Time Stamps

  • 02:36 Deep Dive 1: Bleeding risk of paracentesis and thoracocentesis
  • 05:35 Deep Dive 2: FFP effect on bleeding risk
  • 15:43 Deep Dive 3: Risks of FFP
  • 19:45 Deep Dive 4: Indwelling pleural catheters
  • 30:31 Recap

Show Notes

  • What is the bleeding risk for a paracentesis and thoracocentesis in patients with cirrhosis?
    • Bleeding risk for paracentesis is low!
      • One study looked at 1100 large volume paracenteses performed by skilled practitioners in patients with cirrhosis with platelets as low as 19 and INR as high as 8.7 and found no significant bleeding events.
      • Recommendation: AASLD guidelines recommend not giving FFP prior to paracentesis.
    • Bleeding risk with thoracentesis is low!
      • Recommendation: The Society of Interventional Radiology recommends not checking INR or having a specific threshold prior to doing a thoracentesis in a patient with cirrhosis based on expert consensus
  • What is in FFP?  
      • FFP contains everything you are left with after you removed the cellular elements of blood:
        • Albumin
        • Pro-clotting factors
        • Anti-clotting factors
  • What does and doesn’t the INR tell us? 
    • Patients with cirrhosis have a complicated re-balancing of pro and anti clotting factors
      • INR does not fully capture this
    • Patients with cirrhosis have:
      • Hyperfibrinolysis
      • Hypofibrinogenemia
      • Platelet dysfunction
      • Thrombocytopenia
      • Low levels of clotting factor
      • Anti-clotting factor
    • Giving FFP is a blunt tool that will not address all the coagulation abnormalities for a patient with cirrhosis and therefore will not appreciably affect their procedural bleeding risk.
  • Giving FFP carries risks!
    • The risk of anaphylactic reaction and TRALI is small, but not zero!
    • FFP stays mainly intravascularly and this causes an increase in portal pressure for patients with cirrhosis
      • This further increases their risk for complications of portal hypertension, including:
        • Ascites
        • Hepatic hydrothorax
        • Volume overload
  • Indwelling pleural catheters:
    • Not first line for hepatic hydrothorax but are sometimes appropriate in carefully selected patients:
      • When the infection risk is balanced against a patient being diuretic refractory
      • Not a TIPS candidate
      • In need of frequent thoracenteses
    • Malnutrition is often cited as a reason not to place pleural catheters because it causes drainage of protein with removing pleural fluid.
      • However, this happens with intermittent thoracentesis as well so does not seem to hold up as a reason not to place an indwelling pleural catheter.
    • Infection risk is similar to other types of patients with indwelling pleural catheters.
      • However, the infection can be harder to clear because of the difficulty fully evacuating the hepatic hydrothorax in order to allow for pleurodesis and source control.


Dr. Ali Trainor: Welcome to Gray Matters, where we unpack how medical management is rarely black or white.

Dr. Jason Freed: And we go on deep dives along the way! I’m Dr. Jason Freed and I’m a hematologist at Beth Israel Deaconess Medical Center. 

Dr. Ali Trainor: I’m Dr. Ali Trainor and I’m a pulmonary and critical care fellow at the Harvard combined program at MGH and Beth Israel Deaconess.

Dr. Jason Freed: So, this week we have a special guest joining us. Dr. Elliot Tapper who is a Hepatologist at University of Michigan. He posted a thread on twitter a while back about a patient that he took care of and, Ali, you and I both independently read it and thought, okay we have to have him on to talk through this case with us.

Dr. Ali Trainor: Yeah, exactly. I’ll let Dr. Tapper introduce the case.

Dr. Elliot Tapper: A woman, uh, in her fifties who has alcohol related cirrhosis. And the main reason why she presented for care was because of ascites and she also had hepatic hydrothorax. So, when we first met her, our goal was to try to control her volume overload with diuretics. The problem was that as we tried to increase those, the dosage of those medications, we started to run into trouble with kidney injury or hyperkalemia, hyponatremia. She was diuretic resistant. So, she was in a given week getting both a paracentesis and a thoracentesis. And for her, the main complicating factor was that she had an elevated INR. Something like 1.9 to 2.1 and would bounce around.

