Rob Mac Sweeney is an anaesthetist-intensive care doc. His gig is evidence: analysis, assimilation, and dissemination. Tomorrow, you'll hear a ton more about the great stuff he does on sites such as Critical Care Reviews. For today, we discuss the topics raised in my recent posting of my SMACC Intra-Arrest Talk.
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An ED Intensivist from NY. No conflicts of interest (coi).
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Comment on VSE: right now I like to think of Vasopressin, Steroids & Epinephrine like the initial Early Goal Directed Therapy paper – single centre RCT by talented clinicians with impressive results. It’s not the absolute answer, but will guide the way.
Brent, Though I don’t disagree with your take-home; remember, they did the single-center RCT years ago, the recent JAMA pub. was a repeat, multi-centre RCT
Here is what Dr. Jacobs, et al. wrote in the paper – This study was designed as a multicentre trial involving five ambulance services in Australia and New Zealand and was accordingly powered to detect clinically important treatment effects. Despite having obtained approvals for the study from Institutional Ethics Committees, Crown Law and Guardianship Boards, the concerns of being involved in a trial in which the unproven “standard of care” was being withheld prevented four of the five ambulance services from participating. In addition adverse press reports questioning the ethics of conducting this trial, which subsequently led to the involvement of politicians, further heightened these concerns. Despite the clearly demonstrated existence of clinical equipoise for adrenaline in cardiac arrest it remained impossible to change the decision not to participate. I have been a very vocal critic of the lack of evidence to support the use of epinephrine in cardiac arrest, but I have not presented the Jacobs study as negative. The study is neutral, because it was decimated by the politicians and the media. To view it as positive is also probably a mistake. The average time of EMS arrival was 10 minutes and the outcomes were 2% survival and… Read more »
Agree with all of that, and I think Rob and I mentioned why the Jacobs trial was crippled, though the actual quote is very welcome–you don’t see stuff like that written in major journals very often. I actually was a thorough disbeliever in epi, from an ebm perspective, up until the Jacobs trial. I now am in a state of equipoise, just as Rob is. We need to be very cognizant of the difference between a trend from a properly powered study=bullshit, vs. a trend like this in a study that recruited 1/8 of it.s patients. The latter certainly doesn’t make the study positive, but I see it as slightly more than neutral as well. I think Rob put it best, “There is a signal there.” Enough signal to do another RCT, enough signal to continue using the med if you want; enough signal to leave it in as a IIB in ACLS. Now as to your mention of the 4% survival. Let’s zone in here, this is survival to hospital discharge of OOHCA, AFTER you have already stripped out the VF/VT patients that responded to initial 3 shocks. It is my understanding that these pts did not receive ther.… Read more »
I completely agree with more research. My criticism of epinephrine, and the many other treatments we have that are not supported by valid evidence, is that we need to find out what works. Both type 1 (false positive/excessive gullibility) and type 2 errors (false negative/excessive pessimism) are errors. The problem is the lack of adequate evidence. If the evidence is inadequate (as in the Jacobs paper, through no fault of Dr. Jacobs), the analysis is just a derivative – weaker than the original paper. On the other hand, a negative trend is something we should pay attention to. Not so much because it is more likely to be true, but because the consequences are likely to be more harmful. I forgot that the 4% was after initial defibrillation and without therapeutic hypothermia. I think that it is likely that epinephrine does increase survival in some patients, but that we have no valid evidence to tell us which patients. I think that it is likely that epinephrine does decrease survival in some patients, but that we have no valid evidence to tell us which patients. Your approach of targeting diastolic blood pressure is certainly reasonable – it is in no way… Read more »
ha! Dont get so hung up on epinephrine alone! the two VSE RCT add weight to the fact that epinephrine has a role in Cardiac arrest. combined with the Jacobs trial, there is enough SIGNAL to certainly say it is reasonable in hospital cardiac arrest and in my view, still has a role in OHCA. You dont consider the alternative explanation to why the 4/5 ambulance services chose not to participate in the Jacobs trial….that they were right! Rouge, you can argue all you like about lots of other things not holding water and being proven wrong..thats merely a distraction. If you want to argue the EBM extremist view then what Scott says is all true. VSE RCT x 2 all positive for improved neuro outcomes in hospital arrest, Jacobs trial underpowered but signal of benefit. More research we agree is the way forward. thats all you can say. the evangelistic pulpit bashing is not helpful. comparing trends in cardiac arrest trials to lottery numbers is emotively entertaining but has no inherent validity. the consequences of one are totally different to the other. Lets focus on the science of which gladly there is more http://www.bmj.com/content/348/bmj.g3028?etoc In hospital arrest of non… Read more »
ha! Dont get so hung up on epinephrine alone! Does epinephrine contribute to the improved outcomes with VSE, or would the outcomes be better with just vasopressin and methylprednisolone? Would a different cocktail be better? We do not know. – the two VSE RCT add weight to the fact that epinephrine has a role in Cardiac arrest. combined with the Jacobs trial, there is enough SIGNAL to certainly say it is reasonable in hospital cardiac arrest and in my view, still has a role in OHCA. The reason the Jacobs paper does not answer that question is that there were too few patients to be able to tell the difference between a genuine trend and the normal statistical variation in outcomes that we should expect. – You dont consider the alternative explanation to why the 4/5 ambulance services chose not to participate in the Jacobs trial….that they were right! Do you really want medically naive politicians and lawyers to overturn doctors medical decisions? Be careful what you wish for. As with running a test, the result of a bad decision to test for something does not turn the bad decision into a good decision. That the test found something is… Read more »
Do you advocate we stop using epinephrine in cardiac arrest until some more research is done that satisfies you either way?
