Post-intensive care syndrome results from continuous inflammation | Hacker News Reader

Post-intensive care syndrome results from continuous inflammation

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84 pointsJPLeRouzic29 comments

This topic is interesting to me for a few reasons...

Cognitive impairment has long been associated with inflammation in older adults: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3390758/

As well as the general population where illness is involved: https://psychcentral.com/news/2019/12/01/inflammation-linked...

And it contributes to a variety of disorders (potentially almost all of them). The research here is pretty broad, Google if interested. Notably, depression, anxiety and other behavior impacting problems are among the aforementioned disorders.

We know that exercise levels and diet can lower or increase inflammation.

So we have this sort of rare magic bullet when it comes to health, cognition and aging. Lowering inflammation won't fix everything of course, but it will lower your risk of pretty much everything.

And yet this truth is less a part of the zeitgeist than you'd expect, given it's impact. Maybe because it's simple but not easy to change your lifestyle. Or more importantly, the lifestyles of a population. Especially when part of the problem is financial insecurity.

>This topic is interesting to me for a few reasons...

>Cognitive impairment has long been associated with inflammation in older adults: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3390758/

Once upon a time, when I was an itty bitty grad student, I had an appointment with an immunology PI to ask to be involved in their research.

One of the first questions they asked me was, what's inflammation?

"You want the layman's answer or the real answer?"

"Both."

"The layman's answer is that set of cellular and biochemical reactions involved with infections and their resolution."

"And the real answer?"

"There's no such thing. 'Inflammation' is the set of cellular and molecular biology that immunologists discovered before everyone else did. There isn't a single molecule in the body that isn't involved in a wide variety of functions, and there isn't a single function -be it extracellular remodeling, monitoring of cells for expression of abnormal proteins, cell signaling, cell life cycle regulation, etc. - that doesn't hook into a hundred different functions in a hundred different contexts. 'Inflammation' refers to the lens of the person studying the thing, not the thing."

I got a happy smile and a welcome handshake with that answer.

"Inflammation" as an explanation in medicine ranks alongside "Quantum Physics" as an explanation in everything else. When someone starts citing "quantum physics" for why anything, you can safely tune them out 99.99% of the time.

Well now that's interesting. A lot of medical/health/nutrition information these days seems to revolve around inflammation. Much of it is supposedly backed by studies (that I don't really have the time or understanding to dive into), but there's just so many things that supposedly cause it and are supposedly caused by it that I get the feeling that we don't really have any idea at all what it is and what it does. It's like it's some magic spell that is caused by whatever thing you're ideologically against, and causes basically everything you don't like.

We do know a lot about it, though, much more, I'm assuming, than we did when the previous poster was a grad student.

We know about different types of inflammation and the cellular processes involved, we know how it turns on and off, we know more about how it effects different systems and organs in the body. We can distinguish between short term and chronic inflammation and differentiate between types of inflammation that are beneficial and types that aren't.

There are, of course, lots of articles and trends out there that over simplify and make unreasonable associations and leaps... the comparison to quantum mechanics is apt in that way. But irresponsible reporting doesn't invalidate the source.

Our understanding is well beyond abstract at this point, despite how much we still don't know. The bulk of what we don't know outweighs what we do in most areas of biology.

OP went on to medical school after finishing that grad degree. We know a lot more about molecular biology. That we clump stuff under the header of "inflammation" is a categorization/naming issue, not a biology issue :)

This topic is also interesting to me and I’ve thankfully had some opportunity to observe friends and family in a way that verifies a lot of the claims.

Here are my thoughts on why it’s not in the zeitgeist to the level you’d expect:

1) A lot of people have normalized to inflammation and just assume that’s how their brains function

2) In addition to the “obvious” things like diet and exercise, there’s a significant impact through environment: lack of clean fresh air, mold, detergents, building material (and/or furniture) off-gassing, dust and dander especially in the sleeping space, and so-on. In cases like this people “try eating properly”, don’t see the kind of benefits that people talk about, and write off the whole thing as a not working “for them” before going back to their original diet.

3) We rarely talk socially about symptoms like brain fog, memory lapses, mild pain, anxiousness, speediness, etc as anything related to diet or environmental exposure. Previous generations seem to have mental and emotional wellbeing the same attention as they gave to the supernatural, and we seem to have to continually shake off mindsets like “if I can’t measure it it doesn’t exist”

> there’s a significant impact through environment

Yes environment is a better term (it includes diet, medically speaking). Modern life isn't something we're well suited for from an evolutionary standpoint.

