be assumed to respond the same to insults. I hate the pressure to give TPA. Often times I give my patient my understanding of the literature and we conclude together to forgo it. This beautiful retort will give me even more ammo. Thanks again David!
I appreciate the information given. It gave me some numbers and data to give to my consultants and helped me get a full grasp of the topic. Great Job!!!
For Jennifer M A response to your questions... "In the studies discussed on emrap, these pt were better off getting tpa, but if you are out of the time window, (the italian study that compared tpa with interventions was in the time window) isn't a neuro-intervention better than nothing?" Well maybe yes and maybe no. The fact is that we don't know for sure. No one has taken the patients from 4.5+ hours and randomized them to procedure vs none. So until, someone does should we be paying thousands of dollars per-procedure for something that may or may not work? One step beyond this is that the theory by which a neuro-intervention would be better than nothing is the open-vessels theory. As we saw with the original IV-tPA trials as in this segment that doesn't seem to work in the brain.
"We have nothing to offer our pts, where the university hospital has an option for them. Is this possibly where neuro-interventions are best used - when pts are out of the time window for tpa?" This is exactly the uncertainty aimed at above. Our nature as humans is that we think doing something is better than doing nothing. Indeed our ability to function as Emergency Physicians depends on this concept. It's not always true. To quote Jerry Hoffman..."Don't just do something, stand there!" Sometimes the lesser of two evils is to do nothing rather than to subject a patient to a treatment that does not benefit them but does subject them to risk, cost, time.
"In the podcast, we learn that time is not brain as no association between giving the drug earlier and better response to therapy. Then, why can't we go beyond 4.5 hrs with tpa?" This all stems directly from the original tPA studies. Multiple studies failed to show any benefit of IV-tPA over placebo. The first that did was NINDS-II that looked only at patients who received tPA in < 180 minutes. Hence the approval for patients with < 180 minutes. Subsequently ECASS-3 suggested benefit out to 4.5 hours. No study has ever shown benefit > 4.5 hours. These two studies are the basis upon which we treat only up to 4.5 hours. As you point out time seems to not matter so it adds credence to the suggestion that NINDS-II and ECASS-3 have been misunderstood and likely do not show the benefit they have been held up as showing.
PS I forgot to add that both the Ciccone study and the Broderick study did include IA-tPA on the list of procedures that were used. As you know neither study found a benefit. It is possible that IA-tPA is beneficial, but only if one or more of the other procedures (Merci, Penumbra, etc) are harmful, thus balancing out the benefit of the tPA and showing overall no change. Further study with ONLY IA-tPA would have to occur to further elucidate this.
PPS Also I forgot to mention that IMS-III (AKA the IV-tPA vs IV-tPA + Procdure) study also compared reperfusion rates among the different methods. IA-tPA did the worst of any method (71%) vs say 85% for the Penumbra system which did the best. This argues against IA-tPA being better than any procedure. Of course this is a DO not a PO so could be misleading.
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Fred L. - November 8, 2013 3:29 PM
Many thanks to Dr. Dave Newman for his superb Mini Journal Club on stroke interventions. However, as someone who trained in emergency medicine when the only thing we had to learn was whether to bleed or to purge and how much, I must take issue with his somewhat disparaging comments on bloodletting. I’m sure those negative trials on bloodletting that he mentions would have shown benefit if they had only used the newer and more effective instruments that we have for bloodletting today. Further, I have no doubt that many of the patients in those trials really were patients who should have been purged, so of course bloodletting could not be expected to work. Finally, I do not think it is fair to draw a parallel between bloodletting and neurovascular interventions for stroke. Bloodletting is obviously different, as it is orders of magnitude less expensive.
Jennifer M. - November 12, 2013 6:42 PM
This was great. Thanks :)
A few questions, What about intra-arterial tpa? It is not clot retrieval, and it allows a greater time window for treatment. More beneficial or less than traditional systemic tpa?
I am at a hospital that does some basic stroke care, such as tpa and following pts who received tpa. However, when a pt is beyond the 3 or 4.5 hr window but under the 6 -12 hour window or a 3 hour window pt who is not a candidate for tpa, we often transfer them to the university based hospital for further evaluation and possible neuro-intervention. In the studies discussed on emrap, these pt were better off getting tpa, but if you are out of the time window, (the italian study that compared tpa with interventions was in the time window) isn't a neuro-intervention better than nothing? We have nothing to offer our pts, where the university hospital has an option for them. Is this possibly where neuro-interventions are best used - when pts are out of the time window for tpa? I don't think most of our pts end up getting an intervention, but I do not know how the ones who get it, end up doing. Hopefullly, they do well.
In the podcast, we learn that time is not brain as no association between giving the drug earlier and better response to therapy. Then, why can't we go beyond 4.5 hrs with tpa?
Sorry for so many questions. Thank you!
