SCCM Resource Library-Guidelines for the Management of Adult Acute and Acute-on-Chronic Liver Failure in the ICU: Cardiovascular, Endocrine, Hematologic, Pulmonary, and Renal Considerations

Video Transcription

So I'll be focusing on cardiovascular and pulmonary considerations, and just to follow  up on Waleed's introduction, as you can imagine, a lot of the evidence in these two organ systems was indirect.  There was no real direct evidence in the setting of liver failure, so you'll see a lot of recommendations that are predominantly conditional.  So with that preface, just a moment to acknowledge all the authors in this guideline.  Their tireless efforts and passion and dedication are just a word of appreciation for this great group that I had a chance to work with. So cardiovascular.  The first question was choice of initial resuscitation fluid, and so a couple of recommendations as  far as pertinent negatives we recommend against using hydroxyethyl starch for initial fluid resuscitation in patients with ALF and ACLF.  This was a strong recommendation with moderate quality evidence. And number two, we suggest against using gelatin solutions for initial fluid resuscitation  in patients with ALF and ACLF. And this was a conditional recommendation with low quality evidence.  And just the rationale for these two above statements, and by the way, all the references  are in the guidelines, meta-analysis of trials in critically ill patients suggests no benefit, as you know, of hydroxyethyl starch or gelatin solutions over crystalloids.  And then specifically with regard to liver disease and liver failure, there's some suggestion,  in general clinical care as well, of increased risk related to hydroxyethyl starch compared to crystalloids, including exacerbation of coagulopathy in liver failure.  Reason number two, and this is an interesting question as we debated this, albumin as resuscitation fluid.  So the recommendation we came up with is we suggest using albumin for resuscitation of patients with ALF or ACLF over other fluids, especially when serum albumin is low, defined  as less than 3 milligrams per deciliter. And this was a conditional recommendation with low quality evidence.  Just to go over the rationale for this recommendation, as you may be aware, in liver failure patients  there may be both a quantitative and a qualitative dysfunction in the albumin molecule in these patients.  And so in addition to volume expansion in this set of patients, albumin administration may improve hemodynamics using both via antioxidant and immunomodulatory pathways in addition  to just being a volume expander. And the third sort of interesting piece of evidence is that when you look at meta-analysis  directed to this question, there's benefit of albumin in preventing post-paracentesis circulatory dysfunction with that specific odds ratio and decreasing mortality.  So as we thought about this evidence, extrapolating it to shock, we felt that there is a reasonable  support for thinking about albumin earlier than later as far as using it as a resuscitation fluid in this patient population.  All right, moving on to blood pressure targets, very similar to septic shock. We suggest targeting a mean arterial pressure of 65 millimeters of mercury in patients with  ALF and ACLF with concomitant assessment of perfusion. This was a conditional recommendation with moderate quality evidence.  And just with a caveat or with a remark that some patients will have adequate perfusion at a lower MAP, as you know, some of these patients with a normal MAP maybe 60, and others  will have an improvement of perfusion at higher mean arterial pressures. Another comment here, and this will be addressed more when we publish a part B of these guidelines  related to neurologic issues. In the setting of severe ALF and possible risk of intracranial hypertension, there may  be a benefit of targeting a higher MAP to optimize cerebral perfusion pressure. And just as far as the rationale, again, we're extrapolating data, indirect evidence from  the surviving sepsis guidelines that recommended a target MAP of 65, and that we use the rationale  that the form of shock in these patients, which is distributive shock, is similar to what we see in septic shock. So that is indirect evidence supporting this recommendation.  Let's move on to hemodynamic monitoring. So recommendation one is we suggest placing an arterial catheter for blood pressure monitoring in patients with ACLF or ALF and shock.  This was conditional, recommendation with low quality evidence. And the rationale for this is that compared to cuff, non-invasive cuff measurements, A-line  readings provide a more accurate and continuous assessment of arterial blood pressure in the setting of shock in this patient population.  Recommendation two, we suggest using invasive hemodynamic monitoring to guide therapy for shock in patients with ALF or ACLF, conditional, low quality evidence.  Just a remark that there's an evolving role of echocardiography in hemodynamic monitoring and assessment.  And the rationale for this, as you can imagine, imagine that really sick cirrhotic who has massive anusaka, the non-invasive assessment of intravascular volume and cardiac output  is very challenging in these patients, hence the support for or recommending invasive hemodynamic monitoring. Moving on to choice of vasopressor agents.  Recommendation one, we recommend using norepinephrine as the first-line vasopressor agent of choice  in patients with ALF or ACLF who have shock that's refractory to fluid resuscitation. We made this a strong recommendation with moderate quality evidence.  And again, this is based on indirect evidence from data in septic shock and given the similarity of the shock, the distributed shock in liver failure.  