Perioperative Management of the Liver Transplant Recipient.

Perioperative management of the liver transplant recipient is a team effort that requires close collaboration between intensivist, surgeon, anesthesiologist, hepatologist, nephrologist, other specialists, and hospital staff before and after surgery. Transplant viability must be reassessed regularly and particularly with each donor organ. Regular discussions with patient and family facilitate realistic determinations of goals based on patient aspirations and clinical realities. Early attention to hemodynamics with optimal resuscitation and judicious vasopressor support, respiratory care designed to minimize iatrogenic injury, and early renal support is key. Preoperative and postoperative nutritional support and physical rehabilitation should remain a focus.

The Liver in Critical Illness.

Caring for critically ill patients with acute and/or chronic liver dysfunction poses a unique challenge. Proper resuscitation and early consideration for transfer to liver transplant centers have resulted in improved outcomes. Liver support devices and cellular models have not yet shown mortality benefit, but they hold promise in the critical care of patients with liver disease. This article reviews pertinent anatomic and physiologic considerations of the liver in critical illness, followed by a selective review of associated organ dysfunction.

Perioperative Care of the Liver Transplant Patient.

With the evolution of surgical and anesthetic techniques, liver transplantation has become "routine," allowing for modifications of practice to decrease perioperative complications and costs. There is debate over the necessity for intensive care unit admission for patients with satisfactory preoperative status and a smooth intraoperative course. Postoperative care is made easier when the liver graft performs optimally. Assessment of graft function, vigilance for complications after the major surgical insult, and optimization of multiple systems affected by liver disease are essential aspects of postoperative care. The intensivist plays a vital role in an integrated multidisciplinary transplant team.

Scedosporiosis in a Combined Kidney and Liver Transplant Recipient: A Case Report of Possible Transmission from a Near-Drowning Donor.

Scedosporium spp. are saprobic fungi that cause serious infections in immunocompromised hosts and in near-drowning victims. Solid organ transplant recipients are at increased risk of scedosporiosis as they require aggressive immunosuppression to prevent allograft rejection. We present a case of disseminated Scedosporium apiospermum infection occurring in the recipient of a combined kidney and liver transplantation whose organs were donated by a near-drowning victim and review the literature of scedosporiosis in solid organ transplantation.

Outcomes following liver transplantation in intensive care unit patients.

AIM: To determine feasibility of liver transplantation in patients from the intensive care unit (ICU) by estimating graft and patient survival. METHODS: This single center retrospective study included 39 patients who had their first liver transplant directly from the intensive care unit and 927 non-ICU patients who were transplanted from hospital ward or home between January 2005 and December 2010. RESULTS: In comparison to non-ICU patients, ICU patients had a higher model for end-stage liver disease (MELD) at transplant (median: 37 vs 20, P < 0.001). Fourteen out of 39 patients (36%) required vasopressor support immediately prior to liver transplantation (LT) with 6 patients (15%) requiring both vasopressin and norepinephrine. Sixteen ICU patients (41%) were ventilator dependent immediately prior to LT with 9 patients undergoing percutaneous tracheostomy prior to transplantation. Twenty-five ICU patients (64%) required dialysis preoperatively. At 1, 3 and 5 years after LT, graft survival was 76%, 68% and 62% in ICU patients vs 90%, 81% and 75% in non-ICU patients. Patient survival at 1, 3 and 5 years after LT was 78%, 70% and 65% in ICU patients vs 94%, 85% and 79% in non-ICU patients. When formally comparing graft survival and patient survival between ICU and non-ICU patients using Cox proportional hazards regression models, both graft survival [relative risk (RR): 1.94, 95%CI: 1.09-3.48, P = 0.026] and patient survival (RR: 2.32, 95%CI: 1.26-4.27, P = 0.007) were lower in ICU patients vs non-ICU patients in single variable analysis. These findings were consistent in multivariable analysis. Although not statistically significant, graft survival was worse in both patients with cryptogenic cirrhosis (RR: 3.29, P = 0.056) and patients who received donor after cardiac death (DCD) grafts (RR: 3.38, P = 0.060). These findings reached statistical significance when considering patient survival, which was worse for patients with cryptogenic cirrhosis (RR: 3.97, P = 0.031) and patients who were transplanted with DCD livers (RR: 4.19, P = 0.033). Graft survival and patient survival were not significantly worse for patients on mechanical ventilation (RR: 0.91, P = 0.88 in graft loss; RR: 0.69, P = 0.56 in death) or patients on vasopressors (RR: 1.06, P = 0.93 in graft loss; RR: 1.24, P = 0.74 in death) immediately prior to LT. Trends toward lower graft survival and patient survival were observed for patients on dialysis immediately before LT, however these findings did not approach statistical significance (RR: 1.70, P = 0.43 in graft loss; RR: 1.46, P = 0.58 in death). CONCLUSION: Although ICU patients when compared to non-ICU patients have lower survivals, outcomes are still acceptable. Pre-transplant ventilation, hemodialysis, and vasopressors were not associated with adverse outcomes.

