The Effect of Molecular Adsorbent Recirculating System in Patients With Liver Failure: A Case Series of 44 Patients.

BACKGROUND: Liver failure is associated with a high mortality rate, with many patients requiring transplant for definitive treatment. The Molecular Adsorbent Recirculating System (MARS) is a nonbiologic system that provides extracorporeal support. Literature on MARS therapy is mixed: outcomes support MARS therapy for patients with isolated acute liver failure, but data on patients with chronic disease is varied. Several case studies report success using MARS as a bridging treatment for patients awaiting transplant. The purpose of this case series is to present the outcomes of 44 patients who underwent MARS therapy for liver failure, 19 of whom used MARS therapy as a bridging therapy to transplant. METHODS: This study retrospectively identified 44 patients who underwent MARS therapy for liver failure at Mayo Clinic, Jacksonville, between January 2014 and April 2021. Variables of interest included changes in laboratory markers of hepatic functioning, number and length of MARS therapy sessions, transplantation status, and mortality. RESULTS: Following MARS therapy, there were improvements in mean serum bilirubin, ammonia, urea, creatinine, International Normalized Ratio, alanine aminotransferase, and aspartate aminotransferase levels. Twenty-seven patients (61.36%) survived the hospital stay; 17 (38.63%) died in the hospital. The majority of surviving patients (n = 19; 73.07%) received liver transplant. Six did not require transplant (22.22%). All but 1 patient who received MARS as a bridging treatment to transplant survived the follow-up period (n = 18; 94.74%). CONCLUSIONS: Outcomes of these 44 cases suggest that MARS improves liver failure-associated laboratory parameters and may be effective therapy as a bridge to liver transplant.

Lateral-Apical Approach to Pericardiocentesis for Treatment of Cardiac Tamponade Immediately Post-orthotopic Liver Transplantation.

Cardiac tamponade is a rare complication following orthotopic liver transplantation (OLT). The incidence and treatment specific to the immediate postoperative OLT patient have never been reported. Here, we describe a case of OLT complicated by coagulopathy and difficult intraoperative pulmonary artery catheter placement with subsequent postoperative hemopericardium resulting in tamponade. An emergent, ultrasound-guided, lateral-apical pericardiocentesis was successfully performed, suggesting a possible procedural technique for pericardiocentesis in the immediate postoperative period for liver transplant patients.

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.

A heart of stone: a case of acute development of cardiac calcification and hemodynamic collapse.

Acute cardiac calcification is a clinical entity that may develop over days to months and is usually localized to areas of healed myocardial infarction, cardiac surgery or trauma. We present an unusual case of rapidly developing non-ischemic cardiac calcification in the setting of sepsis and end stage renal disease resulting in acute diastolic dysfunction and cardiac collapse diagnosed by computed tomography (CT) and confirmed by autopsy. We propose that dedicated cardiac CT may provide the most accurate means to detect cardiac calcification.

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.

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.

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.

Emergent, controlled lumbar drainage for intracranial pressure monitoring during orthotopic liver transplantation.

BACKGROUND: Measurement of intracranial pressure (ICP) is recommended in comatose acute liver failure (ALF) patients due to risk of rapid global cerebral edema. External ventricular drains (EVD) can be placed to drain cerebrospinal fluid and monitor ICP simultaneously although this remains controversial in the neurosurgical community given the risk of hemorrhagic complications. We describe a patient with ALF and global cerebral edema whose EVD failed immediately before orthotopic liver transplantation (OLT) in which a lumbar drain (LD) was used temporarily to monitor ICP. METHODS: We describe a 36 year old patient with ALF and brain edema from acetaminophen overdose who had an EVD placed for ICP monitoring and management. The EVD failed repeatedly (i.e., lost CSF drainage and ICP waveform) despite several saline irrigations and three doses intraventricular tissue plasminogen activator (1 mg) in the hours that immediately preceded her planned emergency OLT. An LD was placed emergently and controlled cerebrospinal fluid (CSF) drainage and ICP measurement was performed by setting the LD at 20 mmHg and leveling at the ear level (foramen of Monro). The LD was removed once the EVD flow was re-established post-OLT. RESULTS: The EVD and LD ICP measurements were reported to be the same just prior to removing the LD. CONCLUSIONS: Controlled CSF drainage using a lumbar drain can be used to monitor ICP when leveled at the foramen of Monro if EVD failure occurs perioperatively. The LD can temporarily guide ICP management until the EVD flow can be re-established after OLT.

Intraoperative intracardiac thrombosis in a liver transplant patient.

A 66-year-old female with cryptogenic cirrhosis complicated by ascites, hepatic encephalopathy, variceal bleeding and malnutrition with MELD of 34 underwent orthotopic deceased donor liver transplantation performed with piggyback technique. Extensive eversion thromboendovenectomy was performed for a portal vein thrombus which resulted in an excellent portal vein flow. The liver graft was recirculated without any hemodynamic instability. Subsequently, the patient became hypotensive progressing to asystole. She was resuscitated and a transesophageal probe was inserted which revealed a mobile right atrial thrombus and an underfilled poorly contractile right ventricle. The patient was noted to be coagulopathic at the time. She became progressively more stable with a TEE showing complete resolution of the intracardiac thrombus.

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.

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.

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.

Management of sepsis in patients with liver failure.

PURPOSE OF REVIEW: Sepsis constitutes the most common cause of death in the ICU. Liver dysfunction is manifested among previously normal subjects with sepsis but even more so in populations with preexisting liver disease. Managing these patients is more challenging. We will review recent literature in sepsis and liver disease, and their bedside application. RECENT FINDINGS: At the cellular-chemical level, studies showed that platelet aggregation and neutrophil activation occur before and are independent of microcirculatory changes which are apparent in all animal septic models. At the clinical level, early goal-directed therapy, euglycemia, low tidal volume ventilation, and early and appropriately dosed renal replacement therapy among others are all tools to improve sepsis survival. Acknowledgement of liver disease as an immunocompromised host, and identification and treatment of complications can positively change the outcome of sepsis in liver disease. SUMMARY: Much has been advanced in the field of sepsis management. Understanding the pathophysiology of liver dysfunction and decompensation of a diseased liver incites questions for future research. Early goal-directed therapy, lactate clearance, glycemic control, low volume ventilation strategies, nutrition, adrenal insufficiency, renal dysfunction, hepatorenal syndrome prevention and treatment are some of the issues in the management of sepsis, with or without liver disease, that are relevant in this review.