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Summary Introduction Eosinophilic esophagitis (EoE) is a chronic immune-mediated disease of the esophagus with increasing incidence and dysphagia as the main symptom. The management of suspected or known EoE by Austrian endoscopists has not been investigated yet. Methods A web-based survey with 13 questions about the management of EoE was sent to endoscopists via the Austrian Society of Gastroenterology and Hepatology (ÖGGH). Results A total of 222 endoscopists (74% gastroenterologists, 23% surgeons, and 2% pediatricians; 68% working in a hospital) from all 9 states participated. In patients with dysphagia but a normal appearing esophagus, 85% of respondents reported always taking biopsies; however, surgeons were less likely to obtain biopsies compared to gastroenterologists (“always” 69% vs. 90%, “sometimes” 29% vs. 10%, “never” 2% vs. 0%, p Conclusion The vast majority of Austrian endoscopists adhere to the European and US guidelines in cases of suspected EoE. In contrast, despite the chronic disease course, a significant percentage of providers indicate not to use maintenance therapy and monitor the patients routinely.

Background Prophylactic endoscopic band ligation (EBL) is used to prevent variceal bleeding in patients with liver cirrhosis. The association of thrombocytopenia, high INR (international normalized ratio) and liver dysfunction with the risk of procedure-related bleeding (PRB) remains debated and recommendations are controversial. Methods We analyzed real-life data of cirrhotic patients undergoing elective EBL at two large Viennese centers between Q1/2000–Q1/2018. PRB was defined as bleeding occurring within 30 days after EBL. Results We included 617 patients undergoing a total of 1178 prophylactic EBL procedures (median 2 per patient). Sixteen (2.6%) of 617 patients experienced PRB after a median of 12.5 (IQR 17.3) days with no difference in characteristics and laboratory values between the two groups. The proportion of patients with platelets (PLT) Conclusion EBL is safe and procedure-related bleedings are rare (2.6%) including in patients with thrombocytopenia

Introduction Ulcerative colitis (UC) is a chronic disease with rising incidence and unclear etiology. Deep molecular phenotyping by multi omics analyses may provide novel insights into disease processes and characteristic features of remission states. Methods UC pathomechanisms were assessed by proteome profiling of human tissue specimen, obtained from five distinct colon locations for each of the 12 patients included in the study. Systemic disease-associated alterations were evaluated thanks to a cross-sectional setting of mass spectrometry-based multi-omics analyses comprising proteins, metabolites and eicosanoids of plasma obtained from UC patients during acute episodes and upon remission in comparison to healthy controls. Results Tissue proteome profiling indicated colitis-associated activation of neutrophils, macrophages, B- and T-cells, fibroblasts, endothelial cells and platelets, and hypoxic stress, and suggested a general down-regulation of mitochondrial proteins accompanying the establishment of apparent wound healing-promoting activities including scar formation. While pro-inflammatory proteins were apparently upregulated by immune cells, the colitis-associated epithelial cells, fibroblasts, endothelial cells and platelets seemed to predominantly contribute anti-inflammatory and wound healing-promoting proteins. Blood plasma proteomics indicated chronic inflammation and platelet activation, whereas plasma metabolomics identified disease-associated deregulations of gut and gut microbiome-derived metabolites. Upon remission, several, but not all, molecular candidate biomarker levels recovered back to normal. Conclusions The findings may indicate that microvascular damage and platelet deregulation hardly resolve upon remission but apparently persist as disease-associated molecular signature. This study presents local and systemic molecular alterations integrated in a model for UC pathomechanisms potentially supporting the assessment of disease and remission states in UC patients.

Background Prophylactic endoscopic band ligation (EBL) is used to prevent variceal bleeding in patients with liver cirrhosis. The association of thrombocytopenia, high INR (international normalized ratio) and liver dysfunction with the risk of procedure-related bleeding (PRB) remains debated and recommendations are controversial. Methods We analyzed real-life data of cirrhotic patients undergoing elective EBL at two Viennese centers between Q1/2000-Q1/2018. PRB was defined as bleeding occurring within 30 days after EBL. Results We included 626 patients undergoing a total of 1519 prophylactic EBL procedures (median 2 per patient). Sixteen (2.6%) of 626 patients experienced PRB after a median of 12.5 (IQR 17.3) days with no difference in characteristics and laboratory values between the two groups. The proportion of patients with platelets (PLT) Conclusion EBL is safe and procedure-related bleedings are rare (2.6%) including in patients with thrombocytopenia

Summary Background Portal hypertension (PH) causes severe complications in patients with liver cirrhosis, such as variceal bleeding and ascites; however, data on the knowledge and perceptions on guideline recommendations for the management of varices and the use of albumin is scarce. Methods We designed two structured surveys on (i) the management of varices and (ii) the use of albumin for Austrian physicians of specialized Gastro-Intestinal (GI) centers. The interviewed physicians were confronted spontaneously and provided ad hoc responses to the questionnaire. Results In total, 158 surveys were completed. Interestingly, many specialists (30%) would recommend a follow-up gastroscopy after 1 year in patients with compensated cirrhosis without varices (i.e., overtreatment). For small varices, 81.5% would use non-selective beta blockers (NSBB) for primary prophylaxis (PP). For PP in patients with large varices, endoscopic band ligation (EBL) plus NSBB was preferred by 51.4% (i.e., overtreatment). Knowledge on the indication criteria for early TIPS (transjugular intrahepatic portosystemic shunt) was reported by 54.3%, but only 20% could report these criteria correctly. The majority (87.1%) correctly indicated a preference to use NSBB and EBL for secondary prophylaxis (SP). The majority of participating gastroenterologists reported no restrictions on the use of albumin (89.8%) in their hospitals. Of the interviewed specialists, 63.6% would use albumin in patients with SBP; however, only 11.4% would use the doses recommended by guidelines. The majority of specialists indicated using albumin at the recommended doses for hepatorenal syndrome (HRS-AKI, 86.4%) and for large volume paracentesis (LVP, 73.3%). The individual responses regarding albumin use for infections/sepsis, hyponatremia, renal impairment, and encephalopathy were heterogeneous. Conclusion The reported management of PH and varices is mostly adherent to guidelines, but endoscopic surveillance in patients without varices is too intense and EBL is overused in the setting of PP. Knowledge on the correct use of early TIPS must be improved among Austrian specialists. Albumin use is widely unrestricted in Austria; however, albumin is often underdosed in established indications.

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.

