WEBVTT - Ep 107 Sepsis: It's a mess 0:00:02.000 --> 0:00:04.640 Hi. My name is Katie Granger, and four years ago 0:00:04.680 --> 0:00:07.920 this month, I lost seven of my fingertips and both 0:00:07.960 --> 0:00:11.440 of my lower legs to sepsis. One thing that's interesting 0:00:11.440 --> 0:00:13.760 about my story is that the reason that it got 0:00:13.760 --> 0:00:16.640 so severe with me I actually ended up in septic shock, 0:00:16.840 --> 0:00:18.840 is because I did not know the signs and symptoms. 0:00:18.840 --> 0:00:20.960 So when I tell my story, I can't stop myself 0:00:20.960 --> 0:00:24.000 from kind of highlighting where I made some mistakes. So 0:00:24.239 --> 0:00:26.880 in September of twenty eighteen, I was living in Hawaii 0:00:26.960 --> 0:00:30.400 with my husband. We were new empty nesters and I 0:00:30.440 --> 0:00:33.640 had just gone to visit my kids in California for 0:00:33.720 --> 0:00:36.320 a week and my husband had taken that opportunity to 0:00:36.320 --> 0:00:39.760 go on a fishing trip to very remote Idaho. So 0:00:39.880 --> 0:00:42.680 went down to California, hung out with my kids, and 0:00:42.720 --> 0:00:45.159 then it was time to return back to Hawaii. I 0:00:45.200 --> 0:00:47.440 got on an airplane flew home, and when I got 0:00:47.479 --> 0:00:50.360 to the airport, this is when I remember noticing that 0:00:50.440 --> 0:00:52.440 I had this bump on my finger and it was oozing. 0:00:52.560 --> 0:00:54.960 It was kind of pink, and it had clear fluid 0:00:54.960 --> 0:00:56.840 coming out of it, so it looked different than anything 0:00:56.880 --> 0:00:59.400 I'd seen before. So I was on my way home 0:01:00.080 --> 0:01:02.360 my house is actually an hour from the airport. It's 0:01:02.400 --> 0:01:04.080 also an hour from the hospital, which is going to 0:01:04.120 --> 0:01:06.480 be relevant later on, so I did decide to go 0:01:06.480 --> 0:01:09.080 buy the emergency clinic. When I got there, I showed 0:01:09.080 --> 0:01:11.080 them the cut and they agreed that it did look 0:01:11.080 --> 0:01:14.040 infected and looked like it could possibly be MRSA. They 0:01:14.120 --> 0:01:16.199 took a little swab of it and said basically they'd 0:01:16.200 --> 0:01:18.680 call me in a few days if anything grew out 0:01:18.680 --> 0:01:20.520 of it. So they gave me a prescription for antibiotics, 0:01:20.520 --> 0:01:21.760 and they said to start taking them if it got 0:01:21.800 --> 0:01:24.600 worse over the weekend. At the emergency clinic, when they 0:01:24.680 --> 0:01:27.399 checked my vital signs, everything was great, so they didn't 0:01:27.400 --> 0:01:29.520 have any indication that I had sepsis at this point, 0:01:29.520 --> 0:01:32.280 and I really didn't. I just had an infection. So 0:01:32.520 --> 0:01:35.199 on Saturday morning, I woke up, I happed in the shower. 0:01:35.360 --> 0:01:37.360 It was warm there in Hawaii, I was kind of warm, 0:01:37.480 --> 0:01:40.199 but I never was registering a fever, so I didn't 0:01:40.200 --> 0:01:42.840 think there was anything wrong. I did notice that the 0:01:42.840 --> 0:01:44.720 infection on my finger was getting a little worse, so 0:01:44.800 --> 0:01:47.440 I went ahead and took an antibiotic. Well soon thereafter, 0:01:47.480 --> 0:01:50.120 I threw up, but I just thought it was because 0:01:50.120 --> 0:01:52.360 I'd taken an antibiotic on an empty stomach, and I 0:01:52.360 --> 0:01:55.200 wrote it off. But I ended up sleeping through the 0:01:55.200 --> 0:01:58.880 afternoon and sleeping through the evening, and sometime in the 0:01:58.920 --> 0:02:00.600 middle of the night, I got up and I probably 0:02:00.600 --> 0:02:02.640 went into the bathroom, which is two steps up from 0:02:02.640 --> 0:02:05.200 my bedroom. And what we think may have happened is 0:02:05.200 --> 0:02:08.240 that I maybe stood up quickly and low blood pressure 0:02:08.240 --> 0:02:10.679 in my body caused me to pass out. But what 0:02:10.800 --> 0:02:13.079 the result was is that I broke my left foot, 0:02:13.200 --> 0:02:16.240 I sprayed my right ankle, and I had just a 0:02:16.280 --> 0:02:18.040 mark on my kneehere I had fallen on the floor. 0:02:18.600 --> 0:02:20.919 So this is a sign for me of mental decline, 0:02:20.919 --> 0:02:23.720 because instead of calling for help like a normal person would, 0:02:23.800 --> 0:02:26.920 I crawled back in bed. So the next morning was Sunday, 0:02:27.440 --> 0:02:29.240 and I woke up at sunrise, like at the crack 0:02:29.280 --> 0:02:31.120 of dawn. I could hear the roosters outside. It was 0:02:31.120 --> 0:02:35.120 still dark, and I don't really remember much. I do 0:02:35.280 --> 0:02:37.160 know that I texted my friend and I said to 0:02:37.200 --> 0:02:39.400 my friend, can you take me to the hospital. She 0:02:39.440 --> 0:02:41.120 asked if we could go to the emergency clinic, and 0:02:41.120 --> 0:02:44.200 I said no. I have never been so sick So 0:02:44.280 --> 0:02:46.680 my friend took this seriously, as one should. She came 0:02:46.760 --> 0:02:49.320 right down to my house, let herself in, and she 0:02:49.400 --> 0:02:52.400 found me nearly unresponsive in my bed, and we tried 0:02:52.400 --> 0:02:54.040 to stand up, and that's when we realized that my 0:02:54.080 --> 0:02:56.079 feet hurt. We found out later that it was the 0:02:56.120 --> 0:02:57.960 break in the one foot, and then I also could 0:02:58.000 --> 0:03:00.360 have had some nerve pain from something you're going to 0:03:00.360 --> 0:03:03.000 hear about in a second. But it was about an 0:03:03.000 --> 0:03:05.880 hour drive and about fifteen minutes out, I started crying 0:03:05.880 --> 0:03:08.200 in the backseat, saying, are we there yet? Are we close? 0:03:08.600 --> 0:03:11.000 My hands and feet are on fire. So she went 0:03:11.040 --> 0:03:13.240 ahead and called the hospital and let them know that 0:03:13.280 --> 0:03:15.560 we were coming in. When we got to the hospital, 0:03:15.560 --> 0:03:17.160 they met us with a gurney. They got me out 0:03:17.160 --> 0:03:19.120 of the car, loaded me onto it, They took me 0:03:19.240 --> 0:03:21.760 right into the emergency room, and they did the things 0:03:21.760 --> 0:03:23.960 that they should do. It took my vital signs. So 0:03:24.000 --> 0:03:25.720 it turns out that my blood pressure at that point 0:03:25.760 --> 0:03:30.120 was fifty over thirty, which is extremely low. And it's 0:03:30.120 --> 0:03:31.800 funny because I've read my chart and they said I 0:03:31.840 --> 0:03:34.360 was conversive and pleasant, and I'm like, well that's my 0:03:34.880 --> 0:03:37.920 go to. I mean, I was faking conversive and pleasant. 0:03:38.320 --> 0:03:40.080 I also had an increased heart rate and I had 0:03:40.120 --> 0:03:43.440 low blood oxygen, so they immediately put an oxygen canulate 0:03:43.480 --> 0:03:46.480 in my nose just to let me breathe oxygen. Later 0:03:46.520 --> 0:03:48.440 in the day, the oxygen levels got worse and I 0:03:48.440 --> 0:03:51.160 actually had a mask forcing air into my lungs. So 0:03:51.240 --> 0:03:55.000 what was happening is that my organs began failing. I 0:03:55.040 --> 0:03:57.520 stopped urinating, so that was a sign that my kidneys 0:03:57.520 --> 0:03:59.680 were failing, and it was becoming really clear that I 0:03:59.760 --> 0:04:02.160 was at higher levels of steps is called septic shock. 0:04:02.760 --> 0:04:04.800 The whole thing with my hands and fingers are on 0:04:04.880 --> 0:04:08.800 fire is showing that my circulation at my extremities was very, 0:04:09.040 --> 0:04:13.440 very bad, and my fingers began turning purple, and so 0:04:13.600 --> 0:04:15.760 did my toes, although I didn't see them at the beginning. 0:04:16.240 --> 0:04:18.640 I ended up having a condition later that they diagnosed 0:04:18.640 --> 0:04:23.279 called disseminated intravascular coagulation. So if this had not happened 0:04:23.279 --> 0:04:26.320 in the hospital, I would have run out of platelets. 0:04:26.800 --> 0:04:29.080 So at that point in time, I was on an 0:04:29.080 --> 0:04:31.360 outer island in Hawaii. We lived on the island of Kawaii. 0:04:31.680 --> 0:04:33.440 Anyone in Hawaii, if you get sick on an outer 0:04:33.560 --> 0:04:35.279 Island and you get very sick and you need an 0:04:35.480 --> 0:04:39.480 ICU or you need severe help, they will transport you 0:04:39.880 --> 0:04:42.120 by air ambulance over to a Wahoo, which is where 0:04:42.120 --> 0:04:45.560 Honolulu is. So on Monday morning a bed became available 0:04:45.600 --> 0:04:48.360 at the hospital at Queen's Hospital, it was decided that 0:04:48.360 --> 0:04:51.240 they would fly me over to Honolulu. So they ended 0:04:51.279 --> 0:04:53.360 up giving medication to put me in a drug and discoma. 0:04:53.760 --> 0:04:56.240 They intubated me and they sent me over to a Wahoo. 0:04:57.000 --> 0:04:59.440 When I got there, my husband had, actually, thank goodness, 0:04:59.440 --> 0:05:01.880 had landed on a Wahoo about an hour before I did, 0:05:01.920 --> 0:05:03.320 so he was able to meet me at the hospital, 0:05:03.400 --> 0:05:05.840 so now I have my family with me. When they 0:05:05.839 --> 0:05:08.440 came out, they told him that I was not stable, 0:05:08.560 --> 0:05:11.840 and that started asking questions like does she have a will, 0:05:12.440 --> 0:05:14.800 and what are her desires? If we need to do 0:05:14.960 --> 0:05:17.880 you know, if we need to resuscitate. But they did 0:05:17.920 --> 0:05:20.479 say that he should call our children, who again were 0:05:20.480 --> 0:05:23.200 in California and have them come because they weren't sure 0:05:23.200 --> 0:05:25.320 I was going to make it. So my family was 0:05:25.320 --> 0:05:27.039 by my side for five days as I sat in 0:05:27.040 --> 0:05:30.960 the ICU, or as I laid in the ICU, and 0:05:31.000 --> 0:05:33.760 they were praying over me and watching my hands and 0:05:33.800 --> 0:05:36.120 feet turn more and more purple up to my wrists 0:05:36.120 --> 0:05:38.960 and up to my ankles, and it became clear, I 0:05:38.960 --> 0:05:40.960 think to them during that week that I was going 0:05:41.000 --> 0:05:45.080 to lose at least my fingers and toes, and likely 0:05:45.160 --> 0:05:48.599 more than that. On my daughter's twenty third birthday, my 0:05:48.640 --> 0:05:51.000 oldest daughter's twenty third birthday, which was five days later, 0:05:51.080 --> 0:05:52.960 I woke up and when that happened, I saw my 0:05:53.040 --> 0:05:55.080 husband in front of me, and he got right into 0:05:55.080 --> 0:05:57.280 my face to just let me know he was there, 0:05:57.400 --> 0:05:59.359 and then everything was going to be okay. I was 0:05:59.440 --> 0:06:02.080 extremely confused. But one thing that happened is I saw 0:06:02.080 --> 0:06:04.920 my fingers go in front of my face and seven 0:06:05.000 --> 0:06:08.160 my fingertips were black. My thumbs, the tips of my 0:06:08.200 --> 0:06:10.160 thumbs were black. It looked like I was going to 0:06:10.240 --> 0:06:13.479 lose all of my fingers, and I was absolutely terrified. 0:06:13.560 --> 0:06:16.080 I didn't know what had happened. I mean, whilst I remembered, 0:06:16.120 --> 0:06:18.159 I was being cheerful talking to people in the hospital, 0:06:18.320 --> 0:06:21.600 and then I'm waking up and I'm realizing that I 0:06:21.640 --> 0:06:23.680 can see these clearly dead fingers. I realized I'm going 0:06:23.760 --> 0:06:26.680 to lose these fingers. So we spent three weeks at 0:06:26.720 --> 0:06:31.279 the hospital, doing hyperbaric chamber every day and doing nitrogliscer 0:06:31.279 --> 0:06:33.839 and cream on my hands and feet three times a day. 0:06:34.240 --> 0:06:36.880 It was extremely painful, but we were able to save 0:06:36.920 --> 0:06:39.400 my hands. Right now, I have my hands and most 0:06:39.400 --> 0:06:42.120 of my fingers up to those seven tips that were black. 0:06:42.279 --> 0:06:44.279 My thumbs are fine. I have them one hundred percent. 0:06:44.640 --> 0:06:47.839 I'm really fortunate that that's what my outcome was. At 0:06:47.839 --> 0:06:50.080 the time, I was really trying hard to save my feet, 0:06:50.120 --> 0:06:52.000 and I was having a hard, as you can imagine, 0:06:52.040 --> 0:06:54.560 a very hard time admitting that we might not be 0:06:54.600 --> 0:06:57.000 able to After three weeks, I finally looked at my 0:06:57.040 --> 0:06:59.960 husband and said, I understand that we can't save my feet, 0:07:00.560 --> 0:07:02.760 and I just want to move on to whatever the 0:07:02.800 --> 0:07:06.080 next steps are after. You know, after a couple months, 0:07:06.120 --> 0:07:09.920 I got the amputations. I did recovery at home. I 0:07:10.000 --> 0:07:12.840 got my prosthetic legs right around Christmas time. This happened 0:07:12.880 --> 0:07:16.160 in the middle of September. Initially and I was able 0:07:16.160 --> 0:07:18.400 to stand on them immediately, but it was painful, so 0:07:18.760 --> 0:07:21.760 I just built up my tolerance to walking around in 0:07:21.800 --> 0:07:23.800 them just slowly. I stayed in my wheelchair a lot 0:07:23.840 --> 0:07:27.280 of the time and Anyways, I started getting better and 0:07:27.320 --> 0:07:29.320 I started realizing I could get my life back. I 0:07:29.400 --> 0:07:32.200 went and visited my daughter who she went to Rome 0:07:32.480 --> 0:07:34.920 for study abroad, and my husband and my best friend 0:07:35.040 --> 0:07:37.080 arranged for me to go as well, so I got 0:07:37.080 --> 0:07:39.040 to go visit her like I had always dreamed of doing. 0:07:39.280 --> 0:07:42.080 And since then I'm living a really full life. A 0:07:42.160 --> 0:07:44.240 year later, I was invited onto the board of directors 0:07:44.240 --> 0:07:46.320 of Sepsist Alliance and now I share my story to 0:07:46.320 --> 0:07:47.080 spread awareness. 0:08:34.600 --> 0:08:38.840 Katie, thank you so so much for being willing to 0:08:38.880 --> 0:08:41.840 share your story and taking the time to tell your story. 0:08:43.080 --> 0:08:43.920 It's terrifying. 0:08:44.080 --> 0:08:46.440 It's terrifying. And thank you too for all of the 0:08:46.480 --> 0:08:49.760 work that you do raising awareness and sharing your story, 0:08:49.800 --> 0:08:51.640 not just with us, but with so many people. 0:08:52.040 --> 0:08:53.920 Yeah, it's amazing. 0:08:54.440 --> 0:08:55.480 Yeah. 0:08:55.480 --> 0:08:59.560 Well hi, I'm erin Welsh and I'm Aaron Allman updyke. 0:09:00.160 --> 0:09:01.960 This is this podcast will kill you. 0:09:02.360 --> 0:09:06.679 It's a big old episode today, it really really is. 0:09:07.000 --> 0:09:07.760 It's a big one. 0:09:08.000 --> 0:09:08.400 It is. 0:09:08.960 --> 0:09:14.840 We're covering sepsis. Fish is not like a one size 0:09:14.880 --> 0:09:16.199 fits all definition. 0:09:16.640 --> 0:09:17.520 Oh I can't wait. 0:09:17.559 --> 0:09:20.680 I have a whole paragraph called definition. Never had that before. 0:09:22.679 --> 0:09:27.679 Yeah, it's it's a big one, but it's also tremendously important, 0:09:27.720 --> 0:09:30.080 and I don't think I realized before we started digging 0:09:30.080 --> 0:09:36.520 into this just how prevalent and scary and kind of 0:09:36.559 --> 0:09:38.600 still there are a lot of open questions. 0:09:38.840 --> 0:09:42.000 Oh, Aaron, I feel like all I have are open 0:09:42.080 --> 0:09:46.720 questions when it comes to sepsis. So yeah, it's gonna 0:09:46.720 --> 0:09:49.800 be probably heavy at times, but it's gonna be I think, 0:09:49.800 --> 0:09:51.600 a really good episode and really interesting. 0:09:51.960 --> 0:09:56.040 Yeah, yeah, for sure. Well, should we start off this 0:09:56.200 --> 0:10:00.600 episode like we do every other episode with the Quarantiny, 0:10:00.679 --> 0:10:03.440 time with the quarantin any time? What are we drinking 0:10:03.480 --> 0:10:04.040 this week? 0:10:04.480 --> 0:10:10.000 We're drinking let Us Spray. I love it so much. 0:10:10.480 --> 0:10:14.880 I do too. So this is a reference to Joseph 0:10:14.920 --> 0:10:18.480 Lister and his carbolic acid spray, which will make up 0:10:18.559 --> 0:10:22.040 a big part of the history section later on in 0:10:22.080 --> 0:10:24.320 the episode. And I just want to give credit to 0:10:24.640 --> 0:10:28.080 Doug for giving us the idea to use this as 0:10:28.200 --> 0:10:30.559 our Quarantini title. It is one of my favorites. 