WEBVTT 00:00:07.869 --> 00:00:10.890 Thanks for joining us again at the Canadian Breakpoint, 00:00:11.089 --> 00:00:14.349 a Canadian infectious diseases podcast by Canadian 00:00:14.349 --> 00:00:17.370 infectious diseases physicians. I'm Summer Stewart 00:00:17.370 --> 00:00:20.469 here with Dr. Rupina Pirawal, Pediatric Infectious 00:00:20.469 --> 00:00:23.289 Diseases Physician in Saskatoon. For today's 00:00:23.289 --> 00:00:26.010 episode, we invite Dr. Alison Fox Robichaud. 00:00:26.399 --> 00:00:29.640 to discuss sepsis and some of the important sepsis 00:00:29.640 --> 00:00:32.020 initiatives that her team is involved with here 00:00:32.020 --> 00:00:35.600 in Canada. Dr. Pierwal. Perfect. So welcome to 00:00:35.600 --> 00:00:37.640 another episode of our podcast, the Canadian 00:00:37.640 --> 00:00:40.560 Breakpoint. Today, we have a very special guest 00:00:40.560 --> 00:00:44.600 with us. It's Dr. Alison Fox Robichaux, who, 00:00:44.759 --> 00:00:48.689 as many of you might be aware. has done a lot 00:00:48.689 --> 00:00:50.929 of work around an important topic that we're 00:00:50.929 --> 00:00:53.189 going to be discussing today, which is sepsis. 00:00:53.649 --> 00:00:57.770 So to give a formal introduction, Dr. Fox Robichaux 00:00:57.770 --> 00:01:00.710 is a professor of medicine, the Hamilton Health 00:01:00.710 --> 00:01:03.890 Sciences Chair in Sepsis Research at McMaster 00:01:03.890 --> 00:01:06.909 University, and a critical care medicine specialist, 00:01:07.290 --> 00:01:10.129 head of service for the critical care response 00:01:10.129 --> 00:01:12.829 team, and the director of medical education at 00:01:12.829 --> 00:01:15.930 Hamilton Health Sciences. She's also the scientific 00:01:15.930 --> 00:01:20.530 director of Sepsis Canada. She has over 160 peer 00:01:20.530 --> 00:01:23.189 -reviewed publications reflecting broad academic 00:01:23.189 --> 00:01:26.750 interests, including animal models of sepsis, 00:01:26.750 --> 00:01:29.310 translational medicine, health services research, 00:01:29.450 --> 00:01:32.939 and clinical trials. A leader in the critical 00:01:32.939 --> 00:01:35.739 care community, she was the first female president 00:01:35.739 --> 00:01:39.040 of the Canadian Critical Care Society from 2015 00:01:39.040 --> 00:01:43.000 to 2018 and the first female chair of the Canadian 00:01:43.000 --> 00:01:47.900 Critical Care Examination Board. Well done. Internationally, 00:01:47.900 --> 00:01:50.780 she's also a member of the Global Sepsis Alliance 00:01:50.780 --> 00:01:53.260 Board, the Advisory Board of the International 00:01:53.260 --> 00:01:56.540 Society for Rapid Response Systems, the Council 00:01:56.540 --> 00:01:59.060 of the World Federation of Intensive and Critical 00:01:59.060 --> 00:02:02.760 Care. She is the organizing chair of the 17th 00:02:02.760 --> 00:02:05.780 World Congress of Intensive and Critical Care 00:02:05.780 --> 00:02:09.159 to be held in Vancouver this September. She's 00:02:09.159 --> 00:02:11.740 been honored nationally for her work in electronic 00:02:11.740 --> 00:02:14.960 early warning scores to prevent patient deterioration 00:02:14.960 --> 00:02:17.900 and received the King Charles III Coronation 00:02:17.900 --> 00:02:22.340 Medal for her national sepsis leadership. Internationally, 00:02:22.340 --> 00:02:25.680 in 2018, the Global Sepsis Alliance awarded her 00:02:25.680 --> 00:02:28.280 an individual award for her sepsis leadership. 00:02:29.020 --> 00:02:32.180 So as you can see, we have an expert with us 00:02:32.180 --> 00:02:35.060 today, and we're really fortunate to have you 00:02:35.060 --> 00:02:37.800 today. Thank you very much, Dr. Perwell, for 00:02:37.800 --> 00:02:41.520 inviting me to speak on your podcast. I'm honored 00:02:41.520 --> 00:02:45.620 to be here. Thank you. So, you know, I've been 00:02:45.620 --> 00:02:48.500 wanting to talk about sepsis for a while, just 00:02:48.500 --> 00:02:51.280 because it's, as we all know, a very important 00:02:51.280 --> 00:02:55.039 topic, something we... as healthcare professionals 00:02:55.039 --> 00:02:59.219 of kind of nurses, specialists, you know, if 00:02:59.219 --> 00:03:00.900 you're at the forefront, even family doctors, 00:03:01.139 --> 00:03:03.979 pharmacists, critical care physicians, obviously, 00:03:03.979 --> 00:03:08.310 are always involved in. I think there's a lot 00:03:08.310 --> 00:03:12.430 of information that has changed or is ongoing. 00:03:12.550 --> 00:03:14.409 There's a lot of research in this area. So I 00:03:14.409 --> 00:03:16.830 think for our listeners and also for myself, 00:03:16.909 --> 00:03:19.229 it would be nice if we could maybe start with 00:03:19.229 --> 00:03:22.889 the basics and let's just define sepsis. So how 00:03:22.889 --> 00:03:25.250 is it diagnosed? Are there clinical criteria? 00:03:25.969 --> 00:03:28.969 And are these being applied in clinical practice? 