Introduction to MARS Albumin Dialysis
Dr. Subramanian gives an introduction to MARS Albumin Dialysis. Dr. Subramanian explains how Molecular Adsorbent Recirculating System (MARS) works, how it was discovered, how to understand it, the best applications for MARS in critical care toxicology, and what are the logistics of starting a MARS program.
Featuring:
Ram Subramanian, MD, MBA
Dr. Subramanian is Professor of Medicine and Surgery, the Medical Director of Liver Transplantation, and Director of Liver Critical Care Services. In his dual role as a transplant hepatologist and intensivist, Dr. Subramanian is involved particularly in the outpatient and inpatient care of patients before and after liver transplantation. His clinical and research interests are focused on critical care issues related to hepatic failure and liver transplantation. Transcription:
Baxter Ad: This podcast is sponsored by Baxter healthcare corporation. When you choose Baxter for your C R R T program, you're not only choosing true patient focused treatment with industry leading CRRT technology. You're also selecting a partner dedicated to optimizing your clinical success in treating patients with acute kidney injury.
Our commitment to you starts with a program individualized to your facility's needs and provides complete support every step of the way for more information, visit us at www dot renal, acute.com. Baxter healthcare corporation has provided funding for this podcast, but all content was developed independently by the.
Therefore the views expressed on the podcast are those of the speaker and should not be attributed to Baxter healthcare corporation for prescription use only for the safe and proper use of this product. Please refer to the owner's manual.
Mars Eleni: Mars is indicated for the treatment of drug overdose and poisonings. The only requirement is that the drug or chemical will be dialyzed bubble in Unbound form and bound by charcoal and or ion exchange resins. Mars is not indicated for the treatment of chronic liver disease conditions or as a bridge to liver trans.
Safety and efficacy has not been demonstrated for those indications in controlled randomized clinical trials. The effectiveness of the Mars device in patients that are sedated could not be established in clinical studies and therefore can not be predicted in sedated patients.
Pam Peeke, MD, MPH, FACP, FACSM (Host):
Hello and welcome to the Society of Critical Care Medicine's iCritical Care Podcast. I'm your host, Dr. Pam Peeke. Today, we're going to be talking about an introduction to molecular adsorbent recirculating system, albumin dialysis, and I'm joined by Dr. Ram Subramanian. Dr. Subramanian is Professor of Medicine and Surgery and Medical Director of Liver Transplantation and Liver Critical Care Services at Emory University. Welcome Dr. Subramanian.
Ram Subramanian, MD, MBA (Guest): Thank you for having me.
Host: Excellent. Before we start, do you have any disclosures to report?
Dr. Subramanian: I am a consultant for Baxter Incorporated, which makes the MARS device.
Host: And any other disclosures relative to this podcast?
Dr. Subramanian: I have no other disclosures relevant to this.
Host: Excellent. And before we begin, just know that the learning objectives include describing the principle of albumin dialysis related to the molecular adsorbent recirculating system, known as MARS, want to outline the current indication for MARS,highlight application to MARS in critical care toxicology, describe logistics related to starting a MARS program.
And why is this podcast needed? Well, it's needed to educate ICU and other clinicians on MARS as a therapy. The knowledge gaps that this podcast will address, include allowing clinicians to understand how MARS works and engage in understanding what patients are ideal for this therapy. Now to put this in context, the extra corporeal techniques most frequently employed for the removal of toxins, and that includes drug overdoses and intoxication are hemodialysis, continuous hemofiltration techniques, hemoperfusion, and the molecular adsorbent recirculating system known as MARS. Dr. Subramanian, how did MARS come about? We have all of these other options. What was the genesis of MARS?
Dr. Subramanian: So MARS was actually discovered by two German nephrologists. And this was just a date, the device, this was back when we had East Germany and West Germany. So these are two nephrologists in East Germany that came up with it. And the rationale was to create a system that would change the dialysate to an albumen dialysate instead of an aqueous dialysate that is used in traditional haemodialysis and therefore to be able to extract a whole other class of toxins from the patient's plasma that are specifically albumin bound. So, that was the original genesis of and the rationale behind this device.