0:10:30.679 --> 0:10:34.760 It's really fantastic, Thanks Doug, Aaron. What is in let 0:10:34.840 --> 0:10:35.440 us Spray? 0:10:35.760 --> 0:10:40.240 Let Us Spray is a delicious little blended cocktail with 0:10:40.520 --> 0:10:45.400 cherries and ice cream and lime juice and maybe some 0:10:45.440 --> 0:10:48.080 whipped cream on top. Oh and some vodka if you 0:10:48.120 --> 0:10:52.760 want to toss that in there. Yeah, And we will 0:10:52.760 --> 0:10:56.320 post the full recipe for let us spray both the 0:10:56.440 --> 0:10:59.640 quarantini as well as the non alcoholic Plasy Burta on 0:10:59.679 --> 0:11:02.439 our website This podcast will Kill You dot com, as 0:11:02.480 --> 0:11:04.319 well as on all of our social media. 0:11:04.120 --> 0:11:07.760 Channels any other business narn I don't think so. 0:11:08.080 --> 0:11:10.319 I think we should just get started because I have 0:11:10.360 --> 0:11:12.280 the feeling this is going to be a big episode. 0:11:12.400 --> 0:11:13.480 Oh, it's going to be great. 0:11:13.840 --> 0:11:16.439 We will take a short break and then get into it. 0:11:43.320 --> 0:11:49.080 I think, probably more so than any condition or infection 0:11:49.280 --> 0:11:54.160 or disease that we've covered on this podcast, sepsis is 0:11:54.160 --> 0:12:00.480 something where the actual definitions of sepsis have changed so. 0:12:00.160 --> 0:12:02.520 Many times, even in recent years. 0:12:02.600 --> 0:12:06.240 So I can't wait to compare, like how we identify 0:12:06.280 --> 0:12:09.119 sepsis today to how we understood it historically. 0:12:09.880 --> 0:12:11.840 I don't know if I'm going to be going into 0:12:11.920 --> 0:12:13.719 any of that, oh. 0:12:13.360 --> 0:12:16.640 But I bet we'll learn a lot about it perhaps. 0:12:18.040 --> 0:12:19.920 But so what I wanted to start off with was 0:12:20.040 --> 0:12:24.559 just what are the definitions of sepsis? Because there's kind 0:12:24.600 --> 0:12:27.720 of a lot floating out there. So here's one from 0:12:27.760 --> 0:12:32.080 a twenty nineteen paper. I will quote quote sepsis is 0:12:32.120 --> 0:12:37.160 a medical emergency that describes the body's systemic immunological response 0:12:37.320 --> 0:12:40.640 to an infectious process that can lead to end stage 0:12:40.800 --> 0:12:42.520 organ dysfunction and death. 0:12:43.400 --> 0:12:45.439 Boom boom boom. 0:12:45.800 --> 0:12:51.840 Another that comes from the Third International Consensus Definition's task 0:12:51.920 --> 0:12:55.520 Force and is kind of the consensus definition known as 0:12:55.559 --> 0:13:00.720 sepsis three. The third iteration of this is a bit shorter. 0:13:01.320 --> 0:13:05.160 Sepsis is a life threatening organ dysfunction caused by a 0:13:05.320 --> 0:13:08.280 disregulated host response to infection. 0:13:09.240 --> 0:13:11.000 Okay, that makes sense, right. 0:13:10.960 --> 0:13:11.360 It does. 0:13:12.200 --> 0:13:16.800 And they go further to then identify a specific subset 0:13:16.840 --> 0:13:19.960 of sepsis, and that is septic shock, which is a 0:13:20.000 --> 0:13:26.040 subset of sepsis in which underlying circulatory, cellular, and metabolic 0:13:26.160 --> 0:13:32.200 abnormalities are severe enough to substantially increase the risk of mortality. 0:13:32.520 --> 0:13:35.080 Basically, very very serious and severe. 0:13:37.000 --> 0:13:41.600 But even that definition of sepsis and septic shock, even 0:13:41.640 --> 0:13:46.440 though they are considered consensus definitions, have changed a lot 0:13:46.520 --> 0:13:51.640 over time, and even today that definition doesn't necessarily precisely 0:13:51.679 --> 0:13:55.640 apply in pediatric populations, which happen to be at particular 0:13:55.760 --> 0:14:00.000 risk for sepsis. As we'll talk about later, So because 0:14:00.000 --> 0:14:03.040 what does the definitions of sepsis have changed over time? 0:14:03.160 --> 0:14:06.880 So has the diagnosis or the criteria that are used 0:14:06.920 --> 0:14:07.680 to diagnose it. 0:14:08.520 --> 0:14:09.479 And I think. 0:14:09.240 --> 0:14:12.680 That that's kind of the best way to think about sepsis. 0:14:13.160 --> 0:14:17.200 It is a process, but it's also a diagnosis that's 0:14:17.360 --> 0:14:22.000 used to kind of triage and determine management if somebody. 0:14:21.760 --> 0:14:24.240 Ends up in a hospital setting. Does that make sense? 0:14:24.680 --> 0:14:30.040 Yeah, And it's interesting that the criteria have changed so much, Like, 0:14:30.320 --> 0:14:34.440 first of all, why is that? And second of all, 0:14:34.480 --> 0:14:37.320 how has that affected this maybe like way jumping the gun, 0:14:37.360 --> 0:14:41.280 but how has that affected more current numbers or being 0:14:41.280 --> 0:14:45.160 able to compare throughout even the past few decades. Yeah, 0:14:45.160 --> 0:14:47.880 how our ability to control sepsis has changed? 0:14:48.640 --> 0:14:53.680 That's that is all very important and really good questions. Basically, 0:14:53.800 --> 0:14:56.560 it's made it difficult. So our numbers on sepsis, as 0:14:56.560 --> 0:14:59.640 we'll talk about later in this episode, aren't great, especially 0:14:59.680 --> 0:15:02.320 our nderstanding of the rates of sepsis and control of 0:15:02.360 --> 0:15:06.120 sepsis in low and middle income countries. And you do 0:15:06.240 --> 0:15:10.040 have to kind of take into consideration every study that's done, 0:15:10.200 --> 0:15:13.480 what were the criteria that were used to identify sepsis 0:15:13.560 --> 0:15:17.640 versus to rule people out for sepsis or whatever. But 0:15:17.720 --> 0:15:20.800 basically the definitions have changed in part because of our 0:15:20.880 --> 0:15:24.760 understanding of sepsis and what the underlying causes are, as 0:15:24.800 --> 0:15:29.160 well as how we identify it in an emergency setting, 0:15:29.240 --> 0:15:32.520 for example. And the truth is there are a whole 0:15:32.640 --> 0:15:36.440 host of what are often called screening tools that are 0:15:36.520 --> 0:15:42.040 used to kind of identify, in ideally a highly sensitive way, 0:15:42.240 --> 0:15:45.600 what people might either have sepsis or be at high 0:15:45.720 --> 0:15:49.600 risk for sepsis. One of these screening tools is called 0:15:49.800 --> 0:15:56.880 sers SIRS. It stands for systemic inflammatory response syndrome, and 0:15:56.920 --> 0:16:00.720 these criteria are like an increased or decreased temper, an 0:16:00.800 --> 0:16:04.480 increased heart rate, an increased respiratory rate, an increased white 0:16:04.520 --> 0:16:08.040 blood cell count, or a severely decreased white blood cell count, 0:16:08.960 --> 0:16:12.680 things like that. So having two of those criteria and 0:16:13.240 --> 0:16:17.520 a known or suspected source of an infection would in 0:16:17.560 --> 0:16:20.680 a lot of cases rule people in so make us 0:16:20.720 --> 0:16:23.360 think this person has sepsis. We're going to call them 0:16:23.480 --> 0:16:29.160 stepsis until proven otherwise. There are a lot of other criteria. 0:16:29.280 --> 0:16:33.479 There's the SOFA, which stands for sequential organ failure assessment, 0:16:33.640 --> 0:16:37.120 which is mostly based on a list of laboratory values 0:16:37.240 --> 0:16:41.280 or respiratory status values to kind of try and determine 0:16:41.600 --> 0:16:45.920 and triage the degree of organ damage. So getting a 0:16:45.920 --> 0:16:49.240 certain score on that screening tool plus having a known 0:16:49.360 --> 0:16:52.640 or suspected infection would then meet criteria for sepsis. But 0:16:52.640 --> 0:16:55.560 there are also a lot of others. There's one called NEWS, 0:16:55.600 --> 0:16:59.000 there's one called MUSE. There's likely different versions in different 0:16:59.000 --> 0:17:00.520 countries that I don't even know about. 0:17:01.200 --> 0:17:04.480 And so what determines which screening tool you use is 0:17:04.640 --> 0:17:07.000 just where you are or what hospital you work in. 0:17:07.720 --> 0:17:10.239 Exactly that where you are and what hospital you work in, 0:17:10.520 --> 0:17:13.800 so I can tell you we use SERS very often. 0:17:14.680 --> 0:17:18.240 SURS has a number of detractors, and it definitely is 0:17:18.359 --> 0:17:19.920 not a perfect screening tool. 0:17:20.000 --> 0:17:23.760 No screening tool is perfect, but it is used. 0:17:23.640 --> 0:17:27.879 Very often as one of these possible screening tools. Now, 0:17:27.960 --> 0:17:30.960 there is an organization I think you would call it 0:17:31.000 --> 0:17:34.680 an organization. It's called the Surviving Sepsis Campaign, and it's 0:17:34.680 --> 0:17:39.920 an international organization that really tries to go through all 0:17:39.960 --> 0:17:42.840 of the data that we have on sepsis and outcomes 0:17:42.840 --> 0:17:46.760 of sepsis and come up with a consensus set of 0:17:46.800 --> 0:17:53.399 guidelines on how to identify, diagnose, and manage sepsis in 0:17:53.440 --> 0:17:56.280 the hospital and ic you setting, and so they have 0:17:56.359 --> 0:17:58.800 like a set of guidelines and things where they say, 0:17:58.840 --> 0:18:01.080 you know, this screening tool is not the best and 0:18:01.119 --> 0:18:03.359 this one is okay, and et cetera, et cetera. 0:18:04.520 --> 0:18:07.760 I have a question, okay, so about the number of 0:18:07.800 --> 0:18:12.320 all these screening tools. Yeah, does that mean that sepsis 0:18:12.560 --> 0:18:17.000 is difficult to recognize because the symptoms are varied? Or 0:18:17.119 --> 0:18:19.160 is it because there are a lot of other things 0:18:19.160 --> 0:18:21.600 that can look like sepsis and a treatment is different. 0:18:22.040 --> 0:18:25.400 Yes, and both, Okay, Okay. 0:18:25.080 --> 0:18:28.399 So yeah, it's hard to tell you exactly what these 0:18:28.480 --> 0:18:35.920 symptoms of sepsis are because they're incredibly nonspecific. So, in general, 0:18:36.080 --> 0:18:40.960 according to our definition, people have some sign of an infection. 0:18:41.320 --> 0:18:43.320 This could be a pneumonia, which. 0:18:43.160 --> 0:18:45.560 Tends to be, at least in hospital settings, the most 0:18:45.720 --> 0:18:49.880 common identified cause of sepsis, but certainly not the only one. 0:18:50.600 --> 0:18:54.440 It could be like a urinary infection. It could be cellulaitis. 0:18:54.520 --> 0:18:57.520 It could be a tiny cut on your finger, so 0:18:57.560 --> 0:19:01.040 that could be the initial infection. But then in terms 0:19:01.040 --> 0:19:03.960 of the other symptoms that you might see, people may 0:19:04.119 --> 0:19:07.560 or may not have a fever, They may or may 0:19:07.600 --> 0:19:11.280 not have an elevated heart rate as like a physiologic 0:19:11.359 --> 0:19:15.320 response to this infection. They may or may not have 0:19:15.600 --> 0:19:19.080 difficulty breathing, or if you put an oxygen meter on them, 0:19:19.119 --> 0:19:21.920 have hypoxia, decrease in their oxygen status. 0:19:22.640 --> 0:19:23.919 They may or may not. 0:19:24.040 --> 0:19:27.880 Already have progressed to the point of hypotension, so decrease 0:19:27.920 --> 0:19:30.720 blood pressure, which is when you're getting into the point 0:19:30.720 --> 0:19:32.439 of having septic shock. 0:19:32.800 --> 0:19:34.000 And we'll get more into that. 0:19:35.160 --> 0:19:35.840 They may or. 0:19:35.800 --> 0:19:39.200 May not if you look at laboratory numbers, have changes 0:19:39.240 --> 0:19:42.640 in their liver or their kidney function, or their platelets. 0:19:43.160 --> 0:19:44.480 They may or may. 0:19:44.320 --> 0:19:48.879 Not have altered mental status, or even be unconscious. But 0:19:48.960 --> 0:19:52.280 it's a really mixed bag, and any and all of 0:19:52.320 --> 0:19:56.160 those signs and symptoms could point to sepsis as a cause. 0:19:56.840 --> 0:19:59.199 But there are plenty of people that come into a 0:19:59.240 --> 0:20:02.240 hospital setting or are already in a hospital setting that 0:20:02.400 --> 0:20:05.240 have many of those signs or symptoms but do not 0:20:05.359 --> 0:20:06.119 have sepsis. 0:20:07.000 --> 0:20:07.600 What do they have? 0:20:08.200 --> 0:20:10.400 They could have any number of other things. 0:20:10.800 --> 0:20:14.159 They could have cancer, they could have just meningitis but 0:20:14.200 --> 0:20:15.160 not have sepsis. 0:20:15.200 --> 0:20:17.960 They can have I mean anything. 0:20:18.040 --> 0:20:24.240 Okay, question, do the symptoms that somebody has very more 0:20:24.400 --> 0:20:28.159 based on you know, who that person is, maybe their age, 0:20:28.200 --> 0:20:32.080 maybe their history, et cetera, or the infection that has 0:20:32.320 --> 0:20:34.240 caused or led to sepsis. 0:20:34.520 --> 0:20:38.120 That's a good question. It's hard. 0:20:38.200 --> 0:20:41.000 It's a hard one to answer. I would say there 0:20:41.080 --> 0:20:43.919 are things that we tend to look out for in 0:20:44.000 --> 0:20:46.760 certain age groups as an indicator that might make us 0:20:46.760 --> 0:20:50.000 more worried about sepsis, versus might make us more worried 0:20:50.000 --> 0:20:53.920 about something else in like a different age group. For example, 0:20:54.160 --> 0:20:57.600 altered mental status is one, especially in the elderly, that 0:20:57.680 --> 0:21:00.240 you might not see as much in younger people well 0:21:00.280 --> 0:21:03.919 with sepsis, though you certainly can. And then you know, 0:21:04.080 --> 0:21:07.280 same thing, for if they have respiratory symptoms, you might 0:21:07.320 --> 0:21:11.720 think that they have a predominantly respiratory infection. 0:21:11.480 --> 0:21:12.800 That's the cause of sepsis. 0:21:13.280 --> 0:21:16.320 But sepsis can lead to respiratory symptoms even if the 0:21:16.359 --> 0:21:19.800 infection is elsewhere in the body. So it's a whole mess. 0:21:20.200 --> 0:21:23.240 I think this might be even more complicated than whatever 0:21:23.280 --> 0:21:27.959 one has. It's complicated in the title, right the episode. 0:21:27.920 --> 0:21:29.600 I know, and the truth is like we have. 0:21:29.720 --> 0:21:32.280 All we've done is try to define what sepsis is, right, 0:21:32.359 --> 0:21:34.800 That's all We've tried to do, and it's really difficult, 0:21:36.080 --> 0:21:38.679 but I think that at its core, that short and 0:21:38.720 --> 0:21:43.800 sweet like sepsis three definition, organ dysfunction as a result 0:21:43.960 --> 0:21:47.439 of a combination of both an overwhelming infection, or at 0:21:47.520 --> 0:21:49.560 least I like to think of it as an overwhelming 0:21:49.560 --> 0:21:55.080 infection and a disregulated immune response to that infection. I 0:21:55.080 --> 0:21:59.320 think that those things can tell us a lot about 0:21:59.359 --> 0:22:03.680 the pros sus underlying sepsis, even in the face of 0:22:03.720 --> 0:22:08.560 the fact that specific criteria to call someone septic might 0:22:08.600 --> 0:22:14.000 be different at one hospital versus another. So at its core, 0:22:14.520 --> 0:22:18.920 sepsis requires first an infection, and this, like I said, 0:22:19.000 --> 0:22:23.359 can be an infection of literally any body area cellulitis, pneumonia. 0:22:23.880 --> 0:22:27.200 And often we think. 0:22:27.080 --> 0:22:31.400 I think classically of sepsis as resulting from a bacterial infection, 0:22:32.760 --> 0:22:35.320 and some papers even go so far as to say, 0:22:35.400 --> 0:22:38.840 like GRAM positive Coxi things like staff and strip, which 0:22:38.880 --> 0:22:42.040 are common all over our skin, are the most common 0:22:42.080 --> 0:22:44.080 cause of sepsis related mortality. 0:22:44.320 --> 0:22:45.760 Some statistics say. 0:22:45.600 --> 0:22:48.160 That, and then they'll go on to say that GRAM 0:22:48.200 --> 0:22:51.960 negative rods like E. Coli, which commonly cause UTIs, are 0:22:52.080 --> 0:22:55.919 like the second most common cause of sepsis related mortality. 