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Oncologic Emergencies
17 Plays2 years ago
In this episode of the podcast, we will discuss oncologic emergencies. Dr. Zanotti is joined by Dr. R Scott Stephens, a pulmonary/critical care physician and associate professor of medicine and oncology at the Johns Hopkins University School of Medicine. He is the Director of Oncology and Bone Marrow Transplant Critical Care at Johns Hopkins Hospital and the Sidney Kimmel Comprehensive Cancer Center. A recognized clinician, educator, and researcher Dr. Stephens has expertise and interest in ARDS, ECMO, and oncologic critical care.
Additional Resources:
Oncologic Emergencies for the Intensivist – the Old, the New, and the Deadly. Thandra K, et al. J Intensive Care Med 2020: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6886674/
Oncologic Emergencies – Traditional and Contemporary. Spring J, and Munshi L. Crit Care Clin 2020: https://pubmed.ncbi.nlm.nih.gov/33190777/
Critically Ill Patients with Cancer: A Clinical Perspective. Martos-Benitez F, et al. World J clin Onco 2020: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643188/
Management of Febrile Neutropenia: ESMO Clinical Practice Guidelines. Annals of Oncology 2016: https://www.annalsofoncology.org/article/S0923-7534(19)31643-6/pdf
Books Mentioned in this Episode:
The Elements of Style. By William Strunk and EB White: https://amzn.to/3KddG7C
The Structure of Scientific Revolutions: By William Kuhn: https://bit.ly/43HkS34
The Physicists: The History of a Scientific Community in Modern America. By Daniel Kevles: https://bit.ly/477Z8jO
American Prometheus: The Triumph and Tragedy of j. Robert Oppenheimer. By Kai Bird and Martin Sherwin: https://bit.ly/479AEqn
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Transcript
Introduction to Critical Matters Podcast
00:00:06
Speaker
Welcome to Critical Matters, a sound podcast covering a broad range of topics related to the practice of intensive care medicine.
00:00:14
Speaker
Sound provides comprehensive critical care programs to hospitals across the country.
00:00:19
Speaker
To learn more about our programs and career opportunities, visit www.soundphysicians.com.
00:00:26
Speaker
And now, your host, Dr. Sergio Zanotti.
Cancer in ICU: A Critical Overview
00:00:34
Speaker
Cancer continues to be a leading cause of death.
00:00:37
Speaker
Patients with cancer are often admitted to the ICU for treatment of critical illness related to their underlying cancer or for complications related to their cancer treatment.
00:00:46
Speaker
In today's episode of the podcast, we will discuss common oncologic emergencies from the perspective of the intensivist.
00:00:53
Speaker
Our guest is Dr. R. Scott Stevens, a pulmonary critical care physician and an associate professor of medicine and oncology at the Johns Hopkins University School of Medicine.
00:01:02
Speaker
He is the director of oncology and bone marrow transplant critical care at Johns Hopkins Hospital and the Sidney Kimmel Comprehensive Cancer Center, a recognized clinician, educator, and researcher with an expertise and interest in ARDS, ECMO, and oncologic critical care.
00:01:18
Speaker
Scott, welcome to Critical Matters.
00:01:21
Speaker
Thank you so much for having me.
00:01:22
Speaker
It's really a pleasure to be here.
00:01:25
Speaker
So today we want to talk about oncologic emergencies that would be of interest for the intensivist in practice.
Common Oncologic Emergencies
00:01:31
Speaker
Now, this obviously is a very broad topic, and there are some common oncologic emergencies that everybody might be exposed to, and then there's some that, as we were discussing pre-recording, that are quite specific to very specialized emergencies.
00:01:48
Speaker
cancer-related ICUs and treatments that are very tertiary care-centered.
00:01:55
Speaker
So we're going to focus on what we consider to be most important and most common.
00:01:59
Speaker
And I would like to start maybe as a matter of introduction, if you could just give us an overview of the epidemiology of cancer patients in the common ICU.
00:02:09
Speaker
Yeah, sure.
00:02:10
Speaker
So, um,
00:02:17
Speaker
Kettering has published some data on this.
00:02:19
Speaker
Somewhere between 15 and 20% of patients admitted to the ICU in the United States have cancer.
00:02:26
Speaker
Now, that's a little misleading because that includes patients who
00:02:30
Speaker
who, it's not misleading, but it doesn't mean that everyone's admitted for medical complications of cancer.
00:02:38
Speaker
That's a lot of patients who are in the ICU post-resection, post-surgical resection of a lung cancer or a GI cancer, who don't really have the same specific ICU complications that
00:02:53
Speaker
patients admitted as a complication of their medical therapy of cancer might have.
00:02:57
Speaker
But still, it's a large burden on the healthcare system.
00:03:03
Speaker
When you look at the specific reasons that medical oncology patients are being admitted, meaning patients who have not undergone or have not, you know, proximally undergone resective surgery but are getting chemotherapy, getting immunotherapy, getting bone marrow transplants, things like that,
00:03:22
Speaker
If you look at the reasons why those patients are admitted, there are really the three main reasons.
00:03:27
Speaker
The first is respiratory failure.
00:03:29
Speaker
That's the single most common cause of admission for oncologic patients.
00:03:33
Speaker
Second is sepsis.
00:03:35
Speaker
And the third is renal failure.
00:03:38
Speaker
And then, you know, there are a number of less common diagnoses that we see over and over again, but not at the level of those top three.
00:03:48
Speaker
And I think that underscores a really important point is that
00:03:52
Speaker
While there are some idiosyncrasies about oncologic critical care, most of oncologic critical care is just good, basic, fundamental critical care.
00:04:01
Speaker
Management of respiratory failure, management of sepsis, management of other organ dysfunction.
00:04:07
Speaker
And I think we'll hit some of the idiosyncrasies that are important to know, but honestly probably make up, you know, certainly less than a majority, probably closer to 25% of the care that we actually provide in the oncology ICU.
00:04:22
Speaker
Absolutely.
00:04:22
Speaker
And I think that when you think about it, respiratory failure, sepsis, and renal failure are also probably top three diagnosis of well patients without cancer are admitted to the ICU.
00:04:34
Speaker
So I think that is very much aligned with what you were stating, that most of the critical care we provide to patients with cancer is
00:04:43
Speaker
is going to be similar to the problems that people who don't have cancer present to.
00:04:47
Speaker
But there are some that presentations or clinical presentations, syndromes, diseases, whatever we want to call them, that are quite unique to the cancer population.
00:04:58
Speaker
And this is what we commonly refer to as oncologic emergencies.
00:05:02
Speaker
Can you tell us a little bit more about as a way of introduction on these specific, like you said, maybe 25% of what we see in the ICU with patients with cancer?
Neutropenic Fever: Diagnosis and Treatment
00:05:11
Speaker
Yeah, so oncologic emergencies, these are things that are specific either to the cancer itself or to the treatment of the cancer.
00:05:20
Speaker
And there's a lot of interrelationship there, right?
00:05:25
Speaker
But these are things, as you said, that we see specifically in cancer patients, whether due to a complication of the malignancy or due to a complication of the treatment.
00:05:35
Speaker
And I think there are really the ones that we consider
00:05:38
Speaker
hammer home to our fellows that they're probably only ever going to see in the oncologic ICU are complications like neutropenia and neutropenic sepsis and neutropenic fever, complications of acute leukemia, tumor lysis syndrome, I think we'll go through all of these in more detail, and then some chemotherapy or treatment-related toxicities.
00:06:05
Speaker
Probably the other thing that we see that is a little unique in our patient population is the approach to respiratory failure in the immunocompromised patient.
00:06:14
Speaker
It's a little different, mostly because there are just more things to consider in the immunocompromised patient than in an immunocompetent patient.
00:06:23
Speaker
But that probably is also kind of a key knowledge base in oncologic critical care.
00:06:30
Speaker
Excellent.
00:06:31
Speaker
So let's dive into some of these in a little bit more detail.
00:06:34
Speaker
And maybe we can start with white cells.
00:06:36
Speaker
And I guess when I think of oncologic emergencies as a general intensivist, I think of white cells as being either too few or too many.
00:06:46
Speaker
And neutropenic fever is something that through training in internal medicine and critical care is a topic that is always addressed, although it's not something that we see on a super regular basis, but something that I believe is important.
