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AKI In COVID - 19
5 Plays5 years ago
In this episode of the Critical Matters, we will discuss acute kidney injury (AKI) in patients with COVID-19.
Our guest is Dr. Claudio Ronco, a thought leader in the field of acute kidney injury and nephrology critical care. Dr. Ronco is professor of Nephrology at the University of Padua. Dr. Ronco is also Director of the Department of Nephrology Dialysis & Transplantation and of the International Renal Research Institute (IRRIV) at San Bortolo Hospital in Vicenza, Italy.
Additional Resources:
Acute Kidney Injury: https://bit.ly/3daKxaD
Management of Acute Kidney Injury in Patients with COVID-19: https://bit.ly/3daKyLJ
Extracorporeal Blood Purification and Organ Support in the Critically Ill Patient During COVID-19 Pandemic: Expert Review and Recommendation: https://bit.ly/3c6fxre
Video - Cappuccino with Claudio Ronco: https://bit.ly/2B5X3dr
Books Mentioned in this Episode:
Carpediem by Claudio Ronco: https://amzn.to/3ekVMxm
From Fish to Philosopher by Homer W. Smith: https://amzn.to/3c8j8F9
Recommended
Transcript
Introduction to Critical Matters Podcast
00:00:06
Speaker
Welcome to Critical Matters, a sound critical care podcast covering a broad range of topics related to the practice of intensive care medicine.
00:00:14
Speaker
Sound Critical Care provides comprehensive critical care programs to hospitals across the country.
00:00:20
Speaker
To learn more about our programs and career opportunities, visit www.soundphysicians.com.
00:00:27
Speaker
And now your host, Dr. Sergio Zanotti.
Impact of COVID-19 on ICUs
00:00:32
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The COVID-19 pandemic has resulted in thousands of patients developing critical illness and requiring admission to the intensive care unit.
00:00:39
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Amongst these critically ill COVID-19 patients, the most common organ failure has been respiratory failure.
00:00:45
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However, a large proportion have developed acute renal failure.
00:00:49
Speaker
In today's episode of the podcast, we will discuss acute kidney injury in the context of COVID-19.
Introduction of Dr. Claudio Ronco
00:00:54
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We are extremely fortunate and honored to have Dr. Claudio Ronco as our guest.
00:00:58
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Dr. Ronco is a world-class thought leader in all matters related to acute kidney injury and renal critical care.
00:01:04
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He is a professor of nephrology at the University of Padua.
00:01:07
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Dr. Ronco is also director of the Department of Nephrology, Dialysis and Transplantation, and director of the International Renal Research Institute at San Bartolo Hospital in Vicenza, Italy.
00:01:19
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He's an extremely accomplished clinician, researcher, and educator, with truly an impressive number of peer-reviewed publications.
00:01:26
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Dr. Ronco is also a champion for the FOM community, free open access medical education, and hosts a wonderful YouTube channel, Cappuccino with Claudio Ronco.
Defining and Diagnosing Acute Kidney Injury
00:01:35
Speaker
Claudio, welcome to Critical Matters.
00:01:38
Speaker
Hello, how are you everyone?
00:01:42
Speaker
So I think that as we dive into the topic of acute kidney injury and COVID-19, I thought that maybe a good starting point would be just to talk a little bit about acute kidney injury
00:01:53
Speaker
in critical patients outside of the context of COVID-19 and maybe start by definitions of AKI, which I think have been something that you have been championing and working diligently around the world for many years now.
00:02:08
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Well, yes, I think first of all, you cannot cure what you don't know and you don't know what you cannot define.
00:02:18
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So definition is extremely important.
00:02:20
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We have learned that
00:02:22
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Depending on definition, the incidence of AKI may be very different and therefore we need a definition which take us to a different dimension and help us in terms of possibility to use definition in clinical practice, to use it for trials, to use it for quality assurance.
Evolution of AKI Definitions
00:02:47
Speaker
So today, after a long series of discussion where the diagnosis of AKI was basically based on signs and symptoms for almost two centuries, it was called the disorder of larynglans.
00:03:09
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After Second World War, after the London bombing, when the studies
00:03:16
Speaker
on autopsy showed patching necrosis in the kidneys of patients dying for acute rhabdomyolysis.
00:03:27
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The term used was acute tubular necrosis.
00:03:31
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And this was considered a kind of equating the term acute renal failure, which is an abrupt reduction in kidney function
00:03:45
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as demonstrated by an increase in serum creatinine and decrease in GFR and urine output.
00:03:51
Speaker
However, after many different definitions around the world and in the literature, we have finally come to a point in which we can now study better epidemiology of AKI because we have
00:04:11
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a common definition that started from a process called Acute Dialogies Quality Initiative here in Vicenza in 2002 and then evolved into what today people know as KDGO guidelines.
00:04:31
Speaker
So the definition today
AKI Stages and Diagnosis
00:04:34
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is a definition based on
00:04:38
Speaker
serum creatinine and urine output.
00:04:44
Speaker
And we define AKI as any one of the following three stages.
