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HELP Apheresis in the Treatment of Sepsis
Artificial Organs
1998;22:43-46.
W. Samtleben, S. Bengsch, KS. Boos, D. Seidel
Sepsis as a result of gram-negative infection remains a major concern in intensive
care units in developed countries. While new therapies based on the administration
of immune globulins or binding and neutralization of endotoxins (lipopolysaccharides
[LPS]) and the primary inflammatory cytokine TNF-α have been developed, they
have not improved the overall prognosis for sepsis. As a result, numerous extracorporeal
therapies aimed at removing LPS and the proinflammatory cytokines have been incorporated
into the treatment modalities. This paper describes the findings of studies investigating
the effectiveness of LDL-apheresis via the heparin-induced method for the removal
of toxic products.
Nine treatments of four patients with severe gram-negative sepsis were preformed.
Six of the treatments were done with the standard heparin-induced buffer and three
treatments were performed with a modified buffer in which the heparin was removed.
Removal of the heparin was necessary to avoid further fibrinogen depletion in patients
with low postoperative fibrinogen levels.
Clinical results indicated a mean reduction in LPS concentrations of 50% ±
3% with the standard protocol and 57% for the modified protocol. Interestingly,
C-reactive protein (CRP), a sensitive marker for inflammation, was also significantly
reduced (by 49% ± 4% and 55% for the standard and modified procedures, respectively)
and reduction in TNF-α levels were approximately 25% with the standard procedure.
While average reduction rates for LPS and CRP were similar in both treatment protocols,
decreases in concentrations of TNF-α fibrinogen, total cholesterol, and apolipoprotein
B were negligible when the modified procedure was used. Regardless of the significant
decreases in LPS and CRP, only one of the four patients survived (the other three
patients died 5, 16, and 33 days following their last LDL-apheresis treatment via
the heparin-induced method).
A novel adsorption system was developed consisting of a closed-loop circuit in which
a plasma separator was followed by two absorbers in series. One absorber (dextran
sulfate modified cellulose) was used for removal of TNF-α and the other (a
DEAE-cellulose column) for removal of LPS. An in vitro evaluation to characterize
the novel adsorption system confirmed the efficient extraction of LPS and TNF-α.
The heparin-induced method may prove beneficial in the treatment of patients with
gram-negative sepsis. The development of a novel procedure may provide the capability
to effectively remove LPS and TNF-α during the hyperinflammatory stage of
sepsis.
Click for full abstract.
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