Nathan L. - November 16, 2013 10:59 AM
Hello. I agree with the content of the MJC commentary. However, there is one consideration I would like to bring up that wasn't mentioned. Essentially, the studies reported essentially showed (overall) improved patency of the major artery but no significant improvement in overall patient outcomes. OK so if it doesn't help patients then it doesn't matter that the artery is open. I'm with you there. But the issue of the 'wishfullness' of neurointerventionalists in terms of new devices may deserve more consideration in the future... if there is a qualitative difference in the functionality of the new devices. And that consideration (in my mind) is that if the old devices did not do a good job of preventing distal embolization at the time of intervention, then they wouldn't be expected to due as much for actual brain perfusion. The theory behind at least some of the new devices is design change to prevent this distal embolization of clot fragments. I'm not saying they work and I have no data and we should believe that they do until we see data to prove it. I just wanted to bring up a point that a potential qualitative change in the intervention of question may warrant more consideration that was alluded to in the segment. There may (not there is but there may) be merit to different and not just 'new' devices. I'm a 2nd-year-out community EM provider with no industry or neurointerventionalist associations.
Andrew R., M.D. - November 18, 2013 2:06 AM
Mel & David,
Absolutely wonderful segment. Having Mike politely interview the primary authors then having a polite rebuttal was extremely constructive. I liked your explanation of "wishful thinking" as a strong source of bias in addition to obvious financial incentives. I agree with you, Mel, in that this would have been even better had this been included in the same issue as Mike's interview, just as NEJM put all three articles in their same issue.
I would greatly enjoy hearing similar discussions between Jerry Hoffman and David on Perry's article regarding CT in SAH. I am like Al Sachetti in that I listen to EMA and EmRAP every month. When Jerry and David disagree on a given article, it would be interesting to hear them respond to eachother directly.
Lastly, I think this segment also shows that EmRAP would be the best forum to interview the ACEP leadership that decided to recommend TPA for stroke. Hold their feet to the fire.
Keep up the great work, "what you do matters"!
Sean G., M.D. - November 22, 2013 9:42 AM
Fantastic! Three thumbs up (Don't ask) ! A roller coaster ride truly phenomenal! EmRap segment of the year IMO, maybe the decade! Listen to this, listen to it now! Bring the kids! Fun for the whole family! Honestly David I thank u from the bottom of my cortex, perfused or not it sees this as a truly insightful and necessary rebuttal. When I heard the original piece where the interventionalist made that comment about "not needing research....I've seen it with my own eyes" I had to stop my iPhone and double check I was on EmRap....hard to fathom one so far along in their career making such a foolish statement. Statements such as these are usually followed by an immediate interject from Mel..."wha wha wha what???????? Then a rational disclaimer for the foolishness. Its nice to know that even the Great Sheep Husband has his down days.... perhaps his local mini mart was out of Monster that day....Kudos to Mel for halting his waltz with Matilda to add your "retort". God I could listen to that all day. Love it!
Colin K. - November 23, 2013 1:34 AM
Love the segment and commentary on how wishful thinking can override data! It happens all the time in medicine and in the real world!
While listening to this discussion on my way home after a shift in the emergency department, I started pondering the ischemic penumbra. We routinely treat the" ischemic penumbra" with hyperbaric oxygen in patients who have various types of chronic wounds. We see a very significant response in diabetic foot ulcers and other types of injuries that involve an area of ischemia, with surrounding areas of variably ischemic tissue that may respond if it is re-oxygenated. We also know that even if a small artery is blocked, collateral circulation can provide oxygenation to the ischemic area if the plasma delivered by the collateral is hyper-oxygenated. Oxygen delivery extends 3x the distance with hyper oxygenated plasma than when delivered by red cells. If we placed the patient with an acute stroke in the hyperbaric chamber and we saw a dramatic improvement shortly after getting them to pressure, (approximately 2.5 atm to 3 atm absolute), would that not give us a good idea that permanent reperfusion of the affected areas by recanalization might result in a benefit? We know from previous studies in human stroke patients, that they did not benefit from hyperbaric oxygen, however these were performed at a timeframe outside of what we would consider an acceptable window for treatment. We do know that in animal studies where the carotid artery is tied off and blood flow is interrupted and the animal goes into the hyperbaric chamber, there is an improvement in outcome after the tie is released, compared to the no HBO group. The human studies have not been done in the acute phase of a stroke. I think this is unfortunate. Hyperbaric oxygen has very few complications when used in the appropriate patient population. We also know that despite creating very high levels of oxygen, there is a well-documented inhibition of reperfusion injury. Despite huge partial pressures of oxygen, the release of toxic oxygen radicals is substantially reduced when patients undergo hyperbaric therapy acutely for a compartment syndrome. Hyperbaric oxygen may be able to assist in preventing some of the reperfusion changes in CVA also. This would be a very interesting way to test the hypothesis that the ischemic penumbra reperfusion actually matters. Just saying'...