Liver transplantation in the critically ill: donation after cardiac death compared to donation after brain death grafts.

 Patients with end stage liver disease may become critically ill prior to LT requiring admission to the intensive care unit (ICU). The high acuity patients may be thought too ill to transplant; however, often LT is the only therapeutic option. Choosing the correct liver allograft for these patients is often difficult and it is imperative that the allograft work immediately. Donation after cardiac death (DCD) donors provide an important source of livers, however, DCD graft allocation remains a controversial topic, in critically ill patients. Between January 2003-December 2008, 1215 LTs were performed: 85 patients at the time of LT were in the ICU. Twelve patients received DCD grafts and 73 received donation after brain dead (DBD) grafts. After retransplant cases and multiorgan transplants were excluded, 8 recipients of DCD grafts and 42 recipients of DBD grafts were included in this study. Post-transplant outcomes of DCD and DBD liver grafts were compared. While there were differences in graft and survival between DCD and DBD groups at 4 month and 1 year time points, the differences did not reach statistical significance. The graft and patient survival rates were similar among the groups at 3-year time point. There is need for other large liver transplant programs to report their outcomes using liver grafts from DCD and DBD donors. We believe that the experience of the surgical, medical and critical care team is important for successfully using DCD grafts for critically ill patients.

Asystole to cross-clamp period predicts development of biliary complications in liver transplantation using donation after cardiac death donors.

This study sought to determine the procurement factors that lead to development of intrahepatic bile duct strictures (ITBS) and overall biliary complications in recipients of donation after cardiac death (DCD) liver grafts. Detailed information for different time points during procurement (withdrawal of support; SBP < 50 mmHg; oxygen saturation <30%; mandatory wait period; asystole; incision; aortic cross clamp) and their association with the development of ITBS and overall biliary complications were examined using logistic regression. Two hundred and fifteen liver transplants using DCD donors were performed between 1998 and 2010 at Mayo Clinic Florida. Of all the time periods during procurement, only asystole-cross clamp period was significantly different between patients with ITBS versus no ITBS (P = 0.048) and between the patients who had overall biliary complications versus no biliary complications (P = 0.047). On multivariate analysis, only asystole-cross clamp period was significant predictor for development of ITBS (P = 0.015) and development of overall biliary complications (P = 0.029). Hemodynamic changes in the agonal period did not emerge as risk factors. The results of the study raise the possibility of utilizing asystole-cross-clamp period in place of or in conjunction with donor warm ischemia time in determining viability or quality of liver grafts.

Do long radiology workdays affect nodule detection in dynamic CT interpretation?

