Perioperative Dexamethasone Is Associated With Higher Short-Term Mortality in Reconstructive Head and Neck Cancer Surgery.

PURPOSE: Studies of the effects of perioperative dexamethasone (DEX) during oncologic surgery are scarce. The first aim of the present study was to clarify whether perioperative DEX affects the short-term mortality in patients with head and neck cancer (HNC). The second aim was to analyze the causes of death and predictors affecting long-term mortality. PATIENTS AND METHODS: The present prospective, double-blind randomized, controlled study included patients with HNC who had undergone microvascular reconstruction from 2008 through 2013. The patients were randomized into 2 groups: the receipt of perioperative DEX for 3 days (study group) or no DEX (control group). The patients' data and cause of death were registered until the end of 2017. The primary cause of death was used in the analyses. RESULTS: A total of 93 patients were included in the present study: 51 in the DEX group (study group) and 42 in the NON-DEX group (control group). Altogether 38 patients died during a median follow-up period of 5.3 years. During the first year, more deaths had occurred in the DEX group than in the NON-DEX group: at 1 month, 4% versus 0%; at 6 months, 14% versus 0%; and at 12 months, 22% versus 5% (P = .043). The overall survival rate for all patients was 59%. HNC was the primary cause of death for most of the patients who died. On univariate analysis, the deceased patients had more advanced disease (higher T classification, P = .002; higher stage, P = .008), a greater need for a gastrostoma (P = .002), more often received postoperative chemotherapy (P = .005), and more often had locoregional (P = .025) or distal (P < .001) metastases. In the multivariate Cox model, the most important long-term predictors of death were the presence of distant metastases (P < .001), a Charlson comorbidity index (CCI) of 5 to 9 (P < .001), and the use of perioperative DEX (P = .004). CONCLUSIONS: The use of perioperative DEX was associated with higher short-term mortality after reconstructive HNC surgery. The most important long-term predictors of death were the receipt of DEX, the presence of distant metastases, and a CCI of 5 to 9. These findings do not encourage the routine use of perioperative DEX for these patients.

More Harm Than Benefit of Perioperative Dexamethasone on Recovery Following Reconstructive Head and Neck Cancer Surgery: A Prospective Double-Blind Randomized Trial.

PURPOSE: Prospective studies on the effect of dexamethasone after microvascular reconstructive head and neck surgery are sparse despite the widespread use of dexamethasone in this setting. The aim of this study was to clarify whether perioperative use of dexamethasone would improve the quality and speed of recovery. The authors hypothesized that dexamethasone would enhance recovery and diminish pain and nausea. MATERIALS AND METHODS: Ninety-three patients with oropharyngeal cancer and microvascular reconstruction were included in this prospective double-blinded randomized controlled trial. Patients in the study group (n = 51) received dexamethasone 60 mg over 3 perioperative days; 42 patients did not receive dexamethasone and served as controls. Patient rehabilitation, postoperative opioid and insulin consumption, postoperative nausea and vomiting (PONV), and C-reactive protein (CRP), leukocyte, and lactate levels were recorded. RESULTS: There was significantly less pain in the study group (P = .030) and the total oxycodone dose for 5 days postoperatively was lower (P = .040). Dexamethasone did not significantly lessen PONV for 5 days postoperatively (P > .05). There were no differences between groups in intensive care unit or hospital stay or in other clinical measures of recovery. Patients receiving dexamethasone required significantly more insulin compared with patients in the control group (P < .001). Lactate and leukocyte levels were significantly higher (P < .001) and CRP levels were significantly lower in the study group. CONCLUSION: The only benefit of perioperative dexamethasone use was lower total oxycodone dose; however, the disadvantages were greater. Because dexamethasone can have adverse effects on the postoperative course, routine use of dexamethasone as a pain or nausea medication during reconstructive head and neck cancer surgery is not recommended.

Analgesic Effect of Perioperative Systemic Dexamethasone on Blowout Fracture Surgery.