0:22:55.960 --> 0:23:00.400 But the thing is that sepsis can be caused by 0:23:00.920 --> 0:23:05.399 any bacterial infection, true, but also fungal infections and even 0:23:05.600 --> 0:23:10.800 viral infections. And so then it gets even more complicated 0:23:10.920 --> 0:23:14.920 because you have culture negative sepsis where you are maybe 0:23:15.119 --> 0:23:18.560 treating like it's a bacterial infection, but with no evidence 0:23:19.000 --> 0:23:22.000 of bacteria growing from any body source. 0:23:23.000 --> 0:23:25.560 Okay, I have a couple of questions your brain. 0:23:25.680 --> 0:23:28.200 I can see your face being like, why did we Why? 0:23:28.760 --> 0:23:30.960 No, my brain is like, wait, you have to stop 0:23:30.960 --> 0:23:33.080 because I have too many questions for you to go on. 0:23:34.280 --> 0:23:38.439 Number one is what's the breakdown of bacterial versus viral 0:23:38.560 --> 0:23:40.600 versus fungal and how much of that is just sort 0:23:40.640 --> 0:23:43.840 of in the culture negative ones like we don't know 0:23:44.200 --> 0:23:47.200 what this sepsis was caused by because we're not detecting 0:23:47.240 --> 0:23:49.639 any bacteria, but could it still be bacteria? 0:23:49.840 --> 0:23:52.359 Yeah, we don't know. We don't have great numbers on that. 0:23:52.440 --> 0:23:55.919 In general, forty percent of sepsis cases can come back 0:23:55.960 --> 0:24:00.399 as culture negative, and we have some stats like the 0:24:00.400 --> 0:24:03.600 most common sights of infection, so like sixty four percent 0:24:03.640 --> 0:24:06.320 of cases at least that we have numbers on, are 0:24:06.840 --> 0:24:10.320 starting in the lung twenty percent in the abdomen, fifteen 0:24:10.359 --> 0:24:14.000 percent in the bloodstream, fifteen percent in the genito urinary tract. 0:24:14.920 --> 0:24:18.439 But that still doesn't tell us that it's necessarily a 0:24:18.440 --> 0:24:21.439 bacterial infection, though those most commonly are going to be 0:24:21.480 --> 0:24:25.760 ones that we've identified as bacterial infections, Fungal infections tend 0:24:25.760 --> 0:24:29.480 to be probably the least common but the most severe. 0:24:29.600 --> 0:24:32.920 If you have an overwhelming fungal infection, you're likely very very, 0:24:33.040 --> 0:24:41.160 very sick, and viral infections are probably way underdiagnosed. And 0:24:41.680 --> 0:24:45.639 this is where it gets both more interesting and so 0:24:45.760 --> 0:24:48.880 much more complicated, because if you think as an easily 0:24:48.920 --> 0:24:53.800 recognizable example of COVID nineteen, the vast majority of people 0:24:54.000 --> 0:24:56.800 hospitalized like that ended up in the hospital or the 0:24:57.000 --> 0:25:01.600 ICU for COVID nineteen would meet many, if not all, 0:25:01.920 --> 0:25:05.480 of the common criteria that we would use to diagnose sepsis. 0:25:05.960 --> 0:25:08.919 They're probably tachcartic, their heart rates through the roof, They 0:25:09.000 --> 0:25:11.919 probably have an oxygen requirement, they may or may not 0:25:12.080 --> 0:25:15.840 have a low blood pressure, they probably have some evidence 0:25:15.880 --> 0:25:19.040 of further organ damage like kidney or liver damage, and 0:25:19.160 --> 0:25:22.919 certainly they have an overwhelming infection in their lungs and 0:25:23.040 --> 0:25:26.679 a huge amount of inflammatory response in those lungs, causing 0:25:26.760 --> 0:25:32.560 acute respiratory distress. So people with COVID nineteen would, by 0:25:32.600 --> 0:25:36.760 many definitions or many sets of screening protocols, meet quote 0:25:36.800 --> 0:25:42.760 sepsis criteria. And yet it's probably only either in an 0:25:42.800 --> 0:25:46.760 emergency like triage setting or in the very early days 0:25:46.800 --> 0:25:49.760 of the COVID pandemic that most of those people were 0:25:49.800 --> 0:25:56.280 actually classified as having sepsis, because now on their discharge paperwork, 0:25:56.400 --> 0:26:00.439 they would be called having COVID nineteen, right, because we 0:26:00.560 --> 0:26:03.359 know that that damage is being wrought by stars CoV 0:26:03.480 --> 0:26:08.679 two and our disregulated immune response to that virus. But 0:26:08.840 --> 0:26:14.800 instead of calling it sepsis, necessarily we call it COVID nineteen. 0:26:15.040 --> 0:26:17.120 And so some people might argue you should still call 0:26:17.160 --> 0:26:20.080 that sepsis, and some people might argue you shouldn't. 0:26:21.119 --> 0:26:25.359 So, yeah, I wonder if sepsis in the future is 0:26:25.400 --> 0:26:28.560 going to be one of those things where people are 0:26:28.600 --> 0:26:31.080 going to look back and go you use this catch 0:26:31.080 --> 0:26:33.919 all term to describe something like fever, you know, like 0:26:33.920 --> 0:26:36.800 we look at fever back in the seventeen hundreds. 0:26:36.960 --> 0:26:42.560 Yeah, yeah, it's really interesting. It's a good question because 0:26:42.560 --> 0:26:45.960 a similar thing happens in pediatric populations, And that's part 0:26:45.960 --> 0:26:50.119 of why sometimes the definition for sepsis in pediatric populations 0:26:50.200 --> 0:26:54.600 might be a little different than adult populations because there 0:26:54.640 --> 0:26:59.320 are so many respiratory viral infections, especially that children get 0:26:59.359 --> 0:27:04.760 hospitalized or all the time that might meet some sepsis 0:27:04.800 --> 0:27:08.480 criteria but aren't generally classified as sepsis because we know 0:27:08.680 --> 0:27:11.360 that it's bronchiolitis or whatever. 0:27:12.119 --> 0:27:16.720 Okay, So sepsis is a diagnosis of exclusion, kind. 0:27:16.520 --> 0:27:17.440 Of the opposite. 0:27:17.520 --> 0:27:22.359 Sepsis is a diagnosis of inclusion. Sepsis is this is 0:27:22.400 --> 0:27:24.879 a person who is very sick, and we might not 0:27:24.960 --> 0:27:27.520 know exactly what they have yet, but they're very, very 0:27:27.560 --> 0:27:30.320 sick and they look like they're going to get sicker, 0:27:31.240 --> 0:27:34.120 so we treat it like sepsis until we can determine 0:27:34.160 --> 0:27:35.120 if it's something else. 0:27:36.000 --> 0:27:41.520 Okay, So, using the example of COVID nineteen, could somebody 0:27:41.600 --> 0:27:45.960 have severe COVID nineteen, and then could somebody else have 0:27:46.200 --> 0:27:50.880 COVID nineteen sepsis or is sepsis not really directly ever 0:27:51.000 --> 0:27:53.959 tied to a specific infection, and then how does that 0:27:54.040 --> 0:27:55.240 impact treatment? 0:27:55.760 --> 0:27:57.200 Yeah? Great questions. 0:27:58.160 --> 0:28:02.960 Yes, people can have an infection like COVID and still 0:28:02.960 --> 0:28:10.280 have sepsis. People can also seem to have sepsis initially 0:28:10.840 --> 0:28:15.680 but then recover very quickly, and so then you kind 0:28:15.720 --> 0:28:18.800 of get into the like, you know, did we just 0:28:18.840 --> 0:28:21.199 treat the sepsis very well at the beginning, and so 0:28:21.320 --> 0:28:23.920 now they didn't, you know, move on to septic shock, 0:28:23.960 --> 0:28:27.399 et cetera. So then I don't know, there's just so 0:28:27.600 --> 0:28:30.639 much still up in the air when it comes to 0:28:30.720 --> 0:28:34.320 how you like fully draw that line of is this 0:28:34.359 --> 0:28:36.480 sepsis or is this not sepsis? And I think a 0:28:36.480 --> 0:28:42.440 lot of that is place dependent, but the treatment does vary, 0:28:42.560 --> 0:28:45.080 at least according to kind of what we have for 0:28:45.200 --> 0:28:49.680 now as consensus guidelines when it comes to early identification 0:28:50.160 --> 0:28:53.240 and treatment of sepsis. So let's get into a little 0:28:53.280 --> 0:28:55.840 bit more of like why do we even have to 0:28:55.880 --> 0:28:59.920 have this definition of like sepsis and what does that mean? 0:29:00.200 --> 0:29:02.560 What's going on in our bodies, and then we can 0:29:02.640 --> 0:29:05.560 talk about how we then treat that because of what's happening. 0:29:05.560 --> 0:29:06.200 Does that make sense? 0:29:07.000 --> 0:29:11.760 Yeah, So, while sepsis requires an infection, as we talked about, 0:29:11.840 --> 0:29:15.440 it is not purely an infection. Not every person with 0:29:15.520 --> 0:29:18.680 a UTI or an ammonia or covid is going to go. 0:29:18.680 --> 0:29:20.560 On to have sepsis. 0:29:21.160 --> 0:29:25.360 Sepsis is what happens when an infection gets so severe 0:29:26.360 --> 0:29:31.040 that our immune system reacts to it in such a 0:29:31.080 --> 0:29:34.760 way as to cause severe damage to one or more 0:29:34.800 --> 0:29:38.360 of our other organs as a result. And if this 0:29:38.520 --> 0:29:44.160 process continues unchecked, our immune system and the infection can 0:29:44.240 --> 0:29:48.400 continue to spiral, which will lead to septic shock and 0:29:48.480 --> 0:29:49.720 eventually death. 0:29:50.720 --> 0:29:54.800 And when you say severe infection, does that mean bacterial 0:29:54.920 --> 0:29:57.800 load viral load? What does that mean? 0:29:58.200 --> 0:29:58.960 Yeah? 0:29:59.000 --> 0:30:01.000 I don't have an answer as to what that means, 0:30:01.280 --> 0:30:04.280 because we don't have an answer as to like why 0:30:04.520 --> 0:30:07.480 did that person with a UTI go on to be 0:30:07.600 --> 0:30:09.800 septic and this person with a UTI didn't. 0:30:10.280 --> 0:30:13.440 Like two people could have the same vireemia and one 0:30:13.440 --> 0:30:15.520 person could develop sepsis and the other one may not. 0:30:15.800 --> 0:30:19.400 Right, because what did their immune system do initially to 0:30:19.440 --> 0:30:22.400 try and counteract that. Did they suppress it well enough 0:30:22.480 --> 0:30:23.000 or did they not? 0:30:24.080 --> 0:30:24.880 Okay right? 0:30:25.240 --> 0:30:28.040 Did they overreact? Did they underreact? Did they do a 0:30:28.040 --> 0:30:33.720 little bit of both? Yeah, okay, I know that's not it. 0:30:33.920 --> 0:30:35.640 I can tell it's not a satisfying answer. 0:30:36.200 --> 0:30:36.840 It's fun. 0:30:39.480 --> 0:30:42.200 To talk about septic shock for a quick minute because 0:30:42.520 --> 0:30:45.680 it's a really important part of sepsis. We've talked about 0:30:45.720 --> 0:30:48.520 this concept of shock on the podcast a number of times. 0:30:49.320 --> 0:30:53.400 Shock is essentially when you aren't getting enough perfusion. You're 0:30:53.440 --> 0:30:57.760 not getting enough blood flow and therefore oxygen to your organs. 0:30:58.400 --> 0:31:02.360 So shock is enough one of these catch all definitions 0:31:02.920 --> 0:31:05.040 where you can have shock from a whole bunch of 0:31:05.040 --> 0:31:10.760 different processes. But shock is characterized specifically by hypotension low 0:31:10.880 --> 0:31:13.760 low blood pressure, and so that means that your organ's 0:31:13.800 --> 0:31:15.920 like your kidney's, your liver, or your brain, your heart, 0:31:15.960 --> 0:31:18.600 they're not getting enough blood and oxygen to functions, so 0:31:18.640 --> 0:31:21.600 they begin to shut down, and that is what leads 0:31:21.600 --> 0:31:24.560 to death in sepsis. It's multi organ failure as a 0:31:24.600 --> 0:31:29.560 result of septic shock. So what exactly is our immune 0:31:29.560 --> 0:31:35.200 system doing in response to an infection that eventually results 0:31:35.440 --> 0:31:37.200 in this all the way down the line? No more 0:31:37.240 --> 0:31:39.680 blood getting to our organs, not enough oxygen getting to 0:31:39.720 --> 0:31:44.960 our organs. So, unsurprisingly, we don't fully understand this mechanism 0:31:45.560 --> 0:31:47.400 at all, especially. 0:31:46.920 --> 0:31:49.120 When we get into the nitty gritty details of it. 0:31:49.520 --> 0:31:52.680 But what we do know is that sepsis is characterized 0:31:52.720 --> 0:31:55.840 by a very disregulated. 0:31:55.000 --> 0:31:56.640 Response to infection. 0:31:57.680 --> 0:32:02.560 So what we see is both pro inflammatory and anti 0:32:02.680 --> 0:32:09.040 inflammatory mediators being released at the same time, which we 0:32:09.160 --> 0:32:11.720 used to think that it was like pro inflammatory first 0:32:11.800 --> 0:32:13.959 and then you went through a phase and then you 0:32:14.080 --> 0:32:16.320 like your immune system shut it down and then went 0:32:16.360 --> 0:32:19.200 into this anti inflammatory phase. But it turns out that 0:32:19.240 --> 0:32:21.360 this is all happening at the same time. It's like 0:32:21.400 --> 0:32:23.960 our immune system is just on overdrive, just trying to 0:32:23.960 --> 0:32:25.080 do anything that it can. 0:32:25.480 --> 0:32:27.640 It's just like kitchen sinking it exactly. 0:32:28.600 --> 0:32:31.600 One of the major pathways that we think is involved 0:32:31.800 --> 0:32:36.240 in this severe pro and anti inflammatory response is this 0:32:36.320 --> 0:32:42.560 specific group of receptors known as pamps pathogen associated molecular patterns, 0:32:43.480 --> 0:32:48.280 and these are like kind of specific antigen specific sugars 0:32:48.360 --> 0:32:53.080 or proteins that are present commonly on pathogens like bacteria 0:32:53.240 --> 0:32:57.040 on their surface that all tend to fall into certain patterns. 0:32:57.520 --> 0:33:01.160 There's one, as an example, called LPs or pypo polysachride 0:33:01.360 --> 0:33:02.560 that's one type of PAMP. 0:33:02.680 --> 0:33:04.120 There's a lot of different. 0:33:03.800 --> 0:33:07.720 Like variations that many different types of bacteria might have, 0:33:08.400 --> 0:33:11.000 but they all have these patterns that lets our immune 0:33:11.040 --> 0:33:13.120 system recognize, like and. 0:33:13.040 --> 0:33:15.680 That's one of those lps's, and then. 0:33:15.560 --> 0:33:19.320 We have these receptors toll like receptors that recognize these 0:33:20.200 --> 0:33:25.520 and this hugely stimulates our innate immune response, which tends 0:33:25.560 --> 0:33:29.200 to be like our first pathway of protection against pathogens. 0:33:30.120 --> 0:33:34.760 So these receptors see these pamps and they send out 0:33:34.760 --> 0:33:38.520 alerts and activate both of these systems. At the same time, 0:33:38.760 --> 0:33:43.000 they're stimulating systems to increase the amount of inflammation, and 0:33:43.080 --> 0:33:46.680 at the same time they're stimulating systems that are anti 0:33:46.800 --> 0:33:51.080 inflammatory as well. And then those systems, those like pro 0:33:51.120 --> 0:33:54.960 inflammatory actors are releasing cytokines. They're telling the whole rest 0:33:54.960 --> 0:33:57.440 of our immune system like get in gear, bring all 0:33:57.480 --> 0:34:02.440 the leukocytes, like, tell everyone, this is war. I don't 0:34:02.480 --> 0:34:05.920 like that analogy, but it's like really good, and it 0:34:06.000 --> 0:34:10.160 basically like sends our immune system into overdrive. All of 0:34:10.200 --> 0:34:15.319 this inflammatory process causes vasodilation, so it opens up our 0:34:15.360 --> 0:34:18.759 blood vessels really wide so that the inflammatory stuff can 0:34:18.800 --> 0:34:22.680 get to where it's trying to go. And this inflammation 0:34:22.800 --> 0:34:27.560 also causes damage to the blood vessel walls and inflammatory 0:34:27.800 --> 0:34:31.200 changes to the layers of our blood vessel walls so 0:34:31.280 --> 0:34:34.400 that things can squeeze out and get into tissues to 0:34:34.520 --> 0:34:37.840 like help heal them. But what this ends up, leading 0:34:37.880 --> 0:34:41.719 to is leaky blood vessels, a edema of the tissues, 0:34:41.920 --> 0:34:45.600 fluid getting out to where it doesn't belong. And so 0:34:45.760 --> 0:34:49.040 if that fluid gets into something like our lungs, then 0:34:49.120 --> 0:34:53.040 that can lead to severe difficulty breathing called acute respiratory 0:34:53.040 --> 0:34:56.239 distress syndrome because of fluid filling up your lungs that's 0:34:56.239 --> 0:35:00.000 supposed to be in your blood vessels. This also leads 0:35:00.120 --> 0:35:03.080 to a decrease in permeability of your blood brain barrier. 0:35:03.360 --> 0:35:05.799 So then infections can spread to the brain where they 0:35:05.800 --> 0:35:12.440 maybe couldn't before. And that's all just the inflammatory pathways 0:35:12.480 --> 0:35:14.279 that are happening during sepsis. 