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From Everest To The ICU
14 Plays6 years ago
In this episode of Critical Matters, we explore the intersection of high-altitude medicine and physiology with critical care. Our guest is Robert B. Shoene, MD, FACP.
Dr. Shoene is Associate Director, ICU and Critical Care, at St. Mary’s Medical Center in San Francisco. Dr. Shoene is a prolific author and researcher with more than 100 publications. His research has focused on pulmonary physiology and altitude medicine, and he has been part of numerous research expeditions to locations such as Mt. Everest and Denali.
Additional Resources:
Arterial Blood Gases and Oxygen Content in Climbers on Mount Everest: https://www.nejm.org/doi/full/10.1056/NEJMoa0801581
A comprehensive review on illnesses at high altitude: https://journal.chestnet.org/article/S0012-3692(08)60216-0/fulltext
Everest: The West Ridge by Thomas Hornbein: https://www.amazon.com/Everest-West-Ridge-Thomas-Hornbein/dp/1594857075/ref=sr_1_1?ie=UTF8&qid=1520812701&sr=8-1&keywords=everest+the+west+ridge
Endurance: Shackleton’s Incredible Journey by Alfred Lansing: https://www.amazon.com/Endurance-Shackletons-Incredible-Alfred-Lansing/dp/0465062881/ref=sr_1_1?s=books&ie=UTF8&qid=1520812797&sr=1-1&keywords=endurance
Being Mortal: Medicine and What Matters in the End by Atul Gawande: https://www.amazon.com/Being-Mortal-Medicine-What-Matters/dp/1250076226/ref=sr_1_1?s=books&ie=UTF8&qid=1520812921&sr=1-1&keywords=Being+mortal
Intensive Care, a poem by Dr. Robert Schoene: https://www.jstor.org/stable/1348231?seq=1#page_scan_tab_contents
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Transcript
Introduction to 'Critical Matters' Podcast
00:00:09
Speaker
Welcome to Critical Matters, a sound critical care podcast covering a broad range of topics related to the practice of intensive care medicine.
00:00:17
Speaker
And now, your host, Dr. Sergio Zanotti.
Cellular Hypoxia and Extreme Environment Parallels
00:00:22
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Cellular hypoxia is a fundamental mechanism of injury and critical illness.
00:00:26
Speaker
The physiological and pathophysiological responses to extreme environmental challenges may be similar to responses seen in critical illness.
00:00:34
Speaker
Today, we will explore the intersection of high-altitude medicine and physiology with critical care.
Dr. Schooney Joins to Discuss High-Altitude Medicine
00:00:40
Speaker
It's an honor to have as a guest Dr. Robert B. Schooney, who is Associate Director of ICU and Critical Care at St.
00:00:47
Speaker
Mary's Medical Center in San Francisco, is also a clinical professor at the Division of Pulmonary and Critical Care Medicine, Department of Medicine at the University of Washington in Seattle,
00:00:58
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Dr. Shuni is a practicing intensivist with a long and distinguished academic and research career.
00:01:03
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As an educator, he has held faculty appointments at the University of Washington and at the University of California, San Diego, where he served as program director for the internal medicine residency.
00:01:13
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Dr. Shuni is a prolific author and researcher with over 100 publications.
00:01:17
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He's the co-author for the book, High Altitude Medicine and Physiology, currently in its fifth edition.
00:01:23
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His research has focused on pulmonary physiology and altitude medicine.
00:01:27
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He has been part of numerous research expeditions to locations such as Mount Everest and Denali.
00:01:32
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Since this is not enough, Dr. Shuni is also a published poet and photographer.
00:01:36
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He is known to his friends as Brownie.
00:01:39
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Brownie, welcome to Critical Matters.
Dr. Schooney's Journey and Passion for Mountains
00:01:41
Speaker
A real pleasure to have you here today.
00:01:44
Speaker
Well, thank you.
00:01:44
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My pleasure, too.
00:01:46
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So I think that a great starting point would be just if you could share with our listeners a little bit about your experience in Mount Everest.
00:01:56
Speaker
Well, it's interesting.
00:01:58
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People ask me how I got interested in mountains, and the fact of the matter is it's because I grew up in Ohio, and there were no mountains there.
00:02:09
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And my parents made the mistake of subscribing to National Geographic magazine where there were a bunch of things that were interesting
00:02:16
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inspirational to a 10 year old kid, one of which was mountains.
00:02:20
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So I always wanted to go to the mountains and never had the opportunity growing up.
00:02:27
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But when I got to medical school at Columbia, there were several classmates of mine who already were fairly accomplished rock and ice climbers.
00:02:37
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So I channeled my athletic enthusiasm to them.
00:02:41
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And then
00:02:42
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After medical school, I had to move west, so I went to Seattle to train and then stayed there for many years.
00:02:48
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During my pulmonary fellowship, I was studying a lot of physiology, exercise physiology, and so forth.
00:02:57
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A man named John West, Dr. West at UCSD, a very preeminent pulmonary physiologist who many of us know, was putting together a research expedition to Mount Everest.
00:03:10
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I had been to the Himalaya before, and I was just finishing my fellowship, and I figured, well, I might be a good candidate to go on this research expedition.
00:03:21
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So I, since I didn't know how to type, I hand wrote a letter, Dear Dr. West, blah, blah, blah, and I was fortunate enough to be chosen to go on that expedition as a climber scientist.
00:03:33
Speaker
And that really launched my enthusiasm for research and physiology and
00:03:40
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It obviously allowed me to combine my passion for the mountains and what was going to be and has been a really fun career.
Research at Everest and ICU Patient Care
00:03:52
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So in that first expedition to Everest with Dr. West, tell us a little bit about what the type of research you were doing and at what altitude was the lab based?
00:04:03
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Yes.
00:04:04
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So this was in August.
00:04:07
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We started in August of 1981.
00:04:10
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and we walked into Everest from pretty much Kathmandu for three weeks, which was a wonderful experience in and of itself.
00:04:20
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We set up a laboratory, several laboratories.
00:04:23
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One was at base camp at about 18,000 feet, where a lot of blood work, sleep studies, and things like that were done.
00:04:32
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And then we set up the main laboratory at 21,000 feet above Everest,
00:04:37
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the Khumbu Icefall up in what's called the Western Khumb, this long, beautiful glacier.
00:04:44
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And that laboratory at 21,000 feet is where we did all of our exercise testing, further sleep studies, nutritional studies, and neuropsychometric testing as well.
