WEBVTT 00:00.031 --> 00:04.619 [SPEAKER_01]: Welcome to the core M5 Pearls podcast, bringing you high-yield evidence-based Pearls. 00:04.639 --> 00:06.582 [SPEAKER_01]: I'm Dr. Schreit, you're ready, and I'm joined by. 00:06.602 --> 00:12.532 [SPEAKER_04]: I am Dr. Noah Markowitz, a PGY3 internal medicine resident at Montefirre in the Bronx. 00:12.552 --> 00:17.199 [SPEAKER_04]: Today's episode is part two of our two-part series All About Hepatorenal Syndrome. 00:17.760 --> 00:23.029 [SPEAKER_01]: And if you haven't done already, go back and listen to the last episode on all things diagnosis. 00:23.810 --> 00:26.595 [SPEAKER_04]: Today's episode will be all things treatment. 00:27.031 --> 00:29.854 [SPEAKER_01]: And let's remind ourselves who our wonderful discussants are. 00:30.655 --> 00:31.776 [SPEAKER_00]: Hi, I'm Marina Sarpur. 00:32.276 --> 00:35.680 [SPEAKER_00]: I am a hepatologist at the University of Pennsylvania. 00:36.701 --> 00:38.542 [SPEAKER_03]: Hi, I am Juan Carval Feliz. 00:38.562 --> 00:42.366 [SPEAKER_03]: I am a nephrologist at Oxford Health in New Orleans. 00:43.367 --> 00:44.288 [SPEAKER_02]: My name is Nick Nizunder. 00:44.528 --> 00:47.291 [SPEAKER_02]: I'm a the trans-bi hepatologist here at University of Michigan. 00:48.312 --> 00:50.815 [SPEAKER_01]: And let's get into the five pearls we're going to be covering today. 00:51.215 --> 00:54.338 [SPEAKER_01]: Remember at the Mori-Tester Self, the deeper you're learning games. 00:58.182 --> 01:00.084 [SPEAKER_04]: Carl one, vasoconstrictors. 01:00.545 --> 01:04.811 [SPEAKER_01]: What are three vasoconstrictors that are used to treat hepatorenal syndrome? 01:08.836 --> 01:10.238 [SPEAKER_04]: Herald two, albumin. 01:10.498 --> 01:17.527 [SPEAKER_01]: What's the role of albumin in treating hepatorenal syndrome? 01:17.547 --> 01:19.670 [SPEAKER_04]: Herald three, volume management. 01:20.091 --> 01:24.156 [SPEAKER_01]: Is it safe to give diuretics in somebody who's in hepatorenal syndrome? 01:27.950 --> 01:29.613 [SPEAKER_04]: Rolfor, transplant. 01:29.973 --> 01:34.561 [SPEAKER_01]: How should we approach dialysis as well as transplant in a person with hepatoidal syndrome? 01:38.707 --> 01:40.410 [SPEAKER_04]: Rolfib, palliative care. 01:40.811 --> 01:44.777 [SPEAKER_01]: What are different options when it comes to palliative care in someone with HRS? 01:48.520 --> 01:56.010 [SPEAKER_04]: Okay, so the main goal for the treatment of HRS, big picture-wise, is to raise the mean arterial pressure or the map. 01:56.391 --> 01:58.574 [SPEAKER_04]: And this is done with vasoconstrictors. 01:59.275 --> 02:01.077 [SPEAKER_01]: Wait, Noah, I'm kind of confused. 02:01.297 --> 02:13.414 [SPEAKER_01]: We spent so much time in the last episode talking about the whole problem with Hepatomyel syndrome and too much renal visit instruction and now you're telling that treatment is to actually give vasoconstrictors something's not adding up here. 02:13.968 --> 02:22.306 [SPEAKER_03]: A question that I often get is, how is on earth is a vasoconstrictor fixing a vasocontrictive pathogenesis? 02:22.686 --> 02:27.176 [SPEAKER_03]: Well, because one's your restore systemic of the ultimate pressure. 02:27.577 --> 02:31.685 [SPEAKER_03]: Number one, that is going to override the renal perfusion pressure. 02:31.966 --> 02:32.567 [SPEAKER_03]: And number two, 02:32.547 --> 02:38.373 [SPEAKER_03]: You're resetting what is actually costs and the local vissroom of friction in the kidneys on the first place. 02:38.553 --> 02:46.241 [SPEAKER_03]: That's why the renal profusion actually improves and they are experimental and translational of data showing that that's the case. 02:47.703 --> 03:01.677 [SPEAKER_01]: Okay, so getting vissoconstructors gets the bearer receptors, gets the kidneys to once again sense that good pressure and volume, and the thought is that this reverses the cascade that actually led up to that vissoconstriction in the first place. 03:02.332 --> 03:03.694 [SPEAKER_04]: That's exactly right, Traia. 03:03.934 --> 03:09.161 [SPEAKER_04]: And we actually have some evidence to help us with what we should aim for in terms of how much to raise that map. 03:09.522 --> 03:19.215 [SPEAKER_04]: A 2023 study that Dr. Velas actually took part in, used 77 HRS patients and divided them into three groups based on how much the map was raised with vasoconstrictors. 03:19.536 --> 03:24.883 [SPEAKER_04]: The lowest group was five to 10, the middle group was 10 to 14, and the highest group was greater than 15. 03:25.264 --> 03:30.010 [SPEAKER_04]: And what was found is that in the group with greater than 15, raise and map, they actually did the best. 03:30.800 --> 03:45.297 [SPEAKER_01]: Just to say that loud because I know he's in so much time in the last episode, really differentiate between who had a renal over his ATM and pre-renal, just to say that loud, based of construction is really the treatment when he comes to hepata renal syndrome, the idea is to restore that map, or reset he mutiniam mix. 03:45.317 --> 03:57.010 [SPEAKER_01]: Let's say your game dealing with pre-renal, AKEI, that treatment is really a volume expansion without a human, for example, no need for visa constructors, similarly ATM, treatment supportive care, 03:57.682 --> 04:03.749 [SPEAKER_04]: With that understanding, let's talk through the three treatment options we have to raise that map and try and reverse HRS. 04:05.110 --> 04:08.634 [SPEAKER_00]: So, Charlie Preston is a vasopressant agonist. 