0:35:14.600 --> 0:35:21.360 Okay, so I have a question about, Okus, this seems 0:35:22.200 --> 0:35:27.640 like a very maladaptive response to infection, and so is 0:35:27.760 --> 0:35:33.400 this process, does this whole cascade of inflammatory and anti 0:35:33.440 --> 0:35:37.400 inflammatory response or whatever is that good in moderation And 0:35:37.520 --> 0:35:40.800 is it only in this specific context or certain context 0:35:40.880 --> 0:35:43.480 that it can be triggered to this like massive overdrive 0:35:43.520 --> 0:35:46.440 that leads to just like oh that was too much, buddy, 0:35:46.480 --> 0:35:47.920 We're okay, that's it. 0:35:48.520 --> 0:35:51.680 I think that's kind of a fundamental question that we 0:35:51.719 --> 0:35:55.319 still have about the underlying path of physiology of sepsis 0:35:55.360 --> 0:35:58.000 and who's at risk for sepsis and why. 0:35:58.840 --> 0:36:01.920 That's my other question. Yeah, so I know that sepsis 0:36:01.920 --> 0:36:05.319 can happen to anyone, but why does it seem to 0:36:05.440 --> 0:36:09.640 happen in the highest rates in elderly people and in 0:36:10.080 --> 0:36:10.920 like young children. 0:36:11.239 --> 0:36:14.480 So one of the biggest risk factors for sepsis, and 0:36:14.520 --> 0:36:17.319 I think this is really interesting in the context of 0:36:17.719 --> 0:36:21.880 a disregulated immune response rather than just thinking of it 0:36:21.960 --> 0:36:26.560 as like an overactive immune response, is that one of 0:36:26.600 --> 0:36:30.840 the biggest risk factors for sepsis is immunosuppression, whether that's 0:36:31.000 --> 0:36:36.160 primary immunosuppression or an poorly controlled HIV or very elderly 0:36:36.280 --> 0:36:38.600 the immune system is just not what it used to be, 0:36:38.760 --> 0:36:42.040 or the very very young, like infants and neonates, don't 0:36:42.080 --> 0:36:44.560 have like a fully onboarded immune system. 0:36:44.640 --> 0:36:46.640 Yet those are the. 0:36:46.560 --> 0:36:49.000 Groups that are at highest risk for sepsis. 0:36:49.400 --> 0:36:51.560 That makes sense. And so, you know, because when you 0:36:51.600 --> 0:36:54.920 were talking about that inflammatory cascade and just like this 0:36:55.080 --> 0:36:59.640 overwhelming response, it was reminding me of the nineteen eighteen 0:36:59.800 --> 0:37:02.840 flu mm hmm and the cytokine storm. But that's a 0:37:02.960 --> 0:37:04.680 different thing or is it the same thing? 0:37:05.000 --> 0:37:07.560 Well, that's that's the thing right, that's the same thing 0:37:07.600 --> 0:37:10.400 that we think happens in COVID. Yeah, so is it 0:37:10.440 --> 0:37:12.359 a different thing or is it actually the same thing 0:37:12.520 --> 0:37:14.319 that's what's happening in sepsis? 0:37:14.880 --> 0:37:15.080 Right? 0:37:15.360 --> 0:37:19.440 We maybe have a better understanding of the process in 0:37:19.840 --> 0:37:25.520 very limited disease settings, right, Like we understand that, Okay, 0:37:25.520 --> 0:37:30.280 maybe it was these particular cytokines in the nineteen eighteen pandemic. 0:37:30.760 --> 0:37:35.840 Maybe it is these particular processes in something like HLH 0:37:36.000 --> 0:37:41.359 or like other kind of immune driven disorders. But sepsis 0:37:41.400 --> 0:37:46.600 because it's a catch all, because it's any overwhelming infection 0:37:46.800 --> 0:37:51.280 that our body is responding to in a dysregulated fashion 0:37:52.000 --> 0:37:57.440 that's causing this unregulated inflammation. Is it just one process 0:37:57.600 --> 0:38:00.840 or is it you know, each case of sepsis is 0:38:00.840 --> 0:38:03.399 a slightly different process, And is that part of what's 0:38:03.400 --> 0:38:06.120 making it so difficult to study and to understand. 0:38:07.560 --> 0:38:10.560 Whoa, yeah, whoa, whoa, whoa. 0:38:10.600 --> 0:38:15.200 And I'm not even done because there's more. The second 0:38:15.239 --> 0:38:20.160 consequence of sepsis besides all of that inflammation, is that 0:38:20.320 --> 0:38:24.640 all of that inflammation has an interaction with our hemostatic 0:38:24.719 --> 0:38:30.160 pathways in addition to those inflammatory pathways. So this will 0:38:30.160 --> 0:38:35.680 be a callback to our hemophilia episode. So all of 0:38:35.719 --> 0:38:40.239 this inflammation and these inflammatory changes end up causing damage 0:38:40.400 --> 0:38:44.080 to our endothelial cells, those cells that line our blood vessels. 0:38:44.960 --> 0:38:46.520 And we talked. 0:38:46.239 --> 0:38:50.200 In detail in our hemophilia episode about when our blood 0:38:50.280 --> 0:38:55.840 vessels get damaged, they release something called tissue factor, and 0:38:55.960 --> 0:38:59.200 tissue factor is one of the first things that stimulates 0:38:59.280 --> 0:39:05.040 our code co wagulation cascade. Coagulation is the process of 0:39:05.080 --> 0:39:07.040 being able to clot our blood so that we don't 0:39:07.040 --> 0:39:10.759 bleed out every time that our skin gets cut or 0:39:10.800 --> 0:39:15.080 a vessel gets cut. So this coagulation cascade, this process 0:39:15.160 --> 0:39:18.000 is going to first recruit platelets to come in and 0:39:18.120 --> 0:39:22.000 plug the holes of that damaged blood vessel, and then 0:39:22.120 --> 0:39:25.120 tissue factor is going to start the process of activating 0:39:25.160 --> 0:39:27.920 this whole entire cascade that I'm not going to go 0:39:28.000 --> 0:39:33.160 back through, but it's factors seven, eight, nine, five, four, ten, 0:39:33.360 --> 0:39:39.000 et cetera. And this whole process ends up getting activated 0:39:39.560 --> 0:39:43.200 in again a disregulated way when it comes to sepsis. 0:39:43.440 --> 0:39:44.560 So what you can end up. 0:39:44.560 --> 0:39:48.960 Seeing in a very mild form is just thrombocyte apenia, 0:39:49.000 --> 0:39:50.359 which is a drop in. 0:39:50.280 --> 0:39:52.600 Platelets, because those are the first. 0:39:52.360 --> 0:39:55.120 Things that come in to plug a hole when we 0:39:55.200 --> 0:39:59.799 have a hole in our tissues. But that's mild. If 0:39:59.800 --> 0:40:03.800 this this process continues out of control, it will progress 0:40:03.840 --> 0:40:09.680 to what's called DIC or disseminated intravascular coagulation, which is 0:40:09.760 --> 0:40:17.560 basically when this coagulation cascade is underway inside of our 0:40:17.600 --> 0:40:22.400 blood vessels and ends up forming these little microthromby, little 0:40:22.480 --> 0:40:26.000 tiny little clots in our vessels as a result of 0:40:26.040 --> 0:40:31.680 this coagulation cascade, and these thrombi not only can block 0:40:31.719 --> 0:40:34.680 off blood vessels by accident, so now you're not getting 0:40:34.719 --> 0:40:37.520 blood flow to say, your fingertips or a part of 0:40:37.560 --> 0:40:41.640 your brain. And at the same time, because our body, 0:40:41.680 --> 0:40:44.839 whenever we make a clot, we eventually need to break 0:40:44.880 --> 0:40:48.920 it down. So when we're forming a whole bunch of 0:40:48.920 --> 0:40:51.959 clots inside our blood vessels, our body is breaking them down. 0:40:52.040 --> 0:40:55.280 At the same time, we end up using up all 0:40:55.360 --> 0:40:58.839 of these coagulation factors. We end up using up all 0:40:58.880 --> 0:41:01.640 of our platelets to the point where now we can't 0:41:01.680 --> 0:41:04.240 clot at all, so you can end up hemorrhaging. 0:41:05.080 --> 0:41:06.600 Oh and that is DIC. 0:41:07.360 --> 0:41:11.759 Okay, Yeah, and this is happening right alongside or is 0:41:11.800 --> 0:41:14.279 there any sort of okay? This is just there's no 0:41:14.400 --> 0:41:18.960 sequence to the inflammation or not a hard and fast rule. 0:41:19.120 --> 0:41:19.880 Yeah, exactly. 0:41:19.920 --> 0:41:21.839 There is not a hard and fast rule, and there's 0:41:21.960 --> 0:41:23.360 not clear sequences. 0:41:23.400 --> 0:41:24.680 We used to think that there were. 0:41:25.280 --> 0:41:30.000 We used to think first there's this overwhelming pro inflammatory response, 0:41:30.360 --> 0:41:34.560 and then our immune system gets suppressed, and then the 0:41:34.600 --> 0:41:37.480 coagulation cascade gets involved. Like we used to think it 0:41:37.520 --> 0:41:40.680 was more step wise, but it's not. If you think 0:41:40.719 --> 0:41:44.480 of it more as a dysregulation. It's that everyone is 0:41:44.520 --> 0:41:46.759 trying to do something at the same time, but there's 0:41:46.960 --> 0:41:51.480 no communicators. There's no leaders saying this is too much, 0:41:52.200 --> 0:41:54.560 this is too little, we need to work together. It's 0:41:54.600 --> 0:41:57.120 like everyone's just a free for all. That's at least 0:41:57.160 --> 0:42:00.000 the way that I my brain has tried to understand. 0:42:00.360 --> 0:42:02.080 Yeah, yeah, yeah, no, I mean that makes sense. 0:42:02.239 --> 0:42:03.919 Yeah. 0:42:03.960 --> 0:42:06.560 And then of course there's also a fair amount of 0:42:06.640 --> 0:42:11.600 immune suppression that's happening because of these anti inflammatory things 0:42:11.640 --> 0:42:16.000 that are going on, and it tends to be that 0:42:16.120 --> 0:42:18.320 T cell lines and in some cases B cell. 0:42:18.239 --> 0:42:21.680 Lines, more of our specific. 0:42:21.120 --> 0:42:25.520 Like adaptive immune response seems to be suppressed, although aspects 0:42:25.600 --> 0:42:28.759 of our more non specific or innate immune responses can 0:42:28.800 --> 0:42:31.920 also be suppressed. But the problem with this is that 0:42:31.960 --> 0:42:35.840 it can end up leaving one more susceptible to another infection, 0:42:35.920 --> 0:42:36.719 a superinfection. 0:42:37.600 --> 0:42:39.560 Right, Oh my gosh. 0:42:39.800 --> 0:42:43.040 Yeah, this is a mess and there is no hard 0:42:43.040 --> 0:42:44.600 and fast rule to anything. 0:42:45.000 --> 0:42:50.840 You've summed it up, sepsis, this is a mess. The 0:42:50.920 --> 0:42:55.600 major consequences, of course, I think I've said are organ failure, 0:42:56.160 --> 0:43:00.919 septic shock, and death. So this is something that can 0:43:01.560 --> 0:43:07.280 very quickly progress to a very very serious emergency situation. 0:43:07.400 --> 0:43:09.680 So that's why a lot of the definitions of sepsis 0:43:09.760 --> 0:43:11.920 kind of try to include that in the definition. 0:43:13.280 --> 0:43:16.759 What is the timeline of that? Like when you say 0:43:16.840 --> 0:43:18.399 very quickly, what could that be? 0:43:18.760 --> 0:43:20.920 I mean it depends on the infection. 0:43:21.600 --> 0:43:23.560 Okay, so it could be a matter of like hours 0:43:23.600 --> 0:43:27.120 to days, but not not a longer drawn out process 0:43:27.160 --> 0:43:27.440 than that. 0:43:27.960 --> 0:43:31.799 Probably not, because once your immune system starts, like once 0:43:31.880 --> 0:43:35.880 you truly have sepsis, this process is just going to 0:43:35.920 --> 0:43:40.720 continue unchecked unless you're being managed. So let me finally 0:43:40.719 --> 0:43:42.759 try and answer some of your questions from before on 0:43:42.880 --> 0:43:44.360 like how do we actually treat this? 0:43:48.160 --> 0:43:49.600 And there are a few I. 0:43:49.560 --> 0:43:52.480 Think pretty important principles when it comes to management. I 0:43:52.520 --> 0:43:57.319 will link to the Surviving Sepsis guidelines from twenty twenty one. 0:43:57.400 --> 0:43:59.279 Those are at least as far as I saw the 0:43:59.560 --> 0:44:02.960 most recent guidelines. But I will also say, and I'll 0:44:02.960 --> 0:44:05.640 talk about this more later in the episode, these are 0:44:05.719 --> 0:44:08.880 imperfect and they are in a lot of cases based 0:44:09.120 --> 0:44:12.200 they say it outright, this is not my words. They're 0:44:12.239 --> 0:44:15.840 based on pretty poor quality of data because we just 0:44:15.960 --> 0:44:19.719 don't have good enough data when it comes to sepsis. 0:44:20.640 --> 0:44:23.520 But there are a few kind of big important things, 0:44:23.960 --> 0:44:28.359 and the first is just identifying people, especially those that 0:44:28.400 --> 0:44:32.000 are at high risk for septic shock, and so that 0:44:32.120 --> 0:44:38.279 means using these various criteria to identify people who have sepsis, 0:44:38.440 --> 0:44:41.680 even if it's early on. The other thing that it 0:44:41.760 --> 0:44:45.040 means is identifying as quickly as you can the source 0:44:45.160 --> 0:44:48.959 of infection and if possible, getting cultures to be able 0:44:49.000 --> 0:44:52.759 to verify if this is a bacterial infection, what bacterium 0:44:52.880 --> 0:44:56.359 it is, or if it's a fungus, what fungus it is. 0:44:57.080 --> 0:45:00.799 It's also possible to do viral testing in some places 0:45:00.880 --> 0:45:06.080 in some areas, but identifying the source of infection and 0:45:06.120 --> 0:45:11.440 then controlling that source if possible, so if there's an abscess, 0:45:11.719 --> 0:45:14.439 it needs to be drained. If there's like a necrotizing 0:45:14.600 --> 0:45:18.080 skin infection, it has to be debrided. If it's an 0:45:18.120 --> 0:45:21.759 infection from an infected line, like a catheter of some 0:45:21.960 --> 0:45:26.960 kind being removed, like finding where the bacteria is seeding 0:45:27.040 --> 0:45:29.880 from or the infection is seeding from and trying to 0:45:30.239 --> 0:45:36.560 remove it. And in the vast majority of cases, starting 0:45:36.640 --> 0:45:40.120 broad spectrum antibiotics, especially if you don't know what is 0:45:40.160 --> 0:45:44.280 causing this. And then one of the kind of most 0:45:44.360 --> 0:45:48.600 well supported things that tend to happen when someone is 0:45:48.640 --> 0:45:53.919 identified as having sepsis is fluid resuscitation because it can 0:45:54.000 --> 0:45:59.560 so quickly progress to septic shock and hypotension. Resuscitating with fluids, 0:45:59.560 --> 0:46:02.120 so like putting it in an IV and getting fluids is 0:46:02.200 --> 0:46:05.480 one of kind of the most well studied, has really 0:46:05.520 --> 0:46:08.400 good data to support that it improves outcomes and mortality. 0:46:09.280 --> 0:46:14.600 Question about endotoxins, ooh yeah, what role do they play? 0:46:15.160 --> 0:46:15.760 Great question. 0:46:15.960 --> 0:46:20.040 So endotoxins are often things like that LPs that I 0:46:20.080 --> 0:46:24.239 talked about. These are can be things that are pathogen 0:46:24.680 --> 0:46:28.439 associated molecular proteins that our body is recognizing. So that's 0:46:28.480 --> 0:46:31.200 one of the main pathways that we've identified that's a 0:46:31.480 --> 0:46:35.560 likely contributor to the initial development of sepsis. 0:46:35.600 --> 0:46:37.560 That's like one of the triggers exactly. 0:46:37.640 --> 0:46:42.240 Okay, if we're talking generally about a bacterium, right, right. 0:46:42.960 --> 0:46:46.280 So with treatment, what are the mortality rates? 0:46:46.600 --> 0:46:52.800 They really really vary place to place and case to case. 0:46:54.239 --> 0:47:00.120 From some data from maybe about ten years ago in Europe, 0:47:00.160 --> 0:47:03.760 mortality rates from sepsis tended to be about forty percent 0:47:05.120 --> 0:47:10.080 versus about twenty eight percent in the US, which is massive. 0:47:10.840 --> 0:47:13.400 Well, it's also interesting too because you know, like you 0:47:13.480 --> 0:47:16.520 brought up earlier, what goes on the sheet in terms 0:47:16.560 --> 0:47:20.439 of diagnosis can ex also very much affect the right 0:47:20.520 --> 0:47:21.319 mortality rates. 0:47:21.360 --> 0:47:24.719 Yeah, and you know, in some of those cases, if 0:47:24.719 --> 0:47:28.279 they use statistical methods to adjust for things like how 0:47:28.320 --> 0:47:31.840 severe was the disease, then those differences where it seems 0:47:31.880 --> 0:47:34.160 like why is sepsist so much more deadly in Europe 0:47:34.160 --> 0:47:36.360 than the US, if you actually look at like disease 0:47:36.440 --> 0:47:41.160 severity and sepsis mortality, then there actually wasn't a difference. 