Outcomes after placement of a SX-ELLA oesophageal stent for refractory variceal bleeding-A national multicentre study.

BACKGROUND: Current guidelines favour the use of bleeding stents over balloon tamponade (BT) for refractory variceal bleeding (VB) from oesophageal varices. However, data on the efficacy and safety of self-expandable metal SX-ELLA Danis stents (SEMS) are limited. METHODS: Cirrhotic patients receiving SEMS for VB at four tertiary care centres were included in this retrospective multicentre study. Rates of failure-to-control bleeding (within 5 days) and bleeding-related mortality (6 weeks) were assessed. RESULTS: SEMS controlled VB in 79.4% (27/34) of patients. In the rest of patients, other rescue treatments including endoscopic band ligation (EBL, n = 3), SEMS renewed (n = 2) or Linton (n = 2) were applied; however, VB was only controlled in one patient. Early rebleeding within six weeks occurred in 17.6% (6/34) patients. Median SEMS dwell time was three (IQR:6) days. Overall n = 13/34 (38.2%) patients died with SEMS in situ. After SEMS removal, rebleeding and bleeding-related death occurred in n = 7 (35%) and n = 5 (14.7%) patients respectively. Only 32.4% (10/34) patients did not experience any rebleeding within six weeks after SEMS removal. Bleeding-related mortality was 47.1% (n = 16/34) and the median survival after SEMS placement was 2.1 months. Notably, no patient received an early transjugular intrahepatic portosystemic shunt (TIPS). The most common adverse events were stent dislocations (n = 13; 38.2%), while ulcers/necrosis of the oesophageal mucosa was seen in only four (11.8%) patients. CONCLUSION: SEMS controlled refractory VB in most patients. However, bleeding-related mortality remained high. While SEMS dislocations were frequent, ulcers/necrosis of the oesophagus was rare. Further studies should investigate whether the wider use of early TIPS reduces bleeding-related mortality after SEMS placement.

D-lactic acidosis - case report and review of the literature.

D-lactic acidosis is a rare complication that occurs mainly in patients with malabsorption due to a surgically altered gastrointestinal tract anatomy, namely in short bowel syndrome or after bariatric surgery. It is characterized by rapid development of neurological symptoms and severe metabolic acidosis, often with a high serum anion gap. Malabsorbed carbohydrates can be fermented by colonic microbiota capable of producing D-lactic acid. Routine clinical assessment of serum lactate covers only L-lactic acid; when clinical suspicion for D-lactic acidosis is high, special assays for D-lactic acid are called for. A serum level of more than 3 mmol/L of D-lactate confirms the diagnosis. Management includes correction of metabolic acidosis by intravenous bicarbonate, restriction of carbohydrates or fasting, and antibiotics to eliminate intestinal bacteria that produce D-lactic acid. We report a case of D-lactic acidosis in a patient with short bowel syndrome and review the pathophysiology of D-lactic acidosis with its biochemical and clinical features. D-lactic acidosis should be considered when patients with short bowel syndrome or other malabsorption syndromes due to an altered gastrointestinal tract anatomy present with metabolic acidosis and neurological symptoms that cannot be attributed to other causes. With the growing popularity of bariatric surgery, this metabolic derangement may be seen more frequently in the future.

Extracorporeal albumin dialysis with the molecular adsorbent recirculating system in acute-on-chronic liver failure: the RELIEF trial.

UNLABELLED: Acute-on-chronic liver failure (ACLF) is a frequent cause of death in cirrhosis. Albumin dialysis with the molecular adsorbent recirculating system (MARS) decreases retained substances and improves hemodynamics and hepatic encephalopathy (HE). However, its survival impact is unknown. In all, 189 patients with ACLF were randomized either to MARS (n=95) or to standard therapy (SMT) (n=94). Ten patients (five per group) were excluded due to protocol violations. In addition, 23 patients (MARS: 19; SMT: 4) were excluded from per-protocol (PP) analysis (PP population n=156). Up to 10 6-8-hour MARS sessions were scheduled. The main endpoint was 28-day ITT and PP survival. There were no significant differences at inclusion, although the proportion of patients with Model for Endstage Liver Disease (MELD) score over 20 points and with spontaneous bacterial peritonitis (SBP) as a precipitating event was almost significantly greater in the MARS group. The 28-day survival was similar in the two groups in the ITT and PP populations (60.7% versus 58.9%; 60% versus 59.2% respectively). After adjusting for confounders, a significant beneficial effect of MARS on survival was not observed (odds ratio [OR]: 0.87, 95% confidence interval [CI] 0.44-1.72). MELD score and HE at admission and the increase in serum bilirubin at day 4 were independent predictors of death. At day 4, a greater decrease in serum creatinine (P=0.02) and bilirubin (P=0.001) and a more frequent improvement in HE (from grade II-IV to grade 0-I; 62.5% versus 38.2%; P=0.07) was observed in the MARS group. Severe adverse events were similar. CONCLUSION: At scheduled doses, a beneficial effect on survival of MARS therapy in patients with ACLF could not be demonstrated. However, MARS has an acceptable safety profile, has significant dialysis effect, and nonsignificantly improves severe HE.

