Rita Gaspari

Advances in extracorporeal detoxification by MARS dialysis in patients with liver failure.

Although liver transplantation has become standard procedure for patients with liver failure, a number of issues in the management of these patients remains to be addressed. Alternative approaches have been tested, such as hepatocytes containing liver-support systems and filtration devices. However, the replacement of detoxification has been difficult, as the majority of toxins accumulating in liver failure is albumin-bound. Albumin dialysis (MARS system) is characterized by the specific removal of albumin-bound toxins through an innovative membrane transport. In particular, the albumin acts as a specific molecular adsorbent that is regenerated on line in a recycling system. Nowadays MARS represents the most frequently used liver support system. This treatment has been shown to remove albumin-bound molecules, such as bilirubin, bile acids, aromatic amino acids and copper. The removal of these toxins is clinically accompanied with an improvement of liver, cardiovascular and renal functions and hepatic encephalopathy. In several trials MARS was found to improve the clinical situation in patients with acute exacerbation of chronic liver failure and acute hepatic failure, but also in hepatorenal syndrome and primary graft non function or chronic rejection after liver transplantation. In summary, a critical analysis of the literature confirms that MARS device can be a safe therapeutic choice to achieve a better clinical outcome, and, sometimes, a survival advantage in patients with liver failure, even if a multi-center randomized trial is the only reliable way to enforce todays results. Further advances in the MARS components will definitively state whether albumin dialysis may represent the future in the field of artificial liver devices.

Molecular adsorbent recirculating system (Mars) in patients with primary nonfunction and other causes of graft dysfunction after liver transplantation in the era of extended criteria donor organs.

Liver dysfunction is an important cause of morbidity and mortality after orthotopic liver transplantation (OLT). The Molecular Adsorbent Recirculating System (MARS) is an albumin-based dialysis system designed to enhance the excretory function of a failing liver. MARS has been successfully used in patients affected by advanced liver disease and presenting with severe cholestasis. The aim of this study was to evaluate the safety and clinical efficacy of MARS in patients with liver dysfunction after OLT. Seven patients (primary nonfunction, 2 patients; graft dysfunction, 5 patients) fulfilled the inclusion criteria of serum bilirubin level >15 mg/dL and least 1 of the following clinical signs: hepatic encephalopathy (HE) > or = grade II, hepatorenal syndrome (HRS), and intractable pruritus. Graft and patient survival rates at 6 months were 42.8% and 57.1%, respectively. All patients tolerated MARS treatment, with no adverse event. In all patients, a decrease in serum bilirubin (P < .05), bile acids (P < .05), serum creatinine, and ammonia levels was observed after treatment with MARS. A considerable improvement of HE, as well as renal and synthetic liver functions, was observed in 4 of 5 patients with graft dysfunction, but not among those with primary nonfunction. The patients with intractable pruritus showed significant improvement of this symptom after MARS therapy. Thus, MARS is a safe, therapeutic option for the treatment of liver dysfunction after OLT. Further studies are necessary to confirm whether this treatment is able to improve both graft and patient survival.

Comparison of two methods to assess blood CO2 equilibration curve in mechanically ventilated patients

In order to compare two mathematical methods to assess the blood CO2 equilibration curve from a single blood gas analysis [Loeppky, J.A., Luft, U.C., Fletcher, E.R., 1983. Quantitative description of whole blood CO2 dissociation curve and Haldane effect. Resp. Physiol. 51, 167-181; Giovannini, I., Chiarla, C., Boldrini, G., Castagneto, M., 1993. Calculation of venoarterial CO2 concentration difference. J. Appl. Physiol. 74, 959-964], arterial and central venous blood gas analyses and oximetry were performed before and after ventilatory resetting, at constant arterial O2 saturation, in 12 mechanically ventilated patients. CO2 equilibration curves obtained from basal arterial blood gas analyses were used to predict arterial CO2 content after ventilatory resetting and vice versa. Internal consistency was very good for both methods and comparable. Method 2 also yielded excellent predictions of changes of arterial pH associated with ventilatory resetting. In determining Haldane effect, method 2 yielded very stable results within the expected range of values, while method 1 yielded a wider spread of results. Method 2 appeared more suitable to determine the Haldane effect in the conditions of the study, probably due to an approach minimizing the effect of potential sources of inaccuracy.

Changes in excitability of motor cortex in severe hepatic failure

Severe liver failure causes accumulation of both albumin bound and water soluble substances that exhibit toxic effects on the brain and lead to hepatic encephalopathy. This is a complex neuropsychiatric syndrome determined by a neurotransmission failure rather than from primary energy deficit.1 Transcranial magnetic stimulation represents a non-invasive method that can be used to study the physiology of the human brain.2 Commonly used transcranial magnetic stimulation parameters include motor thresholds, cortical silent period (CSP), central motor conduction time (CMCT), intracortical inhibition (ICI), and intracortical facilitation. The threshold for producing motor evoked potentials reflects the excitability of a central core of neurons, which arises from the membrane excitability and a balance between inhibitory and excitatory input from local circuits. The CMCT provides information on the corticospinal tract anatomical integrity, CSP and ICI reflect the activity of GABAergic inhibitory circuits.2–6 Additional in vivo information on central motor circuits can be obtained using transcranial electrical stimulation of the motor cortex. transcranial electrical stimulation stimulates the motor areas of the human brain deeply in the white matter and is therefore insensitive to changes in cortical excitability.6 Combining the data from transcranial electrical stimulation and transcranial magnetic stimulation it is possible to determine the site, cortical or subcortical, where brain functional changes have taken place. We used transcranial magnetic stimulation to explore function of the cerebral cortex in five patients affected by severe liver failure. Recently, a molecular adsorbent recirculating system (MARS) has been proposed as a new extracorporeal detoxifying treatment.7 We used transcranial magnetic stimulation to evaluate the effects of MARS treatment on functions of the cerebral cortex in these patients and also the effects of orthotopic liver transplantation in one of them. Clinical and neurophysiological examinations were recorded at baseline and 12–18 hours after the …