00:04:57
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And then we had a lab for a short period of time up at 26,000 feet, which didn't last very long because the wind blew it away.
00:05:04
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But at 21,000 feet,
00:05:07
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we were able to do a number of studies, most of them focused on exploring the limits of performance at extreme altitude.
00:05:18
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In other words, as oxygen availability diminishes, what can the body do and how does it compensate?
00:05:25
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And that's obviously not too dissimilar to our patients, although the patients don't start out quite as healthy.
00:05:31
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And so we had a cyclerogometer.
00:05:34
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We made measurements of
00:05:37
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and ventilatory response and cardiac response and all done by hand in the old-fashioned way because we didn't have all the computerization that we do now.
00:05:46
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But that's where I really learned my physiology when my PO2 was probably in the 30 millimeters of mercury range.
00:05:56
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And so Dr. West and Dr. Millage and Lahiri, who were the senior investigators, I just felt so lucky as a young investigator to be part of that.
00:06:07
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So we did a lot of studies at 21,000 feet with the barometric pressures about 350 millimeters of mercury.
00:06:13
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And then as we got acclimatized, we did simulated higher-altitude studies, breathing first 16% oxygen, which simulated the south call at 26,000 feet, and then 14% oxygen, doing maximum exercise tests at 21,000 feet, breathing 14% oxygen, which mimicked the summit of Mount Everest.
00:06:38
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And to give our listeners a reference, at the summit, the expected PO2, or it's been measured, I think, in subsequent research treks, is probably like the PAO2 is 20, 29.
00:06:50
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Is that correct?
00:06:53
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Yeah, it varies, of course, because everybody has a little bit of a different ventilatory response.
00:06:59
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And one of the things that was my area of research, even before that expedition, was the control of ventilation.
00:07:06
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So I
00:07:07
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hypothesized to Dr. West that there would be a spectrum of ventilatory responses to the altitude, various altitudes, and tested that in Seattle, and then we took it to Mount Everest.
00:07:21
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And so you're exactly right.
00:07:25
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There are PO2.
00:07:26
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Well, first of all, let's do a little bit of quick math for those interested in the alveolar error equation.
00:07:32
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It's the barometric pressure, which we measured on the summit of Everest,
00:07:36
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is about 250 millimeters of mercury.
00:07:39
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So if you do some quick math, take away water vapor and multiply by 21%, all of that, the inspired partial pressure on the summit is 43 millimeters of mercury.
00:07:54
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Whereas here in San Francisco, it's 150.
00:07:58
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So you then have to put that in the alveolus.
00:08:00
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So in order to have any room in the alveolus,
00:08:03
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you have to really hyperventilate a lot.
00:08:06
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So the PCO2 ranges anywhere from about 8 to 11 millimeters of mercury at rest.
00:08:12
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So then that makes the alveolar PO2 about 32, and then with an alveolar arterial gradient, the PO2 from arterial blood, which has been measured, is anywhere from about 19 to 26 millimeters of mercury.
Climbers vs. ICU Patients: Tolerance to Hypoxemia
00:08:30
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Now, one of the things that has always struck me, Rowney, when I've never been to Everest, but when I read about these studies is the ability to tolerate these degrees of hypoxemia.
00:08:41
Speaker
And obviously, like you mentioned, these are healthy climbers who are up there.
00:08:46
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But it also tells us, I think, something when we see a sat in the ICU of 85%, 89% and the response that people might have.
00:08:56
Speaker
You want to dive into that a little bit and talk about that?
00:09:00
Speaker
Yeah, that's really actually one of my bugaboos, so to speak, in the ICU.
00:09:06
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And there are a lot of good data which show now that we're able to measure gene signaling with HIF-1-alpha and then all the transcription of EPO and VEGF and all of those downstream genes that that stimulation from hypoxia is important to start those cascadive events which protect against oxygen.
00:09:30
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And what we end up doing, I think, is give people in the ICU way too much oxygen.
00:09:37
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The therapist and the nurses, oh, the saturation's 90%.
00:09:41
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Well, that's perfectly fine.
00:09:45
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But your point is a good one because everybody, including healthy climbers and patients, adapt differently at different rates and to a different extent.
00:09:59
Speaker
And I think one of the things about human physiology that's so fascinating is that the bell-shaped curve of physiologic responses, whatever they may be, whether it's the ventilatory response to hypoxia, secretion of insulin, all of those things, is pretty broad because we as humans have been able to sort of beat the physical game to a certain degree.
00:10:21
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If you're a cheetah or an antelope,
00:10:24
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and you have a broad bell-shaped curve and you're slow, you're going to starve or be eaten.
00:10:30
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So humans, on the other hand, have this variability, and that's why people get pulmonary hypertension at certain levels of PO2 and others don't, and the same thing with patients in the ICU.
00:10:44
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Now, the thing, too, you have to keep in mind is that the –
00:10:50
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acuity of the exposure to the hypoxia and subsequent hypoxemia varies quite a bit.
00:10:59
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And each of us adapts or acclimatizes at a different rate.
00:11:06
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So some patients with acute hypoxemia will be much more altered, either in terms of their cardiac response, their mental acuity, and so forth, than others to
00:11:18
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even acutely adapt better.
00:11:19
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And that's one of the things, a lesson from high altitude that I think is very important in healthy people is that translates to realizing that patients are different.
Altitude Sickness and ICU Treatment Protocols
00:11:31
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And rather than just following protocols or algorithms, if you approach every patient, whether it's in the ICU or in your clinic, with the curiosity of where they are on the bell-shaped curve, you're a much better physician.
00:11:44
Speaker
And I think that the point that not only individuals have a response that could be quite different, but also just in terms of temporal responses, there's a big difference what happens acutely and what happens chronically as we're exposed to hypoxemia.
00:11:59
Speaker
And that's true for climbers and healthy human beings as for patients, I would imagine.
00:12:05
Speaker
Could you tell us a little bit about... I'm sorry, go ahead.
00:12:09
Speaker
No, I was just going to say that's a very important point.
00:12:12
Speaker
You're absolutely right that
00:12:14
Speaker
And even some of the world's great climbers, for instance, take a while to acclimatize.
00:12:19
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And once they acclimatize, they obviously are performing at the top of the world, so to speak, whereas others acclimatize much more quickly.
00:12:29
Speaker
And that's the same thing for patients.