00:04:50
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Stage one, which is basically characterized by an increase in serum creatinine more than 0.3 milligram per deciliter in the, let's say, within 40
00:05:07
Speaker
eight hours are the stage two is when serum creatinine tend to double the concentration and finally stage three when this is tripling creatinine.
00:05:25
Speaker
Now we have also included our aspects related to definition which is
00:05:32
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The possibility, for example, of an increase in serum creatinine of more than 0.5 milligram per deciliter within seven days, that characterizes also AKI.
00:05:44
Speaker
And finally, urine output is basically considered significant when it decreases to less than 0.5 milliliters per kilogram per hour for at least six hours, stage one.
00:06:00
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or for 12 hours, and this is stage two, or for 24 hours or more, and this is stage three.
00:06:09
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So we have this concept now, definition, that allows us to define prevalence and incidence of AKI in community areas, in hospitals,
00:06:24
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in ICU areas and there is a common agreement that AKI at different stages has a significant impact on outcomes and these outcomes are extremely clear today.
Severity and Management of AKI
00:06:46
Speaker
I think that simply they can be summarized as hospital length of stay
00:06:54
Speaker
ICU length of stay, mortality, cost in general, and other complications which we call MERS, which is major adverse cardiovascular and renal adverse events.
00:07:18
Speaker
Basically, I think it's important to know that moving from non-AKI to stage one, two, and three, we have a progression of the severity of disease, but we also have a progressive increase of the risk for worse outcomes.
00:07:42
Speaker
And the other thing is that we know today that AKI at different stages, it's a marker of severity of disease, but it's also an independent risk factor for mortality.
00:08:03
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And the progression of these outcomes
00:08:09
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related to the progression of AKI stage is the demonstration of this.
00:08:19
Speaker
And Dr. Ronco, I think that the point of an independent risk marker for bad outcomes and also the point you made is very clear that as you progress from no AKI to stage one, to stage two, to stage three, your outcomes get worse, I think is an important reminder
00:08:38
Speaker
for our clinicians not to trivialize some of the iatrogenic damage that sometimes we produce in ICUs to the kidney and recognize that we have to be very conscientious of what we're doing because there might be increased risk just by taking that patient into AKI or worsening their stage in AKI.
00:08:57
Speaker
I think that's something very important.
00:09:00
Speaker
Yeah.
Biomarkers in AKI Prevention
00:09:01
Speaker
Even more than that, we not only should not consider negligible, even small increase in serum creatinine, but we should also consider the possibility actually to prevent today the occurrence of AKI even at mild stages by using early biomarkers, for example, that allow us to detect conditions
00:09:32
Speaker
in which the kidney is under stress, in which we have specific exposures that may be iatrogenic, maybe contrast media, maybe other comorbidities like sepsis, for example, or congestive heart failure, together with the fact that
00:09:57
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we might have a kidney that is highly susceptible because it already went through an episode of AKI, what we call a kidney attack in the past, or because it already has a decrease in the functioning nephron mass, may have a decrease in renal functional reserve, or even have a decrease in baseline GFR showing an incipient
00:10:25
Speaker
form of chronic kidney disease so and this explain in fact why the incidence of AKI is higher in areas like icus like cancer departments or like a cardio cardiac surgery because most of the patients that are operated are with the with the
00:10:51
Speaker
a high susceptible kidney.
00:10:54
Speaker
They are high risk patients.
00:10:56
Speaker
And in these areas, we have probably high probability of exposures.
Role of Biomarkers in Early Detection
00:11:07
Speaker
And I think, can you expand a little bit, Claudio, on the current availability of biomarkers that are utilized clinically at the bedside?
00:11:18
Speaker
Yes.
00:11:19
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We actually,
00:11:22
Speaker
have conducted a long battle to make clear that if we have an increase in serum creatinine, this is already a failure.
00:11:41
Speaker
And this is already representing a situation in which AKI is clearly occurring.
00:11:50
Speaker
we need to possibly identify patients in the early phase when our patients are in the gray zone where we can still impact their outcome by modifying our process of diagnosis and care.
00:12:15
Speaker
uh we have biomarkers that have been known for years like engal like cystatin c we have l fab we have nag but today we have this new generation of biomarkers called cell cycle arrest biomarkers that are basically molecules that are expressed
00:12:40
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in the kidney when the kidney is under stress and they have a very high negative predicted value.
00:12:46
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So when negative, they are really negative, they predict no AKI.
00:12:52
Speaker
And on the other side, when they are positive, they have also highly predicted value within 12 to 24 hours for the patient to develop AKI mild to severe.
00:13:08
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so this type of this type of biomarkers are of course more costly than creatinine but they have shown in our hands at least to to to make us saving a lot of money in terms of need of renal replacement therapy and the need of
00:13:37
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also other measure or simply a.k.a.
00:13:42
Speaker
reducing the number of days in the hospital.
00:13:50
Speaker
So I think that the cost of these biomarkers can be somehow be overcome by the fact that they allow to save some money.