Recommendation two, we suggest adding low-dose vasopressin for shock that's refractory to norepinephrine in patients with ALF or ACLF.  Conditional recommendation, low-quality evidence. And again, this is just an extrapolation of data that we have gleaned or learned from septic shock data with a mortality benefit.  So that's cardiovascular. Let's switch gears and move on to pulmonary considerations. So first question is tidal volumes in mechanical ventilation.  And again, very similar to what we do in the surviving substance guidelines, we suggest using a low tidal volume strategy over a high tidal volume strategy in patients with ALF  or ACLF who have ARDS. Again, this is a conditional recommendation, low-quality evidence.  And again, this is all based on indirect evidence from general critical care that demonstrates  a benefit, as you know, of a low tidal volume strategy in ARDS with respect to mortality. And meta-analyses of low and versus non-volume targeted tidal volume strategies demonstrate  reduction in mortality in the low tidal volume group. What about use of PEEP, positive end-expiratory pressure?  The recommendation is we suggest against using high PEEP over low PEEP in patients with ALF or ACLF and ARDS. This is a conditional recommendation, low-quality evidence.  And just a remark, very similar to what we do in general critical care, a high PEEP strategy  may be considered in moderate to severe ARDS after balancing the potential benefit to risk of increasing ICP and reducing menis return, which may be specific issues of concern in  this patient population. Again, the rationale, again, is indirect. Evidence from general critical care does not demonstrate a mortality benefit of a high  PEEP strategy in ARDS, except possibly in moderate to severe. And as I've mentioned, things to be cognizant of in the patient with ALF is elevated ICP,  and especially in the patient with ACLF, the effects of high PEEP on venous return. Moving on to use of pulmonary arterial hypertension therapy in portopulmonary hypertension.  The recommendation here is we suggest treating portopulmonary hypertension with agents approved  for the treatment of pulmonary arterial hypertension in patients with a mean pulmonary artery pressure greater than 35 millimeters of mercury.  This was conditional, with very low-quality evidence.  And again, the rationale here is that, for those of you who care to take care of these patients, current POPH treatment strategies are based on extrapolation from the broader  literature that addresses treatment of general pulmonary arterial hypertension. And there are some uncontrolled small observational studies suggesting that these general PH-based  therapies, including IV fluorine, for example, sildenafil, and the endothelial receptor antagonist could be beneficial in portopulmonary hypertension as well.  What about hypoxemia in patients with hepatopulmonary syndrome? The recommendation here was we recommend supportive care with supplemental oxygen, as you do,  in the treatment of HPS, pending possible liver transplantation. This was a best practice statement.  And as you already may be aware, there's no effective pharmacological therapies apart from oxygen.  But liver transplantation being the only proven therapy that can reverse hepatopulmonary syndrome. The next question in pulmonary was tube thoracostomy in hepatic out of thorax.  This is another question that created some debate, but this is the recommendation we came up with.  We recommend placing chest tubes with an attempt to pleurodesis for hepatic out of thorax in patients whom tips is not an option or is the palliative intent.  This is a best practice statement. The rationale here, and this is actually data that's coming straight from some liver literature,  is that in a systematic review of patients with hepatic out of thorax undergoing pleurodesis, complete response was reported in 72% of patients.  In addition, tube thoracostomy has been used as a bridge to transplant in a small series of patients.  A caveat to this strategy, just to make you aware, there is a meta-analysis showing there's increased risk of infection with tube thoracostomy in hepatic out of thorax.  So that is a potential point of concern with regard to these patients. Finally, the last question in the pulmonary section, use of high-flow nasal cannula and  non-invasive ventilation. The recommendation here is we suggest using high-flow nasal cannula over non-invasive ventilation in hypoxic critically ill patients with ALF or ACLF.  This is a conditional recommendation, low-quality evidence, and again, this is an extrapolation of evidence from general critical care.  The remark here is in patients with hypercarbia and purely ventilatory failure, it may be more appropriate to use NIPPV over high-flow nasal cannula.  The rationale, again, just to state the evidence or the indirect evidence, in general critical  care, there's demonstrated no differences in mortality or intubation rates in hypoxemic critically ill patients when you compare high-flow nasal cannula versus NIPPV.  And as you're aware, high-flow nasal cannula offers greater patient comfort. And again, from a liver patient or ALF or ACLF standpoint, high-flow nasal cannula may  have lesser impact on ICP and meanness of turn due to a lower effective PEEP compared to NIPPV. I think that concludes the cardiovascular pulmonary. Thank you for your attention.  I'll turn it over to Dean Karvelas. Yeah. Hi. Thanks, Ram. And our final speaker is Dean Karvelas.  And Dean is an associate professor of gastroenterology, hepatology, and critical care at the University of Alberta and, again, one of my other co-chairs. Welcome.  Thank you very much, Ram and Rahul. This next section, we're going to cover the recommendations for the endocrine hematology and renal subgroups.  And as mentioned before, there are still other groups that will be reviewed and published the second part of the guideline.  