Dr. Jason Freed: Yikes, weekly paracentesis and thoracentesis? Also, hepatic hydrothorax has always sort of baffled me that the fluid is somehow sort of getting from your abdomen to your chest cavity. Like, you have a diaphragm in the way!

Dr. Ali Trainor: Haha, right? I was always confused by this too, but what happens is that you have these teeny, tiny defects in your diaphragm and when you breathe you create a negative pleural pressure that sucks some of that fluid from your abdomen up into your pleural space.

Dr. Jason Freed: I mean, I guess that makes sense, but it’s crazy.

Dr. Ali Trainor: Totally! And so this woman is getting weekly paras and thora and then what ended up happening was she would get multiple units of FFP for her elevated INR to reduce her bleeding risk.

Dr. Jason Freed: So, this was what got us interested because we see and do this all the time. We give products prior to a procedure with the intention of reducing bleeding risk, but should we be doing this? 

Dr. Ali Trainor:  Okay, we’re gonna jump right in here with deep dive 1. So, we’re talking about giving FFP to reduce bleeding risk, but is the bleeding risk with paracentesis or thoracentesis even high? Like, do I actually need to be worried here? 

Dr. Elliot Tapper: We have a wealth of old and new data that shows that procedures like paracentesis, thoracentesis, these are really safe. And in order to cause bleeding effectively what you have to do is lacerate a large vessel for which there is no transfusion blood product that can prevent bleeding in that case. So, POCUS all you want for safety. 

Dr. Ali Trainor: So, when you’re doing a paracentesis, quickly pop on the vascular probe and look for the inferior epigastrics, and if they aren’t where you’re intending for your needle track to go then your risk of bleed is exceedingly low. Similarly for thoracentesis, we know our landmarks and know that the neurovascular bundle runs beneath the rib so if you go directly over the rib you should be avoiding the blood vessels. 

Dr. Jason Freed: Okay, and do you know what data he’s referring to?

Dr. Ali Trainor: Yeah, this is one of my favorite studies to cite on rounds. It was published in hepatology in 2004 and looked at 1100 large volume paracentesis in patients with cirrhosis with a range of platelet and INR values with the lowest platelet count being 19 and the highest INR 8.7. And there were no significant bleeding events.

Dr. Jason Freed: Wow, none??

Dr. Ali Trainor: Right?!

Dr. Jason Freed: But, like who was doing the paras in this study? Like a resident who has done 1 para before on a simulator? Or what?

Dr. Ali Trainor: Great point, this study was in trained, high volume providers who were doing dozens of these per year. 

Dr. Jason Freed: Okay, so, paracentesis can be very safe despite thrombocytopenia and elevated INR, if you know what you’re doing. 

Dr. Ali Trainor: Exactly, and this informs the American Association for the Study of Liver Disease guidelines which state that because the bleeding risk with paracentesis is so low, they do not recommend giving FFP prior to the procedure.

Dr. Jason Freed: Okay, that was the quickest, most straightforward deep dive we’ve ever done. Bleeding risk is low, don’t give FFP…. so…why bring this to the gray matters table? 

Dr. Ali Trainor: Well, we’ve talked a lot about paracentesis, but we don’t have as much data to go on for thoracentesis.

Dr. Jason Freed: Do we have anything to go off for thoracentesis?

Dr. Ali Trainor: Well, the society of interventional radiology has these consensus guidelines that recommend not checking INR or having a specific threshold goal for patients with cirrhosis prior to thoracentesis, but this is based on expert opinion.

Dr. Jason Freed: Interesting! So, any idea what they based the expert opinion on? 

Dr. Ali Trainor: Well, it was mostly the fact that thoracentesis is overall a low risk bleeding procedure and so they lumped with other low bleeding risk procedures, but a caveat to keep in mind is they didn’t have any studies specifically in patients with cirrhosis to base this recommendation on.

Dr. Jason Freed: Hah!

Dr. Ali Trainor: Yeah, so I think the bigger question, too, is that we have data telling us that the bleeding risk is low, this data doesn’t tell me what actually happens when I give FFP to a patient with cirrhosis.

