Molecular Adsorbent Recirculating System in Acute Liver Failure.

Acetaminophen (APAP) overdose is the most common cause of acute liver failure (ALF) in the United States. Liver transplantation (LT) is potentially lifesaving for patients with ALF, but its feasibility in clinical practice is limited. Liver assist devices, such as the Molecular Adsorbent Recirculating System (MARS), are used in some centers as a "bridge" to liver transplantation or as a means of liver recovery, but their role in the treatment of ALF is not well-defined. We present the case of a 44-year-old man with APAP-associated ALF who experienced hepatic recovery after treatment with MARS.

A Decision-oriented Approach to Evaluating a Leadership Curriculum in Fellowship.

Background: Graduate Medical Education (GME) emphasizes the role of the annual program evaluation to identify opportunities, create action plans, and track improvements longitudinally. There is a lack of a systematic approach to the evaluation of educational curricula. Comprehensive curriculum evaluation can inform the educators about specific modifications to achieve high standards, desired outcomes, and the anticipated objectives. Objective: To evaluate a leadership in quality improvement program in a pulmonary/critical care fellowship training program using the context, input, process, product (CIPP) model. The CIPP model, given its focus on evaluating different aspects of a program, provides concrete and targeted feedback to guide improvement decisions. Methods: Evaluation questions addressing the four focused areas were created, pilot tested, and revised. The questions were framed toward optimization of alignment (e.g., program activities with stated objectives, program goals with theoretical perspective, program curriculum with trainee needs) and gaining information about the efficacy of the program in achieving the desired outcomes. To enhance the validity of the results, we triangulated the data-gathering approach by administering surveys and conducting interviews and focus groups by random selection from the eligible participants. Qualitative data were transcribed, coded, and categorized into themes aligning with the four aspects of the CIPP model. Results: We interviewed 9 participants and conducted three focus groups with 20 participants. The surveys provided vital quantitative information that was cross-verified with the qualitative data; 23 of the 25 (92%) participants completed the survey. The results of qualitative thematic analysis were organized in the CIPP format. The context evaluation of the program revealed that the fellows and faculty were unfamiliar with the guiding principles of the course. The input evaluation highlighted the competing interests that hampered the engagement of the fellows during the evening weekly report-outs. The process evaluation revealed clustering of didactic sessions at the start of the course. The product evaluation stressed the difficulty in completing the quality improvement projects in the allotted timeframe. Conclusion: Conducting a robust evaluation of an educational curriculum provides insights into gaps in the various stages of the program. Time and resources needed for conducting evaluation by using the CIPP model should be considered.

Comparison of fungal vs bacterial infections in the medical intensive liver unit: Cause or corollary for high mortality?

BACKGROUND: Due to development of an immune-dysregulated phenotype, advanced liver disease in all forms predisposes patients to sepsis acquisition, including by opportunistic pathogens such as fungi. Little data exists on fungal infection within a medical intensive liver unit (MILU), particularly in relation to acute on chronic liver failure. AIM: To investigate the impact of fungal infections among critically ill patients with advanced liver disease, and compare outcomes to those of patients with bacterial infections. METHODS: From our prospective registry of MILU patients from 2018-2022, we included 27 patients with culture-positive fungal infections and 183 with bacterial infections. We compared outcomes between patients admitted to the MILU with fungal infections to bacterial counterparts. Data was extracted through chart review. RESULTS: All fungal infections were due to Candida species, and were most frequently blood isolates. Mortality among patients with fungal infections was significantly worse relative to the bacterial cohort (93% vs 52%, P < 0.001). The majority of the fungal cohort developed grade 2 or 3 acute on chronic liver failure (ACLF) (90% vs 64%, P = 0.02). Patients in the fungal cohort had increased use of vasopressors (96% vs 70%, P = 0.04), mechanical ventilation (96% vs 65%, P < 0.001), and dialysis due to acute kidney injury (78% vs 52%, P = 0.014). On MILU admission, the fungal cohort had significantly higher Acute Physiology and Chronic Health Evaluation (108 vs 91, P = 0.003), Acute Physiology Score (86 vs 65, P = 0.003), and Model for End-Stage Liver Disease-Sodium scores (86 vs 65, P = 0.041). There was no significant difference in the rate of central line use preceding culture (52% vs 40%, P = 0.2). Patients with fungal infection had higher rate of transplant hold placement, and lower rates of transplant; however, differences did not achieve statistical significance. CONCLUSION: Mortality was worse among patients with fungal infections, likely attributable to severe ACLF development. Prospective studies examining empiric antifungals in severe ACLF and associations between fungal infections and transplant outcomes are critical.