00:12:31
Speaker
And I think one of the things we did on Everest is we also looked at neuropsychometric testing, which we ended up
00:12:40
Speaker
getting published in the New England Journal because, again, there was a spectrum of responses and adaptation to these severe degrees of hypoxemia.
00:12:50
Speaker
And that carries right over to patient care.
00:12:55
Speaker
And I think that from a medical perspective at high altitude, and we can talk a little bit more about this next, also there's a spectrum of diseases of those exposed to acute hypoxemia or high altitude, and then there's probably a spectrum of changes or quote-unquote diseases that have been studied in people who have lived at high altitude for very long times.
00:13:17
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So,
00:13:18
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Can we talk a little bit about the mechanisms of injury or some of the common clinical scenarios that we see in high altitude such as acute mountain sickness, high altitude cerebral edema, and high altitude pulmonary edema, and maybe just talk about them clinically and then what correlations you have learned that can be applied to the ICU?
00:13:42
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Yes.
00:13:44
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People who go to high altitude, again, will have symptoms.
00:13:47
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varying susceptibilities to the altitude illnesses that you mentioned.
00:13:53
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Acute mountain sickness, for instance, is pretty common.
00:13:57
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And I did a sabbatical years ago in Colorado looking at a more moderate altitude of 9,000 and 10,000 feet, and we were studying people who came there to go skiing from Atlanta or LA or some low-altitude area, and there was a fairly high incidence of acute mountain sickness.
00:14:17
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It is frustrating.
00:14:20
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A headache is sort of the main symptom, lethargy, loss of appetite.
00:14:25
Speaker
And for instance, people who climb Mount Rainier, which used to be in my backyard in Seattle, two-thirds of the people who climb that get acute mountain sickness.
00:14:35
Speaker
And it is something that is relatively short-lived and usually goes away with just time at altitude.
00:14:45
Speaker
And on something like Mount Rainier, which people go up and climb in a couple of days, they can usually get to the summit and get down without getting worse altitude illnesses.
00:14:56
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So acute mountain sickness is quite common.
00:14:59
Speaker
Many people who go on treks or skiing, vacation and so forth, think they're hungover when in fact it's acute mountain sickness.
00:15:08
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The key thing there is to just try to take it easy for a couple of days
00:15:14
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until the symptoms go away, and it's pretty self-limited.
00:15:19
Speaker
The two more, I guess, dangerous types of altitude illness are, as you mentioned, high-altitude pulmonary edema and cerebral edema.
Pulmonary Edema at High Altitudes vs. ARDS
00:15:31
Speaker
High-altitude pulmonary edema usually occurs a little bit higher than acute mountain sickness, although I've seen it as low as 8,000 feet, but it's more common at 10,000 to 12,000 feet, often incurred
00:15:44
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on weekend climbs of mountains in Colorado and so forth, or people trekking in the Andes or the Himalaya.
00:15:52
Speaker
It is something we studied on Denali back in the 1980s, and we were doing studies at the University of Washington looking at ARDS using lung lavage to look at cellular and vascular response and so forth.
00:16:09
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And so we went up to Denali,
00:16:12
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to do the same type of bronchoscopy and alveolar lavage in climbers who develop high altitude pulmonary edema.
00:16:21
Speaker
High altitude pulmonary edema is associated with those people who end up getting higher degrees of pulmonary hypertension when they go to altitude.
00:16:32
Speaker
That was something that was hypothesized and improved by Herb Holkren back in the 60s and 70s, a Stanford cardiologist.
00:16:41
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And so what we did is compare our lavage data both in our cells.
00:16:46
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We did bronchoscopies in our cells in a tent at 14,000 feet, took that lavage fluid, spun it down and studied, and then took the rest of it down to the University of Washington to look at all the cytokines and the vascular mediators and so forth.
00:17:01
Speaker
And then we did the same thing to climbers who came to our camp at 14,000 feet and did lung lavage on them.
00:17:10
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What was very interesting was the protein leak in these people with hyaluronic pulmonary edema was as high, if not higher, than what we found in ARDS in Seattle at Harborview Medical Center.
00:17:28
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So these people are sick.
00:17:29
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It is initially a non-inflammatory leak.
00:17:33
Speaker
So we learned, no one had ever done this before, as you might imagine, but we were
00:17:39
Speaker
We know that in ARDS you get inflammation and just sort of a potpourri of diffuse vascular injury and permeability leak.
00:17:50
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At high altitude, the initial part of the lung leak is very high in protein, associated with pulmonary hypertension, but it's not inflammatory.
00:18:02
Speaker
So that was something that many people, particularly the
00:18:08
Speaker
pulmonary edema people around the world were very interested in.
00:18:12
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So that was one situation where we were able to compare ARDS patients in the ICU with otherwise healthy but pretty sick climbers at 14,000 feet.
00:18:27
Speaker
Brownian, how does... So I would presume that if you are a... If you develop high altitude pulmonary edema, you either get treated...
00:18:37
Speaker
and things are brought down to a lower altitude and things get better over a couple of days, or you end up dying if that doesn't happen.
00:18:46
Speaker
But you probably don't have patients who've had the high-altitude pulmonary edema for a week or more.
00:18:51
Speaker
Is that correct?
00:18:53
Speaker
That's pretty much true.
00:18:54
Speaker
The treatment of high-altitude pulmonary edema is indeed not to go higher, obviously.
00:19:02
Speaker
On Denali, all we had was supplemental oxygen.
00:19:05
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which we put them on for during the period of time we were studying them, and then we helped them descend.
00:19:13
Speaker
And descent is very important.
00:19:15
Speaker
We were at 14,000 feet.
00:19:17
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We could have them descend to like 10,000 feet, which made a huge difference.
00:19:21
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All of them recovered.
00:19:25
Speaker
The other issue is that because there's an association of
00:19:33
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hyaluronic pulmonary edema with accentuated pulmonary hypertension, a group in Europe led by Peter Berch from Heidelberg did a study of European climbers in the Alps where they had a laboratory on the Monta Rosa at 15,000 feet.
00:19:50
Speaker
And he hypothesized that by pre-treating these individuals with a pulmonary vasodilator, which in those days was primarily an ifetapine, he could
00:20:02
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minimize the rise in pulmonary artery pressures and prevent hate.
00:20:07
Speaker
And in fact, that's what he found.
00:20:09
Speaker
And that was published in the New England Journal that Jack Reeves and I wrote the editorial for.
