2016 Surviving Sepsis Guidelines

[sluggs]

Anybody read them yet?
Anybody have opinions?
I appreciate the statement that we ought not be relying on CVP alone, for starters....

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[engineeredout]

Routine double coverage antibiotic therapy for septic shock? People actually doing this?

I like Josh Farkas's takes on the new guidelines: https://emcrit.org/pulmcrit/sepsis-myths/

 

[deleted171991]

I like Josh Farkas's takes on the new guidelines: https://emcrit.org/pulmcrit/sepsis-myths/

+1. Great article, as usual.

Respectfully, to me, anybody even considering CVP for fluid status monitoring, in 2017, should retire. The SSC guidelines have been mostly irrelevant to good intensivists for years (the CVP was still mentioned there until a year ago), beyond the common sense stuff (early antibiotics etc.). Plus the guidelines seem to be written by career bureaucrats, happy to see more bureaucracy (sepsis bundles, clipboard nurses evaluating compliance with the bundle etc.), who rely more on expert opinion than proven evidence (they would give fluids to everybody etc.). It's ridiculous that when studies have proven that routine removal of central lines doesn't help, they still advocate for it when it is "possible" (not probable) that the central line is a source for sepsis. But placing an A-line for pressor infusions is just a "weak recommendation". They still love their stupid 30-45 degree HOB elevation (why not 10-15?), despite the lack of evidence that the risks of underperfusing an elderly brain by 10 mmHg, when the patient is in shock, outweigh the benefits (and are maybe a component of all those post-ICU cognitive problems). And, of course, nobody would recommend placing the A-line transducer at the level of the auditory meatus for patients on pressors, because there is no A-line recommended in the first place. And so on.

The entire document is full of "weak recommendation", "low quality of evidence" and "BPS" (best practice statement). It's clipboard doctors blind leading the blind. Plus if something has both a weak recommendation and low quality of evidence, how about not even publishing an opinion about it?

 

[SurfingDoctor]

Any impact this iteration or future iterations have on improving outcomes is negligible (this was also relayed to me by one of the primary authors of the guidelines).

Without understanding dynamic mechanisms of inflammation, genetics and epigenerics (there are some cool studies on these... but the clinical application isn't ready for prime time...) survival in sepsis is about as good as it gonna get. The guidelines won't change that.

 

[deleted171991]

Then they should stop producing guidelines for the sake of academic promotion guidelines. For the reasons mentioned here: http://www.anesthesiologynews.com/C...delines-a-Disservice-Except-for-Lawyers/40561 .

 

[SurfingDoctor]

Somewhat relevant...

Doctor Turns Up Possible Treatment For Deadly Sepsis

Let the eye-rolling begin... (though I think some sort of combined immunotherapy is probably the right direction. Also, some of the best discoveries happened by random chance, but all that being said... I'll put on my skeptic hat)

 

[engineeredout]

Somewhat relevant...

Doctor Turns Up Possible Treatment For Deadly Sepsis

Let the eye-rolling begin... (though I think some sort of combined immunotherapy is probably the right direction. Also, some of the best discoveries happened by random chance, but all that being said... I'll put on my skeptic hat)

Definitely had some eye rolling, but then noticed Paul Marik a part of it.

They actually create a double blind placebo controlled RCT regarding this and prove something I'd definitely be impressed

 

[deleted171991]

 

[SurfingDoctor]

Hmmm... the slide that said "Mechanistic Pathways in Sepsis"... Vitamin C reduces NF-kB by being an antioxidant... made me . Granted I get this is a clinical talk, but one of the anti-oxidant properties of Vitamin C is reportedly on increased tetrahydrobiopterin synthesis increasing eNOS coupled and reduced superoxide production. Except that eNOS coupling has nothing to do with NF-kB and has no effect on micovascular permeability, so immediately this hypothesis is false.

Again, maybe he is on to something, but in a study of a treatment on 47 patients with a hypothesis that is wishy-washy... I'm not getting my hopes up.

 

[deleted171991]

I honestly don't care about the hypothesis or mechanism at this point, but about the outcomes. I am not practicing CCM this year, but I really don't see much downside in trying it out in a septic patient with high pressor needs. I also trust the source, despite Dr. Marik's historical tendencies for being passionate. I think that, overall, he is a great intensivist and educator.

 

[SurfingDoctor]

I honestly don't care about the hypothesis or mechanism at this point, but about the outcomes. I am not practicing CCM this year, but I really don't see much downside in trying it out in a septic patient with high pressor needs. I also trust the source, despite Dr. Marik's historical tendencies for being passionate. I think that, overall, he is a great intensivist and educator.

Well, I'll agree with that trying vitamin C doesn't have much downside. The steroids, yep, it'll make the BP higher... but the secondary effects aren't harmless. The thiamine, well, the data says it really doesn't do anything (unless you have proved thiamine deficiency), so I guess that's fine too.