Host: Excellent and, and come forward now. How long has MARS been utilized in contemporary critical care?
Dr. Subramanian: So it is not been used often, especially in North America. There are very, very few centers that are using this with any degree of expertise or knowledge. So it's, it's an area that is attracting more and more attention in the field of critical care toxicology and the other area, and this just for full disclosure, is an off-label indication, there is growing interest in the field of critical care hepatology with regard to the use of the MARS device. And we can talk about that more.
Host: Excellent. Okay so basically the actual therapy itself, the MARS has a fairly ancient history here in terms of evolution in origin and has not been typically used in North America, but now is beginning to emerge as another tool in our toolbox for the treatment of drug overdose and intoxication.
So describe to us the principle of albumin dialysis related to MARS.
Dr. Subramanian: So a useful construct to understand MARS is to compare and contrast it with the regular haemodialysis or CRT. So a couple of major differences. Number one, as I had mentioned before the dialysate has changed from an aqueous dialysate to a 16 perscent albumin solution. So that's the first difference. The second difference is that you change the dialysis membrane pore size and increase it to 50 kilodaltons. And that facilitates the extraction of a whole other class of toxins that are what are described as medium molecular weight substances that would not come out with regular CRT, which has a smaller dialysis membrane size. So, by changing the membrane pore size, and by changing the dialysate to an albumin dialysate, you suddenly create a system where you can extract a whole other class of toxins that are specifically albumin bound, that will not come off with CRT, but suddenly can now come out with the MARS machine.
Host: Give us examples of that.
Ram Subramanian, MD, MBA (Guest): So, when you think about, and we can get more into this when we talk about critical care toxicology, the examples, one example is a calcium channel blocker toxicity, which is well treated with the MARS device. And that is one example in the critical care toxicology field, where you can suddenly start extracting drugs such as calcium channel blockers that are heavily protein bound and using the properties of the MARS device, you can now extract this efficiently using the MARS device, which regular CRT will not do. From an off-label standpoint, another example. And I briefly alluded to the fact that there is growing interest in critical care hepatology.
An example of a molecule that may be clinically important is indogenous benzodiazepines, which are, which represent another example of a molecule that is heavily protein bound. That can come off with a MARS circuit which wouldn't, and will not come off with a CRT machine. So, the clinical relevance of that, and this is based on an RCT level data is that the MARS device has been shown to be very effective in the reversal of refractory hepatic encephalopathy in cirrhosis. And the mechanistic rationale for that may be the extraction of indogenous benzodiazepines. So, just to give you a couple of molecules that are clinically-relevant, if you will, in the context of critical care toxicology and critical care hepatology.
Host: There's quite a few indications with substances, with drugs for which extra corporeal removal is indicated; barbiturates and lithium, metformin, salicylates, valproic acid, toxic alcohols. It goes on. And you're saying that MARS is able to take it to the next level.
Dr. Subramanian: That is correct. And this specifically I would draw attention to the critical care providers about if you see a toxin that has the property of being highly protein-bound; as an example, I'd mentioned calcium channel blocker toxicity, amlodipine is a calcium channel blocker is 98% protein bound.
So, that's a perfect target or a perfect example of a molecule or a drug that can be extracted very effectively with the MARS system because of the high protein bound nature of the, of the toxin.
Host: Excellent. Absolutely. So, what you're saying is, if you were talking to a critical care peer and they asked you to really highlight the best applications for MARS in critical care toxicology; what you're saying is that protein bound substances, as you've mentioned, would definitely be part of the significant application. Anything else?
Dr. Subramanian: So I think that is, that is the major sort of big ticket item to focus on. I'll give you, to give you other examples of some of these drugs. So phenytoin is 90% protein bound. So that's a great example. And this is that there have been case reports written about the successful treatment of phenytoin toxicity.