0:47:41.840 --> 0:47:44.560 So it does, I think, in part, come back to 0:47:45.560 --> 0:47:48.640 how broad this definition is and how it can vary 0:47:48.920 --> 0:47:51.759 place to place and over time. 0:47:53.680 --> 0:48:00.279 Yeah, very very many variables, don't you love it? It's interesting, 0:48:00.360 --> 0:48:01.600 fascinating and scary. 0:48:02.320 --> 0:48:06.439 Yeah, so, Aaron, has it always been with us? 0:48:08.680 --> 0:48:11.880 I presume yes, I do too. I'm not going to 0:48:11.920 --> 0:48:14.080 talk that much about that aspect of it, but I'll 0:48:14.120 --> 0:48:16.880 talk about some other ones. 0:48:17.640 --> 0:48:41.400 Wait and I'll get started right after this break. 0:48:47.600 --> 0:48:51.760 The story of sepsis. How do you tell the history 0:48:52.040 --> 0:48:58.600 of a condition with such varied symptoms, with such varied causes, 0:48:59.040 --> 0:49:02.600 with virtually any viral, bacterial, or fungal infection able to 0:49:02.760 --> 0:49:06.080 lead to its development? Like you talked about a condition 0:49:06.120 --> 0:49:11.000 whose definition and name itself has undergone substantial revision over 0:49:11.040 --> 0:49:14.640 the past one hundred years, and one which we still 0:49:14.719 --> 0:49:20.600 seem to be struggling to effectively treat or even understand. Obviously, 0:49:20.800 --> 0:49:23.000 there are many different ways you could go about it. 0:49:23.560 --> 0:49:27.120 Talk about a particular bacterial cause, or the evolution of 0:49:27.160 --> 0:49:32.160 treatment strategies, or how our understanding and definition of sepsis 0:49:32.160 --> 0:49:37.000 has changed throughout time. Or maybe you could talk about 0:49:37.040 --> 0:49:41.000 a big moment in sepsis history, a period when humanity's 0:49:41.040 --> 0:49:44.160 collective view of the world and how it worked underwent 0:49:44.239 --> 0:49:49.400 a tremendous and life saving shift, even if somewhat reluctantly. Okay, 0:49:49.800 --> 0:49:52.640 and that's my pick for today. That's what I'm gonna do, 0:49:53.280 --> 0:49:55.919 because how could I pass up an opportunity to talk 0:49:55.920 --> 0:49:59.000 about Joseph Lister and the sanitation revolution. 0:50:00.120 --> 0:50:00.840 Simply cannot. 0:50:00.960 --> 0:50:05.040 We cannot. Of course, Lister and his carbolic acid only 0:50:05.040 --> 0:50:08.200 make up a small part of the overall history of sepsis, 0:50:08.640 --> 0:50:11.400 but I wanted to primarily focus on his work today 0:50:11.560 --> 0:50:14.799 because I think it gives us a fascinating insight into 0:50:14.880 --> 0:50:17.799 the early days of germ theory and how we got 0:50:17.920 --> 0:50:21.960 from germ theory as a ridiculed idea to germ theory 0:50:22.000 --> 0:50:26.320 as fact, and from germ theory as theory to germ 0:50:26.360 --> 0:50:30.719 theory in practice. And Joseph Lister is really at the 0:50:30.760 --> 0:50:33.320 heart of so much of that. And I want to 0:50:33.360 --> 0:50:36.160 mention at the top that most of the info about 0:50:36.200 --> 0:50:39.600 Lister and those early days of surgery and germ theory 0:50:40.000 --> 0:50:44.200 I got from the fantastic book The Butchering Art by 0:50:44.239 --> 0:50:45.279 Lindsay Fitzharris. 0:50:46.040 --> 0:50:47.000 Very great books. 0:50:47.120 --> 0:50:50.960 It's truly such a great popular science book that is 0:50:51.200 --> 0:50:55.279 unput downable. I highly recommend it to fill in more 0:50:55.360 --> 0:50:59.239 color and more context and more amazing quotes about the 0:50:59.280 --> 0:51:03.840 early day of the horrific days of surgery to this 0:51:04.000 --> 0:51:09.239 story listeners of the podcast and Aaron, you've heard me 0:51:09.360 --> 0:51:13.600 talk so very much about this time period. But we 0:51:13.719 --> 0:51:16.319 are covering new ground here and I honestly think it's 0:51:16.360 --> 0:51:20.240 one of the most interesting stories yet. Oh but first, 0:51:20.400 --> 0:51:23.120 let's take a step back to get our bearings with sepsis. 0:51:24.080 --> 0:51:27.000 Probably could go without saying, but humans and sepsis go 0:51:27.360 --> 0:51:31.080 way back, and our recognition of the disease also goes 0:51:31.120 --> 0:51:34.319 way back to about twenty seven hundred years ago, when 0:51:34.320 --> 0:51:37.280 it was first used in a medical context in Homer's 0:51:37.320 --> 0:51:43.040 poems in the verb form sepo meaning I rot. Later, 0:51:43.200 --> 0:51:46.560 around four hundred BCE, the word sepsis was introduced in 0:51:46.600 --> 0:51:50.960 the Hippocratic texts, meaning quote the decomposition of animal or 0:51:51.080 --> 0:51:55.640 vegetable or organic matter. And this word or variations of 0:51:55.680 --> 0:51:59.359 it were used extensively in Greek and Roman literature, not 0:51:59.600 --> 0:52:02.600 just in my medical texts, but also classic literature and 0:52:02.640 --> 0:52:07.640 philosophical writings, where it likely held symbolic meaning. Over the 0:52:07.680 --> 0:52:10.840 next hundreds of years, it remained in some use, but 0:52:10.920 --> 0:52:13.360 it seems difficult to say whether that was in the 0:52:13.440 --> 0:52:17.360 medical sense or in the symbolic sense, and in either 0:52:17.400 --> 0:52:21.120 case it's unlikely that the sepsis referred to in most 0:52:21.160 --> 0:52:25.280 historical texts pre nineteenth century would always fit the definition 0:52:25.320 --> 0:52:29.680 that we use today, right, The modern use of sepsis 0:52:29.840 --> 0:52:32.440 more or less can be traced back to sometime in 0:52:32.480 --> 0:52:36.680 the early nineteenth century, depending on the language, also depending 0:52:36.680 --> 0:52:38.440 on the definition. This is why I didn't want to 0:52:38.480 --> 0:52:42.480 go into the changing definitions of sepsis. It just gets 0:52:42.600 --> 0:52:47.239 really messy, really fast. And when it was introduced in 0:52:47.360 --> 0:52:52.759 the early nineteenth century, it meant putrefaction, often accompanied with 0:52:53.040 --> 0:52:55.440 the rotting of the body or parts of the body 0:52:55.520 --> 0:52:59.560 after a wound. And it's really no surprise that it 0:52:59.600 --> 0:53:02.239 was around this time that sepsis came into more and 0:53:02.320 --> 0:53:04.640 more frequent use, as well as other words that were 0:53:04.680 --> 0:53:09.480 related to sepsis, like septosmia or piemia, because much of 0:53:09.480 --> 0:53:12.880 the world was undergoing some pretty drastic changes in terms 0:53:12.880 --> 0:53:18.640 of urbanization, industrialization, and population growth, and these changes could 0:53:18.719 --> 0:53:21.520 also be seen in the medical field, namely in the 0:53:21.520 --> 0:53:25.600 form of hospitals. I talked a bit about the enormous 0:53:25.640 --> 0:53:29.399 increase in hospitals during this time in the Pupil Fever episode. 0:53:31.800 --> 0:53:34.080 Go and listen to it, but in case you need 0:53:34.120 --> 0:53:36.360 a refresher and you don't feel like it. I'm going 0:53:36.440 --> 0:53:39.920 to set the stage again here. The late eighteenth century 0:53:39.960 --> 0:53:43.759 and early nineteenth centuries saw a tremendous growth in hospitals 0:53:43.760 --> 0:53:46.640 in Europe and in the US, mainly as a feature 0:53:46.719 --> 0:53:50.080 of the cities that were constantly and rapidly growing thanks 0:53:50.080 --> 0:53:54.879 to industrialization. In contrast with rural areas where doctors would 0:53:54.880 --> 0:53:58.680 often travel house to house to care for patients, hospitals 0:53:58.719 --> 0:54:01.719 began to be popular in cities where physicians could just 0:54:01.920 --> 0:54:04.160 stay put and wait for their many patients to come 0:54:04.200 --> 0:54:08.200 to them, They could work with other physicians and exchange knowledge, 0:54:08.560 --> 0:54:11.400 and they could use the people seeking care, many of 0:54:11.400 --> 0:54:15.359 whom were in lower economic classes, as a teaching opportunity. 0:54:16.239 --> 0:54:19.880 Prior to the early eighteen hundreds, essentially the only requirement 0:54:19.960 --> 0:54:23.920 for being a surgeon was just calling yourself one. But 0:54:24.120 --> 0:54:27.960 with the growth in hospitals also came tighter, though still 0:54:27.960 --> 0:54:32.520 loose by today's standards, regulations for education and training for 0:54:32.600 --> 0:54:35.960 surgeons and would be surgeons had to spend a certain 0:54:36.000 --> 0:54:40.000 amount of time, say six months or so, learning in hospitals, 0:54:40.080 --> 0:54:44.719 listening to lectures, performing autopsies, or training directly on patients. 0:54:45.880 --> 0:54:49.520 Hospitals were proving to be a tremendous opportunity for the 0:54:49.560 --> 0:54:53.160 growth and spread of medical knowledge, as well as the 0:54:53.200 --> 0:54:59.040 growth and spread of pathogenic microbs. Because these were still 0:54:59.080 --> 0:55:02.440 the days before germ theory, when it was held that 0:55:02.480 --> 0:55:05.120 the dirtier the surgeon's hands or the stiff of their 0:55:05.120 --> 0:55:08.879 coat with dried PUFs and blood, the more respected they were. 0:55:09.400 --> 0:55:15.760 I just it's so yucky, yes, horrible to think about. Yeah, 0:55:15.960 --> 0:55:19.759 the prevailing notion of what caused disease was still miasma, 0:55:20.239 --> 0:55:23.560 foul air that contaminated the body and led to infections. 0:55:24.120 --> 0:55:27.239 How does your coat not be full of foul air? 0:55:28.600 --> 0:55:32.000 Did it stink? It had to have, That's what it's baffling. 0:55:32.680 --> 0:55:36.920 I don't know. But yeah, these blood and puss encrusted 0:55:36.960 --> 0:55:41.960 surgical instruments or soiled bed linens, these weren't viewed as 0:55:42.040 --> 0:55:45.920 dirty or kneading cleaning. It was the bad air in 0:55:45.960 --> 0:55:49.920 the post surgical war that caused the incredibly high mortality 0:55:50.000 --> 0:55:55.320 rates observed. After all, the sight of puss, called laudable 0:55:55.360 --> 0:55:58.000 puss in a wound or surgical sight, was thought to 0:55:58.040 --> 0:56:01.000 indicate that the body was healing wasn't something to be 0:56:01.080 --> 0:56:04.840 worried about. In the first few decades of the nineteenth century, 0:56:05.000 --> 0:56:09.000 mortality rates from surgery were as high as you can imagine, 0:56:09.320 --> 0:56:13.320 but the overall number of surgeries performed was actually fairly low, 0:56:13.920 --> 0:56:16.399 and that was largely due to the lack of anesthesia 0:56:17.280 --> 0:56:20.360 prior to the introduction of ether in the eighteen forties. 0:56:20.719 --> 0:56:23.040 If you had to have surgery of some kind, you 0:56:23.200 --> 0:56:26.359 either had to take your chances with laughing gas, which 0:56:26.400 --> 0:56:29.239 could either kill you or not affect you at all, 0:56:29.960 --> 0:56:33.000 or bite the bullet or more accurately, the leather strap. 0:56:33.840 --> 0:56:37.480 The horror of surgeries made many people reluctant to have 0:56:37.560 --> 0:56:41.040 them unless in cases of dire need, and even made 0:56:41.080 --> 0:56:44.239 many surgeons reluctant to perform them, or at the very 0:56:44.320 --> 0:56:47.280 least encourage them to cut as quickly as they could. 0:56:49.040 --> 0:56:51.799 When ether was first used in eighteen forty two by 0:56:51.840 --> 0:56:55.160 Crawford Long outside of Athens, Georgia, it was the beginning 0:56:55.200 --> 0:56:58.680 of a revolution that would transform surgery from a terrifying 0:56:58.800 --> 0:57:01.520 last resort where had to get in and out as 0:57:01.600 --> 0:57:06.080 quickly as they could, into a viable option and a 0:57:06.239 --> 0:57:10.680 burgeoning field of study. With ether, a surgeon still had 0:57:10.680 --> 0:57:13.240 to be fast, but they at least had a little 0:57:13.280 --> 0:57:16.000 more breathing room to make sure they were suturing the 0:57:16.080 --> 0:57:20.200 right arteries or whatever. Together. As the miracle of ether 0:57:20.320 --> 0:57:23.200 became more widely known across the world, the number of 0:57:23.240 --> 0:57:28.080 surgeries performed climbed up and up and up. With ether, 0:57:28.520 --> 0:57:32.120 one enormous barrier to surgeries had been toppled, but the 0:57:32.160 --> 0:57:38.440 other one, a big one, still remained, infection and infection's 0:57:38.480 --> 0:57:42.480 post surgery loomed bigger and bigger as ether became more 0:57:42.520 --> 0:57:46.800 widely used. Since remember we're still in the days before 0:57:46.920 --> 0:57:52.400 germ theory, right, this is the surgical world that Joseph 0:57:52.440 --> 0:57:55.720 Lister entered into at the age of seventeen in eighteen 0:57:55.800 --> 0:57:59.240 forty four. Lister was born and raised a Quaker, which 0:57:59.280 --> 0:58:02.760 meant a simple childhood. No sport, no theater, no frills. 0:58:02.920 --> 0:58:05.400 Life in general was not about the pursuit of pleasure, 0:58:05.960 --> 0:58:09.840 but about service and honor of God. Fortunately for little 0:58:09.920 --> 0:58:12.760 Joseph Lister and the rest of the world, science was 0:58:12.840 --> 0:58:15.920 considered a worthy pastime and he had the tools to 0:58:16.000 --> 0:58:19.560 explore the natural world at his disposal thanks to his father. 0:58:20.480 --> 0:58:23.440 Although Lister's father had started his career in the family 0:58:23.480 --> 0:58:26.840 biz as a wine merchant, over time he became fascinated 0:58:26.880 --> 0:58:30.680 with the world of microscopes, especially in improving their capabilities 0:58:30.680 --> 0:58:34.800 through fiddling with this lens or adjusting that angle. Lister's 0:58:34.840 --> 0:58:38.760 father's improvements to microscopes earned him great renown, and Lister's 0:58:38.800 --> 0:58:42.000 childhood home was full of the instruments, as well as 0:58:42.000 --> 0:58:46.560 specimens and books of natural history. Given this upbringing, it's 0:58:46.600 --> 0:58:50.600 hardly surprising that at the age of fourteen, Lister decided 0:58:50.640 --> 0:58:53.680 he wanted to better understand life by becoming a surgeon, 0:58:55.040 --> 0:58:59.880 which was not welcome news to his family. At the times. 0:59:00.240 --> 0:59:03.720 Not a well respected bunch, they were seen not so 0:59:03.840 --> 0:59:08.960 much as educated professionals, but more as crude technicians. To 0:59:09.560 --> 0:59:13.080 just give you an idea of this, consider that a 0:59:13.160 --> 0:59:17.520 hospital's chief bug catcher, who was responsible for removing lice 0:59:17.560 --> 0:59:21.160 from mattresses, was paid more than the hospital surgeons. 0:59:21.880 --> 0:59:25.040 WHOA yeah, I mean that does sound like a difficult job. 0:59:25.160 --> 0:59:26.400 It sounds like a horrific job. 0:59:26.480 --> 0:59:28.480 Yeah. 0:59:28.600 --> 0:59:31.800 None of this deterred Lister, though, and so in eighteen 0:59:31.880 --> 0:59:36.320 forty four, at age seventeen, he enrolled in University College London, 0:59:36.560 --> 0:59:39.880 bringing with him, of course, one of his father's microscopes. 0:59:40.840 --> 0:59:44.280 He didn't start right away with medical classes. However, his 0:59:44.400 --> 0:59:48.600 father realized that if he couldn't dissuade Lister from pursuing surgery, 0:59:49.040 --> 0:59:51.280 he could at least require that he complete an art 0:59:51.280 --> 0:59:54.520 degree first, which was effectively a liberal arts degree with 0:59:54.640 --> 0:59:58.800 courses in history, math, literature, and science. I love that 1:00:00.000 --> 1:00:03.040 this was definitely not a requirement or the norm for 1:00:03.120 --> 1:00:07.120 surgeons and training, but Lister later attributed his ability to 1:00:07.160 --> 1:00:11.000 make the important connections he did across disease, sanitation, and 1:00:11.080 --> 1:00:16.080 germ theory to this well rounded education. The other not 1:00:16.200 --> 1:00:19.680 required or not normal thing that Lister did was bring 1:00:19.680 --> 1:00:23.920 his microscope. At the time, microscopes had been around for 1:00:24.040 --> 1:00:26.400 quite a while, over two hundred years. 1:00:26.760 --> 1:00:28.000 Wow, I know. 1:00:28.560 --> 1:00:32.440 I just always forget how early the microscope really came about. 1:00:32.800 --> 1:00:34.720 It's fascinating. 