Removal of Benzodiazepine-like Substances as a Cause of Improvement of Hepatic Encephalopathy during Albumin Dialysis

A new blood purification method based on dialysis against a solution containing albumin as a Molecular Adsorbent that is online regenerated using adsorbent based Recycling System (MARS) has been developed for the selective removal of albumin bound substances Endogenous benzodiazepine-like substances (BLS), that are bound > 90 % to albumin, are blamed to be responsible at least in part for the development of hepatic encephalopathy (HE).

The aim of the present work was to test the capacity of the MAR-System to remove diazepam as a marker molecule for BLS. 200 µg diazepam (ASTA Medica AWD GmbH) were added to 1L human plasma. As an internal control, conventional bicarbonate dialysis (SH-44-HEP, Schiwa GmbH) was performed (plasma flow: 150mL/min, dialysate flow: 1000mL/h, ultrafiltration rate: 20mL/h. After two hours, a continuous albumin dialysis with 1.6 % albumin solution was carried out for another two hours. Diazepam was measured by fluorescence polarisation immunoassay (FPIA) every 30 minutes throughout the experiments.

Fig. 1 Benzodiazepine-removal during conventional dialysis (left) and albumin dialysis (right) in vitro.

Diazepam concentration in plasma decreased only by 7 % during conventional bicarbonate dialysis (171.5 µg/L ± 6.6 to 165.2 µg/L ± 7.8) but was reduced significantly (p < 0.05) to approximately 50 % (165.2 µg/L ± 7.8 to 76.2 µg/L ± 14.8) during albumin dialysis.

In a clinical study, including 13 patients, the changes of their clinical situation during the treatment series with albumin dialysis MARS were investigated. The patients were dialyzed depending from clinical situation 3 to over 20 days. 9 of the patients survived. In all of them the improvement of the global liver situation was accompanied with reduction of HE grade (from 2.9 ± 0.6 to 1.9 ± 0.5 during single treatment).

We conclude that the improvement of HE during MARS-therapy might be also a consequence of the removal of benzodiazepine-like substances. MARS may be very effective in the removal of diazepam from blood of patients in iatrogenic or suicidal poisoning.