Biomedical subjects

Christian Madl

Publications and source records attributed to Christian Madl.

14 recordsLinked to original sources

PubMed2006

Long-term neurocognitive function after mechanical aortic valve replacement.

BACKGROUND: Mechanical aortic valves are a possible source of microemboli potentially causing cerebral injury. Therefore, the long-term impact of mechanical aortic valve replacement on neurocognitive function is uncertain. METHODS: In this prospective, contemporary study, we followed 32 consecutive patients (aged 51 +/- 8 years; range, 38 to 70; EuroSCORE [European System for Cardiac Operative Risk Evaluation] 4.4 +/- 1.7) undergoing isolated aortic valve replacement with a mechanical prosthesis. A cohort of age- and sex-matched patients (n = 28, aged 50 +/- 7 years) served as nonsurgical controls. After aortic valve replacement, neurocognitive function was serially reevaluated at 7-day (n = 32), 4-month (n = 31), and 3-year (n = 29) follow-up. Neurocognitive function was measured by means of P300 auditory evoked potentials. RESULTS: Before the operation, P300 peak latencies were comparable between surgical patients (361 +/- 32 ms) and nonsurgical controls (365 +/- 33 ms, p = 0.783). In patients undergoing aortic valve replacement, P300 peak latencies were prolonged 7 days after surgery (380 +/- 32 ms) as compared with before the operation (361 +/- 32 ms, p < 0.0001) and as compared with nonsurgical controls (364 +/- 34 ms, p = 0.002). At 4-month (369 +/- 30 ms, p = 0.752) and 3-year (370 +/- 31 ms, p = 0.825) follow-up, P300 peak latencies normalized as compared with before operation and as compared with nonsurgical controls (4-month follow-up 363 +/- 31 ms, p = 0.832; 3-year follow-up 366 +/- 32 ms, p = 0.432). We found no difference in patients with different valve types. CONCLUSIONS: Despite previous assumptions based on the potential occurrence of microemboli in patients with mechanical valves, mechanical aortic valve replacement has no adverse long-term impact on neurocognitive function. This finding is only valid for patients with a comparable age range undergoing isolated aortic valve replacement.

Adult↗

PubMed2006

Hepatopulmonary syndrome in patients with hypoxic hepatitis.

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.

Adolescent↗

PubMed2005

Wilson disease.

Wilson disease (WD) is an autosomal recessive inherited disorder of copper metabolism, resulting in pathological accumulation of copper in many organs and tissues. The hallmarks of the disease are the presence of liver disease, neurologic symptoms, and Kayser-Fleischer corneal rings. The leading neurologic symptoms in WD are dysathria, dyspraxia, ataxia, and Parkinsonian-like extrapyramidal signs. Changes in the basal ganglia in brain magnetic resonance imaging (MRI) are characteristic features of the disease. In presence of liver cirrhosis, some features may resemble hepatic encephalopathy. Symptoms and MRI abnormalities may be fully reversible on treatment with zinc or copper chelators. Improvement can be monitored by serial recording of brain-stem-evoked responses. The basic defect is an impaired trafficking of copper in hepatocytes. ATP7B is the gene product of the WD gene located on chromosome 13 and resides in hepatocytes in the trans-Golgi network, transporting copper into the secretory pathway for incorporation into apoceruloplasmin and excretion into the bile. While about 40% of patients preset with neurologic symptoms, little is known about the role of copper and ATP7B in the central nervous system. In some brain areas, like in the pineal gland, ATP7B is expressed and functionally active. Increasing evidence supports an important role for metals in neurobiology. Two proteins related to neurodegeneration are copper-binding proteins (1) the amyloid precursor protein (APP), a protein related to Alzheimer's disease, and (2) the Prion protein, related to Creutzfeldt-Jakob disease. A major source of free-radical production in the brain derives from copper. To prevent metal-mediated oxidative stress, cells have evolved complex metal transport systems. APP is a major regulator of neuronal copper homeostasis and has a copper-binding domain (CuBD). The surface location of this site, structural homology of CuBD to copper chaperones, and the role of APP in neuronal copper homeostasis are consistent with the CuBD acting as a neuronal metallotransporter. There are several copper-containing enzymes in the brain, like dopamine beta hydroxylase or Cu/Zn superoxide dismutase (SOD1). Their function may be altered because of copper overload. WD appears to be associated with a dopaminergic deficit. Mutations in the SOD1gene cause familial amyotrophic lateral sclerosis. Survival of transgenic mice with a mutant SOD1 which fails to incorporate Cu((2+)) in its active site was improved by copper depletion. Wilson disease (WD) is an autosomal recessive inherited disorder in which copper pathologically accumulates primarily within the liver and subsequently in the neurologic system and many other organs and tissues. Presence of liver disease, neurologic symptoms, and Kayser-Fleischer corneal rings are the hallmarks of the disease.

Animals↗

PubMed2004

Brain function after resuscitation from cardiac arrest.

