Ep 107 Sepsis: It's a mess

with my husband. We were new empty nesters and I had just gone to visit my kids in California for a week and my husband had taken that opportunity to go on a fishing trip to very remote Idaho. So went down to California, hung out with my kids, and then it was time to return back to Hawaii. I got on an airplane flew home, and when I got to the airport, this is when I remember noticing that I had this bump on my finger and it was oozing.

It was kind of pink, and it had clear fluid coming out of it, so it looked different than anything I'd seen before. So I was on my way home my house is actually an hour from the airport. It's also an hour from the hospital, which is going to be relevant later on, so I did decide to go buy the emergency clinic. When I got there, I showed them the cut and they agreed that it did look

infected and looked like it could possibly be MRSA. They took a little swab of it and said basically they'd call me in a few days if anything grew out of it. So they gave me a prescription for antibiotics, and they said to start taking them if it got worse over the weekend. At the emergency clinic, when they checked my vital signs, everything was great, so they didn't have any indication that I had sepsis at this point,

and I really didn't. I just had an infection. So on Saturday morning, I woke up, I happed in the shower. It was warm there in Hawaii, I was kind of warm, but I never was registering a fever, so I didn't think there was anything wrong. I did notice that the infection on my finger was getting a little worse, so I went ahead and took an antibiotic. Well soon thereafter, I threw up, but I just thought it was because I'd taken an antibiotic on an empty stomach, and I

wrote it off. But I ended up sleeping through the afternoon and sleeping through the evening, and sometime in the middle of the night, I got up and I probably went into the bathroom, which is two steps up from my bedroom. And what we think may have happened is that I maybe stood up quickly and low blood pressure in my body caused me to pass out. But what the result was is that I broke my left foot, I sprayed my right ankle, and I had just a mark on my kneehere I had fallen on the floor.

So this is a sign for me of mental decline, because instead of calling for help like a normal person would, I crawled back in bed. So the next morning was Sunday, and I woke up at sunrise, like at the crack of dawn. I could hear the roosters outside. It was still dark, and I don't really remember much. I do know that I texted my friend and I said to my friend, can you take me to the hospital. She asked if we could go to the emergency clinic, and I said no. I have never been so sick So

my friend took this seriously, as one should. She came right down to my house, let herself in, and she found me nearly unresponsive in my bed, and we tried to stand up, and that's when we realized that my feet hurt. We found out later that it was the break in the one foot, and then I also could have had some nerve pain from something you're going to hear about in a second. But it was about an hour drive and about fifteen minutes out, I started crying

in the backseat, saying, are we there yet? Are we close? My hands and feet are on fire. So she went ahead and called the hospital and let them know that we were coming in. When we got to the hospital, they met us with a gurney. They got me out of the car, loaded me onto it, They took me right into the emergency room, and they did the things that they should do. It took my vital signs. So it turns out that my blood pressure at that point

was fifty over thirty, which is extremely low. And it's funny because I've read my chart and they said I was conversive and pleasant, and I'm like, well that's my go to. I mean, I was faking conversive and pleasant. I also had an increased heart rate and I had low blood oxygen, so they immediately put an oxygen canulate in my nose just to let me breathe oxygen. Later in the day, the oxygen levels got worse and I actually had a mask forcing air into my lungs. So

what was happening is that my organs began failing. I stopped urinating, so that was a sign that my kidneys were failing, and it was becoming really clear that I was at higher levels of steps is called septic shock. The whole thing with my hands and fingers are on fire is showing that my circulation at my extremities was very, very bad, and my fingers began turning purple, and so did my toes, although I didn't see them at the beginning. I ended up having a condition later that they diagnosed

called disseminated intravascular coagulation. So if this had not happened in the hospital, I would have run out of platelets. So at that point in time, I was on an outer island in Hawaii. We lived on the island of Kawaii. Anyone in Hawaii, if you get sick on an outer Island and you get very sick and you need an ICU or you need severe help, they will transport you by air ambulance over to a Wahoo, which is where

