step. So it's the first case is based off of in an ER. We have a 36-year-old male, two days of severe malaise, abdominal pain, nausea and vomiting, no known medical history, occasional alcohol intake and no smoking. He just returned two weeks ago following a camping with his boyfriend from Haiti. On exam he is hypotensive tachycardic and but he is still alert and oriented. Diffusely achy but no guarding rigidity or rebound tenderness. He is a trick on exam. Normal CBC, normal basic metabolic profile. The LFTs have transaminases in the thousands, bilirubin is 3 and INR is normal. Okay, looks like not working. Viral workup is positive for acute hepatitis A. What is the diagnosis for this patient? Is it acute fulminant viral hepatitis, acute viral hepatitis or subacute viral hepatitis? So in this case we're essentially looking at the answer. Does anyone want to pick the answer? Right, so this is acute viral hepatitis. The only reason this is not in the fulminant part is fulminant viral hepatitis the patient should have hepatic encephalopathy associated with it. The acute hepatitis essentially goes through the spectrum of hyper acute liver failure. These are patients that are mostly related to drug and toxin. Really bad hepatitis A can present as a hyper acute liver failure, can sometimes be acute associated with acute fatty liver pregnancy related or vasculitis. The time frame is generally less than seven days. The next to follow is the acute viral hepatitis. Again, drug toxins, viral pregnancy related or vascular. More in that 8 to 28 days and then following beyond that is a subacute liver failure. And this is a time frame from onset of jaundice to developing hepatic encephalopathy. Liver failure can be associated with multiple organ dysfunctions within our body in an acute viral hepatitis. You can have the whole mirage from the acute lung injury to hypoglycemia, lactic acidosis, bone marrow suppression and even the WBCs that are in the circulation are impaired in function. Hepatic encephalopathy can be there. You can also have associated cerebral edema, intracranial hypertension. It's a high output failure state associated pancreatitis and again adrenal kidneys, portal hypertension and SERS response. Any questions on the first part? Let's see if this works again. Yep, good. The patient is admitted to the hospital but overnight is quickly upgraded to the intensive care unit and is now uptended with a GCS of 7, E2M4V1. Day 2 labs, now the transaminases are all the way up to 2,000 range. Ammonia level of 210, worsening renal function and hypoglycemia, oliguric at 250 mils in the last 18 hours that the patient has been in the hospital. Patient is now intubated, started on volume resuscitation and is given a bolus of 30 mils per kg of balanced fluids. Norepinephrine and vasopressin are started for vasopressor support. Day 3, patient continues to be altered and follow-up labs show worsening transaminases and ammonia levels. What is your next step? Would you still continue to wait and continue supportive care? Do a CT head to rule out bleeding? Invasive ICP monitoring, renal replacement therapy or liver transplant? Any takers for this one? Okay, what was that? Right, so I think if we were to go through the audience response, those two would be the most common answers and at this point in time when your ammonia level is continuing to go up, you have a patient who is becoming more and more altered and a liver failure that is continuing to get worse. We are not expecting this patient's ammonia level to come down anytime soon. Going into this, it's a study published in 2007. It basically looks at an ammonia level to be a pseudomarker for intracranial hypertension or cerebral edema and the area under the curve for ammonia was 0.78 compared to the MELD and MELD plus ammonia of 0.76 and 0.83. A fairly good predictor of patients that are at risk for developing intracranial hypertension. So at this point in time, you would recommend initiating renal replacement therapy to assist with ammonia clearance. So acute kidney injury or renal replacement therapy in acute liver failure. Acute kidney injury in itself is present in approximately 50% of the patients with acute liver failure, mostly in a pre-renal state either because of volume deficit or also because of lack of intravascular vasodilators leading to renal artery or renal vasculature vasoconstriction. So it's intrarenal vasoconstriction that can predispose these patients to liver failure. Renal replacement therapy in patients with acute liver failure is predominantly indicated for these three reasons. You have downstream volume overload. So you're massively giving these patients fluids and the patient's urine output is zero and your average IV infusions that are running are giving three to five liters every day. You want to maintain