LIVER TRANSPLANTATION 21:716–717, 2015
EDITORIAL
Liver Transplantation and the Rubicon J. Michael Millis Section of Transplantation, Department of Surgery, University of Chicago, Chicago, IL Received March 23, 2015; accepted March 23, 2015.
See Article on Page 761 In 49 BC, Julius Caesar famously crossed the Rubicon and started the Second Roman Civil War. Quoting his favorite Greek poet, Menander, he stated “alea iacta est”—the die is cast.1 Since then, the Rubicon River has changed its course and character, and it is difficult to determine exactly where “the die was cast.” Since Starzl reported the first series of liver transplants in 1963,2 those who have followed him have tried to determine when the die is cast for our pretransplant patients. As immunosuppression, techniques, and allocation have changed and improved, the ability to salvage patients before they cross the Rubicon has improved as well.3 Two decades ago, there was a general consensus brewing that patients with chronic liver disease who are in the intensive care unit (ICU) and intubated were marginal candidates for successful liver transplantation. The article by Knaak et al.4 in this issue of Liver Transplantation indicates that at least some of those patients who are in this state and undergo transplantation have a reasonable opportunity for a successful recovery. First, one must understand that the ICU-bound group accounts for approximately 12% of the transplants performed at this center over the time period reviewed. Furthermore, only 4% were the most decompensated as defined by needing mechanical ventilation.4 This statement, however, highlights a large caveat in this study. There is a selection bias in those who receive a transplant, which is to say that not all patients at this center or any center that have the described characteristics are transplanted. It would have added value to the manuscript to identify similar ICU patients [fraction of inspired oxygen (FiO2) 40, positive end-expiratory pressure (PEEP) 10, low pressor requirements, and lack of active infection]
who did not receive a transplant and the reasons why. The authors also do not define the population in terms of how many of the risk factors (intubated, FiO2 40, PEEP 10, low pressor requirements, and lack of active infection) the patients were allowed to exhibit and still be transplant candidates and how the combination of factors might influence posttransplant outcome. This would have provided insight into the keys of clinical judgment. The authors also do not define the characteristics of the 80 patients who required ICU care and who did not require respiratory support. The authors are clear in their message: selected patients in the ICU whether intubated or not, on low-level vasopressors or not can obtain acceptable patient and graft survival. The authors do not state nor should it be assumed at all that patients with chronic liver disease in the ICU should undergo liver transplantation. There must be clinical judgment applied to these very ill patients. The authors also note that there is a price to play in being aggressive with ICU candidates and liver transplantation. The price is that although survival is acceptable, there is a clear decrement in survival for those patients who are intubated (not statistically significant) and a statistically significant decrease for those with significant neurologic impairment. The current regulatory environment that places a severe penalty on decreased 1-year patient and graft survival has been shown to influence center behavior.5 The term “acceptable” may be seen in different phases of regulatory oversight. If a program is close to the area in which there would be increased regulatory oversight, acceptable survival may not be good enough. However, if a program is well above that regulatory threshold, “acceptable” may be enough to give a patient a chance at survival just before they cross the Rubicon. There is also a price in increased resource utilization with extended periods of posttransplant
Abbreviations: ICU, intensive care unit; PEEP, positive end-expiratory pressure. Address reprint requests to J. Michael Millis, M.D., Section of Transplantation, Department of Surgery, MC 5027, 5841 South Maryland Avenue, Chicago, IL 60637. FAX: 773-702-7511; E-mail: [email protected] DOI 10.1002/lt.24130 View this article online at wileyonlinelibrary.com. LIVER TRANSPLANTATION.DOI 10.1002/lt. Published on behalf of the American Association for the Study of Liver Diseases
C 2015 American Association for the Study of Liver Diseases. V
LIVER TRANSPLANTATION, Vol. 21, No. 6, 2015
ICU stay, total hospital stay, and an increased rate of complications in the intubated ICU group. The allocation schema changes over the years, and the projected changes in the future advantage these very ill patients over those in protected local geographic areas and the lessons from the Knaak et al. article and others that will undoubtedly follow will help guide the clinical decision-making process. The ICU care of decompensated liver patients is not similar to most patients in large medical ICUs. The ticket for admission in most medical ICUs is based on ventilatory, cardiac, or systemic blood pressure insufficiency. For patients with decompensated liver disease, these issues are frequently much closer to when the “die is cast” than when most patients should be transplanted. More intensive care of the severely decompensated patient in the ICU may give these patients critical time during a “window period” in which programs can identify a suitable donor. Gatekeepers of the ICU often deprioritize the decompensating liver patient in relationship to the decompensating cardiac or pulmonary patient. As the pressure on programs to maintain and grow volume increases with allocation changes, there
EDITORIAL 717
will be a tendency to push the envelope and to navigate the river before the “die is cast.” Transplant centers and payers will need to understand that the resource utilization and costs will increase as we further define the benefit and push futility further away.