Both acute and chronic pancreatitis are frequent diseases of the pancreas, which, despite being of benign nature, are related to a significant risk of malnutrition and may require nutritional support. Acute necrotizing pancreatitis is encountered in 20% of patients with acute pancreatitis, is associated with increased morbidity and mortality, and may require artificial nutrition by enteral or parenteral route, as well as additional endoscopic, radiological or surgical interventions. Chronic pancreatitis represents a chronic inflammation of the pancreatic gland with development of fibrosis. Abdominal pain leading to decreased oral intake, as well as exocrine and endocrine failure are frequent complications of the disease. All of the above represent risk factors related to malnutrition. Therefore, patients with chronic pancreatitis should be considered at risk, screened and supplemented accordingly. Moreover, osteoporosis and increased facture risk should be acknowledged in patients with chronic pancreatitis, and preventive measures should be considered.

BACKGROUND Endoscopic band ligation (EBL) is used for primary (PP) and secondary prophylaxis (SP) of variceal bleeding. Current guidelines recommend combined use of non-selective beta-blockers (NSBBs) and EBL for SP, while in PP either NSBB or EBL should be used. AIM To assess (re-)bleeding rates and mortality in cirrhotic patients receiving EBL for PP or SP for variceal bleeding. METHODS (Re-)bleeding rates and mortality were retrospectively assessed with and without concomitant NSBB therapy after first EBL in PP and SP. RESULTS Seven hundred and sixty-six patients with oesophageal varices underwent EBL from 01/2005 to 06/2015. Among the 284 patients undergoing EBL for PP, n = 101 (35.6%) received EBL only, while n = 180 (63.4%) received EBL + NSBBs. In 482 patients on SP, n = 163 (33.8%) received EBL only, while n = 299 (62%) received EBL + NSBBs. In PP, concomitant NSBB therapy neither decreased bleeding rates (log-rank: P = 0.353) nor mortality (log-rank: P = 0.497) as compared to EBL alone. In SP, similar re-bleeding rates were documented in EBL + NSBB vs EBL alone (log-rank: P = 0.247). However, EBL + NSBB resulted in a significantly lower mortality rate (log-rank: P

Hypoxic hepatitis (HH) is a frequent and life-threatening complication associated with states of oxygen depletion in critically ill patients. Ischemia and reperfusion contribute to liver injury in HH. Experimental data suggest beneficial effects of statins in hepatic ischemia/reperfusion injury. This study was conducted to investigate whether statin treatment prior to intensive care unit (ICU) admission affects incidence rates and severity of HH.Eight hundred fifty-one patients admitted consecutively to three medical ICUs between December 2008 and December 2009 were prospectively screened for new occurrence of HH within 48 h following ICU admission. Statin treatment prior to ICU admission was assessed. 28-day-, 90-day-, and 1-year-survival as well as new-onset of complications in HH patients were prospectively documented.Eighty-seven patients (10%) developed HH. Statin treatment prior to ICU admission was significantly associated with decreased incidence of HH within 48 h after ICU admission in the multivariate analysis (adjusted OR=0.42 (95% CI 0.19-0.95); p0.05). Cardiogenic shock (p0.001), septic shock (p0.001) and active alcohol consumption (p0.01) were identified as independent risk factors for development of HH. 28-day-, 90-day-, and 1-year-mortality rates in HH were 58%, 67%, and 74%, respectively. Statins were associated with improved 28-day-survival in the total study cohort (p0.05), but did not affect 90-day- and 1-year-mortality, respectively.Cardiogenic shock, septic shock, and active alcohol consumption were independent factors predisposing patients to new onset of HH. Statin treatment prior to ICU admission was the only protective factor regarding the new occurrence of HH in critically ill patients.

Aim In critically ill patients, reduced anti-FXa plasma activity following subcutaneous administration of enoxaparin or nadroparin has been described. In this study, we aimed to investigate the bioactivity of enoxaparin in critically ill patients and controls.

OBJECTIVE To evaluate the impact of real-time continuous glucose monitoring (CGM) on glycemic control and risk of hypoglycemia in critically ill patients. RESEARCH DESIGN AND METHODS A total 124 patients receiving mechanical ventilation were randomly assigned to the real-time CGM group (n = 63; glucose values given every 5 min) or to the control group (n = 61; selective arterial glucose measurements according to an algorithm; simultaneously blinded CGM) for 72 h. Insulin infusion rates were guided according to the same algorithm in both groups. The primary end point was percentage of time at a glucose level RESULTS Percentage of time at a glucose level CONCLUSIONS In critically ill patients, real-time CGM reduces hypoglycemic events but does not improve glycemic control compared with intensive insulin therapy guided by an algorithm.

Loss of high molecular weight von Willebrand factor (VWF) multimers in patients suffering from aortic valve stenosis and gastrointestinal (GI) bleeding has been regarded as the missing link between aortic stenosis and bleeding. Electrophoretic analysis of VWF multimers is laborious and time-consuming. Further, determination of overall haemostatic competence rather than evaluation of restricted portions thereof may be advantageous. Accumulating evidence suggests that, recently developed in vitro and ex vivo platelet reactivity tests under high shear conditions mirror the in vivo situation. We report on a case of a 79-year-old man who presented with recurrent GI bleeding and severe aortic stenosis. Platelet function testing under high shear conditions using the commercially available cone and plate(let) analyser-Impact-R revealed significantly impaired shear dependent platelet function, suggesting VWD. This test offers an easy to use diagnostic tool to evaluate platelet function in suspected Heyde Syndrome thus leading to immediate tailored patient's management.

Background and study aims: Endoscopic treatment of active gastrointestinal bleeding often remains difficult, and considerable technical expertise is required. Our aim was to assess the efficacy and safety of endoscopic hemostasis with a liquid combination of bovine activated factors IIa/VIIa/IXa/Xa (SeraSeal). Methods: Patients with active gastrointestinal bleeding were prospectively included. In group A, 5 mL of bovine activated factors IIa/VIIa/IXa/Xa was topically applied via catheters to the bleeding site as initial hemostasis; group B received a similar application but as rescue therapy after failure of conventional endoscopic hemostasis. Results: In group A, bleeding was stopped by the agent in 15 /22 patients (68 %) and by conventional endoscopic hemostasis in 5 of the other 7, with coiling and surgery required for definitive hemostasis in 2. In group B, the addition of the agent definitively stopped bleeding in 13 /15 patients (87 %), with hemostasis in the remaining 2 achieved with fibrin glue. Rebleeding was observed in 1 patient. Conclusions: Our proof of concept study suggests that the use of bovine activated factors IIa/VIIa/IXa/Xa might be a safe and effective addition to current endoscopic hemostatic strategies, but further studies are necessary. ClinicalTrials.gov identifier: NCT02349490