PURPOSE OF REVIEW: In industrial countries the incidence of cardiac arrest is still increasing. Almost 80% of cardiac arrest survivors remains in coma for varying lengths of time and full cerebral recovery is still a rare event. After successful cardiopulmonary resuscitation, cerebral recirculation disturbances and complex metabolic postreflow derangements lead to death of vulnerable neurons with further deterioration of cerebral outcome. This article discusses recent research efforts on the pathophysiology of brain injury caused by cardiac arrest and reviews the beneficial effect of therapeutic hypothermia on neurologic outcome along with the recent approach to prognosticate long-term outcome by electrophysiologic techniques and molecular markers of brain injury. RECENT FINDINGS: Recent experimental studies have brought new insights to the pathophysiology of secondary postischemic anoxic encephalopathy demonstrating a time-dependent cerebral oxidative injury, increased neuronal expression, and activation of apoptosis-inducing death receptors and altered gene expression with long-term changes in the molecular phenotype of neurons. Recently, nuclear MR imaging and MR spectroscopic studies assessing cerebral circulatory recovery demonstrated the precise time course of cerebral reperfusion after cardiac arrest. Therapeutic hypothermia has been shown to improve brain function after resuscitation from cardiac arrest and has been introduced recently as beneficial therapy in ventricular fibrillation cardiac arrest. SUMMARY: Electrophysiologic techniques and molecular markers of brain injury allow the accurate assessment and prognostication of long-term outcome in cardiac arrest survivors. In particular, somatosensory evoked potentials have been identified as the method with the highest prognostic reliability. A recent systematic review of 18 studies analyzed the predictive ability of somatosensory evoked potentials performed early after onset of coma and found that absence of cortical somatosensory evoked potentials identify patients not returning from anoxic coma with a specificity of 100%.

Brain Injuries↗

PubMed2004

Platelet aggregation and blood rheology in severe sepsis/septic shock: relation to the Sepsis-related Organ Failure Assessment (SOFA) score.

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 (p < 0.01), but lower hematocrit, whole blood viscosity and ADP-induced platelet aggregation than controls (p < 0.01). Platelet aggregation (p < 0.01), but not other rheological variables, were inversely related to the SOFA score. Only platelet count was linked to poor clinical outcome (p < 0.05). 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.

APACHE↗

PubMed2003

Prognostic significance of the hepatopulmonary syndrome in patients with cirrhosis.

BACKGROUND AND AIMS: 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. METHODS: 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. RESULTS: Twenty-seven patients (24%) had HPS. Their mortality was significantly higher (median survival, 10.6 months) compared with patients without HPS (40.8 mo, P < 0.05), 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, P < 0.05]; 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. CONCLUSIONS: 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.

Adult↗

PubMed2003

Neurocognitive deficit following aortic valve replacement with biological/mechanical prosthesis.

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=0.0001). 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.

Adult↗

PubMed2003

Gastrointestinal disorders of the critically ill. Systemic consequences of ileus.

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.

Critical Illness↗

PubMed2003

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

OBJECTIVES: 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). DESIGN: Prospective cohort study. SETTING: Intensive Care Unit, Department of Medicine IV, University Hospital Vienna. PATIENTS: Consecutive critically ill cirrhotic (n = 16) and noncirrhotic patients (n = 16). INTERVENTIONS: 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. MEASUREMENTS AND MAIN RESULTS: 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. CONCLUSIONS: 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.

APACHE↗

PubMed2002

[Recommendations for prognostic assessment of cerebral hypoxia after cardiopulmonary resuscitation--Austrian Interdisciplinary Consensus Conference].

Various clinical parameters, neurological examination models, biochemical tests, electrophysiological procedures and neuro-imaging techniques have been studied with respect to the detection of cerebral hypoxia in patients after cardiopulmonary resuscitation. These parameters were critically evaluated by the members of the Austrian interdisciplinary consensus conference. Based on the results of scientific publications, the consensus meeting identified 26 parameters, which allow the prognostic evaluation of cerebral hypoxia after cardiopulmonary resuscitation. Among these parameters, however, the strength of evidence and the level of recommendation are different.

APACHE↗

PubMed2002

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.

Aged↗

PubMed2002

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.

Adult↗

PubMed2002

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

OBJECTIVE: Sensory 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. DESIGN: Prospective cohort study. SETTING: Medical intensive care unit of a university hospital. PATIENTS: Sixty-eight critically ill patients were studied within 48 hrs after the development of severe sepsis (n = 41) or septic shock (n = 27). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Septic 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. CONCLUSIONS: Septic 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.

Brain Diseases↗

PubMed2002

Neurophysiological evidence of cognitive impairment in patients without hepatic encephalopathy after transjugular intrahepatic portosystemic shunts.

OBJECTIVES: We aimed to test the hypothesis that subclinical cognitive brain dysfunction in cirrhotic patients would deteriorate after a transjugular intrahepatic portosystemic shunt (TIPS) in the absence of clinically detectable hepatic encephalopathy. METHODS: Out of 49 consecutive cirrhotic patients receiving elective TIPS for recurrent variceal hemorrhage, we identified 22 patients who were not encephalopathic and had not undergone liver transplantation at 6-month follow-up and confirmed TIPS patency by Doppler ultrasound. Patients were tested before and 6 months after TIPS implantation using event-related (P300) cognitive evoked potentials, late somatosensory median nerve (N70) potentials, and standard psychometric tests (Mini-Mental State and trailmaking test A). Twenty-two age-matched healthy subjects served as controls. RESULTS: Relative to controls, patients showed significantly impaired P300 and N70 latencies and abnormal psychometric test results at baseline. Six months after the TIPS, a further impairment of P300 latency was observed (p = 0.005), whereas no relevant changes in N70 latency and psychometric test results occurred. CONCLUSIONS: In cirrhotic patients with portal hypertension, neurophysiological signs of cognitive brain dysfunction are detectable in the absence of hepatic encephalopathy. A further subclinical deterioration of cognitive processing was observed 6 months after the TIPS. These findings demonstrate an aggravation of subclinical hepatic encephalopathy after a TIPS.

Adult↗