Dr. Jason Freed: Okay, so for deep dive 2 we want to figure out, does giving FFP to a patient with cirrhosis actually improve their bleeding risk and therefore can we justify giving it prior to paracentesis or maybe thoracentesis where we have less data?

Dr. Ali Trainor: Yeah, maybe a good place to start is just a reminder of what FFP is. Here’s Dr. Alice Ma, a hematologist from UNC.

Dr. Alice Ma: So, FFP or fresh frozen plasma is what you are left with when you take the cellular elements of blood and spin them out. So, you have no platelets, no white cells and no red cells. So, predominantly water, proteins. And um, so you’ll have albumin and clotting factors. Um, and so pro clotting factors and anti-clotting factors, fibrinogen, um, all the factors, uh, 1 through 13 and um, protein C, protein S, antithrombin. 

Dr. Ali Trainor: Yeah, I don’t think we always think of that when giving FFP, you know, that you’re giving both pro and anticoagulant factors. So, good to keep in mind.

Dr. Jason Freed: Yeah and then back to the question we first posed which is, will giving FFP to a patient with cirrhosis reduce their risk of bleeding from a procedure?

Dr. Ali Trainor: Yeah, I’ve heard it said a lot, and then adopted it as part of my vernacular as well, that we are going to “give FFP to correct the INR.”

Dr. Alice Ma: So first off that just gives me the cold willies when I hear that. When you say, okay, the INR is elevated and you are gonna give FFP what you’re really trying to say there is, we think the patient has a risk of bleeding and we’re going to try to ameliorate the risk of bleeding by replacing clotting factors that are in FFP. So then the question becomes what is the risk of bleeding and why is the INR elevated And does the elevated INR really correlate with the risk of bleeding? 

Dr. Elliot Tapper: So, the INR is branded as a tool to assess bleeding risk. And in fact, we give people medications to reduce their ability to clot due to conditions like atrial fibrillation. But the problem is that we have misapplied that association to people with cirrhosis. While the INR is really only measuring those procoagulant factors, it’s missing the bigger picture in people with cirrhosis who have an equal if not greater decrease in anticoagulant factors. So the assay is only telling us one part of the story. So because people have a mistaken but emotional attachment to the idea that it reflects auto anticoagulation in people with cirrhosis. In fact, it has nothing to do with in vivo coagulation function.

Dr. Ali Trainor: So, what that means is the INR is only telling us about the procoagulant factors 1-12, and it doesn’t tell us about the anticoagulant factor levels, protein C, S and antithrombin, which can also be low in patients with cirrhosis.

Dr. Jason Freed: Yeah, to be clear, if I want to know in a patient on warfarin how dangerous a procedure will be from a bleeding perspective their INR is a very good indicator. But if I’m trying to assess the risk of bleeding in a patient with cirrhosis, the INR is not a good indicator for that because there are so many other factors at play. 

Dr. Ali Trainor: And on top of that Dr. Ma taught me that there’s so much more that goes into bleeding risk for a patient with cirrhosis that FFP won’t even touch. 

Dr. Alice Ma: So the question is, is the patient with cirrhosis at risk of bleeding? And the answer is of course they are. But why are they at risk of bleeding? And that’s a complex question. So the first reason is that they have hyperfibrinolysis and that is not going to be fixed with two units of FFP. The second is that they are hypofibrinogenemia, that is very, very unlikely as well to be fixed by two units of FFP. Three. They have platelet dysfunction, again, not greatly fixed by FFP and three, they’re thrombocytopenic. Um, and only, and only at the very bottom of the list do they have clotting factor. And if you actually measure their levels of clotting factor, most of their levels of clotting factor are in the hemostatic range.

Dr. Ali Trainor: There is a TON to unpack there, but I think one of my main takeaways is just how complex the coagulation status of a patient with cirrhosis is. 

Dr. Jason Freed: Right, and if you take a patient with cirrhosis who has all the abnormalities we just mentioned to varying degrees, and you give plasma which has all of the proteins, you can’t always predict what the net response is going to be. 

Dr. Ali Trainor: Yeah, I asked Dr. Tapper what actually happens when you give people with cirrhosis FFP.

