Marik Sepsis Cocktail

[bigdan]

All -

Have any of you tried using the Vit C/Thiamine/Hydrocortisone cocktail that Dr. Marik described to help reverse septic shock? I'm interested in your experiences. My partners and I have tried this in several cases with patients with septic shock, and our success has been nil. Literally no benefit whatsoever.

Dr. Marik described results so extraordinary, they almost seem implausible. I'm no Dr. Marik, but would have hoped to have seen at least some benefit in at least some of the patients. No such luck.

What have you guys seen?

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[jdh71]

Tried it once. And I plan on using it again but the admits lately haven't been right for it by the time I got to them (already getting better after coming in over night). Our group is going track our outcomes and experience with it though two think it's voodoo and refuse to try (which I think is fair enough right now too honest).

 

[Hernandez]

Who remembers Leuven’s intensive glucose control?

Who remembers oxepa (which Apple wants to correct to Oreos interestingly)?

Who remember’s Annane’s steroids for sepsis papers?

Who remembers Xigris?

Hell, let’s throw most of EGDT actual interventions into the mix, who remembers how little those interventions by themselves made diddly squat of an improvement.

Who remembers CVP measurements? (Cough cough dr marik)

Pepperidge Farm remembers.

The data is interesting but woofully under powered. I certainly won’t be an early adopter based off current evidence, I might start using it in a limited fashion as larger single center data comes available and certainly look forward to the large randomized trial.

 

[Vigileo]

Just a lowly fellow, but I'm skeptical. I think the PR thus far is much better than the science

 

[SurfingDoctor]

Each of those things have been tried in isolation without clinical effect. But somehow, in combination they prevent any mortality. This in a heterogeneous disease which most patients don’t die during the acute inflammatory response. Mkay. However, if people want to chase that rabbit down the hole, have at it.

 

[mochief2000]

yes just like @Hernandez said, the data is underpowered and more equivalent to a case series to me. With that being said, the population that this is being used are pretty much hanging on to life by a thread and the cocktail is made up of pretty harmless substances. If you are even thinking about it, you likely have exhausted all other "evidenced based resources". So yeah, throw the kitchen sink, since we already cooking and set what happens....atleast until new data tells us otherwise.

 

[lunaire]

Been using it pretty extensively. Seems to work. Patients tend to struggle less with hemodynamics. Organ failure rate slightly lower. Patient population is purely post open heart, though a significant portion of patients is chronically critical ill, ones that had complications and stayed in the ICU/hospital for weeks. They would behave like the general medical ICU patient population a bit mor

This was one of several things that we changed in our system, however, so take this with a grain of salt. More robust studies would be nice. More information on safety and dosing would also be nice.

Also to consider is Marik's general perspective in ICU care. He keeps patients relatively dry. Read his book on evidence-based critical care to get an insight on his rationale for this... I also keep my postop hearts dry, with diuresis 99% of the time. Water soluble vitamin & electrolyte supplementation makes sense with this management style, as they get diuresed out...

 

[deleted547339]

yes just like @Hernandez said, the data is underpowered and more equivalent to a case series to me. With that being said, the population that this is being used are pretty much hanging on to life by a thread and the cocktail is made up of pretty harmless substances. If you are even thinking about it, you likely have exhausted all other "evidenced based resources". So yeah, throw the kitchen sink, since we already cooking and set what happens....atleast until new data tells us otherwise.

That's awful logic. Applying an untested therapy to a group with a high mortality without knowing its effect is foolish - you have just lulled yourself into complacency. What if you take mortality from 90% to 99% - you just killed 9% of your patients. Why would you say that it's ok to do that, when you wouldn't be OK doing the same thing with a group with 5% mortality?

 

[deleted547339]

Been using it pretty extensively. Seems to work. Patients tend to struggle less with hemodynamics. Organ failure rate slightly lower. Patient population is purely post open heart, though a significant portion of patients is chronically critical ill, ones that had complications and stayed in the ICU/hospital for weeks. They would behave like the general medical ICU patient population a bit mor

This was one of several things that we changed in our system, however, so take this with a grain of salt. More robust studies would be nice. More information on safety and dosing would also be nice.

Also to consider is Marik's general perspective in ICU care. He keeps patients relatively dry. Read his book on evidence-based critical care to get an insight on his rationale for this... I also keep my postop hearts dry, with diuresis 99% of the time. Water soluble vitamin & electrolyte supplementation makes sense with this management style, as they get diuresed out...

Of course they struggle less hemodynamically, you're giving them steroids. That's been known for years....

