Extracorporeal adsorbent-based strategies in sepsis.
Gram-negative bacterial sepsis remains a challenging diagnostic and therapeutic dilemma to the practicing clinician. Bacterial-derived products (eg, gram-negative bacterial lipopolysaccharide or endotoxin) and host inflammatory mediators (eg, tumor necrosis factor-alpha and interleukin-1) are believed to play a pivotal role in the pathogenesis of sepsis and septic shock. Despite the many advances in the treatment of sepsis, mortality rates in septic patients remain high. Indeed, numerous clinical trials using biologically engineered immunotherapies targeting specific inflammatory mediators have proven unsuccessful. This lack of success has led to a renewed interest in blood purification techniques using extracorporeal therapies. During sepsis, circulating bacterial-derived products as well as inflammatory mediators can be reduced and/or eliminated by various extracorporeal adjunctive therapies such as plasma exchange, continuous renal replacement, and adsorbent-based therapies. Adsorbents have commonly been used orally for gastrointestinal removal of toxins or drugs. However, their potential use in sepsis has received little attention. The incorporation of adsorbents in hemoperfusion columns has allowed their use for the removal of toxic compounds from the circulatory system. Adsorbents developed for use in sepsis can bind toxins in a nonselective (eg, charcoal), selective (eg, polymyxin B-immobilized polystyrene-derivative fiber), or specific (eg, antibody-coated microsphere-based detoxification system) way. However, despite an explosive development in the experimental use of these promising therapies, randomized clinical trials are currently lacking. In summary, a multi-disciplinary complex therapeutic approach remains a prerequisite to the successful treatment of sepsis.
Jaber
B L
BL
Department of Medicine, New England Medical Center, Tufts University School of Medicine, Boston, MA 02111, USA.
Pereira
B J
BJ
D000327:Adsorption; D000818:Animals; D016470:Bacteremia / Q000628:therapy*; D004285:Dogs; D016905:Gram-Negative Bacterial Infections / Q000628:therapy*; D006440:Hemofiltration / Q000379:methods*; D006464:Hemoperfusion; D006801:Humans; D051379:Mice