So just once again, to acknowledge all the contributors to this vast amount of work. So we'll start with renal considerations.  And I just want to highlight that there are some subtle differences between acute liver failure, which is a necroinflammatory process, and acute on chronic liver failure, which  is our cirrhotic fibrotic portal hypertensive patient. And you may see a couple of subtle references that's specifically talking about ALF versus ACLF.  So the first recommendation is the timing of renal replacement therapy in patients with AKI in this is acute liver failure only.  And this was a suggestion we suggest using renal replacement therapy early in patients with acute liver failure and acute kidney injury.  This was a conditional recommendation with a very low quality of evidence. The idea here is that continuous renal replacement therapy prior to the development of AKI has  been associated with improved outcomes. And one of the potential theories for this is it might mitigate intracranial hypertension and the formation of cerebral edema.  Just to mention, we know that there's a lot of uncertainty in the general critical care literature in the timing of AKI.  And as such, there's insufficient evidence to issue a recommendation for the ACLF population. Secondly, vasopressors in hepatorenal syndrome.  This is a bit of overlap with the previous group recommendation. We recommend using vasopressors over not using vasopressors in critically ill patients with  acute on chronic liver failure or cirrhosis who have developed hepatorenal syndrome. This was a strong recommendation with moderate quality evidence.  One of the remarks is that vasopressors could be any of turlopressin, norepinephrine, mitadrine, or octreotide.  The rationale has been based on a couple of different systematic reviews. Nine randomized clinical trials comparing turlopressin to placebo in 534 patients with  HRS, which showed 92 fewer deaths per 1,000 HRS patients receiving turlopressin where there's the most robust data.  As you're still aware, we don't have turlopressin in North America, but we hope it's going to be licensed in the next year.  What about interoperative renal replacement therapy during liver transplantation? There's insufficient evidence to issue a recommendation.  The remark that patients with ongoing emergent indications for renal replacement therapy such as hyperkalemia or severe acid-based abnormalities should not have their renal  replacement therapy discontinued prior to transplant. This is essentially based on pooled data, low-quality evidence, and one recent prospective  randomized pilot study that showed a high crossover between control and interoperative CRRT that did not show any benefit in either renal or survival outcomes.  So what about trans-jugular interoperative portosystemic shunt, or TIPS, for the prevention of hepatorenal syndrome?  The recommendation is that there is insufficient evidence to issue a recommendation. Rationale is that the creation of TIPS is an establishment treatment option for major  complications of portal hypertension such as ascites and variceal bleeding. We looked at a meta-analysis of six randomized trials which compared TIPS versus paracentesis  and refractory ascites. There was less AKI in the TIPS group, but there's an increased rate of hepatic encephalopathy.  And unfortunately, these randomized control trials didn't focus on critically ill patients, which quite often are excluded from many of these trials.  So next, we have the hematologic considerations in both ALF and acute on chronic liver failure. So assessment of bleeding or thrombosis risk recommendation.  When available, we suggest using viscoelastic testing such as TEG and Rotem over measuring  INR platelet count and fibrinogen in critically ill patients with acute or acute on chronic liver failure. This is a conditional recommendation with low-quality evidence.  We know that traditional coagulation tests such as INR do not necessarily represent the whole hemostatic profile in these patients, and that viscoelastic testing, including TEG  and Rotem, allow for real-time assessment of global and functional evaluation of altered pro- and anticoagulant pathways. Hemoglobin targets.  The recommendation was we suggest a transfusion threshold of greater than 7 milligrams per deciliter over other thresholds for critically ill patients with ALF and ACLF.  This was a conditional recommendation with low-quality evidence. This was based on one single large randomized trial that included both cirrhotic and non-cirrhotic  patients, where a restrictive transfusion strategy compared to a liberal strategy conferred significant fewer transfusion reactions and adverse events.  As mentioned, this study had non-cirrhotic patients as well, but when looking only at the cirrhotic subgroups, the restrictive strategy was not significantly different to a liberal  strategy for death at six weeks, but there may have been actually a potential mortality benefit in child's PUA and B cirrhotic patients. So venous thromboembolism prophylaxis.  We suggest using low-molecular weight heparin over pneumatic compression stockings for DVT prophylaxis in hospitalized patients.  This is only in acute on chronic liver failure, and this is a conditional recommendation with low-quality evidence.  The remark is that there's insufficient evidence to allow a recommendation for patients with ALF.  The rationale is that cirrhotic ACLF patients are at increasing risk of developing venous thrombosis.  And this was largely based on one single-centered study that was borrowed literature. It was outpatient cirrhotic patients where they were stratified to low-molecular weight  heparin versus control. And this study found that there was decreasing rates of portal vein thrombosis and rates of hepatic decompensation with no difference in bleeding.  