PURPOSE: To clarify the effect of systemic dexamethasone (DXM) on pain and postoperative opioid (oxycodone) consumption after blowout fracture surgery. MATERIALS AND METHODS: A prospective randomized observer-blinded trial of 20 patients who had a blowout fracture requiring surgical intervention was conducted. Patients were randomly assigned to receive a total dose of intravenous DXM 30 mg perioperatively or no DXM (controls). Pain was assessed postoperatively using a 10-cm visual analog scale (VAS) each time analgesics (acetaminophen every 6 hours or oxycodone upon request) were administered. The VAS area under the curve (VAS AUC) for 24 hours postoperatively represented the outcome. Data were analyzed using χ2 test, Student t test, 2-tailed Mann-Whitney U test, and linear regression, with a P value less than .05 indicating significance. RESULTS: Patients with blowout fracture receiving perioperative systemic DXM exhibited a significantly lower average VAS AUC (P = .04). After controlling for other confounding variables, this result remained significant (P = .03). CONCLUSIONS: DXM appears to decrease postoperative pain and thus is recommended as a pre-emptive analgesic in blowout fracture surgery.

Pulp necrosis of teeth retained at the mandibular fracture site and the effect of dexamethasone on its occurrence.

OBJECTIVES: The main purpose was to determine the occurrence of pulp necrosis (PN) of teeth retained at the mandibular fracture site. An additional purpose was to investigate whether perioperative use of dexamethasone increases the risk of PN. PATIENTS AND METHODS: A follow-up study on 24 adult dentate patients with mandibular body, symphysis or parasymphysis fracture. These patients had been selected from a larger cohort who had participated in a randomized study of maxillofacial fractures and dexamethasone. All patients who were suspected of having a need for endodontic treatment were evaluated by an endodontist. RESULTS: PN was diagnosed in six patients (25.0%) in one or two teeth. Of a total of 33 teeth situated in the fracture line, six (18.2%) were diagnosed as having PN. PN was more common in teeth in which the fracture line ran through the apex (21.7%) than in those in which the fracture line was in contact with the tooth cranially to the apex (10.0%). The association between PN and dexamethasone was not significant. CONCLUSION: PN is common after mandibular fractures, particularly when the fracture line runs through the apex of the tooth. Use of short-term, high-dose dexamethasone perioperatively did not significantly increase the risk for PN.

Frontal electroencephalogram variables are associated with the outcome and stage of hepatic encephalopathy in acute liver failure.

Acute liver failure (ALF) and hepatic encephalopathy (HE) can lead to an elevated intracranial pressure (ICP) and death within days. The impaired liver function increases the risks of invasive ICP monitoring, whereas noninvasive methods remain inadequate. The purpose of our study was to explore reliable noninvasive methods of neuromonitoring for patients with ALF in the intensive care unit (ICU) setting; more specifically, we wanted to track changes in HE and predict the outcomes of ALF patients treated with albumin dialysis. The study included 20 patients with severe ALF at admission who had been referred to the ICU of the liver transplantation (LT) center for albumin dialysis treatment and evaluation for transplantation. Data were collected from all study patients in the form of continuous frontal electroencephalography (EEG) recordings and transcranial Doppler (TCD) measurements of cerebral blood flow. Among the studied EEG variables, the 50% spectral edge frequency decreased and the delta power increased as the HE stage increased. Both variables were predictive of the stage of HE [prediction probability (PK) of 50% spectral edge frequency = 0.23, standard error (SE) = 0.03; PK of delta power = 0.76, SE = 0.03]. The total wavelet subband entropy, a novel variable that we used for tracking abnormal EEG activity, predicted the outcome of ALF patients treated with albumin dialysis (PK = 0.88, SE = 0.09). With a threshold value of 1.6, the TCD pulsatility index had an odds ratio of 1.1 (95% confidence interval = 0.1-9.3) for a poor outcome (LT or death). In conclusion, EEG variables are useful for the monitoring of HE and can be used to predict outcomes of ALF. TCD measurements do not predict patient outcomes.

Prothrombin complex concentrate in the reduction of blood loss during orthotopic liver transplantation: PROTON-trial.