00:14:03
Speaker
And it sounds like, obviously, used in a rational way for high-risk patients, it makes a lot more sense,
Action Bundles and Biomarkers
00:14:09
Speaker
right?
00:14:09
Speaker
Not maybe to everybody you're seeing, but directed at the high-risk patients can prevent complications.
00:14:15
Speaker
And like you said, if you can save a patient from requiring renal replacement therapy, I'm sure it will pay for the cost of the biomarkers in space.
00:14:25
Speaker
Yeah.
00:14:28
Speaker
There is, of course, a continuous debate whether this requires more evidence.
00:14:34
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I think that there is now a large number of papers showing that, first of all, there is this capability to predict AKI.
00:14:44
Speaker
And there is also a utility in the possibility to trigger specific bundles of actions that are maybe very simple, like the
00:14:56
Speaker
the KDGO bundles for prevention of AKI that we all think we are applying anyway, but this is not the case.
00:15:03
Speaker
We have done a study, Alex Zarbock has done a study, and it was clearly shown that when you trigger a bundle of action with an early biomarker, then the incidence of AKI decrease and the need of renal replacement therapy decrease.
00:15:24
Speaker
Excellent.
00:15:24
Speaker
Well, I think this is a great,
00:15:26
Speaker
introduction to the topic of AKI and COVID-19.
AKI Prevalence in COVID-19 Patients
00:15:30
Speaker
And maybe we could start, Claudio, by just sharing with us.
00:15:33
Speaker
I know that obviously Italy was at the forefront and now the epicenter has moved to the United States and South America, but tremendous experience has been achieved over the last several months and weeks with this new disease.
00:15:49
Speaker
But maybe start by telling us a little bit about the prevalence of AKI and COVID-19 and what do we know at this point?
00:15:57
Speaker
Well, we are in these days working on a consensus conference with people from all over the world to try to exactly analyze what is the incidence and prevalence of AKI in patients with COVID-19.
00:16:18
Speaker
The reason for this uncertainty is because we're not sure about the denominator.
00:16:25
Speaker
When you speak about the percent of patients developing AKI, some people speak about the entire community, some people speak about the hospitalized patients, and the criteria for hospitalization may be different.
00:16:40
Speaker
And some people speak about the percent of patients in the ICU.
00:16:47
Speaker
So I think that we can speak for us.
00:16:51
Speaker
We have seen
00:16:54
Speaker
basically something like 10% of the overall patients resulting positive at the swab test being hospitalized.
00:17:05
Speaker
And of these, approximately 10%, 20% entering ICU.
00:17:12
Speaker
In the ICU, we have seen developing AKI in approximately 30% to 40% of the patients, all stages.
00:17:21
Speaker
while approximately 20% have a requirement of renal replacement therapy.
00:17:29
Speaker
So these obviously, with the numbers that we've seen in ICUs of patients, are big numbers in terms of a requirement of further support for renal dysfunction as well.
Mechanisms of AKI in COVID-19
00:17:39
Speaker
I mean, I think that, I don't know exactly what happened in Italy, but just from some of our programs in New York City, the need for dialysis machines, the need for dialysis catheters,
00:17:49
Speaker
was something that they had never experienced, so clearly not a trivial problem.
00:17:55
Speaker
And in terms of pathophysiology, Claudio, why do patients with COVID-19 develop AKI?
00:18:01
Speaker
Well, I would like first to say that already on February 6th, we published in Lancet a paper saying coronavirus epidemic preparing for extracorporeal organ support in intensive care.
00:18:19
Speaker
And we recommended to alert the intensive care units that a tsunami was coming and the need for a replacement therapy and the demand would have been greater than ever.
00:18:32
Speaker
I'm surprised that in areas like New York, they experienced a shortage of devices and supplies because we, for example, did not do that.
00:18:46
Speaker
This may have to do with the characteristics of the system before the COVID-19.
00:18:52
Speaker
And I think this is very important because it shows whether or not you are prepared for an emergency.
00:19:05
Speaker
And this, in fact, is a situation that should be considered.
00:19:11
Speaker
Absolutely.
00:19:19
Speaker
We have looked at the type of the disease that COVID-19 patients experienced and we were astonished by the characteristics.
00:19:35
Speaker
And in the most recent publication in Lancet of last week,
00:19:40
Speaker
we clarified very well that the infection may lead to a completely asymptomatic situation, may lead to mild symptoms that may or may not convert into more severe symptoms.
00:19:55
Speaker
Some patients got a very sudden problem of pulmonary exchanges and had to be hospitalized immediately and intubated.
00:20:06
Speaker
Some patients remain with mild symptoms.
00:20:09
Speaker
for a long time.
Organ Interactions and AKI
00:20:11
Speaker
Now, some patients come to the hospital with pneumonia, and these patients have a typical triad.
00:20:21
Speaker
They have pneumonia, they have an hypercoagulability state, and they have a high increase in cytokine production that has been defined as cytokine storm.