Honolulu is. So on Monday morning a bed became available at the hospital at Queen's Hospital, it was decided that they would fly me over to Honolulu. So they ended up giving medication to put me in a drug and discoma. They intubated me and they sent me over to a Wahoo. When I got there, my husband had, actually, thank goodness, had landed on a Wahoo about an hour before I did, so he was able to meet me at the hospital,

so now I have my family with me. When they came out, they told him that I was not stable, and that started asking questions like does she have a will, and what are her desires? If we need to do you know, if we need to resuscitate. But they did say that he should call our children, who again were in California and have them come because they weren't sure

I was going to make it. So my family was by my side for five days as I sat in the ICU, or as I laid in the ICU, and they were praying over me and watching my hands and feet turn more and more purple up to my wrists and up to my ankles, and it became clear, I think to them during that week that I was going to lose at least my fingers and toes, and likely

more than that. On my daughter's twenty third birthday, my oldest daughter's twenty third birthday, which was five days later, I woke up and when that happened, I saw my husband in front of me, and he got right into my face to just let me know he was there, and then everything was going to be okay. I was extremely confused. But one thing that happened is I saw my fingers go in front of my face and seven my fingertips were black. My thumbs, the tips of my

thumbs were black. It looked like I was going to lose all of my fingers, and I was absolutely terrified. I didn't know what had happened. I mean, whilst I remembered, I was being cheerful talking to people in the hospital, and then I'm waking up and I'm realizing that I can see these clearly dead fingers. I realized I'm going to lose these fingers. So we spent three weeks at the hospital, doing hyperbaric chamber every day and doing nitrogliscer and cream on my hands and feet three times a day.

It was extremely painful, but we were able to save my hands. Right now, I have my hands and most of my fingers up to those seven tips that were black. My thumbs are fine. I have them one hundred percent.

I'm really fortunate that that's what my outcome was. At the time, I was really trying hard to save my feet, and I was having a hard, as you can imagine, a very hard time admitting that we might not be able to After three weeks, I finally looked at my husband and said, I understand that we can't save my feet, and I just want to move on to whatever the next steps are after. You know, after a couple months, I got the amputations. I did recovery at home. I

got my prosthetic legs right around Christmas time. This happened in the middle of September. Initially and I was able to stand on them immediately, but it was painful, so I just built up my tolerance to walking around in them just slowly. I stayed in my wheelchair a lot of the time and Anyways, I started getting better and

I started realizing I could get my life back. I went and visited my daughter who she went to Rome for study abroad, and my husband and my best friend arranged for me to go as well, so I got to go visit her like I had always dreamed of doing. And since then I'm living a really full life. A year later, I was invited onto the board of directors of Sepsist Alliance and now I share my story to spread awareness.

versus to rule people out for sepsis or whatever. But basically the definitions have changed in part because of our understanding of sepsis and what the underlying causes are, as well as how we identify it in an emergency setting, for example. And the truth is there are a whole host of what are often called screening tools that are used to kind of identify, in ideally a highly sensitive way, what people might either have sepsis or be at high

risk for sepsis. One of these screening tools is called sers SIRS. It stands for systemic inflammatory response syndrome, and these criteria are like an increased or decreased temper, an increased heart rate, an increased respiratory rate, an increased white blood cell count, or a severely decreased white blood cell count, things like that. So having two of those criteria and a known or suspected source of an infection would in a lot of cases rule people in so make us

think this person has sepsis. We're going to call them stepsis until proven otherwise. There are a lot of other criteria. There's the SOFA, which stands for sequential organ failure assessment, which is mostly based on a list of laboratory values or respiratory status values to kind of try and determine and triage the degree of organ damage. So getting a certain score on that screening tool plus having a known or suspected infection would then meet criteria for sepsis. But

there are also a lot of others. There's one called NEWS, there's one called MUSE. There's likely different versions in different countries that I don't even know about.

an organization. It's called the Surviving Sepsis Campaign, and it's an international organization that really tries to go through all of the data that we have on sepsis and outcomes of sepsis and come up with a consensus set of guidelines on how to identify, diagnose, and manage sepsis in the hospital and ic you setting, and so they have like a set of guidelines and things where they say, you know, this screening tool is not the best and this one is okay, and et cetera, et cetera.

response to this infection. They may or may not have difficulty breathing, or if you put an oxygen meter on them, have hypoxia, decrease in their oxygen status.

with sepsis, though you certainly can. And then you know, same thing, for if they have respiratory symptoms, you might think that they have a predominantly respiratory infection.

infection and a disregulated immune response to that infection. I think that those things can tell us a lot about the pros sus underlying sepsis, even in the face of the fact that specific criteria to call someone septic might be different at one hospital versus another. So at its core, sepsis requires first an infection, and this, like I said, can be an infection of literally any body area cellulitis, pneumonia.

viral infections. And so then it gets even more complicated because you have culture negative sepsis where you are maybe treating like it's a bacterial infection, but with no evidence of bacteria growing from any body source.

