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 Submitted by Dr LAU Chun Wing Arthur, ICU, PYNEH on 9 March 2009
This stack of "biscuits" costs HK$20000, what is it?
Answer: LPS Adsorber (Alteco Medical, Lund, Sweden)
It is used for the treatment of endotoxaemia by haemoperfusion of whole blood.
A casual search of Medline just now on "lipopolysaccharide adsorber" gives the following returns (abstracts further abridged):
1. Kulabukhov VV. Use of an endotoxin adsorber in the treatment of severe abdominal sepsis. Acta Anaesthesiol Scand. 2008 Aug;52(7):1024-5. Epub 2008 May 20.
A case with severe Gram-negative sepsis, treated with a novel device for LPS adsorption (Alteco LPS Adsorber, Alteco Medical AB, Lund, Sweden). After LPS adsorption, the level of LPS in the patient's bloodstream was almost eliminated: from 1.44 EU/ml
before treatment to 0.03 EU/ml post treatment). The procalcitonin level and inflammatory cytokines were concurrently reduced. Also, an obvious improvement in the status of the patient's hemodynamics was seen.
2. Umgelter A, Reindl W, Lutz J, Kreymann B, Ronco C, Huber W, Frank H, Schmid RM, Heemann U. Treatment of septic patients with an arginine-based endotoxin adsorber column improves hemodynamics and reduces oxidative stress: results of a feasibility
study. Blood Purif. 2008;26(4):333-9. Epub 2008 May 16.
Prospective feasibility study with plasma separation and adsorption (PSA) treatment using a novel arginine-coated adsorber
column was performed in a tertiary care gastroenterological intensive care unit. RESULTS: 10 patients with severe sepsis/septic shock (median APACHE II score: 27, hospital mortality 40%) were treated with PSA on 5 consecutive days. There were no serious adverse events. No patient died during the treatment period. During treatment sessions, mean arterial pressure and cardiac power index increased while vasopressors could be reduced. Advanced oxidation protein products and in vitro pro- apoptotic activity of plasma decreased. We could not demonstrate any changes in endotoxin levels.
3. Staubach KH, Boehme M, Zimmermann M, Otto V. A new endotoxin adsorption device in Gram-negative sepsis: use of immobilized albumin with the MATISSE adsorber. Transfus Apher Sci. 2003 Aug;29(1):93-8.
MATISSE is a new endotoxin (ET) adsorption system. It comprises the FRESENIUS hemoadsorption machine 4008 ADS to maintain the extracorporeal circuits and disposables including the MATISSE-adsorber based on macroporous beads immobilized with human serum albumin. Apheresis treatment with the human albumin immobilized adsorber seems to be safe and well tolerable in healthy volunteers. A slight decrease in platelet count as well as insulin level was observed. Similar findings were made in an open uncontrolled trial in six patients with suspected Gram-negative sepsis. Here endotoxin adsorption seems to be safe and well tolerated without adsorber related major adverse events. In the last clinical trial including 145 patients mainly peritonitis patients (104), again no safety concerns were found during the apheresis. Trends in improvement of morbidity and organ dysfunction were found as well as efficient LPS removal in peritonitis patients. LPS whole blood immunoadsorption is a promising new method. No relevant side effects were observed so far. A large controlled study to prove clinical efficacy in patients with severe sepsis and confirmed endotoxemia (e.g. peritonitis) should be necessary.
4. Ullrich H, Jakob W, Fröhlich D, Rothe G, Prasser C, Drobnik W, Taeger K, Meier-Hellmann A, Reinhart K, Zimmermann M, Schmitz G. A new endotoxin adsorber: first clinical application. Ther Apher. 2001 Oct;5(5):326-34.