00:20:14
Speaker
It was a wonderful example of a clinical observation, a physiologic correlation, and then a study to prove the hypothesis in the field.
00:20:25
Speaker
So that
00:20:27
Speaker
And we had done swan-gans catheterizations on our lab in McKinley, and also as echoes got better, we were able to do echoes.
00:20:33
Speaker
And so I think what we were doing is taking the ICU to altitude and then taking that information and those data back to the ICU.
00:20:43
Speaker
Nice.
00:20:44
Speaker
And in terms of another question, I think relating the initial response or the initial injury seems to be a vascular response to hypoxia.
00:20:56
Speaker
Is that a pulmonary hypertension caused by a severe vasoconstriction?
00:21:00
Speaker
Is that what's occurring initially with the response to the hypoxia?
00:21:06
Speaker
Yes.
00:21:06
Speaker
Yes.
00:21:07
Speaker
And that, again, it wasn't really until 1960 that
00:21:12
Speaker
or high-altitude pulmonary edema was recognized as a high-altitude entity occurring in otherwise healthy people.
00:21:21
Speaker
Before that, because it occurred before that, it was thought to be pneumonia or congestive heart failure and so forth.
00:21:28
Speaker
But Herb Holtren, as I mentioned, a cardiologist from Stanford, loved doing high-altitude work.
00:21:35
Speaker
And he went down to South America and did work on the American Rockies.
00:21:39
Speaker
He thought that there's a relationship, so he did a lot of right heart catheterizations in people who had been predisposed to high-altitude pulmonary edema, and he was absolutely right.
00:21:51
Speaker
And so it is the more intense pulmonary vascular response to hypoxia in these people that leads to increased pressures, precapillary pressures, and leak into the interstitium and into the alveoli.
00:22:04
Speaker
And it's a patchy response.
00:22:07
Speaker
Some alveoli are better ventilated than others, so that response of the vasculature to that area will be more intense or less intense.
00:22:15
Speaker
So, again, I think it correlates very well with what we see in patients with pulmonary hypertension or patients even with ARDS.
00:22:24
Speaker
So, radiographically, it resembles ARDS in a diffuse, patchy infiltrate.
00:22:30
Speaker
Are there any studies with CTs showing a predilection for the back basillary areas?
00:22:37
Speaker
Yes.
00:22:38
Speaker
Yes, there are.
00:22:39
Speaker
The European group, I think the first author is Volk, V-O-L-K, a German investigator who also worked in the Alps.
00:22:49
Speaker
He has a couple of studies looking at CT scans in people with hate, and it's exactly that.
00:22:57
Speaker
It's just patchy and some areas that look good, other areas that have obviously opacities.
00:23:05
Speaker
So is there a difference, Brownie, in terms of providing just oxygen without lowering the altitude, or do you have to bring them to a lower altitude to get them better?
00:23:15
Speaker
Yeah, that was often debated because the question is, is it the barometric pressure or is it the oxygen per se?
00:23:23
Speaker
You don't need to get them to descend.
00:23:26
Speaker
I think one of the things when I was on sabbatical in Colorado in the early 90s, the
00:23:34
Speaker
standard of care for high-altitude physicians practicing in those communities when they got somebody with high-altitude pulmonary edema, they almost always sent them down to Denver, usually by helicopter or ambulance.
00:23:48
Speaker
What we took there in 90, based on our experience on Denali, is that they didn't need to do that for almost all the folks.
00:23:57
Speaker
In other words, giving them oxygen,
00:23:59
Speaker
keeping them at 9,000 and 10,000 feet under observation and obviously being prudent.
00:24:05
Speaker
But doing that was certainly adequate enough.
00:24:08
Speaker
What happens, and we saw this on Denali, the PA pressures drop, of course, with oxygen.
00:24:13
Speaker
It's a good pulmonary vasodilator.
00:24:15
Speaker
And then the lymphatics go to work and pick up the edema.
00:24:19
Speaker
Even overnight, within 24 to 36 hours, the patients are much better.
00:24:24
Speaker
So in most folks who are not severely ill with HAPE,
00:24:29
Speaker
at moderate altitude, oxygen is adequate.
00:24:33
Speaker
And I think it's an interesting analogy with what we see in critically ill patients.
00:24:39
Speaker
Acutely, a lot of what we're trying to do is improve oxygen delivery, whether it be by increasing how we provide oxygen, increasing delivery.
00:24:49
Speaker
And the problem is that over time with ARDS, that might not be enough.
00:24:52
Speaker
It's not what really kills them.
00:24:53
Speaker
But that seems to be the case here.
00:24:55
Speaker
The initial responses really provide them with more oxygen.
00:24:59
Speaker
and that will probably relieve or help mitigate that pulmonary hypertension and start turning things around.
00:25:04
Speaker
Is that correct?
00:25:06
Speaker
That is correct.
00:25:07
Speaker
And since Peter Beart's study, the one I mentioned with nifedipine, as you know, there are a number of other pulmonary vasodilators.
00:25:14
Speaker
A lot of people are adding those pulmonary vasodilators to their armamentarium of treatment.
00:25:20
Speaker
It's probably not necessary, but certainly not harmful, and it sort of follows the thesis of
00:25:28
Speaker
trying to decrease the pulmonary artery pressure.
00:25:30
Speaker
So oxygen, nifedipine, and any of the other newer pulmonary vasodilators are being used, but oxygen is still perfectly fine.
00:25:40
Speaker
And in these studies that you had performed in patients with HAPE, as the disease continues and progresses, does that BAL become inflammatory at one point?
00:25:51
Speaker
Is there a switch in the nature of the disease?
00:25:56
Speaker
Yes.
00:25:56
Speaker
That's a...
00:25:57
Speaker
Very good point.
00:25:58
Speaker
Our initial lavage studies, we couldn't time exactly when we got these subjects or these climbers who were sick.
00:26:09
Speaker
We got them when they were sick, and it could be a day after they got sick or a couple days after they began to get sick.
00:26:16
Speaker
So our initial lavage studies that were two studies, one was published in JAMA and the other was in the Journal of Applied Physiology, showed an inflammatory response.
00:26:29
Speaker
Leucotriene before all the arachidonic acid cascade were present.
00:26:35
Speaker
And there were mostly, interestingly though, mostly macrophages and very few neutrophils.