> We rarely talk socially about symptoms like brain fog, memory lapses, mild pain, anxiousness, speediness, etc as anything related to diet or environmental exposure. Previous generations seem to have mental and emotional wellbeing the same attention as they gave to the supernatural, and we seem to have to continually shake off mindsets like “if I can’t measure it it doesn’t exist”

So true, and it's still a thing to a lesser degree in younger generations. Fortunately we increasingly can measure it.

>We know that exercise levels and diet can lower or increase inflammation.

I think it is extremely important to distinguish the types of inflammation. Exercise creates acute inflammation (for example the breakdown of certain muscle tissue in response to being worked) and the inflammation causes the body to repair the muscle, typically the resulting muscle tissue is improved. Whereas dietary inflammation, or inflammation caused by certain foods, is generally chronic and has damaging effects on everything down to DNA in the cells and this damaged DNA can get copied into new cells.

>So we have this sort of rare magic bullet when it comes to health, cognition and aging. Lowering inflammation won't fix everything of course, but it will lower your risk of pretty much everything.

You said it perfectly following this statement, it is simple but unfortunately that does not make it easy.

Sometimes the body gets confused about what it's supposed to be doing and accidentally fixes another problem.

We had a story recently about viral infections and cancer. Someone reminded me the other day that, before antibiotics, one treatment for venereal diseases was to expose yourself to another disease.

I wonder if we're going to figure out that these "dietary inflammation" issues were always in our diets, but that we were so active that muscle tissue repair mopped up most of the problem.

Big part of the problem is that inflammation is beneficial, only chronic inflammation is a problem. But treatments would reduce both.

> Big part of the problem is that inflammation is beneficial, only chronic inflammation is a problem.

But what about anaphylaxis, hay fever, mild allergies etc. There are plenty of acute or non-chronic inflammatory conditions that are a problem.

We have acute antiinflammatories for these cases. And they have serious side effects, especially treatments for asthmatics.

Now interesting part here is the mechanism which is different from the one targeted by current drugs.

> But treatments would reduce both.

Which is why the suggested solution is a lifestyle change to avoid the things that cause inflammation unnecessarily.

This article brings up a specific inflammation-related protein (HMGB1) as being correlated with cognitive impairment after an ICU stay.

Usually an ICU stay is the result of being profoundly and dangerously ill -- going to the ICU likely means that you need significant pharmacological and/or mechanical assistance in the basic things like... circulating blood. Or oxygenation. And once there, you may have tubes/catheters/wires in various orifices and puncturing vessels and organs. You're often medically sedated, and if you become too awake or agitated, you are sedated further. Unsurprisingly, many patients become agitated or delirious -- they don't know where they are or when it is or maybe even who they are. Which makes things worse. I mean, imagine it -- maybe you wake up in the midst of this horrendous state of affairs, and you become understandably upset and confused, but if you move around or holler (if you can) you may well get further sedated. Repeatedly. The cognitive impact of this alone can understandably be immense.

I don't mean to say that ICUs are some evil thing, though surely they could be improved. But the causes of "post-intensive care syndrome" are undoubtedly enormously multi-factorial, what with the level of derangement and insult to your body (and especially your mind!) from whatever illness led to you the ICU to begin with, and the experience of being there. And as such I am skeptical that this single protein could be terrifically useful either as a marker of or a therapeutic target for cognitive impairment in this setting.

(I think as protein mass spec and other technologies improve, we might gain a better understanding of how sets of dozens or hundreds of proteins in the body may be related to disease states, and perhaps therapies will target combinations of proteins or more complex interactions rather than "blocks this one protein".)

I spent 6 weeks in the ICU, half of them in a coma and intubated, it took me weeks to feel my brain was working normally when I was released to a normal recovery floor. I was confused, a little delirious and my memory was screwed up.

I wonder what would the effects be of a "control situation" where you stay at home in bed. You are fed there using the same "nutrients", you get the same amount of exercise (none) and may even be induced to less motion by sleeping.

Also think of all the stuff you're exposed to in the ICU -- lots of patients come back from a hospital stay exposed to a number of things like MRSA or worse.

I'm in my thirties and had unresolved medical issues for a decade. And in that time experienced much of our health system including visiting psychologists and taking antidepressants. And nothing really helped. The only thing that happened is that I learned to live with it.

The only constant in all is an allergy and a cyst causing constant swelling and inflammation. The technical appearance of this, and lab results, never looks very bad, and doctors are quick to discard the cyst as a source of my problems.