This study aimed to examine brain energy metabolism during moderate insulin-induced hypoglycaemia in Type 1 diabetic patients and healthy volunteers.Type 1 diabetic patients (mean diabetes duration 13 +/- 2.5 years; HbA1c 6.8 +/- 0.3%) and matched controls were studied before, during (0-120 min) and after (120-240 min) hypoglycaemic (approximately 3.0 mmol/l) hyperinsulinaemic (1.5 mU x kg(-1) min(-1)) clamp tests. Brain energy metabolism was assessed by in vivo 31P nuclear magnetic resonance spectroscopy of the occipital lobe (3 Tesla, 10-cm surface coil).During hypoglycaemia, the diabetic patients showed blunted endocrine counter-regulation. Throughout the study, the phosphocreatine:gamma-ATP ratios were lower in the diabetic patients (baseline: controls 3.08 +/- 0.29 vs diabetic patients 2.65 +/- 0.43, p0.01; hypoglycaemia: 2.97 +/- 0.38 vs 2.60 +/- 0.35, p0.05; recovery: 3.01 +/- 0.28 vs 2.60 +/- 0.35, p0.01). Intracellular pH increased in both groups, being higher in diabetic patients (7.096 +/- 0.010 vs. 7.107 +/- 0.015, p0.04), whereas intracellular magnesium concentrations decreased in both groups (controls: 377 +/- 33 vs 321 +/- 39; diabetic patients: 388 +/- 47 vs 336 +/- 68 micromol/l; p0.05).Despite a lower cerebral phosphocreatine:gamma-ATP ratio in Type 1 diabetic patients at baseline, this ratio does not change in control or diabetic patients during modest hypoglycaemia. However, both groups exhibit subtle changes in intracellular pH and intracellular magnesium concentrations.

Ileus refers to the partial or complete blockage of the small and/or large intestine either by functional (adynamic or paralytic ileus) or mechanical bowel obstruction. The diffuse gastrointestinal dysmotility during functional and mechanical ileus may result in intestinal dilatation, increased luminal pressure and gut wall ischaemia which may lead to increased intra-abdominal pressure (IAP). Any type of ileus may promote abdominal fluid sequestration with severe systemic hypovolaemia, intestinal bacterial overgrowth with the evolution of bacterial translocation and systemic invasive infections and inflammation of the intestinal wall with concomitant release of cytokines and the development of the systemic inflammatory response syndrome. The most serious complications of ileus are mediated by an increase in IAP. Intra-abdominal hypertension has been found in up to 20% of critically ill patients and may lead to a broad pattern of systemic consequences with multiple organ dysfunction, including cardiovascular, hepatic, pulmonary, renal and neurological function. The abdominal compartment syndrome is an emergency condition which is defined as elevation of IAP above 20 to 25 mmHg and the presence of systemic consequences. Therapeutic considerations include the maintenance of adequate hydration status, avoidance of drugs known to impair intestinal perfusion, stimulation of gastric and intestinal motility and various nutritional aspects. Colonic tube placement after decompressive colonoscopy may be effective in reducing intestinal dilatation. In the abdominal compartment syndrome the 'open abdominal approach' with decompressive laparotomy by opening the peritoneal cavity and temporary abdominal closure is the therapy of choice.

Objective: The aim of this study was to objectively measure neurocognitive deficit following aortic valve replacement with a mechanical or biological prosthesis. Materials and methods: In this prospective. contemporary study we followed 82 consecutive patients undergoing isolated aortic valve replacement with either a mechanical (n = 29, mean age = 52 ± 7 years) or a biological (n = 53, mean age = 68 ± 10 years) valve prosthesis. Neurocognitive function was measured by means of objective P300 auditory evoked potentials (peak latencies, ms) and two standard psychometric tests (Trailmaking Test A, Mini Mental State Examination) before the operation, 7 days and 4 months after the operation, respectively. Results: Since P300 peak latencies increase with age, preoperative P300 measures are lower in patients receiving mechanical valves (360 ± 35 ms. mean 52 years) as compared to patients receiving biological valves (381 ± 34 ms, 68 years, P = 0.0001). Seven days after surgery. P300 peak latencies were prolonged (-worsened) in both groups as compared to preoperative values (mechanical valves: 384 ± 36 ms: P = 0. 0001 and biological valves: 409 ± 39 ms : P = 0. 0001). Although on a different level (-age-related), this development was comparable within both groups (P = 0. 800). Four months after surgery, P300 peak latencies normalized in the mechanical valve group (372 ± 27 ms, P = 0.857 versus preoperative), while in contrast in the biological valve group they remained prolonged (417 ± 37 ms, P = 00001) We found no difference within patients receiving different types of biological or mechanical aortic valves. conclusion: Postoperative neurocognitive damage is not reversible in,( -elderly) patients with biological aortic valve replacement, while in contrast postoperative neurocognitive damage is reversible in (-younger) patients with mechanical valve replacement. For this contrary development, age seems to be most important, whereas damage related to type of valve prosthesis may be overestimated.

Background Hypoxic-ischaemic brain damage in cardiac arrest survivors is global, but postmortem histology could identify parts of the brain that are selectively vulnerable to ischaemia, comprising the thalamus and cortex. We hypothesized that hypoxic-ischaemic brain damage increases along the afferent sensory pathway with a stepwise decrease of detectable somatosensory evoked potential peaks. Methods Somatosensory evoked potentials were recorded within 72 h after cardiac arrest in 305 comatose patients after cardiopulmonary resuscitation. We measured the short latency SEP peaks N9, P15, N20, P25 (reflecting the peripheral-thalamo-cortical pathway) and the long latency SEP peaks N35 and N70 (reflecting complex cortico–cortical interactions). Patients with a Cerebral Performance Category score > 2 at 1 year were defined as patients with hypoxic-ischaemic brain damage. Results Patients with hypoxic-ischaemic brain damage (n = 232) showed a statistically significant decrease of detectable peaks (P

Background Sepsis in critical illness is associated with the progressive failure of multiple organs. This study aims to establish a correlation between the severity of sepsis and exocrine pancreatic dysfunction. Materials and methods In a prospective cohort study pancreatic exocrine function was tested by means of a secretin-cholecystokinin test in 21 critically ill, mechanically ventilated patients with sepsis according to criteria of the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference Committee (ACCP/SCCM): 11 patients with shock and 10 patients without shock. Data were compared with seven healthy controls. Results The volume of duodenal fluid was not statistically different in the three groups. Sepsis patients without shock had significantly reduced content of amylase and chymotrypsin in duodenal juice compared with healthy controls (P

Serum bilirubin levels are commonly used to assess extracorporeal detoxification by liver support systems. We tested the hypothesis that intravenous colloids administered before liver support treatment could confound bilirubin values. Eight cirrhotic patients received an infusion of a 6% hydroxy ethyl starch solution (10 ml/kg, 30 minutes) before detoxification using a liver support system (FPSA). Bilirubin was measured before and 1 hour after infusion, and after FPSA treatment (7 hours). Infusion of hydroxy ethyl starch was associated with a drop in bilirubin values (mean, 18%, range, 1–44%, p=0.03 versus baseline values). Bilirubin levels were further reduced during FPSA treatment (mean, 27%, range, 22–34%; p=0.02 versus pre-treatment values). In conclusion, hydroxy ethyl starch solution may decrease bilirubin levels in hyperbilirubinemic cirrhotic patients receiving extracorporeal detoxification. The role of potentially confounding factors in liver support studies is discussed further.