00:26:43
Speaker
So Eric Swenson, who came up to Denali from the University of Washington, a very dear friend of mine, he sort of took that thesis and later did a study in the Alps with Peter Berch, and they took
00:26:58
Speaker
sort of these hapless European climbers who were predisposed to hate, took them up to the Monorosa hut, and as soon as they started to get sick, he did bronchoscopy and lavage and found that it was not inflammatory.
00:27:10
Speaker
So it was a wonderful study that looked at the mechanism a little bit more thoroughly than we could do in the field.
00:27:16
Speaker
So the point is that this is initially a hydrostatic high-protein leak that with the presence of the protein probably in the interstitium and the alveolus,
00:27:27
Speaker
incites chemotaxis and inflammation.
00:27:31
Speaker
Which is probably exactly what happens in many of our patients with different types of ARDS, whether it be an aspiration with a chemical pneumonitis initially and then turns into inflammatory or a negative pressure type of pulmonary edema and somebody has a severe laryngospasm.
00:27:47
Speaker
Is that correct?
00:27:50
Speaker
Yes, definitely.
00:27:52
Speaker
Brownie, is there any other lessons that we've learned from HAPE in terms of treatment?
00:27:56
Speaker
I know that at one point people had tried steroids.
00:27:59
Speaker
There's also some, I think, some literature on using beta agonists that have been translated or tried to have been translated into ARDS.
00:28:08
Speaker
Any comments on other therapies that maybe failed?
00:28:12
Speaker
Yeah, there are a couple of things.
00:28:14
Speaker
Some of the early studies, there was a big new journal study years ago by
00:28:20
Speaker
an Indian investigator who was looking at the soldiers up on the Indian-Pakistan border many years ago, and they saw 19,000 feet a lot of altitude of illness.
00:28:30
Speaker
He wrote and described these folks in the early 60s, and they were using Lasix.
00:28:36
Speaker
Probably not a good thing to do because these people are pretty volume depleted anyway, and so you're adding another insult, I think, to the hemodynamics of hate.
00:28:46
Speaker
So nobody uses that.
00:28:48
Speaker
The steroid question, it's also been, they've been used in probably, ironically, dexamethasone, which is a medication that's often used for high-altitude cerebral edema, which is very effective for that, may have some salutary effect in HAPE.
00:29:07
Speaker
But again, not very well shown, although a lot of people do use it.
00:29:14
Speaker
And then you also mentioned beta agonists.
00:29:17
Speaker
The beta agonist story is interesting, maybe not a very practical one, but Claudio Sartori, Italy, when he was over here at UCSF, either doing a fellowship or something, he was doing a lot of work in pulmonary edema, and beta agonist increased alveolar fluid clearance through the sodium-potassium ATPH pump on the epithelial lining.
00:29:41
Speaker
So he tested high doses of solmeterol to...
00:29:47
Speaker
HAPE-susceptible individuals in the Alps.
00:29:50
Speaker
And he showed, too, he could minimize or prevent HAPE, probably by increasing alveolar fluid clearance.
00:29:58
Speaker
Some people use it.
00:29:59
Speaker
It's certainly not harmful.
00:30:00
Speaker
It's not really a frontline
00:30:03
Speaker
medication for hate.
00:30:05
Speaker
And that has been translated into the ARDS realm without, I would say, great success, but in the initial studies there was some promise, but it hasn't really panned through to something that I think we use on a regular basis, but it probably came from those observations.
00:30:20
Speaker
Correct.
Genetic Factors in Altitude Sickness and ICU Outcomes
00:30:22
Speaker
One of the myths, I think, that are commonly believed by lay people is
00:30:28
Speaker
or people who are not exposed to altitude very commonly, is that if you're going to go and climb, you need to get really, really fit.
00:30:36
Speaker
But the reality is that you can be very fit and get into a lot of trouble just because of the genes you have.
00:30:41
Speaker
Is that correct?
00:30:44
Speaker
That's a great point.
00:30:45
Speaker
People say, well, I'm going to go get fit.
00:30:47
Speaker
Now, first of all, it does help to be fit.
00:30:52
Speaker
And the reason that is, one, it makes the adventure a little bit more enjoyable.
00:30:58
Speaker
And it also adds a safety factor because if you get caught in a storm and you need to get off the mountain, you've got to be fit and you've got to have speed.
00:31:08
Speaker
Now, having said that, being fit will not prevent you from getting altitude illness.
00:31:14
Speaker
And in fact, what's interesting is I think the fitter people are, the faster and higher they go with lack of acclimatization, the more likely they are to get one of the altitude illnesses.
00:31:27
Speaker
Fitness is great to have, but it really doesn't prevent you from getting any of the altitude illnesses.
00:31:34
Speaker
And in terms of what can be mitigated, obviously, is, like you said, the rate of ascent and acclimatization, which, as you pointed out in your first expedition, you climb to base camp over three weeks, but people probably sometimes do even longer periods in order to prepare for higher altitudes.
00:31:51
Speaker
But can you talk a little bit about what we have found about specific genotypes or genetic predispositions to tolerance to altitude, to tolerance to hypoxia and altitude?
00:32:05
Speaker
Right.
00:32:05
Speaker
There's a fair amount of work going on in that arena right now.
00:32:11
Speaker
I'm not involved in it, but I certainly go to the meetings.
00:32:14
Speaker
And the Chinese actually are one of the leading groups doing all kinds of genetic research.
00:32:21
Speaker
studies looking at gene types and phenotypes and so forth.
00:32:25
Speaker
There are some genes that are associated with high-altitude pulmonary edema.
00:32:30
Speaker
The ACE gene is one of them.
00:32:33
Speaker
And then there are a whole bunch of others that are sort of number and word gibberish, letter gibberish, that are being associated.
00:32:40
Speaker
And most of them appear to be related to the pulmonary vascular response.
00:32:45
Speaker
The other altitude illnesses, such as cerebral edema, which is
00:32:50
Speaker
usually encountered at even higher altitudes, which can be fatal.
00:32:55
Speaker
I don't think there's been much work on that.
00:32:58
Speaker
What's also very interesting is looking at high-altitude populations.
00:33:07
Speaker
And what's fascinating is that if you look at what's called chronic mountain sickness, and that is really, it was described in the Andes,
00:33:18
Speaker
And the markers of it are polycythemia, pulmonary hypertension, eventually right heart failure, mental dulling, and so forth.
00:33:28
Speaker
It's about 15% of the people in the Andes living at 13,000 to 15,000 feet have this chronic mountain sickness.