Randomized, Double-Blind, Placebo-Controlled Trial of Thiamine as a Metabolic Resuscitator in Septic Shock: A Pilot Study. - PubMed - NCBI

Though I get where you are coming from, doing funding clinical trials that have no good hypothesis or mechanism... that's a lot of wasted taxpayer money (which is like every other sepsis trial... ever).

 

[deleted171991]

Many of us would at least try a dose of steroids, once the pressor needs go up. So I don't see much downside to 50 of hydrocortisone. Also, he says that the effects tend to be visible within a few hours, before the next dose of his cocktail. I guess one could try just the vitamins; there is really not much downside there.

 

[SurfingDoctor]

Many of us would at least try a dose of steroids, once the pressor needs go up. So I don't see much downside to 50 of hydrocortisone. Also, he says that the effects tend to be visible within a few hours, before the next dose.

Oh I know people give steroids. People measure cortisol levels of 30 and still give steroids. That drug will continue to be given in the foreseeable future, despite that fact that 30 years of research and its never been shown to improve outcomes (outside of weaning off pressors faster). I heard a talk about steroids and epigentics in sepsis and the comment was made "It is embarrassing that we don't know the role of steroids in sepsis after all this time"... all I can say is "yep"

 

[deleted171991]

I treat patients the way I would want my family members to be treated by others. So I'll use evidence-based medicine as long as it works, and then I'll try whatever could give them a chance based on the literature, as long as it's not likely to harm them. I would rather have them get well under the care of their shaman than die under mine, just because I had to be "right".

 

[engineeredout]

I see parallels to our routine measurement of phosphate levels and supplementation when necessary. One of the main ICUs I work in is in an inner city, full of people who are not in the best health, nutritional status, and who opt for heroin over actual food the majority of the time. They come in with low albumins, undetectable prealbumins, and either low phos right out of the gate, or we watch the phos levels plummet when we actually begin refeeding these people. We know how important it is to provide phos supplementation to avoid metabolic failure. Is vitamin C another such molecule we should be measuring and supplementing in these critically ill patients?

Can't wait for the future trials.

 

[Hernandez]

EGDT is dead....Long live usual care.

 

[Raryn]

EGDT is dead....Long live usual care.

"Usual care" is pretty different in 2017 than in 1997 though. At least somewhat thanks to EGDT.

 

[tux4]

Hmmm... the slide that said "Mechanistic Pathways in Sepsis"... Vitamin C reduces NF-kB by being an antioxidant... made me . Granted I get this is a clinical talk, but one of the anti-oxidant properties of Vitamin C is reportedly on increased tetrahydrobiopterin synthesis increasing eNOS coupled and reduced superoxide production. Except that eNOS coupling has nothing to do with NF-kB and has no effect on micovascular permeability, so immediately this hypothesis is false.

Again, maybe he is on to something, but in a study of a treatment on 47 patients with a hypothesis that is wishy-washy... I'm not getting my hopes up.

Actually the fact that it is an important antioxidant is why cells will readily take it in. It is then oxidized and this oxidized form directly causes downregulation of NFKB. So for the message he is trying to convey, he isn't wrong.

 

[SurfingDoctor]

Actually the fact that it is an important antioxidant is why cells will readily take it in. It is then oxidized and this oxidized form directly causes downregulation of NFKB. So for the message he is trying to convey, he isn't wrong.

There are also papers that show that NF-kB can be reduced by Vitamin C in a redox-independent manner. Maybe I was wrong to state the hypothesis is "false" but it isn't necessarily a true statement as to the cause and effect of anti-oxidants in sepsis. Is knocking down NF-kB even a good thing, since counter-regulatory mechanism are also NF-kB dependent?
Can we predict the effects of NF-kappaB inhibition in sepsis? Studies with parthenolide and ethyl pyruvate. - PubMed - NCBI

There's just so little that we know...

 

[tux4]

There's just so little that we know...

True that. Our understanding of these cellular are definitely too simplistic. We are knocking out/upregulating whole pathways or giving medications that do 100 different things that we don't understand fully understand.

He definitely makes some leaps in his assumptions but I like the picture he is painting overall. Definitely makes me think about this stuff.

 

[SurfingDoctor]

True that. Our understanding of these cellular are definitely too simplistic. We are knocking out/upregulating whole pathways or giving medications that do 100 different things that we don't understand fully understand.

He definitely makes some leaps in his assumptions but I like the picture he is painting overall. Definitely makes me think about this stuff.

Honestly, I hope he is right... I'm just not convinced there is a cure all. I do think treatments aimed at genetic signatures in septic patients is where the field is heading, the technology is just not there yet to make it useful in real-time.