Preston W. - November 27, 2013 12:06 AM
If doubling the patency rate did not result in any improvement in clinical outcome. How can we continue to believe that the "open vessel" theory is applicable to the brain (as applied.) In other words, "How can we continue to believe that TPA works?"
Pesky - December 2, 2013 8:25 PM
"No matter how strongly a thing may be believed, strength of belief is no criterion of truth"-Friedrich Nietzsche
Sean G., M.D. - December 4, 2013 6:01 PM
Fantastic! Three thumbs up (Don't ask) ! A roller coaster ride truly phenomenal! EmRap segment of the year IMO, maybe the decade! Listen to this, listen to it now! Bring the kids! Fun for the whole family! Honestly David I thank u from the bottom of my cortex, perfused or not it sees this as a truly insightful and necessary rebuttal. When I heard the original piece where the interventionalist made that comment about "not needing research....I've seen it with my own eyes" I had to stop my iPhone and double check I was on EmRap....hard to fathom one so far along in their career making such a foolish statement. Statements such as these are usually followed by an immediate interject from Mel..."wha wha wha what???????? Then a rational disclaimer for the foolishness. Its nice to know that even the Great Sheep Husband has his down days.... perhaps his local mini mart was out of Monster that day....Kudos to Mel for halting his waltz with Matilda to add your "retort". God I could listen to that all day. Love it! Had to repost this as it seemed stuck in the cloud....
Paul J. V. - December 5, 2013 8:48 AM
This was fantastic. Thank you David for helping us understand the science behind the literature.
Sean G., M.D. - December 7, 2013 10:21 AM
I agree w prestwig1 above, certainly seems to suggest brain tissue and heart tissue can not be assumed to respond the same to insults. I hate the pressure to give TPA. Often times I give my patient my understanding of the literature and we conclude together to forgo it. This beautiful retort will give me even more ammo. Thanks again David!
David L. - January 4, 2014 11:49 PM
I appreciate the information given. It gave me some numbers and data to give to my consultants and helped me get a full grasp of the topic. Great Job!!!
Gar - February 14, 2014 12:11 PM
For Jennifer M
A response to your questions...
"In the studies discussed on emrap, these pt were better off getting tpa, but if you are out of the time window, (the italian study that compared tpa with interventions was in the time window) isn't a neuro-intervention better than nothing?"
Well maybe yes and maybe no. The fact is that we don't know for sure. No one has taken the patients from 4.5+ hours and randomized them to procedure vs none. So until, someone does should we be paying thousands of dollars per-procedure for something that may or may not work?
One step beyond this is that the theory by which a neuro-intervention would be better than nothing is the open-vessels theory. As we saw with the original IV-tPA trials as in this segment that doesn't seem to work in the brain.
"We have nothing to offer our pts, where the university hospital has an option for them. Is this possibly where neuro-interventions are best used - when pts are out of the time window for tpa?"
This is exactly the uncertainty aimed at above. Our nature as humans is that we think doing something is better than doing nothing. Indeed our ability to function as Emergency Physicians depends on this concept. It's not always true. To quote Jerry Hoffman..."Don't just do something, stand there!" Sometimes the lesser of two evils is to do nothing rather than to subject a patient to a treatment that does not benefit them but does subject them to risk, cost, time.
"In the podcast, we learn that time is not brain as no association between giving the drug earlier and better response to therapy. Then, why can't we go beyond 4.5 hrs with tpa?"
This all stems directly from the original tPA studies. Multiple studies failed to show any benefit of IV-tPA over placebo. The first that did was NINDS-II that looked only at patients who received tPA in < 180 minutes. Hence the approval for patients with < 180 minutes. Subsequently ECASS-3 suggested benefit out to 4.5 hours. No study has ever shown benefit > 4.5 hours. These two studies are the basis upon which we treat only up to 4.5 hours. As you point out time seems to not matter so it adds credence to the suggestion that NINDS-II and ECASS-3 have been misunderstood and likely do not show the benefit they have been held up as showing.
Hope this sheds some clarity.
Gar - February 14, 2014 12:19 PM
PS
I forgot to add that both the Ciccone study and the Broderick study did include IA-tPA on the list of procedures that were used. As you know neither study found a benefit. It is possible that IA-tPA is beneficial, but only if one or more of the other procedures (Merci, Penumbra, etc) are harmful, thus balancing out the benefit of the tPA and showing overall no change. Further study with ONLY IA-tPA would have to occur to further elucidate this.
Gar - February 14, 2014 12:47 PM
PPS
Also I forgot to mention that IMS-III (AKA the IV-tPA vs IV-tPA + Procdure) study also compared reperfusion rates among the different methods. IA-tPA did the worst of any method (71%) vs say 85% for the Penumbra system which did the best. This argues against IA-tPA being better than any procedure. Of course this is a DO not a PO so could be misleading.