Endoscopic radiofrequency ablation for malignant biliary obstruction: a nationwide retrospective study of 84 consecutive applications.

BACKGROUND: Biliary radiofrequency ablation (RFA) using the Habib™ EndoHBP catheter is a new endoscopic palliation therapy for malignant biliary obstruction. The aim of this study was to assess the feasibility and safety of this technique. METHODS: In this nationwide retrospective study of prospectively collected clinical data, all patients treated by biliary RFA in Austria between November 2010 and December 2012 were included. Procedure-related complications, adverse events within 30 days post-intervention, stent patency, and mortality rates were investigated. RESULTS: A total of 58 patients (31 male, 27 female, median age 75 years) underwent 84 RFA procedures at 11 Austrian referral centers for biliary endoscopy. The predominant underlying condition was Klatskin tumor (45 of 58 cases). All 84 RFA procedures were feasible without technical problems. A partial liver infarction was induced by RFA in a 49-year-old Klatskin tumor patient. During 30 days after each RFA procedure, five cases of cholangitis, three cases of hemobilia, two cases of cholangiosepsis, and one case each of gallbladder empyema, hepatic coma, and newly diagnosed left bundle branch block occurred. Median stent patency after last electively performed RFA was 170 days (95 % CI 63-277) and was almost significantly different between metal and plastic stenting (218 vs. 115 days; p = 0.051). Median survival was 10.6 months (95 % CI 6.9-14.4) from the time of the first RFA in each patient and 17.9 months (95 % CI 10.3-25.6) from the time of initial diagnosis. CONCLUSIONS: Except for one severe interventional complication (hepatic infarct), RFA presented as a technically feasible and safe therapeutic option for the palliative treatment of malignant biliary obstruction. The good results of stent patency and survival in this study should be proven in prospective (controlled) trials to further quantify the efficacy of this promising new technique.

Carvedilol for primary prophylaxis of variceal bleeding in cirrhotic patients with haemodynamic non-response to propranolol.

OBJECTIVE: Non-selective ß-blockers or endoscopic band ligation (EBL) are recommended for primary prophylaxis of variceal bleeding in patients with oesophageal varices. Additional α-adrenergic blockade (as by carvedilol) may increase the number of patients with haemodynamic response (reduction in hepatic venous pressure gradient (HVPG) of ≥ 20% or to values <12 mm Hg). DESIGN: Patients with oesophageal varices undergoing measurement of HVPG before and under propranolol treatment (80-160 mg/day) were included. HVPG responders were kept on propranolol (PROP group), while non-responders were placed on carvedilol (6.25-50 mg/day). Carvedilol responders continued treatment (CARV group), while non-responders to carvedilol underwent EBL. The primary aim was to assess haemodynamic response rates to carvedilol in propranolol non-responders. RESULTS: 36% (37/104) of patients showed a HVPG response to propranolol. Among the propranolol non-responders 56% (38/67) eventually achieved a haemodynamic response with carvedilol, while 44% (29/67) patients were finally treated with EBL. The decrease in HVPG was significantly greater with carvedilol (median 12.5 mg/day) than with propranolol (median 100 mg/day): -19 ± 10% versus -12 ± 11% (p<0.001). During a 2 year follow-up bleeding rates for PROP were 11% versus CARV 5% versus EBL 25% (p=0.0429). Fewer episodes of hepatic decompensation (PROP 38%/CARV 26% vs EBL 55%; p=0.0789) and significantly lower mortality (PROP 14%/CARV 11% vs EBL 31%; p=0.0455) were observed in haemodynamic responders compared to the EBL group. CONCLUSIONS: Carvedilol leads to a significantly greater decrease in HVPG than propranolol. Using carvedilol for primary prophylaxis a substantial proportion of non-responders to propranolol can achieve a haemodynamic response, which is associated with improved outcome with regard to prevention of variceal bleeding, hepatic decompensation and death.