PURPOSE: A previous study demonstrated decreased diagnostic accuracy for finding fractures and decreased ability to focus on skeletal radiographs after a long working day. Skeletal radiographic examinations commonly have images that are displayed statically. The aim of this study was to investigate whether diagnostic accuracy for detecting pulmonary nodules on CT of the chest displayed dynamically would be similarly affected by fatigue. METHODS: Twenty-two radiologists and 22 residents were given 2 tests searching CT chest sequences for a solitary pulmonary nodule before and after a day of clinical reading. To measure search time, 10 lung CT sequences, each containing 20 consecutive sections and a single nodule, were inspected using free search and navigation. To measure diagnostic accuracy, 100 CT sequences, each with 20 sections and half with nodules, were displayed at preset scrolling speed and duration. Accuracy was measured using receiver operating characteristic curve analysis. Visual strain was measured via dark vergence, an indicator of the ability to keep the eyes focused on the display. RESULTS: Diagnostic accuracy was reduced after a day of clinical reading (P = .0246), but search time was not affected (P > .05). After a day of reading, dark vergence was significantly larger and more variable (P = .0098), reflecting higher levels of visual strain, and subjective ratings of fatigue were also higher. CONCLUSIONS: After their usual workday, radiologists experience increased fatigue and decreased diagnostic accuracy for detecting pulmonary nodules on CT. Effects of fatigue may be mitigated by active interaction with the display.

Events in procurement as risk factors for ischemic cholangiopathy in liver transplantation using donation after cardiac death donors.

The use of donation after cardiac death (DCD) liver grafts is controversial because of the overall increased rates of graft loss and morbidity, which are mostly related to the consequences of ischemic cholangiopathy (IC). In this study, we sought to determine the factors leading to graft loss and the development of IC and to compare patient and graft survival rates for recipients of DCD liver grafts and recipients of donation after brain death (DBD) liver grafts in a large series at a single transplant center. Two hundred liver transplants with DCD donors were performed between 1998 and 2010 at Mayo Clinic Florida. Logistic regression models were used in the univariate and multivariate analyses of predictors for the development of IC. Additional analyses using Cox regression models were performed to identify predictors of graft survival and to compare outcomes for DCD and DBD graft recipients. In our series, the patient survival rates for the DCD and DBD groups at 1, 3, and 5 years was 92.6%, 85%, and 80.9% and 89.8%, 83.0%, and 76.6%, respectively (P = not significant). The graft survival rates for the DCD and DBD groups at 1, 3, and 5 years were 80.9%, 72.7%, and 68.9% and 83.3%, 75.1%, and 68.6%, respectively (P = not significant). In the DCD group, 5 patients (2.5%) had primary nonfunction, 7 patients (3.5%) had hepatic artery thrombosis, and 3 patients (1.5%) experienced hepatic necrosis. IC was diagnosed in 24 patients (12%), and 11 of these patients (5.5%) required retransplantation. In the multivariate analysis, the asystole-to-cross clamp duration [odds ratio = 1.161, 95% confidence interval (CI) = 1.021-1.321] and African American recipient race (odds ratio = 5.374, 95% CI = 1.368-21.103) were identified as significant factors for predicting the development of IC (P < 0.05). This study has established a link between the development of IC and the asystole-to-cross clamp duration. Procurement techniques that prolong the nonperfusion period increase the risk for the development of IC in DCD liver grafts.

Is a mandatory intensive care unit stay needed after liver transplantation? Feasibility of fast-tracking to the surgical ward after liver transplantation.

The continuation of hemodynamic, respiratory, and metabolic support for a variable period after liver transplantation (LT) in the intensive care unit (ICU) is considered routine by many transplant programs. However, some LT recipients may be liberated from mechanical ventilation shortly after the discontinuation of anesthesia. These patients might be appropriately discharged from the postanesthesia care unit (PACU) to the surgical ward and bypass the ICU entirely. In 2002, our program started a fast-tracking program: select LT recipients are transferred from the operating room to the PACU for recovery and tracheal extubation with a subsequent transfer to the ward, and the ICU stay is completely eliminated. Between January 1, 2003 and December 31, 2007, 1045 patients underwent LT at our transplant program; 175 patients were excluded from the study. Five hundred twenty-three of the remaining 870 patients (60.10%) were fast-tracked to the surgical ward, and 347 (39.90%) were admitted to the ICU after LT. The failure rate after fast-tracking to the surgical ward was 1.90%. The groups were significantly different with respect to the recipient age, the raw Model for End-Stage Liver Disease (MELD) score at the time of LT, the recipient body mass index (BMI), the retransplantation status, the operative time, the warm ischemia time, and the intraoperative transfusion requirements. A multivariate logistic regression analysis revealed that the raw MELD score at the time of LT, the operative time, the intraoperative transfusion requirements, the recipient age, the recipient BMI, and the absence of hepatocellular cancer/cholangiocarcinoma were significant predictors of ICU admission. In conclusion, we are reporting the largest single-center experience demonstrating the feasibility of bypassing an ICU stay after LT.

