Dr Fawad Khattak - ‘Hepatorenal Syndrome’

[00:00:00]hey everyone um hi there my name is fallout i'm one of the gastroenterology registrars and the presentation i'm doing today is on hepatorenal syndrome as i've been told to wait until 105. so i'll stop presenting in a minute it's 105.

[00:00:19]so um essentially battery not syndrome is a term that i commonly see in notes where people essentially label it on people who have renal disease and liver disease and so a lot of people who have liver disease coming in with an aki get labeled hepatorenal syndrome pretty early on quite commonly we see but the actual definition of fatty arena syndrome is a bit more complex than that essentially it's really a diagnosis of exclusion so what you want to do is identify a patient who has advanced liver disease who has no reversible or identifiable cause of renal failure before you label them as adrenal syndrome so essentially hepatorenal syndrome as a concept has existed for a very long period of time over the last few years there's been some changes in how we describe people with arthritis syndrome how they're labeled so in a lot of textbooks hepatorenal syndrome is commonly sort of categorized into hrs1 and hrs2 which i will show in the slide next uh so hrs1 in a textbook sense is the kind of hrs patients who we see being admitted to hospital the patients who have an insult um on the background of having liver sources presenting with a significant aki um obviously requiring quite invasive testing and interventions hrs2 are the kind of patients that we normally see in clinics so the patients who don't have an acute aki who slowly have declining renal functions commonly they'll have very difficult to treat ascites so those are the two kind of classical definitions of hrs hrs1 which is the ones that we see as in patients and shares too which is what we normally see in outpatient settings so the previous diagnosis of hrs it required quite a few criterias as we said before it has to be filled with established liver disease who have advanced liver failure so people having cirrhosis with ascites was the first criteria the second criteria was that the creatinine had to be above 133 and then all the other things you see listed in this presentation essentially trying to exclude identifiable causes before you label them as hrs so you had to make sure that they had no evidence of shock they were not hypovolemic all of these patients with liver sources are commonly on multiple different diuretics including spironolactone frucide a lot of other medications commonly nephrotoxic so you really want to identify patients with advanced liver disease make sure there's no identifiable reversible factors and then once you've done all of that that's when you start labeling them as hrs so this is the previous kind of classification you'd use to diagnose people with hrs1 so the new classification it's quite similar to the previous classification the main difference was that we recognized that we were labeling some people as hrs a bit too late so rather than waiting for the creation to be above 133 what they changed it really was you still had to have advanced liver disease so you still had to have cirrhosis for the societies but your actual cutoff for labeling people as hrs had changed from being above 133 for hrs1 to just having either an increase of 0.3 milligrams per deciliter which in on our system would be about 26 so a rise of crayon of above 26 within a 48-hour period or a 50 increase from whatever their baseline was before admission or the presence of a reduced urine up over a six-hour period so that's kind of the main change between the old classification of hrs type 1 and hrs aki which is essentially replaced that category all the other things are pretty much exactly the same you still had to have liver disease you still had to stop any offending medications still make sure they weren't hypovolemic give them arguments so the recommended dose of albumin is one gram per kilogram of body weight so uh just to give you guys an example 20 human albumin solution which is commonly the agent we'd use has a hundred mils um has 20 grams of albumin so if you had someone who's 60 kilograms you'd give them free loss of 20 house on a daily basis so very similar principles the one thing you'll notice that we commonly don't really do um i've worked in quite a lot of different liver centers we we really don't check urinary sodiums at all as a concept to be honest to kind of differentiate between tubular necrosis and hrs so if you look at the list about the protein and the blood one of the things is checking a fractional sodium excretion so essentially people with acute tubulin necrosis will have high urinary sodiums and people who have hrs will have low urinary surgeons that's kind of the one thing that we just don't really do that much of even uh as um on gastroenterology awards live awards i've seen uranus surgeons being quite underutilized so that's one thing i've noticed so as i said before a lot of this is very technical stuff to be honest um hr is one hrs2 but at least identifying what we mean by each of these terms is quite important so they can be appropriately managed a lot of people with liver sources come and come in under the iq take and there will be a period where sometimes over the weekend there won't be a gastroenterology doctor who can kind of identify who is hrsa aki and who so it is quite important to sort of understand these figures and if you look at the classification system hrs1 like i said is the impatient one that we need to be aware of being replaced by hr's aki and then you'll see the hr2 which was the slower progressive decline has also been subdivided so hr naki means non-acute kidney injury and that's been further subdivided into hr's akd and hr ckd so i will now go to admit these people and then this is how they subdivide it so hrca we've already gone through hr's akd and hr ckd all it really tries to distinguish is these are the patients who do not have