Esmolol for sepsis.

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Its interesting and thought provoking, but I'd like to see it completed in a larger population of patients in more than just one center. Similar to how I feel about the vasopressin/steroids/epinephrine after cardiac arrest and prone positioning for ARDS, it doesn't pass the sniff test that any therapy should be reducing mortality by 30% or a NNT of 3. Still there is some plausibility to how it could improve cardiac performance and V/Q mismatch, but before I jump on the bandwagon I'd like to see it used in more than 100 patients in a single-center study.

Just curious how often do you use esmolol for patients with sinus tach for a variety of reasons in the unit (concomitant ACS with GIB who is still tachy after adequately replacing blood volume and you think is now euvolemic or the other myriad of reasons people are tachycardic that are not directly associated with a reversible pathologic state)?
 
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ORL10 said:
Its interesting and thought provoking, but I'd like to see it completed in a larger population of patients in more than just one center. Similar to how I feel about the vasopressin/steroids/epinephrine after cardiac arrest and prone positioning for ARDS, it doesn't pass the sniff test that any therapy should be reducing mortality by 30% or a NNT of 3. Still there is some plausibility to how it could improve cardiac performance and V/Q mismatch, but before I jump on the bandwagon I'd like to see it used in more than 100 patients in a single-center study.

Just curious how often do you use esmolol for patients with sinus tach for a variety of reasons in the unit (concomitant ACS with GIB who is still tachy after adequately replacing blood volume and you think is now euvolemic or the other myriad of reasons people are tachycardic that are not directly associated with a reversible pathologic state)?
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rarely
 
Wait you don't believe in prone positioning?
 
I suspect you aren't at an institution that issues it regularly.

Proning works better than most drugs short of antibiotics in the ICU!
 
europeman said:
I suspect you aren't at an institution that issues it regularly.

Proning works better than most drugs short of antibiotics in the ICU!
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It works better at improving oxygenation, that I would buy, I do not believe it has the degree of mortality benefit that the study claims. I've also posted link to a good critique of the study in another thread.

And FYI, I am a fellowship trained pulm-cc, I've proned lots of people.
 
Why not believe it? I mean seriously. I think the better question is why would it surprise you that proning could produce a mortality benefit. I mean it's all pretty anecdotal on my part but it sure seems to get more people through in my experience.
 
jdh71 said:
Why not believe it? I mean seriously. I think the better question is why would it surprise you that proning could produce a mortality benefit. I mean it's all pretty anecdotal on my part but it sure seems to get more people through in my experience.
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I do not believe the degree of benefit. Seriously? 16% ABSOLUTE reduction? Bs.....http://medicalevidence.blogspot.com/2013/05/over-easy-recent-history-of-trials-of.html?m=1

Other questions that bug me. In ARMA, which group had the better outcomes? (The Worse pa ratios)

What's the primary cause of death in ARDS PTs? It usually isn't hypoxic induced issues. It's usually the inciting etiology. OR you get barotrauma which leads to a sudden decompensation & death. and does proning decrease barotrauma? Does it reduce GI bleeds? Does it reduces VAP? Does it reduce CLABS?
 
Hernandez said:
I do not believe the degree of benefit. Seriously? 16% ABSOLUTE reduction? Bs.....http://medicalevidence.blogspot.com/2013/05/over-easy-recent-history-of-trials-of.html?m=1

Other questions that bug me. In ARMA, which group had the better outcomes? (The Worse pa ratios)

What's the primary cause of death in ARDS PTs? It usually isn't hypoxic induced issues. It's usually the inciting etiology. OR you get barotrauma which leads to a sudden decompensation & death. and does proning decrease barotrauma?
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Hey man. I don't know. We barely know WHY almost anything we do makes any difference. I would guess that having MORE oxygen benefits SOMETHING.

Proning probably does reduce barotrauama though because there is more available lung to take the sum total pressure divided by available units to accept it.
 
I guess let me put it this way. We know patients die without pressors, right? Why? Because keeping variables closer to those compatible with "normal" life and physiology seem to work better. I've never seen a randomized clinically controlled trial of pressors vs no pressors for septic shock, yet I buy that they improve survival, by a lot.
 