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.

In den letzten Jahren wurden zahlreiche Prognoseparameter zur Beurteilung der cerebralen Hypoxie nach kardiopulmonaler Reanimation untersucht. Diese Parameter umfassen neben klinischen Daten und klinischen Scoresystemen, verschiedene klinisch-neurologische Befunde, biochemische Parameter, elektrophysiologische Untersuchungen und neurodiagnostische bildgebende Verfahren. Ziel der osterreichischen interdisziplinaren Konsensuskonferenz war die kritische Evaluierung dieser Parameter und die Empfehlung welche Parameter bzw. diagnostischen Masnahmen zu welchem Zeitpunkt eine prognostische Aussage uber eine potentielle neurologische Rehabilitation nach cerebraler Hypoxie ermoglichen. Aus mehr als 100 unterschiedlichen Parametern wurden 26 Parameter identifiziert, die, basierend auf Ergebnisse wissenschaftlicher Publikationen, eine prognostische Aussage ermoglichen. Diese Parameter mussen jedoch hinsichtlich der Einschatzung der Evidenz und deren Starkegrad als Grundlage fur prognostische Empfehlungen unterschiedlich beurteilt werden.

Objective: To assess the validity of early sensory evoked potential (SEP) recording for reliable outcome prediction in comatose cardiac arrest survivors within 48 h after restoration of spontaneous circulation (ROSC). Design and setting: Prospective cohort study in a medical intensive care unit of a university hospital. Patients: Twenty-five comatose, mechanically ventilated patients following cardiopulmonary resuscitation Measurements and results: Median nerve short- and long-latency SEP were recorded 4, 12, 24, and 48 h after ROSC. Cortical N20 peak latency and cervicomedullary conduction time decreased (improved) significantly between 4, 12, and 24 h after resuscitation in 22 of the enrolled patients. There was no further change in short-latency SEP at 48 h. The cortical N70 peak was initially detectable in seven patients. The number of patients with increased N70 peak increased to 11 at 12 h and 14 at 24 h; there was no further change at 48 h. Specificity of the N70 peak latency (critical cutoff 130 ms) increased from 0.43 at 4 h to 1.0 at 24 h after ROSC. Sensitivity decreased from 1.0 at 4 h to 0.83 at 24 h after ROSC. Conclusion: Within 24 h after ROSC there was a significant improvement in SEP. Therefore we recommend allowing a period of at least 24 h after cardiopulmonary resuscitation for obtaining a reliable prognosis based on SEP.

Objectives: To switch patients with severe pulmonaryhypertension and previous life-threatening catheter-relatedcomplications from long-term IV epoprostenol therapy to aerosolizediloprost therapy. Design: Open, uncontrolledtrial. Setting: Medical ICU of a universityhospital. Patients: Two patients with primarypulmonary hypertension and one patient with pulmonary hypertensionafter surgical closure of atrial septal defect (mean pulmonary arterypressure ≥ 50 mm Hg). All were classified as New York Heart Association class II under treatment with continuous IV epoprostenolfor 4 years. Interventions: Stepwise reduction of IVepoprostenol (1 ng/kg/min steps every 3 to 10 h) during repeatedinhalations of aerosolized iloprost (150 to 300 μg/d with 6 to 18inhalations/d). Continuous pulmonary and systemic arterial monitoringwere performed. Results: Aerosolized iloprost reducedpulmonary artery pressure by 49%, 49%, and 45%, respectively, andincreased cardiac output by 70%, 75%, and 41% in the three patients. The effect lasted for 20 min and was similar at different doses of IVepoprostenol. Persistent treatment change to inhaled iloprost could notbe achieved because all patients developed signs of right heartfailure. After termination of iloprost inhalations, return to standardepoprostenol therapy led to clinical and hemodynamic restoration. Conclusions: Although aerosolized iloprost demonstratedshort-term hemodynamic effects, it could not be utilized as alternativechronic vasodilator in patients with severe pulmonaryhypertension.

Extracorporeal detoxification has been proposed to treat patients with hepatic encephalopathy (HE) not responding to standard therapy. To investigate the biocompatibility of a cuprophane charcoal-based detoxification device, a prospective, randomized, controlled study was performed. Of 41 consecutive patients with cirrhosis and HE grade II or III who did not improve with conventional treatment, 20 patients (median age, 56 years; range, 33 to 71 years; 13 men) were randomly assigned to either ongoing conventional treatment or one additional 6-hour treatment with a sorbent suspension dialysis system. Main outcome parameters were physiological function and blood parameters of biocompatibility. In the 10 patients undergoing combined conventional and sorbent suspension dialysis treatment, blood pressure remained unchanged and body temperature and heart rate increased (P:0.01). Platelet count decreased (medians, from 75 to 26 g/L; P:0.001) and international normalized ratio increased after combined treatment (2.0 to 2.2; P:0.001). Three patients developed bleeding complications during treatment or shortly after. Treated patients showed increases in levels of plasma elastase (104 to 586 microg/L; P: = 0.001), tumor necrosis factor-alpha (5.4 to 7.5 pg/mL; P: = 0.04), and interleukin-6 (118 to 139 pg/mL; P: = 0.04), but not interferon-gamma and E-selectin. No changes were observed in the 10 patients treated conventionally. In conclusion, despite technical refinements compared with charcoal hemoperfusion, biocompatibility of sorbent suspension dialysis is still very limited. Clinical complications were apparently caused by blood-membrane interactions and disseminated intravascular coagulation. We suggest further developments in design and appropriate strategies of anticoagulation to improve the biocompatibility of artificial liver support.