But that still doesn't tell us that it's necessarily a bacterial infection, though those most commonly are going to be ones that we've identified as bacterial infections, Fungal infections tend to be probably the least common but the most severe. If you have an overwhelming fungal infection, you're likely very very,

very sick, and viral infections are probably way underdiagnosed. And this is where it gets both more interesting and so much more complicated, because if you think as an easily recognizable example of COVID nineteen, the vast majority of people hospitalized like that ended up in the hospital or the ICU for COVID nineteen would meet many, if not all, of the common criteria that we would use to diagnose sepsis.

They're probably tachcartic, their heart rates through the roof, They probably have an oxygen requirement, they may or may not have a low blood pressure, they probably have some evidence of further organ damage like kidney or liver damage, and certainly they have an overwhelming infection in their lungs and a huge amount of inflammatory response in those lungs, causing

acute respiratory distress. So people with COVID nineteen would, by many definitions or many sets of screening protocols, meet quote sepsis criteria. And yet it's probably only either in an emergency like triage setting or in the very early days of the COVID pandemic that most of those people were actually classified as having sepsis, because now on their discharge paperwork, they would be called having COVID nineteen, right, because we know that that damage is being wrought by stars CoV

two and our disregulated immune response to that virus. But instead of calling it sepsis, necessarily we call it COVID nineteen. And so some people might argue you should still call that sepsis, and some people might argue you shouldn't.

sepsis or is this not sepsis? And I think a lot of that is place dependent, but the treatment does vary, at least according to kind of what we have for now as consensus guidelines when it comes to early identification and treatment of sepsis. So let's get into a little bit more of like why do we even have to have this definition of like sepsis and what does that mean? What's going on in our bodies, and then we can talk about how we then treat that because of what's happening.

different processes. But shock is characterized specifically by hypotension low low blood pressure, and so that means that your organ's like your kidney's, your liver, or your brain, your heart, they're not getting enough blood and oxygen to functions, so they begin to shut down, and that is what leads to death in sepsis. It's multi organ failure as a result of septic shock. So what exactly is our immune system doing in response to an infection that eventually results

in this all the way down the line? No more blood getting to our organs, not enough oxygen getting to our organs. So, unsurprisingly, we don't fully understand this mechanism at all, especially.

inflammatory actors are releasing cytokines. They're telling the whole rest of our immune system like get in gear, bring all the leukocytes, like, tell everyone, this is war. I don't like that analogy, but it's like really good, and it basically like sends our immune system into overdrive. All of this inflammatory process causes vasodilation, so it opens up our blood vessels really wide so that the inflammatory stuff can

get to where it's trying to go. And this inflammation also causes damage to the blood vessel walls and inflammatory changes to the layers of our blood vessel walls so that things can squeeze out and get into tissues to like help heal them. But what this ends up, leading to is leaky blood vessels, a edema of the tissues,

fluid getting out to where it doesn't belong. And so if that fluid gets into something like our lungs, then that can lead to severe difficulty breathing called acute respiratory distress syndrome because of fluid filling up your lungs that's supposed to be in your blood vessels. This also leads to a decrease in permeability of your blood brain barrier. So then infections can spread to the brain where they

maybe couldn't before. And that's all just the inflammatory pathways that are happening during sepsis.

have like a fully onboarded immune system.

that's causing this unregulated inflammation. Is it just one process or is it you know, each case of sepsis is a slightly different process, And is that part of what's making it so difficult to study and to understand.

a vessel gets cut. So this coagulation cascade, this process is going to first recruit platelets to come in and plug the holes of that damaged blood vessel, and then tissue factor is going to start the process of activating this whole entire cascade that I'm not going to go back through, but it's factors seven, eight, nine, five, four, ten, et cetera. And this whole process ends up getting activated in again a disregulated way when it comes to sepsis.