uvulemia or control the volume you would initiate renal replacement therapy. Type B lactic acidosis or hyperammonemia. Hyperammonemia for renal replacement therapy is debated, but for the most part when you look at a clinical trajectory of a patient, you can convince your nephrologist to initiate renal replacement therapy for these patients. Having said that, I'm married to a nephrologist and I can tell you it does get contentious sometimes. So continuous renal replacement therapy is not initiated with, is not associated in with increased intracranial pressures unlike hemodialysis. So when you do request your nephrologist to start renal replacement therapy, you want to stay away from intermittent hemodialysis. Primarily because, and I think I do have that slide, I have that slide downstream, but this is a study going all the way back to I think 1990s or late 80s which had looked at intracranial pressures in patients receiving hemodialysis. And that was not in liver failure patients back then, but hemodialysis is associated with increased intracranial hypertension or increased intracranial pressures compared to renal replacement therapy. So if you do want to initiate renal replacement, it has to be a continuous renal venous, continuous renal venous hemodialysis. One of the other options in that last questions was also liver transplant. So that the, that was a wrong answer because you're not going to transplant that patient at that point in time. But if the option said transplant referral, then that would be the correct answer. In any patient who presents with an acute viral hepatitis who is trending to go towards hepatic encephalopathy or continuing to worsen and in acute liver failure, a transplant referral should always be made. There are different guidelines for acetaminophen versus non-acetaminophen, but these five are generally a good cue. Any hepatic encephalopathy, INR which is more than two, metabolic acidosis or deteriorating course, and there are no other contraindications for transplant. Any questions with our first case? I have a quick question regarding the increased amount of ammonia and encephalopathy. Now even we usually advocate for CRRT to remove the ammonia from the blood. It seems to be high flow CRRT. Is there any comments on that? Because sometimes we have some conflict because there is some data that if you really want to remove the ammonia, it needs to be higher flow. And it can sometimes be kind of very difficult with the patient's hypotension. And I have seen our nephrology usually start a very low-flow CRRT. But if you're really trying to remove the ammonia and reduce the intercranial hypertension, that's our goal, it needs to be really higher flow, which might cause more hemodynamic instability and require more viscoprocessor support. And it's always a fine balance. So the flow recommendation for CRRT is the standard is somewhere between 20 and 35. I think it's mil per kg. Depending on what is the indication, so if you're dealing with acidosis, or toxins, or hyper-K, or hyperammonemia, you always start with a higher flow. The recommendation that it comes down to is you need to average over a 24- or 36-hour duration of 20 to 35. So a lot of times, these patients will start at a very high flow, at 40 to 45. But then over two to three hours, then slowly bring it down to 20 to 35. And they look at the urea clearance over time. But that can be initiated. And within the nephrology literature, at least the recommendation is if you have to temporarily use pressors to get over that hump for toxin clearance, it is OK. You can use that. Because once the toxin is cleared, you can always scale back your flows. So yes, you can start with a higher flow. And then you can scale back. OK, we will start with our second case. 35-year-old female brought to the ER with confusion, cough, dyspnea, and a history of drug use. She, again, has no known past medical history, social history of smoking some drugs per family, cold, clammy skin, blood pressure, essentially hypotensive, tachycardic, tachypneic, and febrile, using accessory respiratory muscles with a skin stigma of IV drug abuse. WBC of 31,000, BUN of 40, creatinine of 1.8. Six months ago, it was 0.4 milligrams per deciliter. And chest x-ray shows multilober infiltrates. I will say that this is a little bit of a doozy of a question. Because the question, actually, is really simple. How would you define the renal function for this patient? So we all know that patient probably has endocarditis, really bad sepsis. But can we define the severity of renal function in this patient? So let's go back to our question. We know this patient is in shock. We all can define a pre-renal or an intra-renal by this time, AKI. When we look at a creatinine of 1.8 with a baseline of 0.4, that is nearly a four times increase from