Detoxification as a treatment goal in hepatic failure.

Acute liver failure (ALF) is a dramatic clinical syndrome with high mortality because of cerebral oedema (type A hepatic encephalopathy) and multi-organ failure. With intensive care medicine and emergent liver transplantation being the mainstay of treatment, alternatives to transplantation are increasingly needed. Ammonia has been recognised as a major toxin in patients with ALF. It can be effectively removed by haemodialysis, haemofiltration and artificial liver support (a combination of extracorporeal toxin absorption and haemodialysis). Previous studies of extracorporeal detoxification, however, have either not specifically targeted ammonia or were hampered by poor biocompatibility and obsolete pathophysiological assumptions, ultimately failing to improve the prognosis. Moreover, most patients were treated only late after the emergence of advanced HE and multi-organ failure, while detoxification should prevent these complications. Acute-on-chronic liver failure (AOCLF) occurs in the setting of chronic liver disease and has an equally poor prognosis. Here, the goals of extracorporeal blood detoxification are renal support and haemodynamic stabilisation in order to support recompensation. Patients with AOCLF, unfortunately, are at a risk for treatment-related complications including bleeding, thrombocytopenia, hypotension and acute renal failure, making biocompatibility a critical issue. Peritoneal dialysis could possibly emerge as a more biocompatible way of treating refractory hepatorenal syndrome. This article will critically analyse the pathophysiological concepts and goals of extracorporeal detoxification in acute and chronic liver diseases.

[Disturbances of gastrointestinal motility in intensive care units]. / Gastrointestinale Motilitätsstörungen auf der Intensivstation - Ursachen, Konsequenzen und Therapie.

Maintaining regular function of the intestinal tract is an important prerequisite for successful outcomes in critical illness. Disturbances of gastrointestinal motility are frequently caused by drugs, excessive fluid load, mechanical ventilation, surgical or ischemic damage, and occur frequently in sepsis and SIRS. Impaired gastrointestinal motility may give rise to a vitious circle of enteral nutrition intolerance, edema, and may eventually result in a breakdown of the gastrointestinal barrier. Early diagnosis, patient-adapted treatment and a focus on prophylactic measures are necessary prerequisites to maintain gut function in critically ill patients.

Severity of organ failure is an independent predictor of intracranial hypertension in acute liver failure.

BACKGROUND & AIMS: Ionized ammonia (NH(3)) and partial pressure of the gaseous ammonia (pNH(3)) are associated with hepatic encephalopathy and intracranial hypertension in patients with acute liver failure; NH(3) is also believed to contribute to extrahepatic organ failure. We investigated whether the severity of organ failure was associated with intracranial hypertension and evaluated the correlation between NH(3) and pNH(3) and grade of hepatic encephalopathy. METHODS: In 87 patients with acute liver failure admitted to the intensive care unit, we simultaneously evaluated arterial ammonia, pNH(3), clinical grade of hepatic encephalopathy, the sequential organ failure assessment score (SOFA score), and evidence of intracranial hypertension. RESULTS: In comparing patients with intracranial hypertension (n = 37) with patients without intracranial hypertension (n = 50), the highest NH(3) and pNH(3) levels and SOFA scores before onset of intracranial hypertension were independent predictors of intracranial hypertension (P < .001). Among patients with NH(3) levels less than 146 mumol/L, those with intracranial hypertension had a higher SOFA score than those without intracranial hypertension (median, 10 vs 5.5; P = .004), despite the patients' similar levels of NH(3). NH(3) (r = 0.68, P < .0001) and pNH(3) (r = 0.78, P < .0001) both correlated with grade of hepatic encephalopathy. However, in multiple regression analysis, only pNH(3) (P < .0001) was shown to be a significant independent parameter for predicting grade of hepatic encephalopathy (P = .27). CONCLUSIONS: SOFA score and ammonia levels are independent predictors of intracranial hypertension. In patients with acute liver failure admitted to the intensive care unit, pNH(3) level is a better predictor of clinical grade of hepatic encephalopathy than arterial NH(3) level.