00:06:59
Speaker
Can you tell us how you think about neutropenic fever in terms of first maybe definition and we can go from there?
00:07:05
Speaker
Yeah.
00:07:05
Speaker
So neutropenic fever is, it's pretty, it's relatively simple.
00:07:09
Speaker
It's a fever in a patient with neutropenia.
00:07:12
Speaker
And neutropenia is defined as a neutrophil count less than 500 per cubic millimeter.
00:07:19
Speaker
Um,
00:07:20
Speaker
So really, it's severe neutropenia.
00:07:23
Speaker
This is not just a patient who has less than 1,000 neutrophils.
00:07:25
Speaker
This is a patient who really is pretty profoundly neutropenic.
00:07:29
Speaker
And neutropenic fever is incredibly common in cancer patients.
00:07:34
Speaker
So if you look at heme malignancies patients, upwards of 90% of them will have a neutropenic fever during some part of their treatment course.
00:07:45
Speaker
Now, that doesn't mean that all 90% of those need to come to the ICU because only a fraction of the patients who actually get neutropenic fever end up having neutropenic sepsis.
00:07:56
Speaker
And that's probably closer to 20% to 40% of patients who get neutropenic sepsis.
00:08:02
Speaker
Now, again, not all of those patients need to come to the ICU because –
00:08:08
Speaker
The oncologists have gotten so good at early treatment, meaning getting antibiotics into the patient quickly, and early fluid administration so that patients, even if they start to have a hint of hemodynamic instability, they can often get resuscitated and stay with the oncologic team before developing full-blown sepsis.
00:08:30
Speaker
The causes of neutropenic fever, the most common cause is myelosuppressive chemotherapy.
00:08:39
Speaker
you can see this in liquid tumor patients.
00:08:42
Speaker
It is much more common in liquid tumor patients, both because of the chemotherapies that are used, but also because of their pre-extant hematologic condition.
00:08:54
Speaker
Now, we also see neutropenia in patients who have not gotten chemotherapy.
00:08:58
Speaker
These are leukemia patients typically or patients with severe aplastic anemia who simply have dysfunctional marrow.
00:09:05
Speaker
And so they may come in with neutropenia even before they get any chemotherapy.
00:09:11
Speaker
I think that the pathophysiology of neutropenic sepsis is probably incompletely understood.
00:09:22
Speaker
At a very functional level, I've heard people describe this as a fire without any firefighters or a party without any bouncers.
00:09:35
Speaker
However, in fact, even how we say neutropenic sepsis or neutropenosis,
00:09:46
Speaker
that is just the tip of the iceberg of immune dysfunction in a cytopenic patient.
00:09:53
Speaker
Not only does that ignore the signaling, the intracellular signaling that neutrophils participate in, but it ignores the other immune cells, lymphocytes, T cells, B cells, which are also affected by
00:10:11
Speaker
myelosepressive therapy, and it also ignores things like platelets, which are increasingly recognized to have an important role in antibacterial immune defense.
00:10:20
Speaker
So the insult to the immune system during periods of neutropenia is really profound and broad and incompletely, I think, understood.
00:10:34
Speaker
And is there a difference in terms of outcomes depending on how the neutropenia occurred?
00:10:40
Speaker
Is it meaning a result of treatment versus a result of the cancer itself?
00:10:47
Speaker
Not that we know of, or at least if we know of it, not that I'm aware of.
00:10:52
Speaker
Now, patients with hematologic malignancies tend to have more profound neutropenia.
00:10:57
Speaker
So they tend to do worse results.
00:11:00
Speaker
than patients with solid tumors with neutropenic sepsis.
00:11:04
Speaker
But I'm not aware of a specific difference depending on the etiology of the neutropenia.
00:11:13
Speaker
And in terms of, you mentioned, Scott, that the vast majority of utropinic fever is treated outside of the ICU.
00:11:21
Speaker
Is there anything in particular other than our usual criteria for admitting somebody with an infection that would prompt ICU admission?
00:11:32
Speaker
No, I actually don't think so.
00:11:34
Speaker
I think, I mean, obviously the more, I think that the more,
00:11:39
Speaker
The more incipient organ failure that exists, so the person who's not only has borderline hemodynamics, but has, you know, an increasing oxygen requirement, someone who has comorbidities, they have heart failure, something that's going to make fluid resuscitation potentially a little challenging.
00:11:55
Speaker
But those are features which exist in the vast majority of our patients or in the vast majority of potential ICU admissions.
00:12:05
Speaker
So I don't think there's anything specific that we use to triage the need for critical care in neutropenic patients compared to non-neutropenic patients.
00:12:16
Speaker
So obviously the starting point is, like you said, severe neutropenia, absolute neutrophil count of 500 or less, and fever.
00:12:25
Speaker
And once we see these patients, most often ICU will be called because either oxygen requirements, other organ failure, or they had hypotension of an arrival, like you said, they have a list of comorbidities that are making the clinicians worried.
00:12:42
Speaker
And we start initial therapy.
00:12:44
Speaker
And how would you approach broad spectrum antibiotics in these patients?
00:12:55
Speaker
the choice of antibiotics and the rapidity of antibiotics.
00:12:59
Speaker
And let's hit the rapidity first.
00:13:01
Speaker
So there, you know, there's a, there's been a huge amount of, in general,
00:13:06
Speaker
hospital populations, huge amount of effort looking at timed antibiotic administration.
00:13:12
Speaker
And a lot of the data is relatively mixed as far as specific intervals, right?
00:13:17
Speaker
And we know it's better not to delay it, but we don't know exactly where is that magic hour or that, you know, is there a golden hour equivalent for antibiotics?
00:13:27
Speaker
With neutropenic sepsis and neutropenic fever, there actually is, and it's not even a golden hour.
00:13:33
Speaker
There are data that
00:13:35
Speaker
demonstrate relatively convincingly that patients who get antibiotics within 30 minutes do better than patients who get antibiotics within 60 minutes.
00:13:45
Speaker
So it really is an as soon as possible approach to antibiotic administration in neutropenic sepsis or neutropenic fever.
00:13:57
Speaker
And that speed is just of the essence.
00:14:01
Speaker
And high-performing
00:14:03
Speaker
cancer centers have the ability to give antibiotics, whether it's in the emergency room, in an urgent care clinic, on the inpatient side, within that 30-minute window.
00:14:14
Speaker
So the drugs are on the floor, ready to be mixed up, rather than having to come from the pharmacy and be subject to the delays that are intrinsic there.
00:14:26
Speaker
So speed of administration is key.
00:14:29
Speaker
As far as choice of antibiotic,
00:14:32
Speaker
The main thing that you need to make sure that you cover is pseudomonas and other gram-negative infections.
00:14:41
Speaker
And the reason for this is that if you look at the epidemiology of infections in neutropenic patients, and you look at what we're actually able to culture, remembering that about 50% of the time, despite our best efforts, we don't recover an organism.
00:14:56
Speaker
But if you look at what we are able to culture, gram-positive organisms are the most common.
00:15:02
Speaker
And this is mostly because patients have indwelling lines, they have ports, they have reasons to have gram-positive introduction into their bloodstream.
00:15:15
Speaker
But while gram-positive organisms are the most common, the gram-negative organisms, especially Pseudomonas, kill much faster, and there is nothing...
00:15:25
Speaker
more terrifying once you have seen it as an ICU doc than really for real gram-negative sepsis.
00:15:33
Speaker
It just progresses so quickly.
00:15:35
Speaker
And there are very few other things that make a patient so sick so quick.
00:15:41
Speaker
So covering gram-negatives is essential.
00:15:44
Speaker
So the guidelines, which are –
00:15:49
Speaker
put together by the Infectious Disease Society of America or the European hematologic societies or the German hematologic societies suggest using things like third-generation cephalosporins or fourth-generation cephalosporins or penicillins with anti-pseudomonal coverage.
00:16:06
Speaker
Now, in our institution, that translates into either cefepime or pipercillin-tazabactam.
00:16:15
Speaker
And with the key...
00:16:19
Speaker
that they need to be dosed at anti-pseudomonal dosing levels.
00:16:23
Speaker
So for cefepime, 2 grams Q8, or for piptazo, 6.25 grams rather than 4.25 or whatever the normal, I don't even know what the normal dosing is anymore because I just used the anti-pseudomonal dosing.