an acute kidney jury and you're just trying to figure out whether it's someone who has kidney deterioration over the last three months but if you've been present for more than three months so he tries akd essentially your patients who have an egfr less than 60 seedling the outpatient clinics have no reversible identifiable cause of the aki and it's within that three month period so that's kind of the period where you could potentially have more interventions available to offer them which whoever is hrc kd are the patients who've had this going on for longer than three months duration mostly these patients are much more further along in the disease process so like i said with cirrhosis try not to label them as hrs at the front door consider them like any other aki patient so you still have to consider your diagnosis as if they weren't they did not have liver sources that's the first thing so obviously patients live stresses are in multiple different diuretics commonly they are commonly on a lot of other nephrotoxic medications they commonly get infections so there's a lot of different reasons why they could have an aki so if you look at this list essentially it's exactly the same as any other list apart from it that it differentiates between acute tubular necrosis and pre-renal aki um and renal causes more so through the front door make sure they're not hypovolemic stop any infra toxic medications a common questions that juniors ask me is what to do with your patient who has both peripheral edema and ascites and also has aki everyone always worries about giving them fluid and making that worse when they have quite a significant akai as well the general rule of thumb i tell people is obviously it's not ideal um people who have hrs have poor prognosis overall you have to pick and choose which one of those things is the most significant thing that you need to treat at that given time so the majority of patients with cirrhosis who present with aki it's actually the aqi which is the problem so i would almost always advise people to give argument and give fluid if even if your patient had large volume of heights and a lot of peripheral edema because we can always put an acidic drain in if you fill them up and the akai improves so i've had people who come in with large volumicities peripheral edema we still tell them to give fluids we accept that they will probably need an acidic drain as an inpatient um sometimes i've had people who have hrs we literally fill them up and then afterwards you put them on through somebody infusions it's it's it's not ideal obviously when we only have two conflicting dilemmas you just have to pick and choose which one of these is more important sometimes they can get even more complicated some of these patients have dilated cardiomyopathies because of the alcohol use and then they go into pulmonary edema dentist even more of a challenge to be honest i mean if you have someone who's got hrs and isn't primary edema that's probably time we should call palliative care but i mean it's not an easy thing but generally the rule of thumb is as long as they don't have pulmonary edema we always try and prioritize the akai part rather than uh worrying too much about ascites uh so just like like very similar to pretty much any other aki if you think the hybrid limit given fluid expansion that could be either crystalloids or five percent human albumin solution uh posteriorical is quite rare ex similar causes to any other archive obstructive europa feed the one thing we sometimes notice is that people with 10 societies can have a degree of compression where after you actually train them their kidney function improves uh akin acute tubulin across this like i'm doing this presentation but i'll be honest with you i really don't think that much about you tubular necrosis i've already told you guys that your sodiums aren't really a thing that we do that commonly um most guidelines do recommend doing it properly identifying who has acute tubal in the process who has a pre-rule okay who has hrs but um like i said that's probably one learning point for me specifically is to kind of work up more on that side of things so if you look at disclosure about how you'd go about treating these patients who present with hi it's pretty much like any other aka patient you first of all said the flu status are they hypovolemic hypovolemic uvolemic like i said keeping in mind the caveat that they can be intravascularly dry with ascites and with peripheral edema most of the time we would prioritize the aki rather than the fluid overload side of things so discontinued diuretics one important thing is that these patients commonly will present with hyponatremia obviously if you have a patient with a sodium less than 125 we would not continue spironolactone so it's it's a lot harder to manage than a lot of the avocados because hyponatremia commonly comes into the equation as well so you'd make sure the uv limit give them albumin as recommended also consider intrinsic causes um a lot of these patients on stuff like spironolactone can have renal tubular acidosis they can have a lot of different nephrotoxic medications so stop all of those uh get ultrasound abdomen and most of the time these patients should come in through the front door we'd want to reassess their liver anyway to see if they've developed hepatocellular carcinoma to see if they've got a portal vein from process so at the same time it's probably a good idea to look at the kidney to make sure there's no abstractive bureaucracy as well after 48 hours if you looked at those guidelines from earlier that's really when you reassess once you stop the nephrotoxics once you fill them back up if it's resolved and it's most likely a pre-renal aki or an aki secondary to the medications if it still persists that's when you label them it's hepatorenal syndrome um obviously this divides it into acute tubulino crystalline pathogen syndrome depending on the urinary sodium so if you have a higher nutrition it goes