BACKGROUND The effects of food restriction on energy metabolism have been under investigation for more than a century. Data obtained are conflicting and research has failed to provide conclusive results. OBJECTIVE The objective of this study was to test the hypothesis that in lean subjects under normal living conditions, short-term starvation leads to an increase in serum concentrations of catecholamines and thus to an increase in resting energy expenditure. DESIGN Resting energy expenditure, measured by indirect calorimetry, and hormone and substrate concentrations were measured in 11 healthy, lean subjects on days 1, 2, 3, and 4 of an 84-h starvation period. RESULTS Resting energy expenditure increased significantly from 3.97 +/- 0.9 kJ/min on day 1 to 4.53 +/- 0.9 kJ/min on day 3 (P < 0.05). The increase in resting energy expenditure was associated with an increase in the norepinephrine concentration from 1716. +/- 574 pmol/L on day 1 to 3728 +/- 1636 pmol/L on day 4 (P < 0.05). Serum glucose decreased from 4.9 +/- 0.5 to 3.5 +/- 0.5 mmol/L (P < 0.05), whereas insulin did not change significantly. CONCLUSIONS Resting energy expenditure increases in early starvation, accompanied by an increase in plasma norepinephrine. This increase in norepinephrine seems to be due to a decline in serum glucose and may be the initial signal for metabolic changes in early starvation.

Objective: To compare the prognostic ability of sensory evoked potentials in cardiac arrest survivors with the outcome predicted by a panel of experienced emergency physicians based on detailed prehospital, clinical, and laboratory data. Design: Inception cohort study. Setting: Medical intensive care unit and department of emergency medicine at a university hospital. Patients: A total of 162 unconscious, mechanically ventilated patients who survived ≥24 hrs after resuscitation from cardiac arrest. Interventions: Recording of sensory evoked potentials and outcome prediction after review of detailed clinical and laboratory data by emergency physicians within 24 hrs after cardiac arrest. Measurements and Main Results: At 6 months, the outcome of 36 patients was classified as favorable and 126 patients were rated as poor. After review of prehospital data, emergency physicians predicted favorable vs. poor outcome with a sensitivity of 70% and a specificity of 65%. After additional assessment of data 1 hr after cardiac arrest, the sensitivity of emergency physician predictions increased to 80%, whereas the specificity decreased to 48%. Outcome prediction by emergency physicians was most accurate after obtaining detailed patient data 24 hrs after cardiac arrest (sensitivity, 81%; specificity, 58%). In 35 of 36 patients with favorable outcomes, the cortical evoked potential N70 peak was detected between 72 and 128 msec. Of 113 patients with an N70 peak latency > 130 msec or an absent N70 peak, all except one had a poor outcome. By using a cutoff of 130 msec, the N70 peak latency alone had a sensitivity of 94% and a specificity of 97%. The predictive accuracy of the N70 peak latency was significantly higher than the clinical assessment 24 hrs after cardiac arrest (91% vs. 76%,p= .0003). Conclusion: In unconscious cardiac arrest survivors, a recording of long-latency sensory evoked potentials is more accurate in predicting individual outcome than an emergency physician review of clinical data.

Ammonia is considered the major pathogenetic factor of cerebral dysfunction in hepatic failure. The correlation between total plasma ammonia and the severity of hepatic encephalopathy (HE), however, is variable. Because ammonia that is present in gaseous form readily enters the brain, the correlation with the grade of HE of the pH-dependent partial pressure of gaseous ammonia (pNH(3)) could be better than that of total arterial ammonia levels. To test this hypothesis, 56 cirrhotic patients with acute episodes of clinical HE (median age, 54 years; range, 21-75) were studied by clinical examination and by long-latency median-nerve sensory-evoked potentials (SEPs) N70 peak, an objective and sensitive electrophysiological measure of HE. pNH(3) was calculated from arterial blood according to published methods. The clinical grade of HE correlated (P

In patients with Wilson's disease presenting with liver involvement, the correct diagnosis is often missed or delayed. The aim of this study was to find an algorithm for diagnosis of this difficult patient group.Clinical and laboratory findings of 55 patients with Wilson's disease were evaluated at diagnosis before treatment. Presenting symptom was chronic liver disease in 17 patients, fulminant hepatic failure in 5 patients, hemolysis in 3 patients, and neurological disease in 20 patients, and 10 patients were detected by family screening (siblings). Evaluation included neurological and ophthalmologic examination, routine laboratory tests, and parameters of copper metabolism including liver copper content in 43 liver biopsy specimens.In the whole group, serum ceruloplasmin level was20 mg/dL in 73%, urinary copper excretion was increased in 88%, and liver copper content was elevated in 91% at diagnosis. Kayser-Fleischer rings were detected in 55%. In contrast to patients with neurological disease (90% Kayser-Fleischer rings, 85% low ceruloplasmin), only 65% of patients presenting with liver disease were diagnosed by these typical findings. Ceruloplasmin levels were lower in patients with Kayser-Fleischer rings or with neurological disturbances than in patients without these symptoms.The commonly used clinical and laboratory parameters are not sufficient to exclude the diagnosis of Wilson's disease in patients with liver disease of unknown origin.

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. 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. 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. 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.

Adequate anticoagulation is essential to achieve efficient and cost-effective continuous renal replacement therapy (CRRT). However, in critically ill patients with advanced liver cirrhosis, this goal is challenging because of the concomitant bleeding disorder. Therefore, the evaluation of alternative anticoagulants is necessary.In this retrospective study, we analyzed data of 37 CRRTs in 16 critically ill patients with advanced liver cirrhosis and acute kidney injury admitted to a medical intensive care unit between 2006 and 2008 and included patients undergoing CRRT with either single doses of antithrombin (AT) or continuous low-dose heparin as a sole anticoagulant. The primary outcome measure was lifetime of single CRRT filters.Data were available for 13 CRRT filters for patients anticoagulated with single doses of AT (n = 6), and 24 CRRT filters for patients anticoagulated continuously with low-dose heparin (n = 10). Means of single-filter lifetimes were significantly higher in the AT group compared with the heparin group (45 ± 29 hours [95% confidence interval 27-62 hours] vs 26 ± 23 hours [95% confidence interval 16-36 hours]; P = 0.03), whereas mean filter lifetimes of individual patients were comparable (median [25th-75th percentile] 30 hours [21-59 hours] vs 28 hours [17-70 hours]; P = 0.79).Our data suggest that anticoagulation with single doses of AT may be an alternative to continuously administered low-dose heparin in critically ill patients with advanced liver cirrhosis during CRRT. However, additional controlled trials are necessary to confirm our findings.