00:33:37
Speaker
And we studied it years ago.
00:33:39
Speaker
In fact, I studied one fellow with a hematocritic of 91%.
00:33:42
Speaker
And so there's some...
00:33:46
Speaker
This inhibition of the erythropoietic response in these folks, and a number of genetic studies are going on looking at that, but what's really interesting, it does not exist in Tibetans.
00:34:03
Speaker
And the Han Chinese who have been sent to Tibet get this chronic mountain sickness, whereas the incidence in native Tibetans is about 1% or less.
00:34:17
Speaker
you don't see it in Ethiopia.
00:34:19
Speaker
So if you adhere to the fact that we as humans sort of began in East Africa, migrated north into Europe, across the Mideast, across the Tibetan Plateau, down into Asia, up into Asia, and across the North and South America, these human populations have been deposited in those various areas in a chronology that suggests that, for instance, the Tibetans have been there much longer
00:34:46
Speaker
than the Andean high-altitude natives and have thus adapted much better.
00:34:52
Speaker
They do not have pulmonary hypertension in Tibet, the Tibetan stone, whereas, again, as I mentioned, in South America, it's very, very prevalent.
00:35:02
Speaker
So it's almost evolution, just viewing evolution and process because over the tens and hundreds of thousands of years, it looks like
00:35:15
Speaker
the genetic adaptation is very real.
00:35:21
Speaker
That is fascinating.
00:35:22
Speaker
And as you were explaining that, I was actually thinking, is there a difference in how long they've been living at altitude?
00:35:28
Speaker
And obviously there is, and that probably relates to evolution.
00:35:32
Speaker
And maybe I guess it's like climbers.
00:35:35
Speaker
Most of the very, very accomplished climbers probably have a good genetic predisposition toward tolerance of altitude because otherwise they wouldn't become very great climbers.
00:35:47
Speaker
That's right.
00:35:48
Speaker
The other question I always say.
00:35:51
Speaker
Go ahead.
00:35:53
Speaker
I was just going to say, if you want to go to the Olympics, if you want to win a Nobel Prize, if you want to climb in the Himalaya, you have to choose your parents very well.
00:36:01
Speaker
Exactly.
00:36:03
Speaker
So I was going to ask you a similar question.
00:36:06
Speaker
If you want to survive ARDS, are your parents that important?
00:36:13
Speaker
Well, it is interesting.
00:36:14
Speaker
There are some.
00:36:16
Speaker
genetic studies looking at predisposition to ARDS.
00:36:19
Speaker
And the literature has a number of people who've gotten repeat episodes of ARDS.
00:36:27
Speaker
And right up the hill here at UCSF, they've been looking at some of those people.
00:36:32
Speaker
Michael Mathay and the group here have been trying to look at some genetic predisposition to find some markers.
00:36:39
Speaker
And I think they have found some things that are suggested that there's a predisposition to ARDS.
00:36:46
Speaker
So would it be fair to say that if you have the genes that are associated with a higher frequency of having HABE or other high-altitude injuries, it's probably likely that you would do worse if you got the same intensity RDS than a high-accomplished climber who obviously has shown to have the predisposition not to have those
Applying Altitude Research to ICU Care
00:37:09
Speaker
problems?
00:37:09
Speaker
Is that something that's been looked at?
00:37:11
Speaker
In answer to your question, no.
00:37:13
Speaker
However, your thought is interesting in that
00:37:16
Speaker
There may be those who are predisposed to hyaluronic pulmonary edema that may be predisposed to ARDS, or if they get ARDS, have a more severe.
00:37:26
Speaker
Again, the pulmonary vascular response is so important in HAPE, and I'm not sure it's a primary catalyst for ARDS per se.
00:37:35
Speaker
It may be a post-facto one, but I don't know.
00:37:38
Speaker
No one's looked at that.
00:37:40
Speaker
Well, I think that clearly...
00:37:42
Speaker
The exposure to low oxygen at high altitudes has provided a great laboratory for us to explore and understand responses to hypoxia and try to bring those down to the ICU and understand a little bit more about what happens to our patients.
00:37:58
Speaker
But I think that I'm also very interested, Brownie, in some of the lessons that you've learned of working in these harsh environments in terms of professionalism, teamwork, that you could bring back to the ICUs
Teamwork Lessons from High-Altitude Expeditions
00:38:12
Speaker
today.
00:38:12
Speaker
Yes, I think that this is something I think about a lot.
00:38:17
Speaker
First of all, I feel very fortunate to have had these experiences, but it really comes down to teamwork.
00:38:23
Speaker
And obviously, on an expedition like Everest or on Denali, where the conditions are harsh and you have a diverse group of people there, I will say that John West chose an excellent group to go to Mount Everest.
00:38:38
Speaker
where you can read about expeditions where people quibble and they fight and so forth.
00:38:43
Speaker
This was a very harmonious expedition because I think people weren't there just to climb the mountain because very few people had climbed it in 1981.
00:38:52
Speaker
They were there to try to climb it, which we did and we're lucky to do, but we were there to have another part of the mission and that was to do the research.
00:39:01
Speaker
Many of us are still very close, dear friends and the others have just gone to other
00:39:07
Speaker
parts of life we don't intersect.
00:39:08
Speaker
But that, to me, coming back from that expedition, I just felt so lucky.
00:39:13
Speaker
You know, I was a young investigator, so to speak, just beginning my academic career and just starting my years at Harborview ICU in Seattle.
00:39:22
Speaker
I just felt so lucky.
00:39:24
Speaker
And what I say, a leader is one who treats everybody the same.
00:39:31
Speaker
For instance, John West chose very carefully what I think was a great group of people.
00:39:37
Speaker
And then he let each of us do our duty, run with the ball, and he trusts us.
00:39:46
Speaker
What that means is that each of us upped the ante for our responsibility to each other and to our individual jobs, and we grew because of it, and the whole endeavor was successful.
00:40:01
Speaker
For instance, again, I was just a young kid, so to speak, and John called me.
00:40:08
Speaker
a couple times, but he called me once and said, could you put all the food together for Mount Everest?
00:40:13
Speaker
And I'm thinking, oh my God.
00:40:15
Speaker
But that's the only call I got.
00:40:18
Speaker
And then he called me later and he said, you've been doing some work in the control of ventilation and you wrote a paper on a hypothesis of high altitude.
00:40:27
Speaker
Could you continue that work on our expedition?
00:40:30
Speaker
That's the only call I got on that.