And for the risk of bleeding with invasive procedures, this recommendation, we recommended  viscoelastic testing over measuring INR platelet fibrinogen in critically ill patients with ALF or ACLF undergoing procedures.  This was a strong recommendation with moderate-quality evidence. We know that bleeding risks in ACLF patients with minimally-inviscid patient procedures  such as paracentesis, thoracentesis, and liver biopsy kind of ranges between about 0% and that bleeding does not correlate with INR.  There was a single open-label RCT that looked at patients that were either, they got standard of care blood testing versus TEG and Rotem.  And the patients in the TEG arm had significantly fewer units of blood product transfusion with no difference in bleeding complications or 90-day mortality.  Finally, endocrine considerations. So target glucose control. We recommend targeting a serum blood glucose of between 110 and 180 milligrams per deciliter  in patients with acute or acute-on-chronic liver failure. Strong recommendation, moderate-quality of evidence.  Rationale is that endocrine abnormalities we're aware are common in patients with liver  disease and often necessitate pharmacotherapeutic intervention to prevent adverse events because of adverse changes to glucose metabolism.  Management should incorporate the prevention of both hyper- and hypoglycemia to promote the shortest safe hospital stay and provide an effective transition out of hospital that  prevents acute complications. And this is based on a retrospective study. Role of stress-dose glutocorticoids, which we know there's a lot of controversy and equipoise  in the general septic shock literature. The recommendation is we suggest using stress-dose glutocorticoids in the treatment of septic shock in patients with ALF or ACLF.  This was a conditional recommendation only with low-quality evidence. The remark is that stress-dose glutocorticoids should be used if adequate fluid resuscitation  and vasopressor agents are unable to restore hemodynamic instability. This is based on the fact that relative adrenal insufficiency is actually common in acutely  ill patients with cirrhosis, especially those with septic shock. This is consistent with, as mentioned before, with guidelines in both cirrhotic and non-cirrhotic  patients with septic shock. So dietary protein load, this comes up from time to time because we know that protein  load to the gut can feed ammonia production, which patients with ALF and ACLF may have challenges with metabolizing.  The recommendation was we suggest against the use of a low-protein diet in patients with ALF or ACLF, but rather targeting protein goals comparable to critically ill patients  without liver failure. So this is 1.2 to 2 grams per kilo ideal body weight. Conditional recommendation with very low quality of evidence.  Basically the rationale here was that we know that in patients with cirrhosis often have sarcopenia and are at risk with muscle wasting, and further protein restricting them  will actually deleteriously impact their outcome. There was a RCT of 121 cirrhotic patients randomized to receiving a nutritional therapy  program with 1.1 to 1.5 grams per kilo ideal body weight, and nutrition and education versus no nutrition therapy at all.  And the intervention group received more protein, and yet were less likely to advance to overt hepatic encephalopathy, one of their endpoints of complications of cirrhosis.  So root and timing of feeding. The recommendation was we suggest enteral nutrition over parenteral nutrition in critically  ill hospitalized patients with ALF or ACLF without contradiction to enteral feeding. This is once again a conditional recommendation with low-quality evidence.  The rationale is that the preferential use of enteral nutrition unfortunately has not been studied specifically in patients with ALF or ACLF.  This is based on previous borrowed literature from meta-analysis representing heterogeneous groups of critically ill patients that favored enteral nutrition if were available to use  the gut. And the rationale for this is also to prevent bacterial translocation through trophic feeding of enterocytes. Screening for drug-induced causes of liver failure.  We recommend screening patients with ALF and ACLF for drug-induced liver injury. Drugs that are proven are highly suspected to be the cause of ALF or ACLF should be discontinued.  This is a best practice statement based essentially on the rationale that drug-induced liver injury accounts for more than 50% of acute liver failure in the US.  And while DILI is sometimes a diagnosis of exclusion, the use of a validated score such as the RUCAM score can increase certainty.  There is some data on which has been collected by the DILIN network which you can find at livertalks.gov.  And if there are drugs with proven or highly suspected of being related to ALF in particular  should be immediately discontinued where available an antidote should be administered accompanied by supportive care. Dose adjustments of medications.  In patients with ALF, ACLF, we recommend adjusting the doses of medications that undergo hepatic  metabolism based on the patient's residual hepatic function and using the best available literature. When available, a clinical pharmacist should be consulted.  This is essentially a best practice statement. We're aware that both in ALF and ACLF you get alterations in the hepatic extraction  ratio, biliary extrusion, volume of distribution, and protein binding. So obviously, other confounding factors that may affect this include acute kidney injury  as well as the use of renal replacement therapy where we do have pharmacokinetic data. For other extracorporeal circuits, the data is a little more scant. Thank you very much.