00:20:36
Speaker
All these three conditions may lead to progressive endothelial dysfunction, to progressive myocardial dysfunction, to endothelial lamage and infarction or mycothrombie in the kidney.
00:20:52
Speaker
Together with the fact that recently has been identified a possibility that the virus circulates in the blood and reach the kidney, causing endothelial damage, photocyte localization, proximal tubular localization, mitochondrial dysfunction, and finally acute tubular necrosis.
00:21:15
Speaker
And there is one more mechanism that has been invoked, is the fact that some patients have
00:21:21
Speaker
gastrointestinal syndrome, and they tend to be admitted to the hospital hypovolemic and dehydrated, and this may cause a further chance to develop AKI.
00:21:35
Speaker
Once they have AKI, the increase in fluid retention may cause hypervolemia,
00:21:47
Speaker
On the other hand, the mechanical ventilation and eventually the use of ECMO may cause extra kidney damage.
00:21:57
Speaker
So this implies a vicious circle that actually affects very much kidney and lung function.
00:22:05
Speaker
Endothelial dysfunction provides a syndrome like a capillary leak syndrome, and myocardial dysfunction may cause arterial underfilling or venous congestion.
00:22:18
Speaker
And in this case, AKI develops, and the patient may actually require renal replacement therapy.
00:22:29
Speaker
And in terms of recognizing AKI in COVID-19,
00:22:32
Speaker
I presume that you would be applying the same key DIGO criteria that you would apply to any critically ill patient.
Preventing AKI with KDIGO Guidelines
00:22:39
Speaker
Is that correct?
00:22:40
Speaker
Is there anything particular that you would want to mention?
00:22:43
Speaker
Well, this COVID-19 population was exceptionally carefully monitored and studied.
00:22:55
Speaker
You know, biomarkers,
00:22:58
Speaker
are mostly used in moments of uncertainty.
00:23:04
Speaker
Practically in patients where the risk is very low, there is no point to use a biomarker because they will never develop AKI.
00:23:11
Speaker
Patients who are severely ill, there's no point to use the biomarker because very likely they develop AKI.
00:23:19
Speaker
So there is no need to predict the raining when it is already raining.
00:23:24
Speaker
the area where biomarkers are useful are the area of uncertainty.
00:23:30
Speaker
And several of these patients, let's say, display the clear AKI quite early, but others display the AKI after one or two weeks of ICU stay.
00:23:45
Speaker
In those patients, the use of biomarker was quite useful in identifying
00:23:51
Speaker
when they started to develop a stressed kidney and a condition probably based on hyperinflammation, hypercoagulable state, and filtration of damps from the glomerular basement membrane reaching the tubular level, that may actually lead to AKI.
00:24:14
Speaker
So certainly in these patients,
00:24:18
Speaker
using KDGO criteria to diagnose and classify AKI and using biomarkers to early detect signs of kidney stress allowed us to be extremely prepared in these patients.
00:24:38
Speaker
And Claudio, I would assume that the impact of AKI on outcomes in COVID-19 is similar story to in general ICU patients, right?
00:24:47
Speaker
Yes, although we are studying because I must say that most of the patients who developed AKI had a kidney recovery.
00:24:58
Speaker
Very few patients left the ICU with need of dialysis and therefore it seems that AKI is a very transient syndrome.
00:25:10
Speaker
However, it is clear that when you have patients that start to have
00:25:16
Speaker
Aki, this is a sign of a multiple organ involvement in the syndrome.
00:25:22
Speaker
And this increased the level of severity of these patients.
00:25:27
Speaker
Okay.
AKI Treatment Bundles
00:25:28
Speaker
So maybe we can start by talking about a little bit of treatment.
00:25:32
Speaker
And I know that you mentioned kind of the general treatment bundle that KDIGEL recommends for acute kidney injury, which I think is obviously a great starting point.
00:25:43
Speaker
And as you mentioned,
00:25:44
Speaker
even though people usually say, oh, we do all these things when we look with more attention, especially in a situation like COVID-19, where there's a large number of patients coming in, there might be opportunity for us doing it a little bit better.
00:25:56
Speaker
Yeah, well, for sure, the so-called KDGO bundle is a way to make sure that you're not increasing
00:26:13
Speaker
the level of insult to the kidney.
00:26:20
Speaker
So I think that this is extremely important because it describes very well that the simple series of measures such as avoiding nephrotoxin, monitoring adequate fluid balance in the patient,
00:26:39
Speaker
being able to control blood pressure and others represent the possibility to optimize the condition of the patient, avoiding progression of AKI in case of mild stages or development of AKI in some stages.
00:27:04
Speaker
This, however, represent a
00:27:09
Speaker
one of the different possibilities for patients who are at risk or developing mild AKI.
00:27:17
Speaker
But then we have to deal with patients that are at specific risk for AKI in case of COVID-19, especially when, for example, they are developing a cytokine release syndrome.
