How is sepsis and septic shock without an infection possible and why is the mortality rate higher?

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About two years ago I was admitted to the ER, then the ICU, then kept in the hospital for septic shock/sepsis but no infection was found. Prior to this experience my understanding of sepsis/septic shock was that there had to be an infection to be the underlying cause.

How is it possible for a body to go into this infection reaction without one? How do they know it’s sepsis and not something else if there’s no infection? My limited research also shows that in these cases the mortality rate is higher, why is that? Is that just because if they can’t find a cause it’s harder to treat?

Edit: I’ve also tried to do a lot of reading about septic shock/sepsis in general and don’t really understand it so a baseline explanation of what it is might also help.

In: Biology

Sepsis IS a generalised infection affecting most of all of the body where bacteria or viruses cause an immune reaction.

Such an immune reaction can lead the body to act defensively but dangerously in various ways causing organ failure.

By the time this happens (in about one in seven cases) the infective agents has been reduced below the point of identification.

Quick definitions: sepsis is often defined as a systemic inflammatory response with a known or suspected source of infection (though the definition of sepsis has been frequently revised over the years!). Septic shock is further defined as sepsis with persistent hypotension and/or poor organ perfusion after fluid resuscitation.

Though sepsis technically requires a source of infection to be diagnosed, there are many cases of *presumed* sepsis or septic shock in which no single infectious cause is established. Why? Sepsis is often presumed and treated accordingly because it’s so common in the hospital! So the vast majority of patients with shock in the setting of (1) a normally functioning (or hyperfunctioning) heart and (2) a normal volume status (e.g., not hemorrhaging, anemic, or otherwise hypovolemic) are frequently considered septic until proven otherwise.

Though I wasn’t aware that mortality is necessarily higher in patients without an identified infectious source (please link to an article if you’ve found one!), this finding wouldn’t surprise me. This is because:

* A presumptively septic patient is usually treated with a broader range of antibiotics that aren’t as precisely “targeted” at an identified infection. For example, a patient who has been found to be septic from a confirmed urinary tract infection (UTI) can receive a tailored antibiotic regimen that is more likely to eradicate the underlying UTI, thus resolving the patient’s sepsis. However, if there’s no confirmed infection to treat, clinicians often have to resort to a “scattershot” empiric antibiotic regimen that has broader but comparatively weaker coverage.
* There are a few places that doctors will look for infection first because (1) they’re easier to evaluate and (2) they are more common sources. In the ICU, a common pattern of evaluation for undifferentiated sepsis includes taking cultures from the blood, the urine, and the respiratory tract (sputum or tracheal aspirates) as well as performing a chest x-ray to look for pneumonia. If these preliminary evaluations are negative for infection, we’ll often look for subtler and rarer infections that are also potentially more severe—such as endocarditis, an infection of the heart valves that is much more difficult to eradicate.
* If sepsis hasn’t been confirmed via the detection of an infectious source, it’s possible that other mechanisms are in play that mimic sepsis and will not respond to the same treatments. For example, patients in liver failure often “look septic” on paper because impaired liver function can lead to a critically ill state that resembles septic shock. Treating acute liver failure with antibiotics and fluids alone is highly ineffective (in fact, many types of liver failure are difficult to treat in general). So outcomes in these cases may be worse.

There are various forms of shock, where your body can’t supply organs with blood.

Septic shock occurs specifically in response to infection. However, that infectious source is not always readily identified. In addition, there are various forms of shock that can *mimic* septic shock. Sometimes we admit patients with what appears to be septic shock and we never find an infectious source or other cause. Sometimes patients get better and we don’t know what caused it. Sometimes they don’t. Sometimes we start treating them for septic shock (survival depends on starting antibiotics very early) but further testing and evaluation identifies another cause of shock (like heart failure).