00:16:41
Speaker
But that is the mainstay.
00:16:43
Speaker
Those antipsudomonal penicillins or antipsudomonal cephalosporins are the mainstay of treatment.
00:16:51
Speaker
Then you might think about which patient.
00:16:53
Speaker
There are some patients in which you need to add gram-positive coverage, resistant gram-positive coverage.
00:16:58
Speaker
Remember, the cefepime or peptazel will get most gram-positives.
00:17:02
Speaker
But resistant staph or resistant strep, those are patients who need those are patients who you think are at risk of a staph infection.
00:17:13
Speaker
Patients who have indwelling lines, which actually is a lot of patients.
00:17:16
Speaker
So most patients end up getting vancomycin in addition to their antipsudominal penicillin.
00:17:25
Speaker
Patients with pneumonia, because both staphylococcal pneumonias and resistant strep pneumonias are a real threat in this population.
00:17:31
Speaker
And patients with skin or soft tissue infections.
00:17:35
Speaker
So like you said, I mean, I think that when we're talking about patients getting to the ICU, that's probably going to be the vast majority of patients are going to get double coverage, right?
00:17:43
Speaker
I mean, gram-positive and gram-negative coverage.
00:17:46
Speaker
Excellent.
00:17:46
Speaker
Yes.
00:17:47
Speaker
And then we will add fungal coverage on in patients who have been profoundly neutropenic for a long time.
00:17:56
Speaker
So someone who's had an ANC, you know,
00:17:59
Speaker
less than 500 or in practice, it's closer to zero because patients who are really deeply neutropenic tend to be really deeply neutropenic.
00:18:08
Speaker
For five to seven days, we will add coverage against yeast.
00:18:12
Speaker
So usually that's with an echinocandon like mycofungin or a patient who is just in profound shock.
00:18:20
Speaker
And this is analogous to regular ICU practice, right?
00:18:23
Speaker
Just go ahead and throw the book at them because they are so sick.
00:18:28
Speaker
So because you mentioned that the vast majority of patients will not have an organism identified, we start obviously as soon as possible, broad in concordance with severity, which for our ICU would be making sure you're covering antipsudomonas and MRSA most likely.
00:18:47
Speaker
And then the question of antifungals either is somebody who is extremely sick either by profound neutropenia plus minus shock or from what I understood, Scott, is if you persistently febrile despite appropriate antibiotics and you're not growing anything, that will probably prompt expanding coverage to antifungals, correct?
00:19:09
Speaker
That's right.
00:19:09
Speaker
And it's really interesting.
00:19:12
Speaker
Right.
00:19:12
Speaker
So it's the patient who comes into the ICU.
00:19:15
Speaker
So one patient would be the one very variety would be the patient who comes into the ICU.
00:19:19
Speaker
They are septic.
00:19:20
Speaker
You put them on their antipsedomodal penicillin.
00:19:24
Speaker
You put them on vancomycin and their hemodynamics kind of stabilize out.
00:19:29
Speaker
But they're still febrile after 24, 48 hours.
00:19:33
Speaker
those patients you would probably add an antifungal onto.
00:19:36
Speaker
Okay, perfect.
00:19:37
Speaker
The other variety would be the patient who has been neutropenic for a week, 10 days, and they come in just in profound shock, just in really profound shock.
00:19:48
Speaker
You might hit them with antifungals a little earlier because you know they're at risk of an invasive fungal infection because they have been neutropenic for so long.
Antibiotic and Antifungal Strategies
00:20:00
Speaker
That might actually be the...
00:20:04
Speaker
the cause of their sepsis.
00:20:05
Speaker
I mean, you're going to cover everything else too, but you probably want to add antifungals earlier in that patient.
00:20:10
Speaker
Perfect.
00:20:11
Speaker
So a couple more questions regarding the antibiotic treatment, and they have some other questions that are maybe ancillary treatments.
00:20:18
Speaker
In terms of duration, so if we were to grow something, we probably would target duration to what we grew and where we grew it.
00:20:28
Speaker
But like you said, most cases, we don't grow anything.
00:20:31
Speaker
So how long do you treat with antibiotics?
00:20:34
Speaker
Yeah, so this is a good question, and it's a question that we don't have a lot of good data on.
00:20:40
Speaker
So the historic practice in neutropenic patients has been to once you start antibiotics, you don't stop the antibiotics until the patient recovers their counts.
00:20:53
Speaker
So that could be weeks.
00:20:56
Speaker
More recently, there are data in stable neutropenic patients, so a patient who has a neutropenic fever but is not
00:21:04
Speaker
critically ill, that you can give them a set course of antibiotics, and this is assuming negative cultures, for seven days, ten days, and they're varying data on this as far as duration.
00:21:22
Speaker
But once that duration has passed, you can safely then put them back on their standard
00:21:27
Speaker
prophylactic antibiotics.
00:21:29
Speaker
Remember, all neutropenic patients are on prophylactic antibiotics or should be on prophylactic antibiotics, and usually that's a quinolone and fluconazole.
00:21:40
Speaker
What we don't know is how to extend that data to the critically ill patient, right?
00:21:48
Speaker
How long to treat someone
00:21:56
Speaker
I would say that our practice in general is to continue antibiotics as long as the patient is on vasopressors at least.
00:22:06
Speaker
So if a patient is, you know, they come in and our cultures are negative and they are still sick and on pressors at day seven, probably isn't infectious, but they are certainly at risk of developing an infection.
00:22:19
Speaker
So we will generally continue antibiotics in those patients, assuming they remain neutropenic.
00:22:27
Speaker
and assuming they remain critically ill.
00:22:29
Speaker
The patient who improves quickly, you can probably give them a seven-day, ten-day course, something like that, and then go back to their prophylactic antibiotics, assuming they're safe and they're off-pressors.
00:22:42
Speaker
Perfect.
00:22:42
Speaker
So another question related to shock, and I don't want to go into a deep dive into corticosteroids.
00:22:50
Speaker
There's a lot, I mean, obviously that has been back and forth there.
00:22:54
Speaker
But is there any increased risk of adrenal insufficiency in these patients?
00:22:59
Speaker
When do you start corticosteroids in these patients with neutropenic fever and septic shock?
00:23:05
Speaker
Yeah.
00:23:06
Speaker
Yeah, so I don't, there's not, there's not to my, to my knowledge, there's not an increased risk of immunosuppression.
00:23:14
Speaker
And my approach to this is essentially the same as in the non-immunocompromised patient, that if steroids are probably a reasonable thing to consider, if pressors continue to escalate, if you're continuing to add pressors, it's not crazy to put on, you know, the physiologic dose, um,
00:23:37
Speaker
the steroids, you know, 50Q6 of hydrocortisone or something like that.
00:23:41
Speaker
There are a few caveats to that in the oncologic population.
00:23:46
Speaker
One is that some oncologists and hematologists are wary of steroids in patients who are receiving cellular therapy, bone marrow transplants, immune effector cells, that it might kill the immune effector cells.
00:24:06
Speaker
That is probably less of a concern in practice than it is in theory, but it is the kind of thing that we typically will discuss with the oncologists.
00:24:16
Speaker
Hey, we're thinking about giving steroids.
00:24:18
Speaker
What do you think about this?
00:24:19
Speaker
The other thing is that a lot of cancer patients are already on a lot of steroids.
00:24:26
Speaker
Prednisone is an important part of a lot of antilymphoma regimens.
00:24:31
Speaker
Steroids are frequently used for antitumor efficacy, even in some solid tumors.
00:24:35
Speaker
So you may not need to do it because the patient may already be on large and high doses of steroids.
00:24:42
Speaker
Perfect.
00:24:43
Speaker
The other question I have related to the antibiotics is with catheters.
00:24:49
Speaker
I mean, portacaths, more commonly what we see in these patients.
00:24:54
Speaker
If we grow something in the blood, does that mean the portacath comes out?
00:24:59
Speaker
Yeah, so that's a good question.
00:25:01
Speaker
That's a key point.
00:25:03
Speaker
It depends on the organism.
00:25:06
Speaker
So there are some organisms which you can try to treat through.
00:25:12
Speaker
My personal approach is to remove catheters in patients who have gram-negative sepsis, especially Pseudomonas, because it tends to be a very sticky, tough-to-eradicate organism, and patients with staph aureus.
00:25:34
Speaker
I think in those patients, the catheters need to come out.
