Speaker 1: Hi. My name is Katie Granger, and four years ago
Speaker 1: this month, I lost seven of my fingertips and both
Speaker 1: of my lower legs to sepsis. One thing that's interesting
Speaker 1: about my story is that the reason that it got
Speaker 1: so severe with me I actually ended up in septic shock,
Speaker 1: is because I did not know the signs and symptoms.
Speaker 1: So when I tell my story, I can't stop myself
Speaker 1: from kind of highlighting where I made some mistakes. So
Speaker 1: in September of twenty eighteen, I was living in Hawaii
Speaker 1: with my husband. We were new empty nesters and I
Speaker 1: had just gone to visit my kids in California for
Speaker 1: a week and my husband had taken that opportunity to
Speaker 1: go on a fishing trip to very remote Idaho. So
Speaker 1: went down to California, hung out with my kids, and
Speaker 1: then it was time to return back to Hawaii. I
Speaker 1: got on an airplane flew home, and when I got
Speaker 1: to the airport, this is when I remember noticing that
Speaker 1: I had this bump on my finger and it was oozing.
Speaker 1: It was kind of pink, and it had clear fluid
Speaker 1: coming out of it, so it looked different than anything
Speaker 1: I'd seen before. So I was on my way home
Speaker 1: my house is actually an hour from the airport. It's
Speaker 1: also an hour from the hospital, which is going to
Speaker 1: be relevant later on, so I did decide to go
Speaker 1: buy the emergency clinic. When I got there, I showed
Speaker 1: them the cut and they agreed that it did look
Speaker 1: infected and looked like it could possibly be MRSA. They
Speaker 1: took a little swab of it and said basically they'd
Speaker 1: call me in a few days if anything grew out
Speaker 1: of it. So they gave me a prescription for antibiotics,
Speaker 1: and they said to start taking them if it got
Speaker 1: worse over the weekend. At the emergency clinic, when they
Speaker 1: checked my vital signs, everything was great, so they didn't
Speaker 1: have any indication that I had sepsis at this point,
Speaker 1: and I really didn't. I just had an infection. So
Speaker 1: on Saturday morning, I woke up, I happed in the shower.
Speaker 1: It was warm there in Hawaii, I was kind of warm,
Speaker 1: but I never was registering a fever, so I didn't
Speaker 1: think there was anything wrong. I did notice that the
Speaker 1: infection on my finger was getting a little worse, so
Speaker 1: I went ahead and took an antibiotic. Well soon thereafter,
Speaker 1: I threw up, but I just thought it was because
Speaker 1: I'd taken an antibiotic on an empty stomach, and I
Speaker 1: wrote it off. But I ended up sleeping through the
Speaker 1: afternoon and sleeping through the evening, and sometime in the
Speaker 1: middle of the night, I got up and I probably
Speaker 1: went into the bathroom, which is two steps up from
Speaker 1: my bedroom. And what we think may have happened is
Speaker 1: that I maybe stood up quickly and low blood pressure
Speaker 1: in my body caused me to pass out. But what
Speaker 1: the result was is that I broke my left foot,
Speaker 1: I sprayed my right ankle, and I had just a
Speaker 1: mark on my kneehere I had fallen on the floor.
Speaker 1: So this is a sign for me of mental decline,
Speaker 1: because instead of calling for help like a normal person would,
Speaker 1: I crawled back in bed. So the next morning was Sunday,
Speaker 1: and I woke up at sunrise, like at the crack
Speaker 1: of dawn. I could hear the roosters outside. It was
Speaker 1: still dark, and I don't really remember much. I do
Speaker 1: know that I texted my friend and I said to
Speaker 1: my friend, can you take me to the hospital. She
Speaker 1: asked if we could go to the emergency clinic, and
Speaker 1: I said no. I have never been so sick So
Speaker 1: my friend took this seriously, as one should. She came
Speaker 1: right down to my house, let herself in, and she
Speaker 1: found me nearly unresponsive in my bed, and we tried
Speaker 1: to stand up, and that's when we realized that my
Speaker 1: feet hurt. We found out later that it was the
Speaker 1: break in the one foot, and then I also could
Speaker 1: have had some nerve pain from something you're going to
Speaker 1: hear about in a second. But it was about an
Speaker 1: hour drive and about fifteen minutes out, I started crying
Speaker 1: in the backseat, saying, are we there yet? Are we close?
Speaker 1: My hands and feet are on fire. So she went
Speaker 1: ahead and called the hospital and let them know that
Speaker 1: we were coming in. When we got to the hospital,
Speaker 1: they met us with a gurney. They got me out
Speaker 1: of the car, loaded me onto it, They took me
Speaker 1: right into the emergency room, and they did the things
Speaker 1: that they should do. It took my vital signs. So
Speaker 1: it turns out that my blood pressure at that point
Speaker 1: was fifty over thirty, which is extremely low. And it's
Speaker 1: funny because I've read my chart and they said I
Speaker 1: was conversive and pleasant, and I'm like, well that's my
Speaker 1: go to. I mean, I was faking conversive and pleasant.
Speaker 1: I also had an increased heart rate and I had
Speaker 1: low blood oxygen, so they immediately put an oxygen canulate
Speaker 1: in my nose just to let me breathe oxygen. Later
Speaker 1: in the day, the oxygen levels got worse and I
Speaker 1: actually had a mask forcing air into my lungs. So
Speaker 1: what was happening is that my organs began failing. I
Speaker 1: stopped urinating, so that was a sign that my kidneys
Speaker 1: were failing, and it was becoming really clear that I
Speaker 1: was at higher levels of steps is called septic shock.
Speaker 1: The whole thing with my hands and fingers are on
Speaker 1: fire is showing that my circulation at my extremities was very,
Speaker 1: very bad, and my fingers began turning purple, and so
Speaker 1: did my toes, although I didn't see them at the beginning.
Speaker 1: I ended up having a condition later that they diagnosed
Speaker 1: called disseminated intravascular coagulation. So if this had not happened
Speaker 1: in the hospital, I would have run out of platelets.
Speaker 1: So at that point in time, I was on an
Speaker 1: outer island in Hawaii. We lived on the island of Kawaii.
Speaker 1: Anyone in Hawaii, if you get sick on an outer
Speaker 1: Island and you get very sick and you need an
Speaker 1: ICU or you need severe help, they will transport you
Speaker 1: by air ambulance over to a Wahoo, which is where
Speaker 1: Honolulu is. So on Monday morning a bed became available
Speaker 1: at the hospital at Queen's Hospital, it was decided that
Speaker 1: they would fly me over to Honolulu. So they ended
Speaker 1: up giving medication to put me in a drug and discoma.
Speaker 1: They intubated me and they sent me over to a Wahoo.
Speaker 1: When I got there, my husband had, actually, thank goodness,
Speaker 1: had landed on a Wahoo about an hour before I did,
Speaker 1: so he was able to meet me at the hospital,
Speaker 1: so now I have my family with me. When they
Speaker 1: came out, they told him that I was not stable,
Speaker 1: and that started asking questions like does she have a will,
Speaker 1: and what are her desires? If we need to do
Speaker 1: you know, if we need to resuscitate. But they did
Speaker 1: say that he should call our children, who again were
Speaker 1: in California and have them come because they weren't sure
Speaker 1: I was going to make it. So my family was
Speaker 1: by my side for five days as I sat in
Speaker 1: the ICU, or as I laid in the ICU, and
Speaker 1: they were praying over me and watching my hands and
Speaker 1: feet turn more and more purple up to my wrists
Speaker 1: and up to my ankles, and it became clear, I
Speaker 1: think to them during that week that I was going
Speaker 1: to lose at least my fingers and toes, and likely
Speaker 1: more than that. On my daughter's twenty third birthday, my
Speaker 1: oldest daughter's twenty third birthday, which was five days later,
Speaker 1: I woke up and when that happened, I saw my
Speaker 1: husband in front of me, and he got right into
Speaker 1: my face to just let me know he was there,
Speaker 1: and then everything was going to be okay. I was
Speaker 1: extremely confused. But one thing that happened is I saw
Speaker 1: my fingers go in front of my face and seven
Speaker 1: my fingertips were black. My thumbs, the tips of my
Speaker 1: thumbs were black. It looked like I was going to
Speaker 1: lose all of my fingers, and I was absolutely terrified.
Speaker 1: I didn't know what had happened. I mean, whilst I remembered,
Speaker 1: I was being cheerful talking to people in the hospital,
Speaker 1: and then I'm waking up and I'm realizing that I
Speaker 1: can see these clearly dead fingers. I realized I'm going
Speaker 1: to lose these fingers. So we spent three weeks at
Speaker 1: the hospital, doing hyperbaric chamber every day and doing nitrogliscer
Speaker 1: and cream on my hands and feet three times a day.
Speaker 1: It was extremely painful, but we were able to save
Speaker 1: my hands. Right now, I have my hands and most
Speaker 1: of my fingers up to those seven tips that were black.
Speaker 1: My thumbs are fine. I have them one hundred percent.
Speaker 1: I'm really fortunate that that's what my outcome was. At
Speaker 1: the time, I was really trying hard to save my feet,
Speaker 1: and I was having a hard, as you can imagine,
Speaker 1: a very hard time admitting that we might not be
Speaker 1: able to After three weeks, I finally looked at my
Speaker 1: husband and said, I understand that we can't save my feet,
Speaker 1: and I just want to move on to whatever the
Speaker 1: next steps are after. You know, after a couple months,
Speaker 1: I got the amputations. I did recovery at home. I
Speaker 1: got my prosthetic legs right around Christmas time. This happened
Speaker 1: in the middle of September. Initially and I was able
Speaker 1: to stand on them immediately, but it was painful, so
Speaker 1: I just built up my tolerance to walking around in
Speaker 1: them just slowly. I stayed in my wheelchair a lot
Speaker 1: of the time and Anyways, I started getting better and
Speaker 1: I started realizing I could get my life back. I
Speaker 1: went and visited my daughter who she went to Rome
Speaker 1: for study abroad, and my husband and my best friend
Speaker 1: arranged for me to go as well, so I got
Speaker 1: to go visit her like I had always dreamed of doing.
Speaker 1: And since then I'm living a really full life. A
Speaker 1: year later, I was invited onto the board of directors
Speaker 1: of Sepsist Alliance and now I share my story to
Speaker 1: spread awareness.
Speaker 2: Katie, thank you so so much for being willing to
Speaker 2: share your story and taking the time to tell your story.
Speaker 2: It's terrifying.
Speaker 3: It's terrifying. And thank you too for all of the
Speaker 3: work that you do raising awareness and sharing your story,
Speaker 3: not just with us, but with so many people.
Speaker 2: Yeah, it's amazing.
Speaker 4: Yeah.
Speaker 3: Well hi, I'm erin Welsh and I'm Aaron Allman updyke.
Speaker 2: This is this podcast will kill you.
Speaker 3: It's a big old episode today, it really really is.
Speaker 2: It's a big one.
Speaker 4: It is.
Speaker 2: We're covering sepsis. Fish is not like a one size
Speaker 2: fits all definition.
Speaker 4: Oh I can't wait.
Speaker 3: I have a whole paragraph called definition. Never had that before.
Speaker 2: Yeah, it's it's a big one, but it's also tremendously important,
Speaker 2: and I don't think I realized before we started digging
Speaker 2: into this just how prevalent and scary and kind of
Speaker 2: still there are a lot of open questions.
Speaker 3: Oh, Aaron, I feel like all I have are open
Speaker 3: questions when it comes to sepsis. So yeah, it's gonna
Speaker 3: be probably heavy at times, but it's gonna be I think,
Speaker 3: a really good episode and really interesting.
Speaker 2: Yeah, yeah, for sure. Well, should we start off this
Speaker 2: episode like we do every other episode with the Quarantiny,
Speaker 2: time with the quarantin any time? What are we drinking
Speaker 2: this week?
Speaker 4: We're drinking let Us Spray. I love it so much.