Venous thromboembolism is a frequent complication in critically ill patients that has a negative impact on patient outcomes. Critically ill patients have significantly lower plasma anti-factor-Xa activity levels compared with control patients after administration of subcutaneous heparin. The clinical relevance of the different anti-factor-Xa levels after prophylactic doses of low molecular weight heparin (LMWH) in critically ill patients is not completely understood.The standard dose of 40 mg enoxaparin led to a significant increase in anti-FXa levels in this selected cohort of ICU patients with normal renal function. This study found only subtle pharmacokinetic differences, but a comparable pharmacodynamic action, after enoxaparin administration in critically ill and normal medical ward patients. Thrombin generation with TGA RC-low and TGARC-high reagents was significantly reduced in ICU and normal ward patients after receiving LMWH. Both readouts appear equally useful for estimating the pharmacodynamics of enoxaparin. The ex vivo model of thrombosis was used for the first time in patients to evaluate the anti-thrombotic activity of LMWH. This method did not show any difference in thrombus formation after administration of enoxaparin in the individual group of patients.In critically ill patients, reduced anti-FXa plasma activity following subcutaneous administration of enoxaparin or nadroparin has been described. In this study, we aimed to investigate the bioactivity of enoxaparin in critically ill patients and controls.A prospective, controlled, open label study was performed on a medical intensive care unit (ICU) and a general medical ward. Fifteen ICU patients (male = 12, median age 52 years [IQR 40-65], with a median Simplified Acute Physiology Score of 30 [IQR 18-52]) and sex- and age-matched medical ward patients were included. The anti-FXa plasma activity was measured after a single subcutaneous dose of40 mg enoxaparin. The thrombus size of a clot formed in an ex vivo perfusion chamber and endogenous thrombin potential (ETP) were measured.The anti-FXa plasma activity increased significantly after enoxaparin administration, with peak levels at 3 h after treatment, but was comparable between the ICU and medical ward groups (median 0.16 IU ml-1 [IQR 0-0.22 IU ml-1] vs. 0.2 IU ml-1 [IQR 0.15-0.27 IU ml-1],respectively, P = 0.13). The area under the anti-FXa activity curve from 0–12 h was similar between the groups (median 0.97 IU ml-1 h [IQR0.59-2.1] and 1.48 IU ml-1 h1 [IQR 0.83-1.62], P = 0.42 for the ICU group compared with the control group, respectively). The ETP was lower in the ICU group (P0.05) at baseline, but it was comparable at 3 h between the groups. Thrombus size decreased at 3 h compared with pre-dose (P = 0.029) and was not different between the groups.Similar bioactivity was achieved with a standard dose of subcutaneous enoxaparin in this selected cohort of ICU and general ward patients with normal renal function.

Sensory evoked potentials are markedly changed in patients with fulminant liver failure. It is unknown, however, whether serial recordings of sensory evoked potentials provide useful prognostic informations for patient management in fulminant liver failure. Ninety recordings of bilateral median nerve—stimulated short-and long-latency sensory evoked potentials were performed in 25 patients with fulminant liver failure (9 patients spontaneously recovered and survived, 8 patients were referred to emergency liver transplantation and 8 patients died). In all nine survivors the cortical long-latency sensory evoked potential N70 peak was constantly detectable between 74 and 162 ms. In all eight patients who subsequently underwent liver transplantation and in seven of eight patients who died, loss of the N70 peak developed during the course of fulminant liver failure. In 4 of 15 patients who were selected for liver transplantation according to the King's College criteria, the N70 peak was constantly detectable. All four transplantation candidates spontaneously recovered and survived without transplantation. In contrast, eight patients never did fulfill the criteria for liver transplantation. Five of them with constantly detectable N70 peak recovered spontaneously. However, in the remaining three patients loss of the N70 peak developed, and they ultimately died. The probability of correct outcome prediction by sensory evoked potentials is superior to that based on clinical criteria alone (0.96 vs. 0.72). Therefore serial recording of sensory evoked potentials may help identify (a) a subgroup among liver transplantation candidates who may spontaneously recover without transplantation and (b) a subgroup of patients with severe brain dysfunction who should undergo early liver transplantation even though they do not fulfill King's College criteria. (Hepatology 1994;20:1487–1494).

Atherosclerotic stenosis of the carotid arteries decreases cerebral flow volume and perfusion, and may result in brain dysfunction. We studied the relationship between the degree of carotid artery stenosis and cognitive brain function in non-demented patients. Cognitive brain function was assessed in 76 patients with carotid artery stenosis (38 patients with low-grade stenosis of 50% or less, and 38 patients with high-grade stenosis of 75% or more) by recording of cognitive P300 auditory evoked potentials and trailmaking test. Results were compared to 70 age-matched healthy subjects. The P300 peak latency was prolonged in patients with high-grade carotid artery stenosis as compared to patients with low-grade stenosis (403 vs. 371 ms, P < 0.01, vertex; 400 vs. 370 ms, P < 0.01, frontal; means). Analysis of variance revealed that the degree of carotid artery stenosis is an independent predictor of prolonged P300 peak latency (P = 0.0001). P300 amplitude (12 vs. 15 microV, vertex; 13 vs. 15 microV, frontal, NS) and trailmaking test (60 vs. 54 s; NS) tended to be worse in the high-grade stenosis group. There was no difference in cognitive brain function between patients with low-grade stenosis and age-matched healthy subjects. Confirmed on sensitive cognitive P300 measurements, we conclude that (a) cognitive brain function is impaired in non-demented patients with high-grade carotid artery stenosis but unaffected in low-grade stenosis; and (b) cognitive brain dysfunction is directly related to the degree of carotid artery stenosis.

Background Continuous glucose monitoring has been proposed to optimize glucose control in critically ill patients. To achieve strict glucose regulation, accurate and reliable continuous glucose-monitoring systems are essential. Objective Evaluation of a subcutaneous continuous glucose-monitoring system for use in critically ill patients. Design Pooled-data analysis of two prospective, randomized, controlled trials. Setting An eight-bed medical intensive care unit of a university hospital. Patients A total of 174 critically ill patients on intensive insulin therapy. Interventions Subcutaneous continuous glucose monitoring. Measurements Two thousand forty-five continuous glucose-monitoring system sensor glucose values were compared with arterial reference blood glucose levels, determined by a blood gas analyzer. Continuous glucose monitoring data were recorded continuously for up to 72 hrs by using a subcutaneous continuous glucose-monitoring sensor. The correlation of both methods and differences between continuous glucose-monitoring systems and reference values were calculated, as well as the conformity of continuous glucose-monitoring values with the International Organization for Standardization criteria ( 4.12 mmol/L [>75 mg/dL]). Results The Pearson correlation coefficient was 0.92, showing strong correlation between the two methods. The intraclass correlation coefficient was 0.92, indicating that 92% of the variability is due to subjects and measurement occasions. Mean difference between continuous glucose-monitoring system and reference values was -0.10 mmol/L (confidence interval: -0.13 to -0.07) (-2 mg/dL [confidence interval: -2 to -1]) (continuous glucose-monitoring system minus reference) and absolute difference 0.44 mmol/L (confidence interval: 0.41-0.47) (8 mg/dL [confidence interval: 7-8]). According to the insulin titration error grid analysis, 99.1% of continuous glucose-monitoring system values were in the acceptable treatment zone. No continuous glucose-monitoring system measurements were found in the life-threatening zone, and 92.9% of the continuous glucose-monitoring system glucose values met the International Organization for Standardization criteria. Conclusion The subcutaneous continuous glucose-monitoring system is reliable for use in critically ill patients and showed glucose values with a strong correlation to arterial reference blood glucose levels, determined by a blood gas analyzer.