00:25:39
Speaker
And in patients who have
00:25:41
Speaker
refractory shock, there are actually some data that in, I mean, in neutropen patients who have profound shock that even before you get a culture, the catheter should come out.
00:25:53
Speaker
Um, and so that's kind of in our standard approach to the really sick patient.
00:25:57
Speaker
Does this catheter need to get yanks?
00:26:00
Speaker
Um, it is, no one likes to do that, but it is sometimes a necessary thing to do.
00:26:08
Speaker
It is why I am always, uh,
00:26:11
Speaker
I always prefer it when our patients come in and they have a catheter, even if it's a tunnel catheter, as opposed to an implanted port, because it is so much easier and faster to get the tunnel catheter out, even for us to do it potentially, rather than calling interventional radiology or surgery to dig it out, than it is to get a port out.
00:26:31
Speaker
So, you know, from an ICU doc's perspective, catheters, tunnel catheters, PICS, much preferable because we can get them out quickly.
00:26:41
Speaker
I agree.
00:26:42
Speaker
And the last question is I trained many years ago in internal medicine and started my first week as an intern, I think, in the bone marrow transplant and oncology floor.
00:26:54
Speaker
And back in the day, we prescribed a lot of GCSF.
00:26:57
Speaker
What's the stance today?
00:27:01
Speaker
So it is variable.
00:27:04
Speaker
A lot of it is protocolized.
00:27:07
Speaker
in a patient's treatment regimens.
00:27:09
Speaker
You know, there are some patients in whom you absolutely don't want to give GCSF, right?
00:27:13
Speaker
So the acute leukemic, who is a low counter and is pancytopenic and neutropenic for that, you don't want to give them GCSF because you may convert a low count.
00:27:23
Speaker
This is the patient who hasn't gotten treatment yet for the leukemia.
00:27:26
Speaker
You may convert a low count leukemia to a high count leukemia.
00:27:30
Speaker
So that is someone in whom you would avoid GCSF.
00:27:34
Speaker
In other patients, so a patient who is neutropenic after getting chemotherapy for a solid tumor or even sometimes leukemia or lymphoma, or a patient who is getting a bone marrow transplant, GCSF is often part of their treatment plans.
00:27:53
Speaker
And it's an interesting question whether to give GCSF to a critically ill patient.
00:27:58
Speaker
There has been some historic leaning not to because of some not bad data that giving GCSF and causing an explosion in immune cells can potentiate the off-target damage from the immune system.
00:28:16
Speaker
So you can get ARDS, you could get worsening sepsis if you crank up the body's inflammation with GCSF.
00:28:24
Speaker
There are some newer data out of MD Anderson in particular that suggest the opposite, that maybe GCSF is beneficial in patients with sepsis.
00:28:34
Speaker
But this has not been studied in a randomized controlled fashion.
00:28:39
Speaker
And so I think a lot of this is stylistic rather than data-driven.
00:28:47
Speaker
Perfect.
00:28:47
Speaker
And I think that might be a good lead way to talking about too many white cells.
00:28:52
Speaker
So let's talk a little bit about hypolucositosis and when we should be worried about it and when it might be something to be dealt with in the ICU.
Leukostasis and Tumor Lysis Syndrome
00:29:02
Speaker
Yeah, so leukostasis is a severe complication of generally acute leukemias.
00:29:09
Speaker
And it is almost always acute myeloid leukemias.
00:29:14
Speaker
So you rarely see it in
00:29:17
Speaker
lymphoid leukemias, like ALL, and you very rarely see it in chronic leukemias like CML or CLL, even with really high white counts, you know, 300, 400,000, you rarely see it in those diseases.
00:29:32
Speaker
Where we do see it is in acute myeloid leukemia and in some of its variants.
00:29:37
Speaker
And typically you will see it, typically you don't see it in patients who have a white count less than 100,000.
00:29:44
Speaker
in acute myeloid leukemia.
00:29:46
Speaker
But there are some leukemias that, for one of a better descriptor, are stickier than others.
00:29:51
Speaker
And so you actually can see leukostasis in patients with a white blood cell count as low as 35,000 if it is all blasts and all really sticky myeloid blasts.
00:30:06
Speaker
But that is rare, and usually we don't see this until they get over 100,000 or they're approaching 100,000.
00:30:12
Speaker
It can manifest in a number of different ways.
00:30:17
Speaker
It can affect any organ system in the body.
00:30:20
Speaker
The most common manifestations are respiratory distress and neurologic symptoms, headache, confusion, things like that, but also respiratory failure.
00:30:33
Speaker
And it looks on an x-ray like pulmonary edema.
00:30:36
Speaker
But you can see myocardial infarctions.
00:30:40
Speaker
And on pathology, the coronaries will just look packed with white blood cells, like they're clotted with white blood cells.
00:30:48
Speaker
You can see acute limb ischemia.
00:30:50
Speaker
You can see gut ischemia from occlusions of vessels with white blood cells.
00:30:56
Speaker
But the most common manifestations are neurologic manifestations and respiratory manifestations.
00:31:02
Speaker
And by definition, if these patients present to the hospital, they're likely going to end up in the ICU with that severity, right?
00:31:10
Speaker
I mean, if they need respiratory support, yes.
00:31:12
Speaker
The neurologic manifestations, it depends on how altered they are, if they just have a little bit of a headache or if they have a head bleed because they've got a pressure backup from the leukostasis or if they're actually obtunded or seizing.
00:31:30
Speaker
So I think...
00:31:32
Speaker
I think at a specialty cancer hospital, these patients, there may be some leeway as to which patients can be managed on a regular oncology floor rather than in an ICU.
00:31:46
Speaker
In a general hospital, so if a patient presents with de novo acute leukemia at a community hospital that doesn't have a leukemia center, those patients probably should be managed in the ICU until they can get transferred to a leukemia center.
00:31:58
Speaker
Yeah.
00:31:59
Speaker
And what would be the treatment for leukostasis?
00:32:03
Speaker
Yeah, so this has evolved.
00:32:05
Speaker
And so the fundamental things are almost what not to do.
00:32:13
Speaker
So hydration is the first-line approach.
00:32:17
Speaker
So you want to give fluids just to decrease viscosity, increase the flow characteristics of the blood, and that is the first thing to do.
00:32:28
Speaker
Now, this often causes people some –
00:32:32
Speaker
cognitive dissonance or dyspepsia because the patient may present with an x-ray that looks like pulmonary edema.
00:32:40
Speaker
But if the white count is really high, 100,000 or so, and it looks like pulmonary edema, it's probably leukostasis.
00:32:47
Speaker
And you may actually get benefit from giving fluids.
00:32:51
Speaker
And if that makes them worse, they just need to be intubated or have escalating respiratory support.
00:32:59
Speaker
What you should not do is give diuretics.
00:33:02
Speaker
Even if the x-ray looks like classic pulmonary edema, you don't want to give diuretics because that will just decrease the plasma volume and make the blood even stickier and you will worsen and even potentiate leukostasis.
00:33:15
Speaker
This, by the way, and this is something we see relatively commonly.
00:33:18
Speaker
A patient will come into an emergency room, their white count is really high, they get an x-ray and it looks like they've got pulmonary edema, they get diuretics, and next thing you know, the patient is
00:33:28
Speaker
becomes a tundin because their leukostasis has progressed and that diuresis just pushed them over the edge.
00:33:35
Speaker
The other thing you should not do is give them red blood cells.
00:33:40
Speaker
And this again is also, it's an understandable error because a lot of times in acute leukemia, the patient will be neutropenic, or I'm sorry, will be anemic, right?
00:33:50
Speaker
They might have a hemoglobin of only four or five and it's very naturally, oh, they need blood.
00:33:56
Speaker
But if you give red cells to someone, packed red cells to someone who has a weight count of 100,000, 120,000 is already hyperviscous, you give them that additional viscous red blood cells, it's going to make that even worse.
00:34:11
Speaker
And we have seen patients just die from getting red cells on top of a leukostatic type syndrome.
00:34:21
Speaker
So you really don't want to diurese them and you don't want to transfuse them.
00:34:26
Speaker
And that is kind of, those are the things that we try to nail into our fellows and our ICU docs heads, right, is not to do those things.
00:34:38
Speaker
Then there's the question of how do you, but those are only temporizing measures, right?