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jdh71 said:
I guess let me put it this way. We know patients die without pressors, right? Why? Because keeping variables closer to those compatible with "normal" life and physiology seem to work better. I've never seen a randomized clinically controlled trial of pressors vs no pressors for septic shock, yet I buy that they improve survival, by a lot.
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In the age of "permissive hypercapnic" and "permissive hypotension", normal is over rated.
 
I agree with Hern here. There have been a bunch of proning studies, if there was a HUGE mortality benefit (say similar to antibiotics in the pre to post-PCN era) You should see a signal in most of the trials (yes yadaada about early vs. late versus and duration as the difference). However, an ARR of 10% for mortality, with a NNT 10? I think not. Is it potentially beneficial, and do I prone patients, yeah. We have a pretty aggressive ecmo department, especially if this is a bridge to transplant so a lot of our patients go on V-V ECMO (for what thats worth). What I'm saying is the sniff test, which is my clinical gestault is that a study that tells me if I treat 10 patients with proning I'll save one life despite multiple negative other trials seems to not fit. It has nothing to do with being in a department who "prones-patients frequently."
The one thing that happens over and over in medicine is one study suggesting a benefit gets published and suddenly all the negative studies are forgotten. This happened with tPA for CVA (something like 11-12 studies 2 positive, several stopped early for harm), and seems to be pressing for endovascular therapy for ischemic stroke (except there still is no positive studies for outcomes that patients care about.)

Anyways, back to esmolol I'm interested to see what others have to say?
 
Anyways, back to esmolol I'm interested to see what others have to say?[/quote]
I tried it last week for the first time: male in his 20s; Septic shock, APACHE 2 score 24, fluid resuscitated, moderately high dose of levo, sinus tachy 130s-- started the esmolol-- BP tanked!!! Stopped it. Pateint did ok. Of note, he was not on steroids like they used in the article (I am more conservative with roids a la Surviving Sepsis 2013). Would try it again, maybe??
 
20 y/o male? Let him tach. He's just sick.

I of course don't buy this esmolol stuff. Why? I just don't. And I'm a bad doctor. But everyone knows this.

Heh.
 
I also don't know that I believe the results of this study. If I remember correctly, the mortality in the non-esmolol group seemed high to me. I also don't know that it's generalizable to the way we typically treat septic shock here in the U.S. as we virtually never place swans in everyone, start them on Hydrocortisone drips even if their MAP is at goal on Levophed, and I don't even think Levosimendan is available here in the U.S. I also think it runs counter to using Dobutamine if the Scv02 is persistently < 70, so I'm not sure how it would be integrated into EGDT. That is, unless the upcoming PROCESS studies disprove EGDT and everyone stops doing it.
 
I also don't know that I believe the results of this study. If I remember correctly, the mortality in the non-esmolol group seemed high to me. I also don't know that it's generalizable to the way we typically treat septic shock here in the U.S. as we virtually never place swans in everyone, start them on Hydrocortisone drips even if their MAP is at goal on Levophed, and I don't even think Levosimendan is available here in the U.S. I also think it runs counter to using Dobutamine if the Scv02 is persistently < 70, so I'm not sure how it would be integrated into EGDT. That is, unless the upcoming PROCESS studies disprove EGDT and everyone stops doing it.
 
80% of the people in the control group died. Septic shock, one pressor about half on an ionotrope.

Is this anyone else's experience with septic shock? It ain't mine.
 
jdh71 said:
I guess let me put it this way. We know patients die without pressors, right? Why? Because keeping variables closer to those compatible with "normal" life and physiology seem to work better. I've never seen a randomized clinically controlled trial of pressors vs no pressors for septic shock, yet I buy that they improve survival, by a lot.
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I had a experience with an aging oncologist as an intern who came to the bedside and argued with us while we were coding his 84 year old lung ca with brain mets in septic shock from post obs PNA. Will never forget it. He literally said to me "you know pressors don't work in septic shock right, the answer is fluids, now open up that D5-1/2NS wide open!". The MICU nurse looked at me not knowing what to say, I looked at my attending with the same stare, and he was looking at the oncologist with this utter look of disdain and disgust and finally just said gtfo of my unit now. It was fabulous.