00:03:29.770 --> 00:03:31.930 I'm going to take it a step back. I think when 00:03:31.930 --> 00:03:35.509 sepsis and the word sepsis has been around since 00:03:35.509 --> 00:03:40.180 the Greeks, they called it poisoning. And recognize 00:03:40.180 --> 00:03:43.300 that it was a condition with a high mortality 00:03:43.300 --> 00:03:46.060 when, you know, people got an infection, got 00:03:46.060 --> 00:03:49.520 really, really sick with it. But the modern definitions 00:03:49.520 --> 00:03:52.900 have changed. And I really think that intensivists 00:03:52.900 --> 00:03:55.840 have gotten too smart sometimes in terms of that's 00:03:55.840 --> 00:03:58.379 been our biggest community. We are, you know, 00:03:58.379 --> 00:04:01.000 this is our disease and I'm going to call it 00:04:01.000 --> 00:04:04.050 a disease. We've been calling it a condition, 00:04:04.150 --> 00:04:06.449 a syndrome, but I'm going to call it a disease, 00:04:06.469 --> 00:04:10.250 same way as oncologists call cancer a disease, 00:04:10.449 --> 00:04:13.270 because I think that's important for the audience 00:04:13.270 --> 00:04:17.470 to understand. And it means that it's a disorder 00:04:17.470 --> 00:04:21.290 that affects how your body functions. It's more 00:04:21.290 --> 00:04:23.209 likely to have a known cause. And in this case, 00:04:23.209 --> 00:04:27.110 the known cause of sepsis is infections. And 00:04:27.110 --> 00:04:31.120 more likely in a distinct course. That is, there 00:04:31.120 --> 00:04:34.519 is a pattern to this. And the pattern for sepsis 00:04:34.519 --> 00:04:40.279 is organ dysfunction. That varies based on what 00:04:40.279 --> 00:04:43.000 the pathogen is, whether it's bacterial or viral 00:04:43.000 --> 00:04:47.180 or fungal. The host factors, whether your immune 00:04:47.180 --> 00:04:50.100 system's up to par or not. And some environmental 00:04:50.100 --> 00:04:53.139 and probably social factors that may make us, 00:04:53.160 --> 00:04:56.860 some individuals, more at risk than others. And 00:04:56.860 --> 00:05:00.259 it has some established treatments, maybe not 00:05:00.259 --> 00:05:03.339 enough in our field. But that definition now 00:05:03.339 --> 00:05:06.500 culminates in something that we call life -threatening 00:05:06.500 --> 00:05:10.519 organ dysfunction due to a host response to that 00:05:10.519 --> 00:05:14.420 infection. So it's really driven by how our body 00:05:14.420 --> 00:05:17.660 responds to infections. And some people can have 00:05:17.660 --> 00:05:21.560 an infection and not get sick at all. And other 00:05:21.560 --> 00:05:24.019 people get organ dysfunction that ends them up 00:05:24.019 --> 00:05:27.910 in our ICU. Yeah. So really a clinical like spectrum 00:05:27.910 --> 00:05:31.949 that we see. So are there some key warning signs? 00:05:32.110 --> 00:05:34.310 Because sepsis can obviously deterioration can 00:05:34.310 --> 00:05:37.250 happen very quickly. So are there any distinct 00:05:37.250 --> 00:05:39.610 warning signs or like you mentioned, there are 00:05:39.610 --> 00:05:42.050 obviously a risk factors. So you can you know 00:05:42.050 --> 00:05:45.790 that individuals are predisposed or may be predisposed 00:05:45.790 --> 00:05:50.100 to having this. But are there anything that physicians 00:05:50.100 --> 00:05:54.000 can look for? I think this is probably our biggest 00:05:54.000 --> 00:05:58.339 challenge. So unlike a heart attack, where we 00:05:58.339 --> 00:06:01.100 have biomarkers, you come into the hospital, 00:06:01.220 --> 00:06:03.980 you do it. We don't have the same thing for sepsis. 00:06:03.980 --> 00:06:07.800 So there's a lot of it depends on patient intuition. 00:06:09.399 --> 00:06:11.439 Something's wrong with me. I seek help. I've 00:06:11.439 --> 00:06:13.720 not felt like this before. And a lot of it depends 00:06:13.720 --> 00:06:16.300 on clinician intuition. This is an infection. 00:06:16.519 --> 00:06:20.079 But it also depends on doing some measurements, 00:06:20.300 --> 00:06:23.720 the simplest of which is, are your vital signs 00:06:23.720 --> 00:06:27.339 normal? Things like your respiratory rate, your 00:06:27.339 --> 00:06:30.040 blood pressure, your heart rate. Now, young people 00:06:30.040 --> 00:06:32.899 can hide that away sometimes and elder people 00:06:32.899 --> 00:06:37.189 may not get a fever. But those abnormal vital 00:06:37.189 --> 00:06:40.629 signs that include confusion, our patients, when 00:06:40.629 --> 00:06:43.589 they tell us about experiencing sepsis, can say 00:06:43.589 --> 00:06:46.389 it feels like everything from, you know, I'm 00:06:46.389 --> 00:06:49.589 not thinking clearly, I can't make urine, I've 00:06:49.589 --> 00:06:53.670 got nausea, vomiting, through to, you know, I 00:06:53.670 --> 00:06:55.709 just feel horrible and I'm not sure what's going 00:06:55.709 --> 00:06:58.680 on with me. And then I know like in the past, 00:06:58.839 --> 00:07:01.279 there's obviously some like vital sign parameters 00:07:01.279 --> 00:07:04.139 that we can use. So like somebody has, you know, 00:07:04.139 --> 00:07:06.740 a really elevated temperature, a very low temperature 00:07:06.740 --> 00:07:09.959 that could be in correlation if they have a really 00:07:09.959 --> 00:07:13.759 fast heart rate, as we see with that. So those, 00:07:13.800 --> 00:07:17.800 some of those criteria are being assessed at 00:07:17.800 --> 00:07:21.019 that time to kind of see if this patient is currently 00:07:21.019 --> 00:07:24.500 as critically ill as we think they are. I'm part 00:07:24.500 --> 00:07:27.519 of the upcoming Surviving Sepsis Campaign Guidelines. 