http://prehospitalmed.com/2012/05/20/pharm-podcast-012-epinephrine-and-ohca-with-paramedic-tim-noonan/
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ha! stop living in the past!
I take it you ignore the last 2 yrs of further research published that Scott and I have cited. lack of evidence does not mean lack of benefit especially when you admit epinephrine improves ROSC. you can give yourself permission to change your dogmatic views of the past.
I take it you ignore the last 2 yrs of further research published that Scott and I have cited. The statistically insignificant result in the 3 year old Jacobs paper is neutral. It does not support epinephrine. Vasopressors in cardiac arrest: a systematic review. Larabee TM, Liu KY, Campbell JA, Little CM. Resuscitation. 2012 Aug;83(8):932-9. Epub 2012 Mar 15. PMID: 22425731 [PubMed – in process] In examining the results of the studies of vasopressors, the authors classified the results of the Jacobs paper as neutral. The authors were not impressed by a statistically insignificant trend. – The last two years of research that you cited? A cocktail paper that may demonstrate that vasopressin and methylprednisolone cause more benefit than the harm caused by epinephrine. Again, it is neutral on epinephrine. A timing paper that may just demonstrate when epinephrine is most harmful. This is also neutral on epinephrine. After over half a century of use, there is not a single study of epinephrine in cardiac arrest that is positive. The one study that might have provided an answer was decimated. You seem to praise the people who stopped the study – You dont consider the alternative explanation to why the… Read more »
avoiding the simple question again with dramatics
do you advocate we abandon epinephrine in cardiac arrest?
we both agree more study is useful
do you walk the walk or just talk the talk?
at least Newman puts his money where his mouth is!
Please point out the dramatics.
Do I walk what walk?
I admit that we do not know whether epinephrine improves outcomes.
I am not going to pretend that I know more than I could know in order to behave in a way that you want.
What does Dr. Newman do that you claim is putting his money where his mouth is?
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Guys-think you two should hash it out on G+ or similar where threading and long form is easier. –S
oh and you dont need evidence to change your view
its called common sense and being human
making mistakes in pursuit of improvement is allowed in the human condition
the dogmatic EBM view that we need to know everything with statistically significant certainty before we make a decision needs to be challenged and I challenge it
oh and you dont need evidence to change your view its called common sense and being human Bleeding patients to get rid of the bad humors was common sense. Evidence demonstrated that common sense was wrong. Doctors having to wash their hands between autopsy and delivery of a baby was contrary to common sense. Evidence demonstrated that common sense was wrong. Prehospital IV fluids for therapeutic hypothermia was common sense. Evidence demonstrated that common sense was wrong. – the dogmatic EBM view that we need to know everything with statistically significant certainty before we make a decision needs to be challenged and I challenge it This is a fiction that made up by opponents of EBM. We know that most treatments based on the rationale of the current understanding of pathophysiology will be more harmful than beneficial, so we should have good evidence that a treatment works before we expose patients to what is expected to be more harmful than beneficial. We know that improving surrogate endpoints (ROSC, blood pressure, . . . . ) are low standards that are encouraging, but often misleading. Many of these drugs will be found to be more harmful than beneficial after enough evidence… Read more »
Rogue, Tim, we agree to disagree. Scott the host, called time out.
have some respect
I have no problem with that. I did not see Scott’s comment until after I posted my last one. This page does not automatically refresh for me.