baseline. I will say there is no stage four KDGO. If it was stage four KDGO, that would be the answer. But a very good way of remembering this is here. So there have been multiple AKI terminologies in the past. KDGO has been easiest because it helps you. Stage one is one to two times of creatinine elevation. Stage two is two to three times. And stage three is if you're more than three times of creatinine, baseline creatinine. If your urine output definitely is lower for six to 12 hours, so I consider that as your first shift. If your urine output's been low for only one shift, it's stage one. If it's been low for two shifts, it's stage two. If it's low for more than three shifts, it's stage three. So the reason why KDGO criteria is important is in terms of indications for starting RRT in patients with shock or with AKI, both the critical care and the nephrology recommendations are now based off of KDGO criterias. So it's just something which is helpful to know. So this patient has KDGO stage three AKI. What would we do next? Fluids, fluids, and fluids. But I think we've all come a really long way from the many reverse time to now. The fluids have to be given, but we have to keep an eye on how much. So it has to be a judicious and needs to be guided. I think the jury is still up in the air of what is the correct way of identifying our volume status. It can go anywhere from the capillary refill time, that was done from a study in Brazil, to looking at lactic acidosis, to looking at the non-invasive cardiac output monitoring, to going back to the pulmonary artery catheter directed or bedside echocardiograms. We can use any. Something that we use, and I think I can contend for most of my partners at IU, we always go to at least two or more. The suggestion always is just don't rely on one criteria for volume assessment. At least correlate from two. If you are a CVP fan, that's fine. Use the CVP, but also use your bedside echo to look at IVC. If you're looking at passive leg raise tests, then correlate that with your cardiac output monitoring at the same time. And you can use non-invasive, or we still have the invasive cardiac output monitoring devices. Crystalloids are superior to colloids. That is very well defined at this point in time. The only colloid that is still considered that can be used is 5% albumin. That is still not considered a resuscitation fluid. But the heta starch and all the other colloids are pretty much not considered for resuscitation. Balanced crystalloids are better. And let's go through the three studies. And the reason I added the question mark in front of it is January of this year, or February of this year, we got the plus study group from Australia and New Zealand that essentially talked against it. So the SMART trial, which was one of the first studies that looked at normal saline and balanced solutions, looked at essentially did not identify mortality benefits. So fluids as a crystalloid are still good. What they identified was that there were higher major adverse kidney events in 30 days in patients with normal saline. Rationale being the pH for normal saline is 4. And you are essentially causing these patients to develop non-gap metabolic or hyperchloremic metabolic acidosis, which can then cause your body's pH to get worse, can then affect the function of your WBCs, can affect the function of different organs, can worsen acidosis, can worsen cardiac function because of the non-gap acidosis. And the other thing they also identified was renal replacement therapy. Three days were more in balanced solution. Rationale, again, being you're causing less acidosis, that doesn't become your indication for dialysis at that point. So this did cause a fairly significant shift in the utilization of the lactated ringers or the plasmolytes against the normal saline from a resuscitation fluid standpoint. The next is the SALT-ED trial, which then looked at the same thing, but this then identified no difference in the hospital stay. As I said, even with the SMART trial, no difference in the hospital stay, no difference in mortality. The only thing they found was the kidney events were better with balanced solution. SALT-ED also identified that higher make is essentially the short form for major adverse kidney events in normal saline group. The Australia and the New Zealand conglomeration of ICUs, they published the PLUS study group. It was published, I think, last year or earlier this year. January or February of this year it was published. And at this point in time, they identified no difference with the normal saline and the balanced solution group. So I'm going to open this up for discussion and just to hear what the practices are within different areas and how do you guys approach this. From a critical care board standpoint, I personally don't think that