00:07:27.680 --> 00:07:30.480 And one of the things is looking for those diagnostic 00:07:30.480 --> 00:07:34.319 tools. May not have great biomarkers yet, but 00:07:34.319 --> 00:07:38.439 we have that constellation of our vital signs 00:07:38.439 --> 00:07:42.319 put together into some things such as early warning 00:07:42.319 --> 00:07:44.740 scores. And some of my work, I say, well, is 00:07:44.740 --> 00:07:47.500 she working on early warning scores for patient 00:07:47.500 --> 00:07:50.399 deterioration? It's because I know that that's 00:07:50.399 --> 00:07:53.540 one of those things to pick up those early. signs 00:07:53.540 --> 00:07:56.420 of this infection is affecting the whole body 00:07:56.420 --> 00:08:00.259 and my body's ability to maintain homeostasis 00:08:00.259 --> 00:08:03.420 and that may show up before you have measurable 00:08:03.420 --> 00:08:09.019 organ dysfunction creatinine rising o2 sats falling 00:08:09.019 --> 00:08:12.300 platelet count dropping Yeah. And I guess like 00:08:12.300 --> 00:08:14.379 we mentioned some of the biomarkers, or you mentioned 00:08:14.379 --> 00:08:18.100 biomarkers in general. So in my world, I think 00:08:18.100 --> 00:08:19.980 in some of the other hospitals too, of some of 00:08:19.980 --> 00:08:23.120 the listeners that are tuning in today, there's 00:08:23.120 --> 00:08:26.620 a few that are commonly used, I would say. So 00:08:26.620 --> 00:08:29.420 like procalcitonin in certain centers is being 00:08:29.420 --> 00:08:31.939 used now, even sometimes more frequently than 00:08:31.939 --> 00:08:35.740 CRP. And obviously CRP has like historically 00:08:35.740 --> 00:08:38.899 been used a lot. So what are your thoughts on 00:08:38.899 --> 00:08:42.340 this? I mean, obviously we have to interpret 00:08:42.340 --> 00:08:45.240 medicine from like the patient and their clinical 00:08:45.240 --> 00:08:47.340 standpoint, and we shouldn't be using a lot of 00:08:47.340 --> 00:08:49.000 the diagnostic criteria, but they're supporting 00:08:49.000 --> 00:08:52.080 evidence in certain situations. But what do you 00:08:52.080 --> 00:08:56.320 feel about that? So let me start with most of 00:08:56.320 --> 00:09:00.139 the biomarker, diagnostic biomarker work in sepsis 00:09:00.139 --> 00:09:02.220 has unfortunately been done in the critically 00:09:02.220 --> 00:09:05.539 ill and not where 80 % of the septic patients 00:09:05.539 --> 00:09:08.850 present the emergency department. Probably the 00:09:08.850 --> 00:09:11.370 last time I wrote a little study on this was 00:09:11.370 --> 00:09:15.549 about only about 11 studies may have seen the 00:09:15.549 --> 00:09:17.830 headlines in the Globe and Mail this week that 00:09:17.830 --> 00:09:19.870 our colleagues and some of our colleagues in 00:09:19.870 --> 00:09:22.269 the network in Toronto have think they've got 00:09:22.269 --> 00:09:26.690 this panel of genomic markers that may may have 00:09:26.690 --> 00:09:29.129 and that they're working on this lovely device 00:09:29.129 --> 00:09:33.509 that so there are some signals from genomics, 00:09:33.570 --> 00:09:37.090 but I think we need to. quarterback sort of pull 00:09:37.090 --> 00:09:39.950 all of this together. So if I talk about procalcitonin, 00:09:40.049 --> 00:09:43.029 the evidence for procalcitonin is probably strongest 00:09:43.029 --> 00:09:45.549 in the patient population you look after, which 00:09:45.549 --> 00:09:48.950 is the neonates. And there's at least one really 00:09:48.950 --> 00:09:51.610 good study that shows that tells me whether I 00:09:51.610 --> 00:09:54.350 really can continue the antibiotics or I can 00:09:54.350 --> 00:09:57.230 stop the antibiotics. Similarly, in the adult 00:09:57.230 --> 00:10:00.110 population, it tells me I can stop antibiotics 00:10:00.110 --> 00:10:03.330 because it's less likely to be a bacterial infection. 00:10:03.870 --> 00:10:05.879 Unfortunately, people haven't changed this in 00:10:05.879 --> 00:10:08.120 their practice to actually do that when you go 00:10:08.120 --> 00:10:11.039 back and look at you know has that been translated 00:10:11.039 --> 00:10:14.299 it's not so great in the diagnostic end because 00:10:14.299 --> 00:10:19.840 it has some bacterias don't cause an elevated 00:10:19.840 --> 00:10:23.159 procalcitonin it's lousy for viruses and for 00:10:23.159 --> 00:10:27.250 fungal infections Similarly, CRP, well, CRP is 00:10:27.250 --> 00:10:28.929 just running the rounds of who's going to use 00:10:28.929 --> 00:10:30.990 it, the latest biomarker. The cardiologists were 00:10:30.990 --> 00:10:34.070 using it for a while. Now we're using it, but 00:10:34.070 --> 00:10:37.649 it's an acute phase reactant. So it goes up, 00:10:37.649 --> 00:10:41.429 like fibrinogen goes up and albumin goes down. 00:10:41.509 --> 00:10:43.850 So it really just tells you you've got an acute 00:10:43.850 --> 00:10:46.330 inflammatory reaction that's been turned on. 00:10:46.720 --> 00:10:50.679 And so people are looking at pancreatic stone 00:10:50.679 --> 00:10:53.580 protein and other markers in the inflammatory 00:10:53.580 --> 00:10:56.360 cascade. And we've been doing some work because 00:10:56.360 --> 00:11:00.019 we understand that coagulation is intimately 00:11:00.019 --> 00:11:03.799 linked to this inflammatory response from the 00:11:03.799 --> 00:11:06.080 very earliest stages. So we've actually been 00:11:06.080 --> 00:11:09.139 looking at some coagulation markers that may. 00:11:09.980 --> 00:11:13.259 be equally important. And surprisingly, it's 00:11:13.259 --> 00:11:15.299 not their going up that's important. It's their 00:11:15.299 --> 00:11:18.600 going down that's important. Yeah, that's fair. 00:11:18.720 --> 00:11:21.820 And so I guess economically, so I know some centers 00:11:21.820 --> 00:11:24.440 don't have procalcitonin because it's a little 00:11:24.440 --> 00:11:28.360 bit more expensive, as I find in kind of talking 00:11:28.360 --> 00:11:32.139 to microbiologists and other lab techs. And so 00:11:32.139 --> 00:11:37.490 how does that kind of I guess, impact which biomarkers 00:11:37.490 --> 00:11:40.129 are in which. I think many centers are now using 00:11:40.129 --> 00:11:42.610 CRP because it had been used by the cardiologist. 