Can we really predict the change in serum sodium levels? An analysis of currently proposed formulae in hypernatraemic patients.

BACKGROUND: Hypernatraemia is common in intensive care patients and may present an independent risk factor of mortality. Several formulae have been proposed to guide infusion therapy for correction of serum sodium. Unfortunately, these formulae have never been validated comparatively. We assessed the predictive potential of four different formulae (Adrogué-Madias, Barsoum-Levine, Kurtz-Nguyen and a simple formula based on electrolyte-free water clearance) in correction and maintenance of serum sodium in 66 hyper- and normonatraemic ICU patients. METHODS: With daily measurements of sodium/potassium and fluid/electrolyte balances, a day-to-day prediction of serum sodium levels was calculated using the four formulae. This was compared to the measured changes in serum sodium. RESULTS: Six hundred and eighty-one patient-days (194 hypernatraemic) in 66 patients were available for calculations. Prediction of serum sodium levels using all four formulae correlated significantly (P < 0.05) with measured changes in serum sodium. Individual variations were extreme, and the mean differences (+/-SD) for predicted versus measured serum sodium were within the range of 3.4-4.5 (+/-4.4-4.7) mmol/l similar for the Adrogué-Madias, Barsoum-Levine and Nguyen-Kurtz formulae. In comparison, our proposed formula underestimated the changes of serum sodium (mean +/- SD -1.5 +/- 5.3). During hypernatraemia, the differences between predicted and measured values were even greater (mean +/- SD 5.0-6.7 +/- 3.9-4.3) using the published formulae compared to our formula (mean +/- SD 0.2 +/- 4.0). CONCLUSIONS: Currently available formulae to guide infusion therapy in hyper- and normonatraemic states do not accurately predict changes of serum sodium in the individual ICU patient. In clinical practice, infusion therapy should be based on the reasons for hypernatraemia and serial measurements of serum sodium to avoid evolution of derangements.

Hypernatremia in the critically ill is an independent risk factor for mortality.

BACKGROUND: Hypernatremia is common in the intensive care unit (ICU). We assessed the prevalence of hypernatremia and its impact on mortality and ICU length of stay (LOS). STUDY DESIGN: Retrospective analysis. SETTING & PARTICIPANTS: All patients admitted to a medical ICU of a university hospital during a 35-month observation period. PREDICTOR: Hypernatremia (serum sodium > 149 mmol/L) after admission to the ICU. OUTCOMES & MEASUREMENTS: Main outcomes were 28-day hospital mortality and ICU LOS. Demographic factors, main diagnosis, and severity of illness. Cox proportional hazards regression models were used for data analysis. RESULTS: Of 981 patients, 90 (9%) had hypernatremia, on admission to the ICU in 21 (2%) and developed during the ICU stay in 69 patients (7%). Of these 981 patients, 235 (24%) died; LOS was 8 +/- 9 (SD) days. Mortality rates were 39% and 43% in patients with hypernatremia on admission or that developed after admission compared with 24% in patients without hypernatremia (P < 0.01). LOS was 20 +/- 16 days in patients with hypernatremia compared with 8 +/- 10 days in patients without hypernatremia (P < 0.001). In multivariable analysis, hypernatremia was an independent risk factor for mortality (relative risk, 2.1; 95% confidence interval, 1.4 to 3.3). LIMITATIONS: Retrospective design, absence of data for long-term mortality. CONCLUSIONS: Most cases of hypernatremia in the ICU developed after admission, suggesting an iatrogenic component in its evolution. Hypernatremia is associated with increased mortality. Strategies for preventing hypernatremia in the ICU should be encouraged.

Relative impact of fatigue and subclinical cognitive brain dysfunction on health-related quality of life in chronic hepatitis C infection.