BACKGROUND: In patients with cirrhosis, the synthesis of coagulation factors can fall short, reflected by a prolonged prothrombin time. Although anticoagulants factors are decreased as well, blood loss during orthotopic liver transplantation can still be excessive. Blood loss during orthotopic liver transplantation is currently managed by transfusion of red blood cell concentrates, platelet concentrates, fresh frozen plasma, and fibrinogen concentrate. Transfusion of these products may paradoxically result in an increased bleeding tendency due to aggravated portal hypertension. The hemostatic effect of these products may therefore be overshadowed by bleeding complications due to volume overload.In contrast to these transfusion products, prothrombin complex concentrate is a low-volume highly purified concentrate, containing the four vitamin K dependent coagulation factors. Previous studies have suggested that administration of prothrombin complex concentrate is an effective method to normalize a prolonged prothrombin time in patients with liver cirrhosis. We aim to investigate whether the pre-operative administration of prothrombin complex concentrate in patients undergoing liver transplantation for end-stage liver cirrhosis, is a safe and effective method to reduce perioperative blood loss and transfusion requirements. METHODS/DESIGN: This is a double blind, multicenter, placebo-controlled randomized trial.Cirrhotic patients with a prolonged INR (≥1.5) undergoing liver transplantation will be randomized between placebo or prothrombin complex concentrate administration prior to surgery. Demographic, surgical and transfusion data will be recorded. The primary outcome of this study is RBC transfusion requirements. DISCUSSION: Patients with advanced cirrhosis have reduced plasma levels of both pro- and anticoagulant coagulation proteins. Prothrombin complex concentrate is a low-volume plasma product that contains both procoagulant and anticoagulant proteins and transfusion will not affect the volume status prior to the surgical procedure. We hypothesize that administration of prothrombin complex concentrate will result in a reduction of perioperative blood loss and transfusion requirements. Theoretically, the administration of prothrombin complex concentrate may be associated with a higher risk of thromboembolic complications. Therefore, thromboembolic complications are an important secondary endpoint and the occurrence of this type of complication will be closely monitored during the study. TRIAL REGISTRATION: The trial is registered at http://www.trialregister.nl with number NTR3174. This registry is accepted by the ICMJE.

[Liver disease and hemostasis--evaluation of bleeding risk]. / Maksan vajaatoiminta ja hemostaasi--verenvuotovaaran arviointi.

In severe liver disease, simultaneous abnormalities in procoagulant and anticoagulant pathways seem to maintain the hemostatic balance, provided that the platelet level is sufficient. Common coagulation screening tests such as INR fail to measure the concomitant anticoagulant deficiencies and fibrinolytic abnormalities, and do not predict bleeding in patients with compensated liver disease undergoing invasive procedures. Thus, specific INR cut-off levels and prophylactic use of fresh-frozen plasma are discouraged. Volume expansion, hemodynamic disruption, endothelial dysfunction, and infections increase the bleeding risk. Individualized bleeding risk assessment mandates evaluation of the patient's clinical condition and a comprehensive assessment of the hemostatic system.

Cost of a quality-adjusted life year in liver transplantation: the influence of the indication and the model for end-stage liver disease score.

Cost issues in liver transplantation (LT) have received increasing attention, but the cost-utility is rarely calculated. We compared costs per quality-adjusted life year (QALY) from the time of placement on the LT waiting list to 1 year after transplantation for 252 LT patients and to 5 years after transplantation for 81 patients. We performed separate calculations for chronic liver disease (CLD), acute liver failure (ALF), and different Model for End-Stage Liver Disease (MELD) scores. For the estimation of QALYs, the health-related quality of life was measured with the 15D instrument. The median costs and QALYs after LT were €141,768 and 0.895 for 1 year and €177,618 and 3.960 for 5 years, respectively. The costs of the first year were 80% of the 5-year costs. The main cost during years 2 to 5 was immunosuppression drugs (59% of the annual costs). The cost/QALY ratio improved from €158,400/QALY at 1 year to €44,854/QALY at 5 years, and the ratio was more beneficial for CLD patients (€42,500/QALY) versus ALF patients (€63,957/QALY) and for patients with low MELD scores versus patients with high MELD scores. Although patients with CLD and MELD scores > 25 demonstrated markedly higher 5-year costs (€228,434) than patients with MELD scores < 15 (€169,541), the cost/QALY difference was less pronounced (€59,894/QALY and €41,769/QALY, respectively). The cost/QALY ratio for LT appears favorable, but it is dependent on the assessed time period and the severity of the liver disease.

Cytokine profiles in acute liver failure treated with albumin dialysis.