Dr. Elliot Tapper: There are some people about one in a hundred where you’re actually going to increase their thrombin generation. But for every one of those people, there’s at least 10 who have a decrease in their thrombin generation probably because we are diluting the biological space in which that hemostatic cascade is occurring. And for the vast majority of people, there’s no difference whatsoever on coagulation function. And that doesn’t mean that it’s benign, right?

Dr. Jason Freed: So, to summarize, the coagulation status of a patient with cirrhosis is complicated. You have increased fibrinolysis, low fibrinogen, thrombocytopenia, decreased pro and anticoagulant proteins, so we don’t always know the balance of the pro and anticoagulant factors. And giving FFP is a blunt tool that will not necessarily reduce the bleeding risk in a patient with cirrhosis.

Dr. Ali Trainor: Okay, so from deep dive 1, we know that the bleeding risk is already low, and from deep dive 2, FFP isn’t going to reduce it further, so….why are we doing this?

Dr. Elliot Tapper: There’s a whole series in a journal called “Things that we do for no reason,” but in fact it’s not true. It’s things that we do for a reason that we were raised to believe in these sorts of things. They are part of our upbringing, they’re part of our culture. And challenging that is, is very difficult and it will be very difficult for patients with cirrhosis for a number of reasons. Number one, is that there is death that’s involved with this decision. It’s not like it’s a, uh, walk in the park to do a procedure in somebody who has a high risk of dying in the next seven to 90 days. So as long as there is that, it will always be very difficult to overcome it simply through education.

Dr. Jason Freed: And we aren’t always the one doing the procedure right? Sometimes we are, but other times we’re referring our patient to another service to do the paracentesis. So they’re taking on the risk, and we’re like oh okay, yeah this patient has an INR of 3 and platelets of 20, but you don’t need to give any product, and they’re like well that’s easy for you to say, you’re not the one putting the needle in, BRO!

Elliot: Well, they’re worried. They’re worried that there will be a complication of their, uh, procedure. And I think by and large, clinicians are more worried that, if a complication were to arise, if we could have done something to prevent it, uh, then we have sinned and these sins of omission are weighted more heavily in our mind then sins of commission, which is exactly what my patient suffered from.

Dr. Ali Trainor: So, he’s foreshadowing what’s to come with this patient which we’ll get into a bit later, but before we get there it might be helpful to delve a bit more into why we’re doing these things even if we have data and guidelines telling us that it isn’t necessary.

Dr. Jason Freed: There are a lot of things at play here, but I think a big one is confirmation bias.

Dr. Ali Trainor: Do you want to share a bit more about what you mean, specifically in this context?

Dr. Jason Freed: So, there’s data out there saying giving FFP is not going to reduce the bleeding risk, but let’s say I don’t know that and I believe FFP will reduce the bleeding risk and so I give FFP, and they don’t bleed from the procedure, therefore I conclude that my giving the FFP prevented the bleeding.

Dr. Ali Trainor: Okay, and how do you think this would play out if you gave FFP and the patient does bleed?

Dr. Jason Freed: I mean, I think confirmation bias can be so strong that even in that scenario you might still conclude that giving FFP was the right thing because maybe you’ll say to yourself, “oh, thank goodness I gave FFP or the bleeding could have been a lot worse.”

Dr. Ali Trainor: I agree, and so then the question is what do we do here. 

Dr. Jason Freed: And again, we aren’t always the one doing the procedure. It can be really hard to combat your own cognitive biases and cultural influences, but it can get more complicated when working with colleagues. It was interesting to hear how Dr. Tapper tries to navigate this scenario.

Dr. Elliot Tapper: The first  is to take ownership of the procedure, which at my center, that’s effectively what we’ve done for the vast majority of paracentesis. Number two, is that if you are relying on another procedurist, either you have to give them time to become familiar and comfortable with, uh, increasing the INR threshold, or you use, you build a relationship with them where you can negotiate to try to come up with a way to, uh, both communicate your understanding and help get them on board, but ultimately, you’re deferring to them. So I’ll always reach out and try my best, but if they’re the ones that are helping my patients, I, I must settle for that case. 

Dr. Ali Trainor: And so for Dr. Tapper’s patient that we’re talking about, she lived far from the main hospital campus so was getting her procedures at a satellite location. 