But I agree with hern. I totally buy it improving oxygenation, dead space, and overall survival in ards. But teh degree to which they showed mortality reduction....it just seems too much to me. Let's see a per study or two reproduce the same results.
 
Gave esmolol a second shot in septic shock today-- female, 50s, multiple (untreated) foci of infection; no longer fluid responsive; norepi, epi, vaso; tachy 130s; ScVO2 70s; started esmolol-- sinus 70s, decreasing pressor requirements... worked like the study??????
 
sluggs said:
Gave esmolol a second shot in septic shock today-- female, 50s, multiple (untreated) foci of infection; no longer fluid responsive; norepi, epi, vaso; tachy 130s; ScVO2 70s; started esmolol-- sinus 70s, decreasing pressor requirements... worked like the study??????
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Do 80% of your septic patients not on Esmolol die?
 
This study's outcome makes no sense to me. Maybe the decreased tachy decreases o2 reqs? No way that 30% 28 mortality benefit is real. I generally think having people on bb + pressors is a bad combo, although there are definitely some patients that we use both in.
 
leviathan said:
What happened to that whole unopposed alpha thing anyway? ;) 80% mortality in the control group? It's a weird study but something to think about.
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Well the unopposed alpha tone would only be a problem if your septic patient was hypertensive;)
 
yeah it bothered me that essentially THE ENTIRE CONTROL GROUP DIED BEFORE LEAVING THE HOSPITAL (like 90+%?)

i like the idea and ill use it on occasion, but they got the ICU mortality down to 50% with it...DOWN to 50% :nailbiting:
 
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risnwb said:
Well the unopposed alpha tone would only be a problem if your septic patient was hypertensive;)
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ultimately, i decided that this was where they had their success. they must be gaining traction in the patient population that was so refractory to pressors that they needed that arterial constriction that is provided by even the tiniest bit of beta-2 (i know, esmolol is supposedly completely beta-1 selective...), or they needed that unopposed alpha. i mean did you see their pressor doses? ive never had someone on 0.4 of norepi and that was their median dose in the control group.

91% hospital mortality 88% ICU mortality...if you can identify the sickest of the sick sepsis players early then get that esmolol on...i just think that isnt reflective of what i see
 
Idiopathic said:
ultimately, i decided that this was where they had their success. they must be gaining traction in the patient population that was so refractory to pressors that they needed that arterial constriction that is provided by even the tiniest bit of beta-2 (i know, esmolol is supposedly completely beta-1 selective...), or they needed that unopposed alpha. i mean did you see their pressor doses? ive never had someone on 0.4 of norepi and that was their median dose in the control group.

91% hospital mortality 88% ICU mortality...if you can identify the sickest of the sick sepsis players early then get that esmolol on...i just think that isnt reflective of what i see
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Wait you've never had someone on 0.4 of levophed? That's the max dose and although if they get to it they are most likely on vasopressin as well, I have to say I have had many many septic shock pts on 0.4. What do you do, stop at 0.25 or so, add vaso 0.04 and then add another alpha agonist like neo or dop when your still not at map goal? Add low dose Epi? We are obviously presuming fluid status is optimized, hct is acceptable and you've already given stress dose roids. I'm aware of the data from high dose levophed in the new trials but if your not at map goal, your not at map goal. I tend to start in vaso around 0.25-0.3 mark of my Levo, then up the Levo to 0.4 before adding a third pressor. And let's be honest If you've maxed Levo and have vaso on and still need a third pressor, their dead anyway.
 