00:11:42.690 --> 00:11:45.330 So it's a good rough screen that just says, you 00:11:45.330 --> 00:11:47.490 know what, this person's got an ongoing inflammatory 00:11:47.490 --> 00:11:50.570 reaction and we've got organ dysfunction. And 00:11:50.570 --> 00:11:53.730 maybe we've got to go looking for other markers 00:11:53.730 --> 00:11:57.509 of coagulation or other things that may be disrupted 00:11:57.509 --> 00:12:02.100 that says there's an ongoing. immunothrombotic, 00:12:02.159 --> 00:12:04.500 there's a new word for people perhaps, where 00:12:04.500 --> 00:12:06.919 the immune system and the clotting system have 00:12:06.919 --> 00:12:10.419 been over activated as part of the response to 00:12:10.419 --> 00:12:13.480 infection. Got it. Yeah. And so it's a good thing 00:12:13.480 --> 00:12:16.279 you mentioned. It's more of a spot test, I would 00:12:16.279 --> 00:12:19.519 say, instead of some people are using procalcitonin 00:12:19.519 --> 00:12:22.200 and trending it. And I always find that very 00:12:22.200 --> 00:12:25.139 difficult to explain because it really isn't 00:12:25.139 --> 00:12:27.179 a trend. Like, I don't think that we have good 00:12:27.179 --> 00:12:30.120 information in terms of its clearance from the 00:12:30.120 --> 00:12:32.639 body. And there haven't been a lot of studies 00:12:32.639 --> 00:12:35.519 that look at it mostly as a spot check. Right. 00:12:35.639 --> 00:12:39.730 In terms of its diagnosis. Okay, fantastic. Yeah. 00:12:39.809 --> 00:12:43.789 And so going back to obviously our sepsis and 00:12:43.789 --> 00:12:46.389 the disease that we're talking about today. So 00:12:47.179 --> 00:12:49.519 I mean, the important things, and I think you 00:12:49.519 --> 00:12:52.179 have seen this in your clinical world a lot, 00:12:52.299 --> 00:12:57.320 is the acute complications that you can get from 00:12:57.320 --> 00:13:00.360 this type of disease and why we're talking about 00:13:00.360 --> 00:13:03.120 it and why it's so important to identify. So 00:13:03.120 --> 00:13:05.720 do you have any shared experiences that you want 00:13:05.720 --> 00:13:08.980 to share today with our audience in terms of 00:13:08.980 --> 00:13:11.820 some of the both either acute or long -term consequences 00:13:11.820 --> 00:13:14.840 just to kind of weigh some light or shine some 00:13:14.840 --> 00:13:18.049 light on this disease? Well, let's talk the acute. 00:13:18.169 --> 00:13:21.710 The most common cause of sepsis in North America, 00:13:21.710 --> 00:13:25.730 at least, is pneumonia. It's still the most common 00:13:25.730 --> 00:13:29.909 cause. In many parts of the world, sub -Saharan 00:13:29.909 --> 00:13:32.210 Africa, for example, it's diarrheal disease. 00:13:32.629 --> 00:13:36.669 But in North America, it's pneumonia. We still 00:13:36.669 --> 00:13:39.990 see urinary tract infections leading to sepsis 00:13:39.990 --> 00:13:43.120 in the elderly. bad intra -abdominal infections, 00:13:43.500 --> 00:13:46.159 whether it's your gallbladder or your appendix 00:13:46.159 --> 00:13:49.899 can lead to that, and skin infections, right? 00:13:50.179 --> 00:13:54.039 So skin infections, diabetics from some work 00:13:54.039 --> 00:13:56.299 that we've done are not necessarily at increased 00:13:56.299 --> 00:13:59.340 risk, short -term risk for getting sepsis, but 00:13:59.340 --> 00:14:01.779 there's long -term complications of diabetics 00:14:01.779 --> 00:14:05.019 having sepsis. Yeah, and so definitely I think 00:14:05.019 --> 00:14:09.019 the acute deterioration and the multi -organ 00:14:09.019 --> 00:14:13.559 dysfunction are some of the challenges that you 00:14:13.559 --> 00:14:16.899 guys probably see. Oh, like supporting organs. 00:14:16.960 --> 00:14:20.259 So, you know, certainly the organ support that 00:14:20.259 --> 00:14:24.149 we do. ventilators so people on ventilators long 00:14:24.149 --> 00:14:27.669 times on like months on ventilators you know 00:14:27.669 --> 00:14:32.190 i've got young patients young people who've ended 00:14:32.190 --> 00:14:36.710 up with legionella and then that's a bad one 00:14:36.710 --> 00:14:39.149 because the liver fails the kidney fails and 00:14:39.149 --> 00:14:42.090 we've seen a rise in legionella in the last little 00:14:42.090 --> 00:14:44.629 while you know i'm not sure people are cleaning 00:14:44.629 --> 00:14:49.259 out their ventilation systems And then the other 00:14:49.259 --> 00:14:54.620 one that we're seeing is a lot of rise in Staph 00:14:54.620 --> 00:14:58.100 aureus. And this is the worst year I've ever 00:14:58.100 --> 00:15:01.279 seen for group A strep. So skin -based inspections, 00:15:01.539 --> 00:15:05.039 like it's just a bad season. And I get all the 00:15:05.039 --> 00:15:07.360 notifications for the contact tracing in the 00:15:07.360 --> 00:15:10.259 hospital and yet another group A strep contact 00:15:10.259 --> 00:15:13.960 tracing. Yeah. We've seen an uptick of that too. 00:15:14.120 --> 00:15:16.440 I don't even, I can't recall in my sort of 25 00:15:16.440 --> 00:15:19.100 years as an attending in the ICU that I've had 00:15:19.100 --> 00:15:21.759 four. And this year I had four patients with 00:15:21.759 --> 00:15:24.539 group A strep, two of them very sick and two 00:15:24.539 --> 00:15:27.500 of them just with wounds that, you know, whether 00:15:27.500 --> 00:15:29.980 we caught it early or otherwise. And I guess 00:15:29.980 --> 00:15:31.879 one of the things with, you know, like obviously 00:15:31.879 --> 00:15:34.399 many diseases you want to pick up early with 00:15:34.399 --> 00:15:37.679 sepsis, I think the, we always talk about, you 00:15:37.679 --> 00:15:41.259 know, starting treatment very early in this condition, 00:15:41.299 --> 00:15:44.799 right? Or in this disease. And so, and so it 00:15:44.799 --> 00:15:48.690 has that. Any of the, you know, obviously there's 