Dr. Jason Freed: So option 1 we were talking about, take ownership of the procedure yourself was not possible here. 

Dr. Ali Trainor: And the physicians doing the procedure were in the practice of giving FFP prior to paracentesis and thoracentesis for elevated INR. 

Dr. Elliot Tapper: And for her, this resulted in increased volume overload. In the days that would follow and not infrequently, she would end up with either flash pulmonary edema and once even had transfusion reaction.

Dr. Jason Freed: Oh man…. So for deep dive 3, I think we should get into what are the actual risks associated with giving FFP. In order to educate ourselves, but also frame our discussions with procedural colleagues

Dr. Ali Trainor: Okay, I’m glad we’re talking about this because I can be sympathetic to that physician who was giving FFP prior to the paracentesis and thoracentesis, because you know sometimes I’m the one doing the thoracentesis. I know the data behind paracentesis. And just to play devil’s advocate I can understand  I getting nervous about causing a patient with cirrhosis to bleed from a thoracentesis so you know, maybe it’s ok to just give a little FFP just in case.

Dr. Alice Ma: I say, that’s incorrect. Star ranger! Um, you know, uh, FFP kills people, you know, TRALI, TACO. Absolutely! It’s just terrible. Plus, you know, um, if yes, blah, it does it, it, stop it!

Dr. Ali Trainor: LOL, holding no punches, but I think I have to admit she’s right? I mean it’s not without risk. Do you know, Jason, what the transfusion risk is with FFP?

Dr. Jason Freed: Overall, risk isn’t zero but it is rare. For an allergic or anaphylactic transfusion reaction we’re talking less than 0.001% for FFP transfusion. For TRALI the data is harder to pin down, but risk is fairly low. The risk is so low that it’s hard to say that it is reckless or negligent to give FFP to patient with cirrhosis prior to a procedure on this information alone, but we do need to keep in mind that the risk isn’t zero.

Dr. Ali Trainor: Okay, and then the other risk we talked about is volume overload which we know this patient was having after getting her FFP transfusions, but those bags of FFP look pretty small. So, is she really getting volume overload from a few units of FFP?

Dr. Jason Freed: Yeah, good question! Each unit of FFP is about 250ml so to make our math easy let’s say she gets 4 units then that would be about 1L. 

Dr. Ali Trainor: I’m guessing that she’s getting more than 1L of fluid taken off with the para and thora. So, she has more coming out than coming, so can we really say, again, she’s getting volume overloaded from the FFP transfusions? 

Dr. Jason Freed: I think the important thing we aren’t factoring in when we give FFP, is most of that stays intravascular, at least initially. There is a whole 5 Pearls episode on fluids. But, long story short, giving 4 units of FFP is probably similar to giving nearly 4 liters of normal saline since, again, most of that that FFP stays intravascular. 

Dr. Ali Trainor: It’s hard to justify when you put it that way, because I would never give 4L of IV fluid to a stable patient with cirrhosis who has ascites and a pleural effusion.

Dr. Jason Freed: Right? Dr. Tapper also shared this really interesting article with me that portal pressure increases almost linearly with increasing blood volume and we’ll link that in our show notes. 

Dr. Ali Trainor: That’s a great point, because if her refractory ascites and pleural effusions are a consequence of portal hypertension, and then we’re giving product that is going to stay almost entirely intravascular and  exacerbate portal hypertension, it feels like we’re just chasing our tails.

Dr. Jason Freed: Okay, so summarizing here, FFP, just like any blood product carries a risk of transfusion reaction, including TRALI, but the big thing we really need to keep in mind for patients with cirrhosis is, giving FFP, because almost all of it stays intravascular will lead to increased portal pressure.

Dr. Ali Trainor: Okay, so back to our patient, she’s getting frequent paracenteses and thoracenteses and getting FFP prior to these. Dr. Tapper walks us through what happened next…

Dr. Elliot Tapper: So after she was admitted multiple times, including twice to the ICU at an outside hospital, we needed to come up with a way of short circuiting this vicious cycle of needing a procedure and then having complications due to the management of her, uh, uh, so-called cirrhosis coagulopathy. And for us, the lesser of two evils was to place an indwelling catheter in her right pleural space. Now, typically you get nervous about things like infection, so you try to withhold indwelling catheters and people, particularly people that you’re hoping to get onto the liver transplant wait list. But for her, the cumulative risk of infection was so much lower than the ever-present risk of volume overload and ICU care.