04:08.955 --> 04:11.037 [SPEAKER_00]: It acts on the V1 receptors. 04:11.317 --> 04:14.020 [SPEAKER_00]: It causes planknic vasoconstriction. 04:14.421 --> 04:20.668 [SPEAKER_00]: It was approved in the United States in 2022, but has been used in Europe for many, many years. 04:20.648 --> 04:25.580 [SPEAKER_00]: So, the pivotal data in the United States for Charlie Preston comes from the confirmed trial. 04:25.901 --> 04:38.472 [SPEAKER_00]: So, in the confirmed trial, among patients with HRSAKI, 32% of patients who received Charlie Preston plus albumin had HRS reversal versus 17% with albumin alone. 04:38.452 --> 04:51.650 [SPEAKER_00]: and they were less likely to require renal replacement therapy at 30 days or have recurrence of HLS-AKI, but they had a lot more respiratory events, and there had never been demonstration that 90-day outcomes have improved. 04:52.751 --> 05:01.303 [SPEAKER_04]: So the confirmed trial not only showed that turtle press and raises the map, but put turtle press in on the map as one of our best agents for HRS. 05:01.385 --> 05:03.970 [SPEAKER_01]: I see what you did there with the map pun. 05:04.030 --> 05:05.633 [SPEAKER_01]: Yeah, putting trailer person on the map. 05:05.754 --> 05:06.515 [SPEAKER_01]: Nice, nice. 05:06.776 --> 05:07.176 [SPEAKER_04]: Thank you. 05:07.256 --> 05:07.657 [SPEAKER_04]: Thank you. 05:08.238 --> 05:19.360 [SPEAKER_04]: With this trial, we saw less need for dialysis and reversal of HRS in 32% of patients who got trailer press and plus albumin, versus only 17% of patients with albumin alone. 05:20.268 --> 05:32.279 [SPEAKER_00]: The main side effects of Torlipressin are diarrhea, volume overload, cardiovascular schemium, less common side effect is limb-ish schemium, which I have seen clinically. 05:32.620 --> 05:36.370 [SPEAKER_00]: It's a splegnik vasoconstrictor, so it shunts blood from this... 05:36.350 --> 05:40.878 [SPEAKER_00]: Blank-naked basculature to the central circulation, so increases your preload. 05:41.218 --> 05:46.428 [SPEAKER_00]: And then it also increases your SVR, systemic breath versus this, so increases your afterload. 05:46.708 --> 05:52.037 [SPEAKER_00]: And then Albumin adds to that too, because it increases your plasma uncotted pressure. 05:52.478 --> 05:59.370 [SPEAKER_00]: So patients who are already volume overloaded are almost volume overloaded, or have corduaries, schemia, 05:59.350 --> 06:03.996 [SPEAKER_00]: They're at significant potential risk of compromise and side effects of trail aggressive. 06:04.016 --> 06:07.133 [SPEAKER_00]: So I think understanding the physiology is really helpful. 06:07.973 --> 06:12.600 [SPEAKER_04]: So what type of a skinia is actually enough for someone to think about holding off on Terlipressin? 06:12.960 --> 06:21.452 [SPEAKER_04]: One of our peer reviewers, Dr. Belcher, told us his practice, is anyone with active coronary artery disease or untreated a skinia should avoid Terlipressin? 06:21.833 --> 06:27.360 [SPEAKER_04]: But if they have CAD that was stented in the past and they're doing okay, it's probably fine to give Terlipressin. 06:27.761 --> 06:36.293 [SPEAKER_04]: But what's really important to keep in mind is these patients have such a high, very short term mortality that you might just take the risk anyway. 06:37.201 --> 06:58.450 [SPEAKER_00]: And then another pearl is creatinine greater than five melts or greater than or equal to 35 so really high melt scores or great 3 ACLF that's essentially multiple organ failures you don't really get a lot of bang for your buck with early breast and it's kind of too late in that scenario so we don't usually start that that's associated with higher mortality. 06:59.628 --> 07:12.756 [SPEAKER_01]: Okay, so no trail of press in if the kidney disease really bad, the crannies over five or with the liver failure, if it's grade three acute on chronic liver failure, aka it's person just has a really high melt trail of press in Sanago. 07:13.838 --> 07:17.907 [SPEAKER_04]: Okay, thanks for summarizing trail of press in for us next up is nor up enough room. 07:18.950 --> 07:21.836 [SPEAKER_00]: So, nor up in effort and tried and true vasopress are right. 07:21.876 --> 07:28.149 [SPEAKER_00]: We use in the ICU all the time, very potent, has good evidence, decent evidence, I would say, in HRS. 07:28.550 --> 07:35.845 [SPEAKER_00]: So, the mechanism, it is alpha1 agonist, causing vasopinstruction, beta1 agonist, causing increased cardiac output. 07:36.753 --> 07:44.202 [SPEAKER_01]: So neuropy is an infusion typically requires an ICU transfer, which can be difficult depending on how comfortable nurses and the floors are. 07:44.242 --> 07:51.271 [SPEAKER_01]: And so it kind of needs to be think like the decision-aching trail across San versus neuropy for this patient really comes down to where our patient physically is. 07:52.453 --> 07:56.618 [SPEAKER_04]: Finally, let's talk about our last phase of constrictor mid-Adr and octreotide. 