In an open, uncontrolled pilot study, 5 men and 1 woman with suspected gram-negative sepsis were treated with a new whole-blood endotoxin adsorption system. Lipopolysaccharide (LPS) adsorption was carried out by hemoperfusion over high-affinity polymethacrylate-bound albumin (Fresenius Endotoxin Adsorber EN 500). All patients suffered from endotoxemia (>20 pg/ml LAL) and met at least two systemic inflammatory response syndrome (SIRS) criteria. Four patients suffered from pneumonia due to mechanical ventilation, one from peritonitis, and one from pneumonia and peritonitis. Endotoxin adsorption was very well tolerated, and
efficient LPS removal was shown in all patients. Apache II score immediately before immunoadsorption was 23.5 and was 22.3 after the last treatment. All 6 critically ill patients improved substantially and were discharged from the intensive care unit. LPS whole blood immunoadsorption is a promising new method. No side effects have been observed thus far. A large controlled study to prove
clinical efficacy in patients with severe sepsis is under way.
5. Zimmermann M, Busch K, Kuhn S, Zeppezauer M. Endotoxin adsorbent based on immobilized human serum albumin.Clin Chem Lab Med. 1999 Mar;37(3):373-9.
Here we describe lipopolysaccharide (LPS) and cytokine adsorption characteristics of a new adsorbent based on purified human serum
albumin (HSA) covalently linked to macroporous polymer beads (iHSA). Multipoint attachment of HSA to acrylic beads via carboxyl groups of the protein resulted in an increased affinity to LPS. Depending on the means of immobilization, iHSA shows higher affinity for LPS than native albumin present in plasma. We demonstrated an efficient removal of LPS from plasma in vitro. Adsorption over immobilized HSA appears to be a simple and effective means of removing LPS and perhaps pro-inflammatory cytokines from the circulation.
6. Reinhart K, Meier-Hellmann A, Beale R, Forst H, Boehm D, Willatts S, Rothe KF, Adolph M, Hoffmann JE, Boehme M, Bredle DL; EASy-Study Group. Open randomized phase II trial of an extracorporeal endotoxin adsorber in suspected Gram-negative sepsis.Crit Care Med. 2004 Aug;32(8):1662-8.
An initial phase II trial to investigate the safety and therapeutic effect of the endotoxin adsorber system EN 500 in septic patients suffering from presumed Gram-negative infection. DESIGN: Open, controlled, prospective, randomized, multiple-center, parallel-group clinical trial. SETTING: Intensive care units of 31 university-affiliated and community hospitals in Europe. PATIENTS: One hundred forty-five patients with a clinical diagnosis of severe sepsis or septic shock due to suspected Gram-negative infection. INTERVENTIONS: Patients were randomized to receive either standard therapy alone for sepsis (n = 76) or standard therapy plus extracorporeal endotoxin adsorption (n = 67) daily for the first 4 days following study entry. MEASUREMENTS AND MAIN RESULTS: The primary end point was the proportion of responders (defined as a decrease in Acute Physiology and Chronic Health Evaluation II score by > or =4 points from study entry to day 4). Secondary outcomes were the Sequential Organ Failure Assessment score and its components, length of intensive care unit stay, survival rate, and safety of the adsorber treatment. Patient characteristics at entry were well balanced between the two treatment groups, except for a higher Sequential Organ Failure Assessment score in the adsorber group. On all-subjects-treated analysis, 65% of the adsorber group were responders vs. 57% for the standard (p =.389). A planned interim analysis restricted further enrollment to patients with peritonitis, in whom a slightly higher proportion of responders was observed with the adsorber treatment (69%) vs. standard treatment (54%, p =.159). There were no differences in survival, but adsorption treatment in peritonitis patients was associated with trends toward a reduction in length of intensive care unit stay and a more rapid decline in plasma endotoxin concentrations. There was a significantly greater reduction in platelet count with the adsorber; however, this did not require extra treatment. CONCLUSIONS: The endotoxin adsorber system did not result in a significantly improved primary end point in patients with presumed Gram-negative sepsis. In patients with peritonitis, the adsorber treatment likewise did not result in significantly improved Acute Physiology and Chronic Health Evaluation II scores. There were no clinically important side effects. These results provide encouragement for further study of adsorber treatment in patients with high likelihood of Gram-negative sepsis (e.g., peritonitis).
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