00:27:38
Speaker
While you want to absolutely avoid nephrotoxin, possibly avoid contrast media, antibiotics, or other drugs that are known as nephrotoxic,
00:27:51
Speaker
while you want to avoid the hyper hydration or dehydration, keeping the patient in the right window of hydration, which is probably optimal.
00:28:02
Speaker
While you want to make hemodynamic monitoring to make sure that you have adequate organ perfusion and you want to monitor renal function
00:28:11
Speaker
possibly by urine output and by, of course, GFR measurement or creatinine measurement, I think that you have to be ready to consider those conditions that represent a true risk for patients with COVID-19 to develop AKI.
00:28:33
Speaker
And these are the hypercoagulable state, which may require actually treatment
00:28:40
Speaker
with low molecular weight aparin or systemic anticoagulation.
00:28:46
Speaker
Patients who are at a high level of cytokine release levels, so they may actually require immunomodulatory treatment, although it has not been yet validated, but something like tucilizumab or anti-enterleukin-6
00:29:06
Speaker
drugs or other anti-inflammatory drugs like anti-maladic drugs and so on seems to be an important aspect.
00:29:18
Speaker
There is a third option that should be considered in this phase, and it is the use of all these techniques that have been described as extracorporeal organ support therapy
00:29:33
Speaker
that can be applied before there is organ dysfunction, but they can be used to remove cytokines from the circulation.
00:29:45
Speaker
And I'm namely mentioning emo perfusion with specific cartridges that absorb endotoxin or cytokines.
00:29:58
Speaker
other filters with membranes that are characteristically absorbing cytokines on their surface, or membranes with specific cutoff values that allow clearance of cytokines through the pores of the membrane itself.
00:30:17
Speaker
All these therapies should be considered, and we wrote that in our Lancet paper,
00:30:24
Speaker
in special cases in patients in which there is no response to any other therapy, there is high risk of developing multiple organ failure due to the hyperinflammation state and should be considered also in the context of randomized clinical trials where we can probably get the level of evidence we are searching for.
00:30:50
Speaker
Absolutely.
00:30:52
Speaker
So Dr. Ronco, before we dive into a little bit more in terms of renal replacement therapy, you did, I mean, mention a lot in terms of general approaches to treatment and potential treatments for specific situations within COVID-19.
00:31:05
Speaker
There are two things I wanted to ask you if you could dive in a little
Nephrotoxic Risks of COVID-19 Treatments
00:31:08
Speaker
bit deeper.
00:31:08
Speaker
One is, step one, obviously, is avoiding nephrotoxins.
00:31:12
Speaker
Are there any specific drugs that are being utilized for...
00:31:17
Speaker
COVID-19, either experimentally or as a, under emergency uses, that we should consider altering or monitoring differently when the patient has AKI, and specifically hydrochloroquine, you mentioned the antimalarials, some of the antivirals like remdesivir can be excreted by the kidney.
00:31:36
Speaker
Any specific comments you can make on those drugs that are being utilized within the context of COVID-19 that might have an, might be impacted by acute kidney injury?
00:31:45
Speaker
Well, you know, drugs in general are a double-edged sword and we should certainly use when there are indications, but we must be aware, for example, the anti-maladic drugs, they have a certain degree of nephrotoxicity.
00:32:03
Speaker
So we must be aware that there is a possibility to induce a damage at the tubular level or at the interstitial level in the kidney.
00:32:13
Speaker
And this should be bear in mind also when we use immunomodulating agents like Tucilizumab or others because these kidneys are particularly susceptible.
00:32:28
Speaker
Absolutely.
00:32:29
Speaker
And the second question I wanted to touch, we did talk about, but I think it's an important point to reemphasize is fluid management and trying to keep the patients at the adequate intravascular volume, obviously,
00:32:42
Speaker
is a lot harder than it sounds.
Fluid Balance in COVID-19
00:32:44
Speaker
But I do believe that a lot of these patients with COVID-19 are usually sick for several days at home, might have GI losses, might have increased losses from insensible losses, from fever and increased respiratory rates.
00:32:58
Speaker
Yet early on, I think a lot of people, especially in emergency departments, have been very aggressive with diuresing these patients, thinking of the respiratory status.
00:33:07
Speaker
And maybe in some of these patients early on,
00:33:10
Speaker
we need to give them a little bit more attention in terms of their intravascular volume, recognizing that later on, maybe we change that.
00:33:17
Speaker
Any comments on that?
00:33:19
Speaker
Absolutely.
00:33:20
Speaker
In the early phases, these patients tend to be more dehydrated than over hydrated.
00:33:26
Speaker
So we have to be careful and forcing diuresis may not be the right solution.
00:33:32
Speaker
Plus, we know that the
00:33:36
Speaker
diuretics do not preserve the kidney from AKI nor they affect the outcome of AKI.
00:33:45
Speaker
It is clear that it is more easy to treat the patient that is non-oliguric versus a patient that is oliguric.
00:33:52
Speaker
However, we should be careful because this patient needs to be optimized in terms of fluid administration.
