Edith Bauer

Citrate pharmacokinetics and metabolism in cirrhotic and noncirrhotic critically ill patients.

ObjectivesTo 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). DesignProspective cohort study. SettingIntensive Care Unit, Department of Medicine IV, University Hospital Vienna. PatientsConsecutive critically ill cirrhotic (n = 16) and noncirrhotic patients (n = 16). InterventionsInfusion 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. Measurements and Main ResultsTotal 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. ConclusionsThis 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.

Subclinical impairment of brain function in chronic hepatitis C infection.

BACKGROUND/AIMS Central nervous system abnormalities such as fatigue and depression occur more frequently in chronic hepatitis C virus (HCV) infection than in many other causes of chronic liver disease. The finding that fatigue is unrelated to activity of hepatitis or mode of infection could indicate an independent effect of HCV on brain function. This study tested the hypothesis of a subclinical cognitive dysfunction in HCV-infected patients. METHODS One-hundred untreated HCV-RNA positive biopsy-proven patients were investigated by P300 event-related potentials, a sensitive electrophysiologic test of cognitive processing. Health-related quality of life and fatigue were assessed using the SF-36 questionnaire and the Fatigue Impact Scale, respectively. RESULTS Cognitive brain function was subclinically impaired in the cohort of HCV-infected patients as indicated by significantly prolonged P300 latencies (P=0.01 for comparison to matched healthy subjects) and reduced P300 amplitudes (P<0.001, respectively). Seventeen of the 100 HCV-infected patients had P300 latencies outside the age-adjusted normal range. Abnormal P300 characteristics were not related to the degree of histologic or biochemical activity of hepatitis, severity of fatigue or mental health impairment. CONCLUSIONS This study demonstrates that patients with HCV infection showed a slight but significant neurocognitive impairment, possibly indicating a further extrahepatic manifestation of chronic hepatitis C.

Impaired subcortical and cortical sensory evoked potential pathways in septic patients.

ObjectiveSensory evoked potential (SEP) peak latencies were recorded in order to evaluate the incidence and severity of septic encephalopathy, testing the hypothesis that the occurrence of septic encephalopathy is more frequent than generally assumed. DesignProspective cohort study. SettingMedical intensive care unit of a university hospital. PatientsSixty-eight critically ill patients were studied within 48 hrs after the development of severe sepsis (n = 41) or septic shock (n = 27). InterventionsNone. Measurements and Main ResultsSeptic encephalopathy was defined as prolongation of SEP peak latencies beyond the upper limit of the reference range of subcortical (N13–N20 interpeak latency) and cortical SEP pathways (N20–N70 interpeak latency), as well as asymmetry of peak latencies marked by the presence of subclinical cerebral focal signs. Subcortical SEP pathways were impaired in 34% and cortical SEP pathways in 84% of all patients. The prolongation of the cortical SEP pathway correlated with the Acute Physiology and Chronic Health Evaluation III score (r = 0.23;p < .0001). SEP peak latencies did not differ in patients with severe sepsis compared with those with septic shock. Subclinical cerebral focal signs were present in 24% of the subcortical SEP pathways and in 6% of the cortical SEP pathways. ConclusionsSeptic encephalopathy occurs more frequently than generally assumed, and its severity is associated with the severity of illness. The impairment of subcortical and cortical SEP pathways was not different between patients with severe sepsis and those with septic shock.

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

ZusammenfassungDas durch MDMA (Ecstasy) ausgelöste fulminante Leberversagen weist — insbesondere exzessive Mortalität auf. Die notfallmäßige Lebertransplantation ist die einzige etablierte Behandungsform. Wir berichten über einen jungen Patienten mit kombinierter Ecstasy/Kokain-Intoxikation mit akutem Leberversagen, Rhabdomyolyse, Septuminfarkt und Multiorganversagen. Die Lebertransplantation wurde aufgrund des rezenten intravenösen Drogenkonsums trotz Erfüllung der Transplantationskriterien abgelehnt. Infolge massiver Hyperammoniämie (318 μmol/l) und refraktärer zerebraler Herniation begannen wir eine kontinuierliche extrakorporale Behandlung mit dem FPSA-Prometheus System, welches adsorptive und dialytische Toxinentfernung kombiniert. Nach rascher Normalisierung des Ammoniakwertes kam es innerhalb von 4 Tagen zu Einsetzen von Leberregeneration und vollständiger Rückbildung des Hirnödems. Der Patient konnte das Krankenhaus nach Rehabilitation mit geringgradigen neurologischen Folgeerscheinungen verlassen. Effiziente extrakorporale Detoxifikation kann durch eine rasche Normalisierung von Hyperammoniämie und Hirnödem bei Ecstasy/Kokaininduziertem akutem Leberversagen eine therapeutische Option darstellen.SummaryEcstasy-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 μmol/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.

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.