Lamotrigine is another example, which is, which has less protein bound at 55%. But the general consensus is if you have a drug or a molecule that is greater than 50% protein bound and especially at a higher levels, then you should definitely consider this strategy in the treatment of that specific toxidrome.
Host: Absolutely. And, and in drug overdoses per se, are there a top three to five that really seem to be most ideal for MARS in drug overdoses?
Dr. Subramanian: So I think the data is still emerging as we discover its utility. I think it just a matter of time before poison control centers and critical care providers start identifying and looking at the algorithm or the protein bound nature of these substances, things that have already been written about is calcium channel blocker toxicity.
So, diltiazem, amlodipine are perfect examples. As I've mentioned, phenytoin has also been mentioned and written about, so I think, as there's more awareness of this technology, you'll see a greater uptick in its application and its utilization. The other thing I like to mention is there is a, an epidemic if you will, of herbal hepatoxicity, which is a whole class of drugs or toxins that, that this is sort of an unregulated market. And as we think about herbal toxicity and including hepatotoxicity, I think there may be an increasing application of the MARS device in that specialty context, especially if you start identifying molecules that are highly protein.
Host: Okay. When you're talking about herbal toxicity what are examples?
Dr. Subramanian: So, if you look at and again, it's hard to sort of tease this out because sometimes it's unclear, which is the active ingredients, some of these herbal meds, but cases of, of the, we have treated here is retreated, kava, kava toxicity. We've treated chaparral toxicity, we've treated even cases of green, green tea overdose.
We've treated examples of sort of including hi androgen containing or testosterone containing compounds which don't exactly fall in the herbal category, but they can be mixed in with it. So I share this with the audience, because I think that is a, a, toxicology domain that is, that is emerging, if you will, as we see more of it in a ICUs and healthcare systems. And that may be an interesting opportunity to apply this device to.
Host: Very interesting and correct me if I'm wrong. So many people out there in the populace who do overdose often times too with more than one substance. This complicates things, doesn't it?
Dr. Subramanian: It does, it does, and then becomes very challenging to identify the true inciting agent. As you mentioned, especially as if you have a co-ingestion. And as healthcare providers, we sometimes forget to ask whether there is a consumption of an herbal agent, because we are looking at the conventional medication list. And so I think it behooves the provider to the asking about potential herbal toxicity especially when you have cryptogenic, cryptogenic toxidrome.
Host: I think that this is such an important point because people are now basically self-medicating, they may be on RX medications and then add herbals. And there are interactions which can be problematic and they can also basically creative creatively come up with her own idea about what will be good for them. If one is good, three is better, kind of a concept which we see in our patients so often. And this really is important. Most people out there, not our peers; we're talking about our patients consider herbal to be, and I quote natural, therefore safe, and you can take as much of it as you want. So I think to your point, it is imperative to ask the question because we don't know.
Dr. Subramanian: And just to add onto this, the other application that we have used at our center is the treatment of severe jaundice. And just to add to the list bilirubin is another example of a molecule that is well extracted by the MARS device, which will not happen with the regular CRT or intermittent haemodialysis system.
And in the context of drug toxicity and especially drug hepatotoxicity, we've had very good success with reversing severe hyperbilirubinemia. So we're talking about bilirubins to 50, 60, that patients can languish with and, and that could eventually progress to fibrosis and chronic liver disease. So we've had very good success in reversing severe hyperbilirubinemia associated with drug toxicity which is more of an example of a focused toxicology hit on the liver. So I just wanted to add that to the conversation.
Host: That's very important. And I want everyone out there to know that Dr. Subramanian is author of a an article, a study, The Current Evidence for Extra Corporeal Liver Support Systems and Acute Liver Failure and Chronic Liver Failure and I believe you're really drawing from that article when you're talking about jaundice. Were there any other high points from that specific piece of literature?
Dr. Subramanian: Yeah. So they, as I alluded to before the one specific indication, again, just to underline the fact this is off label use, but the one scenario where MARS works really well is a reversal of refractory hepatic encephalopathy in cirrhosis. So, I think that's an important take home point for the listener.