00:34:00
Speaker
Now, some patients with optimal hemodynamic condition may benefit from a slight reduction of the hydration status when pulmonary exchanges are extremely compromised.
00:34:15
Speaker
But this is a marginal percent of patients because, in general, these patients do not have atypical conditions of pulmonary exchanges impaired
00:34:28
Speaker
due to over hydration state, something like similar, what we call pseudo ARDS.
00:34:35
Speaker
These patients have entire areas of the lungs that are compromised and not because of fluid overload.
00:34:42
Speaker
So absolutely, yes, we need to accurately monitor the fluid balance, avoiding unnecessary forced diuresis and
00:34:56
Speaker
and decreasing the hydration status of this patient.
00:35:03
Speaker
Even more in light of the possibility that in some cases there is a myocardial dysfunction, and this may lead to uncontrollable hypotension or arterial underfilling or decrease in venous return and cardiac output and therefore
00:35:24
Speaker
leading to decrease in organ perfusion pressure.
00:35:29
Speaker
You had mentioned that up to 20% of patients that admitted to the ICU with COVID-19 might require renal replacement therapy.
Renal Replacement Therapy Considerations
00:35:37
Speaker
So I thought that way we could talk a little bit about renal replacement therapy in COVID and maybe start by indications for renal replacement therapy in COVID-19.
00:35:48
Speaker
Yeah, interestingly enough, in many of the patients, the main indication was oliguria.
00:35:56
Speaker
I think that these patients did not present with a very high hypercatabolic state or hyperkalemia and so on.
00:36:07
Speaker
So probably fluid management was one of the most important indications.
00:36:14
Speaker
Some of these patients, however,
00:36:16
Speaker
have developed superimposed septic syndromes or have superimposed rhabdomyolysis, and they may require renal replacement therapy due to oliguria secondary to these conditions.
00:36:31
Speaker
In these cases, however, we have, at the end, tried to treat the patient a little bit in the early stages
00:36:44
Speaker
knowing that it was probably helpful to restore a certain level of homeostasis in terms of electrolytes, acid base, and also uremic toxin removal.
00:37:02
Speaker
And I was going to ask you about timing, which I know timing of RRT in critically ill patients is still a topic that has been much debated in the field of renal critical care.
00:37:12
Speaker
But clearly, I mean, what you're sharing with us is that in these COVID-19 patients, you would rather initiate RRT earlier than later, considering everything that you mentioned.
00:37:23
Speaker
Yeah, well, we are early starters in general.
00:37:26
Speaker
The reason for this is that we do not consider RRT as a major risk or hazard for the patient.
00:37:34
Speaker
So,
00:37:35
Speaker
We prefer to start earlier and in case interrupt if no need shows later on.
00:37:44
Speaker
It is true, however, that these patients need a placement of a catheter and this catheter has to be a specific catheter because since there is this hypercoagulable state, we want to have extracorporeal blood flow
00:38:04
Speaker
as high as possible in the range of 200 to 150 milliliters per minute.
00:38:10
Speaker
In some cases, these treatments are combined with ECMO, but in general, we prefer in any case to use a separate vascular access so the patient requires a dialysis catheter access.
00:38:24
Speaker
This is very important in terms of placement and also in terms of
00:38:32
Speaker
anchoring the catheter.
00:38:34
Speaker
Most of them are in the jugular vein because this patient may require prone positioning.
00:38:41
Speaker
And prone in the patient represents a maneuver that may actually displace the catheter.
00:38:50
Speaker
That's why in terms of modality of renal replacement therapy, we took two decisions.
00:38:57
Speaker
to use CVVHD instead of CVVH in order to reduce filtration fraction inside the filter and reducing in this way the risk for emo concentration inside the filter and clotting.
00:39:15
Speaker
Second, we used in some cases prolonged intermittent renal replacement therapy like 12 hours over 24 hours.
00:39:26
Speaker
in order to leave the patient free of the circuit, from the circuit for 12 hours, enabling the team to prone position the patient and so on.
Practical Aspects of RRT
00:39:40
Speaker
And I think that just two things I want to re-emphasize, which I think have tremendous practical applicability.
00:39:47
Speaker
One is, I mean, the selection of the site, like you said, the right internal jugular with good securement,
00:39:53
Speaker
seems to be the way to go in these patients for many reasons, one of which is that a lot of these patients end up being proning, and that is a good access to have in terms of if you have to prone the patient, which is something that I think you had mentioned in the Lancet article as well, and we'll link those in the show notes.
00:40:11
Speaker
And the second thing that you've also mentioned, Claudio, was that in those patients who we know is a small percent, but they have occurred that end up requiring ECMO, you can run
00:40:22
Speaker
CVVH through the ECMO circuit, but it seems that because of the flows that are required, if possible, it's preferable to have an independent dialysis catheter for those patients.
00:40:32
Speaker
Is that correct?
00:40:34
Speaker
Yeah, absolutely.
00:40:36
Speaker
And I think this also has an impact on anticoagulation.