07:57.678 --> 08:07.955 [SPEAKER_00]: So midadrin, selective alpha one agonist, and then actually a tied inhibits the release of leukogon and helps also with the splank neck vasodilation. 08:08.055 --> 08:14.605 [SPEAKER_00]: And actually after I've dug into the literature, we really, especially now, we I think we use it to make ourselves feel better. 08:14.705 --> 08:21.897 [SPEAKER_00]: And it does increase your map, so you can increase your map with midadrin, but it's just not as potent of a vasoconstrictor cocktail. 08:21.877 --> 08:32.751 [SPEAKER_00]: And definitely, enough studies have been done with Charlotte Preston versus M-A-O mid-a-drenacterial type albumin, and Charlotte Preston is much more potent. 08:32.771 --> 08:37.097 [SPEAKER_01]: So it sounds like we should try to reach for Charlotte Preston in terms of potency, at least with the evidence that we have. 08:37.197 --> 08:40.361 [SPEAKER_01]: But say our patient might have a contrary indication to Charlotte Preston. 08:40.461 --> 08:43.345 [SPEAKER_01]: We could reach for the mid-a-dren 08:43.443 --> 08:53.814 [SPEAKER_04]: A more controversial point would be if you're hedging and not entirely sure about the diagnosis of HRS, it's probably safer to start with mid-a-drunk to your tides since it has less side effects. 08:54.555 --> 08:54.995 [SPEAKER_01]: That's fair. 08:55.095 --> 08:56.097 [SPEAKER_01]: That's very an important point. 08:56.737 --> 09:01.743 [SPEAKER_01]: Okay, so let's summarize Pearl 1 on Bezou constructive treatment for Hepatorenal syndrome. 09:02.143 --> 09:13.315 [SPEAKER_01]: The goal here is to raise that map by 10 to 15 millimeters per mercury, and know why don't you summarize a different Bezou constructor as maybe in reverse order or 09:13.717 --> 09:14.619 [SPEAKER_04]: The entry-a. 09:14.920 --> 09:19.190 [SPEAKER_04]: So, mid-dren octreated tide is the least effective, but has the least side effects. 09:19.491 --> 09:22.478 [SPEAKER_04]: So, if you aren't entirely sure if it's HRS, you can start here. 09:22.518 --> 09:27.149 [SPEAKER_04]: If you're seeing a rise in the map with mid-dren octreated alone, you should continue it. 09:27.450 --> 09:31.540 [SPEAKER_04]: But if you're worried that it's not working, then you have to think about escalating. 09:31.520 --> 09:38.314 [SPEAKER_01]: And if you're in the position of escalating, that might be terlopressin or nor up an effort in depending on where your patient physically is. 09:38.935 --> 09:50.980 [SPEAKER_01]: And then some nuances about terlopressin, it was really the confirmed trial that put terlopressin on the map to borrow your fund with more reversal of her battery loss syndrome and less need for dials as compared to Albumin. 09:50.960 --> 10:06.032 [SPEAKER_01]: The counter-indications, though, to trouble a lesson, to be aware of is if a creatine is over 5, if they have acute liver failure, great 3 signs of overload that would risk respiratory compromise or any signs of active ischemia. 10:09.691 --> 10:14.141 [SPEAKER_01]: Okay, I think I have a good handle on the three different phasoconstrictors that we have. 10:14.321 --> 10:16.606 [SPEAKER_01]: What about albumin and have outer renal syndrome? 10:16.646 --> 10:21.777 [SPEAKER_01]: I think sometimes I see albumin given with one of these three basic constructors sometimes we don't. 10:22.853 --> 10:34.267 [SPEAKER_02]: early in give album into a cheap you believe me at day one or two or have a many days you think and that if there's some other reason to use album I will like beginning a person thesis or we think that that's B.P. 10:34.547 --> 10:41.455 [SPEAKER_02]: Now I'm going to go with that novel protocol, unless there's some underindication as far as the respiratory volume status, but it's otherwise I don't. 10:41.476 --> 10:43.138 [SPEAKER_02]: And in fact, did you look at confirmed trials? 10:43.158 --> 10:50.987 [SPEAKER_02]: I was one of the big criticisms was that they kept giving patients album an over and over again and that may have contributed to some of the respiratory failure outcomes as well. 10:51.642 --> 11:01.738 [SPEAKER_04]: In the confirmed trial, 14% of patients in the Turlopressin Plus albumin group had respiratory failure versus 5% in the albumin only group. 11:01.758 --> 11:07.187 [SPEAKER_01]: That is wild to think that in terms of the amount of respiratory failure with a combo Turlopressin Plus albumin. 11:07.859 --> 11:16.813 [SPEAKER_04]: Yeah, and what's even more wild is 17 patients in the Turlopresson group died of respiratory failure versus only one in the albumin alone group. 11:16.833 --> 11:31.555 [SPEAKER_04]: Wow, I think what really came up in a lot of journal clouds after this trial was was it just the Turlopresson that was the problem or was it that they were continuing to give albumin with the Turlopresson and that was what really pushed patients over the edge in terms of their 11:31.636 --> 11:33.680 [SPEAKER_01]: Yeah, yeah, looking at the protocol, right? 