Conflicting data are available concerning energy metabolism in liver disease. Changes should be most pronounced in acute hepatic failure in which loss of 85% of liver cell mass is reported. Metabolic rate could be decreased due to impairment in liver mass but may also be increased as a result of systemic-mediator actions. To clarify this issue we studied energy metabolism in acute hepatic failure.Energy metabolism was evaluated by indirect calorimetry in 12 patients with acute liver failure and 22 sex-, age-, and body size-matched healthy individuals. In controls and 5 patients, studies were performed in the postabsorptive state; the remaining 7 patients received glucose at a rate of 8 mumol/kg body weight.min to prevent hypoglycemia.Resting energy expenditure was increased in acute liver failure compared with healthy controls (5.1 +/- 0.14 kJ.min-1 x 1.73 m-2 vs. 3.97 +/- 0.08 kJ.min-1 x 1.73 m-2; mean +/- SEM; P0.001). Respiratory quotient and oxidation rates for major fuels were not different between the total patient-group and controls. In patients without glucose supply, energy derived from fat was higher and from carbohydrate lower than in healthy controls and patients with glucose supply.Energy expenditure is increased in acute liver failure. Altered substrate oxidation can be normalized by glucose supply.

Prediction of individual outcome after cardiopulmonary resuscitation is of major medical, ethical, and socioeconomic interest but uncertain. We studied the early predictive potency of evoked potential recording after cardiac arrest in 66 resuscitated patients who returned to spontaneous circulation but were unconscious and mechanically ventilated. Detailed long-latency and short-latency sensory evoked potentials were recorded and neurological evaluations were done 4-48 h after admission to intensive care. In all 17 patients with favourable outcome (cerebral performance categories 1 and 2) the cortical evoked potential N70 peak, a reliable measure of cortical function, was detected between 74 and 116 ms. In 49 patients with bad outcome (categories 4 and 5) the N70 peak was absent in 35 or found with a delay between 121 and 171 ms in 14 (p < 0.05 vs favourable outcome). Thus the predictive ability was 100% with cutoff of 118 ms. To confirm reproducibility and validity, repeated tracings, and linked-earlobe referenced techniques were done and gave similar results. Early recording of long-latency evoked potentials after cardiopulmonary resuscitation is highly predictive of outcome.

Two chronically ill patients with limited nutritional intake during several weeks developed prolonged lactic acidosis. As no other causes of hyperlactaemia could be identified, thiamine deficiency was suspected. Supplementation of 600 mg thiamine resulted in a rapid normalisation of serum lactate levels (in patient 1 from 10.9-2.4 mmol/l; in patient 2 from 11.8-2.0 mmol/l) and acid base status (patient 1: pH from 7.11-7.30, bicarbonate from 8.6–21.2 mmol/l; patient 2: pH from 7.24-7.46, bicarbonate from 16–28 mmol/l; before and after treatment, respectively). Thiamine deficiency was confirmed by the degree of stimulation of erythrocyte transketolase activation by adding thiamine pyrophosphate, evaluated before and after thiamine replacement therapy. Stimulation decreased in patient 1 from 170% to 17% and in patient 2 from 20% to 0%, respectively. In addition to the metabolic derangement right ventricular heart failure was confirmed by echocardiography in both patients and again this was rapidly reversible by thiamine supplementation. We conclude that in malnourished patients unexplained prolonged lactic acidosis may result from thiamine deficiency, which is rapidly reversible by thiamine replacement therapy.

Objective: Head-to-head comparison of the success rate of jejunal placement of a new electromagnetically visualized jejunal tube with that of the endoscopic technique in critically ill patients. Design: Prospective, randomized clinical trial. Setting: Two intensive care units at a university hospital. Patients: A total of 66 critically ill patients not tolerating intragastric nutrition. Interventions: Patients were randomly assigned (2:1 ratio) to receive an electromagnetically visualized jejunal feeding tube or an endoscopically placed jejunal tube. The success rate of correct jejunal placement after 24 hrs was the main outcome parameter. Measurements and Main Results: The correct jejunal tube position was reached in 21 of 22 patients using the endoscopic technique and in 40 of 44 patients using the electromagnetically visualized jejunal tube (95% vs. 91%; relative risk 0.9524, confidence interval 0.804–1.127, p = .571). In the remaining four patients, successful endoscopic jejunal tube placement was performed subsequently. The implantation times, times in the right position, and occurrences of nose bleeding were not different between the two groups. The electromagnetically visualized technique resulted in the correct jejunal position more often at the first attempt. Factors associated with successful placement at the first attempt of the electromagnetically visualized jejunal tube seem to be a higher body mass index and absence of emesis. This trial is registered at ClinicalTrials.gov, number NCT00500851. Conclusions: In a head-to-head comparison correct jejunal tube placement using the new electromagnetically visualized method was as fast, safe, and successful as the endoscopic method in a comparative intensive care unit patient population.

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.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.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).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.

Imaging of tumors with cationic tracers, especially with technetium-99 methoxy isobutyl isonitrile ((99m)Tc-MIBI), revealed high specificity for the diagnosis and follow up of various malignancies. However, these radiopharmaceuticals are of limited value for the diagnosis of malignancies of the abdominal region due to the immediate biliary secretion of the tracer and the associated high background activity. In a prospective, single-blinded protocol, patients with endoscopically diagnosed gastrointestinal malignancies were assigned to undergo (99m)Tc-MIBI imaging of the abdomen. To overcome biliary secretion of cationic tracer we administered 0.04 mg/kg morphine hydrochloride intravenously before the administration of 600 MBq (99m)Tc-MIBI. Planar images were performed in the anterior and posterior views with a double-headed gamma camera and with 3 min acquisition time, followed by single photon emission tomography images (3 degrees, 20 sec/frame). Results were compared to findings of endoscopy, computed tomography scan and surgery. Twenty four patients 17 male and 7 female , mean age 69 years, range 52-83, years were enrolled. All patients suffered from adenocarcinoma, (19 from colorectum, 3 from gastric, 1 from pancreatic and one patient had both gastric and colorectal adenocarcinoma, for a total of 25 tumor lesions). The primary objective- inhibition of biliary secretion- was achieved in 23 of the 24 patients. (99m)Tc-MIBI-imaging was accumulated intra-abdominally in 19 patients. In 2 patients the tumor was endoscopically completely removed before the scan. In these two patients (99m)Tc-MIBI imaging showed no intra-abdominal tracer accumulation. When compared to the endoscopic findings, (99m)Tc-MIBI imaging showed time positive results in 13 of the 23 remaining individual tumor lesions, false positive in 6 and false negative in 4. This study showed a sensitivity of 57% and a specificity of 20% of the above technique for the identification of intra-abnominal adenocarcinomas. Correct diagnosis did not correlate with tumor size. In conclusion, prescintigraphic morphine administration inhibits background activity coming from biliary secretion, and enables better intra-abdominal (99m)Tc-MIBI imaging but with limited sensitivity and poor specificity.