00:40:32
Speaker
And that's what a leader does.
00:40:34
Speaker
You get good people,
00:40:36
Speaker
give them the responsibility, you don't micromanage, and you're there for each other and everybody's treated with respect.
00:40:43
Speaker
And also camaraderie and teamwork.
00:40:46
Speaker
That's what a good ICU does as well.
00:40:49
Speaker
And by treating everybody the same, the thing that has always bothered me is that the echelons of the historic authorities of physicians, nurses, therapists, and so forth, I've always been uncomfortable with that.
00:41:03
Speaker
I think
00:41:05
Speaker
The nurses have been there, that's their career, that's their job.
00:41:08
Speaker
They are just as important as we are and if you treat them with respect, they up the ante for their performance.
00:41:15
Speaker
You're a better team, you communicate.
00:41:18
Speaker
The same with therapists.
00:41:20
Speaker
And the most important person in the ICU is usually the ward clerk.
00:41:24
Speaker
And that person is also just as important.
00:41:27
Speaker
So as a leader, I think you don't micromanage.
00:41:31
Speaker
You get good people, treat them with respect,
00:41:35
Speaker
have camaraderie, and the endeavor, whether it's on Mount Everest or Denali or in the ICU, is much more successful.
00:41:44
Speaker
And plus, I just love the camaraderie.
00:41:46
Speaker
I love people.
00:41:47
Speaker
I love the people I work with and the whole group.
00:41:52
Speaker
And so I think that that's really critical.
00:41:55
Speaker
The other thing from these high-altitude expeditions to foreign countries and so forth is you learn so much about
00:42:04
Speaker
culture and other people.
00:42:05
Speaker
And you see that in the ICU.
00:42:08
Speaker
You have such a diverse group of patients and families.
00:42:12
Speaker
And again, never judge your patient.
00:42:15
Speaker
Everybody's sick, they're scared, and that fear may manifest itself as anger, drunkenness, gratitude, passivity, whatever it may be.
00:42:27
Speaker
But if you treat everybody the same, make no judgment,
00:42:31
Speaker
People see that.
00:42:32
Speaker
Your team sees that.
00:42:34
Speaker
And again, the endeavor is much more successful.
00:42:38
Speaker
I so strongly believe in that credo, so to speak, that I feel very lucky to have worked with teams, and a lot of it was sort of an example where on these high-altitude expeditions.
00:42:54
Speaker
And I think that those are phenomenal, phenomenal insights.
00:42:58
Speaker
And I think of three recurrent themes in terms of high-performing teams, in terms of creating a culture that's really of a successful intensive care unit that you mentioned.
00:43:09
Speaker
And the first one is shared purpose.
00:43:12
Speaker
When the leaders can really express and make everybody see the shared purpose of the mission, I think everybody is significantly more engaged and cohesive.
00:43:24
Speaker
And that is something that I think sometimes we forget why we are in the ICU and what is our shared purpose.
00:43:30
Speaker
Number two, I think what you talked about, Dr. West as the leader, I always say that if you have a leader and follower, at the best you get compliance.
00:43:40
Speaker
If you have a leader and multiple leaders, you'll get engagement.
00:43:44
Speaker
And the idea of giving people the power to do their best, and that I think ultimately leads to the third, which is the basis of all this, which is respect of each other and what everybody brings to the table.
00:43:57
Speaker
That is phenomenal, phenomenal insight.
00:44:00
Speaker
I usually close with three questions not related to medicine.
Influential Books and Personal Growth
00:44:07
Speaker
I'm almost inclined to stop here because those insights were so powerful.
00:44:13
Speaker
But I think we'll go ahead and do it as well, if that's okay with you, Brownie.
00:44:16
Speaker
Sure.
00:44:17
Speaker
You bet.
00:44:18
Speaker
So the first question is, what book or books have influenced you the most or what book have you gifted most often to others?
00:44:25
Speaker
Yeah.
00:44:26
Speaker
Well,
00:44:27
Speaker
There are, of course, tons of books I've really liked, but there are maybe three arenas.
00:44:34
Speaker
One is Adventure in Altitude, and so there are two books that have influenced me and that I've also given to many people.
00:44:45
Speaker
One is called Everest to West Ridge, written by Tom Hornbein, H-O-R-N-B-E-I-N.
00:44:53
Speaker
He was a member of the 1963...
00:44:56
Speaker
American Everest expedition.
00:44:58
Speaker
He then went on to a very illustrious academic career in anesthesiology at the University of Washington.
00:45:05
Speaker
So I got to know Tom very well.
00:45:08
Speaker
And he sort of took me under his wing and mentored me.
00:45:10
Speaker
In fact, I just talked with him this morning.
00:45:12
Speaker
He's in his mid-80s now, and he's still out climbing.
00:45:17
Speaker
The words of wisdom that he brought from his expedition where he climbed the West Ridge and his insights, that's a phenomenal book.
00:45:26
Speaker
Another one is Endurance by Alfred Lansing.
00:45:30
Speaker
It's, of course, the story of the Ernest Shackleton expedition to Antarctica back in the 1910s.
00:45:37
Speaker
That is a wonderful, mesmerizing read.
00:45:42
Speaker
And Shackleton has come down over the years as probably one of the greatest leaders of all time because he took these people down there.
00:45:50
Speaker
They got into trouble.
00:45:51
Speaker
Their ship got locked into ice.
00:45:54
Speaker
And
00:45:56
Speaker
19 members of that expedition, all the trials and tribulations, largely through his leadership, returned to England.
00:46:04
Speaker
That's a great book.
00:46:05
Speaker
I've given that book to a number of people.
00:46:08
Speaker
I also am a great fan of poetry, and Pablo Neruda, the great Chilean Nobel Prize-winning poet, has a number of volumes, many, many, but I really have given volumes to many people.
00:46:26
Speaker
The other category are more contemporary, but also books that are very relevant that are bestsellers, actually, that I'm sure many of the listeners have read.
00:46:35
Speaker
One is Being Mortal by Atul Gawande, and just about the dignity of life and the dignity at the end of life.
00:46:47
Speaker
If people haven't read it, that I've given to a number of people because we deal with that every day.
00:46:52
Speaker
and we deal with it in ourselves, having dignity at the end of life, but that's also an important part of life.
00:46:59
Speaker
And the other one is, and I'm blocking on the author's name, but it too is a recent book called When Breath Becomes Air.