Hemodynamic profile of cirrhotic patients with sepsis and septic shock: A propensity score matched case-control study.

PURPOSE: Our understanding of hemodynamics in cirrhotic patients with sepsis remains limited. Our study aims to investigate differences in hemodynamic profiles using echocardiography between septic patients with and without cirrhosis. MATERIALS AND METHODS: This is a single-center, retrospective study of septic patients with echocardiogram within 3 days of ICU admission. We compared baseline characteristics, echocardiographic markers of LV systolic function arterial load between patients with and without cirrhosis. A propensity score-matched case-control model was developed to describe the differences in those echocardiography derived parameters between the groups. RESULTS: 3151 patients with sepsis were included of which 422 (13%) had cirrhosis. In the propensity score matched group with 828 patients, cirrhotic patients had significantly higher left ventricular ejection fraction (64 vs.56%, p < 0.001) and stroke volume (72 vs.48 ml, p < 0.001) along with lower arterial elastance (Ea) (1.35 1vs.20.3, p < 0.001) and systemic vascular resistance (SVR) (851 vs.1209 dynes/s/m-5, p = 0.001). The left ventricular elastance (Ees) (2.83 vs 2.45, p = 0.002) was higher and ventricular-arterial coupling (Ea/Ees) (0.48 vs. 0.86, p < 0.001) lower in cirrhotic compared to non-cirrhotic. CONCLUSIONS: Septic patients with cirrhosis had higher LVEF with lower Ea and SVR with higher Ees and significantly lower Ea/Ees suggesting vasodilation as the principal driver of the hyperdynamic profile in cirrhosis.

Evaluation of a protocol for rifaximin discontinuation in critically ill patients with liver disease receiving broad-spectrum antibiotic therapy.

BACKGROUND: Rifaximin is frequently administered to critically ill patients with liver disease and hepatic encephalopathy, but patients currently or recently treated with antibiotics were frequently excluded from studies of rifaximin efficacy. Due to overlapping spectrums of activity, combination therapy with broad-spectrum antibiotics and rifaximin may be unnecessary. A pharmacist-driven protocol was piloted to reduce potentially overlapping therapy in critically ill patients with liver disease. It was hypothesized that withholding rifaximin during broad-spectrum antibiotic therapy would be safe and reduce healthcare costs. AIM: To determine the clinical, safety, and financial impact of discontinuing rifaximin during broad-spectrum antibiotic therapy in critically ill liver patients. METHODS: This was a single-center, quasi-experimental, pre-post study based on a pilot pharmacist-driven protocol. Patients in the protocol group were prospectively identified via the medical intensive care unit (ICU) (MICU) protocol to have rifaximin withheld during broad-spectrum antibiotic treatment. These were compared to a historical cohort who received combination therapy with broad-spectrum antibiotics and rifaximin. All data were collected retrospectively. The primary outcome was days alive and free of delirium and coma (DAFD) to 14 d. Safety outcomes included MICU length of stay, 48-h change in vasopressor dose, and ICU mortality. Secondary outcomes characterized rifaximin cost savings and protocol adherence. Multivariable analysis was utilized to evaluate the association between group assignment and the primary outcome while controlling for potential confounding factors. RESULTS: Each group included 32 patients. The median number of delirium- and coma-free days was similar in the control and protocol groups [3 interquartile range (IQR 0, 8) vs 2 (IQR 0, 9.5), P = 0.93]. In multivariable analysis, group assignment was not associated with a reduced ratio of days alive and free of delirium or coma at 14 d. The protocol resulted in a reduced median duration of rifaximin use during broad-spectrum antibiotic therapy [6 d control (IQR 3, 9.5) vs 1 d protocol (IQR 0, 1); P < 0.001]. Rates of other secondary clinical and safety outcomes were similar including ICU mortality and 48-h change in vasopressor requirements. Overall adherence to the protocol was 91.4%. The median estimated total cost of rifaximin therapy per patient was reduced from $758.40 (IQR $379.20, $1200.80) to $126.40 (IQR $0, $126.40), P < 0.01. CONCLUSION: The novel pharmacist-driven protocol for rifaximin discontinuation was associated with significant cost savings and no differences in safety outcomes including DAFD.