:corny:
Bostonredsox said:
Wait you've never had someone on 0.4 of levophed? That's the max dose and although if they get to it they are most likely on vasopressin as well, I have to say I have had many many septic shock pts on 0.4. What do you do, stop at 0.25 or so, add vaso 0.04 and then add another alpha agonist like neo or dop when your still not at map goal? Add low dose Epi? We are obviously presuming fluid status is optimized, hct is acceptable and you've already given stress dose roids. I'm aware of the data from high dose levophed in the new trials but if your not at map goal, your not at map goal. I tend to start in vaso around 0.25-0.3 mark of my Levo, then up the Levo to 0.4 before adding a third pressor. And let's be honest If you've maxed Levo and have vaso on and still need a third pressor, their dead anyway.
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Bostonredsox said:
Wait you've never had someone on 0.4 of levophed? That's the max dose and although if they get to it they are most likely on vasopressin as well, I have to say I have had many many septic shock pts on 0.4. What do you do, stop at 0.25 or so, add vaso 0.04 and then add another alpha agonist like neo or dop when your still not at map goal? Add low dose Epi? We are obviously presuming fluid status is optimized, hct is acceptable and you've already given stress dose roids. I'm aware of the data from high dose levophed in the new trials but if your not at map goal, your not at map goal. I tend to start in vaso around 0.25-0.3 mark of my Levo, then up the Levo to 0.4 before adding a third pressor. And let's be honest If you've maxed Levo and have vaso on and still need a third pressor, their dead anyway.
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okay that was fairly hyperbolic, so i hardly ever go above 30 of norepi. in some people that is 0.4, Ill admit. that was their MEDIAN dose in this study. and if i recall, they did not add a second pressor. i try not to GET to 30 of norepi without adding vaso and other modalities.

so, i will add norepi, add vaso if rapidly escalating, check indices if PAC in place vs LIDCO/TEE if i presume distributive shock before adding steroids and (next time) methylene blue (which i will use in my post-CPB vasoplegia patients). ive gone higher than 0.04 U/min on vaso (up to 0.06 in some cases) and ive even added neo. i think low dose epi actually promotes vasodilation, so i wont add it unless ive got a significant cardiogenic component. i would consider dopamine in the same patient, but it would be a hail mary.

i hate relying on one thing, even a time tested one, that doesnt appear to be working, so ill make sure my calcium is high normal/supranormal, add vaso early. ultimately, we may not be getting as much alpha as we think with our norepi, yet we eventually do ratchet up our heart rate. i dont know, ultimately i think this study highlights the sickest of the sick septic patients, and so in that patient id consider esmolol, however, their practice patterns are not similar to mine, and they use levosimendan, which i dont have access to.
 
Idiopathic said:
okay that was fairly hyperbolic, so i hardly ever go above 30 of norepi. in some people that is 0.4, Ill admit. that was their MEDIAN dose in this study. and if i recall, they did not add a second pressor. i try not to GET to 30 of norepi without adding vaso and other modalities.

so, i will add norepi, add vaso if rapidly escalating, check indices if PAC in place vs LIDCO/TEE if i presume distributive shock before adding steroids and (next time) methylene blue (which i will use in my post-CPB vasoplegia patients). ive gone higher than 0.04 U/min on vaso (up to 0.06 in some cases) and ive even added neo. i think low dose epi actually promotes vasodilation, so i wont add it unless ive got a significant cardiogenic component. i would consider dopamine in the same patient, but it would be a hail mary.

i hate relying on one thing, even a time tested one, that doesnt appear to be working, so ill make sure my calcium is high normal/supranormal, add vaso early. ultimately, we may not be getting as much alpha as we think with our norepi, yet we eventually do ratchet up our heart rate. i dont know, ultimately i think this study highlights the sickest of the sick septic patients, and so in that patient id consider esmolol, however, their practice patterns are not similar to mine, and they use levosimendan, which i dont have access to.
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Fair enough
 
agreed, and they demonstrate this in their paper. however, it would be foolish to hit such high doses (>40-50mcg/min) and feel like you are headed in the right direction

edit: i guess technically, there is no such thing as "max" anything until toxicity sets in...how would you know you were norepi toxic? i dont know, refractory tachycardia, vasoplegia, renal failure, perhaps ;)
 
Idiopathic said:
agreed, and they demonstrate this in their paper. however, it would be foolish to hit such high doses (>40-50mcg/min) and feel like you are headed in the right direction

edit: i guess technically, there is no such thing as "max" anything until toxicity sets in...how would you know you were norepi toxic? i dont know, refractory tachycardia, vasoplegia, renal failure, perhaps ;)
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When fingers and toes start falling off.
 
nah, if you dont feed the gut it probably wont get necrotic...even then, you can take out the gut - PRESS ON WITH MORE NOREPI!
 