I'm at the end of my wits, and my mind and body are deteriorating further and I find it hard to muster up the energy to try and resolve this with ever more visits to doctors. My physicians are not concerned enough to try and resolve this quickly, because I still appear fine. I can function normally for a while. But working 9-5 and having a life is honestly above my limit. I don't dare press the issue too much because doctors are quick to jump to psychological-issues-are-the-source (https://en.wikipedia.org/wiki/Somatic_symptom_disorder) . Physician visits and different things are spaced so widely that a lot of times passes, and I'm still supposed to wait longer and go step-by-step.

After all this time, and a lot chasing ideas and trying out smaller remedies, I arrived at the conclusion/idea that it was the cyst and the inflammation and possibly recurrent colonisation with bacertia from it all along. The cyst that I was told was not an issue.

It's a miracle that I founded and still have a family. I appreciate all the good things I received and achieved, but honest to god large parts of the way were miserable, and I'm afraid to find out that it's not going to get better.

P.S.: Sorry for venting

Somewhat similar. 3 years of intense effort to find out what was wrong.

Constantly told it was depression or anxiety.

Turned out it was an auto immune problem.

Anti depressants made me care less about problems but didn’t fix them.

"Humans and other mammals have two seahorses, one on each side of the brain."

Today I learned that "hippocampus" comes from the Greek for "seahorse", because it looks like a seahorse: https://images.squarespace-cdn.com/content/v1/52ec8c1ae4b047...

I am not sure you need inflammation as an explanation. People in the ICU are there because they are extremely sick. Often they have problems with blood pressure and oxygenation. This probably leads to neuron death. In addition, because they are getting checked on continuously they likely have poor sleep and loss of day-night cycles. I am not sure how you can differentiate between very sick people are in the ICU, and very sick people often have a lot of inflammation.

This makes me wonder what is happening during an extreme tooth ache. During those times when I have had a bad tooth it is like my mind is in slow motion and the ability to think is gone. I have had extreme pain and still been able to think clearly but with an inflamed tooth it’s a different experience.

Teeth are fairly near the brain and are part of the skeleton. Except for teeth, bone infections are typically considered to be very, very serious.

Bone marrow is an important part of the immune system. White blood cells and what not originate there.

I feel like if you look at a tooth ache as a skeletal issue, the seriousness of it begins to make more sense.

Anyone know if this is anyway related to PANDAS condition (RE: inflammation -> cognitive changes)? We were recently introduced to the condition and my understanding is the theory is inflammation is caused by the bodies immunity response to strep virus (I might be off on that explanation). The idea inflammation could give rise to cognitive impairments/changes would appear to lend some credence (or maybe that is just already established??). We have a daughter who checks some of the boxes on what people describe as the condition and are just getting an understanding.

Here's something I've never understood, although I suspect the question is an open one even among medical professionals:

Given that inflammation is an immune response, is it the inflammation itself that's bad, or the underlying condition? If we only treated inflammation symptoms without curing any of the underlying diseases, would there be a significant improvement in outcomes? Or would they be worse because you'd be interfering with the body's response?

There's plenty of cases where inflammation is not helpful at all, such as arthritis and psoriasis. When the body is attacking itself in an immune disorder, there's really no down side to preventing the body from attacking itself. Unfortunately, such disorders become more and more common the older you get, so you can think of it as the immune system accidentally triggering rather than it triggering too much on some particular thing.

It's true, though, that for really severe inflammation disorders that doctors start prescribing systemic immunosuppressants, which then result in the patient getting real illnesses more often. Often the patient has such a bad condition at that point - my psoriasis leads to skin flaking off in bloody patches and smearing blood on the things I touch and my hands feeling like sand paper to other people, for example - that they prefer this overall.

Even the localized topical immunosuppressants like hydrocortisone cream have negative side effects like skin thinning, but I think everyone using those agrees it's better than the extra inflammation.

Inflammation is catch-all term that in this context can only mean "excessive immune activity", just like "protest" in society can mean a bunch of things. Hence, the only safe thing to say in the general case is that it depends!

The article describes negative effects of inflammation which persists long after the underlying condition has been addressed, due to persistently elevated levels of the HMGB1 protein. It notes that "anti-HMGB1 treatment given several days after a serious illness can reduce cognitive decline in mice" and proposing that these results might some day be replicated in humans.

Inflammation is an immune response, so it is required to keep foreign agents from spreading, essentially. My understanding is that immune cells can become damaged, when this happens they malfunction and inflame the system when it doesn't need to be inflamed.

Sounds similar to chemo brain, which is mental impairment that happens in cancer patients as a side effect of treatment.

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