Speaker 2: I do too. So this is a reference to Joseph
Speaker 2: Lister and his carbolic acid spray, which will make up
Speaker 2: a big part of the history section later on in
Speaker 2: the episode. And I just want to give credit to
Speaker 2: Doug for giving us the idea to use this as
Speaker 2: our Quarantini title. It is one of my favorites.
Speaker 3: It's really fantastic, Thanks Doug, Aaron. What is in let
Speaker 3: us Spray?
Speaker 2: Let Us Spray is a delicious little blended cocktail with
Speaker 2: cherries and ice cream and lime juice and maybe some
Speaker 2: whipped cream on top. Oh and some vodka if you
Speaker 2: want to toss that in there. Yeah, And we will
Speaker 2: post the full recipe for let us spray both the
Speaker 2: quarantini as well as the non alcoholic Plasy Burta on
Speaker 2: our website This podcast will Kill You dot com, as
Speaker 2: well as on all of our social media.
Speaker 4: Channels any other business narn I don't think so.
Speaker 2: I think we should just get started because I have
Speaker 2: the feeling this is going to be a big episode.
Speaker 4: Oh, it's going to be great.
Speaker 3: We will take a short break and then get into it.
Speaker 3: I think, probably more so than any condition or infection
Speaker 3: or disease that we've covered on this podcast, sepsis is
Speaker 3: something where the actual definitions of sepsis have changed so.
Speaker 4: Many times, even in recent years.
Speaker 3: So I can't wait to compare, like how we identify
Speaker 3: sepsis today to how we understood it historically.
Speaker 2: I don't know if I'm going to be going into
Speaker 2: any of that, oh.
Speaker 4: But I bet we'll learn a lot about it perhaps.
Speaker 3: But so what I wanted to start off with was
Speaker 3: just what are the definitions of sepsis? Because there's kind
Speaker 3: of a lot floating out there. So here's one from
Speaker 3: a twenty nineteen paper. I will quote quote sepsis is
Speaker 3: a medical emergency that describes the body's systemic immunological response
Speaker 3: to an infectious process that can lead to end stage
Speaker 3: organ dysfunction and death.
Speaker 4: Boom boom boom.
Speaker 3: Another that comes from the Third International Consensus Definition's task
Speaker 3: Force and is kind of the consensus definition known as
Speaker 3: sepsis three. The third iteration of this is a bit shorter.
Speaker 3: Sepsis is a life threatening organ dysfunction caused by a
Speaker 3: disregulated host response to infection.
Speaker 2: Okay, that makes sense, right.
Speaker 4: It does.
Speaker 3: And they go further to then identify a specific subset
Speaker 3: of sepsis, and that is septic shock, which is a
Speaker 3: subset of sepsis in which underlying circulatory, cellular, and metabolic
Speaker 3: abnormalities are severe enough to substantially increase the risk of mortality.
Speaker 4: Basically, very very serious and severe.
Speaker 3: But even that definition of sepsis and septic shock, even
Speaker 3: though they are considered consensus definitions, have changed a lot
Speaker 3: over time, and even today that definition doesn't necessarily precisely
Speaker 3: apply in pediatric populations, which happen to be at particular
Speaker 3: risk for sepsis. As we'll talk about later, So because
Speaker 3: what does the definitions of sepsis have changed over time?
Speaker 3: So has the diagnosis or the criteria that are used
Speaker 3: to diagnose it.
Speaker 4: And I think.
Speaker 3: That that's kind of the best way to think about sepsis.
Speaker 3: It is a process, but it's also a diagnosis that's
Speaker 3: used to kind of triage and determine management if somebody.
Speaker 4: Ends up in a hospital setting. Does that make sense?
Speaker 2: Yeah, And it's interesting that the criteria have changed so much, Like,
Speaker 2: first of all, why is that? And second of all,
Speaker 2: how has that affected this maybe like way jumping the gun,
Speaker 2: but how has that affected more current numbers or being
Speaker 2: able to compare throughout even the past few decades. Yeah,
Speaker 2: how our ability to control sepsis has changed?
Speaker 3: That's that is all very important and really good questions. Basically,
Speaker 3: it's made it difficult. So our numbers on sepsis, as
Speaker 3: we'll talk about later in this episode, aren't great, especially
Speaker 3: our nderstanding of the rates of sepsis and control of
Speaker 3: sepsis in low and middle income countries. And you do
Speaker 3: have to kind of take into consideration every study that's done,
Speaker 3: what were the criteria that were used to identify sepsis
Speaker 3: versus to rule people out for sepsis or whatever. But
Speaker 3: basically the definitions have changed in part because of our
Speaker 3: understanding of sepsis and what the underlying causes are, as
Speaker 3: well as how we identify it in an emergency setting,
Speaker 3: for example. And the truth is there are a whole
Speaker 3: host of what are often called screening tools that are
Speaker 3: used to kind of identify, in ideally a highly sensitive way,
Speaker 3: what people might either have sepsis or be at high
Speaker 3: risk for sepsis. One of these screening tools is called
Speaker 3: sers SIRS. It stands for systemic inflammatory response syndrome, and
Speaker 3: these criteria are like an increased or decreased temper, an
Speaker 3: increased heart rate, an increased respiratory rate, an increased white
Speaker 3: blood cell count, or a severely decreased white blood cell count,
Speaker 3: things like that. So having two of those criteria and
Speaker 3: a known or suspected source of an infection would in
Speaker 3: a lot of cases rule people in so make us
Speaker 3: think this person has sepsis. We're going to call them
Speaker 3: stepsis until proven otherwise. There are a lot of other criteria.
Speaker 3: There's the SOFA, which stands for sequential organ failure assessment,
Speaker 3: which is mostly based on a list of laboratory values
Speaker 3: or respiratory status values to kind of try and determine
Speaker 3: and triage the degree of organ damage. So getting a
Speaker 3: certain score on that screening tool plus having a known
Speaker 3: or suspected infection would then meet criteria for sepsis. But
Speaker 3: there are also a lot of others. There's one called NEWS,
Speaker 3: there's one called MUSE. There's likely different versions in different
Speaker 3: countries that I don't even know about.
Speaker 2: And so what determines which screening tool you use is
Speaker 2: just where you are or what hospital you work in.
Speaker 3: Exactly that where you are and what hospital you work in,
Speaker 3: so I can tell you we use SERS very often.
Speaker 3: SURS has a number of detractors, and it definitely is
Speaker 3: not a perfect screening tool.
Speaker 4: No screening tool is perfect, but it is used.
Speaker 3: Very often as one of these possible screening tools. Now,
Speaker 3: there is an organization I think you would call it
Speaker 3: an organization. It's called the Surviving Sepsis Campaign, and it's
Speaker 3: an international organization that really tries to go through all
Speaker 3: of the data that we have on sepsis and outcomes
Speaker 3: of sepsis and come up with a consensus set of
Speaker 3: guidelines on how to identify, diagnose, and manage sepsis in
Speaker 3: the hospital and ic you setting, and so they have
Speaker 3: like a set of guidelines and things where they say,
Speaker 3: you know, this screening tool is not the best and
Speaker 3: this one is okay, and et cetera, et cetera.
Speaker 2: I have a question, okay, so about the number of
Speaker 2: all these screening tools. Yeah, does that mean that sepsis
Speaker 2: is difficult to recognize because the symptoms are varied? Or
Speaker 2: is it because there are a lot of other things
Speaker 2: that can look like sepsis and a treatment is different.
Speaker 4: Yes, and both, Okay, Okay.
Speaker 3: So yeah, it's hard to tell you exactly what these
Speaker 3: symptoms of sepsis are because they're incredibly nonspecific. So, in general,
Speaker 3: according to our definition, people have some sign of an infection.
Speaker 4: This could be a pneumonia, which.
Speaker 3: Tends to be, at least in hospital settings, the most
Speaker 3: common identified cause of sepsis, but certainly not the only one.
Speaker 3: It could be like a urinary infection. It could be cellulaitis.
Speaker 3: It could be a tiny cut on your finger, so
Speaker 3: that could be the initial infection. But then in terms
Speaker 3: of the other symptoms that you might see, people may
Speaker 3: or may not have a fever, They may or may
Speaker 3: not have an elevated heart rate as like a physiologic
Speaker 3: response to this infection. They may or may not have
Speaker 3: difficulty breathing, or if you put an oxygen meter on them,
Speaker 3: have hypoxia, decrease in their oxygen status.
Speaker 4: They may or may not.
Speaker 3: Already have progressed to the point of hypotension, so decrease
Speaker 3: blood pressure, which is when you're getting into the point
Speaker 3: of having septic shock.
Speaker 4: And we'll get more into that.
Speaker 2: They may or.
Speaker 3: May not if you look at laboratory numbers, have changes
Speaker 3: in their liver or their kidney function, or their platelets.
Speaker 4: They may or may.
Speaker 3: Not have altered mental status, or even be unconscious. But
Speaker 3: it's a really mixed bag, and any and all of
Speaker 3: those signs and symptoms could point to sepsis as a cause.
Speaker 3: But there are plenty of people that come into a
Speaker 3: hospital setting or are already in a hospital setting that
Speaker 3: have many of those signs or symptoms but do not
Speaker 3: have sepsis.
Speaker 2: What do they have?
Speaker 4: They could have any number of other things.
Speaker 3: They could have cancer, they could have just meningitis but
Speaker 3: not have sepsis.
Speaker 4: They can have I mean anything.
Speaker 2: Okay, question, do the symptoms that somebody has very more
Speaker 2: based on you know, who that person is, maybe their age,
Speaker 2: maybe their history, et cetera, or the infection that has
Speaker 2: caused or led to sepsis.
Speaker 4: That's a good question. It's hard.
Speaker 3: It's a hard one to answer. I would say there
Speaker 3: are things that we tend to look out for in
Speaker 3: certain age groups as an indicator that might make us
Speaker 3: more worried about sepsis, versus might make us more worried
Speaker 3: about something else in like a different age group. For example,
Speaker 3: altered mental status is one, especially in the elderly, that
Speaker 3: you might not see as much in younger people well
Speaker 3: with sepsis, though you certainly can. And then you know,
Speaker 3: same thing, for if they have respiratory symptoms, you might
Speaker 3: think that they have a predominantly respiratory infection.
Speaker 4: That's the cause of sepsis.
Speaker 3: But sepsis can lead to respiratory symptoms even if the
Speaker 3: infection is elsewhere in the body. So it's a whole mess.
Speaker 2: I think this might be even more complicated than whatever
Speaker 2: one has. It's complicated in the title, right the episode.
Speaker 4: I know, and the truth is like we have.
Speaker 3: All we've done is try to define what sepsis is, right,
Speaker 3: That's all We've tried to do, and it's really difficult,
Speaker 3: but I think that at its core, that short and
Speaker 3: sweet like sepsis three definition, organ dysfunction as a result
Speaker 3: of a combination of both an overwhelming infection, or at
Speaker 3: least I like to think of it as an overwhelming
Speaker 3: infection and a disregulated immune response to that infection. I
Speaker 3: think that those things can tell us a lot about
Speaker 3: the pros sus underlying sepsis, even in the face of
Speaker 3: the fact that specific criteria to call someone septic might
Speaker 3: be different at one hospital versus another. So at its core,
Speaker 3: sepsis requires first an infection, and this, like I said,
Speaker 3: can be an infection of literally any body area cellulitis, pneumonia.
Speaker 4: And often we think.
Speaker 3: I think classically of sepsis as resulting from a bacterial infection,
Speaker 3: and some papers even go so far as to say,
Speaker 3: like GRAM positive Coxi things like staff and strip, which
Speaker 3: are common all over our skin, are the most common
Speaker 3: cause of sepsis related mortality.
Speaker 4: Some statistics say.
Speaker 3: That, and then they'll go on to say that GRAM
Speaker 3: negative rods like E. Coli, which commonly cause UTIs, are
Speaker 3: like the second most common cause of sepsis related mortality.