00:40:41
Speaker
We use both unfractionated heparin, which is our standard of care,
00:40:50
Speaker
But in these patients, we ended up sometimes delivering dosage as high as 20 units per kilogram per hour as compared to 8 to 10 that we use normally in CRRT.
00:41:07
Speaker
Or we used regional citrate anticoagulation, which allowed us to prolong filter life.
00:41:15
Speaker
In any case, you have to consider the logistics.
00:41:20
Speaker
the less changes or modifications or alarm solving actions that you have in the system, the less you stress the nurse team, which is already overloaded and it is operating under an uncomfortable situation with masks and shields and so on.
00:41:48
Speaker
In terms of... I'm sorry, go ahead.
00:41:52
Speaker
In terms... No, I wanted to say that this allows you to make sure that you effectively deliver what you prescribe.
00:42:00
Speaker
We normally prescribe a dose in the range of 30 milliliters per kilogram per hour, and we find that this is putting us on a safe situation when we even have a little bit of downtime.
00:42:18
Speaker
Of course, if you do prolong the intermittent renal replacement therapy, you want to aim for a little bit higher dose for instantaneous clearance because you know that you're only operating for 12 hours.
00:42:33
Speaker
It is, however, important that you schedule specific monitoring of treatment delivery so that you make sure that you're not under dialyzing the patient.
00:42:45
Speaker
Absolutely.
00:42:46
Speaker
And I think that you mentioned the importance of anticoagulation, which obviously goes beyond just patients on renal replacement therapy with COVID-19.
00:42:53
Speaker
It's been a topic of great interest.
00:42:56
Speaker
But I have a specific question.
00:42:57
Speaker
So you would use low molecular weight heparin, unfractionated heparin, all at systemic doses.
00:43:03
Speaker
When you used a regional citrate anticoagulation, does that produce any systemic anticoagulation or only at the level of the cartridge?
00:43:14
Speaker
Normally, this operates only a level of the cartridge.
00:43:18
Speaker
The very same term regional means that this is the aiming.
00:43:24
Speaker
In general, also, unfractionated epirin should tend to create anticoagulation inside the filter with minimal systemic effects.
00:43:34
Speaker
But this patient may actually require systemic effects.
00:43:37
Speaker
So in some patients, the use of epirin was exceedingly high compared to the standard.
00:43:44
Speaker
For regional citrate anticoagulation, I think we only took care in this case of the circuit and we left to the intensivist the possibility to decide whether other forms of anticoagulation should be delivered to the patient.
00:43:59
Speaker
Yeah.
00:44:00
Speaker
And I think it's an important point because like you said, it's goal is to preserve the cartridge and avoid clotting of the cartridge.
00:44:06
Speaker
But these patients in many cases
00:44:08
Speaker
based on the decision of the team and other factors might require systemic anticoagulation on top of that, which I think is something that we're still learning, but has become very important in a lot of these patients.
Expert Recommendations on Blood Purification
00:44:21
Speaker
Are there any other delivery or practical aspects that you have found interesting as they relate specifically to COVID-19?
00:44:31
Speaker
Well, the interesting thing is that in a few days,
00:44:36
Speaker
In blood purification should come out an expert recommendation paper where we try to summarize all possible recommendations for the use of blood purification techniques in COVID-19 patients.
00:44:54
Speaker
So follow the blood purification journal.
00:45:00
Speaker
It should come out online very, very soon.
00:45:03
Speaker
I'm talking about days.
00:45:05
Speaker
And I think this will be a very important tool on the pocket of the people who operate at the bedside, especially because this is a cooperative work of more than 20 experts around the world.
00:45:22
Speaker
So I think it would be extremely helpful.
00:45:26
Speaker
Excellent.
00:45:26
Speaker
And as we close on the COVID-19 topic, one thing that you did mention that I think is positive
00:45:33
Speaker
with all the negative news that people have been sharing through the last several months, is that a lot of the patients with COVID-19 who survive and require renal replacement therapy seem to have renal recovery.
Renal Recovery Post-AKI in COVID-19
00:45:44
Speaker
Can you comment a little bit more on that, Dr. Ronco?
00:45:47
Speaker
Well, some of these patients were still monitoring to see if there are any further effects.
00:45:54
Speaker
It seems not.
00:45:56
Speaker
It seems that they recover kidney function, but we are planning maybe to take some time to
00:46:04
Speaker
maybe make a control at three or six months to make sure that the recovery is effective.
00:46:11
Speaker
In general, however, we have seen a high percent of renal recovery after AKI.
00:46:18
Speaker
Excellent.
00:46:19
Speaker
So I want to be very respectful of your time, Claudio, but I would like to close the podcast with some questions that are unrelated to AKI that really seek to tap into the wisdom
Dr. Ronco's Book and Recommendations
00:46:30
Speaker
of our guests.
00:46:30
Speaker
Would that be okay?
00:46:32
Speaker
Oh, absolutely.
00:46:34
Speaker
So the first question relates to books, and I was wondering, are there books or books that have influenced you the most or that you have gifted most often to others?