Thromboelastography-Guided Correction of Coagulopathy Before Tunneled Central Venous Access in Critically Ill Patients With Liver Disease: A Propensity Score-Matched Study.

Importance: Optimal blood product transfusion strategies before tunneled central venous catheter (CVC) placement are required in critically ill coagulopathic patients with liver disease to reduce exposure to allogeneic blood products and mitigate bleeding and thrombotic complications. Objectives: This study evaluated the safety and efficacy of a thromboelastography-guided transfusion strategy for the correction of coagulopathy in patients with liver disease compared with a conventional transfusion strategy (using international normalized ratio, platelet count, and fibrinogen) before tunneled CVC insertion. Design Setting and Participants: A retrospective propensity score-matched single-center cohort study was conducted at a quaternary care academic medical center involving 364 patients with liver disease (cirrhosis and acute liver failure) who underwent tunneled CVC insertion in the ICU. Patients were stratified into two groups based on whether they received blood product transfusions based on a thromboelastography-guided or conventional transfusion strategy. Main Outcomes and Measures: Primary outcomes that were evaluated included the volume, units and cost of blood products (fresh frozen plasma, cryoprecipitate, and platelets) when using a thromboelastography-guided or conventional approach to blood transfusions. Secondary outcomes included the frequency of procedure-related bleeding and thrombotic complications. Results: The total number of units/volume/cost of fresh frozen plasma (12 U/3,000 mL/$684 vs. 32 U/7,500 mL/$1,824 [p = 0.019]), cryoprecipitate (60 U/1,500 mL/$3,240 vs. 250 U/6,250 mL/$13,500 [p < 0.001]), and platelets (5 U/1,500 mL/$2,610 vs. 13 units/3,900 mL/$6,786 [p = 0.046]) transfused were significantly lower in the thromboelastography-guided transfusion group than in the conventional transfusion group. No differences in the frequency of bleeding/thrombotic events were observed between the two groups. Conclusions and Relevance: A thromboelastography-guided transfusion strategy for correction of coagulopathy in critically ill patients with liver disease before tunneled CVC insertion, compared with a conventional transfusion strategy, reduces unnecessary exposure to allogeneic blood products and associated costs without increasing the risk for peri-procedural bleeding and thrombotic complications.

Therapeutic plasma exchange in liver failure.

The multi-organ failure syndrome associated with acute and acute-on-chronic liver failure (ACLF) is thought to be mediated by overwhelming systemic inflammation triggered by both microbial and non-microbial factors. Therapeutic plasma exchange (TPE) has been proven to be an efficacious therapy in autoimmune conditions and altered immunity, with more recent data supporting its use in the management of liver failure. Few therapies have been shown to improve survival in critically ill patients with liver failure who are not expected to survive until liver transplantation (LT), who are ineligible for LT or who have no access to LT. TPE has been shown to reduce the levels of inflammatory cytokines, modulate adaptive immunity with the potential to lessen the susceptibility to infections, and reduce the levels of albumin-bound and water-bound toxins in liver failure. In patients with acute liver failure, high volume TPE has been shown to reduce the vasopressor requirement and improve survival, particularly in patients not eligible for LT. Standard volume TPE has also been shown to reduce mortality in certain sub-populations of patients with ACLF. TPE may be most favorably employed as a bridge to LT in patients with ACLF. In this review, we discuss the efficacy and technical considerations of TPE in both acute and acute-on-chronic liver failure.