Dr. Ali Trainor: Alright, so this was the other thing about this case that really caught my eye and what I want to do our fourth deep dive on, because I had always heard said, fairly dogmatically, that we do not place indwelling pleural catheters in patients with cirrhosis, but this patient got an indwelling pleural catheter.

Dr. Elliot Tapper: Indwelling catheter is not first line therapy for hydrothorax. If your patient is a candidate for TIPS, their heart is working, they don’t have severe uncontrolled HE, then TIPS it is. Then, second, you try to get away with diuretics. And if they rarely every few months require a thoracentesis, then that’s always gonna be, uh, preferred. But what the guidelines are saying is that, while we don’t want to put catheters in our patients, sometimes we have to and it’s okay to accommodate those patients.

Dr. Ali Trainor: So, it sounds like a pleural catheter shouldn’t be the first line thing we do for hepatic hydrothorax but it doesn’t mean you NEVER do it for hepatic hydrothorax. 

Dr. Jason Freed: Yeah, and if we think about our patient, she did have some factors that make it seem like an indwelling catheter might be warranted – she’s needing weekly procedures, diuretics aren’t working, she isn’t a TIPS candidate, and it’s HARD for her to get to her weekly appointments, and then in terms of negatives she’s ended up in the ICU because of blood product administration. It seems like there are a lot of good reasons why we might consider a pleural catheter, BUT on the other hand this dogma of avoiding them must have emerged for reason, right?

Dr. Ali Trainor: Maybe the dogma came from the fact that chest tubes are associated with high morbidity, clinical deterioration, and sometimes death. Those chest tubes were large-bore, surgical and continuously draining. But here we’re talking about indwelling pleural catheters, which are different.

Dr. Jason Freed: Ahh, so maybe we were inappropriately extrapolating from what happened with large-bore surgical chest tubes. 

Dr. Ali Trainor: Yeah, exactly. So, I talked to Dr. Mihir Parikh who is an interventional pulmonologist at Beth Israel Deaconess and here is what he had to say about this dogma that we shouldn’t place indwelling catheters in patients with cirrhosis.

Dr. Mihir Parikh: I’ve never, I don’t think I’ve said that. It certainly, it certainly exists out there and I definitely heard it when I was a, a house staff and a fellow as well, too. We still hear it now, infection risk of long-term catheters, uh, that, you know, I think that other commonly one, uh, commonly stated one is the risk of malnutrition from, you know, chronic protein loss, uh, from a pleural catheter. And so it’s, it’s hard. I think it’s, it’s easy to, um, to hold onto these because they’ve been around for so long and also the reason it’s easy to hold onto these is there’s not a lot of evidence to guide them or to refute them. So, it can be an issue.

Dr. Jason Freed: I’ve heard the rationale before about malnutrition being that you’re getting all this protein loss from the frequent drainage, does that hold up?

Dr. Mihir Parikh: Yeah, I actually think this is a rumor that’s been propagated. I have not seen any evidence, uh, to suggest this, but it was something I taught and I was taught and I held onto for a, a while. But I think now I think it’s, it’s, it’s just part of lore. I think, you know, trying to understand, you know, what contribution the plural drainage has in the larger scheme of, you know, patients nutrition, especially with advanced cirrhosis is, is I think a hard thing to pin down.

Dr. Jason Freed: So, it sounds like it’s not the protein thing, but whenever there is a foreign body, in the body, we have to think about infection risk.

Dr. Ali Trainor: I mean that’s true, but we place indwelling catheters in patients for various reasons all the time. Why should we be thinking about the infection risk differently for patients with cirrhosis?