have a hole in our tissues. But that's mild. If this this process continues out of control, it will progress to what's called DIC or disseminated intravascular coagulation, which is basically when this coagulation cascade is underway inside of our blood vessels and ends up forming these little microthromby, little tiny little clots in our vessels as a result of this coagulation cascade, and these thrombi not only can block off blood vessels by accident, so now you're not getting

blood flow to say, your fingertips or a part of your brain. And at the same time, because our body, whenever we make a clot, we eventually need to break it down. So when we're forming a whole bunch of clots inside our blood vessels, our body is breaking them down. At the same time, we end up using up all of these coagulation factors. We end up using up all of our platelets to the point where now we can't clot at all, so you can end up hemorrhaging.

like everyone's just a free for all. That's at least the way that I my brain has tried to understand.

But there are a few kind of big important things, and the first is just identifying people, especially those that are at high risk for septic shock, and so that means using these various criteria to identify people who have sepsis, even if it's early on. The other thing that it means is identifying as quickly as you can the source of infection and if possible, getting cultures to be able to verify if this is a bacterial infection, what bacterium it is, or if it's a fungus, what fungus it is.

It's also possible to do viral testing in some places in some areas, but identifying the source of infection and then controlling that source if possible, so if there's an abscess, it needs to be drained. If there's like a necrotizing skin infection, it has to be debrided. If it's an infection from an infected line, like a catheter of some kind being removed, like finding where the bacteria is seeding from or the infection is seeding from and trying to

remove it. And in the vast majority of cases, starting broad spectrum antibiotics, especially if you don't know what is causing this. And then one of the kind of most well supported things that tend to happen when someone is identified as having sepsis is fluid resuscitation because it can

so quickly progress to septic shock and hypotension. Resuscitating with fluids, so like putting it in an IV and getting fluids is one of kind of the most well studied, has really good data to support that it improves outcomes and mortality.

Talk about a particular bacterial cause, or the evolution of treatment strategies, or how our understanding and definition of sepsis has changed throughout time. Or maybe you could talk about a big moment in sepsis history, a period when humanity's collective view of the world and how it worked underwent a tremendous and life saving shift, even if somewhat reluctantly. Okay,

and that's my pick for today. That's what I'm gonna do, because how could I pass up an opportunity to talk about Joseph Lister and the sanitation revolution.

heart of so much of that. And I want to mention at the top that most of the info about Lister and those early days of surgery and germ theory I got from the fantastic book The Butchering Art by Lindsay Fitzharris.

Probably could go without saying, but humans and sepsis go way back, and our recognition of the disease also goes way back to about twenty seven hundred years ago, when it was first used in a medical context in Homer's poems in the verb form sepo meaning I rot. Later, around four hundred BCE, the word sepsis was introduced in the Hippocratic texts, meaning quote the decomposition of animal or

vegetable or organic matter. And this word or variations of it were used extensively in Greek and Roman literature, not just in my medical texts, but also classic literature and

philosophical writings, where it likely held symbolic meaning. Over the next hundreds of years, it remained in some use, but it seems difficult to say whether that was in the medical sense or in the symbolic sense, and in either case it's unlikely that the sepsis referred to in most historical texts pre nineteenth century would always fit the definition that we use today, right, The modern use of sepsis more or less can be traced back to sometime in

the early nineteenth century, depending on the language, also depending on the definition. This is why I didn't want to go into the changing definitions of sepsis. It just gets really messy, really fast. And when it was introduced in the early nineteenth century, it meant putrefaction, often accompanied with the rotting of the body or parts of the body

after a wound. And it's really no surprise that it was around this time that sepsis came into more and more frequent use, as well as other words that were related to sepsis, like septosmia or piemia, because much of the world was undergoing some pretty drastic changes in terms of urbanization, industrialization, and population growth, and these changes could also be seen in the medical field, namely in the

form of hospitals. I talked a bit about the enormous increase in hospitals during this time in the Pupil Fever episode. Go and listen to it, but in case you need a refresher and you don't feel like it. I'm going to set the stage again here. The late eighteenth century and early nineteenth centuries saw a tremendous growth in hospitals in Europe and in the US, mainly as a feature of the cities that were constantly and rapidly growing thanks

