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.

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.

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.

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.

Automated prone positioning and axial rotation in critically ill, nontrauma patients with acute respiratory distress syndrome (ARDS).

The objective of this study was to evaluate the use of kinetic therapy beds for automated prone positioning and axial rotation in critically ill nontrauma patients with acute respiratory distress syndrome (ARDS). There were 17 patients with ARDS who underwent automated prone positioning using a kinetic therapy bed. The mean age was 51 + 14 years; 12 were females and 12 were Caucasian. The most common admission diagnosis was sepsis (n = 5). The mean Acute Physiology and Chronic Health Evaluation (APACHE) 2 score was 30 + 9 with mean predicted mortality of 65% + 25%. At the time of prone positioning, all patients met the criteria for ARDS. The mean ratio of PaO2 to FIO2 (P/F ratio) before initiation of prone positioning was 89 + 33 and rose to 224 + 92 after at least 30 minutes of prone positioning (P < .0001). There was no significant change in PaCO2 or mean airway pressure. There were no instances of accidental endotracheal tube and central or peripheral venous or arterial catheter dislodgement. Eleven (65%) patients developed new pressure ulcers, 10 (59%) patients developed new skin tears, and all had conjunctival edema during the course of prone positioning. The median duration of automated prone positioning was 6 (interquartile range [IQR] 3.5-8.5) days. Eleven (65%) patients died during hospitalization and 7 required percutaneous tracheostomy for long-term ventilator support. Automated prone positioning using a kinetic therapy bed is a safe and effective means of improving oxygenation in critically ill patients with ARDS. Larger randomized studies are needed to compare it to conventional ventilation strategies, conventional prone positioning, and to assess the impact on mortality.

HCV recurrence in HIV-infected patients after liver transplant.

Patients coinfected with hepatitis C virus (HCV) and HIV undergoing liver transplantation (LT) are at risk of early, aggressive HCV recurrence. This study investigates the use of frequent protocol-driven biopsies to identify HCV recurrence post LT in coinfected patients. Five consecutive HIV/HCV-coinfected patients underwent LT. Liver biopsies were obtained post LT at 1 hour; days 7, 120, and 365; then annually; and as clinically indicated. Stage 2 (Ishak) or higher fibrosis occurred in 4 of the 5 patients by 60, 120, 270, and 365 days. Two patients died of HCV recurrence and liver failure at 6 and 35 months post LT. Three patients survived more than 4 years after LT, 2 having sustained virologic responses to anti-HCV treatment. Another has histologic recurrence not responding to treatment. Hepatitis C virus recurrence can be rapid and aggressive after LT in HIV-coinfected patients. Serial biopsies identify recurrence early, allowing for prompt initiation of treatment.

Transplantation for acute liver failure: perioperative management.

PURPOSE OF REVIEW: A number of conditions can lead to acute liver failure. Determining the cause has important prognostic implications that guide decisions regarding the likelihood of spontaneous recovery, or conversely, the need for transplantation. RECENT FINDINGS: Neurological deterioration is associated with intracranial hypertension, which requires meticulous management. The decision to employ invasive intracranial pressure monitoring is controversial because of associated risks and the lack of controlled studies. Recent literature addressing the use of intracranial pressure monitoring is reviewed. SUMMARY: Even tertiary care units that specialize in liver disease treat acute liver failure patients infrequently. Knowledge of the latest guidelines and treatment protocols can lead to improved patient care.

Unexplained and prolonged perioperative hypotension after orthotopic liver transplantation: undiagnosed systemic mastocytosis.

Arterial vasodilation is common in end-stage liver disease, and systemic hypotension often may develop, despite an increase in cardiac output. During the preparation for and the performance of orthotopic liver transplantation, expected and transient hypotension may be caused by induction agents, anesthetic agents, liver mobilization, or venous clamping. A mild decrease of the already low systemic vascular resistance is often observed, and intermittent use of short-acting agents for vasopressor support is not uncommon. In this report, we describe a patient with unexpected and prolonged hypotension due to vasodilation during and after orthotopic liver transplantation. The preoperative end-stage liver disease evaluation, intraoperative events, and intensive care unit course were reviewed, and no cause for the vasodilation and prolonged hypotension was evident. The explant pathology report was later available and showed systemic mastocytosis. We hypothesize that the unexpected hypotension and vasodilation were caused by mast cell degranulation and its systemic effects on arterial tone.