Dr. Mihir Parikh: As I’ve become, uh, sort of more advanced or more senior, I think I’ve, I’ve come to appreciate the complications a bit more and you know, once these pleural catheters get infected, it can be a real pain. You know, especially in these hepatic hydrothoraces cause what you like to deal with in a, in an infected pleural catheter is you like for the patients to pleurodese, meaning for that space to be fully evacuated and to remain evacuated in order to clear the infection. The problem is with hepatic hydrothorax patients of all recurrent pleural fusions, they’re the worst, they’re hardest to pleurodese just because the volume is so high, uh, and the sort of the output is so high on average in these patients that you never really have an opportunity for the pleural surfaces to oppose and to pleurodese successfully.  So, uh, management becomes really complicated and you’re oftentimes just trying to treat through prolonged antibiotic courses with maybe no real likelihood of success. And so that’s why I do have humility for that. 

Dr. Jason Freed: Okay, so the infection risk concern with indwelling pleural catheters at least does hold up.

Dr. Ali Trainor: Yeah, and we don’t have any randomized controlled trials to look at the role for pleural catheter in these patients, but Dr. Tapper did bring up some interesting data.

Dr. Elliot Tapper: And then you bring up the retrospective single center studies about what happens to people when they have a, uh, a tube placed. And these are helpful in a couple of ways. One, is that they typically show you that some people will still get transplanted when these are placed. So good, good centers are using this when they need to sparingly and they’re helping patients in the long run. And then two, you’re also observing that, uh, patients get sicker over time. And of course we don’t really have a comparison arm. Sometimes you can say, well, let’s look at the intermittent thoracentesis arm, but of course we are, if we could have gone by with intermittent thoracentesis, we would have. So there is something quite ill about that patient that we decided to leap to the, uh, indwelling catheter. And in the absence of a comparison arm, I will simply tell you that the natural history of hydrothorax and refractory ascites without a liver transplant is not great. 

Dr. Jason Freed: So, sounds like these patients have a pretty poor prognosis to begin with and for our patient it seems like they ran out of other options and so they moved forward to an indwelling pleural catheter. So then I’m curious, what happened to our patient?

Dr. Elliot Tapper: So, the interesting thing, uh, that we expected was that we were going to have to closely monitor her for the risk of over, uh, removing fluid, ending up dehydrated because she’d always be removing fluid from the pleural space. And in fact, she was removing something like a liter per day, uh, for, uh, about a week. But then on the second week, the amount of volume that she could pull was less and less, and it was a very short period of time before the overall amount of fluid that was coming out was so low that it almost didn’t make sense to leave that catheter in. And we realized, in retrospect, that probably the number one contributor to her volume overload was the things that we were doing to her. The extra FFP and albumin that she was getting with all of her procedures was simply dumping right back into her pleural space resulting in an everlasting pleural effusion. So, after a while, uh, we were able to get to a place where we could keep her, uh, roughly euvolemic with simply the water pills. Uh, she would require intermittent drainage, and fortunately for her, a match was found and she was able to have a liver transplant. 

Dr. Jason Freed: This is an incredible happy ending! For the first time ever in Gray Matters!

Dr. Elliot Tapper: So, uh, I keep close tabs on, uh, on my patients who now at this point, several years after her transplant, she only follows up every six months or so. But when she does I get a little note from her current transplant hepatologist telling me how she’s doing and what she’s up to. And, uh, it warms my heart twice per year. 

Dr. Ali Trainor: Yeah! Happy ending indeed! But what a humbling plot twist that we were trying to help her with FFP but we were the problem all along. As soon as she stopped getting FFP, her volume overload completely resolved. 

Dr. Jason Freed: Yeah, it is wild! You know, I’m trying to decide if there’s a generalizable learning point for this because not everyone is getting this kind of harm, a lot of people just have bad ascites independent of products that we’re giving. So, I think what was remarkable about this story was that this is not a common story. 

Dr. Ali Trainor: Maybe? I’m also wondering, maybe this is a common story and we just aren’t aware of it.

Dr. Jason Freed: It’s certainly possible. It’s hard to say this is happening to every patient with cirrhosis who gets FFP prior to a procedure but it does at least illustrate, quite dramatically, that the risk of FFP is not just theoretical. Here’s a real person for whom unnecessary FFP use caused volume overload, an ICU stay, and unnecessary procedures. 

