Christian Madl

Prognostic Significance of the Hepatopulmonary Syndrome in Patients With Cirrhosis

BACKGROUND AND AIMSnThe 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.nnnMETHODSnA 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.nnnRESULTSnTwenty-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.nnnCONCLUSIONSnThe 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.

Wilson's disease in patients presenting with liver disease: A diagnostic challenge

BACKGROUND & AIMSnIn patients with Wilsons 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.nnnMETHODSnClinical and laboratory findings of 55 patients with Wilsons 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.nnnRESULTSnIn the whole group, serum ceruloplasmin level was <20 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.nnnCONCLUSIONSnThe commonly used clinical and laboratory parameters are not sufficient to exclude the diagnosis of Wilsons disease in patients with liver disease of unknown origin.

Early prediction of individual outcome after cardiopulmonary resuscitation

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.

Improvement of hepatic encephalopathy treated with flumazenil.

The effects of the benzodiazepine antagonist flumazenil were studied in 20 episodes of hepatic encephalopathy (HE) in 17 patients with acute (n = 9) or chronic (n = 8) liver failure who had not responded to conventional therapy. Patients with a history of benzodiazepine intake were excluded. Changes in HE stage, in Glasgow coma scale, and in somatosensory evoked potentials were measured. In 12 of 20 episodes HE stage improved. The response to treatment occurred rapidly (within 3-60 min). In 8 of these 12 episodes HE worsened 0.5-4 h after treatment. In 5 of the 8 episodes that did not respond to flumazenil patients had clinical evidence of brain oedema. Flumazenil may be valuable in the treatment of HE in acute and chronic liver failure.

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.

Outcome prediction for patients with cirrhosis of the liver in a medical ICU: A comparison of the APACHE scores and liver-specific scoringsystems

ObjectiveTo find the most adequate prognostic scoring system for predicting ICU-outcome in patients with decompensated liver cirrhosis in a medical intensive care unit (ICU).DesignRetrospective analysis of patients records over a 10-year period.SettingA medical ICU at the university medical center of Vienna.Patients and participants: 94% (n=198) of all patients with cirrhosis admitted to our medical ICU throughout the 10-year study period.InterventionsNone.Measurements and resultsFrom data obtained at admission and at 48 h after admission, scores were calculated using the following scoring systems: Acute Physiology and Chronic Health Evaluation (APACHE) II and III, Scale for Composite Clinical and Laboratory Index Scoring (CCLI), Mayo Risk Score, and Childs Classification. Statistical analysis for the prognostic variables was performed using the chi-square test,t-test, Youden index, and area under a receiver operating characteristic (ROC) curve. APACHE III was found to be the most reliable outcome predictor at admission and after 48 h for patients with decompensated liver cirrhosis (AUC=0.75 and 0.8, respectively).ConclusionsTo predict the outcome for patients with decompensated cirrhosis of the liver admitted to a medical ICU liver failure alone is not decisive. Liver-specific scoring systems (Mayo Risk Score, CCLI) are adequate, but the APACHE II and III proved to be more powerful, because they include additional physiologic parameters and therefore also take into account additional complications associated with this liver disorder.

Time-dependency of sensory evoked potentials in comatose cardiac arrest survivors

Abstract.Objective: To assess the validity of early sensory evoked potential (SEP) recording for reliable outcome prediction in comatose cardiac arrest survivors within 48xa0h 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 48xa0h after ROSC. Cortical N20 peak latency and cervicomedullary conduction time decreased (improved) significantly between 4, 12, and 24xa0h after resuscitation in 22 of the enrolled patients. There was no further change in short-latency SEP at 48xa0h. The cortical N70 peak was initially detectable in seven patients. The number of patients with increased N70 peak increased to 11 at 12xa0h and 14 at 24xa0h; there was no further change at 48xa0h. Specificity of the N70 peak latency (critical cutoff 130xa0ms) increased from 0.43 at 4xa0h to 1.0 at 24xa0h after ROSC. Sensitivity decreased from 1.0 at 4xa0h to 0.83 at 24xa0h after ROSC. Conclusion: Within 24xa0h after ROSC there was a significant improvement in SEP. Therefore we recommend allowing a period of at least 24xa0h after cardiopulmonary resuscitation for obtaining a reliable prognosis based on SEP.

Apolipoprotein E Polymorphism: Survival and Neurological Outcome After Cardiopulmonary Resuscitation

Background and Purpose The apolipoprotein E 3/3 (apoE 3/3) genotype is associated with a reduced risk of developing Alzheimer’s disease and with a favorable neurological outcome after traumatic head injury. In vitro studies suggest that the most common genotype, apoE 3/3, may be involved in neuroprotective and neuroregenerative mechanisms. The aim of this study was to determine whether the apoE 3/3 genotype has an impact on survival and neurological outcome after cardiopulmonary resuscitation. Methods Eighty patients with cardiac arrest were investigated prospectively for their apoE genotype. Epidemiological data were assessed according to recommended guidelines. Patients were divided into 2 groups, ie, with the apoE 3/3 genotype present or absent, and tested for differences in survival and neurological outcome. Further statistical analysis with respect to survival and neurological outcome was performed by using a stepwise logistic regression analysis. Results Patients with the apoE 3/3 genotype had a significantly higher survival rate (64% versus 33%, P =0.007) and more often a favorable neurological outcome (55% versus 27%, P =0.013) compared with patients with other apoE genotypes. The apoE 3/3 genotype was shown to be a substantial predictive factor for a favorable neurological outcome (odds ratio 3.2) and was, apart from other essential factors, predictive for survival (odds ratio 4.4) after cardiopulmonary resuscitation. Conclusions These data give evidence that patients with the apoE 3/3 genotype have a better chance of recovery after cardiopulmonary resuscitation than do patients with apoE genotypes other than 3/3.

Energy Metabolism in Acute Hepatic Failure

BACKGROUNDnConflicting 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.nnnMETHODSnEnergy 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.nnnRESULTSnResting 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; P < 0.001). 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.nnnCONCLUSIONSnEnergy expenditure is increased in acute liver failure. Altered substrate oxidation can be normalized by glucose supply.

Evoked potentials in assessment and follow-up of patients with Wilson's disease

Treatment of 9 patients with Wilsons disease was prospectively studied with evoked potentials and magnetic resonance imaging (MRI). Oral penicillamine therapy led to a decrease in auditory brainstem (ABP) and somatosensory (SEP) conduction times in 6 and 4 neurologically symptomatic patients, respectively. ABP and SEP were normal in 3 other symptom-free patients. MRI showed cerebral lesions in 4 of 7 patients. Quantified indices of brain atrophy were unaffected by treatment. ABP and SEP may reveal a reversible component of the disease that cannot be detected by MRI, and may be a more sensitive measure of treatment efficacy.