Background & Aims: The hepatopulmonary syndrome (HPS) is defined as the triad of liver disease, arterial deoxygenation, and widespread pulmonary vasodilatation. Hypoxic hepatitis, also known as ischemic hepatitis, is the leading cause of acute liver impairment in hospitals. It is unknown whether HPS occurs in hypoxic hepatitis. We assessed the prevalence and clinical consequences of HPS in patients with hypoxic hepatitis. Methods: Forty-four patients with hypoxic hepatitis were screened prospectively for HPS using established criteria: (1) presence of hepatic disease, (2) increased alveolar-arterial difference for the partial pressure of oxygen greater than the age-related threshold, and (3) intrapulmonary vasodilatation detected via contrast-enhanced echocardiography. Sixty-two critically ill patients with different cardiopulmonary diseases but without hepatic disease were screened for prevalence of intrapulmonary vasodilatation as a control group. Results: Criteria of HPS were fulfilled in 18 patients with hypoxic hepatitis. HPS-positive patients had a significantly decreased partial pressure of arterial oxygen (P = .001) and partial pressure of arterial oxygen/fraction of inspired oxygen ratio (P = .034) at the time of diagnosis of HPS, a significant decreased area under the curve of the partial pressure of arterial oxygen/fraction of inspired oxygen ratio during the first 48 hours after diagnosis of hypoxic hepatitis (P = .009), and a significantly increased peak serum aspartate transaminase level (P = .028), compared with patients without HPS. Complete resolution of intrapulmonary vasodilatation was observed during follow-up evaluation. Contrast-enhanced echocardiography was negative for intrapulmonary vasodilatation in all 62 control patients. Conclusions: Intrapulmonary vasodilatation indicating HPS frequently occurs in patients with hypoxic hepatitis. It is reversible after normalization of the hepatic dysfunction. Clinicians should consider intrapulmonary vasodilatation and HPS in patients with hypoxic hepatitis.

Abnormalities in blood rheology and platelet dysfunction might play a role in the pathogenesis of multiple organ failure in septic patients by reducing microvascular blood flow. To determine whether alterations in blood rheology and in platelet function are related to the severity of organ dysfunction, we prospectively studied plasma fibrinogen, red cell aggregation, plasma viscosity, hematocrit, whole blood viscosity and platelet aggregation in relation to the Sepsis-related Organ Failure Assessment (SOFA) score in 34 consecutive patients with severe sepsis/septic shock. We found that patients had higher plasma fibrinogen, red cell aggregation and plasma viscosity (p0.01), but lower hematocrit, whole blood viscosity and ADP-induced platelet aggregation than controls (p0.01). Platelet aggregation (p0.01), but not other rheological variables, were inversely related to the SOFA score. Only platelet count was linked to poor clinical outcome (p0.05). We conclude that blood rheology and platelet function are severely altered in patients with severe sepsis/septic shock. Our findings suggest progressive platelet dysfunction with advancing severity of the disease. Platelet dysfunction might play a more important role in the pathogenesis of the multi organ dysfunction syndrome than abnormalities in blood rheology.

To investigate pharmacokinetics and metabolism of sodium citrate in critically ill patients. To determine the risk of citrate accumulation in the setting of liver dysfunction (cirrhosis, hepatorenal syndrome).Prospective cohort study.Intensive Care Unit, Department of Medicine IV, University Hospital Vienna.Consecutive critically ill cirrhotic (n = 16) and noncirrhotic patients (n = 16).Infusion of sodium citrate (0.5 mmol.kg-1.hr-1) and calcium chloride (0.17 mmol.kg-1.hr-1) for 2 hrs. Analysis of serial arterial blood samples.Total body clearance of citrate was normal in noncirrhotic critically ill patients but significantly reduced in cirrhotic patients (710 vs. 340 mL/min, p =.008). Citrate peak concentrations and concentration over time were increased by 65% and 114% in cirrhotic patients (p.001), respectively; volumes of distribution were similar. Net metabolic changes were quantitatively similar, with pH and plasma bicarbonate concentrations increasing more slowly in cirrhotic patients. No citrate-related side effects were noted. Citrate clearance could not be predicted by standard liver function tests and was not appreciably influenced by renal function and Acute Physiology and Chronic Health Evaluation II scores.This first systematic study on citrate pharmacokinetics and metabolism in critically ill patients confirms a major role of hepatic citrate metabolism by demonstrating reduced citrate clearance in cirrhotic patients. Pharmacokinetic data could provide a basis for the clinical use of citrate anticoagulation in critically ill patients. Provided dose adaptation and monitoring of ionized calcium, citrate anticoagulation seems feasible even in patients with decompensated cirrhosis. Metabolic consequences of citrate infusion were not different between groups in this study but may be more pronounced in prolonged infusion.

The hepatopulmonary syndrome (HPS) has been defined by chronic liver disease, arterial deoxygenation, and widespread intrapulmonary vasodilation. Mortality of patients with HPS is considered to be high, but the effect of HPS on survival in patients with cirrhosis remains unclear.A total of 111 patients with cirrhosis were studied prospectively by using transthoracic contrast echocardiography for detection of pulmonary vasodilation, blood gas analysis, and pulmonary function test. Twenty different clinical characteristics and survival times were noted.Twenty-seven patients (24%) had HPS. Their mortality was significantly higher (median survival, 10.6 months) compared with patients without HPS (40.8 mo, P0.05), even after adjusting for liver disease severity (2.9 vs. 14.7 months in Child-Pugh class C with [n = 15] and without HPS [n = 35, P0.05]; 35.3 vs. 44.5 months in Child-Pugh class B with [n = 7] and without HPS [n = 23, P = NS]), and exclusion of patients who underwent liver transplantation during follow-up (median survival 4.8 vs. 35.2 months, P = 0.005). Causes of death were mainly nonpulmonary and liver-related in the 19 patients with and the 35 patients without HPS who died. In multivariate analysis, HPS was an independent predictor of survival besides age, Child-Pugh class, and blood urea nitrogen. Mortality correlates with severity of HPS.The presence of HPS independently worsens prognosis of patients with cirrhosis. This should influence patient management and scoring systems and accelerate the evaluation process for liver transplantation.