Dr. Ali Trainor: Yeah, I think a take home here, too, is just how many down stream effects there were for this patient because of the FFP. She had MULTIPLE procedures because of FFP, not just the weekly thoracentesis and paracenteis, but the pleural catheter too. I mean, if she wasn’t getting the FFP, she never would have even needed the pleural catheter.

Dr. Jason Freed: That’s a great point! I mean if she hadn’t been getting the FFP the whole second half of our episode wouldn’t have needed to happen.

Dr. Ali Trainor: Yeah, I’m so glad we brought this case to Gray Matters because there’s so much nuance and we learned a lot about giving FFP and placing indwelling pleural catheters, but these are just two examples of common practices, but with such wide reaching effects and it makes me wonder how many other similar instances there are out there of things that are common practices, but could be causing our patients harm. 

Dr. Jason Freed: Yeah, I mean I think it’s just such an important reminder to be humble and think about the harm we might be doing despite our best intentions. And that it’s really important to make sure we understand where dogmas or recommendations come from. I mean, this sounds so obvious to say, but like we should know the rationale for what we’re doing 

Dr. Ali Trainor: I mean, it sounds obvious, because it is! But realistically, we need to rely on these common practices sometimes because it is simply not possible to make it through your work day questioning every single common practice, doing a lit search, and essentially creating a gray matters episode, you would never make it through the day.

Dr. Jason Freed: Yeah, you’re definitely right about that! So, then I guess the question is how and when should we be doing this, because like you said, maybe there are lots of things like this?

Dr. Ali Trainor: Yeah, I don’t know if I’ve fully honed my radar for this but I think I am much more likely to question something that is invasive, or time consuming, or when something isn’t having the result I’m expecting. Like, I was never able to lower the INR of a patient with cirrhosis by giving FFP prior to a procedure.

Dr. Jason Freed: Yeah, I like those points! And I think there’s also a risk benefit analysis on the opportunity cost of time.  

Dr. Ali Trainor: Yeah, do you have an example of what you mean by that? 

Dr. Jason Freed: Yeah, the one that first comes to mind for me is people taking vitamin C with their iron for iron deficiency. There was a time when that was so commonly done, and I think a lot of people might still be doing it or recommending it. Now, there has since been a randomized controlled trial and we now know it doesn’t help with iron absorption, but honestly, if people are taking a little extra vitamin C, it’s really no big deal. So, thinking of risk benefit for how you spend your time I probably wouldn’t have spent a lot of time looking into Vitamin C because the likelihood of harm in either direction is pretty low.

Dr. Ali Trainor: I think that’s great advice, so in general, I guess, it might be a good idea to look into something if there is a higher likelihood of harm and if the risk of harm is low, maybe save that for a rainy day.

Dr. Jason Freed: Alright, should we recap?

Dr. Ali Trainor: Alright, In deep dive 1, we talked about how in the hands of someone who routinely does these procedures, both paracentesis and thoracentesis have low bleeding risk at a broad range of INR and platelet values as long as you take measures to avoid hitting major blood vessels.

Dr. Jason Freed: In deep dive 2, we learned that giving FFP will not reduce the bleeding risk of a patient with cirrhosis. 

Dr. Ali Trainor: In deep dive 3, we discussed that giving FFP contains risks – TRALI, TACO, and other transfusion reactions, and particularly in patients with cirrhosis, giving blood products raises the portal pressure, so should always be given with caution and a clear indication.

Dr. Jason Freed: In deep dive 4, we challenged the dogma that indwelling pleural catheters should never be placed in patients with cirrhosis. While there is an infection risk, pleural catheters are sometimes appropriate in carefully selected patients who are diuretic refractory, not a TIPS candidate, and requiring frequent thoracentesis.

Dr. Ali Trainor: And that is a wrap for today! But we also love going through other cases so if you have a case that you want to bring to Gray Matters, please let us know! If you found this episode helpful, please share with your team and colleagues and give it a rating on Apple podcasts or whatever podcast app you use! It really does help people find us! 

Dr. Jason Freed: If you have a case you’d like to bring on air, please email us at hello@coreimpodcast.com. Opinions expressed are our own and do not represent the opinions of any affiliated institutions.