And at this moment in time, we have somebody who's in severe hepatic encephalopathy and we are trying to prevent intubation. And that patient has been refractory to all aggressive pharmacological therapy, including lactulose, rifaximin, zinc, metronidozole. And when you hit that stage, we've had very good success with the timely initiation of MARS to reverse refractory hepatic encephalopathy. So, again, off-label indication, but, but it has been shown in an RCT that from many years ago that actually it does have efficacy in that context. And that has been our experience as well.
Host: That's fantastic. And, you know, describe the logistics that are related to starting a MARS program at your institution.
Ram Subramanian, MD, MBA (Guest): So, this has been an interesting journey. So we've been using MARS at Emory for over 10 years now. And as I reflect back on the experience, a couple of things to share with the, the audience. Number one, it's a, it's a team sport. You need the involvement of the, of an intensivist and these need to be champions and intensivist, a hepatologist and a nephrologist. I think those are the three important players if you will, as you, as you start thinking about starting a program, because they have to put their collective wisdom together to initiate a program.
The second sort of feature as I reflect back on our experiences I have had the good fortune of being part of the process we have, we've created a dedicated ICU for administering this technology. And we have dedicated nursing colleagues who have developed a passion for this technology. And we have a call pool to initiate the MARS system. And so if I, if we decide to trigger MARS on a patient with some urgency, we are able to mobilize that specific cohort of nursing super-users in MARS that are able to trigger timely therapy in a very effective and efficient manner.
So I share that with the audience to say that in addition to the physician champions, you need your nursing colleagues to be passionate about initiating and continuing this therapy as well.
Host: I absolutely love this integrative approach. And so thank you for identifying the team members and the significance and importance of everyone working together to be able to execute an optimal MARS program. Do you have any other thoughts as we wrap up this introduction to molecular adsorbent recirculating system, albumin dialysis, or MARS.
Dr. Subramanian: I look forward to a growing interest in this technology. And as people discover its utility, especially in critical care toxicology related to highly protein bound drugs, I think it's exciting technology moving forward. And I look forward to it's application in the future.
Host: And are you available if somebody out there is wanting to ask you a question since you have a program already up and running?
Dr. Subramanian: Oh, most definitely. I would be glad to be of service to anyone interested in starting such a program.
Host: Excellent. Thank you so very, very much. All right. Well, this concludes another edition of the iCritical Care podcast. Dr. Subramanian, thank you so much for your knowledge and your wisdom with regard to this issue. For the iCritical Care Podcast, I'm Dr. Pam Peeke.
Baxter Ad: This podcast is sponsored by Baxter healthcare corporation. When you choose Baxter for your C R R T program, you're not only choosing true patient focused treatment with industry leading CRRT technology. You're also selecting a partner dedicated to optimizing your clinical success in treating patients with acute kidney injury.
Our commitment to you starts with a program individualized to your facility's needs and provides complete support every step of the way for more information, visit us at www dot renal, acute.com. Baxter healthcare corporation has provided funding for this podcast, but all content was developed independently by the.
Therefore the views expressed on the podcast are those of the speaker and should not be attributed to Baxter healthcare corporation for prescription use only for the safe and proper use of this product. Please refer to the owner's manual.
Mars Eleni: Mars is indicated for the treatment of drug overdose and poisonings. The only requirement is that the drug or chemical will be dialyzed bubble in Unbound form and bound by charcoal and or ion exchange resins. Mars is not indicated for the treatment of chronic liver disease conditions or as a bridge to liver trans.
Safety and efficacy has not been demonstrated for those indications in controlled randomized clinical trials. The effectiveness of the Mars device in patients that are sedated could not be established in clinical studies and therefore can not be predicted in sedated patients.
Dr. Pam Peeke Bio: Pamela M. Peeke, MD, MPH, FACP, FACSM is a nationally-renowned physician scientist expert and thought leader in the field of medicine. Dr. Peeke is a Pew Foundation Scholar in Nutrition and Metabolism, Assistant Professor of Medicine at the University of Maryland, holds dual master's degrees in Public Health and Policy, and is a Fellow of both the American College of Physicians and the American College of Sports Medicine.