REFERENCES 1. Lendering J. Menander. http://www.livius.org/person/ menander/. Accessed March 5, 2015. 2. Starzl TE, Marchioro TL, Vonkaulla KN, Hermann G, Brittain RS, Waddell WR. Homotransplantation of the liver in humans. Surg Gynecol Obstet 1963;117:659-676. 3. Dawwas MF, Gimson AE. Candidate selection and organ allocation in liver transplantation. Semin Liver Dis 2009; 29:40-52. 4. Knaak J, McVey M, Bazerbachi F, Goldaracena N, Spetzler V, Selzner N, et al. Liver transplantation in patients with end-stage liver disease requiring intensive care unit admission and intubation. Liver Transpl 2015; doi: 10.1002/lt.24115. 5. Buccini LD, Segev DL, Fung J, Miller C, Kelly D, Quintini C, Schold JD. Association between liver transplant center performance evaluations and transplant volume. Am J Transplant 2014;14:2097-2105.
EDITORIAL
Liver Transplantation and the Rubicon J. Michael Millis Section of Transplantation, Department of Surgery, University of Chicago, Chicago, IL Received March 23, 2015; accepted March 23, 2015.
See Article on Page 761 In 49 BC, Julius Caesar famously crossed the Rubicon and started the Second Roman Civil War. Quoting his favorite Greek poet, Menander, he stated “alea iacta est”—the die is cast.1 Since then, the Rubicon River has changed its course and character, and it is difficult to determine exactly where “the die was cast.” Since Starzl reported the first series of liver transplants in 1963,2 those who have followed him have tried to determine when the die is cast for our pretransplant patients. As immunosuppression, techniques, and allocation have changed and improved, the ability to salvage patients before they cross the Rubicon has improved as well.3 Two decades ago, there was a general consensus brewing that patients with chronic liver disease who are in the intensive care unit (ICU) and intubated were marginal candidates for successful liver transplantation. The article by Knaak et al.4 in this issue of Liver Transplantation indicates that at least some of those patients who are in this state and undergo transplantation have a reasonable opportunity for a successful recovery. First, one must understand that the ICU-bound group accounts for approximately 12% of the transplants performed at this center over the time period reviewed. Furthermore, only 4% were the most decompensated as defined by needing mechanical ventilation.4 This statement, however, highlights a large caveat in this study. There is a selection bias in those who receive a transplant, which is to say that not all patients at this center or any center that have the described characteristics are transplanted. It would have added value to the manuscript to identify similar ICU patients [fraction of inspired oxygen (FiO2) 40, positive end-expiratory pressure (PEEP) 10, low pressor requirements, and lack of active infection]
who did not receive a transplant and the reasons why. The authors also do not define the population in terms of how many of the risk factors (intubated, FiO2 40, PEEP 10, low pressor requirements, and lack of active infection) the patients were allowed to exhibit and still be transplant candidates and how the combination of factors might influence posttransplant outcome. This would have provided insight into the keys of clinical judgment. The authors also do not define the characteristics of the 80 patients who required ICU care and who did not require respiratory support. The authors are clear in their message: selected patients in the ICU whether intubated or not, on low-level vasopressors or not can obtain acceptable patient and graft survival. The authors do not state nor should it be assumed at all that patients with chronic liver disease in the ICU should undergo liver transplantation. There must be clinical judgment applied to these very ill patients. The authors also note that there