11:33.740 --> 11:46.185 [SPEAKER_01]: They, it's like a kind of a loose requirement they could give Albu Bin on day one, one gram per gig to maximum of 100 grams and then 20 to 40 grams a day thereafter and not kind of defining an end point. 11:46.722 --> 11:56.015 [SPEAKER_04]: I think it's really important to say that technically all the trials and guidelines would recommend vasoconstrictor plus albumin, but the conversations becoming a lot more nuanced. 11:56.276 --> 12:01.383 [SPEAKER_04]: We saw that using Tarlopressin plus albumin literally killed people through respiratory distress. 12:01.724 --> 12:05.389 [SPEAKER_04]: So we need to be careful and not just blindly give every patient albumin. 12:06.179 --> 12:07.281 [SPEAKER_01]: Yeah, yeah, I appreciate that a lot. 12:07.301 --> 12:09.584 [SPEAKER_01]: And it sounds like different people will have different practices. 12:09.624 --> 12:16.735 [SPEAKER_01]: But for Dr. Mazumdur, his practice is to not always give albumin and really only give it to get that patient to a uvalemia. 12:16.875 --> 12:21.943 [SPEAKER_01]: And then in terms of how much albumin to reach uvalemia, again, different practice patterns. 12:22.023 --> 12:27.371 [SPEAKER_01]: But for some, it's one gram per keg, her day up to that 100 grams a day. 12:27.632 --> 12:32.980 [SPEAKER_01]: All right, Noah, why don't you summarize what you want people to take away when it comes to giving albumin in HRS? 12:33.500 --> 12:35.849 [SPEAKER_04]: It's a small, but really important takeaway. 12:36.170 --> 12:41.670 [SPEAKER_04]: In HRS, we should really just give Albumin to get our patients to Uvalinia and then stop. 12:45.397 --> 13:06.882 [SPEAKER_01]: All right, now with all that album and talk, I think we're ready for the next level, which is the volume management and gosh, this is, you know, the stuff that we are humming and hauling about on rounds and the stakes are high and at the same time the answer isn't always clear cut and I really appreciate having a space to discuss and to bring about what their practices are in some of their roles with them. 13:07.385 --> 13:10.035 [SPEAKER_04]: We just talked about the risk of respiratory compromise. 13:10.075 --> 13:17.682 [SPEAKER_04]: So the first thing I really wanted to hear from our discussions was if and how they give LASICs for HR as patients that are grossly volume overloaded. 13:18.978 --> 13:21.961 [SPEAKER_03]: many despisions arrive hypervolimic. 13:22.442 --> 13:27.327 [SPEAKER_03]: If you give him diuretics before the vesoconstrict, some tatherics just don't work. 13:27.488 --> 13:27.808 [SPEAKER_03]: Why? 13:27.848 --> 13:32.113 [SPEAKER_03]: Because, you know, remember that no BP, no BP, right? 13:32.153 --> 13:36.418 [SPEAKER_03]: If you don't have good hemodynamics, your diuretics are not going to kick in. 13:36.798 --> 13:44.547 [SPEAKER_03]: So when you restore the hemodynamics, not only your treat in nature as, you are going to enable successful diureases. 13:44.527 --> 13:47.452 [SPEAKER_03]: But of course, there was this concern, wait a second. 13:47.492 --> 13:50.798 [SPEAKER_03]: You give that right as you're going to throw the patient back into HRS. 13:51.399 --> 13:56.589 [SPEAKER_03]: So what we decided to do is to look at those patients, what was the observation? 13:56.649 --> 14:04.543 [SPEAKER_03]: We have about 20 plus patients in this cohort, very small cohort, of course, but it was a very specific observation that we were targeting. 14:04.523 --> 14:10.991 [SPEAKER_03]: And first of all, additional of intravenous ferrocymite high doses, like 160 Q12, something like that. 14:11.271 --> 14:19.922 [SPEAKER_03]: Two Nourpin F-ring led to a substantial rise in urinal putt from somewhere between 800 mls a day, all the way to over 2 liters a day. 14:19.962 --> 14:22.606 [SPEAKER_03]: So it worked in terms of a diabetic effect. 14:22.786 --> 14:23.106 [SPEAKER_03]: Fine. 14:23.647 --> 14:26.811 [SPEAKER_03]: The next step is what happened with the trajectory of the creatinine. 14:27.051 --> 14:27.612 [SPEAKER_03]: Well, 14:27.592 --> 14:36.865 [SPEAKER_03]: The trajectory of creatinine remains unchanged, in our words, whatever was happening with the creatinine prior to the diuretic, continue to happen with the diuretic. 14:37.265 --> 14:49.482 [SPEAKER_03]: So we're not claiming the diuretic's improved kidney function helped the recovery, nothing of the nature, but will we observe is that the diuretic's did not have a negative impact in the course of A.K.A. 14:49.462 --> 14:51.805 [SPEAKER_03]: though it doesn't put you back into HRS. 14:52.026 --> 14:53.288 [SPEAKER_03]: That's kind of the observation. 14:53.308 --> 15:01.900 [SPEAKER_03]: So I think we have to move a little bit away from this album end, album end approach, and then we start thinking to a more balanced word. 15:02.241 --> 15:05.305 [SPEAKER_03]: Yes, some patients should be treated with album end aggressively. 15:05.706 --> 15:09.251 [SPEAKER_03]: Some patients don't need any of the album end, nothing at all. 15:09.672 --> 15:11.875 [SPEAKER_03]: And some patients may actually need to be diaries. 15:13.070 --> 15:15.074 [SPEAKER_01]: Okay, wow, so much to unpack there. 