00:15:48.690 --> 00:15:51.509 the early warning signs, some of the vital signs 00:15:51.509 --> 00:15:54.250 of the critically ill, and you're thinking about 00:15:54.250 --> 00:15:56.710 sepsis. You know, we all talk about that golden 00:15:56.710 --> 00:16:01.129 hour, the original, where we want to start soon. 00:16:01.350 --> 00:16:05.429 So in your world, is that something over the 00:16:05.429 --> 00:16:07.830 years, has that, have you seen less complications 00:16:07.830 --> 00:16:10.710 since those guidelines have come out? Or is that 00:16:10.710 --> 00:16:13.009 something you guys are working with to see if, 00:16:13.070 --> 00:16:17.639 you know, is that one hour mark ideal? So certainly 00:16:17.639 --> 00:16:20.480 surviving sepsis campaign says if you're in shock 00:16:20.480 --> 00:16:24.700 and you have an obvious source of infection, 00:16:24.899 --> 00:16:28.259 that golden hour, less than an hour is really 00:16:28.259 --> 00:16:31.259 important. If you have a suspicion of sepsis, 00:16:31.259 --> 00:16:35.139 that golden hour is important. And you know where 00:16:35.139 --> 00:16:37.620 the source of infection. If you're not so sure, 00:16:37.799 --> 00:16:40.179 then you've got a little time to wait, do some 00:16:40.179 --> 00:16:42.440 cultures, wait for some things to come back from 00:16:42.440 --> 00:16:45.710 the lab. You know, we've shifted from. relying 00:16:45.710 --> 00:16:51.269 on lab work immediately waiting for that cbc 00:16:51.269 --> 00:16:55.009 to come back for example as like this is obviously 00:16:55.009 --> 00:16:57.389 they've got a source of infection and they're 00:16:57.389 --> 00:17:00.149 obviously got organ dysfunction or they're not 00:17:00.149 --> 00:17:05.119 perfusing jump on it have i seen less i Don't 00:17:05.119 --> 00:17:08.400 think we have enough data in Canada, particularly 00:17:08.400 --> 00:17:11.700 unlike Australia and other places, to say we've 00:17:11.700 --> 00:17:15.019 moved the bar from if you end up in an ICU with 00:17:15.019 --> 00:17:18.559 sepsis, your mortality rate is still around 20 00:17:18.559 --> 00:17:21.940 to 25 percent. If you're older, it's going to 00:17:21.940 --> 00:17:24.599 be higher. If you're immunosuppressed, it's going 00:17:24.599 --> 00:17:28.759 to be higher. And the complications therein afterwards 00:17:28.759 --> 00:17:31.920 as well. Yeah. And I would assume that the earlier 00:17:31.920 --> 00:17:33.500 you start, the earlier you pick up the disease. 00:17:34.259 --> 00:17:37.160 It's always like the earlier you pick it up, 00:17:37.240 --> 00:17:40.460 the more likely we are to reverse the organ dysfunction 00:17:40.460 --> 00:17:43.640 and be able to get people shorter stays through 00:17:43.640 --> 00:17:46.160 the hospital. And so then that leads me to the 00:17:46.160 --> 00:17:49.960 next point, because we actually, I first heard 00:17:49.960 --> 00:17:52.539 about, you know, more the work that you guys 00:17:52.539 --> 00:17:56.460 have been doing with Sepsis Canada at an AMR, 00:17:56.460 --> 00:17:58.859 antimicrobial resistance symposium that was back 00:17:58.859 --> 00:18:02.140 in November in Toronto. And, you know, it was 00:18:02.140 --> 00:18:05.079 really interesting to see because there's this, 00:18:05.200 --> 00:18:09.359 you know, choosing wisely, making sure that we 00:18:09.359 --> 00:18:11.599 are using, you know, antibiotics appropriately, 00:18:11.759 --> 00:18:15.740 because we do have that. concern with the growing 00:18:15.740 --> 00:18:18.759 concerns of antimicrobial resistance as well. 00:18:18.859 --> 00:18:21.900 So for our audience who, you know, is kind of 00:18:21.900 --> 00:18:24.240 thinking, you know, we're saying basically you 00:18:24.240 --> 00:18:27.140 need to treat if there is sepsis and there's 00:18:27.140 --> 00:18:32.019 an infection. How do you balance that with the 00:18:32.019 --> 00:18:36.259 growing concerns of AMR? So let's start with 00:18:36.259 --> 00:18:38.819 what we know between the AMR and sepsis burden. 00:18:38.980 --> 00:18:41.700 Some great data that's come out of John Hopkins 00:18:41.700 --> 00:18:44.079 and the antimicrobial resistance collaborators. 00:18:44.559 --> 00:18:47.960 So if we estimate that there are currently about 00:18:47.960 --> 00:18:52.940 13 million deaths due to sepsis globally, and 00:18:52.940 --> 00:18:57.000 about almost 9 million of those are due to bacterial 00:18:57.000 --> 00:19:01.180 infections, then 5 million of those are due to 00:19:01.180 --> 00:19:07.140 resistant organisms. OK, and associated or attributable, 00:19:07.220 --> 00:19:10.900 you know, is one point. So it's a huge problem. 00:19:11.039 --> 00:19:15.519 And if we know that within the next five years 00:19:15.519 --> 00:19:20.460 or more, the amount of AMR is going to continue 00:19:20.460 --> 00:19:24.519 to rise, particularly in countries in the world 00:19:24.519 --> 00:19:28.500 who have not had the tight regulation that we 00:19:28.500 --> 00:19:31.220 have had over many of our antibiotics. I talked 00:19:31.220 --> 00:19:34.579 to colleagues in India. colleagues in Saudi Arabia, 00:19:34.660 --> 00:19:37.480 where it's a huge problem, where their first 00:19:37.480 --> 00:19:40.759 line antibiotics are meropenem, and they still 00:19:40.759 --> 00:19:43.759 have resistance to it. I know. It's terrifying. 