00:34:42
Speaker
Fluids, not diuresing, not transfusing, those are temporizing measures, and they need cytoreduction.
00:34:49
Speaker
So up until about five or 10 years ago, the approach, and I should say that the need for cytoreduction, this is where you need an oncologist or hematologist involved, right, to decide whether a patient needs cytoreduction and then how to do it.
00:35:06
Speaker
Up until about five or 10 years ago, the predominant approach was leukophoresis.
00:35:11
Speaker
So you'd put a pheresis catheter in someone, you'd hook them up to a pheresis machine, and you'd
00:35:18
Speaker
And this worked quickly.
00:35:20
Speaker
It got the white count down fast.
00:35:23
Speaker
But the white count always rebounded because you weren't changing the natural history of the disease.
00:35:32
Speaker
And in looking at retrospective studies, again, no one's really been randomized for this, but it seemed like patients who got leukopharist rather than who got cytoreductive chemotherapy have worse outcomes.
00:35:46
Speaker
So we at least at Hopkins have moved away from leukopheresis in patients.
00:35:51
Speaker
I actually can't remember the last time that I've leukopherised someone for –
00:35:57
Speaker
leukostasis, and they get cytoreductive chemotherapy.
00:36:02
Speaker
And so this is, again, I'm not the one prescribing the chemotherapy.
00:36:05
Speaker
This is from the oncologist or hematologist.
00:36:08
Speaker
And there are various approaches depending on how certain they are of the diagnosis and increasingly what the molecular features of the cancer are.
00:36:18
Speaker
But they might decide to use something like hydroxyurea.
00:36:21
Speaker
They might decide to give someone a slug of cyclophosphamide.
00:36:26
Speaker
or if they have more information on what the specific
00:36:30
Speaker
leukemia is and what some of the molecular mechanisms they may use a more targeted therapy like gemtuzumab or something like that.
00:36:37
Speaker
And that is all, that is the decision of the oncologist.
00:36:40
Speaker
And our job is to support the patient as they do that.
00:36:44
Speaker
And the biggest complication for this, and I don't, I don't know if we want to, this may be a good segue to, but the biggest complication for cytoreducing someone with a really high white count is tumor lysis syndrome.
00:36:56
Speaker
And so we often need to be prepared to,
00:37:00
Speaker
to manage that.
00:37:02
Speaker
I do think it's a great segue, but I also think that it's probably worthwhile reemphasizing, right, for our listeners that I can see how somebody presents to the ED with vague complaints.
00:37:15
Speaker
They get an x-ray.
00:37:16
Speaker
It looks like pulmonary edema.
00:37:18
Speaker
They get a CBC.
00:37:20
Speaker
It has super high white counts and low hemoglobin.
00:37:24
Speaker
And I could see how very quickly somebody might order diuretics and blood, right, or blood and diuretics.
00:37:31
Speaker
It happens all the time, I'm sure.
00:37:33
Speaker
It happens all the time.
00:37:34
Speaker
And it makes sense, right?
00:37:38
Speaker
This is not an error of either omission or commission, really.
00:37:42
Speaker
These are people trying to do the right thing.
00:37:44
Speaker
And this is just one of the few idiosyncrasies of oncologic critical care.
00:37:50
Speaker
And I believe it's super important to remind our listeners that not to do that.
00:37:56
Speaker
And not to continue it, right?
00:37:57
Speaker
Because you could also see how you get into a vicious cycle.
00:38:00
Speaker
They gave a diuretic.
00:38:02
Speaker
The patient's getting worse.
00:38:04
Speaker
You look at the x-ray.
00:38:05
Speaker
It's worse.
00:38:05
Speaker
You give more diuretics, right?
00:38:08
Speaker
And just recognizing, like you said, that this is something very idiosyncratic about this presentation.
00:38:14
Speaker
But I do believe that, like you said, if you have a high white count and you're doing cytoreduction, the next thing you would worry about is tumor lysis syndrome.
00:38:22
Speaker
So why don't we talk about that?
00:38:25
Speaker
Right, and tumor lysis syndrome is one of the things that really scares me.
00:38:34
Speaker
It is one of the conditions that an oncologic patient can die from very, very quickly.
00:38:40
Speaker
So what tumor lysis syndrome is is essentially electrolyte abnormalities and metabolic abnormalities caused by the rapid death of tumor cells.
00:38:54
Speaker
So tumor cells die and they release their intracellular contents.
00:38:58
Speaker
And these are things like uric acid, calcium, and potassium.
00:39:05
Speaker
And that uric acid can deposit particularly in the kidneys and leading to acute kidney injury, which then obviously reinforces kind of an ambitious cycle, the electrolyte abnormalities because you can't get rid of the potassium.
00:39:22
Speaker
So patients present typically with hypercalcemia, hypophosphatemia, because the phosphate can precipitate, hyperuricemia, and hyperkalemia.
00:39:33
Speaker
And this can manifest as renal failure.
00:39:36
Speaker
It can manifest as mental status changes, seizures.
00:39:42
Speaker
But the most dangerous thing, the thing that kills patients with tumor lysis syndrome is hyperkalemia and cardiac arrest from that.
00:39:55
Speaker
Perfect.
00:39:56
Speaker
And in terms of other considerations for treatment, when should respiracase be part of treatment in the ICU?
00:40:04
Speaker
Yeah, so the fundamental aspect of treatment for tumor lysis syndrome is hydration, right?
00:40:11
Speaker
So if you have a patient who you think is at high risk of tumor lysis, um,
00:40:16
Speaker
then you want to keep them hydrated.
00:40:18
Speaker
You want to keep them peeing so they will urinate out all the uric acid.
00:40:21
Speaker
They will urinate out their potassium.
00:40:24
Speaker
And that is the key.
00:40:25
Speaker
That is the first line therapy is to hydrate these patients.
00:40:29
Speaker
And it doesn't, some people say you shouldn't use lactate ringers because it has potassium in it.
00:40:34
Speaker
The, I don't, the data don't really support that.
00:40:38
Speaker
We do tend to use normal saline just because of that theoretical risk.
00:40:41
Speaker
But I think that,
00:40:43
Speaker
I think that as we learn more about the benefits of balanced solutions for resuscitation, I think it's probably reasonable to use lactate ringers or plasma light.
00:40:53
Speaker
As long as you are keeping the patient urinating, I think that's the most important point.
00:40:58
Speaker
What isotonic fluid you use probably doesn't matter as much.
00:41:03
Speaker
But then the pathophysiology of tumor-lysis syndrome, the thing that you want to interrupt, is the uric acid production and the uric acid deposition.
00:41:14
Speaker
So the first-line drug really is allopurinol.
00:41:19
Speaker
Now, that just blocks uric acid production.
00:41:22
Speaker
It doesn't do anything to get rid of the uric acid that is already there.
00:41:25
Speaker
But as prophylaxis, it's relatively effective.
00:41:30
Speaker
and should be a patient who is at high risk for tumor lysis because they've got bulky lymphoma or a really high white count, they should probably get put on allopurinol before they get induced.
00:41:44
Speaker
Rasburicase, which is a recombinant uric acid-destroying enzyme, it is highly effective at dropping uric acid levels.
00:42:00
Speaker
It is also really highly expensive.
00:42:03
Speaker
So we tend to reserve that to patients who meet specific criteria, and usually that is an elevated uric acid level already above 10 or 11.
00:42:13
Speaker
And different centers have different thresholds for using Rasburacase, but ours tends to be the presence already of an elevated.
00:42:22
Speaker
So we wouldn't give it in someone who does not already have significantly elevated uric acid.
00:42:25
Speaker
We would give it in someone whose uric acid is already high.
00:42:29
Speaker
So really, I mean, for severe cases, probably those coming to the ICU from the floors or people who have failed prophylaxis with allopurinol.
00:42:39
Speaker
Yeah, that's exactly right.
00:42:41
Speaker
Someone whose uric acid has continued to escalate despite being on allopurinol, despite getting hydration.
00:42:48
Speaker
And again, this depends a lot on the center capabilities.
00:42:51
Speaker
They may not need it.
00:42:52
Speaker
It may not be...
00:42:54
Speaker
ICU equals raspiracase, they may get raspiracase in the floor before they come to the ICU.
00:43:00
Speaker
They may come to the ICU and not quite need raspiracase.