Speaker 3: But the thing is that sepsis can be caused by
Speaker 3: any bacterial infection, true, but also fungal infections and even
Speaker 3: viral infections. And so then it gets even more complicated
Speaker 3: because you have culture negative sepsis where you are maybe
Speaker 3: treating like it's a bacterial infection, but with no evidence
Speaker 3: of bacteria growing from any body source.
Speaker 2: Okay, I have a couple of questions your brain.
Speaker 4: I can see your face being like, why did we Why?
Speaker 2: No, my brain is like, wait, you have to stop
Speaker 2: because I have too many questions for you to go on.
Speaker 2: Number one is what's the breakdown of bacterial versus viral
Speaker 2: versus fungal and how much of that is just sort
Speaker 2: of in the culture negative ones like we don't know
Speaker 2: what this sepsis was caused by because we're not detecting
Speaker 2: any bacteria, but could it still be bacteria?
Speaker 3: Yeah, we don't know. We don't have great numbers on that.
Speaker 3: In general, forty percent of sepsis cases can come back
Speaker 3: as culture negative, and we have some stats like the
Speaker 3: most common sights of infection, so like sixty four percent
Speaker 3: of cases at least that we have numbers on, are
Speaker 3: starting in the lung twenty percent in the abdomen, fifteen
Speaker 3: percent in the bloodstream, fifteen percent in the genito urinary tract.
Speaker 3: But that still doesn't tell us that it's necessarily a
Speaker 3: bacterial infection, though those most commonly are going to be
Speaker 3: ones that we've identified as bacterial infections, Fungal infections tend
Speaker 3: to be probably the least common but the most severe.
Speaker 3: If you have an overwhelming fungal infection, you're likely very very,
Speaker 3: very sick, and viral infections are probably way underdiagnosed. And
Speaker 3: this is where it gets both more interesting and so
Speaker 3: much more complicated, because if you think as an easily
Speaker 3: recognizable example of COVID nineteen, the vast majority of people
Speaker 3: hospitalized like that ended up in the hospital or the
Speaker 3: ICU for COVID nineteen would meet many, if not all,
Speaker 3: of the common criteria that we would use to diagnose sepsis.
Speaker 3: They're probably tachcartic, their heart rates through the roof, They
Speaker 3: probably have an oxygen requirement, they may or may not
Speaker 3: have a low blood pressure, they probably have some evidence
Speaker 3: of further organ damage like kidney or liver damage, and
Speaker 3: certainly they have an overwhelming infection in their lungs and
Speaker 3: a huge amount of inflammatory response in those lungs, causing
Speaker 3: acute respiratory distress. So people with COVID nineteen would, by
Speaker 3: many definitions or many sets of screening protocols, meet quote
Speaker 3: sepsis criteria. And yet it's probably only either in an
Speaker 3: emergency like triage setting or in the very early days
Speaker 3: of the COVID pandemic that most of those people were
Speaker 3: actually classified as having sepsis, because now on their discharge paperwork,
Speaker 3: they would be called having COVID nineteen, right, because we
Speaker 3: know that that damage is being wrought by stars CoV
Speaker 3: two and our disregulated immune response to that virus. But
Speaker 3: instead of calling it sepsis, necessarily we call it COVID nineteen.
Speaker 3: And so some people might argue you should still call
Speaker 3: that sepsis, and some people might argue you shouldn't.
Speaker 2: So, yeah, I wonder if sepsis in the future is
Speaker 2: going to be one of those things where people are
Speaker 2: going to look back and go you use this catch
Speaker 2: all term to describe something like fever, you know, like
Speaker 2: we look at fever back in the seventeen hundreds.
Speaker 3: Yeah, yeah, it's really interesting. It's a good question because
Speaker 3: a similar thing happens in pediatric populations, And that's part
Speaker 3: of why sometimes the definition for sepsis in pediatric populations
Speaker 3: might be a little different than adult populations because there
Speaker 3: are so many respiratory viral infections, especially that children get
Speaker 3: hospitalized or all the time that might meet some sepsis
Speaker 3: criteria but aren't generally classified as sepsis because we know
Speaker 3: that it's bronchiolitis or whatever.
Speaker 2: Okay, So sepsis is a diagnosis of exclusion, kind.
Speaker 4: Of the opposite.
Speaker 3: Sepsis is a diagnosis of inclusion. Sepsis is this is
Speaker 3: a person who is very sick, and we might not
Speaker 3: know exactly what they have yet, but they're very, very
Speaker 3: sick and they look like they're going to get sicker,
Speaker 3: so we treat it like sepsis until we can determine
Speaker 3: if it's something else.
Speaker 2: Okay, So, using the example of COVID nineteen, could somebody
Speaker 2: have severe COVID nineteen, and then could somebody else have
Speaker 2: COVID nineteen sepsis or is sepsis not really directly ever
Speaker 2: tied to a specific infection, and then how does that
Speaker 2: impact treatment?
Speaker 4: Yeah? Great questions.
Speaker 3: Yes, people can have an infection like COVID and still
Speaker 3: have sepsis. People can also seem to have sepsis initially
Speaker 3: but then recover very quickly, and so then you kind
Speaker 3: of get into the like, you know, did we just
Speaker 3: treat the sepsis very well at the beginning, and so
Speaker 3: now they didn't, you know, move on to septic shock,
Speaker 3: et cetera. So then I don't know, there's just so
Speaker 3: much still up in the air when it comes to
Speaker 3: how you like fully draw that line of is this
Speaker 3: sepsis or is this not sepsis? And I think a
Speaker 3: lot of that is place dependent, but the treatment does vary,
Speaker 3: at least according to kind of what we have for
Speaker 3: now as consensus guidelines when it comes to early identification
Speaker 3: and treatment of sepsis. So let's get into a little
Speaker 3: bit more of like why do we even have to
Speaker 3: have this definition of like sepsis and what does that mean?
Speaker 3: What's going on in our bodies, and then we can
Speaker 3: talk about how we then treat that because of what's happening.
Speaker 4: Does that make sense?
Speaker 3: Yeah, So, while sepsis requires an infection, as we talked about,
Speaker 3: it is not purely an infection. Not every person with
Speaker 3: a UTI or an ammonia or covid is going to go.
Speaker 4: On to have sepsis.
Speaker 3: Sepsis is what happens when an infection gets so severe
Speaker 3: that our immune system reacts to it in such a
Speaker 3: way as to cause severe damage to one or more
Speaker 3: of our other organs as a result. And if this
Speaker 3: process continues unchecked, our immune system and the infection can
Speaker 3: continue to spiral, which will lead to septic shock and
Speaker 3: eventually death.
Speaker 2: And when you say severe infection, does that mean bacterial
Speaker 2: load viral load? What does that mean?
Speaker 4: Yeah?
Speaker 3: I don't have an answer as to what that means,
Speaker 3: because we don't have an answer as to like why
Speaker 3: did that person with a UTI go on to be
Speaker 3: septic and this person with a UTI didn't.
Speaker 2: Like two people could have the same vireemia and one
Speaker 2: person could develop sepsis and the other one may not.
Speaker 3: Right, because what did their immune system do initially to
Speaker 3: try and counteract that. Did they suppress it well enough
Speaker 3: or did they not?
Speaker 2: Okay right?
Speaker 4: Did they overreact? Did they underreact? Did they do a
Speaker 4: little bit of both? Yeah, okay, I know that's not it.
Speaker 4: I can tell it's not a satisfying answer.
Speaker 2: It's fun.
Speaker 3: To talk about septic shock for a quick minute because
Speaker 3: it's a really important part of sepsis. We've talked about
Speaker 3: this concept of shock on the podcast a number of times.
Speaker 3: Shock is essentially when you aren't getting enough perfusion. You're
Speaker 3: not getting enough blood flow and therefore oxygen to your organs.
Speaker 3: So shock is enough one of these catch all definitions
Speaker 3: where you can have shock from a whole bunch of
Speaker 3: different processes. But shock is characterized specifically by hypotension low
Speaker 3: low blood pressure, and so that means that your organ's
Speaker 3: like your kidney's, your liver, or your brain, your heart,
Speaker 3: they're not getting enough blood and oxygen to functions, so
Speaker 3: they begin to shut down, and that is what leads
Speaker 3: to death in sepsis. It's multi organ failure as a
Speaker 3: result of septic shock. So what exactly is our immune
Speaker 3: system doing in response to an infection that eventually results
Speaker 3: in this all the way down the line? No more
Speaker 3: blood getting to our organs, not enough oxygen getting to
Speaker 3: our organs. So, unsurprisingly, we don't fully understand this mechanism
Speaker 3: at all, especially.
Speaker 4: When we get into the nitty gritty details of it.
Speaker 3: But what we do know is that sepsis is characterized
Speaker 3: by a very disregulated.
Speaker 4: Response to infection.
Speaker 3: So what we see is both pro inflammatory and anti
Speaker 3: inflammatory mediators being released at the same time, which we
Speaker 3: used to think that it was like pro inflammatory first
Speaker 3: and then you went through a phase and then you
Speaker 3: like your immune system shut it down and then went
Speaker 3: into this anti inflammatory phase. But it turns out that
Speaker 3: this is all happening at the same time. It's like
Speaker 3: our immune system is just on overdrive, just trying to
Speaker 3: do anything that it can.
Speaker 2: It's just like kitchen sinking it exactly.
Speaker 3: One of the major pathways that we think is involved
Speaker 3: in this severe pro and anti inflammatory response is this
Speaker 3: specific group of receptors known as pamps pathogen associated molecular patterns,
Speaker 3: and these are like kind of specific antigen specific sugars
Speaker 3: or proteins that are present commonly on pathogens like bacteria
Speaker 3: on their surface that all tend to fall into certain patterns.
Speaker 3: There's one, as an example, called LPs or pypo polysachride
Speaker 3: that's one type of PAMP.
Speaker 4: There's a lot of different.
Speaker 3: Like variations that many different types of bacteria might have,
Speaker 3: but they all have these patterns that lets our immune
Speaker 3: system recognize, like and.
Speaker 4: That's one of those lps's, and then.
Speaker 3: We have these receptors toll like receptors that recognize these
Speaker 3: and this hugely stimulates our innate immune response, which tends
Speaker 3: to be like our first pathway of protection against pathogens.
Speaker 3: So these receptors see these pamps and they send out
Speaker 3: alerts and activate both of these systems. At the same time,
Speaker 3: they're stimulating systems to increase the amount of inflammation, and
Speaker 3: at the same time they're stimulating systems that are anti
Speaker 3: inflammatory as well. And then those systems, those like pro
Speaker 3: inflammatory actors are releasing cytokines. They're telling the whole rest
Speaker 3: of our immune system like get in gear, bring all
Speaker 3: the leukocytes, like, tell everyone, this is war. I don't
Speaker 3: like that analogy, but it's like really good, and it
Speaker 3: basically like sends our immune system into overdrive. All of
Speaker 3: this inflammatory process causes vasodilation, so it opens up our
Speaker 3: blood vessels really wide so that the inflammatory stuff can
Speaker 3: get to where it's trying to go. And this inflammation
Speaker 3: also causes damage to the blood vessel walls and inflammatory
Speaker 3: changes to the layers of our blood vessel walls so
Speaker 3: that things can squeeze out and get into tissues to
Speaker 3: like help heal them. But what this ends up, leading
Speaker 3: to is leaky blood vessels, a edema of the tissues,
Speaker 3: fluid getting out to where it doesn't belong. And so
Speaker 3: if that fluid gets into something like our lungs, then
Speaker 3: that can lead to severe difficulty breathing called acute respiratory
Speaker 3: distress syndrome because of fluid filling up your lungs that's
Speaker 3: supposed to be in your blood vessels. This also leads
Speaker 3: to a decrease in permeability of your blood brain barrier.
Speaker 3: So then infections can spread to the brain where they
Speaker 3: maybe couldn't before. And that's all just the inflammatory pathways
Speaker 3: that are happening during sepsis.