to industrialization. In contrast with rural areas where doctors would often travel house to house to care for patients, hospitals began to be popular in cities where physicians could just stay put and wait for their many patients to come to them, They could work with other physicians and exchange knowledge, and they could use the people seeking care, many of whom were in lower economic classes, as a teaching opportunity. Prior to the early eighteen hundreds, essentially the only requirement

for being a surgeon was just calling yourself one. But with the growth in hospitals also came tighter, though still loose by today's standards, regulations for education and training for surgeons and would be surgeons had to spend a certain amount of time, say six months or so, learning in hospitals, listening to lectures, performing autopsies, or training directly on patients. Hospitals were proving to be a tremendous opportunity for the growth and spread of medical knowledge, as well as the

growth and spread of pathogenic microbs. Because these were still the days before germ theory, when it was held that the dirtier the surgeon's hands or the stiff of their coat with dried PUFs and blood, the more respected they were. I just it's so yucky, yes, horrible to think about. Yeah, the prevailing notion of what caused disease was still miasma, foul air that contaminated the body and led to infections.

worried about. In the first few decades of the nineteenth century, mortality rates from surgery were as high as you can imagine, but the overall number of surgeries performed was actually fairly low, and that was largely due to the lack of anesthesia prior to the introduction of ether in the eighteen forties.

If you had to have surgery of some kind, you either had to take your chances with laughing gas, which could either kill you or not affect you at all, or bite the bullet or more accurately, the leather strap. The horror of surgeries made many people reluctant to have them unless in cases of dire need, and even made many surgeons reluctant to perform them, or at the very least encourage them to cut as quickly as they could.

When ether was first used in eighteen forty two by Crawford Long outside of Athens, Georgia, it was the beginning of a revolution that would transform surgery from a terrifying last resort where had to get in and out as quickly as they could, into a viable option and a burgeoning field of study. With ether, a surgeon still had to be fast, but they at least had a little more breathing room to make sure they were suturing the

right arteries or whatever. Together. As the miracle of ether became more widely known across the world, the number of surgeries performed climbed up and up and up. With ether, one enormous barrier to surgeries had been toppled, but the other one, a big one, still remained, infection and infection's post surgery loomed bigger and bigger as ether became more

widely used. Since remember we're still in the days before germ theory, right, this is the surgical world that Joseph Lister entered into at the age of seventeen in eighteen forty four. Lister was born and raised a Quaker, which meant a simple childhood. No sport, no theater, no frills. Life in general was not about the pursuit of pleasure,

but about service and honor of God. Fortunately for little Joseph Lister and the rest of the world, science was considered a worthy pastime and he had the tools to explore the natural world at his disposal thanks to his father. Although Lister's father had started his career in the family biz as a wine merchant, over time he became fascinated with the world of microscopes, especially in improving their capabilities

through fiddling with this lens or adjusting that angle. Lister's father's improvements to microscopes earned him great renown, and Lister's childhood home was full of the instruments, as well as specimens and books of natural history. Given this upbringing, it's hardly surprising that at the age of fourteen, Lister decided he wanted to better understand life by becoming a surgeon, which was not welcome news to his family. At the times. Not a well respected bunch, they were seen not so

much as educated professionals, but more as crude technicians. To just give you an idea of this, consider that a hospital's chief bug catcher, who was responsible for removing lice from mattresses, was paid more than the hospital surgeons.

courses in history, math, literature, and science. I love that this was definitely not a requirement or the norm for surgeons and training, but Lister later attributed his ability to make the important connections he did across disease, sanitation, and germ theory to this well rounded education. The other not required or not normal thing that Lister did was bring his microscope. At the time, microscopes had been around for quite a while, over two hundred years.