15:15.094 --> 15:18.099 [SPEAKER_01]: I really appreciate hearing all the nuance. 15:18.119 --> 15:26.455 [SPEAKER_01]: And I think, you know, if I step back, when it comes to have had a renal center, we need to really undergy on the patient in front of us and figure out two big questions. 15:26.775 --> 15:32.646 [SPEAKER_01]: One, what are we giving in terms of raising that map up to, you know, 10 to 15 milligrams from mercury? 15:32.666 --> 15:36.934 [SPEAKER_01]: And then is album right or is diaries right or neither? 15:37.690 --> 15:40.599 [SPEAKER_04]: classic fodder to come up every time on rounds, right? 15:40.981 --> 15:49.287 [SPEAKER_04]: And I just felt really relieved to know that once you have successfully raised that map, there is evidence it's safe to give diuretics if the patient needs it. 15:49.992 --> 16:00.484 [SPEAKER_01]: Yeah, and it was also helpful to hear that if you give directs to early, it's not like it'll cause harm, but that kidney just won't have that blood pressure just successfully make urine. 16:00.624 --> 16:07.692 [SPEAKER_01]: And so try and get that blood pressure up first, or the cool kids are the nephrologists say get the BP up before he can get some PPE. 16:08.573 --> 16:11.136 [SPEAKER_04]: I'm glad somebody thanks the nephrologist or the cool kids. 16:11.337 --> 16:12.658 [SPEAKER_01]: Yeah, they're awesome. 16:14.090 --> 16:22.091 [SPEAKER_02]: I think the most common hesitancy which is real is the creatine number, but it's not as important as the patient's status. 16:22.411 --> 16:30.833 [SPEAKER_02]: And so, the physical exam and volume exam, I think is one of the most important things the district which is an internal medicine doctor from other physicians and medical providers. 16:30.813 --> 16:38.885 [SPEAKER_02]: And I think that treating patients as you alluded to based on bioreasing them if they're buying overloaded or providing fluids that they're not sure otherwise. 16:39.105 --> 16:42.831 [SPEAKER_02]: I think is one of the most counterintuitive parts when the creatinine is rising. 16:43.272 --> 16:50.863 [SPEAKER_02]: And I wouldn't jump to diariesis unless the patient really needed it, but I wouldn't hold it the patient didn't need it because the creatinine resolves it. 16:50.843 --> 17:01.516 [SPEAKER_02]: And so we see this often in the outpatient or a German high area where we start them on some dioretics, and their creatinine goes up by like 0.2 or 0.3 or something, but their sighties is totally anchored, so they're not requiring cares and cases. 17:01.876 --> 17:18.336 [SPEAKER_02]: But if you're crimping down on the kidneys a bit and the creatinine's going up, and it's benefiting the patient from a clinical perspective, I think that's the one of the biggest things that I've learned in fellowship and going into being an attendant is like that 0.2.3 of creatinine might be worth it if it's providing some 17:18.316 --> 17:20.380 [SPEAKER_02]: And so it may not be worth it. 17:20.400 --> 17:21.201 [SPEAKER_02]: They're still getting groceries. 17:21.221 --> 17:23.586 [SPEAKER_02]: Teases are really weak and they're not really changing anything. 17:23.746 --> 17:28.856 [SPEAKER_02]: But in those patients, you can kind of move the needle on all your wife or their bad things that are happening to them. 17:29.016 --> 17:35.548 [SPEAKER_02]: I think that's one of the most common areas in which I help is I am comfortable just saying, no, we're just going to keep on dioretics. 17:36.811 --> 17:42.302 [SPEAKER_01]: So, this is also given me flashbacks to our car to real syndrome, where we're really kind of sitting with the idea. 17:42.342 --> 17:47.092 [SPEAKER_01]: It's okay to have some permissive hypercranemia if the patient is clearly improving. 17:47.513 --> 17:57.874 [SPEAKER_01]: No, no, do you want to get a stab, or try to recap the hard and nuanced volume management of a pattern real syndrome, which, to be fair, is way more nuanced and very case-by-case. 17:58.512 --> 18:00.614 [SPEAKER_04]: I will take a stab at it and try my best, Raya. 18:00.954 --> 18:02.996 [SPEAKER_04]: The first thing to do is raise the map. 18:03.376 --> 18:06.239 [SPEAKER_04]: You aren't gonna get good diariesis without blood pressure. 18:06.679 --> 18:14.706 [SPEAKER_04]: Once you've successfully raised the map, we do have some data to say that we will not put the kidneys back into HRS with diariesis. 18:14.726 --> 18:21.111 [SPEAKER_04]: We might have to be okay with some permissive hypercreatin' anemia and prioritize clinical volume status if the patient needs it. 18:21.391 --> 18:28.097 [SPEAKER_04]: But as we've been saying, this is really hard and nuance and all we can do is do our best with what we think the patient's volume status is. 18:31.469 --> 18:38.500 [SPEAKER_01]: So we talked all about treatment, now let's get into when we're getting this treatment, what things aren't going well. 18:38.820 --> 18:47.213 [SPEAKER_01]: I think this brings up the most important point in why people, and they see the paterials syndrome in their one-liner kind of get ugh, is that it has such a high mortality rate. 18:47.533 --> 18:50.878 [SPEAKER_01]: Why is that mortality rate in a paterials syndrome so high? 18:51.938 --> 18:56.206 [SPEAKER_00]: Why is mortality so high in HRs that was a great, I actually really love that question. 