Cytokines are released within the liver in response to hepatic injury, and acute liver failure (ALF) triggers systemic inflammation. Pro-inflammatory (tumor necrosis factor-alpha [TNF-alpha] and interleukin-8 [IL-8]) and anti-inflammatory (interleukin-10 [IL-10] and interleukin-6 [IL-6]) cytokines and the lymphocyte activation marker (interleukin-2-soluble receptor alpha chain [IL-2sRalpha]) were monitored in 49 ALF patients considered for liver transplantation and treated with albumin dialysis (molecular adsorbent recirculating system [MARS]). Twenty-six patients were categorized by clinical outcome as "good" (native liver recovered) and 23 as "poor" (patient bridged to liver transplantation or deceased). MARS did not clearly affect cytokine profiles during treatment; only IL-10 levels decreased in the whole patient population and mostly in patients with the worst prognosis. In the good outcome group, IL-8 and IL-6 levels decreased during treatment; on the contrary, in poor outcome patients IL-6 levels even increased. Initial IL-2sRalpha levels were higher in poor outcome patients relative to the good outcome subset. Cytokine profiles seem to differ in ALF according to patient outcome. A deeper understanding of cytokine patterns during pathogenesis could reveal prognostic markers and aid the development of immunomodulating ALF therapies.

Increased acetaminophen related calls to Finnish PIC better reflect acetaminophen sales than serious poisonings.

OBJECTIVE: Acetaminophen (APAP) or paracetamol is a commonly encountered medicine in poisonings. We studied the changes in APAP related calls to the Finnish poison information centre (FPIC), and serious intoxications, involving hepatotoxicity or death in 2001-2014. These data were compared with paracetamol sales in Finland. METHODS: This is a retrospective analysis of the FPIC database calls, national cause of death registry, registries of liver transplantations and molecular adsorbent recycling system (MARS)-treated patients from Helsinki University Hospital together with the National Institute of Health and Welfare registry of patients hospitalized. Data on APAP sales were obtained from the Finnish Medicines Agency. RESULTS: Between 2001 and 2014, the number of calls/year related to human APAP exposures to the FPIC increased from 227 to 1058. No change in the age distribution of enquiries was seen. Most calls involved minors: 58% (range 52-64%) for children under 6 years old, and 9% (range 6-14%) for children of 6-15 years. In Finland, APAP related fatalities have gradually increased from an average of 7/year (range 4-10) in 2000-2005 to an average of 11/year (range 6-17) in 2010-2013, whereas the number of liver transplantations remained low, average 0.6/year (range 0-2). For patients in need of MARS-treatment, a slight decrease was seen. Total APAP sales increased from 5.6 (47% prescription, 53% OTC) to 29.7 (81% prescription, 19% OTC). DDD/1000 inhabitants/day from 2001 to 2014 is recorded. Best linear relationship (R2 = 0.97; p < .001) was observed between total FPIC calls and total sales of APAP in 2001-2014. Fatalities show a weaker relationship with sales (R2 = 0.317; p = .045). CONCLUSIONS: During the study period, we see an increase in FPIC exposure calls accompanied by an increase in APAP sales. Changes in the chosen indicators for serious poisonings show only a weak association. Despite an evident trend between sales and fatalities, the correlation with fatality remains weak due to the small number of fatalities.

Entropy is more resistant to artifacts than bispectral index in brain-dead organ donors.

OBJECTIVE: To evaluate the usefulness of entropy and the bispectral index (BIS) in brain-dead subjects. DESIGN AND SETTING: A prospective, open, nonselective, observational study in the university hospital. PATIENTS AND PARTICIPANTS: 16 brain-dead organ donors. INTERVENTIONS: Time-domain electroencephalography (EEG), spectral entropy of the EEG, and BIS were recorded during solid organ harvest. MEASUREMENTS AND RESULTS: State entropy differed significantly from 0 (isoelectric EEG) 28%, response entropy 29%, and BIS 68% of the total recorded time. The median values during the operation were state entropy 0.0, response entropy 0.0, and BIS 3.0. In four of 16 organ donors studied the EEG was not isoelectric, and nonreactive rhythmic activity was noted in time-domain EEG. After excluding the results from subjects with persistent residual EEG activity state entropy, response entropy, and BIS values differed from zero 17%, 18%, and 62% of the recorded time, respectively. Median values were 0.0, 0.0, and 2.0 for state entropy, response entropy, and BIS, respectively. The highest index values in entropy and BIS monitoring were recorded without neuromuscular blockade. The main sources of artifacts were electrocauterization, 50-Hz artifact, handling of the donor, ballistocardiography, electromyography, and electrocardiography. CONCLUSION: Both entropy and BIS showed nonzero values due to artifacts after brain death diagnosis. BIS was more liable to artifacts than entropy. Neither of these indices are diagnostic tools, and care should be taken when interpreting EEG and EEG-derived indices in the evaluation of brain death.