Impact of Duration of N-Acetylcysteine in Non-Acetaminophen-Induced Acute Liver Failure.

OBJECTIVES: Studies of the use of IV N-acetylcysteine in the management of non-acetaminophen-induced acute liver failure have evaluated various dosing regimens. The only randomized trial studying this application described a 72-hour regimen. However, observational studies have reported extended duration until normalization of international normalized ratio. This study seeks to compare differences in patient outcomes based on IV N-acetylcysteine duration. DESIGN: Retrospective cohort study. SETTING: Medical ICU at a large quaternary care academic medical institution and liver transplant center. PATIENTS: Adult patients admitted to the medical ICU who received IV N-acetylcysteine for the treatment of non-acetaminophen-induced acute liver failure. INTERVENTIONS: Patients were divided into cohorts based on duration; standard duration of IV N-acetylcysteine was considered 72 hours, whereas extended duration was defined as continuation beyond 72 hours. MEASUREMENTS AND MAIN RESULTS: The primary outcome was time to normalization of international normalized ratio to less than 1.3 or less than 1.5; secondary outcomes included all-cause mortality and transplant-free survival at 3 weeks. In total, 53 patients were included: 40 in the standard duration cohort and 13 in the extended duration. There were no major differences in baseline characteristics. There was no significant difference in time to international normalized ratio normalization between cohorts. Transplant-free survival was higher with extended duration (76.9% extended vs 41.4% standard; p = 0.03). All-cause mortality at 3 weeks was numerically lower in the extended duration group (0% extended vs 24.1% standard; p = 0.08). CONCLUSIONS: Patients with non-acetaminophen-induced acute liver failure who received extended duration N-acetylcysteine were found to have significantly higher transplant-free survival than patients who received standard duration, although there was no significant difference in time to normalization of international normalized ratio or overall survival. Prospective, randomized, multicenter study is warranted to identify subpopulations of patients with non-acetaminophen-induced acute liver failure who could benefit from extended treatment duration as a bridge to transplant or spontaneous recovery.

LIV-4: A novel model for predicting transplant-free survival in critically ill cirrhotics.

BACKGROUND: Critically ill patients with cirrhosis, particularly those with acute decompensation, have higher mortality rates in the intensive care unit (ICU) than patients without chronic liver disease. Prognostication of short-term mortality is important in order to identify patients at highest risk of death. None of the currently available prognostic models have been widely accepted for use in cirrhotic patients in the ICU, perhaps due to complexity of calculation, or lack of universal variables readily available for these patients. We believe a survival model meeting these requirements can be developed, to guide therapeutic decision-making and contribute to cost-effective healthcare resource utilization. AIM: To identify markers that best identify likelihood of survival and to determine the performance of existing survival models. METHODS: Consecutive cirrhotic patients admitted to a United States quaternary care center ICU between 2008-2014 were included and comprised the training cohort. Demographic data and clinical laboratory test collected on admission to ICU were analyzed. Area under the curve receiver operator characteristics (AUROC) analysis was performed to assess the value of various scores in predicting in-hospital mortality. A new predictive model, the LIV-4 score, was developed using logistic regression analysis and validated in a cohort of patients admitted to the same institution between 2015-2017. RESULTS: Of 436 patients, 119 (27.3%) died in the hospital. In multivariate analysis, a combination of the natural logarithm of the bilirubin, prothrombin time, white blood cell count, and mean arterial pressure was found to most accurately predict in-hospital mortality. Derived from the regression coefficients of the independent variables, a novel model to predict inpatient mortality was developed (the LIV-4 score) and performed with an AUROC of 0.86, compared to the Model for End-Stage Liver Disease, Chronic Liver Failure-Sequential Organ Failure Assessment, and Royal Free Hospital Score, which performed with AUROCs of 0.81, 0.80, and 0.77, respectively. Patients in the internal validation cohort were substantially sicker, as evidenced by higher Model for End-Stage Liver Disease, Model for End-Stage Liver Disease-Sodium, Acute Physiology and Chronic Health Evaluation III, SOFA and LIV-4 scores. Despite these differences, the LIV-4 score remained significantly higher in subjects who expired during the hospital stay and exhibited good prognostic values in the validation cohort with an AUROC of 0.80. CONCLUSION: LIV-4, a validated model for predicting mortality in cirrhotic patients on admission to the ICU, performs better than alternative liver and ICU-specific survival scores.