00:43:03
Speaker
But we typically give it just for elevated, refractory elevated uric acid levels.
00:43:09
Speaker
Perfect.
00:43:10
Speaker
And obviously, you're measuring frequent labs in these patients.
00:43:14
Speaker
Are there any precautions that people should be aware of in terms of before or after raspiracase and lab?
00:43:23
Speaker
No, you know, respiricase is actually really pretty well tolerated.
00:43:28
Speaker
It does, it can cause methemoglobinemia in G6PD deficient patients.
00:43:35
Speaker
And I have seen this once or twice, someone with, you know, really catastrophic methemoglobinemia in a patient who got respiricase.
00:43:45
Speaker
Now, we do not, and this is a point of emphasis, even though it can cause it, we do not routinely
00:43:55
Speaker
if for no other reason than that it takes days sometimes for a G6PD level to come back.
00:44:03
Speaker
So in a patient who is in tumor lysis syndrome, they needed the Raspericase quickly.
00:44:10
Speaker
So we do not routinely check it, but it is something to, you can see methamphetamine and hemolysis in patients who have G6PD efficiency.
00:44:20
Speaker
So it's something to be aware of, but I've only seen it once or twice in,
00:44:25
Speaker
you know, in the last 10 years.
00:44:29
Speaker
So it is something to know about, but not something to prevent you from giving raspberries to someone who needs it.
00:44:37
Speaker
Perfect.
00:44:38
Speaker
And finally, is there anything else that you would comment on the acute renal failure?
00:44:45
Speaker
So you mentioned, Scott, that people die from cardiac arrhythmias and the hyperkalemia if it's untreated, right?
00:44:51
Speaker
But it's like the uric acid that ultimately leads to renal failure.
00:44:55
Speaker
Once we develop renal failure, is there anything different about treating these patients or the goal is to prevent that?
00:45:01
Speaker
I mean, the goal is to prevent that.
00:45:02
Speaker
You know, somewhat the goal is to prevent that.
00:45:07
Speaker
I think that the key thing with tumor lysis syndrome is, you know, to do all that we talked about already hydration, allopurinol, vaspericase, but early this, an early decision about whether renal replacement therapy is needed and really driven by potassium rather than by the renal failure itself.
00:45:28
Speaker
And, you know, the,
00:45:31
Speaker
we really have a very low threshold for starting renal replacement therapy in someone who has tumor lysis syndrome and hyperkalemia because it's not going to get better for a few hours or a few days.
00:45:43
Speaker
And so we have a very low threshold to put a dialysis catheter in and start them on continuous renal replacement therapy.
00:45:52
Speaker
And it's worth emphasizing that
00:45:54
Speaker
replacement therapy.
00:45:55
Speaker
And this is often the indication for ICU transfer is the, either the need or the anticipated need for CRRT.
00:46:03
Speaker
CRRT is far preferred compared to intermittent dialysis because the tumor death is ongoing.
00:46:11
Speaker
And so the production of potassium or the release of potassium is going to be ongoing.
00:46:16
Speaker
And so you may dialyze someone like an intermittent session, and then an hour later you need to do it again.
00:46:23
Speaker
because their potassium is shot right back up.
00:46:25
Speaker
So continuous renal replacement therapy is really the way to go in these patients.
00:46:30
Speaker
Perfect.
00:46:32
Speaker
So let's talk about other complications related to maybe blood, blood, I mean, that accumulates or other fluid in the pericardial sac.
Cardiac Complications in Cancer
00:46:42
Speaker
So pericardial fusion and cardiac tamponade, something that we also see frequently in cancer and might end up in the ICU.
00:46:49
Speaker
Any comments on that that we should be aware of, Scott?
00:46:53
Speaker
We see this very frequently.
00:46:55
Speaker
A lot of times we don't know why they have it.
00:46:59
Speaker
Sometimes, you know, you'll do a pericardiosynthesis and you'll get, you know, tumor cells, lymphoma cells in the pericardial fluid and you know exactly what it is.
00:47:07
Speaker
But we also see a lot of kind of cryptic pericardial effusions, especially after bone marrow transplant.
00:47:15
Speaker
And whether that is just, you know, the overall inflammatory state and kind of a sericitis.
00:47:23
Speaker
which is what I suspect versus truly a malignant effusion.
00:47:28
Speaker
But as you say, we see pericardial effusion and tamponade in a lot of patients.
00:47:34
Speaker
The other thing that we see, it's not really a pericardial effusion per se, but we will see mediastinal involvement, bulky mediastinal involvement from a lymphoma or from small cell lung cancer or from other primary mediastinal tumors.
00:47:52
Speaker
And these, even though they're not causing pericardial filling, they can cause the same, if not tamponade physiology, the same mediastinal compressive physiology that can result in, you know, hemodynamic deterioration.
00:48:11
Speaker
So, you know, as always, having a high suspicion for pericardial disease and making sure you think about tamponade in the patient who is...
00:48:21
Speaker
deteriorating.
00:48:23
Speaker
You know, the advent of POCUS ultrasound has really helped us here, I think, in that it lets us see a lot of effusions, even some effusions that probably aren't hemodynamically significant.
00:48:35
Speaker
But, you know, that really should be added to the evaluation of a patient who either you know has mediastinal disease or who has undifferentiated shock to make sure that there's not pericardial involvement.
00:48:50
Speaker
The other thing that it
00:48:51
Speaker
complicates is airway management, right?
00:48:53
Speaker
The patient with a mediastinal mass, with tamponade, this can be a very challenging patient from a physiologic standpoint to intubate, you know, because you give them an induction agent and their pressure plummets and suddenly their cardiac output goes to zero after you give them the induction agent.
00:49:13
Speaker
And then they may or may not tolerate the positive pressure of mechanical ventilation terribly well.
00:49:18
Speaker
So these are patients that we really have to think very carefully about what is the safest way to intubate them and where it should be done.
00:49:26
Speaker
So a lot of times this will be done as an awake fiber optic intubation or a minimally sedated fiber optic intubation rather than a traditional intubation.
00:49:39
Speaker
intubation.
00:49:40
Speaker
We collaborate a lot with our anesthesia colleagues on this, especially if we think a patient needs to go to the operating room to be intubated, to do it in a more controlled setting.
00:49:49
Speaker
But mediastinal involvement, pericardial tamponade, a big complicator of endotracheal intubation.
00:49:58
Speaker
And in terms of pericardial diffusion with cancer, usually the nature of it is that it doesn't occur in a short period of time.
00:50:05
Speaker
So you might have a large amount of fluids before you have hemodynamic impact.
00:50:11
Speaker
And once that is drained or it's recognized as treatment, any comments on things that we should monitor post-drainage?
00:50:18
Speaker
And also any comments on what are the best drainage management techniques later on with these cancer patients?
00:50:29
Speaker
Yeah, so a lot of it depends on the etiology.
00:50:32
Speaker
So, for instance, a patient who has a lymphoma dispericardial infusion, that will get better, or it usually gets better as they get treated for their lymphoma.
00:50:41
Speaker
So that has a relatively low risk of recurring.
00:50:44
Speaker
The patient who has a malignant solid tumor infusion, those don't generally get
00:50:51
Speaker
better as fast or at all.
00:50:53
Speaker
And so that, um, that may change how you approach it, but obviously you want to watch for recurrent tamponade.
00:51:01
Speaker
Um, you know, much like, uh, the patient, as you say, you know, these are different than like the post-op cardiac surgery patient who can get tamponade with just a few CCs of blood in the right place.
00:51:12
Speaker
These tend to be bigger effusions, but just like, um,
00:51:18
Speaker
a post-op cardiac patient, you know, if the pericardial drain suddenly stops putting out fluid, that's something to pay attention to, right?
00:51:27
Speaker
To think that there might be an onion, it's gotten clogged and it's not appropriately draining.
00:51:31
Speaker
So that can be reassessed with ultrasound, can be reassessed by trying to flush the drain.
00:51:38
Speaker
But that's something to keep in mind.
00:51:41
Speaker
These patients do have, they are typically immunosuppressed, so at least in theory, the risk of infectious pericarditis from a drain in place that stays in too long is a real one.
00:51:56
Speaker
I actually have never seen it in one of these patients, but I know that the cardiologists worry a lot about it.
00:52:02
Speaker
So, you know, you do want to get the drain out as safely as possible.