 

[SurfingDoctor]

Steroids are great at increasingly blood pressure (even in healthy people)...

Incidentally, they are also great at killing lymphocytes needed for recovery...

 

[lunaire]

Of course they struggle less hemodynamically, you're giving them steroids. That's been known for years....

Yeah, my group actually reduced the overall steroids use with this protocol... The surgeons here is very liberal with steroids. We've poor general baseline health in this area, so a lot of patients have chronic uncontrolled issues and behave like adrenal insufficiency patients when they get really sick. We supplement steroids regularly before, and just added the vitamins.

In the open heart patient, vitamin C is already a supplement we use, for A. fib prevention. This makes the jump to high dose vit C and the addition of thiamine a bit easier, I guess.

Like I said, one of several changes; but seems to work. I suppose I could stop using it for a while and see if the patient go back to stuggling to get off pressors, but I'd hesistate doing so since we've literally no side effects from the supplemental vitamins.

 

[mochief2000]

That's awful logic. Applying an untested therapy to a group with a high mortality without knowing its effect is foolish - you have just lulled yourself into complacency. What if you take mortality from 90% to 99% - you just killed 9% of your patients. Why would you say that it's ok to do that, when you wouldn't be OK doing the same thing with a group with 5% mortality?

See you are dealing in the imaginary and making up numbers to fit your agenda, which i also think is awful logic. I was talking about people with a 99% mortality (3 pressors kind of people). How much of what you have learned has turned out to be false. How much of what you are doing now may actually harm. You don't know and are probably using untested dogma that has being going around for decades with no real evidence behind it. Your rationale to me is even more foolish. Your telling me somebody on the brink of death , you would not try it because the evidence behind it is weak?? In the population that I choose to use it in, my worse outcome would be no difference in mortality. In the same population, your worse outcome would be a difference i.e. improved mortality (like I said, in the population I use it in). Are you ok with that? Are YOU ok with a increased mortality??

 

[deleted547339]

See you are dealing in the imaginary and making up numbers to fit your agenda, which i also think is awful logic. I was talking about people with a 99% mortality (3 pressors kind of people). How much of what you have learned has turned out to be false. How much of what you are doing now may actually harm. You don't know and are probably using untested dogma that has being going around for decades with no real evidence behind it. Your rationale to me is even more foolish. Your telling me somebody on the brink of death , you would not try it because the evidence behind it is weak?? In the population that I choose to use it in, my worse outcome would be no difference in mortality. In the same population, your worse outcome would be a difference i.e. improved mortality (like I said, in the population I use it in). Are you ok with that? Are YOU ok with a increased mortality??

Your condescension aside, sure, I do things that are wrong, but I’m at least going by what I consider reasonable evidence. We can’t give a pass for <insert medical therapy> because historically we’ve missed on things in the past - if anything, that’s more of a reason to prove our therapies before implementing them. The fact that we are doing and have done things that harm patients because we don’t/didn’t know better should be an argument to be more careful about studying both newly implemented and longstanding medical therapies, not less.

Not just that, but think about the downstream consequences. Maybe it doesn’t hurt people in your 99% mortality group, but what about the 50% mortality group? You start using it in your 99% cohort, then someone thinks your slick and it starts getting used in a 90% preintervention group, then 80%, then 50%. Before you know it, it’s standard of care and you no longer can convince the IRB that you should have a rigorous study. Maybe it increased mortality 1-2% in the 50% cohort - we would never know.

 

[mochief2000]

Your condescension aside, sure, I do things that are wrong, but I’m at least going by what I consider reasonable evidence. We can’t give a pass for <insert medical therapy> because historically we’ve missed on things in the past - if anything, that’s more of a reason to prove our therapies before implementing them. The fact that we are doing and have done things that harm patients because we don’t/didn’t know better should be an argument to be more careful about studying both newly implemented and longstanding medical therapies, not less.

Not just that, but think about the downstream consequences. Maybe it doesn’t hurt people in your 99% mortality group, but what about the 50% mortality group? You start using it in your 99% cohort, then someone thinks your slick and it starts getting used in a 90% preintervention group, then 80%, then 50%. Before you know it, it’s standard of care and you no longer can convince the IRB that you should have a rigorous study. Maybe it increased mortality 1-2% in the 50% cohort - we would never know.

You called my logic awful then say I'm condescending?? With that said you do bring up a really valid argument in your second paragraph. I have seen the extrapolation of weak data and i am probably guilty of that myself. Point well taken, I see where your coming from and agree with you on that.