is a price to play in being aggressive with ICU candidates and liver transplantation. The price is that although survival is acceptable, there is a clear decrement in survival for those patients who are intubated (not statistically significant) and a statistically significant decrease for those with significant neurologic impairment. The current regulatory environment that places a severe penalty on decreased 1-year patient and graft survival has been shown to influence center behavior.5 The term “acceptable” may be seen in different phases of regulatory oversight. If a program is close to the area in which there would be increased regulatory oversight, acceptable survival may not be good enough. However, if a program is well above that regulatory threshold, “acceptable” may be enough to give a patient a chance at survival just before they cross the Rubicon. There is also a price in increased resource utilization with extended periods of posttransplant
Abbreviations: ICU, intensive care unit; PEEP, positive end-expiratory pressure. Address reprint requests to J. Michael Millis, M.D., Section of Transplantation, Department of Surgery, MC 5027, 5841 South Maryland Avenue, Chicago, IL 60637. FAX: 773-702-7511; E-mail: [email protected] DOI 10.1002/lt.24130 View this article online at wileyonlinelibrary.com. LIVER TRANSPLANTATION.DOI 10.1002/lt. Published on behalf of the American Association for the Study of Liver Diseases
C 2015 American Association for the Study of Liver Diseases. V
LIVER TRANSPLANTATION, Vol. 21, No. 6, 2015
ICU stay, total hospital stay, and an increased rate of complications in the intubated ICU group. The allocation schema changes over the years, and the projected changes in the future advantage these very ill patients over those in protected local geographic areas and the lessons from the Knaak et al. article and others that will undoubtedly follow will help guide the clinical decision-making process. The ICU care of decompensated liver patients is not similar to most patients in large medical ICUs. The ticket for admission in most medical ICUs is based on ventilatory, cardiac, or systemic blood pressure insufficiency. For patients with decompensated liver disease, these issues are frequently much closer to when the “die is cast” than when most patients should be transplanted. More intensive care of the severely decompensated patient in the ICU may give these patients critical time during a “window period” in which programs can identify a suitable donor. Gatekeepers of the ICU often deprioritize the decompensating liver patient in relationship to the decompensating cardiac or pulmonary patient. As the pressure on programs to maintain and grow volume increases with allocation changes, there
EDITORIAL 717
will be a tendency to push the envelope and to navigate the river before the “die is cast.” Transplant centers and payers will need to understand that the resource utilization and costs will increase as we further define the benefit and push futility further away.
REFERENCES 1. Lendering J. Menander. http://www.livius.org/person/ menander/. Accessed March 5, 2015. 2. Starzl TE, Marchioro TL, Vonkaulla KN, Hermann G, Brittain RS, Waddell WR. Homotransplantation of the liver in humans. Surg Gynecol Obstet 1963;117:659-676. 3. Dawwas MF, Gimson AE. Candidate selection and organ allocation in liver transplantation. Semin Liver Dis 2009; 29:40-52. 4. Knaak J, McVey M, Bazerbachi F, Goldaracena N, Spetzler V, Selzner N, et al. Liver transplantation in patients with end-stage liver disease requiring intensive care unit admission and intubation. Liver Transpl 2015; doi: 10.1002/lt.24115. 5. Buccini LD, Segev DL, Fung J, Miller C, Kelly D, Quintini C, Schold JD. Association between liver transplant center performance evaluations and transplant volume. Am J Transplant 2014;14:2097-2105.