Speaker 2: Okay, so I have a question about, Okus, this seems
Speaker 2: like a very maladaptive response to infection, and so is
Speaker 2: this process, does this whole cascade of inflammatory and anti
Speaker 2: inflammatory response or whatever is that good in moderation And
Speaker 2: is it only in this specific context or certain context
Speaker 2: that it can be triggered to this like massive overdrive
Speaker 2: that leads to just like oh that was too much, buddy,
Speaker 2: We're okay, that's it.
Speaker 3: I think that's kind of a fundamental question that we
Speaker 3: still have about the underlying path of physiology of sepsis
Speaker 3: and who's at risk for sepsis and why.
Speaker 2: That's my other question. Yeah, so I know that sepsis
Speaker 2: can happen to anyone, but why does it seem to
Speaker 2: happen in the highest rates in elderly people and in
Speaker 2: like young children.
Speaker 3: So one of the biggest risk factors for sepsis, and
Speaker 3: I think this is really interesting in the context of
Speaker 3: a disregulated immune response rather than just thinking of it
Speaker 3: as like an overactive immune response, is that one of
Speaker 3: the biggest risk factors for sepsis is immunosuppression, whether that's
Speaker 3: primary immunosuppression or an poorly controlled HIV or very elderly
Speaker 3: the immune system is just not what it used to be,
Speaker 3: or the very very young, like infants and neonates, don't
Speaker 3: have like a fully onboarded immune system.
Speaker 4: Yet those are the.
Speaker 3: Groups that are at highest risk for sepsis.
Speaker 2: That makes sense. And so, you know, because when you
Speaker 2: were talking about that inflammatory cascade and just like this
Speaker 2: overwhelming response, it was reminding me of the nineteen eighteen
Speaker 2: flu mm hmm and the cytokine storm. But that's a
Speaker 2: different thing or is it the same thing?
Speaker 3: Well, that's that's the thing right, that's the same thing
Speaker 3: that we think happens in COVID. Yeah, so is it
Speaker 3: a different thing or is it actually the same thing
Speaker 3: that's what's happening in sepsis?
Speaker 4: Right?
Speaker 3: We maybe have a better understanding of the process in
Speaker 3: very limited disease settings, right, Like we understand that, Okay,
Speaker 3: maybe it was these particular cytokines in the nineteen eighteen pandemic.
Speaker 3: Maybe it is these particular processes in something like HLH
Speaker 3: or like other kind of immune driven disorders. But sepsis
Speaker 3: because it's a catch all, because it's any overwhelming infection
Speaker 3: that our body is responding to in a dysregulated fashion
Speaker 3: that's causing this unregulated inflammation. Is it just one process
Speaker 3: or is it you know, each case of sepsis is
Speaker 3: a slightly different process, And is that part of what's
Speaker 3: making it so difficult to study and to understand.
Speaker 4: Whoa, yeah, whoa, whoa, whoa.
Speaker 3: And I'm not even done because there's more. The second
Speaker 3: consequence of sepsis besides all of that inflammation, is that
Speaker 3: all of that inflammation has an interaction with our hemostatic
Speaker 3: pathways in addition to those inflammatory pathways. So this will
Speaker 3: be a callback to our hemophilia episode. So all of
Speaker 3: this inflammation and these inflammatory changes end up causing damage
Speaker 3: to our endothelial cells, those cells that line our blood vessels.
Speaker 4: And we talked.
Speaker 3: In detail in our hemophilia episode about when our blood
Speaker 3: vessels get damaged, they release something called tissue factor, and
Speaker 3: tissue factor is one of the first things that stimulates
Speaker 3: our code co wagulation cascade. Coagulation is the process of
Speaker 3: being able to clot our blood so that we don't
Speaker 3: bleed out every time that our skin gets cut or
Speaker 3: a vessel gets cut. So this coagulation cascade, this process
Speaker 3: is going to first recruit platelets to come in and
Speaker 3: plug the holes of that damaged blood vessel, and then
Speaker 3: tissue factor is going to start the process of activating
Speaker 3: this whole entire cascade that I'm not going to go
Speaker 3: back through, but it's factors seven, eight, nine, five, four, ten,
Speaker 3: et cetera. And this whole process ends up getting activated
Speaker 3: in again a disregulated way when it comes to sepsis.
Speaker 4: So what you can end up.
Speaker 3: Seeing in a very mild form is just thrombocyte apenia,
Speaker 3: which is a drop in.
Speaker 4: Platelets, because those are the first.
Speaker 3: Things that come in to plug a hole when we
Speaker 3: have a hole in our tissues. But that's mild. If
Speaker 3: this this process continues out of control, it will progress
Speaker 3: to what's called DIC or disseminated intravascular coagulation, which is
Speaker 3: basically when this coagulation cascade is underway inside of our
Speaker 3: blood vessels and ends up forming these little microthromby, little
Speaker 3: tiny little clots in our vessels as a result of
Speaker 3: this coagulation cascade, and these thrombi not only can block
Speaker 3: off blood vessels by accident, so now you're not getting
Speaker 3: blood flow to say, your fingertips or a part of
Speaker 3: your brain. And at the same time, because our body,
Speaker 3: whenever we make a clot, we eventually need to break
Speaker 3: it down. So when we're forming a whole bunch of
Speaker 3: clots inside our blood vessels, our body is breaking them down.
Speaker 3: At the same time, we end up using up all
Speaker 3: of these coagulation factors. We end up using up all
Speaker 3: of our platelets to the point where now we can't
Speaker 3: clot at all, so you can end up hemorrhaging.
Speaker 4: Oh and that is DIC.
Speaker 2: Okay, Yeah, and this is happening right alongside or is
Speaker 2: there any sort of okay? This is just there's no
Speaker 2: sequence to the inflammation or not a hard and fast rule.
Speaker 4: Yeah, exactly.
Speaker 3: There is not a hard and fast rule, and there's
Speaker 3: not clear sequences.
Speaker 4: We used to think that there were.
Speaker 3: We used to think first there's this overwhelming pro inflammatory response,
Speaker 3: and then our immune system gets suppressed, and then the
Speaker 3: coagulation cascade gets involved. Like we used to think it
Speaker 3: was more step wise, but it's not. If you think
Speaker 3: of it more as a dysregulation. It's that everyone is
Speaker 3: trying to do something at the same time, but there's
Speaker 3: no communicators. There's no leaders saying this is too much,
Speaker 3: this is too little, we need to work together. It's
Speaker 3: like everyone's just a free for all. That's at least
Speaker 3: the way that I my brain has tried to understand.
Speaker 2: Yeah, yeah, yeah, no, I mean that makes sense.
Speaker 4: Yeah.
Speaker 3: And then of course there's also a fair amount of
Speaker 3: immune suppression that's happening because of these anti inflammatory things
Speaker 3: that are going on, and it tends to be that
Speaker 3: T cell lines and in some cases B cell.
Speaker 4: Lines, more of our specific.
Speaker 3: Like adaptive immune response seems to be suppressed, although aspects
Speaker 3: of our more non specific or innate immune responses can
Speaker 3: also be suppressed. But the problem with this is that
Speaker 3: it can end up leaving one more susceptible to another infection,
Speaker 3: a superinfection.
Speaker 4: Right, Oh my gosh.
Speaker 2: Yeah, this is a mess and there is no hard
Speaker 2: and fast rule to anything.
Speaker 3: You've summed it up, sepsis, this is a mess. The
Speaker 3: major consequences, of course, I think I've said are organ failure,
Speaker 3: septic shock, and death. So this is something that can
Speaker 3: very quickly progress to a very very serious emergency situation.
Speaker 3: So that's why a lot of the definitions of sepsis
Speaker 3: kind of try to include that in the definition.
Speaker 2: What is the timeline of that? Like when you say
Speaker 2: very quickly, what could that be?
Speaker 4: I mean it depends on the infection.
Speaker 2: Okay, so it could be a matter of like hours
Speaker 2: to days, but not not a longer drawn out process
Speaker 2: than that.
Speaker 3: Probably not, because once your immune system starts, like once
Speaker 3: you truly have sepsis, this process is just going to
Speaker 3: continue unchecked unless you're being managed. So let me finally
Speaker 3: try and answer some of your questions from before on
Speaker 3: like how do we actually treat this?
Speaker 4: And there are a few I.
Speaker 3: Think pretty important principles when it comes to management. I
Speaker 3: will link to the Surviving Sepsis guidelines from twenty twenty one.
Speaker 3: Those are at least as far as I saw the
Speaker 3: most recent guidelines. But I will also say, and I'll
Speaker 3: talk about this more later in the episode, these are
Speaker 3: imperfect and they are in a lot of cases based
Speaker 3: they say it outright, this is not my words. They're
Speaker 3: based on pretty poor quality of data because we just
Speaker 3: don't have good enough data when it comes to sepsis.
Speaker 3: But there are a few kind of big important things,
Speaker 3: and the first is just identifying people, especially those that
Speaker 3: are at high risk for septic shock, and so that
Speaker 3: means using these various criteria to identify people who have sepsis,
Speaker 3: even if it's early on. The other thing that it
Speaker 3: means is identifying as quickly as you can the source
Speaker 3: of infection and if possible, getting cultures to be able
Speaker 3: to verify if this is a bacterial infection, what bacterium
Speaker 3: it is, or if it's a fungus, what fungus it is.
Speaker 3: It's also possible to do viral testing in some places
Speaker 3: in some areas, but identifying the source of infection and
Speaker 3: then controlling that source if possible, so if there's an abscess,
Speaker 3: it needs to be drained. If there's like a necrotizing
Speaker 3: skin infection, it has to be debrided. If it's an
Speaker 3: infection from an infected line, like a catheter of some
Speaker 3: kind being removed, like finding where the bacteria is seeding
Speaker 3: from or the infection is seeding from and trying to
Speaker 3: remove it. And in the vast majority of cases, starting
Speaker 3: broad spectrum antibiotics, especially if you don't know what is
Speaker 3: causing this. And then one of the kind of most
Speaker 3: well supported things that tend to happen when someone is
Speaker 3: identified as having sepsis is fluid resuscitation because it can
Speaker 3: so quickly progress to septic shock and hypotension. Resuscitating with fluids,
Speaker 3: so like putting it in an IV and getting fluids is
Speaker 3: one of kind of the most well studied, has really
Speaker 3: good data to support that it improves outcomes and mortality.
Speaker 2: Question about endotoxins, ooh yeah, what role do they play?
Speaker 4: Great question.
Speaker 3: So endotoxins are often things like that LPs that I
Speaker 3: talked about. These are can be things that are pathogen
Speaker 3: associated molecular proteins that our body is recognizing. So that's
Speaker 3: one of the main pathways that we've identified that's a
Speaker 3: likely contributor to the initial development of sepsis.
Speaker 2: That's like one of the triggers exactly.
Speaker 3: Okay, if we're talking generally about a bacterium, right, right.
Speaker 2: So with treatment, what are the mortality rates?
Speaker 3: They really really vary place to place and case to case.
Speaker 3: From some data from maybe about ten years ago in Europe,
Speaker 3: mortality rates from sepsis tended to be about forty percent
Speaker 3: versus about twenty eight percent in the US, which is massive.
Speaker 2: Well, it's also interesting too because you know, like you
Speaker 2: brought up earlier, what goes on the sheet in terms
Speaker 2: of diagnosis can ex also very much affect the right
Speaker 2: mortality rates.
Speaker 3: Yeah, and you know, in some of those cases, if
Speaker 3: they use statistical methods to adjust for things like how
Speaker 3: severe was the disease, then those differences where it seems
Speaker 3: like why is sepsist so much more deadly in Europe
Speaker 3: than the US, if you actually look at like disease
Speaker 3: severity and sepsis mortality, then there actually wasn't a difference.
Speaker 3: So it does, I think, in part, come back to
Speaker 3: how broad this definition is and how it can vary
Speaker 3: place to place and over time.