they're going to ask us a question of whether we're going to bulldoze with normal saline or plasma light. Go. I'll just be boisterous. One concern I always have, this actually happened on my critical care board. Oh, wow. Questions are a little behind the time. So even though this study is actually a practice, I don't have access to it. I'm just saying they may still have those questions. When I was in practice, as a fellow, we stopped doing looking for responders and non-responders. But the question on the board is clearly one of that answer rather than a general. So yes, but just be cognizant. Thank you. In non-neuro ICU patients, we, of course, favor balanced crystalloids. The pendulum has been swinging. The board exam questions are generally about maybe two or three years behind, and so as Dr. Efron was saying, you know, they may not like just put anything that's controversial. The pendulum seems to be swinging back to, you know, where maybe they're equivalent, but I think there's more data saying that saline is bad for the kidney and high chloride and volume overload and all of that. So I think there's a board question on this topic, it will probably be just to let the test taker know about the potential harm of too much saline and maybe some favoring for the use of balanced crystalloids. And lactated ringers, although it might transiently raise your lactate levels when you're pulling a lactate level, it doesn't cause lactic acidosis, and so it can be used as a resuscitation fluid just like normal saline is. So again, those would probably be the points that they'd be looking at is making you know about the harmful effects of saline on the kidney and that maybe in most patients, particularly the ones we see like septic patients, swinging over to balanced crystalloids are generally now I think the practice. If I could just point out, there's clearly the evidence that comes out for those guidelines is at the time that they come out, and sometimes those guidelines turn out to be wrong when a new study comes out, i.e. type glucose control, use of activated protein C, following a CVP. And so it is likely that when the PLUS study gets put in there, that the next guidelines may take a step back, which unfortunately makes our lives more difficult as clinicians at the bedside when you're trying to change something that you get used to doing. But we ought to change our practice based on new evidence that comes out. So that's not going to help anybody with the boards, knowing that the things are always changing, and appreciate your being willing to listen to a number of people who have or have not changed their practice coming up. But guidelines are only as good as the evidence that gets put into them, and they ought to be a living document, and we're getting closer towards having them. OK, great discussion. I'm going to leave this slide. I'm not going to go through this slide in detail, but this is how the nephrologists look at volume resuscitation, and you're going to get access to this slide when you're towards the end of it. But it's essentially salvage the patient, optimize the volume status, then stabilize your fluids, and then de-escalate. Last case, and we're going to go through this one. I think we'll be done just in time. So patient had, no, this is actually the same case. So patient had cultures drawn, vancomycin, cefepime, and metronidazole was initiated. The vanc trough was 15 to 20, we know that vancomycin does cause AKI, with the AKI incidence of 5 to 43%, depending on the trough. Patient is now intubated on dexmedetomidate, on pressers, and develops anuria. Day four labs, you have a white blood cell count of 20, creatinine continues to go up, BUN's going up, bicarb's normal, potassium is normal. What is our next step? Initiate hemodialysis, CVVH, continue to monitor, start bicarbonate infusion, or peritoneal dialysis. So at this point in time, we know AKI is getting worse. We're on day four for this patient, but no urgent indications to initiate renal replacement therapy. So the answer here is we will continue to monitor. Now day five, now we're starting to see electrolyte abnormalities. You have a bicarb of 15, K is continuing to go up. What is our next step at this point in time? This is when we would initiate renal replacement therapy. So this comes down to our discussion of when do we start renal replacement therapy. Five things that we should consider before calling our nephrology colleagues is what do we see in terms of severity of illness and trajectory for these patients? The labs and the AKI trends, the fluid balance, other organ dysfunction, necessity of the procedure, urine output, is it getting better or worse, toxin exposure, risks associated with the procedure for that particular patient at that point in time, is the patient too far gone and it's