Intensive care of the patient with cirrhosis.

Acute deterioration of patients with cirrhosis manifests as multiple organ failure requiring admission to an intensive care unit. Precipitating events may be viral hepatitis, typically in Asia, and drug or alcoholic hepatitis and variceal hemorrhage in the West. Patients with cirrhosis in the intensive care unit have a high mortality, and each admission is associated with a mean charge of US $116,200. Prognosis is determined by the number of organs failing (sequential organ failure assessment [SOFA] score), the presence of infection, and the degree of liver dysfunction (Child-Turcotte-Pugh or Model for End-Stage Liver Disease scores). The most common organ failing is the kidney; sepsis is associated with further deterioration in liver function by compromise of the microcirculation. Care of these critically ill patients with impending multiple organ failure requires a team approach with expertise in both hepatology and critical care. Treatment is aimed at preventing further deterioration in liver function, reversing precipitating factors, and supporting failing organs. Liver transplantation is required in selected patients to improve survival and quality of life. Treatment is futile in some patients, but it is difficult to identify these patients a priori. Artificial and bioartificial liver support systems have thus far not demonstrated significant survival benefit in these patients.

Long-term outcomes after third liver transplant.

OBJECTIVES: Orthotopic liver transplant is the treatment of choice for patients with end-stage liver disease. Patients with first graft failure requiring liver retransplant are commonly seen at most liver transplant centers. However, patients with a second graft failure requiring a third graft are uncommon. Liver retransplant in this setting has only been pursued at a few large transplant centers. MATERIALS AND METHODS: This is a retrospective analysis of the long-term outcomes of recipients who underwent 3 or more orthotopic liver transplants. Between February 1998 and August 2009, 24 patients had 3 or more orthotopic liver transplants at the Mayo Clinic in Florida. RESULTS: Mean patient survival was 103.8 months for the study cohort. Actuarial patient survival after the last orthotopic liver transplant in -1, -5, and -10 years was 60%, 40%, 33%. Patients were transplanted with lower donor risk index score grafts in each subsequent orthotopic liver transplant. Patients who had a graft with a donor risk index score > 1.6 at the time of the third orthotopic liver transplant had significantly lower survival rate compared with those with grafts with a donor risk index score ≤ 1.6. CONCLUSIONS: Multiple liver retransplants offer acceptable patient survival. Each transplant program must decide whether to do multiple orthotopic liver transplants based on the program's transplant volume and outcomes to help this subgroup of patients. The concerns of potentially decreasing access to first time orthotopic liver transplant candidates should also be weighed in the decision to move forward.

Improving graft survival for patients undergoing liver transplantation.

Liver transplant (LT) outcomes are reported to be improving in non-HCV recipients but not for those infected with HCV. Our aim was to evaluate graft survival and predictors of outcome in HCV and non-HCV patients before and after 2003. Patients with primary LT between February 1, 1998, and December 31, 2005, were included. Patients were divided into Era 1 (1998-2002) and Era 2 (2003-2005) with follow-up through May 31, 2009. Graft survival was compared for HCV, non-HCV, and all patients. There was significant improvement in graft survival in Era 2 for HCV patients. Graft survival in Era 2 of HCV patients was equivalent to non-HCV patients. The most significant improvement between eras was in outcomes of grafts from donors ≥60 yr with three-yr graft survival 58.6 (51.3-65.9) vs. 75.4 (68.9-81.9), p = 0.002. The use of donors ≥60 did not change between eras: 31% vs. 34%; however, utilization in HCV recipients decreased from 36% to 3% (p < 0.001). In conclusion, graft survival of HCV patients has improved significantly since 2003 and was comparable to non-HCV patients up to three yr. The change in management of donor organs into HCV and non-HCV patients likely contributed to this outcome.