Treatment of adult patients with sepsis-induced coagulopathy and purpura fulminans using a plasma-derived protein C concentrate (Ceprotin®)

Background and Objectives  The aim of this study was to document the effects of supplementation with a plasma‐derived protein C concentrate in adult patients with infectious purpura fulminans.

A controlled study of sorbent suspension dialysis in chronic liver disease and hepatic encephalopathy.

To investigate the role of extracorporeal detoxification in cirrhotic patients with advanced hepatic encephalopathy not responding to medical treatment, 20 patients were randomized to receive six hours of additional sorbent dialysis or ongoing standardized medical treatment. Following treatment, the clinical stage of encephalopathy remained unchanged in both groups. Abnormal sensory evoked potentials improved following sorbent dialysis (N70 latency, 128 ms before versus 110 ms after treatment, P<0,05; cervico-cranial transmission, 7.7 ms versus 6.8 ms, P<0.01) indicating improvement in important aspects of cerebral function. In contrast, brain function remained unchanged following medical treatment (N70 latency, 114 ms versus 113 ms; cervico-cranial transmission, 7.7 ms versus 7.2 ms, P=NS, respectively). Serum benzodiazepine levels decreased significantly after sorbent dialysis but not after medical treatment. Biocompatibility of sorbent dialysis was limited and clinical complications occurred in a proportion of patients. In conclusion, a six-hour treatment with sorbent suspension dialysis did not ameliorate the clinical stage of HE but improved neurophysiologic function in cirrhotic patients who had not responded to conventional medical treatment.

Severe interstitial pneumonitis secondary to pegylated interferon alpha-2b and ribavirin treatment of hepatitis C infection.

Interferon (INF) α, a naturally occurring glycoprotein, inhibits intracellular replication of many viruses. It is the cornerstone of treatment for chronic hepatitis C virus (HCV) infection. Pegylated interferon (PEGINF) α-2b (PEG-Intron; Schering–Plough, Ireland) reduces the frequency of administration and increases the efficacy of INF α-2b by delaying its clearance and reducing its immunogenicity (1). Various side effects are well known for INF α treatment (2–10). We report a case of severe interstitial pneumonitis in a patient treated with a combination therapy of PEGINF α-2b and ribavirin for chronic HCV infection.

A woman with red eyes and hypokalemia: A case of acquired Gitelman syndrome

ZusammenfassungDas Gitelman Syndrom ist eine sehr seltene Mutation des NaCl Transporters der distalen Tubuluszellen in der Niere. In den letzten Jahren wurden aber auch vermehrt Berichte publiziert, wonach es bei Autoimmunerkrankungen (Sjögren Syndrom, SLE, …) zu ähnlichen renalen Elektrolytverlusten kommt wie bei verschiedenen hereditären Tubulopathien. Eine 62-jährige Frau suchte wegen schmerzhafter beidseitiger Augenrötung die Augenabteilung auf. In der weiteren diagnostischen Abklärung konnte ein Sjögren Syndrom für die Ursache der Keratitis mit beginnender Endophthalmitis identifiziert werden. In der Laboranalyse war weiters eine, früher nicht bekannte ausgeprägte Hypokaliämie, eine metabole Alkalose und eine Hypomagnesiämie auffällig. Zusammen mit der Analyse der Elektrolyte im Harn konnte die Diagnose eines seltenen Falles von erworbenen Gitelman Syndrom gestellt werden. Die Substitution von Kalium und Magnesium führte zu einer Besserung des initial bestehenden Schwächegefühls. Trotz einer immunsuppressiven Therapie des Sjögren Syndrom kam es jedoch zu einem persistierenden renalen Elektrolytverlustes. Bei Patienten mit Autoimmunerkrankungen sollte deshalb gezielt nach Elektrolytstörungen gesucht werden, da renal tubuläre Funktionsstörungen zu schweren Hypokaliämien führen können.SummaryGitelman syndrome is a rare hereditary disorder of the thiazide-sensitive NaCl transporter in the distal renal tubular cells, but mimicking of such hereditary tubular disorders has been described in different autoimmune diseases (Sjögren syndrome, SLE, …). A 62-year-old woman with painful red eyes and sicca syndrome presented at the ophthalmological department. The diagnostic evaluation identified a Sjögren syndrome with early endophthalmitis as the reason for the red eyes. Results of laboratory examination indicated severe hypokalemia, metabolic alkalosis and hypomagnesemia, although this had not been seen years earlier. Together with the urine analysis, a rare case of an acquired Gitelman syndrome was diagnosed. Substitution with potassium and magnesium improved the initial symptoms of weakness, but renal electrolyte wasting persisted even after treatment of Sjögren syndrome. In patients with autoimmune disease, laboratory analysis of serum electrolytes should be performed because different acquired tubular disorders can lead to severe hypokalemia.

Electropyhsiological assessment of the afferent sensory pathway in cardiac arrest survivors

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.