1. What flaws did you find impressive? Even the neutral editorial piece, which I didn't link, thought the study was at least well-designed. Do you think there's at least equipoise? Because if not, there are 5 or so active trials that shouldn't have gotten ethics approval--and all of those intensivists seem to take the data seriously enough.
2. I've already been called-out for being too aggressive with clinicians, so I'll hold my tounge, but I don't quite agree with that definition of sepsis (which itself is a pathophysiologically heterogeneous entity, far beyond just clinical definitions offered by Surviving Sepsis or Sepsis 3 or whatever), and I'm not sure how esmolol at 24 hours in an HR-directed fashion after haemodynamic optimisation would necessarily result in any kind of "quick kill." The example above was for metoprolol.
http://lifeinthefastlane.com/ccc/sepsis-definitions/
all I'll say is to point out I said ONE definition, meaning it's one way of looking at it. Obviously it's more complicated than what I said.
I went back to read the articles you linked to try to pick out points - and basically, all of it.
http://link.springer.com/article/10.1007/s00134-016-4407-3
Is why I hate the idea. It seems like someone has fallen in love with the math and theory and has lost sight of being practical.
I don't want to sit here and summarize the whole article - if you push, I might.
The next point, is that even the article that you presented that was in favor of it, actually provided me with the point that you're putting brakes on a system that could be at the patient's peril.
"However, the therapeutic concept of “setting the brake” by β-blockade seems deceptively simple and could be effective in carefully chosen septic shock patients (excluding those with hypovolemia, known complex cardiac comorbidities, tachyarrhythmias, hemodynamic instability despite vasopressor treatment, or systolic cardiac dysfunction)."
I agree, deceptively simple, relies on a lot of math in the face of common sense, and the above rules out so many patients in the ICU, to essentially be useful in patients that are cardiovascularly healthy - oh yeah, except for being in septic shock and on pressors. That is a very narrow demographic of septic shock.
"So the important, conceptual cardiovascular question still needs to be answered: how much preload is necessary for safe and effective β-blockade in septic shock?"
Part of the challenge of preload in these patients and why we have to pour so much fluid in them is because they 3rd space it - even with perfect hearts, because of the peripheral vascular dysfunction I mentioned. And as you mentioned, the heterogeneity is such that you don't know how much fluid it will take until you start pouring it in, and it can be a challenge not to overshoot. So this whole theory rests on fluid balance which is one of the most important things we manage in the hospital - and a huge PITA. It's a moving target that can only be assessed clinically. You can't go by numbers you have to listen to the lungs and squeeze the ankles.
So you're relying on what the fluid level is in a leaky boat for applying this brake.
As far as crumping the patient with esmolol vs metoprolol - fair point. I looked this up, but a 1/2 life of 9 minutes? I guess if you're following the above exclusions I'm less worried that 20 min (let's say) of decreased CO from esmolol is going to be unsurvivable.
On the other hand, 20 minutes is all it takes to watch someone lose consciousness, turn blue, and die. I'm seen it more than once from HR and BP drop. So I don't know that the the half life of esmolol vs metoprolol on the brake makes me feel any safer using it.
But I don't claim to have a lot of experience with esmolol and admittedly the n=2 quick clean kills described in this thread were metoprolol. These are my thoughts based on the reading and what I've seen. Admittedly, and maybe it's telling, I probably have PTSD from witnessing a beta blocker induced death in a septic patient.
To balance all these "caveats" in the positive review article, they go one about the immune system, and gene expression, and etc etc. That's what I meant by someone fell in love with theory and missed the forest for the trees. None of that **** matters if the patient isn't perfusing their limbs because I dropped their HR and CO.