1:00:35.160 --> 1:00:36.560 Yeah, it's really impressive. 1:00:37.280 --> 1:00:40.000 But even though these microscopes had been around for that 1:00:40.680 --> 1:00:43.960 long of a time, they weren't yet seen as integral 1:00:44.000 --> 1:00:47.960 to medicine. Instead, they were considered a distraction, a waste 1:00:48.000 --> 1:00:51.040 of time, or even a threat to the medical community 1:00:51.200 --> 1:00:54.400 since they promised answers that physicians could not provide with 1:00:54.440 --> 1:01:00.000 the naked eye. Yeah, but slowly the tides were returned. 1:01:00.040 --> 1:01:04.040 Learning as scientists jotted down observations about how some diseases 1:01:04.120 --> 1:01:07.120 acted on different tissue types rather than on just the 1:01:07.280 --> 1:01:11.400 entire body or whole organs as had been thought. It 1:01:11.400 --> 1:01:14.040 would still take some time, though, before the value of 1:01:14.120 --> 1:01:18.080 microscopes in diagnosis and other aspects of medicine was made clear, 1:01:18.680 --> 1:01:22.000 and so Lister certainly was unusual in owning one, and 1:01:22.120 --> 1:01:26.040 maybe even more unusual was that he used it. As 1:01:26.040 --> 1:01:28.880 a senior medical student, Lister was appointed to be a 1:01:29.000 --> 1:01:33.200 dresser for John Eric Erickson, who was the senior surgeon 1:01:33.240 --> 1:01:37.800 at University College Hospital. Part of Lister's duties included standing 1:01:37.800 --> 1:01:40.560 by with a box of supplies to dress wounds during 1:01:40.600 --> 1:01:44.040 surgery or to change the bandages in post surgical care. 1:01:44.960 --> 1:01:49.040 In eighteen fifty two, during one of these routine bandage changes, 1:01:49.440 --> 1:01:53.360 he unraveled the cloth on a patient's seeping, rotting wound 1:01:53.560 --> 1:01:57.480 and was met with a horrific odor. It was the 1:01:57.560 --> 1:02:02.600 dreaded hospital gangreen in the day's pre germ theory. Gangreen 1:02:02.760 --> 1:02:06.600 was one of the big four exceedingly common hospital infections 1:02:06.600 --> 1:02:09.560 that cause the most death and disease, with the other 1:02:09.640 --> 1:02:14.360 three being arispolis, septicemia, and piemia, which is a development 1:02:14.400 --> 1:02:19.640 of pus filled abscesses. No one knew precisely why hospitals 1:02:19.680 --> 1:02:23.040 in particulars seemed to be so susceptible to these conditions, 1:02:23.240 --> 1:02:27.160 but they certainly were. You may remember some of the 1:02:27.200 --> 1:02:30.520 stats about pupil fever in the countryside compared to hospitals 1:02:30.560 --> 1:02:33.880 from the pupil fever episode, and here I'm going to 1:02:33.920 --> 1:02:37.000 do the same thing but with amputations, oh dear. 1:02:38.160 --> 1:02:38.440 Yeah. 1:02:38.760 --> 1:02:43.919 For instance, in one year in the countryside, twenty three 1:02:44.040 --> 1:02:48.920 double amputations were performed and seven died, which still seems 1:02:48.960 --> 1:02:49.320 like a lot. 1:02:49.960 --> 1:02:50.080 Hm. 1:02:50.200 --> 1:02:51.640 Definitely still a lot. 1:02:51.560 --> 1:02:55.040 Until you compare with the Royal Infirmary of Edinburgh for 1:02:55.080 --> 1:03:01.160 that same period eleven double amputations, of whom died. 1:03:02.080 --> 1:03:03.240 Wow m hm. 1:03:04.680 --> 1:03:07.520 And it wasn't just those seeking care at hospitals that 1:03:07.560 --> 1:03:11.840 were at risk. Many physicians, surgeons, medical students and surgical 1:03:11.840 --> 1:03:15.640 assistants were just the tiniest scalpel slice away from introducing 1:03:15.720 --> 1:03:19.520 one of these deadly infections into their own bodies. At 1:03:19.560 --> 1:03:23.760 one hospital, Saint bartholomewse Hospital, over the period from eighteen 1:03:23.840 --> 1:03:28.040 forty three to eighteen fifty nine, forty one medical students 1:03:28.160 --> 1:03:31.040 died after developing fatal infections. 1:03:30.800 --> 1:03:32.040 Oh my gosh. 1:03:32.080 --> 1:03:34.600 And of course I can't not mention the three hundred 1:03:34.640 --> 1:03:38.960 percent mortality rate surgery where the quote fastest knife in 1:03:38.960 --> 1:03:42.840 the West End, doctor Robert Liston was cutting so quickly 1:03:43.280 --> 1:03:46.680 that he sliced off his assistant's fingers and then slashed 1:03:46.720 --> 1:03:50.640 a spectator's coat. The patient and the assistant died of infection, 1:03:50.960 --> 1:03:54.200 of course, while the spectator died of shock, or so 1:03:54.280 --> 1:04:03.160 the story goes. Yeah, that possibly true, possibly made up 1:04:03.200 --> 1:04:07.160 dramatic story. Aside, the high mortality rate at hospitals and 1:04:07.200 --> 1:04:11.560 in the cities themselves had come to be expected. Industrial accidents, 1:04:11.720 --> 1:04:15.600 lack of access to clean water or nutritious foods, crowd diseases. 1:04:16.040 --> 1:04:19.000 Even if you managed to avoid cholera from the contaminated 1:04:19.000 --> 1:04:23.080 Broad Street pump, or tuberculosis from your overcrowded building, or 1:04:23.200 --> 1:04:27.000 arsenic from your wallpaper, you couldn't just as easily die 1:04:27.040 --> 1:04:30.360 from septocemia. After having the gash on your hand. You 1:04:30.360 --> 1:04:34.360 got it, the factory stitched up at the hospital. Deadly 1:04:34.440 --> 1:04:39.080 infections haunted every hospital wing, and once one appeared, there 1:04:39.160 --> 1:04:42.680 was not really anything doctors could do to slow it spread. 1:04:43.000 --> 1:04:46.040 Within a matter of days, the gangrene that Lister observed 1:04:46.080 --> 1:04:49.840 in that one patient had swept the entire surgical wards, 1:04:50.600 --> 1:04:53.760 and Lister was put in charge of wound care. This 1:04:53.880 --> 1:04:57.280 involved him scraping off the dead, decaying tissue from the 1:04:57.360 --> 1:05:00.840 wounds and then applying mercury per night, which is both 1:05:00.880 --> 1:05:06.080 caustic and toxic, an excruciatingly painful process that thankfully was 1:05:06.120 --> 1:05:11.200 done while the patient was under anesthesia. Lister, observant as always, 1:05:11.600 --> 1:05:14.880 noticed that the wounds that had been very carefully cleaned 1:05:15.000 --> 1:05:18.880 and that had received this caustic treatment healed surprisingly well. 1:05:19.640 --> 1:05:22.480 What was it about this process that prevented the gangreen 1:05:22.520 --> 1:05:25.800 from getting worse? Maybe the answer wasn't in the air, 1:05:26.120 --> 1:05:30.040 as many of Lister's contemporaries thought, but in the wound itself. 1:05:31.240 --> 1:05:33.200 He took some of the pus that he had scraped 1:05:33.200 --> 1:05:36.200 from patient's wounds and made slides to check out under 1:05:36.240 --> 1:05:40.640 the microscope. Later he wrote about what he saw, quote, 1:05:41.240 --> 1:05:44.640 I examined microscopically the slough from one of the sores, 1:05:44.960 --> 1:05:47.280 and I made a sketch of some bodies of pretty 1:05:47.360 --> 1:05:52.440 uniform size, which I imagined might be the material's morbi morbid substances. 1:05:53.240 --> 1:05:56.320 The idea that it was probably of parasitic nature was 1:05:56.400 --> 1:06:00.680 at that early period already present in my mind. End quote. 1:06:01.400 --> 1:06:03.000 And this is pre germ theory. 1:06:03.120 --> 1:06:06.400 This is pre germ theory. But I believe that that 1:06:06.760 --> 1:06:11.640 was a reflection later on, Okay, in his life. Okay, 1:06:12.120 --> 1:06:15.560 But in any case, the seed of a revolutionary idea 1:06:15.760 --> 1:06:18.720 was planted, but it would take several more years to 1:06:18.800 --> 1:06:19.400 fully form. 1:06:19.880 --> 1:06:20.200 Okay. 1:06:21.040 --> 1:06:23.520 As Lister neared the end of his medical training, he 1:06:23.640 --> 1:06:27.480 was given awards and accolades and recognition of his exceptional 1:06:27.480 --> 1:06:31.200 abilities and achievements. But while his professors could see great 1:06:31.240 --> 1:06:34.840 promise in him, he wasn't so sure. He couldn't decide 1:06:34.840 --> 1:06:38.080 whether he wanted to go into medicine or surgery, so 1:06:38.200 --> 1:06:41.040 one of his professors recommended he spent some time in 1:06:41.200 --> 1:06:45.680 Edinburgh with clinical surgeon James Syme. What was supposed to 1:06:45.680 --> 1:06:49.520 be a month long stay turned into years as Sime 1:06:49.640 --> 1:06:54.760 became not only Lister's respected mentor, but eventually father in law. 1:06:54.920 --> 1:06:57.720 In Scotland. He fell back in love with surgery and 1:06:57.920 --> 1:07:00.640 dove back into the topic that had he first grabbed 1:07:00.640 --> 1:07:05.200 his attention in his surgical training, inflammation in wounds. He 1:07:05.280 --> 1:07:08.640 spent his free time examining more puffs and tissue samples 1:07:08.680 --> 1:07:11.479 under the scope and jotting down any patterns he saw. 1:07:12.120 --> 1:07:15.480 When did inflammation appear? When did a fever develop? Was 1:07:15.520 --> 1:07:19.080 fever a good thing or a bad thing? What about inflammation? 1:07:19.720 --> 1:07:23.480 Did sepsis always come after inflammation or only some of 1:07:23.480 --> 1:07:26.680 the time. He could only get so far with the 1:07:26.720 --> 1:07:29.160 dead and dying tissue he was looking at, so he 1:07:29.240 --> 1:07:31.920 turned to other living animals to take a closer look. 1:07:32.320 --> 1:07:34.720 A colony of frogs that he kept at his house. 1:07:35.880 --> 1:07:39.600 He would injure their webs in various ways using heat 1:07:39.720 --> 1:07:42.240 or chemicals, and then look at what happened to their 1:07:42.240 --> 1:07:46.480 blood vessels. What these experiments told Lister was that inflammation 1:07:46.720 --> 1:07:49.880 was a normal part of the healing process, and sepsis 1:07:50.040 --> 1:07:56.120 didn't necessarily follow. He was getting closer. In eighteen fifty nine, 1:07:56.400 --> 1:07:58.920 six years after he moved to Edinburgh to work with 1:07:59.040 --> 1:08:02.920 Sime who was then thirty two, applied for and was 1:08:02.960 --> 1:08:06.920 given a prominent surgery professorship at the University of Glasgow. 1:08:08.120 --> 1:08:11.400 Although at the time the academic atmosphere at Glasgow was 1:08:11.440 --> 1:08:16.320 conservative where Edinburgh was daring traditional, while Edinburgh lean progressive. 1:08:17.000 --> 1:08:20.160 New Hires like Lister were injecting a bit of freshness 1:08:20.200 --> 1:08:23.719 into the university, which attracted more and more medical students, 1:08:24.479 --> 1:08:28.839 students who loved their new professor for his riveting lectures 1:08:29.160 --> 1:08:34.280 focus on clarity and modern thinking. Alongside his appointment at 1:08:34.320 --> 1:08:37.160 the university, Lister was also given a position at the 1:08:37.200 --> 1:08:41.120 city's hospital, which he viewed as essential for connecting theory 1:08:41.200 --> 1:08:45.000 and practice, demonstrating the procedures that he had lectured about 1:08:45.000 --> 1:08:48.479 in class. Even though the surgical ward that Lister was 1:08:48.479 --> 1:08:54.479 assigned to was basically newly constructed, it was already filthy. 1:08:55.840 --> 1:08:59.320 All the classic infections haunted the wards. The graveyard was 1:08:59.400 --> 1:09:04.240 constantly overflowing, and there was practically nowhere to wash your 1:09:04.280 --> 1:09:09.280 hands or instruments or bed linens, even like the surgical 1:09:09.439 --> 1:09:13.280 tools that were used were ornately carved, which meant that 1:09:13.320 --> 1:09:17.839 they were impossible to clean if the surgeon actually attempted 1:09:17.880 --> 1:09:18.800 to clean it at all. 1:09:20.000 --> 1:09:24.400 Yeah, I just, I really, I know. We talked on 1:09:24.439 --> 1:09:25.640 this podcast about. 1:09:25.400 --> 1:09:29.599 Trying to like separate what we know now from what 1:09:29.680 --> 1:09:34.000 we knew back then, But like I can't get this one, 1:09:34.400 --> 1:09:39.120 you know, I know, like I can't get there, like 1:09:39.240 --> 1:09:41.080 a pus filled knife. 1:09:41.240 --> 1:09:43.000 How are you not gonna wash that? 1:09:43.760 --> 1:09:44.960 Because puss was good. 1:09:45.160 --> 1:09:49.320 It was logical, like dirt and blood. Come on, I know, 1:09:50.760 --> 1:09:55.320 I know, it's it's very horrible, but interesting to think about. 1:09:57.200 --> 1:10:02.920 Yeah, Lister's house surge, get a load of this said quote. 1:10:03.640 --> 1:10:07.799 When almost every wound was foul with separation, it seemed 1:10:07.920 --> 1:10:11.160 natural at the time to postpone the complete cleansing of 1:10:11.240 --> 1:10:15.360 hands and instruments until the program of dressings and probings 1:10:15.400 --> 1:10:19.080 had been finished. Basically, what point is there to clean 1:10:19.160 --> 1:10:21.160 something that's just going to get dirty again? 1:10:21.720 --> 1:10:22.240 Yeah? 1:10:22.400 --> 1:10:29.400 All right, okay, with this attitude, is it any wonder 1:10:29.600 --> 1:10:32.679 that mortality rates post surgery were sky high. 1:10:33.520 --> 1:10:38.040 Surgeons weren't being wilfully malicious, they simply didn't know any better, 1:10:38.680 --> 1:10:41.320 But it was still a tragedy to those dying of 1:10:41.360 --> 1:10:44.600 infection and their loved ones who had to sit by helplessly, 1:10:45.120 --> 1:10:47.559 as well as to the surgeons who would take great 1:10:47.640 --> 1:10:50.200 care in treating people only to watch them die of 1:10:50.200 --> 1:10:55.000 infection a few days later. Lister felt this very keenly, 1:10:55.360 --> 1:10:58.240 and as a result, he became very invested in trying 1:10:58.280 --> 1:11:04.240 to prevent these post surgery dens, starting with cleanliness. The 1:11:04.320 --> 1:11:09.160 concept of cleanliness has not remained constant throughout history. 1:11:09.960 --> 1:11:11.639 Ooh, is that a whole other episode. 1:11:11.880 --> 1:11:15.599 Yeah, I think it could be. Nowadays, we may think 1:11:15.640 --> 1:11:18.280 of a clean hospital room as one that has been 1:11:18.439 --> 1:11:22.479 sprayed and wiped down with interseptic, freshly mopped, fresh linens 1:11:22.479 --> 1:11:25.439 and paper on the beds, sterilize instruments, and so on. 1:11:26.680 --> 1:11:29.840 In Lister's day, a clean room was one that had 1:11:29.920 --> 1:11:35.080 been recently swept and the windows opened. That was basically it. 1:11:35.320 --> 1:11:39.160 That was it because fresh air. Yeah, okay, fresh air granted. 1:11:39.520 --> 1:11:44.880 New ideas were continually being proposed, such as cleanliness and 1:11:44.960 --> 1:11:48.960 cold water, which held that surgical instruments should be cleaned 1:11:48.960 --> 1:11:51.880 with water that had been boiled and then allowed to cool. 1:11:52.600 --> 1:11:55.960 And the idea behind this was that cold water was 1:11:56.000 --> 1:11:59.560 supposed to prevent the heat that caused fever and inflammation. 1:12:00.720 --> 1:12:03.080 Why boil it and then cool it? 1:12:03.560 --> 1:12:10.800 Great question, I don't know. And of course Igna's Semmelweiss 1:12:10.880 --> 1:12:14.120 went further than just washing instruments in cold water. He 1:12:14.200 --> 1:12:18.080 also famously advocated for better hand washing and instrument washing 1:12:18.200 --> 1:12:22.000 using a chloride solution, but as we know, he was 1:12:22.120 --> 1:12:25.880 ridiculed and his ideas did not become widely known until 1:12:25.920 --> 1:12:29.519 after his death, so Lister didn't hear about him until 1:12:29.600 --> 1:12:34.160 much later on. Instead, Lister tried out the cleanliness and 1:12:34.280 --> 1:12:39.240 cold water approach and became increasingly disappointed at the results 1:12:39.680 --> 1:12:45.040 or black thereof. It didn't seem to do anything. He 1:12:45.160 --> 1:12:48.800 expressed his frustration to his students, saying, quote, it is 1:12:48.840 --> 1:12:52.840 a common observation that when some injury is received without 1:12:52.880 --> 1:12:57.120 the skin being broken, the patient invariably recovers, and that 1:12:57.200 --> 1:13:01.320 without any severe illness. On the other hand, trouble of 1:13:01.400 --> 1:13:04.720 the gravest kind is always apt to follow, even in 1:13:04.800 --> 1:13:07.799 trivial injuries, when a wound of the skin is present. 