00:19:43.940 --> 00:19:46.779 So I think, you know, are we in good shape? Because 00:19:46.779 --> 00:19:49.319 we've controlled to a certain extent, some of 00:19:49.319 --> 00:19:53.539 the misuse of antibiotics, right? Do we have 00:19:53.539 --> 00:19:57.519 good antimicrobial stewardship programs in our 00:19:57.519 --> 00:20:00.059 hospitals, at least our academic centers? We 00:20:00.059 --> 00:20:04.859 do. It helps to say, OK, are we getting evidence 00:20:04.859 --> 00:20:08.000 like the balance trial that says if you've got 00:20:08.000 --> 00:20:10.519 a gram negative bacteremia, you don't need 14 00:20:10.519 --> 00:20:14.480 days, seven days is adequate. So we're not persisting. 00:20:14.480 --> 00:20:18.079 And some really interesting work coming about 00:20:18.079 --> 00:20:22.200 being careful about what antibiotics you're using. 00:20:22.799 --> 00:20:25.839 for the most sick because you may be adding to 00:20:25.839 --> 00:20:28.799 the problem. Some fantastic work coming out of 00:20:28.799 --> 00:20:31.519 Michigan where a natural experiment where they 00:20:31.519 --> 00:20:35.700 lost Peptazole. They didn't have it for a period 00:20:35.700 --> 00:20:38.200 of time. And they were only using gram -negative 00:20:38.200 --> 00:20:41.339 coverage. And in fact, they had better outcomes, 00:20:41.579 --> 00:20:44.180 statistically significant better outcomes during 00:20:44.180 --> 00:20:47.140 that period. And so they're now going and looking 00:20:47.140 --> 00:20:50.299 at this. But, you know, sometimes you don't kill 00:20:50.299 --> 00:20:53.450 the anaerobes. And I would say pneumonia is probably 00:20:53.450 --> 00:20:56.529 our biggest gap. Like don't kill the anaerobes 00:20:56.529 --> 00:20:59.789 there. And certain skin infections don't kill 00:20:59.789 --> 00:21:02.990 the anaerobes, right? They may in fact be beneficial. 00:21:03.490 --> 00:21:07.220 Yeah. Yeah. And so definitely, I think. Like 00:21:07.220 --> 00:21:10.380 you mentioned, an important thing is knowing 00:21:10.380 --> 00:21:13.779 kind of your local system and having, you know, 00:21:13.779 --> 00:21:17.079 the pharmacists involved. I think like what we've 00:21:17.079 --> 00:21:18.920 done locally, even if you don't have an established 00:21:18.920 --> 00:21:21.559 stewardship program, is working with the local 00:21:21.559 --> 00:21:24.039 pharmacist to create stop dates and that type 00:21:24.039 --> 00:21:26.940 of thing, which even if you are, you know, worried 00:21:26.940 --> 00:21:30.579 about sepsis and you're going to start antibiotics 00:21:30.579 --> 00:21:34.440 and kind of reminding ourselves that we can follow 00:21:34.440 --> 00:21:36.329 cultures, you can follow the patient. clinically 00:21:36.329 --> 00:21:38.829 and getting them off as soon as possible and 00:21:38.829 --> 00:21:41.349 remember sepsis is the body's response to that 00:21:41.349 --> 00:21:44.029 infection it doesn't mean the infection's continuing 00:21:44.029 --> 00:21:47.130 the organ dysfunction may be continuing you've 00:21:47.130 --> 00:21:49.829 killed the antibiotics with the appropriate things 00:21:49.829 --> 00:21:53.349 you just don't want to add to the antimicrobial 00:21:53.349 --> 00:21:55.829 resistance problem yeah so it's a really like 00:21:55.829 --> 00:22:00.569 a fine balance um and and why like there's multidisciplinary 00:22:00.569 --> 00:22:03.589 teams that are involved yeah in these cases yeah 00:22:04.569 --> 00:22:07.609 Perfect. So moving forward. So you mentioned 00:22:07.609 --> 00:22:09.029 some of the research that you guys are doing. 00:22:09.490 --> 00:22:13.109 So what is the future in sepsis research? What 00:22:13.109 --> 00:22:15.869 does it look like? Are we going to get more information 00:22:15.869 --> 00:22:18.950 on some of these biomarkers or novel biomarkers 00:22:18.950 --> 00:22:23.890 or just overall defining sepsis in general? So 00:22:23.890 --> 00:22:26.309 we've done some really great work in the network 00:22:26.309 --> 00:22:29.390 over the past six years. I think we're still 00:22:29.390 --> 00:22:32.079 working on getting that. prevalence across the 00:22:32.079 --> 00:22:34.859 country. That's hard data. We're relying on two 00:22:34.859 --> 00:22:37.700 things. First of all, we're relying on discharge 00:22:37.700 --> 00:22:40.700 abstract data, which means people have to write 00:22:40.700 --> 00:22:43.400 that on the chart. If somebody's septic, write 00:22:43.400 --> 00:22:47.480 it on the chart, please. And so we're starting 00:22:47.480 --> 00:22:49.980 to pull that. We've got this conflict between 00:22:49.980 --> 00:22:53.680 the modern research definitions, SEP3, organ 00:22:53.680 --> 00:22:56.839 dysfunction, and what we currently use for discharge 00:22:56.839 --> 00:22:59.960 abstracting, which is ICD -10 codes. We're not 00:22:59.960 --> 00:23:02.589 at ICD -10. ICD -11, which gives a little better 00:23:02.589 --> 00:23:07.269 definition. And everybody's had a version of 00:23:07.269 --> 00:23:09.970 how many codes do you put in? We've published 00:23:09.970 --> 00:23:12.609 some work looking at probably what is a broader 00:23:12.609 --> 00:23:15.509 definition for sepsis, and we're applying that 00:23:15.509 --> 00:23:17.829 to some CHI -HI data along with some traditional 00:23:17.829 --> 00:23:21.230 ones. So look for that coming. The other thing 00:23:21.230 --> 00:23:24.769 we've done is look at both the costs and the 00:23:24.769 --> 00:23:29.400 outcomes of sepsis. The cost is staggering. Even 00:23:29.400 --> 00:23:32.720 before the pandemic in a province of Ontario, 00:23:33.059 --> 00:23:36.400 sepsis cost the province approximately a billion 00:23:36.400 --> 00:23:39.759 dollars a year in Ontario. And that was only 00:23:39.759 --> 00:23:41.579 the adults. It wasn't the kitties. It wasn't 00:23:41.579 --> 00:23:44.779 the long -term outcomes. And that mortality after 00:23:44.779 --> 00:23:48.660 sepsis was 50 % in the next five years. So you 00:23:48.660 --> 00:23:51.180 had 20 % not survive if you're in ICU, another 00:23:51.180 --> 00:23:54.539 50%. And the why of that we're starting to understand. 