Effects of perioperatively administered dexamethasone on surgical wound healing in patients undergoing surgery for zygomatic fracture: a prospective study.

OBJECTIVE: The aims of the study were to clarify the occurrence of disturbance in surgical wound healing (DSWH) after surgery of zygomatic complex (ZC) fractures and to determine whether perioperatively applied dexamethasone increases the risk for DSWH. STUDY DESIGN: Of 64 patients who were included in a single-blind prospective trial, 33 perioperatively received a total dose of 10 mg or 30 mg of dexamethasone. The remaining 31 patients served as controls. RESULTS: DSWH occurred in 9 patients (14.1%). Occurrence of DSWH was 24.4% in patients who received dexamethasone and 3.2% in controls. The association between DSWH and dexamethasone was significant (P = .016). Intraoral approach also was associated with DSWH significantly (P = .042). No association emerged between DSWH and age, gender, time span from accident to surgery, or duration of surgery. CONCLUSIONS: DSWH occurred significantly more frequently in patients who received perioperative dexamethasone. Because of increased risk of DSWH, perioperative dexamethasone cannot be recommended in open reduction and fixation of ZC fractures.

Cost-utility of molecular adsorbent recirculating system treatment in acute liver failure.

AIM: To determine the short-term cost-utility of molecular adsorbent recirculating system (MARS) treatment in acute liver failure (ALF). METHODS: A controlled retrospective study was conducted with 90 ALF patients treated with MARS from 2001 to 2005. Comparisons were made with a historical control group of 17 ALF patients treated from 2000 to 2001 in the same intensive care unit (ICU) specializing in liver diseases. The 3-year outcomes and number of liver transplantations were recorded. All direct liver disease-related medical expenses from 6 mo before to 3 years after ICU treatment were determined for 31 MARS patients and 16 control patients. The health-related quality of life (HRQoL) before MARS treatment was estimated by a panel of ICU doctors and after MARS using a mailed 15D (15-dimensional generic health-related quality of life instrument) questionnaire. The HRQoL, cost, and survival data were combined and the incremental cost/quality-adjusted life years (QALYs) was calculated. RESULTS: In surviving ALF patients, the health-related quality of life after treatment was generally high and comparable to the age- and gender-matched general Finnish population. Compared to the controls, the average cost per QALY was considerably lower in the MARS group (64,732 euros vs 133,858 euros) within a timeframe of 3.5 years. The incremental cost of standard medical treatment alone compared to MARS was 10,928 euros, and the incremental number of QALYs gained by MARS was 0.66. CONCLUSION: MARS treatment combined with standard medical treatment for ALF in an ICU setting is more cost-effective than standard medical treatment alone.

Early molecular adsorbents recirculating system treatment of Amanita mushroom poisoning.

Acute poisoning due to ingestion of hepatotoxic Amanita sp. mushrooms can result in a spectrum of symptoms, from mild gastrointestinal discomfort to life-threatening acute liver failure. With conventional treatment, Amanita phalloides mushroom poisoning carries a substantial risk of mortality and many patients require liver transplantation. The molecular adsorbent recirculating system (MARS) is an artificial liver support system that can partly compensate for the detoxifying function of the liver by removing albumin-bound and water-soluble toxins from blood. This treatment has been used in acute liver failure to enable native liver recovery and as a bridging treatment to liver transplantation. The aim of the study is to evaluate the outcome of 10 patients with Amanita mushroom poisoning who were treated with MARS. The study was a retrospectively analyzed case series. Ten adult patients with accidental Amanita poisoning of varying severity were treated in a liver disease specialized intensive care unit from 2001 to 2007. All patients received MARS treatment and standard medical therapy for mushroom poisoning. The demographic, laboratory, and clinical data from each patient were recorded upon admission. The one-year survival and need for liver transplantation were documented. The median times from mushroom ingestion to first-aid at a local hospital and to MARS treatment were 18 h (range 14-36 h) and 48 h (range 26-78 h), respectively. All 10 patients survived longer than one year. One patient underwent a successful liver transplantation. No serious adverse side-effects were observed with the MARS treatment. In conclusion, MARS treatment seems to offer a safe and effective treatment option in Amanita mushroom poisoning.

Survival predictors in patients treated with a molecular adsorbent recirculating system.