1:13:09.120 --> 1:13:12.080 How is this? The man who is able to explain 1:13:12.120 --> 1:13:17.280 this problem will gain undying fame. Ha ha I know end quote. 1:13:19.200 --> 1:13:22.400 As eighteen sixty four drew to a close, Lister was 1:13:22.439 --> 1:13:25.760 still deep in his depression over the seemingly inevitable death 1:13:25.800 --> 1:13:29.360 of his patients when a colleague brought some new articles 1:13:29.400 --> 1:13:35.800 to his attention, research involving fermentation and putrefaction, authored by 1:13:35.840 --> 1:13:40.879 none other than Louis Pasture HM. In these articles, Pasture 1:13:40.960 --> 1:13:45.240 noted that microscopic rod shaped organisms were found in spoiled wine, 1:13:45.600 --> 1:13:48.280 and he believed that they were responsible for the spoilage. 1:13:48.840 --> 1:13:52.280 But he also looked beyond wine, proposing that these tiny 1:13:52.320 --> 1:13:55.880 germs were also responsible for certain diseases in humans and 1:13:55.960 --> 1:13:59.720 other animals. Pasture's ideas were met with quite a bit 1:13:59.720 --> 1:14:03.320 of resistance and ridicule from the medical and scientific community, 1:14:03.760 --> 1:14:06.960 but Lister found them exciting and felt hopeful that the 1:14:07.000 --> 1:14:09.240 answers he had long been looking for it might be 1:14:09.280 --> 1:14:13.200 found in these articles. To Lister, this concept of germ 1:14:13.240 --> 1:14:17.840 theory explained why disease appeared after surgery and how it 1:14:17.880 --> 1:14:20.519 could be spread from one person to the next, all 1:14:20.560 --> 1:14:24.439 the way down the ward. He wasn't entirely right in 1:14:24.479 --> 1:14:28.280 his conclusions, believing that it was microbes carried in the 1:14:28.320 --> 1:14:32.600 air rather than like on instruments, for instance, but he 1:14:32.720 --> 1:14:34.880 was on the right track enough to try out some 1:14:35.040 --> 1:14:39.800 infection control strategies, namely by attacking these germs after their 1:14:39.840 --> 1:14:44.479 introduction into the wound. On this he also turned to Pasture, 1:14:44.680 --> 1:14:47.439 who had demonstrated that these germs could be killed by 1:14:47.520 --> 1:14:52.080 any number of different things. Heat or filtration couldn't really 1:14:52.120 --> 1:14:55.160 be put to practical use for Lister, so he turned 1:14:55.200 --> 1:14:59.840 towards finding an antiseptic that would kill germs on contact. Again, 1:15:00.160 --> 1:15:03.599 this was not an entirely new notion. Aniseptics had been 1:15:03.720 --> 1:15:07.800 used by surgeons for years to irrigate wounds, but two 1:15:08.000 --> 1:15:12.120 main things prevented them from being recognized as incredibly powerful 1:15:12.160 --> 1:15:17.120 sepsis prevention tools. The first was that surgeons typically waited 1:15:17.160 --> 1:15:19.479 to use the antiseptic on a wound until it was 1:15:19.560 --> 1:15:23.120 obviously infected, at which point there was little the aniseptic 1:15:23.120 --> 1:15:27.840 could do because the infection was likely systemic. And second 1:15:28.160 --> 1:15:32.000 was that the antiseptics themselves often caused substantial damage to 1:15:32.040 --> 1:15:37.200 the surrounding skin, allowing for further infection. Because of this, 1:15:37.439 --> 1:15:39.840 the jury was still out on the value of aniseptics 1:15:39.840 --> 1:15:43.280 in medicine. Lister wondered if there was more to the 1:15:43.320 --> 1:15:46.920 story of aniseptics, though, so he decided to test different 1:15:46.920 --> 1:15:49.360 ones out to see which were the most effective in 1:15:49.439 --> 1:15:52.680 preventing infection. Instead of waiting for the pus to be 1:15:52.720 --> 1:15:56.479 freely flowing and the surrounding skin hot and tight and 1:15:56.560 --> 1:16:01.200 red with inflammation, he applied the aniseptics prof lactically and 1:16:01.280 --> 1:16:05.280 waited to see which one did the best. After going 1:16:05.320 --> 1:16:08.639 through a few that didn't show much promise, he reached 1:16:08.680 --> 1:16:12.640 for the carbolic acid aka phenol, remembering that he had 1:16:12.680 --> 1:16:16.160 heard carbolic acid was sometimes used at sewage works to 1:16:16.200 --> 1:16:21.920 counteract the smell of rotting liquid waste. Yeah, he thought, 1:16:22.320 --> 1:16:25.439 if it can cover up those horrific smells, maybe it'll 1:16:25.520 --> 1:16:28.280 kill whatever is putrefying these wounds. And I feel like 1:16:28.280 --> 1:16:35.000 that was also Semmelweis's train of thought. But yeah, carbolic 1:16:35.240 --> 1:16:38.519 acid didn't work that great on the first two people 1:16:38.560 --> 1:16:41.360 he tried it out on, but the third time was 1:16:41.400 --> 1:16:44.920 the charm. In August of eighteen sixty five, eleven year 1:16:45.000 --> 1:16:49.760 old James Greenlea's was brought to Lister's Hospital three hours 1:16:49.960 --> 1:16:53.799 after his leg had been crushed under a cart, tibia 1:16:53.960 --> 1:16:56.160 cracked and jutting through his skin. 1:16:56.760 --> 1:16:57.920 Ah. 1:16:58.040 --> 1:17:02.360 Yeah, the wound was already, of course, filthy from the 1:17:02.439 --> 1:17:05.880 road and from the journey to the hospital. But Lister 1:17:05.960 --> 1:17:10.000 knew that amputation, which was probably safest in terms of infection, 1:17:10.640 --> 1:17:13.680 would forever change this young boy's life, and so he 1:17:13.760 --> 1:17:16.600 wanted to see what he could do. He put the 1:17:16.640 --> 1:17:19.800 boy under chloroform and went to work cleaning out the 1:17:19.840 --> 1:17:22.640 wound as best he could with dilute carbolic acid and 1:17:22.720 --> 1:17:26.720 getting the bone reset, And he continued to take meticulous 1:17:26.760 --> 1:17:29.360 care of the wound over the next days and weeks, 1:17:29.800 --> 1:17:33.439 carefully cleaning it with carbolic acid and putting some olive 1:17:33.439 --> 1:17:36.799 oil on as a soother, and checking for signs of infection. 1:17:37.960 --> 1:17:41.320 Six weeks and two days after James Greenlea's had been 1:17:41.400 --> 1:17:45.439 carried into the hospital with his horrifically broken leg, he 1:17:45.520 --> 1:17:46.800 walked out on his own. 1:17:47.439 --> 1:17:48.679 Wow Yeah. 1:17:50.120 --> 1:17:52.880 Lister felt that he finally held the key to the 1:17:52.880 --> 1:17:57.559 hospital infection problem. He continued to try out his carbolic 1:17:57.600 --> 1:18:00.920 acid technique on other people with compound frack xtures with 1:18:01.000 --> 1:18:03.960 a success rate of eighty percent, and then moved on 1:18:04.120 --> 1:18:08.200 to other injuries before he finally felt ready to publish. 1:18:08.320 --> 1:18:12.200 On March sixteenth, eighteen sixty seven, two years after he 1:18:12.280 --> 1:18:16.759 first began experimenting with carbolic acid, Lister published the first 1:18:16.800 --> 1:18:20.360 part of a five part article in The Lancet describing 1:18:20.360 --> 1:18:25.200 his findings quote on a new method of treating compound fracture, 1:18:25.439 --> 1:18:31.200 absess etc. With Observations on the conditions of separation. This 1:18:31.400 --> 1:18:34.920 was not only groundbreaking in its support for germ theory, 1:18:35.120 --> 1:18:39.360 but his articles also provided step by step instructions to 1:18:39.479 --> 1:18:44.880 prevent post operative infections. The Glasgow Royal Infirmary where Lister worked, 1:18:44.960 --> 1:18:48.439 went from being among the deadliest to the cleanest with 1:18:48.479 --> 1:18:53.160 the lowest mortality rates. Wow, Lister wrote, quote, I now 1:18:53.200 --> 1:18:56.240 perform an operation for the removal of a tumor, etc. 1:18:56.720 --> 1:18:59.720 With a totally different feeling from what I used to have. 1:19:00.680 --> 1:19:05.280 In fact, surgery is becoming a different thing altogether. End quote. 1:19:05.720 --> 1:19:06.320 Wow. 1:19:06.439 --> 1:19:10.760 I just it's it's hard to imagine what a tremendous 1:19:11.320 --> 1:19:16.960 relief and how much hope that would have inspired. I guess, like, 1:19:17.240 --> 1:19:19.679 finally this isn't a death sentence. 1:19:20.000 --> 1:19:23.720 Yeah, yeah, especially to have like dedicated. 1:19:23.320 --> 1:19:26.880 Your whole life to something and then finally feel like 1:19:27.840 --> 1:19:33.320 you can do it and like not only have horrific outcomes, 1:19:33.360 --> 1:19:36.120 Like yeah, yeah, I can't I can't even imagine. 1:19:36.400 --> 1:19:40.400 Yeah, And I have some numbers to back up just 1:19:40.520 --> 1:19:45.040 how incredible this was. So sixteen of the thirty five 1:19:45.120 --> 1:19:49.120 people that had undergone amputations between eighteen sixty four and 1:19:49.200 --> 1:19:54.160 eighteen sixty six before carbolic acid, sixteen of those thirty 1:19:54.200 --> 1:19:57.840 five had died, while that number dropped down to only 1:19:58.000 --> 1:20:01.679 six of forty between eighteen sixty seven and eighteen sixty 1:20:01.680 --> 1:20:03.280 eight after carbolic acid. 1:20:03.600 --> 1:20:04.080 Wow. 1:20:04.760 --> 1:20:07.560 Yeah, it's it's amazing, and I do just want to 1:20:07.600 --> 1:20:10.559 point out because I realize I'm talking mostly about Lister 1:20:10.840 --> 1:20:16.400 and antiseptic technique in the history of sepsis, and a 1:20:16.439 --> 1:20:20.719 lot of these post surgery deaths were due to wound 1:20:20.840 --> 1:20:24.439 sepsis basically that was caused by an infection that they 1:20:24.479 --> 1:20:27.760 had gotten from the surgery, not something they came into 1:20:27.760 --> 1:20:28.479 the hospital with. 1:20:29.080 --> 1:20:29.800 Right. Yeah. 1:20:30.160 --> 1:20:35.200 Yeah. As you might expect, Lister's articles weren't immediately accepted 1:20:35.280 --> 1:20:39.280 with open arms by the medical and surgical community. Shocked 1:20:39.320 --> 1:20:43.559 of all shocking, shocking, though he did seem to have 1:20:43.760 --> 1:20:48.559 more supporters than someone like Semmelweis. His old mentor sign 1:20:48.720 --> 1:20:51.559 was on his side, as were many of Lister's students 1:20:51.680 --> 1:20:55.559 and Pasture himself, whom he became close pen pals with. 1:20:57.680 --> 1:21:00.360 But there was quite a bit of resistance and even 1:21:00.439 --> 1:21:05.000 ridicule in response to his ideas of antisepsis, most notably 1:21:05.040 --> 1:21:08.240 from the famous surgeon James Y. Simpson, who had first 1:21:08.320 --> 1:21:11.680 introduced the use of chloroform as anesthesia and was a 1:21:11.680 --> 1:21:16.759 big proponent of acute pressure for sepsis prevention, which didn't work. 1:21:17.120 --> 1:21:20.880 Simpson seemed to have a personal vendetta against blister. Maybe 1:21:20.920 --> 1:21:23.960 he was frustrated that no one seemed to like acutpressure. 1:21:24.880 --> 1:21:27.519 Maybe he felt protective of his own fame and was 1:21:27.600 --> 1:21:30.040 jealous of Lister, but there did seem to be a 1:21:30.120 --> 1:21:33.800 variety of reasons that Simpson and others were so quick 1:21:33.880 --> 1:21:35.400 to dismiss Lister's ideas. 1:21:36.240 --> 1:21:36.920 To some, it. 1:21:36.920 --> 1:21:40.639 Seemed like the newest version of put this mysterious ointment 1:21:40.680 --> 1:21:43.599 on it and hope for the best. To others, it 1:21:43.720 --> 1:21:47.680 was a passing fad. Some believed Lister to be overstating 1:21:47.680 --> 1:21:51.519 his results, and others dismissed it out of hand due 1:21:51.560 --> 1:21:54.400 to its reliance on germ theory, which had by no 1:21:54.600 --> 1:21:58.720 means been widely accepted yet. But perhaps one of the 1:21:58.760 --> 1:22:02.479 biggest reasons for resisting Lister's ideas was that if he 1:22:02.640 --> 1:22:06.440 was right, that meant that these surgeons had been inadvertently 1:22:06.560 --> 1:22:09.920 causing the deaths of so many of the people that 1:22:09.960 --> 1:22:14.559 they were supposed to have been helping. Lister fought the 1:22:14.560 --> 1:22:18.200 disappointment he felt from all this criticism by focusing his 1:22:18.280 --> 1:22:22.639 efforts on improving surgery in other ways, such as changing 1:22:22.640 --> 1:22:25.640 the material that the ligatures were made of to catgut, 1:22:25.720 --> 1:22:28.280 which could be absorbed by the body and reduce the 1:22:28.360 --> 1:22:34.000 risk of infection. He also concentrated on teaching, realizing that well, 1:22:34.080 --> 1:22:37.799 if he couldn't convince older generations of doctors of his methods, 1:22:37.880 --> 1:22:41.360 then he could train the new ones. Over the next 1:22:41.360 --> 1:22:45.040 few years, years in which so many people continued to 1:22:45.120 --> 1:22:48.760 die because their surgeons refused to test out Lister's techniques, 1:22:49.320 --> 1:22:52.679 Lister kept at it, touring across the US to give 1:22:52.760 --> 1:22:57.080 talks where some hospitals like Mass General for example, had 1:22:57.120 --> 1:23:02.280 actually banned Lister's techniques, and then later it became they 1:23:02.280 --> 1:23:04.879 were like the first hospital to make it hospital policy 1:23:04.920 --> 1:23:10.400 to practice wow and also continuing to publish his results. 1:23:10.800 --> 1:23:13.519 I hate that this is a lesson in published, publish, published, 1:23:13.520 --> 1:23:19.280 but whatever, it all paid off. The medical community grew 1:23:19.320 --> 1:23:24.000 to accept Lister's carbolic acid practices in preventing post surgical infection, 1:23:24.640 --> 1:23:28.200 and the enormous contribution he made to the field of 1:23:28.240 --> 1:23:31.840 not just surgery but all of medicine was recognized in 1:23:31.880 --> 1:23:35.880 his lifetime. Unlike so many of the other people that 1:23:35.920 --> 1:23:40.000 we talk about on this podcast, Yeah, Lister spent the 1:23:40.000 --> 1:23:44.639 rest of his life showered in awards, accolades, honorary degrees, 1:23:44.800 --> 1:23:47.559 and was even given the dubious honor of having a 1:23:47.680 --> 1:23:52.719 hygiene product created in his name of Lister Reade. 1:23:53.120 --> 1:23:55.960 Oh my gosh, I don't know if I ever put 1:23:56.000 --> 1:23:59.760 those two together. Lister Reid's been around that long. 1:24:00.080 --> 1:24:02.840 It was developed by someone who who saw his talk, 1:24:03.080 --> 1:24:07.479 one of Lister's talks in the US, and then later 1:24:07.600 --> 1:24:11.160 like the rights to advertise it were sold and the 1:24:11.240 --> 1:24:14.679 person who bought them advertised it as a Dan Dreff treatment, 1:24:14.760 --> 1:24:18.639 a cure for gonorrhea, a floor cleaner, and of course 1:24:18.880 --> 1:24:23.400 oral antiseptic. And that's how it came. That's how it 1:24:23.439 --> 1:24:28.560 has remained. And it wasn't just Listerine that Lister inspired. 1:24:29.240 --> 1:24:33.960 Lister's antiseptic techniques kicked off a craze for antiseptic products 1:24:34.000 --> 1:24:38.200 and inspired someone named Robert Wood Johnson, who had also 1:24:38.280 --> 1:24:41.240 seen Lister speak, to join up with his brothers to 1:24:41.320 --> 1:24:46.200 start a company manufacturing sterile surgical dressings and sutures. They 1:24:46.280 --> 1:24:48.200 named it Johnson and Johnson. 1:24:49.240 --> 1:24:56.040 How interesting, Yeah wow, but mouthwash aside. 1:24:56.640 --> 1:25:01.360 Lister's two biggest legacies are that he provided an effective 1:25:01.439 --> 1:25:06.000 means to prevent one of the biggest causes of surgical deaths, 1:25:06.760 --> 1:25:12.639 which absolutely changed the practice of surgery forever and medicine period, 1:25:13.520 --> 1:25:17.280 and also that he demonstrated germ theory in action, which 1:25:17.360 --> 1:25:20.559 greatly helped it to become accepted or at least more 1:25:20.600 --> 1:25:26.840 closely examined. With the widespread adoption of Lister's antiseptic practices, 1:25:27.160 --> 1:25:32.880 hospital sepsis cases dropped tremendously. Over the next decades, Researchers 1:25:32.920 --> 1:25:36.960 learned more about the underlying pathophysiology of sepsis, such as 1:25:37.000 --> 1:25:40.559 the role of endotoxins and the immune system response, and 1:25:40.640 --> 1:25:43.759 they discovered new ways to diagnose and treat the condition. 