00:52:06
Speaker
Okay.
00:52:09
Speaker
But really, recurrent effusions and myocardial injury from the drain placement are the two things that I tend to most worry about.
00:52:18
Speaker
So if you start seeing bright red blood or fresh blood coming out of the pericardial drain, something's wrong.
00:52:26
Speaker
And it can be very easy with percutaneous pericardial drain placement to actually hit the ventricle.
00:52:33
Speaker
And so that is something to at least be aware of as a potential complication.
00:52:39
Speaker
As far as management, usually our first-line management is percutaneous pericardial drainage, if for no other reason than that it's faster.
00:52:50
Speaker
But in a patient who is at high risk for recurrent disease or who has proven themselves to have recurrent effusions despite drainage, and assuming that it fits within goals of care and all the other things
00:53:06
Speaker
considerations, then a surgical pericardial window is the next step.
00:53:13
Speaker
Perfect.
00:53:15
Speaker
So you mentioned at the beginning of the podcast, Scott, that respiratory failure is the most common reason why patients with cancer come to the ICU.
Advancements in Oncologic Critical Care
00:53:25
Speaker
And you also mentioned that there might be some specific points to consider when we are providing respiratory support for immunocompromised patients for cancer.
00:53:36
Speaker
So maybe as we close, we can touch on that a little bit.
00:53:42
Speaker
Yeah.
00:53:42
Speaker
So, um,
00:53:44
Speaker
I think the key aspects of respiratory failure management
00:53:48
Speaker
One is that when a patient is intubated, they need the same, and they've got hypoxemic respiratory failure and ARDS, they need low tidal volume ventilation.
00:54:00
Speaker
And all of the things that we think about in the non-cancer patient with ARDS, we need to think about in the cancer patient.
00:54:09
Speaker
Are they getting low tidal volume ventilation?
00:54:11
Speaker
Are their lung pressures adequately protective?
00:54:16
Speaker
Are we thinking about proning them if their P to F ratio is less than 150?
00:54:20
Speaker
You know, all of those things, these interventions tend to be underused in cancer patients.
00:54:26
Speaker
And so we need to make sure that we're giving the cancer patients the same standard of care we would give any other ARDS patient.
00:54:35
Speaker
The other thing to think about in immunocompromised patients is that there is...
00:54:40
Speaker
more benefit to a bronchoscopy with alveolar lavage in an immunocompromised patient than in a non-immunocompromised patient.
00:54:52
Speaker
Because they can get things like pneumocystis or other opportunistic infections, which we're not going to see in an immunocompetent patient, but we may only be able to make the diagnosis with from a BAL.
00:55:05
Speaker
So I tend to, if a patient, you know, an oncology patient gets intubated for respiratory failure, I will bronch them and get a good sample.
00:55:15
Speaker
You know, it doesn't take that long.
00:55:19
Speaker
It is almost always safe.
00:55:21
Speaker
You know, the biggest risk of bronchoscopy is that they're going to desaturate during the bronchoscopy because you may de-recruit them.
00:55:29
Speaker
But even on someone who is on high levels of PEEP, high levels of FiO2,
00:55:33
Speaker
They generally tolerate a quick BAL very well, and if it gives you information that changes their therapy, it can really affect their outcomes.
00:55:44
Speaker
I will say I do not worry about platelets when I do a BAL through an intratheal tube.
00:55:49
Speaker
They can have no platelets, and I'm fine with doing that.
00:55:51
Speaker
They're not going to bleed.
00:55:54
Speaker
And early platelets.
00:55:57
Speaker
is really key.
00:55:58
Speaker
The yield goes down dramatically with delay.
00:56:00
Speaker
So we try to do it in our ICU the day they are intubated, usually right after intubation.
00:56:05
Speaker
The tube goes in, makes sure everything's relatively copacetic, and then do a quick BAL.
00:56:13
Speaker
But that is really probably the biggest difference in
00:56:18
Speaker
As far as practice, they still need the same ventilator management.
00:56:21
Speaker
They still need the same daily awakening trials.
00:56:25
Speaker
They still need physical therapy and rehabilitation.
00:56:27
Speaker
All those things we do in immunocompromised, competent patients, we should do in immunocompromised patients.
00:56:32
Speaker
The big difference from my perspective is the early bronchoscopy.
00:56:36
Speaker
Perfect.
00:56:37
Speaker
And as we close the oncologic emergency topic, are there other emergencies that you just want to mention very briefly for people to be aware without going into death?
00:56:47
Speaker
And these might be things that are probably more of the scope of cancer and specific hospitals and ICUs.
00:56:57
Speaker
Yeah, I think that the things that we are seeing now, we see relatively few in our ICU of kind of the classic oncologic, of things like cord compression.
00:57:11
Speaker
We see that occasionally, but not very often.
00:57:15
Speaker
We don't see a lot of superior vena cava syndrome occasionally, but not very often, but most of those that doesn't really need, that's not usually the level of an ICU emergency cord compression can be the things that we, the other complications that we see.
00:57:27
Speaker
So head bleeds, um, especially in neutropin and, uh, in leukemia patients who have no platelets, um, you know, any headache is a head bleed until proven otherwise.
00:57:39
Speaker
So these patients get head CTs all the time.
00:57:42
Speaker
Um, um,
00:57:45
Speaker
And they often need to come to the ICU for frequent monitoring after a head bleed or for aggressive blood product correction of factors after a head bleed.
00:57:54
Speaker
The other things that we see are complications of immunotherapy.
00:58:00
Speaker
So pneumonitis from checkpoint inhibitors or encephalitis from checkpoint inhibitors or myocarditis from checkpoint inhibitors.
00:58:08
Speaker
This is increasingly common.
00:58:11
Speaker
And I think it is also increasingly common
00:58:14
Speaker
bleeding as these drugs become more and more commonly used, these complications, pneumonitis, um, encephalitis, myocarditis, um, adrenalitis, really any autoimmune type disease can be precipitated by checkpoint inhibitors.
00:58:33
Speaker
These are going to bleed out into community hospitals because so many more patients are going to be on these drugs because they do work.
00:58:41
Speaker
Um,
00:58:42
Speaker
Their management is probably a topic for a whole podcast in and unto itself, but it basically is, if that is what you think the diagnosis is and you have excluded infection, it's steroids and maybe IVIG.
00:58:59
Speaker
But so checkpoint complications, I think are going to become increasingly common in the community.
00:59:04
Speaker
The other thing that's going to be increasingly common in the community are the complications of immune effector cells like CAR T cells.
00:59:11
Speaker
You know, these are cells that have been modified to engage a tumor epitope, but they can have off-target effect.
00:59:20
Speaker
And the most common sequelae from them are cytokine release syndrome, which is a febrile syndrome, which can progress to hypotension, hemodynamic instability, and respiratory failure, and responds very well to steroids and...
00:59:39
Speaker
cytokine blockade with IL-6 agents like tocilizumab.
00:59:44
Speaker
And then neurologic symptoms, so-called ICANS, from these immune effector cells, which is an encephalopathy, which starts as confusion and then can progress to cerebral edema.
00:59:59
Speaker
And the treatment for that is early steroids.
01:00:03
Speaker
I think these are mostly still seen at tertiary centers for the moment, but CAR T cells are exploding in usage both for liquid tumors but also increasingly for solid tumors.
01:00:16
Speaker
And some of the new formulations, while highly effective,
01:00:23
Speaker
do have really very commonly caused these side effects.
01:00:27
Speaker
And so I think that community intensivists and community ER docs, you need to be increasingly aware of these, of the complications from immune effector cells because people are going to be given them for everything because they really work.
01:00:42
Speaker
Perfect.
01:00:42
Speaker
And maybe that will be, like you said, a topic for a future podcast.
01:00:47
Speaker
So, Scott, we'd like to close the podcast with a couple of questions that are unrelated to the clinical topic.
01:00:54
Speaker
Would that be okay?
01:00:56
Speaker
Yeah, of course.
01:00:57
Speaker
The first question relates to books.
01:00:59
Speaker
Is there any book or books that have influenced you the most or that you have gifted often to others?
01:01:05
Speaker
Yeah.
01:01:06
Speaker
Yeah, the book that I have probably gifted the most to others, and usually it's been to mentees, is E.B.
01:01:15
Speaker
Strunk and Ed White's The Elements of Style, which is a writing guide.