00:23:54.980 --> 00:24:00.150 Part of that why is cardiovascular disease. ongoing 00:24:00.150 --> 00:24:04.329 thrombosis, strokes, heart attacks. I said that, 00:24:04.329 --> 00:24:07.309 you know, diabetics are at particular risk. So 00:24:07.309 --> 00:24:09.430 if you're not a diabetic, that risk in the next 00:24:09.430 --> 00:24:12.089 five years is about 10 % for cardiovascular disease 00:24:12.089 --> 00:24:14.549 after an episode of sepsis. If you're diabetic, 00:24:14.690 --> 00:24:18.210 that goes up to 40%. So the combination of the 00:24:18.210 --> 00:24:21.150 endothelial damage that occurs with diabetes 00:24:21.150 --> 00:24:24.509 gets exacerbated with sepsis and makes your risk 00:24:24.509 --> 00:24:27.549 for cardiovascular disease even higher. The other 00:24:27.549 --> 00:24:30.809 thing we've learned is that those survivors of 00:24:30.809 --> 00:24:35.269 sepsis become the highest cost users, at least 00:24:35.269 --> 00:24:37.890 in the province of Ontario, based on ICS data 00:24:37.890 --> 00:24:42.849 for the next 90 days, like the top 1%, even after 00:24:42.849 --> 00:24:45.130 hospital discharge, they cost the healthcare 00:24:45.130 --> 00:24:48.630 system a lot of money. So I think the next big 00:24:48.630 --> 00:24:52.490 field is. understanding why that mortality beyond 00:24:52.490 --> 00:24:54.869 cardiovascular disease, what treatments can we 00:24:54.869 --> 00:24:59.109 apply? And what impact can we have? So in fact, 00:24:59.109 --> 00:25:01.930 we're working right now as text going on, I can 00:25:01.930 --> 00:25:04.390 hear them background on my phone, because we're 00:25:04.390 --> 00:25:07.529 working on a meeting grant to start talking about 00:25:07.529 --> 00:25:09.890 a registry for sepsis survivors, we don't have 00:25:09.890 --> 00:25:12.730 any way of tracking those survivors afterwards. 00:25:12.930 --> 00:25:16.849 And many of them have significant cognitive impairment, 00:25:17.150 --> 00:25:20.920 organs that are barely functioning. I shared 00:25:20.920 --> 00:25:24.299 a story recently in the media about a young girl 00:25:24.299 --> 00:25:27.680 who is a quad amputee. And we have a number of 00:25:27.680 --> 00:25:31.140 amputees who work in the network who have had 00:25:31.140 --> 00:25:34.440 such bad septic shock that, and with the supports 00:25:34.440 --> 00:25:37.059 that we have to provide, that they've lost limbs. 00:25:37.259 --> 00:25:40.980 And that's a big complication. Yeah. We're learning 00:25:40.980 --> 00:25:43.980 a lot about who's being taught about sepsis as 00:25:43.980 --> 00:25:47.490 healthcare professionals. Right. And how we might 00:25:47.490 --> 00:25:50.029 teach even school children. One of my honors 00:25:50.029 --> 00:25:53.549 thesis students just completed a little pilot 00:25:53.549 --> 00:25:55.390 study with a bunch of high school students and 00:25:55.390 --> 00:25:57.569 their teachers about sepsis and what they could 00:25:57.569 --> 00:26:00.869 learn. So educating the public is really important. 00:26:01.190 --> 00:26:04.630 Figuring out what the barriers are in the emergency 00:26:04.630 --> 00:26:07.009 department. We have all of these lovely, we have 00:26:07.009 --> 00:26:10.109 stroke protocols and we have trauma teams. And 00:26:10.109 --> 00:26:13.710 the evidence for team sepsis or code sepsis teams 00:26:13.710 --> 00:26:17.740 not as strong. Literature suggesting maybe if 00:26:17.740 --> 00:26:20.119 we just improve the performance in the hospitals, 00:26:20.220 --> 00:26:22.900 we don't need to go to specialized units like 00:26:22.900 --> 00:26:25.680 we do for strokes and trauma, but that's an involving 00:26:25.680 --> 00:26:30.119 literature. And then finally, what tools do we 00:26:30.119 --> 00:26:34.359 have to treat this? Vic2 is not doing well. We 00:26:34.359 --> 00:26:38.259 have a serious problem that 30 plus years of 00:26:38.259 --> 00:26:41.859 really not having any novel therapeutics aside 00:26:41.859 --> 00:26:44.059 from antibiotics, fluid and supportive care. 00:26:45.069 --> 00:26:48.009 So looking for novel therapeutics, we've got 00:26:48.009 --> 00:26:51.670 trials running based out of Winnipeg where plasma 00:26:51.670 --> 00:26:54.170 exchange might be. And I know there's people 00:26:54.170 --> 00:26:56.569 thinking, oh, this is the latest greatest, but 00:26:56.569 --> 00:26:58.710 we need to study it and find out if it actually 00:26:58.710 --> 00:27:01.430 is going to work. I've got colleagues in Ottawa 00:27:01.430 --> 00:27:05.289 who are starting a stem cell therapy for septic 00:27:05.289 --> 00:27:09.690 shock patients. Colleague today just registered 00:27:09.690 --> 00:27:13.069 another support. What other? ways can we support 00:27:13.069 --> 00:27:16.069 for blood pressure? You know, there's a double 00:27:16.069 --> 00:27:18.609 edged sword for supporting with the medications 00:27:18.609 --> 00:27:20.849 we use to support blood pressure. Can we use 00:27:20.849 --> 00:27:22.990 other adjuncts to support blood pressure in the 00:27:22.990 --> 00:27:25.990 ICU? So those are some of the clinical trials 00:27:25.990 --> 00:27:28.789 going on. And then we're really doing some innovative 00:27:28.789 --> 00:27:31.450 work to try and understand the pathophysiology 00:27:31.450 --> 00:27:34.769 better as well with preclinical work. So a lot 00:27:34.769 --> 00:27:38.210 of work that's, you know, even in years and years, 00:27:38.329 --> 00:27:42.170 like this is not a disease. But