18:56.367 --> 19:02.599 [SPEAKER_00]: So because we have the portal hypertension physiology, so we know we have a very hard liver for the most part. 19:03.040 --> 19:09.913 [SPEAKER_00]: We have portal hypertension, and that comes with all of this bacterial translocation predisposition to infections. 19:09.893 --> 19:20.084 [SPEAKER_00]: And so, so that's one part of it is that your liver portal hypertension plus synthetic dysfunction, plus the other thing is what triggers HRS is like the company it keeps so to speak. 19:20.385 --> 19:25.891 [SPEAKER_00]: So, sepsis, organ failure, severe bleeding, so that's why the mortality is high. 19:27.312 --> 19:36.863 [SPEAKER_01]: Alright, let's continue with the dark side of things and what if the vasoconstrictors that we 19:37.231 --> 19:47.164 [SPEAKER_04]: So we tried to prevent renal failure in HRS, but the creatinine still rising, the tassium's up to six, despite the tassium binders, the patient's not peed in two days. 19:47.544 --> 19:51.630 [SPEAKER_04]: The next question to ask yourself is, is this patient a liver transplant candidate? 19:52.110 --> 19:57.417 [SPEAKER_04]: The reason we have to ask ourselves that is, because we have reached AEIOU indications for dialysis. 19:57.838 --> 20:02.884 [SPEAKER_04]: And now we have to think to ourselves, can we use dialysis as a bridge to liver transplant? 20:03.556 --> 20:12.896 [SPEAKER_01]: Uh, okay, so I guess that makes sense and to connect it back to episode one, you know, we learned that most patients in her pattern wheels syndrome, their kidneys are actually fine. 20:13.137 --> 20:15.362 [SPEAKER_01]: So dialysis here is just temporary, right? 20:15.642 --> 20:23.860 [SPEAKER_01]: Once that patient gets a liver and has return of good blood flow to their kidney, the kidney will get back up and just do its thing like the olden days. 20:24.548 --> 20:27.175 [SPEAKER_04]: The question is, how do we know who gets the liver, though? 20:27.496 --> 20:33.212 [SPEAKER_04]: I think the ethics of liver transplant have always fascinated me, but that's probably a whole other episode for itself. 20:33.513 --> 20:39.148 [SPEAKER_04]: So for us to remember right now, it is the meld score that determines a liver transplant priority. 20:40.293 --> 20:58.792 [SPEAKER_00]: So the new meld scores the meld 3.0, which is your total Billy Rubin, your INR, your creatinine, sodium, and now albumin and also sex, because women were disadvantaged, because women have lower muscle mass, they have lower creatinine for GFR, and there were some other issues. 20:59.233 --> 21:00.636 [SPEAKER_00]: So that's the meld 3.0. 21:00.836 --> 21:01.137 [SPEAKER_00]: So. 21:01.117 --> 21:13.228 [SPEAKER_00]: creatinine has a pretty hefty weight in the melt 3.0 and the melts score to remind everyone, prioritizes people on the liver for the liver transplant weight list based on likelihood of mortality. 21:13.328 --> 21:15.190 [SPEAKER_00]: So it's urgency-based prioritization. 21:15.290 --> 21:21.156 [SPEAKER_00]: So the worse your AKI, the higher your creatinine, the higher your liver transplant priority. 21:21.296 --> 21:23.238 [SPEAKER_00]: And that's because your mortality is high. 21:23.498 --> 21:28.002 [SPEAKER_00]: But there's a paradox here that if we get your kidney function better, your melt score, 21:27.982 --> 21:33.708 [SPEAKER_00]: will improve, and then you were very ill at one point, but you've lost your melt points, right? 21:34.088 --> 21:42.037 [SPEAKER_00]: So this is a little bit nuanced, but in the United States, if you're melt scores above 25, you have to update that melt score every seven days. 21:42.117 --> 21:54.310 [SPEAKER_00]: So if you imagine someone comes in at an AKI, create an NF3, and then they're on truly present, and then they improve, and a week later, their creatiners 1.5, their melt score went down, and their priority is lower. 21:54.290 --> 22:00.138 [SPEAKER_00]: Is it possible that some people with hold to early press and in this setting potentially when the meld is really high? 22:00.218 --> 22:04.444 [SPEAKER_00]: Because you know that the most durable treatment for this patient is actually transplant. 22:06.207 --> 22:10.052 [SPEAKER_04]: Just as I was saying, the ethics of alert of transplant are a thing in its own. 22:10.373 --> 22:13.197 [SPEAKER_04]: It gets complicated so fast. 22:13.217 --> 22:24.212 [SPEAKER_01]: Yeah, and it makes me think if the creatine is part of the meld score, Sarah patient gets dialysis as a temporary bridge won't 22:25.559 --> 22:28.784 [SPEAKER_00]: So if you're on dialysis, it's as if your creatinine is three. 22:29.025 --> 22:29.926 [SPEAKER_00]: It's the same thing. 22:30.287 --> 22:33.933 [SPEAKER_00]: So you get the biggest benefit for kidney injury if you're on dialysis. 22:34.273 --> 22:41.826 [SPEAKER_00]: And even if you have extremely low muscle mass and your creatinine is only 1.5 or 2, you're still going to get the maximum points if you're on dialysis. 