 

[leviathan]

I've done it on a few cases and they did survive, but hard to really say it was the cocktail. None of them weaned off pressors immediately like Marik claims he's seen happen on almost all his cases. I will say this is different than something like Xigris because it's cheap, and seems to be safe, has a good physiologic rationale for its action, and there are already a few studies that support its use. Don't get me wrong though, I will definitely not be surprised if the ongoing RCTs show no benefit.

 

[deleted171991]

I've done it on a few cases and they did survive, but hard to really say it was the cocktail. None of them weaned off pressors immediately like Marik claims he's seen happen on almost all his cases. I will say this is different than something like Xigris because it's cheap, and seems to be safe, has a good physiologic rationale for its action, and there are already a few studies that support its use. Don't get me wrong though, I will definitely not be surprised if the ongoing RCTs show no benefit.

Honestly, I would be surprised. As far as I remember, Marik claimed such a huge benefit in his first group of patients that he stopped his trial early and gave everybody the cocktail.

There is one thing though: he does give the cocktail early, not as a last resort.

 

[leviathan]

Honestly, I would be surprised. As far as I remember, Marik claimed such a huge benefit in his first group of patients that he stopped his trial early and gave everybody the cocktail.

There is one thing though: he does give the cocktail early, not as a last resort.

Yes that's true. I've only given it up front as well, both cases actually were necrotizing fasciitis. I've seen a few cases where they had been in a few days in with mods so decided probably too late to see benefit.

 

[SurfingDoctor]

Good rationale? The problem is that people throw around “oxidative stress”, “free radicals” and “cytokines storm” and typically have no understanding of what those mean... which are actually useless buzz words to sell people crap supplements at GNC.

People like to measure levels of stuff in sepsis, find at that low (without understand why), claim deficiencies and suggest hormone/vitamin replacements. Except no one bothers to ask are those low levels a normal response, they just like to assume it isn’t.

 

[chessknt]

Good rationale? The problem is that people throw around “oxidative stress”, “free radicals” and “cytokines storm” and typically have no understanding of what those mean... which are actually useless buzz words to sell people crap supplements at GNC.

People like to measure levels of stuff in sepsis, find at that low (without understand why), claim deficiencies and suggest hormone/vitamin replacements. Except no one bothers to ask are those low levels a normal response, they just like to assume it isn’t.

The entire state of sepsis is an inappropriate response otherwise people would live through it without our help.

 

[SurfingDoctor]

The entire state of sepsis is an inappropriate response otherwise people would live through it without our help.

Which part is inappropriate? I’m not suggesting that people don’t need help to get through sepsis, just asking which specific mechanism is inappropriate.

 

[lunaire]

Which part is inappropriate? I’m not suggesting that people don’t need help to get through sepsis, just asking which specific mechanism is inappropriate.

I wouldn't say inappropriate, maybe exaggerated is more accurate? The way I see it, if you can neutralize the bacterial etiology with antibiotics & source control, then spread out the massive inflammatory response over days as opposed to hours, the patient's got a better chance of getting through sepsis without developing shock/end organ failure.

 

[SurfingDoctor]

I wouldn't say inappropriate, maybe exaggerated is more accurate? The way I see it, if you can neutralize the bacterial etiology with antibiotics & source control, then spread out the massive inflammatory response over days as opposed to hours, the patient's got a better chance of getting through sepsis without developing shock/end organ failure.

That’s kinda my point. It’s a whole slew of processes, pro inflammatory, anti inflammatory, normal, exaggerated and suppressed. The underpinnng of that is temporal expression via genetics and epigenetics. These cocktail recipes of course are blanket approaches to an incredibly complex pathophysiology so to suggest they have their foundation in good rationale, is woefully inaccurate.

 

[Hernandez]

I'm surprised CMS hasn't rolled this into the SEP1 Bundle yet

 

[leviathan]

Good rationale? The problem is that people throw around “oxidative stress”, “free radicals” and “cytokines storm” and typically have no understanding of what those mean... which are actually useless buzz words to sell people crap supplements at GNC.

People like to measure levels of stuff in sepsis, find at that low (without understand why), claim deficiencies and suggest hormone/vitamin replacements. Except no one bothers to ask are those low levels a normal response, they just like to assume it isn’t.

One rationale is in combating endothelial dysfunction; vitamin C helps to tighten the endothelial junctions / decrease vascular permeability and third-spacing. We know for sure in the burn population that it significantly (both clinically/statistically) decreases the fluid requirements. There are also antioxidant and antithrombotic effects as you mentioned, which help to improve microvascular circulation, but as you said those are more buzzwords to me that I couldn't explain at a cellular level, though I'm sure others could. You're absolutely right that sepsis is a very heterogeneous disease, so it may not help everyone. I don't think it's a panacea like Marik has claimed.