it's just, I 00:27:42.170 --> 00:27:45.970 guess, like not very well understood and parts 00:27:45.970 --> 00:27:47.890 we know of it. But again, like you mentioned, 00:27:47.970 --> 00:27:50.029 it's a clinical spectrum, right? So not everybody 00:27:50.029 --> 00:27:53.490 presents the same way. And I think that's probably 00:27:53.490 --> 00:27:56.049 the challenging part here. And look at, you know, 00:27:56.089 --> 00:27:59.369 if you compare us to the oncology field and how 00:27:59.369 --> 00:28:02.920 long it took to get. precision treatments and 00:28:02.920 --> 00:28:06.880 more understanding of each individual kind of 00:28:06.880 --> 00:28:08.940 cancer and what treatments you could or could 00:28:08.940 --> 00:28:12.279 not use. I think we're behind with sepsis as 00:28:12.279 --> 00:28:14.779 a disease. Will we get there eventually? I hope 00:28:14.779 --> 00:28:17.839 so, in a coordinated effort, but it's a similar 00:28:17.839 --> 00:28:20.440 problem, but just a shorter time frame, right? 00:28:20.539 --> 00:28:24.400 We've got minutes to hours as opposed to something 00:28:24.400 --> 00:28:27.420 that's a little more slowly. to evolve. Yeah, 00:28:27.440 --> 00:28:29.839 that's fantastic. You're doing some really good 00:28:29.839 --> 00:28:31.480 work out there and a lot of your colleagues. 00:28:31.680 --> 00:28:34.940 And so it's obviously something that we deal 00:28:34.940 --> 00:28:37.000 with all the time in infectious diseases. We're 00:28:37.000 --> 00:28:39.740 working very closely with those that are in sepsis 00:28:39.740 --> 00:28:43.140 and septic shock. So yeah, it would be really 00:28:43.140 --> 00:28:45.000 interesting to see some of the findings of those 00:28:45.000 --> 00:28:48.619 research projects. So I guess just to end off 00:28:48.619 --> 00:28:51.299 today, because that was a wealth of information 00:28:51.299 --> 00:28:54.559 for myself as well, but also for I'm sure our 00:28:54.559 --> 00:28:58.460 listeners that are really fortunate to have tuned 00:28:58.460 --> 00:29:01.519 into today's episode. So what's one key message, 00:29:01.559 --> 00:29:04.079 I guess, that, I mean, there's multiple messages 00:29:04.079 --> 00:29:06.420 you probably want to send out, but one key message, 00:29:06.440 --> 00:29:08.880 if you want our listeners today to take away 00:29:08.880 --> 00:29:12.839 from this episode. I think similar to the thing 00:29:12.839 --> 00:29:15.420 we're asking our patients to do, we're asking 00:29:15.420 --> 00:29:17.859 health professionals just to think about this. 00:29:18.490 --> 00:29:21.029 Educate. We know there's gaps in health professional 00:29:21.029 --> 00:29:24.970 education related to sepsis. It's not being taught 00:29:24.970 --> 00:29:27.430 in programs. It's not being taught in a lot of 00:29:27.430 --> 00:29:30.640 subspecialty programs. Could it be sepsis? Just 00:29:30.640 --> 00:29:33.900 ask yourself that question. Could it be sepsis, 00:29:33.900 --> 00:29:36.920 this unwell patient? And that includes, oh, it's 00:29:36.920 --> 00:29:41.059 just flu, but could it be flu -associated sepsis 00:29:41.059 --> 00:29:44.660 where secondary infections can occur and where 00:29:44.660 --> 00:29:47.779 the mortality rate is so high? It's higher than 00:29:47.779 --> 00:29:50.660 myocardial infarctions in this country, right? 00:29:50.720 --> 00:29:55.539 Higher than the top three cancers combined, right? 00:29:56.890 --> 00:29:59.890 So definitely something that we should be aware 00:29:59.890 --> 00:30:03.670 of. And for those, you know, the family docs 00:30:03.670 --> 00:30:06.650 who see on one end, but particularly after end, 00:30:06.789 --> 00:30:11.289 like think about the complications that if somebody 00:30:11.289 --> 00:30:13.730 says, oh, I came to the hospital, I was in the 00:30:13.730 --> 00:30:16.869 ICU with my infection, that means they had sepsis. 00:30:16.930 --> 00:30:21.190 And that means they may need psychological support, 00:30:21.430 --> 00:30:26.799 extra rehab, other things that we have not. considered. 00:30:26.819 --> 00:30:29.059 You know, we're building this syndrome called 00:30:29.059 --> 00:30:32.000 post -sepsis syndrome, and it's clear that there 00:30:32.000 --> 00:30:34.339 are things that these patients have. So on the 00:30:34.339 --> 00:30:36.559 front end, could it be sepsis? On the back end, 00:30:36.660 --> 00:30:38.980 what are the complications if you've survived 00:30:38.980 --> 00:30:43.059 a hospital stay -in or an ICU, say, with a bad 00:30:43.059 --> 00:30:45.599 infection? Yeah, well, that's really important 00:30:45.599 --> 00:30:48.099 and really key information. Thank you so much. 00:30:48.180 --> 00:30:51.420 And we really appreciate you coming again on 00:30:51.420 --> 00:30:53.299 the podcast, supporting the podcast and talking 00:30:53.299 --> 00:30:56.519 about a very, very important topic today. And 00:30:56.519 --> 00:30:58.960 yeah, thank you for taking the time to do that. 00:30:59.299 --> 00:31:02.799 You're very welcome. It's a pleasure. Thank you, 00:31:02.799 --> 00:31:05.900 Dr. Fox Robichaud for joining us. For links to 00:31:05.900 --> 00:31:08.640 more information, educational material and to 00:31:08.640 --> 00:31:11.279 Sepsis Canada, please see the episode description. 00:31:11.680 --> 00:31:14.599 Have a topic suggestion? Or would you like to 00:31:14.599 --> 00:31:16.359 talk about your infectious diseases research? 00:31:16.880 --> 00:31:21.039 Email us at thecanadianbreakpoint at gmail .com 00:31:21.039 --> 00:31:25.680 or X us, is that a thing, at cabreakpoint. See 00:31:25.680 --> 00:31:27.839 you again soon at the Canadian Breakpoint.