Speaker 2: Yeah, very very many variables, don't you love it? It's interesting,
Speaker 2: fascinating and scary.
Speaker 3: Yeah, so, Aaron, has it always been with us?
Speaker 2: I presume yes, I do too. I'm not going to
Speaker 2: talk that much about that aspect of it, but I'll
Speaker 2: talk about some other ones.
Speaker 5: Wait and I'll get started right after this break.
Speaker 2: The story of sepsis. How do you tell the history
Speaker 2: of a condition with such varied symptoms, with such varied causes,
Speaker 2: with virtually any viral, bacterial, or fungal infection able to
Speaker 2: lead to its development? Like you talked about a condition
Speaker 2: whose definition and name itself has undergone substantial revision over
Speaker 2: the past one hundred years, and one which we still
Speaker 2: seem to be struggling to effectively treat or even understand. Obviously,
Speaker 2: there are many different ways you could go about it.
Speaker 2: Talk about a particular bacterial cause, or the evolution of
Speaker 2: treatment strategies, or how our understanding and definition of sepsis
Speaker 2: has changed throughout time. Or maybe you could talk about
Speaker 2: a big moment in sepsis history, a period when humanity's
Speaker 2: collective view of the world and how it worked underwent
Speaker 2: a tremendous and life saving shift, even if somewhat reluctantly. Okay,
Speaker 2: and that's my pick for today. That's what I'm gonna do,
Speaker 2: because how could I pass up an opportunity to talk
Speaker 2: about Joseph Lister and the sanitation revolution.
Speaker 4: Simply cannot.
Speaker 2: We cannot. Of course, Lister and his carbolic acid only
Speaker 2: make up a small part of the overall history of sepsis,
Speaker 2: but I wanted to primarily focus on his work today
Speaker 2: because I think it gives us a fascinating insight into
Speaker 2: the early days of germ theory and how we got
Speaker 2: from germ theory as a ridiculed idea to germ theory
Speaker 2: as fact, and from germ theory as theory to germ
Speaker 2: theory in practice. And Joseph Lister is really at the
Speaker 2: heart of so much of that. And I want to
Speaker 2: mention at the top that most of the info about
Speaker 2: Lister and those early days of surgery and germ theory
Speaker 2: I got from the fantastic book The Butchering Art by
Speaker 2: Lindsay Fitzharris.
Speaker 4: Very great books.
Speaker 2: It's truly such a great popular science book that is
Speaker 2: unput downable. I highly recommend it to fill in more
Speaker 2: color and more context and more amazing quotes about the
Speaker 2: early day of the horrific days of surgery to this
Speaker 2: story listeners of the podcast and Aaron, you've heard me
Speaker 2: talk so very much about this time period. But we
Speaker 2: are covering new ground here and I honestly think it's
Speaker 2: one of the most interesting stories yet. Oh but first,
Speaker 2: let's take a step back to get our bearings with sepsis.
Speaker 2: Probably could go without saying, but humans and sepsis go
Speaker 2: way back, and our recognition of the disease also goes
Speaker 2: way back to about twenty seven hundred years ago, when
Speaker 2: it was first used in a medical context in Homer's
Speaker 2: poems in the verb form sepo meaning I rot. Later,
Speaker 2: around four hundred BCE, the word sepsis was introduced in
Speaker 2: the Hippocratic texts, meaning quote the decomposition of animal or
Speaker 2: vegetable or organic matter. And this word or variations of
Speaker 2: it were used extensively in Greek and Roman literature, not
Speaker 2: just in my medical texts, but also classic literature and
Speaker 2: philosophical writings, where it likely held symbolic meaning. Over the
Speaker 2: next hundreds of years, it remained in some use, but
Speaker 2: it seems difficult to say whether that was in the
Speaker 2: medical sense or in the symbolic sense, and in either
Speaker 2: case it's unlikely that the sepsis referred to in most
Speaker 2: historical texts pre nineteenth century would always fit the definition
Speaker 2: that we use today, right, The modern use of sepsis
Speaker 2: more or less can be traced back to sometime in
Speaker 2: the early nineteenth century, depending on the language, also depending
Speaker 2: on the definition. This is why I didn't want to
Speaker 2: go into the changing definitions of sepsis. It just gets
Speaker 2: really messy, really fast. And when it was introduced in
Speaker 2: the early nineteenth century, it meant putrefaction, often accompanied with
Speaker 2: the rotting of the body or parts of the body
Speaker 2: after a wound. And it's really no surprise that it
Speaker 2: was around this time that sepsis came into more and
Speaker 2: more frequent use, as well as other words that were
Speaker 2: related to sepsis, like septosmia or piemia, because much of
Speaker 2: the world was undergoing some pretty drastic changes in terms
Speaker 2: of urbanization, industrialization, and population growth, and these changes could
Speaker 2: also be seen in the medical field, namely in the
Speaker 2: form of hospitals. I talked a bit about the enormous
Speaker 2: increase in hospitals during this time in the Pupil Fever episode.
Speaker 2: Go and listen to it, but in case you need
Speaker 2: a refresher and you don't feel like it. I'm going
Speaker 2: to set the stage again here. The late eighteenth century
Speaker 2: and early nineteenth centuries saw a tremendous growth in hospitals
Speaker 2: in Europe and in the US, mainly as a feature
Speaker 2: of the cities that were constantly and rapidly growing thanks
Speaker 2: to industrialization. In contrast with rural areas where doctors would
Speaker 2: often travel house to house to care for patients, hospitals
Speaker 2: began to be popular in cities where physicians could just
Speaker 2: stay put and wait for their many patients to come
Speaker 2: to them, They could work with other physicians and exchange knowledge,
Speaker 2: and they could use the people seeking care, many of
Speaker 2: whom were in lower economic classes, as a teaching opportunity.
Speaker 2: Prior to the early eighteen hundreds, essentially the only requirement
Speaker 2: for being a surgeon was just calling yourself one. But
Speaker 2: with the growth in hospitals also came tighter, though still
Speaker 2: loose by today's standards, regulations for education and training for
Speaker 2: surgeons and would be surgeons had to spend a certain
Speaker 2: amount of time, say six months or so, learning in hospitals,
Speaker 2: listening to lectures, performing autopsies, or training directly on patients.
Speaker 2: Hospitals were proving to be a tremendous opportunity for the
Speaker 2: growth and spread of medical knowledge, as well as the
Speaker 2: growth and spread of pathogenic microbs. Because these were still
Speaker 2: the days before germ theory, when it was held that
Speaker 2: the dirtier the surgeon's hands or the stiff of their
Speaker 2: coat with dried PUFs and blood, the more respected they were.
Speaker 2: I just it's so yucky, yes, horrible to think about. Yeah,
Speaker 2: the prevailing notion of what caused disease was still miasma,
Speaker 2: foul air that contaminated the body and led to infections.
Speaker 4: How does your coat not be full of foul air?
Speaker 2: Did it stink? It had to have, That's what it's baffling.
Speaker 2: I don't know. But yeah, these blood and puss encrusted
Speaker 2: surgical instruments or soiled bed linens, these weren't viewed as
Speaker 2: dirty or kneading cleaning. It was the bad air in
Speaker 2: the post surgical war that caused the incredibly high mortality
Speaker 2: rates observed. After all, the sight of puss, called laudable
Speaker 2: puss in a wound or surgical sight, was thought to
Speaker 2: indicate that the body was healing wasn't something to be
Speaker 2: worried about. In the first few decades of the nineteenth century,
Speaker 2: mortality rates from surgery were as high as you can imagine,
Speaker 2: but the overall number of surgeries performed was actually fairly low,
Speaker 2: and that was largely due to the lack of anesthesia
Speaker 2: prior to the introduction of ether in the eighteen forties.
Speaker 2: If you had to have surgery of some kind, you
Speaker 2: either had to take your chances with laughing gas, which
Speaker 2: could either kill you or not affect you at all,
Speaker 2: or bite the bullet or more accurately, the leather strap.
Speaker 2: The horror of surgeries made many people reluctant to have
Speaker 2: them unless in cases of dire need, and even made
Speaker 2: many surgeons reluctant to perform them, or at the very
Speaker 2: least encourage them to cut as quickly as they could.
Speaker 2: When ether was first used in eighteen forty two by
Speaker 2: Crawford Long outside of Athens, Georgia, it was the beginning
Speaker 2: of a revolution that would transform surgery from a terrifying
Speaker 2: last resort where had to get in and out as
Speaker 2: quickly as they could, into a viable option and a
Speaker 2: burgeoning field of study. With ether, a surgeon still had
Speaker 2: to be fast, but they at least had a little
Speaker 2: more breathing room to make sure they were suturing the
Speaker 2: right arteries or whatever. Together. As the miracle of ether
Speaker 2: became more widely known across the world, the number of
Speaker 2: surgeries performed climbed up and up and up. With ether,
Speaker 2: one enormous barrier to surgeries had been toppled, but the
Speaker 2: other one, a big one, still remained, infection and infection's
Speaker 2: post surgery loomed bigger and bigger as ether became more
Speaker 2: widely used. Since remember we're still in the days before
Speaker 2: germ theory, right, this is the surgical world that Joseph
Speaker 2: Lister entered into at the age of seventeen in eighteen
Speaker 2: forty four. Lister was born and raised a Quaker, which
Speaker 2: meant a simple childhood. No sport, no theater, no frills.
Speaker 2: Life in general was not about the pursuit of pleasure,
Speaker 2: but about service and honor of God. Fortunately for little
Speaker 2: Joseph Lister and the rest of the world, science was
Speaker 2: considered a worthy pastime and he had the tools to
Speaker 2: explore the natural world at his disposal thanks to his father.
Speaker 2: Although Lister's father had started his career in the family
Speaker 2: biz as a wine merchant, over time he became fascinated
Speaker 2: with the world of microscopes, especially in improving their capabilities
Speaker 2: through fiddling with this lens or adjusting that angle. Lister's
Speaker 2: father's improvements to microscopes earned him great renown, and Lister's
Speaker 2: childhood home was full of the instruments, as well as
Speaker 2: specimens and books of natural history. Given this upbringing, it's
Speaker 2: hardly surprising that at the age of fourteen, Lister decided
Speaker 2: he wanted to better understand life by becoming a surgeon,
Speaker 2: which was not welcome news to his family. At the times.
Speaker 2: Not a well respected bunch, they were seen not so
Speaker 2: much as educated professionals, but more as crude technicians. To
Speaker 2: just give you an idea of this, consider that a
Speaker 2: hospital's chief bug catcher, who was responsible for removing lice
Speaker 2: from mattresses, was paid more than the hospital surgeons.
Speaker 4: WHOA yeah, I mean that does sound like a difficult job.
Speaker 2: It sounds like a horrific job.
Speaker 4: Yeah.
Speaker 2: None of this deterred Lister, though, and so in eighteen
Speaker 2: forty four, at age seventeen, he enrolled in University College London,
Speaker 2: bringing with him, of course, one of his father's microscopes.
Speaker 2: He didn't start right away with medical classes. However, his
Speaker 2: father realized that if he couldn't dissuade Lister from pursuing surgery,
Speaker 2: he could at least require that he complete an art
Speaker 2: degree first, which was effectively a liberal arts degree with
Speaker 2: courses in history, math, literature, and science. I love that
Speaker 2: this was definitely not a requirement or the norm for
Speaker 2: surgeons and training, but Lister later attributed his ability to
Speaker 2: make the important connections he did across disease, sanitation, and
Speaker 2: germ theory to this well rounded education. The other not
Speaker 2: required or not normal thing that Lister did was bring
Speaker 2: his microscope. At the time, microscopes had been around for
Speaker 2: quite a while, over two hundred years.
Speaker 4: Wow, I know.
Speaker 3: I just always forget how early the microscope really came about.
Speaker 2: It's fascinating.
Speaker 4: Yeah, it's really impressive.