Dr. Peeke has been named one of America's top physicians by the Consumer's Research Council of America. She is a regular in-studio medical commentator for the National Networks and an acclaimed TEDx presenter and National Keynote Speaker.
Dr. Peeke is a three-time New York Times bestselling author and is a science and health advisor for Apple.
Disclaimer: The iCritical Care podcast is the copyrighted material of the Society of Critical Care Medicine, and all rights are reserved. Statements of fact and opinion expressed in this podcast are those of authors and participants, and do not imply an opinion or endorsement on the part of the Society of Critical Care Medicine, its officers, volunteers, or members, or that of the podcast commercial supporter.
Baxter Ad: This podcast is sponsored by Baxter healthcare corporation. When you choose Baxter for your C R R T program, you're not only choosing true patient focused treatment with industry leading CRRT technology. You're also selecting a partner dedicated to optimizing your clinical success in treating patients with acute kidney injury.
Our commitment to you starts with a program individualized to your facility's needs and provides complete support every step of the way for more information, visit us at www dot renal, acute.com. Baxter healthcare corporation has provided funding for this podcast, but all content was developed independently by the.
Therefore the views expressed on the podcast are those of the speaker and should not be attributed to Baxter healthcare corporation for prescription use only for the safe and proper use of this product. Please refer to the owner's manual.
Mars Eleni: Mars is indicated for the treatment of drug overdose and poisonings. The only requirement is that the drug or chemical will be dialyzed bubble in Unbound form and bound by charcoal and or ion exchange resins. Mars is not indicated for the treatment of chronic liver disease conditions or as a bridge to liver trans.
Safety and efficacy has not been demonstrated for those indications in controlled randomized clinical trials. The effectiveness of the Mars device in patients that are sedated could not be established in clinical studies and therefore can not be predicted in sedated patients.
Pam Peeke, MD, MPH, FACP, FACSM (Host):
Hello and welcome to the Society of Critical Care Medicine's iCritical Care Podcast. I'm your host, Dr. Pam Peeke. Today, we're going to be talking about an introduction to molecular adsorbent recirculating system, albumin dialysis, and I'm joined by Dr. Ram Subramanian. Dr. Subramanian is Professor of Medicine and Surgery and Medical Director of Liver Transplantation and Liver Critical Care Services at Emory University. Welcome Dr. Subramanian.
Ram Subramanian, MD, MBA (Guest): Thank you for having me.
Host: Excellent. Before we start, do you have any disclosures to report?
Dr. Subramanian: I am a consultant for Baxter Incorporated, which makes the MARS device.
Host: And any other disclosures relative to this podcast?
Dr. Subramanian: I have no other disclosures relevant to this.
Host: Excellent. And before we begin, just know that the learning objectives include describing the principle of albumin dialysis related to the molecular adsorbent recirculating system, known as MARS, want to outline the current indication for MARS,highlight application to MARS in critical care toxicology, describe logistics related to starting a MARS program.
And why is this podcast needed? Well, it's needed to educate ICU and other clinicians on MARS as a therapy. The knowledge gaps that this podcast will address, include allowing clinicians to understand how MARS works and engage in understanding what patients are ideal for this therapy. Now to put this in context, the extra corporeal techniques most frequently employed for the removal of toxins, and that includes drug overdoses and intoxication are hemodialysis, continuous hemofiltration techniques, hemoperfusion, and the molecular adsorbent recirculating system known as MARS. Dr. Subramanian, how did MARS come about? We have all of these other options. What was the genesis of MARS?
Dr. Subramanian: So MARS was actually discovered by two German nephrologists. And this was just a date, the device, this was back when we had East Germany and West Germany. So these are two nephrologists in East Germany that came up with it. And the rationale was to create a system that would change the dialysate to an albumen dialysate instead of an aqueous dialysate that is used in traditional haemodialysis and therefore to be able to extract a whole other class of toxins from the patient's plasma that are specifically albumin bound. So, that was the original genesis of and the rationale behind this device.