entire body or whole organs as had been thought. It would still take some time, though, before the value of microscopes in diagnosis and other aspects of medicine was made clear, and so Lister certainly was unusual in owning one, and maybe even more unusual was that he used it. As a senior medical student, Lister was appointed to be a dresser for John Eric Erickson, who was the senior surgeon

at University College Hospital. Part of Lister's duties included standing by with a box of supplies to dress wounds during surgery or to change the bandages in post surgical care. In eighteen fifty two, during one of these routine bandage changes, he unraveled the cloth on a patient's seeping, rotting wound and was met with a horrific odor. It was the

dreaded hospital gangreen in the day's pre germ theory. Gangreen was one of the big four exceedingly common hospital infections that cause the most death and disease, with the other three being arispolis, septicemia, and piemia, which is a development of pus filled abscesses. No one knew precisely why hospitals in particulars seemed to be so susceptible to these conditions,

but they certainly were. You may remember some of the stats about pupil fever in the countryside compared to hospitals from the pupil fever episode, and here I'm going to do the same thing but with amputations, oh dear.

in the cities themselves had come to be expected. Industrial accidents, lack of access to clean water or nutritious foods, crowd diseases. Even if you managed to avoid cholera from the contaminated Broad Street pump, or tuberculosis from your overcrowded building, or arsenic from your wallpaper, you couldn't just as easily die from septocemia. After having the gash on your hand. You

got it, the factory stitched up at the hospital. Deadly infections haunted every hospital wing, and once one appeared, there was not really anything doctors could do to slow it spread. Within a matter of days, the gangrene that Lister observed in that one patient had swept the entire surgical wards,

and Lister was put in charge of wound care. This involved him scraping off the dead, decaying tissue from the wounds and then applying mercury per night, which is both caustic and toxic, an excruciatingly painful process that thankfully was done while the patient was under anesthesia. Lister, observant as always, noticed that the wounds that had been very carefully cleaned and that had received this caustic treatment healed surprisingly well.

What was it about this process that prevented the gangreen from getting worse? Maybe the answer wasn't in the air, as many of Lister's contemporaries thought, but in the wound itself. He took some of the pus that he had scraped from patient's wounds and made slides to check out under

the microscope. Later he wrote about what he saw, quote, I examined microscopically the slough from one of the sores, and I made a sketch of some bodies of pretty uniform size, which I imagined might be the material's morbi morbid substances. The idea that it was probably of parasitic nature was at that early period already present in my mind. End quote.

Edinburgh with clinical surgeon James Syme. What was supposed to be a month long stay turned into years as Sime became not only Lister's respected mentor, but eventually father in law. In Scotland. He fell back in love with surgery and dove back into the topic that had he first grabbed his attention in his surgical training, inflammation in wounds. He spent his free time examining more puffs and tissue samples under the scope and jotting down any patterns he saw.

When did inflammation appear? When did a fever develop? Was fever a good thing or a bad thing? What about inflammation? Did sepsis always come after inflammation or only some of the time. He could only get so far with the dead and dying tissue he was looking at, so he turned to other living animals to take a closer look. A colony of frogs that he kept at his house. He would injure their webs in various ways using heat or chemicals, and then look at what happened to their

blood vessels. What these experiments told Lister was that inflammation was a normal part of the healing process, and sepsis didn't necessarily follow. He was getting closer. In eighteen fifty nine, six years after he moved to Edinburgh to work with Sime who was then thirty two, applied for and was given a prominent surgery professorship at the University of Glasgow.

Although at the time the academic atmosphere at Glasgow was conservative where Edinburgh was daring traditional, while Edinburgh lean progressive. New Hires like Lister were injecting a bit of freshness into the university, which attracted more and more medical students, students who loved their new professor for his riveting lectures

focus on clarity and modern thinking. Alongside his appointment at the university, Lister was also given a position at the city's hospital, which he viewed as essential for connecting theory and practice, demonstrating the procedures that he had lectured about in class. Even though the surgical ward that Lister was assigned to was basically newly constructed, it was already filthy.

All the classic infections haunted the wards. The graveyard was constantly overflowing, and there was practically nowhere to wash your hands or instruments or bed linens, even like the surgical tools that were used were ornately carved, which meant that they were impossible to clean if the surgeon actually attempted to clean it at all.

to prevent these post surgery dens, starting with cleanliness. The concept of cleanliness has not remained constant throughout history.