Speaker 2: But even though these microscopes had been around for that
Speaker 2: long of a time, they weren't yet seen as integral
Speaker 2: to medicine. Instead, they were considered a distraction, a waste
Speaker 2: of time, or even a threat to the medical community
Speaker 2: since they promised answers that physicians could not provide with
Speaker 2: the naked eye. Yeah, but slowly the tides were returned.
Speaker 2: Learning as scientists jotted down observations about how some diseases
Speaker 2: acted on different tissue types rather than on just the
Speaker 2: entire body or whole organs as had been thought. It
Speaker 2: would still take some time, though, before the value of
Speaker 2: microscopes in diagnosis and other aspects of medicine was made clear,
Speaker 2: and so Lister certainly was unusual in owning one, and
Speaker 2: maybe even more unusual was that he used it. As
Speaker 2: a senior medical student, Lister was appointed to be a
Speaker 2: dresser for John Eric Erickson, who was the senior surgeon
Speaker 2: at University College Hospital. Part of Lister's duties included standing
Speaker 2: by with a box of supplies to dress wounds during
Speaker 2: surgery or to change the bandages in post surgical care.
Speaker 2: In eighteen fifty two, during one of these routine bandage changes,
Speaker 2: he unraveled the cloth on a patient's seeping, rotting wound
Speaker 2: and was met with a horrific odor. It was the
Speaker 2: dreaded hospital gangreen in the day's pre germ theory. Gangreen
Speaker 2: was one of the big four exceedingly common hospital infections
Speaker 2: that cause the most death and disease, with the other
Speaker 2: three being arispolis, septicemia, and piemia, which is a development
Speaker 2: of pus filled abscesses. No one knew precisely why hospitals
Speaker 2: in particulars seemed to be so susceptible to these conditions,
Speaker 2: but they certainly were. You may remember some of the
Speaker 2: stats about pupil fever in the countryside compared to hospitals
Speaker 2: from the pupil fever episode, and here I'm going to
Speaker 2: do the same thing but with amputations, oh dear.
Speaker 6: Yeah.
Speaker 2: For instance, in one year in the countryside, twenty three
Speaker 2: double amputations were performed and seven died, which still seems
Speaker 2: like a lot.
Speaker 1: Hm.
Speaker 4: Definitely still a lot.
Speaker 2: Until you compare with the Royal Infirmary of Edinburgh for
Speaker 2: that same period eleven double amputations, of whom died.
Speaker 4: Wow m hm.
Speaker 2: And it wasn't just those seeking care at hospitals that
Speaker 2: were at risk. Many physicians, surgeons, medical students and surgical
Speaker 2: assistants were just the tiniest scalpel slice away from introducing
Speaker 2: one of these deadly infections into their own bodies. At
Speaker 2: one hospital, Saint bartholomewse Hospital, over the period from eighteen
Speaker 2: forty three to eighteen fifty nine, forty one medical students
Speaker 2: died after developing fatal infections.
Speaker 4: Oh my gosh.
Speaker 2: And of course I can't not mention the three hundred
Speaker 2: percent mortality rate surgery where the quote fastest knife in
Speaker 2: the West End, doctor Robert Liston was cutting so quickly
Speaker 2: that he sliced off his assistant's fingers and then slashed
Speaker 2: a spectator's coat. The patient and the assistant died of infection,
Speaker 2: of course, while the spectator died of shock, or so
Speaker 2: the story goes. Yeah, that possibly true, possibly made up
Speaker 2: dramatic story. Aside, the high mortality rate at hospitals and
Speaker 2: in the cities themselves had come to be expected. Industrial accidents,
Speaker 2: lack of access to clean water or nutritious foods, crowd diseases.
Speaker 2: Even if you managed to avoid cholera from the contaminated
Speaker 2: Broad Street pump, or tuberculosis from your overcrowded building, or
Speaker 2: arsenic from your wallpaper, you couldn't just as easily die
Speaker 2: from septocemia. After having the gash on your hand. You
Speaker 2: got it, the factory stitched up at the hospital. Deadly
Speaker 2: infections haunted every hospital wing, and once one appeared, there
Speaker 2: was not really anything doctors could do to slow it spread.
Speaker 2: Within a matter of days, the gangrene that Lister observed
Speaker 2: in that one patient had swept the entire surgical wards,
Speaker 2: and Lister was put in charge of wound care. This
Speaker 2: involved him scraping off the dead, decaying tissue from the
Speaker 2: wounds and then applying mercury per night, which is both
Speaker 2: caustic and toxic, an excruciatingly painful process that thankfully was
Speaker 2: done while the patient was under anesthesia. Lister, observant as always,
Speaker 2: noticed that the wounds that had been very carefully cleaned
Speaker 2: and that had received this caustic treatment healed surprisingly well.
Speaker 2: What was it about this process that prevented the gangreen
Speaker 2: from getting worse? Maybe the answer wasn't in the air,
Speaker 2: as many of Lister's contemporaries thought, but in the wound itself.
Speaker 2: He took some of the pus that he had scraped
Speaker 2: from patient's wounds and made slides to check out under
Speaker 2: the microscope. Later he wrote about what he saw, quote,
Speaker 2: I examined microscopically the slough from one of the sores,
Speaker 2: and I made a sketch of some bodies of pretty
Speaker 2: uniform size, which I imagined might be the material's morbi morbid substances.
Speaker 2: The idea that it was probably of parasitic nature was
Speaker 2: at that early period already present in my mind. End quote.
Speaker 4: And this is pre germ theory.
Speaker 2: This is pre germ theory. But I believe that that
Speaker 2: was a reflection later on, Okay, in his life. Okay,
Speaker 2: But in any case, the seed of a revolutionary idea
Speaker 2: was planted, but it would take several more years to
Speaker 2: fully form.
Speaker 4: Okay.
Speaker 2: As Lister neared the end of his medical training, he
Speaker 2: was given awards and accolades and recognition of his exceptional
Speaker 2: abilities and achievements. But while his professors could see great
Speaker 2: promise in him, he wasn't so sure. He couldn't decide
Speaker 2: whether he wanted to go into medicine or surgery, so
Speaker 2: one of his professors recommended he spent some time in
Speaker 2: Edinburgh with clinical surgeon James Syme. What was supposed to
Speaker 2: be a month long stay turned into years as Sime
Speaker 2: became not only Lister's respected mentor, but eventually father in law.
Speaker 2: In Scotland. He fell back in love with surgery and
Speaker 2: dove back into the topic that had he first grabbed
Speaker 2: his attention in his surgical training, inflammation in wounds. He
Speaker 2: spent his free time examining more puffs and tissue samples
Speaker 2: under the scope and jotting down any patterns he saw.
Speaker 2: When did inflammation appear? When did a fever develop? Was
Speaker 2: fever a good thing or a bad thing? What about inflammation?
Speaker 2: Did sepsis always come after inflammation or only some of
Speaker 2: the time. He could only get so far with the
Speaker 2: dead and dying tissue he was looking at, so he
Speaker 2: turned to other living animals to take a closer look.
Speaker 2: A colony of frogs that he kept at his house.
Speaker 2: He would injure their webs in various ways using heat
Speaker 2: or chemicals, and then look at what happened to their
Speaker 2: blood vessels. What these experiments told Lister was that inflammation
Speaker 2: was a normal part of the healing process, and sepsis
Speaker 2: didn't necessarily follow. He was getting closer. In eighteen fifty nine,
Speaker 2: six years after he moved to Edinburgh to work with
Speaker 2: Sime who was then thirty two, applied for and was
Speaker 2: given a prominent surgery professorship at the University of Glasgow.
Speaker 2: Although at the time the academic atmosphere at Glasgow was
Speaker 2: conservative where Edinburgh was daring traditional, while Edinburgh lean progressive.
Speaker 2: New Hires like Lister were injecting a bit of freshness
Speaker 2: into the university, which attracted more and more medical students,
Speaker 2: students who loved their new professor for his riveting lectures
Speaker 2: focus on clarity and modern thinking. Alongside his appointment at
Speaker 2: the university, Lister was also given a position at the
Speaker 2: city's hospital, which he viewed as essential for connecting theory
Speaker 2: and practice, demonstrating the procedures that he had lectured about
Speaker 2: in class. Even though the surgical ward that Lister was
Speaker 2: assigned to was basically newly constructed, it was already filthy.
Speaker 2: All the classic infections haunted the wards. The graveyard was
Speaker 2: constantly overflowing, and there was practically nowhere to wash your
Speaker 2: hands or instruments or bed linens, even like the surgical
Speaker 2: tools that were used were ornately carved, which meant that
Speaker 2: they were impossible to clean if the surgeon actually attempted
Speaker 2: to clean it at all.
Speaker 4: Yeah, I just, I really, I know. We talked on
Speaker 4: this podcast about.
Speaker 3: Trying to like separate what we know now from what
Speaker 3: we knew back then, But like I can't get this one,
Speaker 3: you know, I know, like I can't get there, like
Speaker 3: a pus filled knife.
Speaker 4: How are you not gonna wash that?
Speaker 2: Because puss was good.
Speaker 6: It was logical, like dirt and blood. Come on, I know,
Speaker 6: I know, it's it's very horrible, but interesting to think about.
Speaker 2: Yeah, Lister's house surge, get a load of this said quote.
Speaker 2: When almost every wound was foul with separation, it seemed
Speaker 2: natural at the time to postpone the complete cleansing of
Speaker 2: hands and instruments until the program of dressings and probings
Speaker 2: had been finished. Basically, what point is there to clean
Speaker 2: something that's just going to get dirty again?
Speaker 4: Yeah?
Speaker 7: All right, okay, with this attitude, is it any wonder
Speaker 7: that mortality rates post surgery were sky high.
Speaker 2: Surgeons weren't being wilfully malicious, they simply didn't know any better,
Speaker 2: But it was still a tragedy to those dying of
Speaker 2: infection and their loved ones who had to sit by helplessly,
Speaker 2: as well as to the surgeons who would take great
Speaker 2: care in treating people only to watch them die of
Speaker 2: infection a few days later. Lister felt this very keenly,
Speaker 2: and as a result, he became very invested in trying
Speaker 2: to prevent these post surgery dens, starting with cleanliness. The
Speaker 2: concept of cleanliness has not remained constant throughout history.
Speaker 4: Ooh, is that a whole other episode.
Speaker 2: Yeah, I think it could be. Nowadays, we may think
Speaker 2: of a clean hospital room as one that has been
Speaker 2: sprayed and wiped down with interseptic, freshly mopped, fresh linens
Speaker 2: and paper on the beds, sterilize instruments, and so on.
Speaker 2: In Lister's day, a clean room was one that had
Speaker 2: been recently swept and the windows opened. That was basically it.
Speaker 2: That was it because fresh air. Yeah, okay, fresh air granted.
Speaker 2: New ideas were continually being proposed, such as cleanliness and
Speaker 2: cold water, which held that surgical instruments should be cleaned
Speaker 2: with water that had been boiled and then allowed to cool.
Speaker 2: And the idea behind this was that cold water was
Speaker 2: supposed to prevent the heat that caused fever and inflammation.
Speaker 4: Why boil it and then cool it?
Speaker 2: Great question, I don't know. And of course Igna's Semmelweiss
Speaker 2: went further than just washing instruments in cold water. He
Speaker 2: also famously advocated for better hand washing and instrument washing
Speaker 2: using a chloride solution, but as we know, he was
Speaker 2: ridiculed and his ideas did not become widely known until
Speaker 2: after his death, so Lister didn't hear about him until
Speaker 2: much later on. Instead, Lister tried out the cleanliness and
Speaker 2: cold water approach and became increasingly disappointed at the results
Speaker 2: or black thereof. It didn't seem to do anything. He
Speaker 2: expressed his frustration to his students, saying, quote, it is
Speaker 2: a common observation that when some injury is received without
Speaker 2: the skin being broken, the patient invariably recovers, and that
Speaker 2: without any severe illness. On the other hand, trouble of
Speaker 2: the gravest kind is always apt to follow, even in
Speaker 2: trivial injuries, when a wound of the skin is present.