OBJECTIVES: To assess the relative impact of fatigue and subclinical cognitive brain dysfunction on the impairment of health-related quality of life (HRQL) in hepatitis C virus (HCV) infection. DESIGN AND METHODS: We performed a cross-sectional study in 120 patients with untreated chronic HCV infection to test the hypothesis that the severity of fatigue had an independent effect on HCV-associated impairment of HRQL. Patients were investigated using the short-form-36 questionnaire, the fatigue impact scale, the brief fatigue inventory, and P300 event-related potentials, as an objective correlate of neurocognitive function. Patients with decompensated cirrhosis or clinical depression were excluded. RESULTS: Relative to healthy controls, HCV-infected patients showed significant levels of fatigue (Fatigue Impact Scale, 49 versus 26 points, brief fatigue inventory, 3.0 versus 1.6 points, P < 0.001). Fatigue impact scale and brief fatigue inventory scores were highly correlated (r = 0.77, P < 0.001), demonstrating concurrent validity. Severity of fatigue and age were the only factors independently associated with the impairment of HRQL (P < 0.001). Fatigue was not related to the severity of hepatitis or the degree of subclinical brain dysfunction. CONCLUSION: In untreated patients with chronic HCV infection, fatigue severity and age but not neurocognitive dysfunction or hepatic function are independently associated with impaired HRQL. Both the fatigue impact scale and the brief fatigue inventory are suitable tools to assess the subjective burden of fatigue. Our findings stress the need for effective therapeutic interventions to reduce the burden of fatigue in patients with HCV infection.

An international, multicenter, prospective study of a prothrombin complex concentrate, Prothromplex Total®, in anticoagulant reversal.

INTRODUCTION: Prothrombin complex concentrates (PCCs) are a common treatment option for the reversal of oral anticoagulation with vitamin K antagonists (VKAs). This study assessed efficacy and safety of Prothromplex Total®. MATERIALS AND METHODS: Patients (≥18 years) with acquired prothrombin complex coagulation factor deficiency (international normalized ratio [INR] ≥ 2 at screening) due to oral VKAs, requiring reversal of anticoagulation, were treated with 25, 35, or 50 IU/kg BW PCC. After infusion, efficacy was assessed for 72 ± 4 hours. Adverse events (AEs) were captured for 15 days. RESULTS: Sixty-one subjects, 48 requiring interventional procedures and 13 with acute bleeds, received a single infusion of PCC. Of 59 subjects analyzed, all achieved normalization of INR (≤ 1.3) within 30 ± 5 minutes of infusion, demonstrating effective anticoagulant reversal. IVRs of factors II, VII, IX, and X ranged from 1.12-2.03 IU/dL:IU/kg. Median INRs remained between 1.00 and 1.18 for up to 6 hours. Overall efficacy of treatment was rated "excellent" for 60 subjects. Three AEs were deemed possibly related to treatment: 1 serious AE (SAE) of acute myocardial infarction (rated severe), 1 SAE of deep vein thrombosis (rated mild), and 1 AE of pyrexia (rated mild). Thrombotic adverse events (2/61, 3.3%) reported here are comparable to rates observed in other PCC studies. CONCLUSIONS: While there is a risk of thromboembolic events following treatment with PCC products, the number of events reported here was low and could have occurred without PCC treatment. The individualized, INR-based dosing of PCC used here for VKA anticoagulant reversal produces rapid normalization of INR to ≤ 1.3 within 30 minutes.

Hepatorenal syndrome.

The hepatorenal syndrome is defined as functional renal failure in advanced chronic or acute liver disease with portal hypertension. Morphologic abnormalities of the kidneys are frequently absent and tubular function is preserved. Patients with the hepatorenal syndrome are characterized by progressive splanchnic and systemic vasodilation and decreased effective arterial blood volume. Compensatory activation of vasoconstrictory systems maintains systemic hemodynamic stability but causes progressive afferent renal vasoconstriction, leading to reduction of glomerular filtration rate. Renal failure may be rapidly progressive (type I hepatorenal syndrome, frequently associated with spontaneous bacterial peritonitis) or may develop more slowly (type II). Orthotopic liver transplantation is the best current treatment and leads to a gradual recovery of renal function in the vast majority of patients. Because mortality of type I hepatorenal syndrome is excessive, supportive treatment by vasoconstrictor drugs, transjugular intrahepatic portosystemic shunt, and renal replacement therapy has been investigated to achieve stability until transplantation. The definite role of these promising developments, however, is still uncertain, emphasizing the need for large prospective multicentric investigations.

Cognitive deficit after aortic valve replacement.