Host: Excellent and, and come forward now. How long has MARS been utilized in contemporary critical care?
Dr. Subramanian: So it is not been used often, especially in North America. There are very, very few centers that are using this with any degree of expertise or knowledge. So it's, it's an area that is attracting more and more attention in the field of critical care toxicology and the other area, and this just for full disclosure, is an off-label indication, there is growing interest in the field of critical care hepatology with regard to the use of the MARS device. And we can talk about that more.
Host: Excellent. Okay so basically the actual therapy itself, the MARS has a fairly ancient history here in terms of evolution in origin and has not been typically used in North America, but now is beginning to emerge as another tool in our toolbox for the treatment of drug overdose and intoxication.
So describe to us the principle of albumin dialysis related to MARS.
Dr. Subramanian: So a useful construct to understand MARS is to compare and contrast it with the regular haemodialysis or CRT. So a couple of major differences. Number one, as I had mentioned before the dialysate has changed from an aqueous dialysate to a 16 perscent albumin solution. So that's the first difference. The second difference is that you change the dialysis membrane pore size and increase it to 50 kilodaltons. And that facilitates the extraction of a whole other class of toxins that are what are described as medium molecular weight substances that would not come out with regular CRT, which has a smaller dialysis membrane size. So, by changing the membrane pore size, and by changing the dialysate to an albumin dialysate, you suddenly create a system where you can extract a whole other class of toxins that are specifically albumin bound, that will not come off with CRT, but suddenly can now come out with the MARS machine.
Host: Give us examples of that.
Ram Subramanian, MD, MBA (Guest): So, when you think about, and we can get more into this when we talk about critical care toxicology, the examples, one example is a calcium channel blocker toxicity, which is well treated with the MARS device. And that is one example in the critical care toxicology field, where you can suddenly start extracting drugs such as calcium channel blockers that are heavily protein bound and using the properties of the MARS device, you can now extract this efficiently using the MARS device, which regular CRT will not do. From an off-label standpoint, another example. And I briefly alluded to the fact that there is growing interest in critical care hepatology.
An example of a molecule that may be clinically important is indogenous benzodiazepines, which are, which represent another example of a molecule that is heavily protein bound. That can come off with a MARS circuit which wouldn't, and will not come off with a CRT machine. So, the clinical relevance of that, and this is based on an RCT level data is that the MARS device has been shown to be very effective in the reversal of refractory hepatic encephalopathy in cirrhosis. And the mechanistic rationale for that may be the extraction of indogenous benzodiazepines. So, just to give you a couple of molecules that are clinically-relevant, if you will, in the context of critical care toxicology and critical care hepatology.
Host: There's quite a few indications with substances, with drugs for which extra corporeal removal is indicated; barbiturates and lithium, metformin, salicylates, valproic acid, toxic alcohols. It goes on. And you're saying that MARS is able to take it to the next level.
Dr. Subramanian: That is correct. And this specifically I would draw attention to the critical care providers about if you see a toxin that has the property of being highly protein-bound; as an example, I'd mentioned calcium channel blocker toxicity, amlodipine is a calcium channel blocker is 98% protein bound.
So, that's a perfect target or a perfect example of a molecule or a drug that can be extracted very effectively with the MARS system because of the high protein bound nature of the, of the toxin.
Host: Excellent. Absolutely. So, what you're saying is, if you were talking to a critical care peer and they asked you to really highlight the best applications for MARS in critical care toxicology; what you're saying is that protein bound substances, as you've mentioned, would definitely be part of the significant application. Anything else?
Dr. Subramanian: So I think that is, that is the major sort of big ticket item to focus on. I'll give you, to give you other examples of some of these drugs. So phenytoin is 90% protein bound. So that's a great example. And this is that there have been case reports written about the successful treatment of phenytoin toxicity.
Lamotrigine is another example, which is, which has less protein bound at 55%. But the general consensus is if you have a drug or a molecule that is greater than 50% protein bound and especially at a higher levels, then you should definitely consider this strategy in the treatment of that specific toxidrome.