New ideas were continually being proposed, such as cleanliness and cold water, which held that surgical instruments should be cleaned with water that had been boiled and then allowed to cool. And the idea behind this was that cold water was supposed to prevent the heat that caused fever and inflammation.

or black thereof. It didn't seem to do anything. He expressed his frustration to his students, saying, quote, it is a common observation that when some injury is received without the skin being broken, the patient invariably recovers, and that without any severe illness. On the other hand, trouble of the gravest kind is always apt to follow, even in trivial injuries, when a wound of the skin is present. How is this? The man who is able to explain

this problem will gain undying fame. Ha ha I know end quote. As eighteen sixty four drew to a close, Lister was still deep in his depression over the seemingly inevitable death of his patients when a colleague brought some new articles to his attention, research involving fermentation and putrefaction, authored by

none other than Louis Pasture HM. In these articles, Pasture noted that microscopic rod shaped organisms were found in spoiled wine, and he believed that they were responsible for the spoilage. But he also looked beyond wine, proposing that these tiny germs were also responsible for certain diseases in humans and

other animals. Pasture's ideas were met with quite a bit of resistance and ridicule from the medical and scientific community, but Lister found them exciting and felt hopeful that the answers he had long been looking for it might be found in these articles. To Lister, this concept of germ theory explained why disease appeared after surgery and how it could be spread from one person to the next, all

the way down the ward. He wasn't entirely right in his conclusions, believing that it was microbes carried in the air rather than like on instruments, for instance, but he was on the right track enough to try out some infection control strategies, namely by attacking these germs after their introduction into the wound. On this he also turned to Pasture, who had demonstrated that these germs could be killed by

any number of different things. Heat or filtration couldn't really be put to practical use for Lister, so he turned towards finding an antiseptic that would kill germs on contact. Again, this was not an entirely new notion. Aniseptics had been used by surgeons for years to irrigate wounds, but two main things prevented them from being recognized as incredibly powerful

sepsis prevention tools. The first was that surgeons typically waited to use the antiseptic on a wound until it was obviously infected, at which point there was little the aniseptic could do because the infection was likely systemic. And second was that the antiseptics themselves often caused substantial damage to the surrounding skin, allowing for further infection. Because of this, the jury was still out on the value of aniseptics

in medicine. Lister wondered if there was more to the story of aniseptics, though, so he decided to test different ones out to see which were the most effective in preventing infection. Instead of waiting for the pus to be freely flowing and the surrounding skin hot and tight and red with inflammation, he applied the aniseptics prof lactically and

waited to see which one did the best. After going through a few that didn't show much promise, he reached for the carbolic acid aka phenol, remembering that he had heard carbolic acid was sometimes used at sewage works to counteract the smell of rotting liquid waste. Yeah, he thought, if it can cover up those horrific smells, maybe it'll kill whatever is putrefying these wounds. And I feel like

that was also Semmelweis's train of thought. But yeah, carbolic acid didn't work that great on the first two people he tried it out on, but the third time was the charm. In August of eighteen sixty five, eleven year old James Greenlea's was brought to Lister's Hospital three hours after his leg had been crushed under a cart, tibia cracked and jutting through his skin.

wanted to see what he could do. He put the boy under chloroform and went to work cleaning out the wound as best he could with dilute carbolic acid and getting the bone reset, And he continued to take meticulous care of the wound over the next days and weeks, carefully cleaning it with carbolic acid and putting some olive oil on as a soother, and checking for signs of infection.

Six weeks and two days after James Greenlea's had been carried into the hospital with his horrifically broken leg, he walked out on his own.

On March sixteenth, eighteen sixty seven, two years after he first began experimenting with carbolic acid, Lister published the first part of a five part article in The Lancet describing his findings quote on a new method of treating compound fracture, absess etc. With Observations on the conditions of separation. This was not only groundbreaking in its support for germ theory, but his articles also provided step by step instructions to

prevent post operative infections. The Glasgow Royal Infirmary where Lister worked, went from being among the deadliest to the cleanest with the lowest mortality rates. Wow, Lister wrote, quote, I now perform an operation for the removal of a tumor, etc. With a totally different feeling from what I used to have. In fact, surgery is becoming a different thing altogether. End quote.