BACKGROUND: Impairment of cognitive brain function after coronary artery bypass grafting (CABG) is well known. In contrast the potential neurocognitive damage related to aortic valve replacement (AVR) is uncertain. METHODS: In this contemporary case-matched control study we followed 30 patients (mean age 70 years) receiving isolated AVR with a biological prosthesis. A cohort of sex-and age-matched patients (n = 30, mean age 70 years) receiving CABG with cardiopulmonary bypass served as controls. Cognitive brain function was measured by means of auditory evoked P300 potentials (peak latencies, ms) before the operation and 7 days and 4 months after the operation. Additionally, two standard psychometric tests (Mini-Mental State Examination and the Trailmaking Test A) were performed. RESULTS: In preoperative measures there was no difference between patients undergoing AVR and patients undergoing CABG (AVR 378 +/- 37 ms, CABG 374 +/- 32 ms, p = 0.629). One week after surgery P300 peak latencies were prolonged (impaired) in both groups compared with preoperative values (AVR 405 +/- 43 ms, p = 0.001; CABG 398 +/- 44 ms, p = 0.004). At this point of follow-up there was no difference between the groups (p = 0.607). Finally, 4 months after surgery P300 auditory evoked potentials returned to normal in the CABG group (380 +/- 24 ms, p = 0.940) while in contrast in the valve group they continued to become prolonged (worsened) compared with preoperative values (410 +/- 47 ms, p = 0.005). At this time of follow-up P300 peak latencies were prolonged in AVR patients as compared with CABG patients (p = 0.032). The Trailmaking Test A and Mini-Mental State Examination failed to discriminate any difference. CONCLUSIONS: Four-month impairment of cognitive brain function is more pronounced in patients undergoing biological AVR as compared with age-matched control patients undergoing CABG. Further studies are needed to clarify the potential pathologic mechanisms causing an ongoing cognitive impairment in patients with biological aortic valve prostheses.

Neurocognitive deficit following mitral valve surgery.

OBJECTIVE: Neurocognitive deficit is an important complication in patients undergoing open heart surgery. The aim of this prospective, contemporary study was to objectively measure neurocognitive brain function following mechanical mitral valve replacement and mitral valve repair. METHODS: Forty consecutive, unselected patients (mechanical valve replacement n=20, mean age 65+/-14; valve repair n=20, mean age 64+/-7, P=0.896) entered this prospective, contemporary study. Neurocognitive function was objectively measured by means of P300 auditory evoked potentials (peak latencies, ms) and two standard psychometric tests (Mini Mental State Examination, Trailmaking Test A (TTA)), preoperatively, 7 days and 4 months postoperatively. RESULTS: Before operation, neurocognitive brain function was comparable in both patients groups (mechanical valve replacement versus valve repair: P300 potentials 374+/-25 versus 378+/-46 ms; P=0.791 and TTA 57+/-15 versus 54+/-10 s; P=0.552). Following mechanical valve replacement, neurocognitive function continuously worsened (7 day-follow-up: P300 potentials 392+/-28, P=0.001 versus preop and TTA 65+/-17, P=0.0001; 4-month follow-up: P300 potentials 406+/-39, P=0.0004; TTA 69+/-17, P=0.0001). Interestingly, neurocognitive brain function was unaffected in patients undergoing valve repair (7-day follow-up: P300 potentials 386+/-40, P=0.890 versus preop and TTA: 53+/-10, P=0.644; 4-month follow-up: P300 potentials 374+/-36, P=0.166 and TTA 54+/-11, P=0.147). At 4-month follow-up, patients with mechanical prostheses performed worse as compared to valve repair (P300 potentials: P=0.024; TTA P=0.014). CONCLUSION: As shown by P300 auditory evoked potentials and Trailmaking Test A, there is marked neurocognitive damage related to mechanical valve replacement, whereas mitral valve repair does not affect neurocognitive function. This finding supports the beneficial effect of mitral valve repair over mechanical valve replacement in the decision-making tree of borderline cases, which are suitable for both types of procedure.

Acute liver failure.

Acute liver failure is a rare and life-threatening clinical syndrome following severe hepatic injury. Depending on the rapidity of its development, two distinct complications contribute to a high mortality: in hyperacute liver failure, rapid development of massive hepatic necrosis and apoptosis gives rise to severe hyperammonemia, hepatic encephalopathy and life-threatening cerebral edema. The high risk of cerebral herniation requires early listing for emergency liver transplantation. Patients with hyperacute liver failure surviving the initial episode of cerebral edema have a substantial potential for hepatic recovery. If progressive hepatic failure develops more slowly, astrocytic osmoregulation prevents cerebral herniation in most instances. Unfortunately, these patients have a small potential of hepatic regeneration and transplantation should be performed before renal failure, sepsis or multiorgan failure emerge. Experimental treatment methods including detoxification by artificial or bioartificial liver support or by stimulating hepatic regeneration are currently evaluated. Recognition of ammonia toxicity has stimulated the search for early ammonia-lowering strategies and strongly renewed the interest in dialytic therapies. Anti-apoptotic interventions are among the most promising pharmacological options for the near future.