Host: Absolutely. And, and in drug overdoses per se, are there a top three to five that really seem to be most ideal for MARS in drug overdoses?
Dr. Subramanian: So I think the data is still emerging as we discover its utility. I think it just a matter of time before poison control centers and critical care providers start identifying and looking at the algorithm or the protein bound nature of these substances, things that have already been written about is calcium channel blocker toxicity.
So, diltiazem, amlodipine are perfect examples. As I've mentioned, phenytoin has also been mentioned and written about, so I think, as there's more awareness of this technology, you'll see a greater uptick in its application and its utilization. The other thing I like to mention is there is a, an epidemic if you will, of herbal hepatoxicity, which is a whole class of drugs or toxins that, that this is sort of an unregulated market. And as we think about herbal toxicity and including hepatotoxicity, I think there may be an increasing application of the MARS device in that specialty context, especially if you start identifying molecules that are highly protein.
Host: Okay. When you're talking about herbal toxicity what are examples?
Dr. Subramanian: So, if you look at and again, it's hard to sort of tease this out because sometimes it's unclear, which is the active ingredients, some of these herbal meds, but cases of, of the, we have treated here is retreated, kava, kava toxicity. We've treated chaparral toxicity, we've treated even cases of green, green tea overdose.
We've treated examples of sort of including hi androgen containing or testosterone containing compounds which don't exactly fall in the herbal category, but they can be mixed in with it. So I share this with the audience, because I think that is a, a, toxicology domain that is, that is emerging, if you will, as we see more of it in a ICUs and healthcare systems. And that may be an interesting opportunity to apply this device to.
Host: Very interesting and correct me if I'm wrong. So many people out there in the populace who do overdose often times too with more than one substance. This complicates things, doesn't it?
Dr. Subramanian: It does, it does, and then becomes very challenging to identify the true inciting agent. As you mentioned, especially as if you have a co-ingestion. And as healthcare providers, we sometimes forget to ask whether there is a consumption of an herbal agent, because we are looking at the conventional medication list. And so I think it behooves the provider to the asking about potential herbal toxicity especially when you have cryptogenic, cryptogenic toxidrome.
Host: I think that this is such an important point because people are now basically self-medicating, they may be on RX medications and then add herbals. And there are interactions which can be problematic and they can also basically creative creatively come up with her own idea about what will be good for them. If one is good, three is better, kind of a concept which we see in our patients so often. And this really is important. Most people out there, not our peers; we're talking about our patients consider herbal to be, and I quote natural, therefore safe, and you can take as much of it as you want. So I think to your point, it is imperative to ask the question because we don't know.
Dr. Subramanian: And just to add onto this, the other application that we have used at our center is the treatment of severe jaundice. And just to add to the list bilirubin is another example of a molecule that is well extracted by the MARS device, which will not happen with the regular CRT or intermittent haemodialysis system.
And in the context of drug toxicity and especially drug hepatotoxicity, we've had very good success with reversing severe hyperbilirubinemia. So we're talking about bilirubins to 50, 60, that patients can languish with and, and that could eventually progress to fibrosis and chronic liver disease. So we've had very good success in reversing severe hyperbilirubinemia associated with drug toxicity which is more of an example of a focused toxicology hit on the liver. So I just wanted to add that to the conversation.
Host: That's very important. And I want everyone out there to know that Dr. Subramanian is author of a an article, a study, The Current Evidence for Extra Corporeal Liver Support Systems and Acute Liver Failure and Chronic Liver Failure and I believe you're really drawing from that article when you're talking about jaundice. Were there any other high points from that specific piece of literature?
Dr. Subramanian: Yeah. So they, as I alluded to before the one specific indication, again, just to underline the fact this is off label use, but the one scenario where MARS works really well is a reversal of refractory hepatic encephalopathy in cirrhosis. So, I think that's an important take home point for the listener.