Video Summary

In this video, the speaker discusses the cardiovascular and pulmonary considerations in patients with acute liver failure (ALF) and acute-on-chronic liver failure (ACLF). The recommendations are based on indirect evidence as there is limited direct evidence in this population. The first recommendation is against using hydroxyethyl starch or gelatin solutions for initial fluid resuscitation in ALF and ACLF patients. The rationale is that crystalloids are preferred over these solutions as there is no demonstrated benefit and potential risks. The use of albumin for resuscitation is suggested when serum albumin is low, as it may improve hemodynamics and prevent complications. Blood pressure targets should be aimed at maintaining a mean arterial pressure of 65 mmHg, with consideration for optimizing cerebral perfusion pressure in severe ALF patients. Arterial catheter placement for blood pressure monitoring and invasive hemodynamic monitoring to guide therapy for shock are suggested. Norepinephrine is recommended as the first-line vasopressor agent, with the addition of low-dose vasopressin if refractory to norepinephrine. In terms of pulmonary considerations, a low tidal volume strategy is recommended for mechanical ventilation in ALF and ACLF patients with ARDS, along with the use of positive end-expiratory pressure (PEEP) based on individual patient assessment. The use of pulmonary arterial hypertension therapy in portopulmonary hypertension and supportive care with supplemental oxygen in hepatopulmonary syndrome are also discussed. Lastly, high-flow nasal cannula is suggested over non-invasive ventilation for hypoxic critically ill patients with ALF or ACLF. The renal, hematologic, and endocrine considerations in these patient populations are also discussed in the video.

Asset Subtitle

GI and Nutrition, Renal, 2020

Asset Caption

The Society of Critical Care Medicine's Critical Care Congress features internationally renowned faculty and content sessions highlighting the most up-to-date, evidence-based developments in critical care medicine. This is a presentation from the 2020 Critical Care Congress held February 16-19, 2020, in Orlando, Florida, USA.

Learning Objectives

Apply new knowledge and strategies to optimize the care of the critically ill patient as provided by the multiprofessional team
Examine research results and evidence-based medicine techniques to evaluate and improve patient care
Review and integrate guidelines to measure performance and identify areas for further study and improvement

Guidelines for the Management of Adult Acute and Acute-on-Chronic Liver Failure in the ICU: Cardiovascular and Pulmonary Considerations

Ram M. Subramanian

Guidelines for the Management of Adult Acute and Acute-on-Chronic Liver Failure in the ICU: Endocrine, Hematologic and Renal Considerations

Constantine J. Karvellas

Meta Tag

Content Type Presentation

Knowledge Area Renal

Knowledge Area GI and Nutrition

Knowledge Level Advanced

Membership Level Select

Membership Level Professional

Membership Level Associate

Tag Liver

Tag Kidney

Year 2020

Keywords

cardiovascular

pulmonary

resuscitation

hemodynamics

mechanical ventilation

renal considerations

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