22:43.469 --> 22:47.575 [SPEAKER_01]: Okay, so dialysis will give our patient the most amount of points when it comes to creatinine. 22:47.595 --> 22:48.597 [SPEAKER_01]: So we're okay there. 22:49.522 --> 22:56.139 [SPEAKER_04]: I just think transplants are so cool and what's even cooler is we have the ability to replace two organs at the same time. 22:56.179 --> 22:59.468 [SPEAKER_01]: Two organs, you mean the liver and the kidney? 22:59.748 --> 23:06.265 [SPEAKER_01]: No, while we need the kidney, we just spent a bunch of time talking about how the kidneys are fine at a renal syndrome. 23:06.734 --> 23:13.063 [SPEAKER_04]: Most of the time they are, but the longer HRS goes on, the more likely it is that the kidneys won't recover. 23:13.544 --> 23:18.271 [SPEAKER_04]: It's also important to think about patients who start it off with some baseline chronic kidney disease. 23:18.592 --> 23:21.135 [SPEAKER_04]: Those scarred kidneys probably won't recover. 23:21.516 --> 23:26.363 [SPEAKER_04]: You can refer to our show notes for the full criteria of when to do a simultaneous kidney liver transplant. 23:26.782 --> 23:27.943 [SPEAKER_01]: Yeah, interesting. 23:28.023 --> 23:31.447 [SPEAKER_01]: What if our patient gets called that they have a liver available to them? 23:31.807 --> 23:36.672 [SPEAKER_01]: And they go through the liver transplant, and the kidney doesn't recover as we expect it to. 23:37.633 --> 23:43.679 [SPEAKER_04]: So what's really nice is for patients that aren't initially simultaneous liver kidney transplants, there's something called the safety net. 23:44.019 --> 23:51.507 [SPEAKER_04]: The safety net moves the patient who only got a liver to the top of the kidney transplant list if their kidney doesn't wake up after the liver transplant surgery. 23:52.367 --> 23:53.008 [SPEAKER_01]: Oh, man. 23:52.988 --> 23:54.369 [SPEAKER_01]: I'm glad they have these in place. 23:54.570 --> 24:08.844 [SPEAKER_01]: I think there's so much nuances to go into, but I guess why don't we pause and recap some of the more salient points and I think for me, what I'm understanding now is that liver transplant, we base it off the meld, which is very heavily dependent on how the kidney is doing. 24:08.884 --> 24:19.695 [SPEAKER_01]: And I think the big learning for me was that dialysis is just a bridge to liver transplant in the criteria for that is the same for any new dialysis, right? 24:19.915 --> 24:19.975 [SPEAKER_01]: The 24:19.955 --> 24:25.088 [SPEAKER_01]: And because with most liver transplants, we expect the kidneys to recover just fine. 24:25.188 --> 24:30.522 [SPEAKER_01]: We don't jump to a simultaneous liver kidney transplant and prioritize the liver transplant first. 24:34.163 --> 24:37.029 [SPEAKER_01]: All right, now let's get into the real dark side of things. 24:37.510 --> 24:40.656 [SPEAKER_01]: Say our patient is not a liver transplant candidate. 24:40.836 --> 24:44.884 [SPEAKER_01]: Say for example, they have some type of active cancer that is outside the liver. 24:44.924 --> 24:55.665 [SPEAKER_01]: Or I think the real sad situation is that when if this patient doesn't have the social support, they need to come to appointments or get labs with the immunosuppressants they would be on after a transplant. 24:56.540 --> 24:59.064 [SPEAKER_00]: That's when we have to think about goals of care discussions. 24:59.324 --> 25:10.381 [SPEAKER_00]: If the patient is not on a liver transplant list and they have rapid liprogress of renal injury that requires dialysis with no ability to reverse the underlying liver physiology. 25:10.421 --> 25:19.054 [SPEAKER_00]: This is where I strongly believe we should involve palliative care because we don't really have dialysis as a bridge to an improvement. 25:20.131 --> 25:21.934 [SPEAKER_04]: what an impossible situation. 25:21.994 --> 25:29.608 [SPEAKER_04]: Do we pursue dialysis for this patient knowing that there aren't any options to fix the liver and they're going to die even with dialysis? 25:30.590 --> 25:33.855 [SPEAKER_01]: Yeah, it just seems like dialysis here is such a temporary band aid, right? 25:34.036 --> 25:38.123 [SPEAKER_01]: I mean, for how long and to what quality of life are we bridging to? 25:39.284 --> 25:57.917 [SPEAKER_00]: And I do try to be frank, very frank from a liver standpoint and explain that this is what's going on with your liver, this is how we would treat the liver problem and transplant normal, you know, could be a way that we would treat this, but however in this scenario, we cannot do liver transplant for XYZ reason. 25:57.897 --> 26:08.166 [SPEAKER_00]: And then I explained, so in the case of, let's say, HRSAKI and other subsistly compensations and the need for dialysis, let's say. 26:08.186 --> 26:19.976 [SPEAKER_00]: I explained that putting them on dialysis will generally not improve the subsist will not resolve the liver dysfunction and so that's not something that will help them get to back to where they were. 26:20.117 --> 26:26.402 [SPEAKER_00]: So I think it's better to try to get on the same page, 26:26.382 --> 26:30.448 [SPEAKER_00]: and explain what medically is feasible versus not. 26:30.948 --> 26:37.157 [SPEAKER_00]: And I know that some people like the best case scenario was worst case scenario rubric, right? 