And at this moment in time, we have somebody who's in severe hepatic encephalopathy and we are trying to prevent intubation. And that patient has been refractory to all aggressive pharmacological therapy, including lactulose, rifaximin, zinc, metronidozole. And when you hit that stage, we've had very good success with the timely initiation of MARS to reverse refractory hepatic encephalopathy. So, again, off-label indication, but, but it has been shown in an RCT that from many years ago that actually it does have efficacy in that context. And that has been our experience as well.
Host: That's fantastic. And, you know, describe the logistics that are related to starting a MARS program at your institution.
Ram Subramanian, MD, MBA (Guest): So, this has been an interesting journey. So we've been using MARS at Emory for over 10 years now. And as I reflect back on the experience, a couple of things to share with the, the audience. Number one, it's a, it's a team sport. You need the involvement of the, of an intensivist and these need to be champions and intensivist, a hepatologist and a nephrologist. I think those are the three important players if you will, as you, as you start thinking about starting a program, because they have to put their collective wisdom together to initiate a program.
The second sort of feature as I reflect back on our experiences I have had the good fortune of being part of the process we have, we've created a dedicated ICU for administering this technology. And we have dedicated nursing colleagues who have developed a passion for this technology. And we have a call pool to initiate the MARS system. And so if I, if we decide to trigger MARS on a patient with some urgency, we are able to mobilize that specific cohort of nursing super-users in MARS that are able to trigger timely therapy in a very effective and efficient manner.
So I share that with the audience to say that in addition to the physician champions, you need your nursing colleagues to be passionate about initiating and continuing this therapy as well.
Host: I absolutely love this integrative approach. And so thank you for identifying the team members and the significance and importance of everyone working together to be able to execute an optimal MARS program. Do you have any other thoughts as we wrap up this introduction to molecular adsorbent recirculating system, albumin dialysis, or MARS.
Dr. Subramanian: I look forward to a growing interest in this technology. And as people discover its utility, especially in critical care toxicology related to highly protein bound drugs, I think it's exciting technology moving forward. And I look forward to it's application in the future.
Host: And are you available if somebody out there is wanting to ask you a question since you have a program already up and running?
Dr. Subramanian: Oh, most definitely. I would be glad to be of service to anyone interested in starting such a program.
Host: Excellent. Thank you so very, very much. All right. Well, this concludes another edition of the iCritical Care podcast. Dr. Subramanian, thank you so much for your knowledge and your wisdom with regard to this issue. For the iCritical Care Podcast, I'm Dr. Pam Peeke.
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Mars Eleni: Mars is indicated for the treatment of drug overdose and poisonings. The only requirement is that the drug or chemical will be dialyzed bubble in Unbound form and bound by charcoal and or ion exchange resins. Mars is not indicated for the treatment of chronic liver disease conditions or as a bridge to liver trans.
Safety and efficacy has not been demonstrated for those indications in controlled randomized clinical trials. The effectiveness of the Mars device in patients that are sedated could not be established in clinical studies and therefore can not be predicted in sedated patients.
Dr. Pam Peeke Bio: Pamela M. Peeke, MD, MPH, FACP, FACSM is a nationally-renowned physician scientist expert and thought leader in the field of medicine. Dr. Peeke is a Pew Foundation Scholar in Nutrition and Metabolism, Assistant Professor of Medicine at the University of Maryland, holds dual master's degrees in Public Health and Policy, and is a Fellow of both the American College of Physicians and the American College of Sports Medicine.
Dr. Peeke has been named one of America's top physicians by the Consumer's Research Council of America. She is a regular in-studio medical commentator for the National Networks and an acclaimed TEDx presenter and National Keynote Speaker.
Dr. Peeke is a three-time New York Times bestselling author and is a science and health advisor for Apple.
Disclaimer: The iCritical Care podcast is the copyrighted material of the Society of Critical Care Medicine, and all rights are reserved. Statements of fact and opinion expressed in this podcast are those of authors and participants, and do not imply an opinion or endorsement on the part of the Society of Critical Care Medicine, its officers, volunteers, or members, or that of the podcast commercial supporter.