AIM: To identify prognostic factors for survival in patients with liver failure treated with a molecular adsorbent recirculating system (MARS). METHODS: MARS is a liver-assisting device that has been used in the treatment of liver failure to enable native liver recovery, and as a bridge to liver transplantation (LTX). We analyzed the 1-year outcomes of 188 patients treated with MARS, from 2001 to 2007, in an intensive care unit specializing in liver disease. Demographic, clinical and laboratory parameters were recorded before and after each treatment. One-year survival and the number of LTXs were recorded. Logistic regression analysis was performed to determine factors predicting survival. RESULTS: The study included 113 patients with acute liver failure (ALF), 62 with acute-on-chronic liver failure (AOCLF), 11 with graft failure (GF), and six with miscellaneous liver failure. LTX was performed for 29% of patients with ALF, 18% with AOCLF and 55% with GF. The overall 1-year survival rate was 74% for ALF, 27% for AOCLF, and 73% for GF. The poorest survival rate, 6%, was noted in non-transplanted patients with alcohol-related AOCLF and cirrhosis, whereas, patients with enlarged and steatotic liver had 55% survival. The etiology of liver failure was the most important predictor of survival (P < 0.0001). Other prognostic factors were encephalopathy (P = 0.001) in paracetamol-related ALF, coagulation factors (P = 0.049) and encephalopathy (P = 0.064) in non-paracetamol-related toxic ALF, and alanine aminotransferase (P = 0.013) and factor V levels (P = 0.022) in ALF of unknown etiology. CONCLUSION: The etiology of liver disease was the most important prognostic factor. MARS treatment appears to be ineffective in AOCLF with end-stage cirrhosis without an LTX option.

Is it possible to gain extra waiting time to liver transplantation in acute liver failure patients using albumin dialysis?

Hepatic encephalopathy (HE)-associated brain edema is a common cause of death in acute liver failure (ALF). Molecular Adsorbent Recirculating System (MARS) albumin dialysis detoxifies endogenous and exogenous toxins from blood and improves HE. In this study we assessed the effect of MARS on increasing the length of time available while waiting for liver graft. Thirty-seven patients with ALF who received a high-urgent liver transplant (LTx) were divided into three groups according to the amount of histological necrosis in the explanted liver: group I = 100% necrosis; group II = 80-99% necrosis; group III = less than 80% necrosis. MARS was used continuously until LTx. Median time (range) on MARS treatment prior to LTx in groups I-III was 7 days (2-26), 6 days (1-17), and 5 days (1-15), and the median time on the waiting list was 5 days (1-11), 3 days (0-13), and 1 day (0-12), respectively. The HE grade prior to and after MARS was similar in all groups. In two patients the HE grade decreased during MARS treatment, even though the explanted liver showed a complete lack of viable cells. Overall 30-day and one-year survival were 97% and 92%, respectively, without differences between the three groups. In ALF patients the liver cell damage progressed to total or near total necrosis of the liver when the waiting time was prolonged. Yet, with MARS treatment some patients with total hepatic necrosis showed an absence of encephalopathy. With MARS treatment some patients might be able to wait longer for a LTx with good results.

The effect of molecular adsorbent recirculating system treatment on survival, native liver recovery, and need for liver transplantation in acute liver failure patients.

Acute liver failure (ALF) is a medical emergency. Molecular adsorbent recirculating system (MARS), an artificial liver support system, can partly compensate for the detoxifying function of the liver by removing toxins from blood. To analyze the efficacy of MARS treatment, the outcomes of 113 ALF patients, treated with MARS between 2001 and 2007, were compared with a historical control group of 46 ALF patients treated without MARS between 1995 and 2001. Overall survival of transplanted patients was 94% in the MARS group and 77% in the control group (P=0.06). Without transplantation, survival was 66% and 40% (P=0.03), respectively. However, the etiological distribution of ALF differed significantly between the groups. In ALF patients with unknown etiology, groups were comparable at baseline; 91% and 69% of transplanted patients survived the MARS and control groups and the native liver recovered in 20% and 8% of the patients, respectively. Of the originally nonencephalopathic patients of unknown etiology, 36% underwent liver transplantation in the MARS group compared to 100% in the control group. Interpretation of the results was difficult in toxic etiology patients on account of differing baseline statuses. MARS treatment might partly explain the trend toward increased survival of ALF patients with unknown etiology.