futile to even offer renal replacement therapy at this point in time, and then logistics in terms of whether you have options of CVVH or not, and family discussion. Just like our volume discussion, renal replacement therapy initiation has always been a discussion topic for the nephrologists. The AKIKI trial, which is one of their oldest studies, was a randomized control trial, multi-center but all centers in France. The 60 day survival was similar in patients when the dialysis, when renal replacement therapy was started just because someone hit GADIGO stage 3 versus it was started when there was an actual indication to start dialysis like hyperkalemia, metabolic acidosis, volume overload, or altered mentation. Elaine's study, which was again in 2016, this was only in surgical patients, it's the only study that has been shown that early initiation of renal replacement therapy at AKI stage 2 showed 90 day mortality. The critique for this study has always been, did we actually just have lead bias because a lot of these patients really didn't need dialysis to start with and were going to have a good outcome anyways. So that did not really change the treatment approach. Going back to another study in France at the same time, the ideal ICU study 2016, septic shock patients showed no difference in the 90 day mortality. And then the last one was the START-AKI trial, 2020, it was a multi-continent randomized control trial, looked at accelerated groups as soon as the creatinine hit 4, there was a doubling of creatinine or a urine output less than 6 mils, versus the standard, again indication based. You meet one of these three or four criterias of hyperkalemia, acidosis, volume, or mentation, then you start CVVH. No difference in mortality or renal recovery. Again a picture for all the studies that have been done, you will have access to this when you get the slides. Which modality do we start, intermittent hemodialysis or CVVH? There's no mortality benefit shown with either of these. They should be considered as complementary, not a competitive therapy. CRRT should be used for hemodynamically unstable patients or patients with increased intracranial pressure or cerebral edema or brain edema. Toxin removals is always better with intermittent hemodialysis, and as we discussed earlier, you start at 20 to 25 mils per kg per hour, but higher rates can be used for hyper-K acidosis or hyperphosphatemia. Last one quickly, do I have time, one minute, okay. Patient presents with multiple episodes of bloody vomit since last night, presents with lightheadedness, dizziness, or symptomatic hypotensive tachycardic. Hemoglobin is lowish, not terribly low. What is your choice of access for this patient? The choice of access for a shock patient is always large bore peripheral IVs. The answer is never central lines. What is the bolus fluid of choice? As we discussed earlier, crystalloids is the bolus fluid of choice. Restrictive transfusion of less than 7 grams is known to have better mortality versus liberal hemoglobin of going up to 10. Patient goes endoscopy and esophageal varix is identified, banding is done, patient is now stable from a hemodynamic standpoint. Which intervention is known to improve mortality for this patient? So esophageal varix, bleeding, antibiotics for SPP prevention is the only thing that is shown to improve mortality for these patients. Three days later, this patient comes back to the ICU. It's not an uncommon thing that all of us see. This patient's back in ICU, now in a much worse state. What do we do at this point? Do we refer this patient for TIPs, call hepatology for transplant, consult palliative care and hospice, last one, consult GI again for re-EGD. All the guidelines have recommended every patient should go through two EGDs before you refer these patients for TIPs. Two EGDs fail, they come back for bleeding, you refer them for TIPs. So, contraindication for TIPs essentially is if you have thrombosis, you have downstream, you never do TIPs in a patient with pulmonary hypertension or RV dysfunction or a really high MELD score. Peptic ulcer disease, this is the last slide, I think we're done. Early EGD in peptic ulcer disease reduces length of stay. Endoscopic therapy reduces risk of re-bleeding. If patient re-bleeds, just like variceal bleeding, consider re-EGD, EGD times two, they fail, then IR is consulted for intervention for gastric artery or GDA embolization. Pre-EGD PPI infusion reduces EGD intervention, so you want to start these patients on PPI, but reduce the likelihood that they need to do something when they do an EGD, but EGD is still recommended. Thrombosis versus intermittent PPI, there's no difference in mortality. Thank you.

medical cases

acute viral hepatitis

septic shock

AKI

renal function

balanced crystalloids

esophageal variceal bleeding