My point was that adding a second pressor to hit the EXACT same receptor is really missing the point. I know we all have to deal with nurses and pharmacy people who insist on "maxes" and ask for another pressor, but a patient isn't in any worse shape whether a second alpha-agonist is added or you just turn up the one you are already using.
 
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Idiopathic said:
nah, if you dont feed the gut it probably wont get necrotic...even then, you can take out the gut - PRESS ON WITH MORE NOREPI!
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The one case I had that necrosed the bowels from pressors, I went 30mcg/min levo 300 mcg/min neo, .08 vaso, and I can't remember where we topped off on Epi, 2mcg/kg/min?(it was obscene) with intermittent pushes of bicarb, calcium and more Epi. She did well for 3 days, even got her down to reasonable pressor levels.....until we fed her. The surgeons exact words when they opened her up were "liquified" in describing the small bowel.
 
Hernandez said:
The one case I had that necrosed the bowels from pressors, I went 30mcg/min levo 300 mcg/min neo, .08 vaso, and I can't remember where we topped off on Epi, 2mcg/kg/min?(it was obscene) with intermittent pushes of bicarb, calcium and more Epi. She did well for 3 days, even got her down to reasonable pressor levels.....until we fed her. The surgeons exact words when they opened her up were "liquified" in describing the small bowel.
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Did she live?
 
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Hernandez said:
The one case I had that necrosed the bowels from pressors, I went 30mcg/min levo 300 mcg/min neo, .08 vaso, and I can't remember where we topped off on Epi, 2mcg/kg/min?(it was obscene) with intermittent pushes of bicarb, calcium and more Epi. She did well for 3 days, even got her down to reasonable pressor levels.....until we fed her. The surgeons exact words when they opened her up were "liquified" in describing the small bowel.
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thats an impressive regimen...still, i could argue that she necrosed the bowel from feeding rather than from pressors
 
jdh71 said:
My point was that adding a second pressor to hit the EXACT same receptor is really missing the point. I know we all have to deal with nurses and pharmacy people who insist on "maxes" and ask for another pressor, but a patient isn't in any worse shape whether a second alpha-agonist is added or you just turn up the one you are already using.
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i disagree. i think the beta-agonist effect of norepi at higher doses is clinically significant, and adding a drug with with more/pure alpha (i.e. phenylephrine) to a high dose norepi may be exactly the right answer. i think thats at the root of this esmolol data as well.
 
Idiopathic said:
i disagree. i think the beta-agonist effect of norepi at higher doses is clinically significant, and adding a drug with with more/pure alpha (i.e. phenylephrine) to a high dose norepi may be exactly the right answer. i think thats at the root of this esmolol data as well.
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There is barely any beta agonist response to norepi. I don't buy that you can actually titrate it high enough to give someone any meaningful tachycardia. And using a weak drug like neo to "add anything" is like pissing in a swimming pool to raise the water level (or starting an inhaled corticosteroid in someone on a blast of IV methylpred q6, heh).
 
jdh71 said:
There is barely any beta agonist response to norepi. I don't buy that you can actually titrate it high enough to give someone any meaningful tachycardia. And using a weak drug like neo to "add anything" is like pissing in a swimming pool to raise the water level (or starting an inhaled corticosteroid in someone on a blast of IV methylpred q6, heh).
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Anecdotally, Neo on top of Levo does get added benefit. But that's with a "max" Levo of 0.3 mcg/kg/min
 
Hernandez said:
Anecdotally, Neo on top of Levo does get added benefit. But that's with a "max" Levo of 0.3 mcg/kg/min
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But is there a clinical situation you would add neo to Levo instead of adding vaso to Levo? If you need more vasoconstriction for a vasodilatiory or septic shock, vaso would be better. If you need more CO, Epi would be better. I can't see a situation where I would add a weak alpha agonist like neo to a potent alpha agonist like Levo already bound to most of my alpha receptors instead of adding a far more potent Epi or vaso (depending on the shock source) and hitting different receptors. Enlighten me if I am incorrect.
 
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