Donald E. Blake

Push-pull sorbent based pheresis for treatment of acute hepatic failure : the biologic-detoxifier/plasma filter System

The BIOLOGIC-DTR (detoxifier) System is an extracorporeal blood treatment device that uses the membranes of a cellulosic plate dialyzer to propel blood in and out through a single lumen access (on a 12 sec cycle) and circulates a suspension of powdered charcoal and cation exchanger through the dialysate spaces to absorb many soluble toxins in the treatment of hepatic failure. The BioLogic-DTPF (detoxifier/plasma filter) System adds two Gambro plasma filters downstream from the plate dialyzer, which allows most of the blood plasma to pass out of the blood, contact powdered charcoal in a suspension, and then return to the blood during each 12 sec cycle (creating push-pull sorbent based pheresis). A roller pump exchanges charcoal suspension between the plasma filter case and a 700 ml bag of powdered charcoal suspension. At a blood flow rate of 150–200 ml/min, 100 ml/min of plasma moves bidirectionally through the plasma filter membranes. Direct contact of plasma with charcoal outside the plasma filter membranes removes creatinine with a clearance rate equal to plasma flow (100 ml/min); clearance of strongly protein bound toxins, such as unconjugated bilirubin, is lower (10–40 ml/min). In this article, the authors explain the mechanisms of operation of this system and present in vitro tests that define its chemical efficiency. Also described are potential problems, tests that indicate the severity of these problems, and monitors and algorithms to detect or avoid these problems in clinical use of the system. The results of the treatment of two patients with acute hepatic failure and coma using the BioLogic-DTPF System are reviewed. ASAIO Journal 1998; 44:129–139.

Systemic inflammatory response syndrome treatment by powdered sorbent pheresis: the BioLogic-Detoxification Plasma Filtration System.

Systemic inflammatory response syndrome (SIRS) is one of the most common causes of death in intensive care unit patients. The detoxification plasma filtration (DTPF) system (HemoCleanse, Inc., West Lafayette, IN) combines the DT hemodiabsorption system in series with a push-pull pheresis PF system (a suspension of powdered sorbents surrounding 0.5 microm plasma filter membranes). Bidirectional plasma flow (at 80-100 ml/min) across the PF membranes provides direct contact between plasma proteins and powdered sorbents, as well as clearance of cytokines (tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6) at a rate of 15-25 ml/min, without evidence of saturation for 90 minutes. In a U.S. Food and Drug Administration approved study we treated eight patients with SIRS and organ failure with a single DTPF treatment, using powdered charcoal as sorbent in four patients and powdered charcoal and silica in four patients. Treatments proceeded for 6 hours with proper heparin anticoagulation (activated clotting time 250-300 sec) and appeared safe. All patients improved during the treatments and each had increased blood pressure and decreased need for pressor agents. Plasma cytokine levels stabilized or decreased during treatment and were significantly lower the morning after treatment. Multiple organ dysfunction (MOD) and Acute Physiology Chronic Health Evaluation II scores and organ function gradually improved in most patients, and two patients survived for more than 28 days and two for more than 14 days. The DTPF System may prove beneficial in treatment of patients with sepsis.

Effect of sorbent-based dialytic therapy with the biologic-DT on an experimental model of hepatic failure

An experimental model of hepatic failure in the dog has been developed in which the liver is devascularized in two stages. Under general anesthesia, a portacaval shunt is created, ligatures placed around the hepatic and gastroduodenal arteries, and the dog recovered. Two days later under general anesthesia, the ligatures are pulled, converting hepatic insufficiency to hepatic failure. Five control animals developed hypotension, severe lactic acidosis, hypoglycemia, and increasing liver enzyme levels during 6 hrs of follow-up. The BioLogic-DT system includes a cellulosic plate dialyzer with a suspension of powdered charcoal and cation exchangers as dialysate. Five animals were treated with the BioLogic-DT for 6 hrs after creation of hepatic failure. These animals were more stable physiologically, developed less lactic acidosis and less enzyme elevation, and maintained high normal blood glucose levels. The results help explain the clinical improvement demonstrated in patients with hepatic failure treated by the BioLogic-DT, and confirm that many of the toxins of hepatic failure are dialyzable and bound by simple sorbents such as charcoal and cation exchangers.