00:47:08
Speaker
And that is a book written by a young neurosurgeon who for some reason came down with lung cancer.
00:47:18
Speaker
And it's the story of
00:47:19
Speaker
the beginning of his career, but also his dying of that cancer.
00:47:24
Speaker
It is just heart-rending.
00:47:27
Speaker
But those are the books, along with many others, but the ones that I – well, there's one other called Touching the Void by Joe Simpson.
00:47:37
Speaker
It's a mountain-climbing book in the Andes.
00:47:40
Speaker
That's another one that is just spellbinding.
00:47:45
Speaker
And I think that the common theme where you are on Everest –
00:47:49
Speaker
reading poetry from Pablo Neruda or reading Being Mortal or When Breath Becomes Air is that they all speak to our human nature and to the same challenges and questions that remain over time.
00:48:04
Speaker
Those never change.
00:48:06
Speaker
And I think that that is probably what's most important on a daily basis for us to remember.
00:48:11
Speaker
So these are great, great reads.
00:48:14
Speaker
I've read several of them, not all of them, but I definitely will pick up the ones that I have not.
Career Changes and Physician Learning Gaps
00:48:19
Speaker
So the second question, Brownie, is what do you believe to be true in medicine or in life that most other people don't believe?
00:48:27
Speaker
Well, I think one of the things – well, let me pick this one out.
00:48:35
Speaker
As I mentioned at the onset, I grew up in Columbus, Ohio, and my father was a professor in the Department of Medicine at Ohio State.
00:48:44
Speaker
And one of his best friends was chief of surgery, Dr. Robert Zollinger.
00:48:49
Speaker
who describes Zollinger-Ellison syndrome.
00:48:51
Speaker
And Zollinger was one of these old-fashioned, you know, fire-breathing surgeons, but he was a brilliant, wonderful man.
00:48:59
Speaker
And he sort of followed my career and kept writing me letters as I was in college and medical school.
00:49:05
Speaker
And he'd read my publications.
00:49:07
Speaker
He'd say, oh, you should be a surgeon.
00:49:08
Speaker
It's not too late.
00:49:08
Speaker
You should be a surgeon.
00:49:09
Speaker
So a number of years later, in the middle of my academic career, I went back to Columbus and I called him.
00:49:16
Speaker
He was in his 80s then.
00:49:18
Speaker
And I said, Dr. Zollinger, sir, this is Brown and Shaney.
00:49:22
Speaker
I'd love to come over and say hello and so forth.
00:49:24
Speaker
He said, oh yeah, come on over.
00:49:25
Speaker
So he and I sat down and chatted for a couple of hours in his den.
00:49:30
Speaker
And one of the things he said was, throughout your career, you need to make changes.
00:49:39
Speaker
And at that point, ramping up my academic career, I didn't really know what he meant.
00:49:44
Speaker
But he said,
00:49:45
Speaker
I was chair of surgery for many years at Ohio State, but even within that role, I changed every five to 10 years my focus.
00:49:55
Speaker
The reason I did that, one, that was my nature, but secondly, it kept me growing and learning and invested in a career that I have loved.
00:50:06
Speaker
And so a couple years after that, I had opportunities to make some changes, and I've continued to do that.
00:50:13
Speaker
And so I think
00:50:15
Speaker
A lot of people, well, I'm going to be an assistant professor, an associate professor, full professor, and chair of something at University of such and such.
00:50:25
Speaker
And people do that, and that's very admirable, but they don't believe that it's important to change.
00:50:33
Speaker
And I think – I hope that young trainees now will be as excited about what they're doing as I am now many years later.
00:50:45
Speaker
And I think one of the things that the comrades, patients, science, all those things play a role, but it's also trying to make changes to keep you really motivated and learning.
00:51:02
Speaker
Absolutely.
00:51:02
Speaker
And I think that it's fascinating because one of the things that a topic that I've thought about a lot lately is
00:51:09
Speaker
is the dichotomy of change in terms that a lot of what's happening to the medical professional in terms of burnout relates to the change around them.
00:51:20
Speaker
Yet the antidote to all that is for us to keep changing and growing.
00:51:25
Speaker
And I think that it's a very interesting thought, but that is great advice from a surgeon, absolutely.
00:51:32
Speaker
Yeah, Zollinger was quite something.
00:51:38
Speaker
And the last question, Brownie, is what would you want every intensivist who listens to this podcast to know?
00:51:47
Speaker
I would want that person to know when they don't know.
00:51:53
Speaker
And I've always told house officers or colleagues that the thing that I like to hear the most from my students, my residents, my senior professors, whoever they may be is, wow, I don't know, but let's find out.
00:52:09
Speaker
And I think that by saying that, it means they have confidence in what they're doing.
00:52:15
Speaker
They have confidence in their enthusiasm to want to know.
00:52:19
Speaker
But if they don't know and they pull the wool over somebody's eyes, some patient's going to get hurt.
00:52:25
Speaker
And I think that it's hard.
00:52:27
Speaker
Let's say you're a third-year student and you're on your medicine rotation.
00:52:30
Speaker
There's a lot of pressure.
00:52:31
Speaker
There's your chief resident and there's your attending and they're asking you questions.
00:52:35
Speaker
And, God, you want to know all the answers and you don't.
00:52:39
Speaker
to start the habit of saying, I don't know, but let's find out, is so honest and so important for the integrity of commitment to your patients and to your colleagues.
00:52:53
Speaker
So in answer to your question, what do I want Intensifists to know?
00:52:59
Speaker
I want to know when they don't know, or I want them to know when they don't know, but have the enthusiasm and motivation to find out.
00:53:08
Speaker
I think it's a great, great advice.
00:53:12
Speaker
Vulnerability to be able to say, I don't know, and really having that desire to understand.
00:53:19
Speaker
It's not about the right answers, but the right questions.
00:53:22
Speaker
And I think that's a perfect place to end.
Conclusion and Thanks to Dr. Schooney
00:53:26
Speaker
Brownie, it was a true pleasure to have you on the podcast.
00:53:29
Speaker
We'll have you back soon exploring other topics related to physiology and exercise.
00:53:37
Speaker
So again, thank you very much for your time.
00:53:39
Speaker
My pleasure and my honor too.
00:53:41
Speaker
Thank you, Sergio.
00:53:45
Speaker
Thanks again for listening to Critical Matters.
00:53:47
Speaker
Make sure to subscribe to this podcast on iTunes or Google Play.