 

[SurfingDoctor]

One rationale is in combating endothelial dysfunction; vitamin C helps to tighten the endothelial junctions / decrease vascular permeability and third-spacing. We know for sure in the burn population that it significantly (both clinically/statistically) decreases the fluid requirements. There are also antioxidant and antithrombotic effects as you mentioned, which help to improve microvascular circulation, but as you said those are more buzzwords to me that I couldn't explain at a cellular level, though I'm sure others could. You're absolutely right that sepsis is a very heterogeneous disease, so it may not help everyone. I don't think it's a panacea like Marik has claimed.

Without getting into the specifics, my grant funding and research in “endothelial dysfunction” in response to infections and sterile injury. Within the field, there are at least 3 or 4 mechanistic explanations for endothelial dysfunction, typically related to NOS3 function and NO/ONOO generation, but also membrane exocytosis (none of which may be entirely right or wrong). These are not including not the more ubiquitous idea that people use which associates changes in barrier function of the endothelial layer as “endothelial dysfunction”, but they generally have little idea what that actually means.

As for burns, don’t get me started...

 

[Laryngophed]

Without getting into the specifics, my grant funding and research in “endothelial dysfunction” in response to infections and sterile injury. Within the field, there are at least 3 or 4 mechanistic explanations for endothelial dysfunction, typically related to NOS3 function and NO/ONOO generation, but also membrane exocytosis (none of which may be entirely right or wrong). These are not including not the more ubiquitous idea that people use which associates changes in barrier function of the endothelial layer as “endothelial dysfunction”, but they generally have little idea what that actually means.

As for burns, don’t get me started...

When I think of endothelial dysfunction, I think of it as dysregulation of VSM control by endothelial cells. And want to guess where I fall on the argument of the source of autoregulation? But we know that inflammatory disease processes impair the ability of the endothelium to respond appropriately to "normal" signals for vasodilation/constriction, even if our ability to identify those signals is iffy at best.

 

[SurfingDoctor]

When I think of endothelial dysfunction, I think of it as dysregulation of VSM control by endothelial cells. And want to guess where I fall on the argument of the source of autoregulation? But we know that inflammatory disease processes impair the ability of the endothelium to respond appropriately to "normal" signals for vasodilation/constriction, even if our ability to identify those signals is iffy at best.

I won't disagree with any of this, other than endothelial regulation of vascular smooth muscle is just one aspect of endothelial function. But in the classic literature testing endothelial dysfunction it effect of occlusive brachial artery cuff pressure of doppler flow upon reperfusion or vascular flow/tension in response to acetylcholine, nitroprusside and phenylpherine. The caveat to these studies is the dependent on the endothelium to release NO or EDRF in the setting of chronic, inflammatory vasculopathies (hypertension, diabetes, rheumatoid arthritis, etc.). I've only seen a handful of studies that testing this in acute insults, such as cardiopulmonary bypass and ischemia/reperfusion. There is a paucity of data regarding clinical measurements of acute endothelial dysfunction, particularly in sepsis. Additionally, as I mentioned, while I agree that endothelial-mediated vascular tone is the gold standard of measuring endothelial dysfunction, it ignores many of the other aspect of endothelial function, namely as a barrier (which involved leukocyte trafficking (there are some incredible animal studies demonstrating endothelial function is necessary for bacterial clearance independent of vasomotor tone), homeostasis, permeability and inflammation propagation). For better or worse, when these other functions of the endothelium go awry, it is also labelled as endothelial dysfunction by clinicians, more than researchers. As for what is a "normal" signal in sepsis, while not specific to the endothelium, one doesn't have to look any further than cortisol levels and hydrocortisone treatment to realize currently, we have a very limited ability to define "normal" in sepsis.

 

[jdh71]

I'll leave this here

http://journal.chestnet.org/article/S0012-3692(17)31276-X/abstract

 

[AdmiralChz]

Anecdotal, but our institution joined with several that surround us for a brief study on this. I don't know many details (not in CCM directly), but I know that the overwhelming feeling is poor on the cocktail overall.

 

[SurfingDoctor]

I'll leave this here

http://journal.chestnet.org/article/S0012-3692(17)31276-X/abstract

Good lord, this got published in CHEST? Hmm...

 

[SurfingDoctor]

Can A Cocktail Of Vitamins And Steroids Cure A Major Killer In Hospitals?