But there was quite a bit of resistance and even ridicule in response to his ideas of antisepsis, most notably from the famous surgeon James Y. Simpson, who had first introduced the use of chloroform as anesthesia and was a big proponent of acute pressure for sepsis prevention, which didn't work. Simpson seemed to have a personal vendetta against blister. Maybe he was frustrated that no one seemed to like acutpressure.

Maybe he felt protective of his own fame and was jealous of Lister, but there did seem to be a variety of reasons that Simpson and others were so quick to dismiss Lister's ideas.

they were supposed to have been helping. Lister fought the disappointment he felt from all this criticism by focusing his efforts on improving surgery in other ways, such as changing the material that the ligatures were made of to catgut, which could be absorbed by the body and reduce the risk of infection. He also concentrated on teaching, realizing that well, if he couldn't convince older generations of doctors of his methods,

then he could train the new ones. Over the next few years, years in which so many people continued to die because their surgeons refused to test out Lister's techniques, Lister kept at it, touring across the US to give talks where some hospitals like Mass General for example, had actually banned Lister's techniques, and then later it became they were like the first hospital to make it hospital policy to practice wow and also continuing to publish his results.

I hate that this is a lesson in published, publish, published, but whatever, it all paid off. The medical community grew to accept Lister's carbolic acid practices in preventing post surgical infection, and the enormous contribution he made to the field of not just surgery but all of medicine was recognized in

his lifetime. Unlike so many of the other people that we talk about on this podcast, Yeah, Lister spent the rest of his life showered in awards, accolades, honorary degrees, and was even given the dubious honor of having a hygiene product created in his name of Lister Reade.

Lister's antiseptic techniques kicked off a craze for antiseptic products and inspired someone named Robert Wood Johnson, who had also seen Lister speak, to join up with his brothers to start a company manufacturing sterile surgical dressings and sutures. They named it Johnson and Johnson.

hospital sepsis cases dropped tremendously. Over the next decades, Researchers learned more about the underlying pathophysiology of sepsis, such as the role of endotoxins and the immune system response, and they discovered new ways to diagnose and treat the condition. In the one hundred and fifty five years since Lister published his article, We've come so far and learned so much about sepsis, but as we can gather from the biology section, we have still so very far to go.

And I really hope I haven't disappointed anyone too very much by skipping over most of the recent history of sepsis and the changing definitions. But I figured, Aarin, that you could at least bring us up to speed with sepsis today.

sepsis related deaths. If those numbers are accurate. Like again, these are estimates, that would be almost twenty percent of all global deaths, the vast majority of which, it's estimated eighty five percent of those sepsis related deaths are in low and middle income countries that we just aren't getting good data on.

mortality rate can vary quite a lot. Some papers just that try and estimate it overall, say anywhere between one in three and one in six people with sepsis can die, and so the World Health Organization has understandably made this a huge campaign and a priority as well as the

Surviving Sepsis campaign that I mentioned already. One of the big things that the Surviving Sepsis campaign tries to do, in addition to raising awareness is also just gathering data and analyzing that data in a way to try and actually improve outcomes. And one of the big issues with the data that exists so far is that it generally comes from very high income countries, and so we have to recognize the limitations in how we can interpret and

then apply that data to much less resource rich areas. Right, and importantly, all of these kind of campaigns and policies are largely, like I said, trying to improve outcomes as well as improve our recognition of sepsis and how we treat it to reduce morbidity and reduce mortality.

don't we do not understand it. And so this article really laid out what they feel at least are the major deficits in our understanding and where we should go from here. They did this by looking at three different stages of sepsis before it develops, which is my favorite stage to think about, very important. Who is at risk,

why are they at risk? What kinds of research do we even need to do to better understand this initial process and these specific risks to be able to actually pre event sepsis to begin with.

because these are too broad. So anything that we have tried to do to modulate the immune system ends up making things worse rather than better when it comes to sepsis. So far, and finally the third stage post sepsis, like what are the consequences of having a severe sepsis infection in the long term and what can some of these

consequences teach us about the underlying pathology of secsis. We don't have answers to those, but I think it's just kind of a nice framework to think about where we can go from here.

any other underlying immune conditions that we know of. Of course, there's so much individual immune response differences that we just don't know about. It's a good question as to whether you are at higher risk or not. I think we don't probably know enough to know in those instances.