into the atm category where the obviously the management would not be the same as that of hepatorenal syndrome it will be mainly supportive management rather than going the landlines of the heart renal syndrome and with hepatorenal syndrome it's really two agents that we recommend so the first is we recommend albumin on a daily basis um minimum two three lots of 20 hass alongside a vasoconstrictor so the commonest one we use on water is totally present um there's a slight fuel size data which will tell you about the doses themselves so essentially once you started people on telepresence and albumin you'd have to check the use these on a daily basis monitor the urine functions on a daily basis and uh by this point obviously if you have someone on the wall who has advanced services and has hepatorenal syndrome it's always a poor prognostic marker so uh renal replacement therapy is an option that you guys should keep in the back of your mind but at this point most of these patients do have a very very very poor prognosis so pathophysiology wise uh this essentially this slide shows you what normally happens essentially you'll see that there's a few negative feedback loops which actually make the overall management of art arena syndrome much more complicated so patients with sclerosis develop what hypertension for type tensions causes flanking vasodilation which means that the blood supply to the rest of the body is actually diverted towards the portal system which actually causes central hyperperfusion it causes activation of the renin ideotension system that causes the hyponatremia and the fluid retention which increases the cardiovascular which increases the blood flow and then it kind of goes into this negative feedback cycle which causes kidney dysfunction in ancieties and it's actually quite difficult to break through the cycle so that's why most of the time patients with hepatitis syndrome have pretty poor prognosis risk factors for developing hepatitis syndrome um obviously anyone with advanced liver disease who presents with infections particularly spp they have a very high risk of developing hrs so our protocol normally is is that if you have a patient who has confirmed spp on day one and day three of their infection we would give them a higher uh volume of albumin regardless of their kidney function to prevent them developing hrs um so that's a separate thing all here but if you have a patient with spp we do give albumin on day one and day three to stop them developing hrs regardless of what the kidney function is on day one uh the overall prognosis is very poor so this is something that um uh is quite important once you have once you're getting to the stage of diagnosing hrs you should always be thinking of palliative care telling the family being honest with them that all the studies that we have currently are suggesting that the overall prognosis of these patients is very very poor um hrs1 has a particularly poor prognosis so hrsa similarly has a prognosis so palliative care input by the time you're diagnosing this is actually quite important preventing hrs is very very difficult because most of times you will see these patients who have both declining kidney function and worsening ascites the ascits and the peripheral edema commonly limits their quality of life you obviously want to keep a control of that but sometimes you have to use huge amounts of diuretics to try and control that side of things then if anything else happens like an infection a chest infection or spp or anything else they'll come in they'll be on a huge amount of diuretics they'll be sick and then that is kind of a recipe for them developing eventually developing hrs so obviously if you have someone with liver disease within reversible etiology so the patient's alcoholic liver disease the best thing is asking them to stop drinking letting them know that if they keep on coming in and our hospital the next time might be the time that they actually pass away preventing decomposition again is quite difficult we try and keep them on the minimum amount of diuretics needed to achieve the treatment goal that we want um avoiding agents i will cover in a few slides and preventing factors that impact circulatory status i will also go over in the next few slides um so role of prophylactic algae and there's quite a lot of current studies being done especially in europe looking at outpatient albumin um for patients with liver disease it's something that's currently being investigated um no significant evidence currently is available to suggest that's something that we should be doing as a routine thing um the one thing that we do know is that after patients do develop spp once we um always keep them on prophylactic antibiotics because the chance of them developing sap again in the future is very high the other thing we also recommend is patients who come in with varico bleed or suspected virus obliques the reason why we recommend giving them iv testing on admission is because of the risk of bacterial translocation so the main reason we give the thousand to patients with viruses doesn't specifically anything to do with the bleed it's the high risk of them getting bacterial translocation and then developing svp so if that's uh something you had as a question that was that's mainly the reason why we recommend giving ib antibiotics for various obliques um yeah that's why i was going over so in terms of specific medicines and hrs so beta blockers are something that we're increasingly using quite early on in patients with liver disease so uh a few years back mainly we were using beta blockers for patients with esophageal viruses which did not meet the criteria for banding as a tool to reduce the risk of re-bleeders after we did intervention in certain patients nowadays we recognize that beta blockers have much more of a role before things happen so there's quite a few studies looking at primary use of beta blockers in patients with port hypertension they're very very useful for a