26:37.557 --> 26:38.619 [SPEAKER_00]: That's case scenario. 26:38.899 --> 26:41.242 [SPEAKER_00]: Your infection gets treated and you get a liver transplant. 26:41.262 --> 26:44.106 [SPEAKER_00]: That works if somebody is could be a transplant candidate. 26:44.547 --> 26:48.172 [SPEAKER_00]: And worst case, you know, the liver gets worse and transplants not on the table. 26:48.232 --> 26:49.013 [SPEAKER_00]: That's useful. 26:49.494 --> 26:56.203 [SPEAKER_00]: But some people don't necessarily have a scenario where the best case is returning them to prior function. 26:56.183 --> 27:00.034 [SPEAKER_00]: So best case could be being symptom-free being with family. 27:00.074 --> 27:05.350 [SPEAKER_00]: So you really have to be honest and upfront and it's not always a menu of good options. 27:06.865 --> 27:13.998 [SPEAKER_03]: So if the patient is able to tolerate a session in the hospital and you can prepare for a clinic, then you don't have to explain. 27:14.058 --> 27:14.399 [SPEAKER_03]: Okay. 27:14.679 --> 27:18.065 [SPEAKER_03]: So the expectation is that we don't do dialysis. 27:18.466 --> 27:20.530 [SPEAKER_03]: Your survival may be days. 27:20.911 --> 27:21.752 [SPEAKER_03]: Just as an example. 27:22.153 --> 27:27.743 [SPEAKER_03]: But if we do dialysis, you survival will be three months, six months. 27:27.723 --> 27:31.326 [SPEAKER_03]: is not the we're going to gain a two year unlikely, right? 27:31.747 --> 27:33.308 [SPEAKER_03]: So you present out to the patient. 27:33.428 --> 27:42.857 [SPEAKER_03]: And sometimes that is a meaningful extension of their lives, because they need to go home, they need to get their family together, and they need to process that, right? 27:45.140 --> 27:48.363 [SPEAKER_01]: So heavy to hear, but also helpful, right? 27:48.403 --> 27:56.110 [SPEAKER_01]: Helpful to know that without a liver transplant and have had a renal syndrome, dialysis might only buy someone a few months, three to five months or so. 27:57.102 --> 28:01.006 [SPEAKER_04]: For me, I really loved that best case worst case framework. 28:01.446 --> 28:10.554 [SPEAKER_04]: Sometimes patients need to know that their best case, even with dialysis, may not involve being independent enough to say, take a walk in the park. 28:10.574 --> 28:19.622 [SPEAKER_04]: Even with dialysis, some patients' best case may be just getting medicine to control symptoms, while their with family as long as possible until they peacefully pass away. 28:20.904 --> 28:25.708 [SPEAKER_01]: Yeah, and unfortunately, it gets even trickier when patients can't tolerate that dialysis. 28:26.785 --> 28:49.806 [SPEAKER_02]: one of the tricky parts about offering everybody dialysis is that if they're very high potensive because they're kind of in-state for a high-performance patient often they won't tolerate dialysis you know for example though you put the catheter in your protection to the machine and the blood pressure will be too low for them to actually get dialysis so on paper they're on dialysis but physiologically or biochemically they're out really getting cleaned by machine or getting volume removed. 28:50.748 --> 29:09.837 [SPEAKER_01]: You know, when he said that I was like, wow, why do I think of that earlier that these patients might not be able to tolerate dialysis right, you know, we probably urgently like put in a dialysis catheter, hoping dialysis would help got them connected to these machines and low and behold, after all that they weren't able to tolerate it. 29:10.525 --> 29:12.889 [SPEAKER_04]: I agree Shreya, it is a very humbling thought. 29:13.230 --> 29:24.590 [SPEAKER_04]: So to recap, if liver transplant is not in the cards, unfortunately, the options are a few months of dialysis or just comfort care for a week or two if dialysis is not within their goals of cares. 29:25.031 --> 29:28.197 [SPEAKER_04]: I'm really sorry to end this podcast on such a depressing note. 29:28.177 --> 29:41.241 [SPEAKER_04]: But I think really good palliative care is extremely rewarding in itself, and it's really important to take ownership of this aspect of hepatorenal disease, but also take ownership of our patients and helping them transition to their death. 29:41.947 --> 29:57.827 [SPEAKER_01]: Yeah, I think a patorenal syndrome is not for the faint of heart, it was such a tough disease process, some mortality is so high and I think we did right now by spending this month's time on the dark side and hopefully this will help our patients sit through it if they should come to that crossroads. 29:58.648 --> 30:00.250 [SPEAKER_04]: And that is a wrap for today. 30:00.290 --> 30:09.642 [SPEAKER_01]: If you found this episode helpful, our ask is a new shirt with your team, your colleagues shirt with someone else because 30:09.622 --> 30:17.471 [SPEAKER_04]: Thank you to our reviewers, Dr. Tapper and Dr. Belcher, as always, opinions expressed our own and do not represent the opinions of any affiliate of institutions. 30:17.772 --> 30:19.277 [SPEAKER_04]: Thank you and take care.