00:46:45
Speaker
Well, talking about what book I have gifted most to the others, I must say it is my book, Carpe Diem.
00:46:53
Speaker
Carpe Diem was a book that I wrote describing the story of a baby, the story of a machine that we have developed,
00:47:01
Speaker
Carpe Diem Stays for Cardio-Renal Pediatric Dialogist Emergency Machine.
00:47:06
Speaker
And it's a little bit the story of my life.
00:47:08
Speaker
I think that this book has influenced my life because it has been translated in Chinese, English, Spanish, and you can find it on Amazon.
00:47:19
Speaker
And I suggest you really to read this book because it's somehow interesting.
00:47:27
Speaker
it's also a little bit entertaining and you will definitely know about me a little bit more.
00:47:34
Speaker
So we'll definitely link that in the show notes and I think that it's always interesting for me to find out new things to read.
00:47:41
Speaker
So that sounds like a very interesting read.
00:47:44
Speaker
Are there any other books?
00:47:46
Speaker
Go ahead.
00:47:46
Speaker
I will send you the cover.
00:47:48
Speaker
I will send you the cover.
00:47:49
Speaker
But it's Carpe Diem, one single word.
00:47:51
Speaker
Okay, perfect.
00:47:54
Speaker
Any other books you want to mention, Claudio?
00:47:56
Speaker
Well, one book is important is the book from Homer Smith, 1956, From Fish to Philosopher.
00:48:06
Speaker
Remember that the kidneys allow us to be what we are and we have to preserve the kidneys to make sure that we can keep going with our life.
00:48:17
Speaker
I have to say that you are the second person on the podcast who recommends From Fish to Philosopher and both were nephrologists.
00:48:26
Speaker
So it's a must.
00:48:28
Speaker
We will put that there.
00:48:29
Speaker
The second question relates to something that you believe to be true in medicine or in life that most other people don't believe or at least don't act like they believe it's true.
Humanistic Approach in Medicine
00:48:42
Speaker
Well, I honestly believe that medicine is a humanistic discipline.
00:48:51
Speaker
It's not a mathematical discipline.
00:48:55
Speaker
This has a lot to do with the fact that one thing is to cure the patient, another thing is to take care of the patient.
00:49:05
Speaker
And I think that we have too many computer-aided programs, we have too many technologies, and sometimes we tend to forget the human touch of the physician.
00:49:21
Speaker
Remember, the only
00:49:24
Speaker
job considered a profession was the one of the doctor because profession means profiter from latin which means it comes from faith and it seems to be a job that is more a mission than a job and therefore i think we should take care of patient uh in a kind of holistic way
00:49:50
Speaker
not just because of kidney dysfunction, because of high cytokines or other things.
00:49:57
Speaker
Especially in the area of COVID-19, when patients were isolated from their deers and from relatives, they relied on our eyes, on our human touch, and I think this was of great help for them.
00:50:15
Speaker
And I think it's a very important point, and like you said, I think has been
00:50:19
Speaker
highlighted exponentially with COVID-19.
00:50:22
Speaker
You could almost imagine if you were to have a utopic nightmare many, many decades ago, you might wake up to being an ICU patient with COVID-19 where everybody around you is either a machine or surrounded by masks, helmets, gowns, and really there's almost no personal connection.
00:50:41
Speaker
So I think it's something that's very important for us to remember at the bedside.
00:50:45
Speaker
And the last question, Claudio, is
00:50:47
Speaker
What would you want every intensivist listening to this podcast
Teamwork in Critical Care
00:50:51
Speaker
to know?
00:50:51
Speaker
It could be a quote or a fact to close the podcast.
00:50:55
Speaker
Well, my message could be, which has been more or less the mission of my life.
00:51:03
Speaker
The patient with the critical illness is a complicated patient.
00:51:10
Speaker
It may need really a cooperative effort.
00:51:16
Speaker
So,
00:51:17
Speaker
If we consider our team of doctors like an orchestra, to play a symphony, you need an orchestra.
00:51:27
Speaker
And a symphony is very complex.
00:51:29
Speaker
Now, to play a melody, you need just only one instrument.
00:51:33
Speaker
So we can only play one instrument at a time, but we must be on the same key.
00:51:40
Speaker
So I think that...
00:51:43
Speaker
disciplines that are crossing and cross-fertilizing our knowledge, such as critical care nephrology, probably are the most important achievement that we have made in recent years.
00:52:00
Speaker
Cooperation, sharing ignorance, and multiplying knowledge is a key for success.
00:52:07
Speaker
And I think that's a perfect place to stop.
00:52:10
Speaker
Claudio, I want to thank you so much for
00:52:13
Speaker
your time and being so generous with your expertise.
00:52:16
Speaker
I look forward to seeing you again in person soon, but also hopefully having you back on the podcast.
00:52:21
Speaker
Thank you very much.
00:52:24
Speaker
Thank you for listening to Critical Matters, a sound critical care podcast.
00:52:28
Speaker
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00:52:34
Speaker
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00:52:39
Speaker
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