Liver transplantation using controlled donation after cardiac death donors: an analysis of a large single-center experience.

The use of donation after cardiac death (DCD) donors may provide a valuable source of organs for liver transplantation. Concerns regarding primary nonfunction (PNF) and intrahepatic biliary stricture (IHBSs) have limited the enthusiasm for their use. A retrospective analysis of 1436 consecutive deceased donor liver transplants performed between December 1998 and October 2006 was conducted. These included 108 DCD liver transplants, which were compared to 1328 transplants performed with organs from donors meeting the criteria for donation after brain death (DBD). The median follow-up was 48 months. The 1-, 3-, and 5-year patient survival and graft survival for DCD donors were 91.5%, 88.1%, and 88.1% and 79.3%, 74.5%, and 71.0%, respectively. The 1-, 3-, and 5-year patient survival and graft survival for DBD donors were 87.3%, 81.1%, and 77.2% and 81.6%, 74.7%, and 69.1%, respectively. Patient survival and graft survival were not significantly different between DCD donors less than 60 years old, DCD donors greater than 60 years old, and DBD donors. Causes of graft loss included IHBSs (n = 9), PNF (n = 4), recurrent hepatitis C virus (n = 4), hepatic artery thrombosis (n = 1), rejection (n = 2), and patient death (n = 13). Contrary to previously published data, excellent long-term patient survival and graft survival can be obtained with DCD allografts, and in our experience, they are equivalent to those obtained from DBD allografts.

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.

Application of intensive care medicine principles in the management of the acute liver failure patient.

1. Acute liver failure is a paradigm for multiple system organ failure that develops as a consequence of sepsis. 2. In the United States, systemic inflammatory response, sepsis, and septic shock are common reasons for intensive care unit admission. Intensive care management of these patients serves as a template for the management of patients with acute liver failure. 3. Acute liver failure is attended by high mortality. Although intensive care results in improved survival, the key treatment is liver transplantation. Intensive care unit intervention may open a "window of opportunity" and enable successful liver transplantation in patients who are too ill at presentation. 4. Intracranial hypertension complicates the course for many patients with acute liver failure. Initially, intracranial hypertension results from hyperemia, which is cerebral edema that reduces cerebral blood flow and eventuates in herniation. The precepts of neurocritical care-monitoring cerebral perfusion pressure, cerebral blood flow, and cortical activity-with rapid response to hemodynamic abnormalities, maintenance of normoxia, euglycemia, control of seizures, therapeutic hypothermia, osmotic therapy, and judicious hyperventilation are key to reducing mortality attributable to neurologic failure.

Safety of percutaneous dilatational tracheostomy with direct bronchoscopic guidance for solid organ allograft recipients.

OBJECTIVE: To determine the safety of percutaneous dilatational tracheostomy (PDT) for solid organ allograft recipients, who have increased risks of bleeding and infection. PARTICIPANTS AND METHODS: We reviewed the records of patients who underwent solid organ transplant between January 1, 2001, and September 30, 2005, followed by PDT (using the Ciaglia technique) with direct bronchoscopic guidance. We recorded comorbid conditions, number of days from intubation and transplant, positive end-expiratory pressures, ratios of PaO2 to fraction of inspired oxygen, coagulation study findings, complications, and procedure-related mortality rates. RESULTS: Of the 51 patients in our study, 17 had undergone lung transplant; 32, liver transplant; and 2, kidney transplant. The median age was 55 years (range, 27-73), and 53% of patients were men. The median time from intubation to PDT was 10 days and from transplant to PDT, 22 days. The median ratio of PaO2 to fraction of inspired oxygen was 293, and the median positive end-expiratory pressure was 5 cm H2O. Twenty-one patients were receiving dialysis, and 11 were recovering from sepsis (of these, 8 were receiving vasopressors). Ten had coagulopathies (none of which were associated with bleeding complications). Complications were infrequent (7 periprocedural, 4 postprocedural) and included bleeding, bradycardia, hypotension, tracheal ring fracture, and cannula malfunction. Of the bleeding complications, only 2 were clinically remarkable and required removal of the tracheostomy or surgical revision. No infectious complications or procedure-related deaths were noted. CONCLUSION: Percutaneous dilatational tracheostomy was tolerated well in recipients of solid organ allografts and had a relatively low risk of major complications and a low procedure-related mortality rate. This method should be considered an acceptable alternative to surgical tracheostomy.

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.