Speaker 2: How is this? The man who is able to explain
Speaker 2: this problem will gain undying fame. Ha ha I know end quote.
Speaker 2: As eighteen sixty four drew to a close, Lister was
Speaker 2: still deep in his depression over the seemingly inevitable death
Speaker 2: of his patients when a colleague brought some new articles
Speaker 2: to his attention, research involving fermentation and putrefaction, authored by
Speaker 2: none other than Louis Pasture HM. In these articles, Pasture
Speaker 2: noted that microscopic rod shaped organisms were found in spoiled wine,
Speaker 2: and he believed that they were responsible for the spoilage.
Speaker 2: But he also looked beyond wine, proposing that these tiny
Speaker 2: germs were also responsible for certain diseases in humans and
Speaker 2: other animals. Pasture's ideas were met with quite a bit
Speaker 2: of resistance and ridicule from the medical and scientific community,
Speaker 2: but Lister found them exciting and felt hopeful that the
Speaker 2: answers he had long been looking for it might be
Speaker 2: found in these articles. To Lister, this concept of germ
Speaker 2: theory explained why disease appeared after surgery and how it
Speaker 2: could be spread from one person to the next, all
Speaker 2: the way down the ward. He wasn't entirely right in
Speaker 2: his conclusions, believing that it was microbes carried in the
Speaker 2: air rather than like on instruments, for instance, but he
Speaker 2: was on the right track enough to try out some
Speaker 2: infection control strategies, namely by attacking these germs after their
Speaker 2: introduction into the wound. On this he also turned to Pasture,
Speaker 2: who had demonstrated that these germs could be killed by
Speaker 2: any number of different things. Heat or filtration couldn't really
Speaker 2: be put to practical use for Lister, so he turned
Speaker 2: towards finding an antiseptic that would kill germs on contact. Again,
Speaker 2: this was not an entirely new notion. Aniseptics had been
Speaker 2: used by surgeons for years to irrigate wounds, but two
Speaker 2: main things prevented them from being recognized as incredibly powerful
Speaker 2: sepsis prevention tools. The first was that surgeons typically waited
Speaker 2: to use the antiseptic on a wound until it was
Speaker 2: obviously infected, at which point there was little the aniseptic
Speaker 2: could do because the infection was likely systemic. And second
Speaker 2: was that the antiseptics themselves often caused substantial damage to
Speaker 2: the surrounding skin, allowing for further infection. Because of this,
Speaker 2: the jury was still out on the value of aniseptics
Speaker 2: in medicine. Lister wondered if there was more to the
Speaker 2: story of aniseptics, though, so he decided to test different
Speaker 2: ones out to see which were the most effective in
Speaker 2: preventing infection. Instead of waiting for the pus to be
Speaker 2: freely flowing and the surrounding skin hot and tight and
Speaker 2: red with inflammation, he applied the aniseptics prof lactically and
Speaker 2: waited to see which one did the best. After going
Speaker 2: through a few that didn't show much promise, he reached
Speaker 2: for the carbolic acid aka phenol, remembering that he had
Speaker 2: heard carbolic acid was sometimes used at sewage works to
Speaker 2: counteract the smell of rotting liquid waste. Yeah, he thought,
Speaker 2: if it can cover up those horrific smells, maybe it'll
Speaker 2: kill whatever is putrefying these wounds. And I feel like
Speaker 2: that was also Semmelweis's train of thought. But yeah, carbolic
Speaker 2: acid didn't work that great on the first two people
Speaker 2: he tried it out on, but the third time was
Speaker 2: the charm. In August of eighteen sixty five, eleven year
Speaker 2: old James Greenlea's was brought to Lister's Hospital three hours
Speaker 2: after his leg had been crushed under a cart, tibia
Speaker 2: cracked and jutting through his skin.
Speaker 1: Ah.
Speaker 2: Yeah, the wound was already, of course, filthy from the
Speaker 2: road and from the journey to the hospital. But Lister
Speaker 2: knew that amputation, which was probably safest in terms of infection,
Speaker 2: would forever change this young boy's life, and so he
Speaker 2: wanted to see what he could do. He put the
Speaker 2: boy under chloroform and went to work cleaning out the
Speaker 2: wound as best he could with dilute carbolic acid and
Speaker 2: getting the bone reset, And he continued to take meticulous
Speaker 2: care of the wound over the next days and weeks,
Speaker 2: carefully cleaning it with carbolic acid and putting some olive
Speaker 2: oil on as a soother, and checking for signs of infection.
Speaker 2: Six weeks and two days after James Greenlea's had been
Speaker 2: carried into the hospital with his horrifically broken leg, he
Speaker 2: walked out on his own.
Speaker 4: Wow Yeah.
Speaker 2: Lister felt that he finally held the key to the
Speaker 2: hospital infection problem. He continued to try out his carbolic
Speaker 2: acid technique on other people with compound frack xtures with
Speaker 2: a success rate of eighty percent, and then moved on
Speaker 2: to other injuries before he finally felt ready to publish.
Speaker 2: On March sixteenth, eighteen sixty seven, two years after he
Speaker 2: first began experimenting with carbolic acid, Lister published the first
Speaker 2: part of a five part article in The Lancet describing
Speaker 2: his findings quote on a new method of treating compound fracture,
Speaker 2: absess etc. With Observations on the conditions of separation. This
Speaker 2: was not only groundbreaking in its support for germ theory,
Speaker 2: but his articles also provided step by step instructions to
Speaker 2: prevent post operative infections. The Glasgow Royal Infirmary where Lister worked,
Speaker 2: went from being among the deadliest to the cleanest with
Speaker 2: the lowest mortality rates. Wow, Lister wrote, quote, I now
Speaker 2: perform an operation for the removal of a tumor, etc.
Speaker 2: With a totally different feeling from what I used to have.
Speaker 2: In fact, surgery is becoming a different thing altogether. End quote.
Speaker 4: Wow.
Speaker 2: I just it's it's hard to imagine what a tremendous
Speaker 2: relief and how much hope that would have inspired. I guess, like,
Speaker 2: finally this isn't a death sentence.
Speaker 4: Yeah, yeah, especially to have like dedicated.
Speaker 3: Your whole life to something and then finally feel like
Speaker 3: you can do it and like not only have horrific outcomes,
Speaker 3: Like yeah, yeah, I can't I can't even imagine.
Speaker 2: Yeah, And I have some numbers to back up just
Speaker 2: how incredible this was. So sixteen of the thirty five
Speaker 2: people that had undergone amputations between eighteen sixty four and
Speaker 2: eighteen sixty six before carbolic acid, sixteen of those thirty
Speaker 2: five had died, while that number dropped down to only
Speaker 2: six of forty between eighteen sixty seven and eighteen sixty
Speaker 2: eight after carbolic acid.
Speaker 4: Wow.
Speaker 2: Yeah, it's it's amazing, and I do just want to
Speaker 2: point out because I realize I'm talking mostly about Lister
Speaker 2: and antiseptic technique in the history of sepsis, and a
Speaker 2: lot of these post surgery deaths were due to wound
Speaker 2: sepsis basically that was caused by an infection that they
Speaker 2: had gotten from the surgery, not something they came into
Speaker 2: the hospital with.
Speaker 4: Right. Yeah.
Speaker 2: Yeah. As you might expect, Lister's articles weren't immediately accepted
Speaker 2: with open arms by the medical and surgical community. Shocked
Speaker 2: of all shocking, shocking, though he did seem to have
Speaker 2: more supporters than someone like Semmelweis. His old mentor sign
Speaker 2: was on his side, as were many of Lister's students
Speaker 2: and Pasture himself, whom he became close pen pals with.
Speaker 2: But there was quite a bit of resistance and even
Speaker 2: ridicule in response to his ideas of antisepsis, most notably
Speaker 2: from the famous surgeon James Y. Simpson, who had first
Speaker 2: introduced the use of chloroform as anesthesia and was a
Speaker 2: big proponent of acute pressure for sepsis prevention, which didn't work.
Speaker 2: Simpson seemed to have a personal vendetta against blister. Maybe
Speaker 2: he was frustrated that no one seemed to like acutpressure.
Speaker 2: Maybe he felt protective of his own fame and was
Speaker 2: jealous of Lister, but there did seem to be a
Speaker 2: variety of reasons that Simpson and others were so quick
Speaker 2: to dismiss Lister's ideas.
Speaker 4: To some, it.
Speaker 2: Seemed like the newest version of put this mysterious ointment
Speaker 2: on it and hope for the best. To others, it
Speaker 2: was a passing fad. Some believed Lister to be overstating
Speaker 2: his results, and others dismissed it out of hand due
Speaker 2: to its reliance on germ theory, which had by no
Speaker 2: means been widely accepted yet. But perhaps one of the
Speaker 2: biggest reasons for resisting Lister's ideas was that if he
Speaker 2: was right, that meant that these surgeons had been inadvertently
Speaker 2: causing the deaths of so many of the people that
Speaker 2: they were supposed to have been helping. Lister fought the
Speaker 2: disappointment he felt from all this criticism by focusing his
Speaker 2: efforts on improving surgery in other ways, such as changing
Speaker 2: the material that the ligatures were made of to catgut,
Speaker 2: which could be absorbed by the body and reduce the
Speaker 2: risk of infection. He also concentrated on teaching, realizing that well,
Speaker 2: if he couldn't convince older generations of doctors of his methods,
Speaker 2: then he could train the new ones. Over the next
Speaker 2: few years, years in which so many people continued to
Speaker 2: die because their surgeons refused to test out Lister's techniques,
Speaker 2: Lister kept at it, touring across the US to give
Speaker 2: talks where some hospitals like Mass General for example, had
Speaker 2: actually banned Lister's techniques, and then later it became they
Speaker 2: were like the first hospital to make it hospital policy
Speaker 2: to practice wow and also continuing to publish his results.
Speaker 2: I hate that this is a lesson in published, publish, published,
Speaker 2: but whatever, it all paid off. The medical community grew
Speaker 2: to accept Lister's carbolic acid practices in preventing post surgical infection,
Speaker 2: and the enormous contribution he made to the field of
Speaker 2: not just surgery but all of medicine was recognized in
Speaker 2: his lifetime. Unlike so many of the other people that
Speaker 2: we talk about on this podcast, Yeah, Lister spent the
Speaker 2: rest of his life showered in awards, accolades, honorary degrees,
Speaker 2: and was even given the dubious honor of having a
Speaker 2: hygiene product created in his name of Lister Reade.
Speaker 3: Oh my gosh, I don't know if I ever put
Speaker 3: those two together. Lister Reid's been around that long.
Speaker 2: It was developed by someone who who saw his talk,
Speaker 2: one of Lister's talks in the US, and then later
Speaker 2: like the rights to advertise it were sold and the
Speaker 2: person who bought them advertised it as a Dan Dreff treatment,
Speaker 2: a cure for gonorrhea, a floor cleaner, and of course
Speaker 2: oral antiseptic. And that's how it came. That's how it
Speaker 2: has remained. And it wasn't just Listerine that Lister inspired.
Speaker 2: Lister's antiseptic techniques kicked off a craze for antiseptic products
Speaker 2: and inspired someone named Robert Wood Johnson, who had also
Speaker 2: seen Lister speak, to join up with his brothers to
Speaker 2: start a company manufacturing sterile surgical dressings and sutures. They
Speaker 2: named it Johnson and Johnson.
Speaker 3: How interesting, Yeah wow, but mouthwash aside.
Speaker 2: Lister's two biggest legacies are that he provided an effective
Speaker 2: means to prevent one of the biggest causes of surgical deaths,
Speaker 2: which absolutely changed the practice of surgery forever and medicine period,
Speaker 2: and also that he demonstrated germ theory in action, which
Speaker 2: greatly helped it to become accepted or at least more
Speaker 2: closely examined. With the widespread adoption of Lister's antiseptic practices,
Speaker 2: hospital sepsis cases dropped tremendously. Over the next decades, Researchers
Speaker 2: learned more about the underlying pathophysiology of sepsis, such as
Speaker 2: the role of endotoxins and the immune system response, and
Speaker 2: they discovered new ways to diagnose and treat the condition.
