Extra-Corporeal Systems in Acute Liver Failure: Tips and tricks on ECLS in ALF management

Speakers: Ram Subramanian, Emory University Hospital, Atlanta, US

Ram Subramanian: With respect to the use of ECLS systems in the treatment of ALF, there are two modalities that we use at our center. Number one is high-dose CRRT targeted at treating hyperammonemia in order to prevent intracranial hypertension and herniation. And number two, to treat metabolic acidosis, which can happen in the context of severe hepatic injury. So that's modality number one. The modality number two is high volume plasma exchange. As you a lot of you may know there is RCT level data documenting its efficacy in improving transplant-free survival in ALF. So we use high dose plasma exchange, typically as add-on therapy to high-dose CRRT, with a specific focus on improving severe shock in the context of acute liver failure. So that's the strategy with respect to the ECLS systems. and ALF. Number one is high dose CRRT, number two is high volume plasma exchange.

Ram Subramanian: With respect to the management of coagulation disorders in ALF, I think the first one that needs to be made is that an elevated INR does not necessarily imply that the patient is at increased risk for bleeding. As you know the INR normally measures one side of the coagulation cascade that includes factor V and VII and does not gauge the other side of the coagulation cascade that includes Protein C and Protein S. So despite the high INR, the net state of coagulation may be relatively normal. And ideally, if you have TEG or Rotem, that would give you added value as far as measuring the true state of the coagulation cascade and give you more insight into what pathways need to be corrected. Number two: When you think about, from a practical standpoint, starting ECLS systems in coagulopathic patients, we typically target compressible vascular sites. Were trying to place the dialysis catheter for example. So you can target the internal jugular site or the femoral site that are compressible sites rather than subclavian side. And the other practical take-home point would be that if you need to correct an INR of seven, for example, you can use short-acting agents like profound and complex concentrate in order to induce transient reversal of the coagulopathy, do your invasive procedures, and then the INR can then drift back to where it would have been if you had not intervened with a correcting agent, and therefore you can start using the INR as a prognostic indicator again to give you insight into the trajectory of the ALF casket.

Ram Subramanian: With respect to the application of high-dose CRRT and plasma exchange, I want to share a few other practical take home points. So, the first point is that when you start high-dose CRRT, the dialysis dozing should be almost 2-3 times what you normally do in general septic shocks. So we're looking at dialysis doses as high as 60-90 ml/kg/h. So that is what we define as high dose CRRT. That is based on the fact that those doses of dialysis therapy are required for effective and timely reversal of hyperammonemia in these patients with the goal to bring the cerebral ammonia down to less than 150, and ideally in the younger brain you can argue less than 100. The second point related to CRRT administration is that it corrects severe metabolic acidosis, which is also typically found these patients, and which can have implications regarding hemodynamic management. So you want to optimize your pH so that your pressors can work at an optimal PH. So there's a couple of thoughts regarding CRRT targeting hyperammonemia and targeting metabolic acidosis. Number two is the utility of high volume plasma exchange. In fact, we have slowly moved even regular volume plasma exchange and maintained the same benefits and potentially avoided the side effects of high volume plasma exchange with a longer duration and a higher dose of FFP, which can cause side effects like TRALI. So that is something to mention in the context of plasma exchange. And the second point I would like to make, as I mentioned before, is that we typically add-on plasma exchange to CRRT, especially in the patient with the ALF, who has severe shock. Our experience has been that plasma exchange has been very effective in reversing refractory shock. In these patients, the PLEX almost acts like a cytokine sink to remove pro-inflammatory mediators that may be causing severe shock. So, the sequence of events at our center is to start with high-dose CRRT. Number two, add-on PLEX, especially if you have severe shock. And the last point to be made is that in really complex patients with severe shock, We have even co-administered high-dose CRRT and PLEX through two separate catheters at the same time with the goal to not stop CRRT as we initiate PLEX, given the tenuous nature of the patient.