So no disclosures, again just an acknowledgment of the great work done by the group. So let's talk about neurologic considerations in ALF and ACLF. The first question is utility of invasive intracranial monitoring in acute liver failure. So the recommendation here is that we suggest not using invasive ISP monitoring for critically ill ALF patients with advanced grade encephalopathy. This is again a conditional recommendation with low quality of evidence. And the rationale is that the observational studies in this field so far have not demonstrated a mortality benefit. There's no RCTs. And also from a safety standpoint, there's safety concerns regarding bleeding and infection risk, especially with the subdural and the intraparent chymal devices. Moving on to sort of the second question is application of extracorporeal therapy in acute liver failure. And here we suggest when available using plasma exchange with FFP in critically ill ALF patients who develop hyperammonemia defined as a serum ammonia greater than 150, again, conditional recommendation, low quality of evidence. And the rationale here is there is RCT level data, single RCT, that demonstrate a transplant free survival benefit using high volume plasma exchange defined as 8 to 12 liters of FFP. And there's also newer data for standard plasma exchange with the same efficacy compared to standard of care. And the potential mechanism of action of plasma exchange in ALF is that it mitigates the systemic cytokine surge due to acute hepatic failure and thereby improves systemic hemodynamics, which then translates to improved mortality. And then one thing, just as an acknowledgment, I think this may become more important in the next iteration of the liver failure guidelines is the growing role of high dose CRRT, defined as 60 to 90 mils per kilogram per hour dialysate in the management of hyperammonemia, again, defined as greater than 150. And there's growing evidence of its utility and its benefit both from a neurologic standpoint from a transplant free survival benefit. So I just wanted to highlight the concept of high dose CRRT in this context. Moving on to therapies to decrease ICP and ALF, talking about hypertonic saline. In this recommendation, we suggest using hypertonic saline in critically ill ALF patients who are at risk for developing intracranial hypertension, again, conditional recommendation based on low quality evidence. And the risk factors for intracranial hypertension is hyperammonemia defined as greater than 150, high grade hepatic encephalopathy, and multiple organ system failure. And the rationale here is, again, RCT level data demonstrating a decrease in ICP when you target your serum sodium to 145 to 155 compared to normal sodium levels. Moving on to targeted temperature management, here, the recommendations we suggest not routinely using induced moderate hypothermia defined as less than 34 degrees in this patient population at risk for developing intracranial hypertension, again, a conditional recommendation. The rationale here is that observational studies and multicenter RCT did not demonstrate benefit with respect to ICP decrease or survival. Moving on to switching gears. Now we're talking about ACLF in contrast to ALF here. The recommendation one is to suggest using lactulose in critically ill ACLF patients with overt hepatic encephalopathy, again, conditional recommendation. And there is meta-analysis level data of improvement in HE and mortality in cirrhotic patients. Recommendation two, there is some emerging data regarding the use of polyethylene glycol as an alternative to lactulose in critically ill ACLF patients with overt HE, again, conditional recommendation. And again, this is RCT level data, single center, that demonstrates an improvement, a faster improvement in HE compared to lactulose. And then the last recommendation in this category is use of rifaximin, and what we recommend is we suggest using rifaximin as adjunctive therapy as an add-on to lactulose or PEG in critically ill ACLF patients with overt hepatic encephalopathy, again, a conditional recommendation based on single center RCT data. Moving on to ID. So antibiotic prophylaxis for upper GI bleeding in the ACLF, and here it's a strong recommendation for a change. We recommend using antibiotic prophylaxis in critically ill ACLF patients with any type of upper GI bleeding, variceal and non-variceal. And I think as a lot of you know, upper GI bleeding is a risk factor for subsequent gut translocation that can then cause a cytokine surge and cause increased mortality, and there's meta-analysis level data suggesting the benefit of antibiotic prophylaxis in reducing re-bleeding and in reducing mortality. Moving on to SBP management in ACLF, recommendation one is using albumin in critically ill ACLF patients with SBP. This is a strong recommendation, and here's meta-analysis level data that reduces both AKI and mortality. Recommendation two, use of broad-spectrum antibiotics in the initial management of SBP in ACLF, and this is, again, a strong recommendation, again, based on pooled observational studies. And just to make a point that I think a lot of you take care of nosocomial SBP, imagine the cirrhotic who's been in the hospital for a while. Here, you have to be careful about targeting MDR infections with a broader spectrum of antibiotics. And then finally, for recommendation three, we suggest not performing large-volume paracentesis in critically ill patients with SBP. This is, again, conditional, and the rationale here is that LVP can further make a tenuous hemodynamic status worse as you do a large-volume paracentesis. And then finally, systemic antifungal prophylaxis after liver transplant. Here the recommendation suggests using systemic antifungal prophylaxis in critically ill liver transplant patients with the risk factors for invasive fungal infections, conditional recommendation. And here the risk factors that have been identified are renal failure requiring dialysis, acute liver failure, re-exploration after transplant, re-transplantation, and a bile leak after liver transplant. And just the common pathogens can be in Canada, followed by aspergillus. And then, as you all know, invasive fungal infections are an important cause of morbidity and mortality after liver transplant, and it's becoming more of a problem as our patients are getting sicker and sicker, awaiting transplantation, and there's meta-analysis-level data demonstrating that systemic antifungal prophylaxis reduce risk of IFI and mortality attributable to invasive fungal infections. Thanks for your attention. Thank you all very much. Thank you.

acute liver failure

intracranial monitoring

plasma exchange

hepatic encephalopathy

infection management