Speaker 2: In the one hundred and fifty five years since Lister
Speaker 2: published his article, We've come so far and learned so
Speaker 2: much about sepsis, but as we can gather from the
Speaker 2: biology section, we have still so very far to go.
Speaker 2: And I really hope I haven't disappointed anyone too very
Speaker 2: much by skipping over most of the recent history of
Speaker 2: sepsis and the changing definitions. But I figured, Aarin, that
Speaker 2: you could at least bring us up to speed with
Speaker 2: sepsis today.
Speaker 4: Oh, I can't wait to right after this break.
Speaker 3: Sepsis today, Aaron, it's a bit of a mess.
Speaker 4: In the US.
Speaker 3: In recent years, there are nearly a million sepsis cases
Speaker 3: admitted to hospitals each year.
Speaker 4: Just in the US a million.
Speaker 3: Yeah, and the numbers tend to be on the rise
Speaker 3: year after year.
Speaker 4: Huh m hm.
Speaker 3: Sepsis is also one of, if not the leading expenses.
Speaker 3: And I know we've talked about the problem of using
Speaker 3: like healthcare expenses, especially in the US, because our healthcare
Speaker 3: system is so skewed in terms of how much everything costs.
Speaker 4: But sepsis costs the.
Speaker 3: US healthcare system billions and billions of dollars every year.
Speaker 2: I mean, at the very least, it seems like it
Speaker 2: would be a good proxy for the number of days
Speaker 2: that you spend in the hospital, the number of like
Speaker 2: different specialists that need to see you.
Speaker 4: It's exactly so.
Speaker 3: As one example from a paper, they cited that in
Speaker 3: twenty thirteen, sepsis cost the US over twenty four billion
Speaker 3: dollars in total hospital expenses, which is thirteen percent of
Speaker 3: total US hospital costs. WHOA, even though sepsis accounted for
Speaker 3: about three and a half percent.
Speaker 4: Of hospital stays.
Speaker 3: So it's disproportionate the cost to the amount of.
Speaker 4: Total hospital stays.
Speaker 3: Wow, Okay, because it can be such severe infections. Yeah,
Speaker 3: when we try to look more globally, I think what
Speaker 3: we really have to understand is just how underestimate these
Speaker 3: numbers likely are. Like the true scale of sepsis in
Speaker 3: the US, but also especially in low and middle income
Speaker 3: country across the globe, we really don't have a handle
Speaker 3: on the global burden. A paper from twenty seventeen estimated
Speaker 3: about forty nine million cases worldwide, wow, and eleven million
Speaker 3: sepsis related deaths. If those numbers are accurate. Like again,
Speaker 3: these are estimates, that would be almost twenty percent of
Speaker 3: all global deaths, the vast majority of which, it's estimated
Speaker 3: eighty five percent of those sepsis related deaths are in
Speaker 3: low and middle income countries that we just aren't getting
Speaker 3: good data on.
Speaker 4: Isn't that it's just so horrific?
Speaker 3: True?
Speaker 2: Yeah, it truly is.
Speaker 3: And it's also estimated that almost half of all these
Speaker 3: cases occur among children. So twenty million cases among children
Speaker 3: and two point nine million global deaths in children under
Speaker 3: age five is what this paper is estimating. So it's
Speaker 3: a huge healthcare problem. It's difficult to diagnose. Again, the
Speaker 3: mortality rate can vary quite a lot. Some papers just
Speaker 3: that try and estimate it overall, say anywhere between one
Speaker 3: in three and one in six people with sepsis can die,
Speaker 3: and so the World Health Organization has understandably made this
Speaker 3: a huge campaign and a priority as well as the
Speaker 3: Surviving Sepsis campaign that I mentioned already. One of the
Speaker 3: big things that the Surviving Sepsis campaign tries to do,
Speaker 3: in addition to raising awareness is also just gathering data
Speaker 3: and analyzing that data in a way to try and
Speaker 3: actually improve outcomes. And one of the big issues with
Speaker 3: the data that exists so far is that it generally
Speaker 3: comes from very high income countries, and so we have
Speaker 3: to recognize the limitations in how we can interpret and
Speaker 3: then apply that data to much less resource rich areas. Right,
Speaker 3: and importantly, all of these kind of campaigns and policies
Speaker 3: are largely, like I said, trying to improve outcomes as
Speaker 3: well as improve our recognition of sepsis and how we
Speaker 3: treat it to reduce morbidity and reduce mortality.
Speaker 4: Sepsis is something that has likely.
Speaker 3: Always been with us and will likely always be with us,
Speaker 3: and so it's not something that there are large groups
Speaker 3: saying we should eliminate sepsis entirely. That's not realistic goals,
Speaker 3: at least not at this point. And one I think
Speaker 3: of the reasons is how little we still understand about sepsis.
Speaker 4: Aaron.
Speaker 2: It's shocking, but also not shocking.
Speaker 3: There was a great paper from the Lancet Infectious Disease
Speaker 3: twenty nineteen that was written by people from the European
Speaker 3: Group on Immunology of Sepsis. AGIS loved it, and they
Speaker 3: were really upfront about their feelings on all of this.
Speaker 3: They basically were like, look, the reason that we have
Speaker 3: all these different definitions and all this controversy of like
Speaker 3: is it this criteria or that criteria, et cetera, it's
Speaker 3: because we just don't understand the immunology of sepsis. We
Speaker 3: don't we do not understand it. And so this article
Speaker 3: really laid out what they feel at least are the
Speaker 3: major deficits in our understanding and where we should go
Speaker 3: from here. They did this by looking at three different
Speaker 3: stages of sepsis before it develops, which is my favorite
Speaker 3: stage to think about, very important. Who is at risk,
Speaker 3: why are they at risk? What kinds of research do
Speaker 3: we even need to do to better understand this initial
Speaker 3: process and these specific risks to be able to actually
Speaker 3: pre event sepsis to begin with.
Speaker 2: Maybe change up the animal models we're using.
Speaker 3: Yes, we don't have good animal models for sepsis. Then
Speaker 3: we also have the next stage, the evolution of sepsis.
Speaker 3: What are these specific immune processes that are underlying this
Speaker 3: organ damage and how might we use these to better
Speaker 3: target treatments. There have been a lot, mostly of animal
Speaker 3: model studies of like, well, if you know IL ten
Speaker 3: is involved, let's affect that like these specific you know,
Speaker 3: immune modulators and the short answers they don't work right
Speaker 3: because these are too broad. So anything that we have
Speaker 3: tried to do to modulate the immune system ends up
Speaker 3: making things worse rather than better when it comes to sepsis.
Speaker 3: So far, and finally the third stage post sepsis, like
Speaker 3: what are the consequences of having a severe sepsis infection
Speaker 3: in the long term and what can some of these
Speaker 3: consequences teach us about the underlying pathology of secsis. We
Speaker 3: don't have answers to those, but I think it's just
Speaker 3: kind of a nice framework to think about where we
Speaker 3: can go from here.
Speaker 2: Yeah, I mean, yeah, it's good to have questions. You
Speaker 2: have to have direction exactly.
Speaker 3: Yeah, So it is going to be very interesting to
Speaker 3: see how these definitions continue to change, and how treatments
Speaker 3: then continue to change.
Speaker 2: I have a question about something you said about numbers
Speaker 2: going up? Yeah, is that an increase? Is that an
Speaker 2: apparent increase? Is that a real increase? What do we
Speaker 2: think about that?
Speaker 4: I don't know if we know. Okay, yeah, I don't
Speaker 4: know if we know.
Speaker 3: Is it because of changing definitions and so are we
Speaker 3: broadening our definition in order to capture people at an
Speaker 3: earlier stage to then prevent severe infection or are people
Speaker 3: actually coming in with sepsis and sicker.
Speaker 4: I don't have a great answer to that.
Speaker 2: Another question I had is if you have had sepsis
Speaker 2: one time and recovered, are you more likely to develop
Speaker 2: sepsis a second time?
Speaker 3: That's a very good question. I think it probably in
Speaker 3: large part depends on what the inciting factor was. If
Speaker 3: you have cancer and you are immunosuppressed and you end
Speaker 3: up getting infection that leads to sepsis and you recover
Speaker 3: from that, but you still have cancer and you're still immunosuppressed,
Speaker 3: then yes, you're still at high risk for sepsis. If
Speaker 3: you got a cut and a wound that was infected
Speaker 3: and you ended up with sepsis, but you don't have
Speaker 3: any other underlying immune conditions that we know of. Of course,
Speaker 3: there's so much individual immune response differences that we just
Speaker 3: don't know about. It's a good question as to whether
Speaker 3: you are at higher risk or not. I think we
Speaker 3: don't probably know enough to know in those instances.
Speaker 4: Okay, that makes sense, Yeah, great question though, that's very interesting.
Speaker 4: Any other questions.
Speaker 6: Arin I mean a million, Like do we even know
Speaker 6: what sepsis is at the end of this.
Speaker 2: I'm not sure that I do. Besides, like the very
Speaker 2: broad definition, but it seems it seems like a like
Speaker 2: a moving target. Yeah, and impossible to pin down. Yeah,
Speaker 2: right now, maybe the future, the future holds all the
Speaker 2: answers for sure.
Speaker 3: It is also probably interesting to think though about so
Speaker 3: many things now that maybe are more specific definitions that
Speaker 3: used to have just been called under a catch all
Speaker 3: of sepsis. Yes, so I do wonder how many other
Speaker 3: things might come out of our current definition of sepsis.
Speaker 2: Right, we have a bowl that is sepsis, and we
Speaker 2: can draw out little bits of paper that say, oh,
Speaker 2: that was Actually I don't know any of the things,
Speaker 2: but right we now call that something else that is
Speaker 2: not sepsis.
Speaker 3: Yeah, Yeah, interesting anyways.
Speaker 2: Sources, sources. I have a few papers that talk a
Speaker 2: little bit more about the changing definitions of sepsis and
Speaker 2: the more recent history of sepsis if you'd like to
Speaker 2: check those out. But let me just shout out again
Speaker 2: the fantastic book by Lindsay Fitzharris, The Butchering Art, All
Speaker 2: about Lister, all about early surgery, all about how germ
Speaker 2: theory kind of came to save the day a little
Speaker 2: bit and Lister. It's such a great read, it is,
Speaker 2: it is really great.
Speaker 3: I can also recommend I had a number of sources,
Speaker 3: not as many as sometimes, because the papers that I
Speaker 3: found were actually really comprehensive just on the overall definitions
Speaker 3: and what we know so far about the immunology of sepsis.
Speaker 3: So I will post those as well as the list
Speaker 3: of all of our sources from every single one of
Speaker 3: our episodes on our website This Podcast will Kill You
Speaker 3: dot Com under the episodes tab.
Speaker 2: Thank you again so much, Katie for taking the time
Speaker 2: to chat and sharing your story. It really means a ton.
Speaker 2: And we will also link to some more articles that
Speaker 2: Katie has shared, as well as the Sepsis Alliance website,
Speaker 2: which is sepsis dot org, so be sure to check
Speaker 2: out the sources for this episode and also the show notes.
Speaker 3: Thank you also to Bloodmobile, who provides the music for
Speaker 3: this episode and all of our episodes.
Speaker 2: And thank you too, exactly right, and thank.
Speaker 3: You to you listeners. We hope you enjoyed this episode.
Speaker 2: Yeah, we hope you found it interesting. What are your
Speaker 2: burning questions about sepsis still at the end of this
Speaker 2: let us know I have a lot. Yeah, and a
Speaker 2: special thank you as always to our wonderful general as patrons.
Speaker 2: We appreciate you so so very much.
Speaker 4: Thank you well.
Speaker 2: Until next time, wash your hands, you filthy animals.