Successful treatment of refractory cerebral oedema in ecstasy/cocaine-induced fulminant hepatic failure using a new high-efficacy liver detoxification device (FPSA-Prometheus).

Ecstasy-induced fulminant hepatic failure is associated with high mortality. If complicated by cerebral oedema, orthotopic liver transplantation is the only established treatment. We report a case of combined ecstasy/cocaine-induced fulminant hepatic failure presenting with severe rhabdomyolysis, myocardial infarction and multiorgan failure. Transplantation was declined by the transplant surgeons because of a history of intravenous drug abuse. As excessive hyperammonaemia (318 mumol/l) and refractory transtentorial herniation developed, treatment with a new liver detoxification device combining high-flux haemodialysis and adsorption (FPSA-Prometheus) was initiated. Within a few hours of treatment, ammonia levels normalised. Cerebral oedema was greatly reduced by day 4 and hepatic function gradually recovered. Following neurologic rehabilitation for ischaemic sequelae of herniation, the patient was discharged from hospital with only minimal deficits. In conclusion, efficient extracorporeal detoxification may be an option for reversal of hyperammonaemia and refractory cerebral oedema in ecstasy/cocaine-induced acute liver failure.

Clinical impact of arterial ammonia levels in ICU patients with different liver diseases.

PURPOSE: Increased arterial ammonia levels are associated with high mortality in patients with acute liver failure (ALF). Data on the prognostic impact of arterial ammonia is lacking in hypoxic hepatitis (HH) and scarce in critically ill patients with cirrhosis. METHODS: The patient cohort comprised 72 patients with HH, 43 patients with ALF, 100 patients with liver cirrhosis and 45 patients without evidence for liver disease. Arterial ammonia concentrations were assessed on a daily basis in all patients and the results were compared among these four patient groups and between 28-day survivors and 28-day non-survivors overall and in each group. RESULTS: Overall 28-day mortality rates in patients with HH, ALF and cirrhosis and in the control group were 54, 30, 49 and 27 %, respectively. Peak arterial ammonia levels differed significantly between transplant-free 28-day survivors and non-survivors in the HH and ALF groups (p < 0.01 for both). Multivariate regression identified peak arterial ammonia concentrations as an independent predictor of 28-day mortality or liver transplantation in patients with HH and ALF, respectively (p < 0.01). There was no association between mortality and arterial ammonia in patients with liver cirrhosis and in the control group. Admission arterial ammonia levels were independently linked to hepatic encephalopathy grades 3/4 in patients with HH (p < 0.01), ALF (p < 0.05) and cirrhosis (p < 0.05), respectively. CONCLUSIONS: Elevated arterial ammonia levels indicate a poor prognosis in acute liver injury and are associated with advanced HE in HH, ALF and cirrhosis. Arterial ammonia levels provide additional information in the risk assessment of critically ill patients with liver disease.

Austrian consensus on the definition and treatment of portal hypertension and its complications (Billroth II).

In November 2004, the Austrian Society of Gastroenterology and Hepatology (ÖGGH) held for the first time a consensus meeting on the definitions and treatment of portal hypertension and its complications in the Billroth-Haus in Vienna, Austria (Billroth I-Meeting). This meeting was preceded by a meeting of international experts on portal hypertension with some of the proponents of the Baveno consensus conferences (http://www.oeggh.at/videos.asp). The consensus itself is based on the Baveno III consensus with regard to portal hypertensive bleeding and the suggestions of the International Ascites Club regarding the treatment of ascites. Those statements were modified by new knowledge derived from the recent literature and also by the current practice of medicine as agreed upon by the participants of the consensus meeting. In October 2011, the ÖGGH organized the second consensus meeting on portal hypertension and its complications in Vienna (Billroth II-Meeting). The Billroth II-Guidelines on the definitions and treatment of portal hypertension and its complications take into account the developments of the last 7 years, including the Baveno-V update and several key publications.