01:01:20
Speaker
You know, it's a very thin little, I don't know, 150-page book, but essentially says this is how you write effectively.
01:01:27
Speaker
And it is amazing.
01:01:29
Speaker
well-written, um, but it's also concise enough and accessible and enjoyable enough for people, you know, if you really want, for people who are trying to improve their writing, I think it's really, uh, um, and, uh, an invaluable resource.
01:01:43
Speaker
As far as books that have influenced me the most, probably the two that I would pick, uh, are, um,
01:01:55
Speaker
Scientific Revolutions.
01:01:57
Speaker
Kuhn was at MIT for many years and wrote this beautiful book on how scientific discovery progresses and how we change and challenge paradigms.
01:02:08
Speaker
And it's a really well-written book.
01:02:11
Speaker
And along that same vein, especially now with this new movie about Robert Oppenheimer coming out, there's a wonderful book called The Physicists.
01:02:21
Speaker
which is the history of the physical science community in North America.
01:02:27
Speaker
I found it to be really an enjoyable and enlightening read.
01:02:33
Speaker
Perfect.
01:02:33
Speaker
And definitely, I think all great recommendations.
01:02:37
Speaker
We will include links in the podcast notes.
01:02:40
Speaker
But going to your first book, the one that you gift often, I do believe that communication is a superpower no matter what you do.
01:02:48
Speaker
And that writing effectively, writing correctly, usually reflects organized thought process.
01:02:57
Speaker
And even in medicine today, I think is extremely underrepresented and undervalued.
01:03:03
Speaker
So definitely something for people to think about.
01:03:08
Speaker
Probably the key point in that stop-of-the-ile manual is omit needless words.
01:03:16
Speaker
Absolutely.
01:03:17
Speaker
And I think that is such a key and underappreciated philosophy in writing.
01:03:26
Speaker
And in life.
01:03:28
Speaker
Yeah, no, and I do believe that there are examples that we encounter every day, right?
01:03:34
Speaker
A well written article, especially when we're trying to communicate knowledge like today, right?
01:03:41
Speaker
A review article, sometimes I think is harder to write well than maybe a clinical trial that kind of has, okay, these are the
01:03:48
Speaker
the spots.
01:03:49
Speaker
But then again, there are some discussions that are very well written and there's some that are not so well written.
01:03:53
Speaker
So definitely something worth investing no matter where you are in terms of your medical career.
01:04:00
Speaker
Perfect.
01:04:01
Speaker
And I have not, I definitely read, I mean, the scientific, the revolution, structured scientific revolutions.
01:04:07
Speaker
Again, I think along the lines also of a lot of what Karl Popper wrote, how science evolves and how we develop knowledge is, I think, fascinating.
01:04:16
Speaker
And a lot of times, not the way people think that there's this one eureka moment that revolutionized medicine, right?
01:04:22
Speaker
Slowly, revolutions are built in.
01:04:26
Speaker
And then the physicist I have not read, but I am intrigued by that Oppenheimer movie.
01:04:33
Speaker
There was, I think, a biography of him called Black American Orphils or something along those lines.
01:04:38
Speaker
American Prometheus.
01:04:39
Speaker
Yeah, American Prometheus.
01:04:41
Speaker
That was fascinating.
01:04:42
Speaker
So we'll definitely check that out.
01:04:44
Speaker
Perfect.
01:04:46
Speaker
The second question, Scott, is what do you believe to be true in medicine or life that most other people don't believe or at least don't act as if they believe?
01:04:57
Speaker
Well, this is a little tougher.
01:05:03
Speaker
I think, though, that just like I said, the key point in that style manual was omit needless words.
01:05:10
Speaker
I think that we often in critical care medicine and I think also in life, I think we make things more complicated and
01:05:25
Speaker
than they often need to be.
01:05:28
Speaker
And a lot of times I think that's done as a way of showing or showing off knowledge.
01:05:38
Speaker
And knowledge really does not equate to understanding.
01:05:42
Speaker
You know, there's a big gap there, I think.
01:05:46
Speaker
And the way to...
01:05:49
Speaker
at least I think understanding is really kind of the distillation of all these facts that we can come up with into what is actually applicable.
01:05:58
Speaker
And that is the real challenge for me in medicine.
01:06:01
Speaker
And the part that I enjoy is of all the things that we can learn or we can Google, what is actually applicable to the patient in front of us and figuring that out and understanding that rather than just trying and
01:06:19
Speaker
pursuing that understanding rather than just, you know, regurgitating trial results.
01:06:24
Speaker
I think, um, I think that is the, uh, that is the biggest challenge in medicine and, um, really in life too, because, you know, how do we figure out what is really important in the, um, in the noise of all of our everyday lives?
01:06:44
Speaker
Um,
01:06:46
Speaker
And whether that's athletically, academically, whatever, um, uh, I think that is, things are often much more complicated, made much more complicated than they need to be.
01:06:56
Speaker
Um, and to that effect, I think that, you know, this is not really a, I don't know if this is a truth, but what I find that I need more than anything is to try to find, uh, activities that can let me totally disengage my mind from other things and focus purely on the task at hand.
01:07:14
Speaker
Um,
01:07:15
Speaker
as a way of relaxing.
01:07:18
Speaker
So I'm not thinking about everything else that's bothering my life.
01:07:21
Speaker
I'm focusing purely on the task in front of me.
01:07:23
Speaker
No, I agree.
01:07:24
Speaker
And I think that to the latter, being in flow, right?
01:07:30
Speaker
I mean, really finding an activity enjoyable just for the sake of doing the activity and having real focus on what you're doing, I think is very important.
01:07:39
Speaker
And to what you first mentioned, what comes to mind immediately, Scott, is a Herb Spencer quote that says, the purpose of education is not knowledge, but action, right?
01:07:52
Speaker
And for action,
01:07:53
Speaker
good action, we need understanding.
01:07:55
Speaker
And I think that is something overlooked.
01:07:57
Speaker
I mean, for facts and study results, we have ChatGPT these days, right?
01:08:02
Speaker
We can just ask ChatGPT to give us the facts.
01:08:07
Speaker
But I think that is very powerful and very important.
01:08:10
Speaker
And finally, what would you want every listener to know?
01:08:13
Speaker
Could be a quote, a fact, or just a thought to close.
01:08:18
Speaker
So I think...
01:08:24
Speaker
I think we focus, and I think it's a tactic of self-preservation, right?
01:08:30
Speaker
We focus a lot in critical care medicine on our successes.
01:08:34
Speaker
You know, the patients we managed to save, the shock we've been able to reverse.
01:08:42
Speaker
But, you know, I think that often causes us to forget the patients, the situations we've not been successful in.
01:08:52
Speaker
I think we owe it
01:08:57
Speaker
to our failures to keep working hard and to keep trying to get better at what we do.
01:09:03
Speaker
And I really, there is a quote from Samuel Beckett, who is an Irish poet.
01:09:12
Speaker
And actually, if you're a tennis fan, Stan Valrenka, the Polish player, not Polish, the Swiss player, has this tattooed on his arm.
01:09:21
Speaker
But the quote is, ever tried, ever failed, no matter what,
01:09:26
Speaker
try again, fail again, fail better.
01:09:30
Speaker
And I think that is just, you know, maybe I'm a little nihilistic, but I think that is just such an apt description of critical care medicine, that there are going to be patients that we cannot save.
01:09:45
Speaker
There are going to be diseases that we cannot cure, but we need to just keep doing it
01:09:54
Speaker
over and over and doing it better.
01:09:56
Speaker
And we may continue to fail, but each time we fail, we want to fail a little bit better.
01:10:02
Speaker
And I just think that's a very insightful approach to life and, in our cases, to ICU medicine.
01:10:15
Speaker
I think it's a perfect place to stop.
01:10:19
Speaker
Thank you so much, Scott, for sharing your time and your expertise with us.
01:10:23
Speaker
Definitely there's a lot to talk about in the overlap of oncology and critical care, and we would definitely love to have you back to go deeper on some of these topics.
01:10:34
Speaker
But thanks again for your time.
01:10:37
Speaker
No, thanks so much for having me.
01:10:38
Speaker
This has been great.
01:10:41
Speaker
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01:10:44
Speaker
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01:10:50
Speaker
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01:10:55
Speaker
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