number of different factors however one thing that we have noticed is that patients who present with hrs who are on beta blockers should probably have their beta blocker stop so if you have someone who's presenting with uh decompensated steroids it's particularly advanced and they're developing hrs during that period it is recommended that we do stop the beta blockers because it could cause a decrease in cardio couple that's kind of similar to the previous slide nsaids are definitely no no so if you have a patient with cirrhosis and they're telling you telling you today they're taking ibuprofen you definitely need to tell them the importance of knotting i prevent first of all in terms of bleeding second of all uh for the kidneys it's it's a complete no no so nsaids are really the last medication we'd recommend to anyone with established cirrhosis ace inhibitors and arbs is a bit of a difficult one so um obviously they have such a good use in a lot of different core mobilities a lot of patient sources have multiple different converters including lv dysfunction hypertension other cardiac etiologies um so ace arbs are quite useful in a lot of those things but the the studies looking specifically at the liver suggesting that it's not as ideal for us erotic patients but it's not as clear-cut as you should use them we shouldn't use them it's kind of a more of a balancing thing if you have enough of a good indicator to use aces or arbs you should still continue using them as a primary single anti-hypertensive probably would recommend going with something else but again it's it is not a clear answer to be honest uh aminoglycosides this is again another one if you have someone who's profoundly eurosceptic with an organism which only responds to gentlemycin i mean gentamicin is one of the best bacteria style antibiotics we have you justified using it but the general recommendation from easel is only really use it in the ones that you contrary with any other antibiotics so that's it's again it's not a clear-cut scenario if you have someone who needs gentimizing you should give gentiles in but if it's other options are available would recommend you use the directions diuretics like i said if you have someone who has hrs diuretics should be stopped as a general rule of thumb we can always do trains we can always diarism later on once the aki's improved um it's again a hard one but my rule of thumb is if you have aki and fluid overload focus on the aka when they first bring the hospital then specifically to hrs as i was saying totally present argument is what we mainly recommend in america they use octotried and meditate more than we do here uh noradrenaline is an agent that you could use if your patient was on itu but the ones on the water setting it's mainly telepresent albumin so how we give telepresent uh the commonest starting dust that we tend to go as one milligram qds uh and then up titrate it further if there is an inadequate response uh so telepresent continuous infusions i've never seen anyone give continuous infusions it's mainly always boluses uh there might be a role for that but i've never seen it being used uh like i said monitor the recommendation here is if it's not improved after three days to increase the value present further the main things you have to consider with telepresence is telepresence is a vasoconstrictor so if you have someone with significant ischemic heart disease peripheral vascular disease you can cause a lot of problems with that site so essentially baseline ecg make sure they don't have significant vascular disease and significant ischemic heart disease um if you how do you have someone like this and you're making a risk benefit analysis it's probably safer to go with lower doses of telepressing rather than going straight to milligrams uh renal replacement therapy overall if you have someone who has a established services they have decomposited liver disease and they've got hrs their prognosis is poor so referring them to itu for renal replacement therapies only really if you are sure they're going to get a liver transplant because without a liver transplant that's the only real fix of some of these hrs patients um uh a lot of the times you can make them better they'll come back in in a few months time again with decompositive liver disease that generally with how limited it beds are unless you have someone who you're using as a british transplantation it's generally not the right option for most of our patients obviously there's some cases where we do filter them but it's few and far between and liver transplantation is by far the best option available for hrs but it's an option that's only really appropriate for a few of our patients so again if you had someone who came in with hrs with acute liver failure those are the kind of patients as opposed to the uh chronic alcoholic liver disease patients who continue to drink who wouldn't be a transplant candidate so i think overall my summary really is hrs patients treat them quite similar to any other akai patients keep hrs in the back of your mind but recognizes the diagnosis of exclusion make sure you stop all of the nephrotoxic medications stop the diuretics uh don't worry too much about the ascites and the prophylaedema as long as they've not got pulmonary edema you can fill them up you can have they can have an inpatient drain you can diagram later early palliative care input with anyone who does have hrs because their prognosis overall is very poor um and obviously if you have labeled someone as hrs you should then consider giving them telepresent arguments so sometimes we label them hrs but then it's first of all an inappropriate label secondly we don't even give them the medications for the thing that we've labeled them and so it's quite clear that you make a clear distinction between what is hrs and what's pre-reneked or medication related and once you've labeled it um appropriately treat and obviously involve pilot care as soon as possible thank you very much