What is the role of supplementation with ascorbic acid, zinc, vitamin D, or N-acetylcysteine for prevention or treatment of COVID-19?

Several agents intended to supplement dietary intake or endogenous molecules may have a theoretical role in preventing or treating COVID-19. Because of their potential to influence immune response, ascorbic acid (vitamin C), zinc, vitamin D, and N-acetylcysteine have been hypothesized to be useful for prevention or treatment of COVID-19. The authors outline the biologic plausibility, applicable clinical data, and potential role of each of these agents.

The EMALT Score: An Improved Model for Prediction of Early Mortality in Liver Transplant Recipients.

PURPOSE: Needs, risks, and outcomes of patients admitted to a post liver transplant intensive care unit (POLTICU) differ in important ways from those admitted to pretransplant intensive care units (ICUs). The aim of this study was to create the optimal model to risk stratify POLTICU patients. METHODS: Consecutive patients who underwent first deceased donor liver transplantation (LT) at a large United States center between 2008 and 2014 were followed from admission to LT and to discharge or death. Receiver-operating characteristic analysis was performed to assess the value of various scores in predicting in-hospital mortality. A predictive model was developed using logistic regression analysis. RESULTS: A total of 697 patients underwent LT, and 3.2% died without leaving the hospital. A model for in-hospital mortality was derived from variables available within 24 hours of admission to the POLTICU. Key variables best predicting survival were white blood cell count, 24-hour urine output, and serum glucose. A model using these variables performed with an area under the curve (AUC) of 0.88, compared to the Acute Physiology and Chronic Health Evaluation III and Model for End-Stage Liver Disease, which performed with AUCs of 0.74 and 0.60, respectively. CONCLUSION: An improved model, the early mortality after LT (EMALT) score, performs better than conventional models in predicting in-hospital mortality after LT.

Unusual Presentation of Central Diabetes Insipidus in a Patient With Neurosarcoidosis.

Hypernatremia is a frequent cause of intensive care unit admission. The patient presented in this article had hypernatremia refractory to D5W (dextrose 5% water) therapy, which led to a complex investigation. Workup revealed central diabetes insipidus most likely secondary to flare up of neurosarcoidosis. The challenge in terms of diagnosis was a presentation with low urine output in the setting of hypernatremia resistant to treatment with desmopressin. This case unfolded the role of hypothyroidism causing secondary renal dysfunction and hence needed continued treatment with thyroxine in addition to treatment for hypernatremia.

Acute ischemic optic neuropathy with extended prone position ventilation in a lung transplant recipient.

Prone position ventilation (PPV) improves mortality in severe acute respiratory distress syndrome (ARDS), but outcomes following its use in lung transplant recipients are not known. We report the case of a 42-year-old Caucasian man who presented with severe ARDS from Bordetella pertussis, 5 years after bilateral sequential lung transplant for cystic fibrosis. He was managed with PPV for 22 days and had a prolonged ICU stay complicated by hypoxic ischemic optic neuropathy leading to blindness. Since his discharge from the ICU 6 months ago, his FEV1 has recovered to 47% predicted compared to his pre-ICU peak FEV1 of 85% predicted, suggesting recovery of lung function. This is the first report of optic nerve damage and vision loss in patients undergoing PPV. Our report also suggests that, in appropriately selected lung transplant recipients, severe hypoxemia could potentially be managed with prone ventilation.