1:25:44.960 --> 1:25:47.240 In the one hundred and fifty five years since Lister 1:25:47.360 --> 1:25:51.000 published his article, We've come so far and learned so 1:25:51.120 --> 1:25:55.360 much about sepsis, but as we can gather from the 1:25:55.400 --> 1:25:59.479 biology section, we have still so very far to go. 1:26:00.840 --> 1:26:03.720 And I really hope I haven't disappointed anyone too very 1:26:03.800 --> 1:26:08.000 much by skipping over most of the recent history of 1:26:08.040 --> 1:26:12.439 sepsis and the changing definitions. But I figured, Aarin, that 1:26:12.800 --> 1:26:15.080 you could at least bring us up to speed with 1:26:15.120 --> 1:26:15.920 sepsis today. 1:26:16.400 --> 1:26:20.120 Oh, I can't wait to right after this break. 1:26:52.439 --> 1:26:57.360 Sepsis today, Aaron, it's a bit of a mess. 1:27:00.720 --> 1:27:01.920 In the US. 1:27:02.280 --> 1:27:09.320 In recent years, there are nearly a million sepsis cases 1:27:10.000 --> 1:27:13.400 admitted to hospitals each year. 1:27:15.120 --> 1:27:17.400 Just in the US a million. 1:27:18.200 --> 1:27:23.240 Yeah, and the numbers tend to be on the rise 1:27:23.600 --> 1:27:24.439 year after year. 1:27:25.200 --> 1:27:26.280 Huh m hm. 1:27:28.040 --> 1:27:34.720 Sepsis is also one of, if not the leading expenses. 1:27:35.400 --> 1:27:39.000 And I know we've talked about the problem of using 1:27:39.040 --> 1:27:43.879 like healthcare expenses, especially in the US, because our healthcare 1:27:43.920 --> 1:27:48.000 system is so skewed in terms of how much everything costs. 1:27:48.600 --> 1:27:50.680 But sepsis costs the. 1:27:50.760 --> 1:27:56.080 US healthcare system billions and billions of dollars every year. 1:27:56.640 --> 1:27:58.120 I mean, at the very least, it seems like it 1:27:58.160 --> 1:28:01.240 would be a good proxy for the number of days 1:28:01.240 --> 1:28:03.519 that you spend in the hospital, the number of like 1:28:03.600 --> 1:28:05.640 different specialists that need to see you. 1:28:05.760 --> 1:28:07.120 It's exactly so. 1:28:07.280 --> 1:28:10.720 As one example from a paper, they cited that in 1:28:10.800 --> 1:28:16.799 twenty thirteen, sepsis cost the US over twenty four billion 1:28:16.880 --> 1:28:20.680 dollars in total hospital expenses, which is thirteen percent of 1:28:20.720 --> 1:28:25.840 total US hospital costs. WHOA, even though sepsis accounted for 1:28:25.960 --> 1:28:28.080 about three and a half percent. 1:28:27.880 --> 1:28:29.120 Of hospital stays. 1:28:29.840 --> 1:28:33.200 So it's disproportionate the cost to the amount of. 1:28:33.160 --> 1:28:34.400 Total hospital stays. 1:28:34.960 --> 1:28:40.160 Wow, Okay, because it can be such severe infections. Yeah, 1:28:40.720 --> 1:28:44.960 when we try to look more globally, I think what 1:28:45.000 --> 1:28:50.240 we really have to understand is just how underestimate these 1:28:50.320 --> 1:28:55.800 numbers likely are. Like the true scale of sepsis in 1:28:55.880 --> 1:28:59.479 the US, but also especially in low and middle income 1:28:59.520 --> 1:29:02.920 country across the globe, we really don't have a handle 1:29:03.040 --> 1:29:08.160 on the global burden. A paper from twenty seventeen estimated 1:29:08.760 --> 1:29:16.120 about forty nine million cases worldwide, wow, and eleven million 1:29:16.160 --> 1:29:21.519 sepsis related deaths. If those numbers are accurate. Like again, 1:29:21.600 --> 1:29:24.920 these are estimates, that would be almost twenty percent of 1:29:24.960 --> 1:29:29.640 all global deaths, the vast majority of which, it's estimated 1:29:29.720 --> 1:29:33.200 eighty five percent of those sepsis related deaths are in 1:29:33.280 --> 1:29:37.200 low and middle income countries that we just aren't getting 1:29:37.240 --> 1:29:37.920 good data on. 1:29:39.560 --> 1:29:41.480 Isn't that it's just so horrific? 1:29:42.840 --> 1:29:43.040 True? 1:29:43.120 --> 1:29:44.120 Yeah, it truly is. 1:29:44.680 --> 1:29:47.920 And it's also estimated that almost half of all these 1:29:48.000 --> 1:29:52.920 cases occur among children. So twenty million cases among children 1:29:53.000 --> 1:29:56.760 and two point nine million global deaths in children under 1:29:56.800 --> 1:30:02.000 age five is what this paper is estimating. So it's 1:30:02.040 --> 1:30:08.559 a huge healthcare problem. It's difficult to diagnose. Again, the 1:30:08.560 --> 1:30:12.280 mortality rate can vary quite a lot. Some papers just 1:30:12.360 --> 1:30:16.240 that try and estimate it overall, say anywhere between one 1:30:16.280 --> 1:30:19.400 in three and one in six people with sepsis can die, 1:30:20.320 --> 1:30:23.479 and so the World Health Organization has understandably made this 1:30:23.600 --> 1:30:30.160 a huge campaign and a priority as well as the 1:30:30.200 --> 1:30:33.720 Surviving Sepsis campaign that I mentioned already. One of the 1:30:33.760 --> 1:30:37.200 big things that the Surviving Sepsis campaign tries to do, 1:30:37.439 --> 1:30:42.400 in addition to raising awareness is also just gathering data 1:30:42.960 --> 1:30:46.479 and analyzing that data in a way to try and 1:30:46.600 --> 1:30:50.880 actually improve outcomes. And one of the big issues with 1:30:50.960 --> 1:30:53.960 the data that exists so far is that it generally 1:30:54.040 --> 1:30:56.760 comes from very high income countries, and so we have 1:30:56.800 --> 1:31:00.479 to recognize the limitations in how we can interpret and 1:31:00.520 --> 1:31:05.680 then apply that data to much less resource rich areas. Right, 1:31:07.720 --> 1:31:13.440 and importantly, all of these kind of campaigns and policies 1:31:14.120 --> 1:31:18.120 are largely, like I said, trying to improve outcomes as 1:31:18.160 --> 1:31:22.479 well as improve our recognition of sepsis and how we 1:31:22.520 --> 1:31:26.440 treat it to reduce morbidity and reduce mortality. 1:31:27.600 --> 1:31:30.200 Sepsis is something that has likely. 1:31:29.960 --> 1:31:33.559 Always been with us and will likely always be with us, 1:31:34.439 --> 1:31:37.840 and so it's not something that there are large groups 1:31:37.840 --> 1:31:42.720 saying we should eliminate sepsis entirely. That's not realistic goals, 1:31:42.760 --> 1:31:46.240 at least not at this point. And one I think 1:31:46.280 --> 1:31:52.760 of the reasons is how little we still understand about sepsis. 1:31:52.760 --> 1:31:53.040 Aaron. 1:31:53.439 --> 1:31:56.320 It's shocking, but also not shocking. 1:31:56.640 --> 1:31:59.960 There was a great paper from the Lancet Infectious Disease 1:32:00.040 --> 1:32:03.960 twenty nineteen that was written by people from the European 1:32:04.000 --> 1:32:09.080 Group on Immunology of Sepsis. AGIS loved it, and they 1:32:09.160 --> 1:32:12.400 were really upfront about their feelings on all of this. 1:32:12.600 --> 1:32:15.920 They basically were like, look, the reason that we have 1:32:16.080 --> 1:32:19.960 all these different definitions and all this controversy of like 1:32:20.160 --> 1:32:23.760 is it this criteria or that criteria, et cetera, it's 1:32:23.800 --> 1:32:26.920 because we just don't understand the immunology of sepsis. We 1:32:26.960 --> 1:32:30.240 don't we do not understand it. And so this article 1:32:30.320 --> 1:32:33.400 really laid out what they feel at least are the 1:32:33.479 --> 1:32:36.720 major deficits in our understanding and where we should go 1:32:36.920 --> 1:32:40.360 from here. They did this by looking at three different 1:32:40.360 --> 1:32:44.639 stages of sepsis before it develops, which is my favorite 1:32:44.720 --> 1:32:47.920 stage to think about, very important. Who is at risk, 1:32:48.280 --> 1:32:51.519 why are they at risk? What kinds of research do 1:32:51.560 --> 1:32:55.720 we even need to do to better understand this initial 1:32:55.880 --> 1:32:59.759 process and these specific risks to be able to actually 1:32:59.800 --> 1:33:01.759 pre event sepsis to begin with. 1:33:02.040 --> 1:33:04.360 Maybe change up the animal models we're using. 1:33:04.680 --> 1:33:08.320 Yes, we don't have good animal models for sepsis. Then 1:33:08.400 --> 1:33:12.360 we also have the next stage, the evolution of sepsis. 1:33:13.000 --> 1:33:16.880 What are these specific immune processes that are underlying this 1:33:17.080 --> 1:33:20.000 organ damage and how might we use these to better 1:33:20.040 --> 1:33:25.040 target treatments. There have been a lot, mostly of animal 1:33:25.080 --> 1:33:29.360 model studies of like, well, if you know IL ten 1:33:29.479 --> 1:33:33.000 is involved, let's affect that like these specific you know, 1:33:33.479 --> 1:33:37.960 immune modulators and the short answers they don't work right 1:33:38.040 --> 1:33:41.439 because these are too broad. So anything that we have 1:33:41.520 --> 1:33:44.360 tried to do to modulate the immune system ends up 1:33:44.439 --> 1:33:47.080 making things worse rather than better when it comes to sepsis. 1:33:47.120 --> 1:33:51.880 So far, and finally the third stage post sepsis, like 1:33:52.040 --> 1:33:55.719 what are the consequences of having a severe sepsis infection 1:33:55.880 --> 1:33:58.400 in the long term and what can some of these 1:33:58.439 --> 1:34:04.280 consequences teach us about the underlying pathology of secsis. We 1:34:04.280 --> 1:34:06.960 don't have answers to those, but I think it's just 1:34:07.040 --> 1:34:11.120 kind of a nice framework to think about where we 1:34:11.200 --> 1:34:12.280 can go from here. 1:34:12.720 --> 1:34:16.880 Yeah, I mean, yeah, it's good to have questions. You 1:34:17.000 --> 1:34:18.840 have to have direction exactly. 1:34:19.160 --> 1:34:23.040 Yeah, So it is going to be very interesting to 1:34:23.120 --> 1:34:30.240 see how these definitions continue to change, and how treatments 1:34:30.320 --> 1:34:31.759 then continue to change. 1:34:32.800 --> 1:34:35.880 I have a question about something you said about numbers 1:34:36.080 --> 1:34:41.120 going up? Yeah, is that an increase? Is that an 1:34:41.160 --> 1:34:43.680 apparent increase? Is that a real increase? What do we 1:34:43.720 --> 1:34:44.360 think about that? 1:34:44.680 --> 1:34:48.360 I don't know if we know. Okay, yeah, I don't 1:34:48.360 --> 1:34:49.000 know if we know. 1:34:49.600 --> 1:34:52.720 Is it because of changing definitions and so are we 1:34:52.840 --> 1:34:56.920 broadening our definition in order to capture people at an 1:34:56.960 --> 1:35:03.719 earlier stage to then prevent severe infection or are people 1:35:04.160 --> 1:35:07.080 actually coming in with sepsis and sicker. 1:35:08.640 --> 1:35:10.000 I don't have a great answer to that. 1:35:10.720 --> 1:35:14.280 Another question I had is if you have had sepsis 1:35:14.479 --> 1:35:18.320 one time and recovered, are you more likely to develop 1:35:18.360 --> 1:35:20.120 sepsis a second time? 1:35:20.439 --> 1:35:23.680 That's a very good question. I think it probably in 1:35:23.800 --> 1:35:28.240 large part depends on what the inciting factor was. If 1:35:28.280 --> 1:35:32.360 you have cancer and you are immunosuppressed and you end 1:35:32.439 --> 1:35:35.479 up getting infection that leads to sepsis and you recover 1:35:35.560 --> 1:35:38.440 from that, but you still have cancer and you're still immunosuppressed, 1:35:38.439 --> 1:35:41.519 then yes, you're still at high risk for sepsis. If 1:35:41.560 --> 1:35:46.240 you got a cut and a wound that was infected 1:35:46.640 --> 1:35:49.360 and you ended up with sepsis, but you don't have 1:35:49.439 --> 1:35:54.519 any other underlying immune conditions that we know of. Of course, 1:35:54.560 --> 1:35:58.559 there's so much individual immune response differences that we just 1:35:58.600 --> 1:36:01.559 don't know about. It's a good question as to whether 1:36:02.120 --> 1:36:03.840 you are at higher risk or not. I think we 1:36:03.880 --> 1:36:06.840 don't probably know enough to know in those instances. 1:36:07.800 --> 1:36:11.320 Okay, that makes sense, Yeah, great question though, that's very interesting. 1:36:12.280 --> 1:36:13.600 Any other questions. 1:36:13.280 --> 1:36:19.640 Arin I mean a million, Like do we even know 1:36:19.680 --> 1:36:21.280 what sepsis is at the end of this. 1:36:22.080 --> 1:36:25.280 I'm not sure that I do. Besides, like the very 1:36:25.320 --> 1:36:29.600 broad definition, but it seems it seems like a like 1:36:29.640 --> 1:36:33.600 a moving target. Yeah, and impossible to pin down. Yeah, 1:36:33.720 --> 1:36:36.800 right now, maybe the future, the future holds all the 1:36:36.840 --> 1:36:38.639 answers for sure. 1:36:39.479 --> 1:36:42.840 It is also probably interesting to think though about so 1:36:43.080 --> 1:36:48.280 many things now that maybe are more specific definitions that 1:36:48.560 --> 1:36:50.640 used to have just been called under a catch all 1:36:50.680 --> 1:36:54.599 of sepsis. Yes, so I do wonder how many other 1:36:54.720 --> 1:36:58.280 things might come out of our current definition of sepsis. 1:36:58.479 --> 1:37:01.559 Right, we have a bowl that is sepsis, and we 1:37:01.640 --> 1:37:03.960 can draw out little bits of paper that say, oh, 1:37:04.000 --> 1:37:06.320 that was Actually I don't know any of the things, 1:37:06.360 --> 1:37:09.080 but right we now call that something else that is 1:37:09.120 --> 1:37:09.719 not sepsis. 1:37:09.920 --> 1:37:13.680 Yeah, Yeah, interesting anyways. 1:37:14.120 --> 1:37:19.680 Sources, sources. I have a few papers that talk a 1:37:19.720 --> 1:37:22.599 little bit more about the changing definitions of sepsis and 1:37:22.760 --> 1:37:24.880 the more recent history of sepsis if you'd like to 1:37:24.960 --> 1:37:28.360 check those out. But let me just shout out again 1:37:28.600 --> 1:37:32.920 the fantastic book by Lindsay Fitzharris, The Butchering Art, All 1:37:32.960 --> 1:37:36.960 about Lister, all about early surgery, all about how germ 1:37:37.000 --> 1:37:39.280 theory kind of came to save the day a little 1:37:39.280 --> 1:37:44.280 bit and Lister. It's such a great read, it is, 1:37:44.400 --> 1:37:45.160 it is really great. 1:37:45.200 --> 1:37:48.599 I can also recommend I had a number of sources, 1:37:48.640 --> 1:37:51.200 not as many as sometimes, because the papers that I 1:37:51.240 --> 1:37:56.120 found were actually really comprehensive just on the overall definitions 1:37:56.320 --> 1:37:59.680 and what we know so far about the immunology of sepsis. 1:38:00.080 --> 1:38:04.080 So I will post those as well as the list 1:38:04.240 --> 1:38:06.559 of all of our sources from every single one of 1:38:06.600 --> 1:38:09.120 our episodes on our website This Podcast will Kill You 1:38:09.160 --> 1:38:10.679 dot Com under the episodes tab. 1:38:11.520 --> 1:38:15.160 Thank you again so much, Katie for taking the time 1:38:15.200 --> 1:38:18.360 to chat and sharing your story. It really means a ton. 1:38:18.560 --> 1:38:22.640 And we will also link to some more articles that 1:38:22.720 --> 1:38:26.720 Katie has shared, as well as the Sepsis Alliance website, 1:38:26.760 --> 1:38:29.679 which is sepsis dot org, so be sure to check 1:38:29.680 --> 1:38:33.040 out the sources for this episode and also the show notes. 1:38:33.680 --> 1:38:36.920 Thank you also to Bloodmobile, who provides the music for 1:38:37.040 --> 1:38:39.720 this episode and all of our episodes. 1:38:39.520 --> 1:38:42.439 And thank you too, exactly right, and thank. 1:38:42.280 --> 1:38:45.440 You to you listeners. We hope you enjoyed this episode. 1:38:45.720 --> 1:38:48.439 Yeah, we hope you found it interesting. What are your 1:38:49.200 --> 1:38:52.000 burning questions about sepsis still at the end of this 1:38:52.160 --> 1:38:56.760 let us know I have a lot. Yeah, and a 1:38:56.840 --> 1:39:00.760 special thank you as always to our wonderful general as patrons. 1:39:00.960 --> 1:39:03.599 We appreciate you so so very much. 1:39:04.680 --> 1:39:06.160 Thank you well. 1:39:06.560 --> 1:39:10.520 Until next time, wash your hands, you filthy animals.