History and current status of polymyxin B-immobilized fiber column for treatment of severe sepsis and septic shock

Abstract

Toraymyxin^® (Toray Medical Co., Ltd, Tokyo, Japan) has been developed as a direct hemoperfusion column that contains polymyxin B-immobilized fiber to bind endotoxins in patients' blood. Toraymyxin was approved by the Japanese National Health Insurance system for the treatment of endotoxemia and septic shock in 1994. Since then, PMX (defined as direct hemoperfusion with Toraymyxin) has been safely used in more than 100 000 cases in emergency and intensive care units in Japan. Toraymyxin is currently available for use in clinical settings in 12 countries outside of Japan. We reviewed and analyzed the development, clinical use, and efficacy of Toraymyxin, and assessed the current status of Toraymyxin use for the treatment of severe sepsis and septic shock. Our review shows that PMX appeared to be effective in improving hemodynamics and respiratory function in septic shock requiring emergency abdominal surgery. Recent large-scale ranomized controlled trialscould not demonstrate whether prognosis is improved by PMX. However, the latest meta-analysis revealed that PMX significantly decreased mortality in patients with severe sepsis and septic shock. Combination of PMX with continuous hemodiafiltration and longer duration of PMX might be an effective strategy to improve survival in such patients.

Keywords: Toraymyxin; blood purification; direct hemoperfusion with Toraymyxin (PMX); endotoxin; sepsis.

Figure 1

History of the development of Toraymyxin. EUPHAS, Early Use of Polymyxin B Hemoperfusion in Abdominal Sepsis. ABDO‐MIX trial, Effects of Hemoperfusion with a Polymyxin B Membrane in Peritonitis with Septic Shock. EUPHRATES trial, Evaluating the Use of Polymyxin B Hemoperfusion in a randomized controlled trial of Adults Treated for Endotoxemia and Septic Shock

Figure 2

Physical structure of a Toraymyxin cartridge and of the knitted fabric roll of polymyxin B‐immobilized fibers (provided by Toray Medical Co., Ltd). The Toraymyxin cartridge contains a roll of knitted fibers. Each fiber consists of a bundle of ultrafine fibers with a diameter of approximately 20 μm. The polymyxin B molecules are covalently bound onto the fiber surface and therefore do not leak into the patient. Molecular conformation is shown. Polymyxin B is covalently bound to polystyrene‐based fiber

Figure 3

Specification of Toraymyxin cartridge. Overview of the three Toraymyxin cartridges currently available for clinical use (provided by Toray Medical Co., Ltd)

Figure 4

Results from the first clinical trial of Toraymyxin in Japan. (A) Endotoxin concentration before and after Toraymyxin treatment. (B) Systemic vascular resistance (SVR) before and after Toraymyxin treatment. Toraymyxin treatment decreased the concentration of endotoxin in the blood and improved hemodynamic status in patients with severe sepsis and septic shock. (Reproduced from Aoki et al. 1994.3)

Figure 5

Main results of a meta‐analysis of Toraymyxin treatment. CI, confidence interval; MAP, mean arterial pressure; PaO₂/FIO ₂, ratio of partial pressure arterial oxygen and fraction of inspired oxygen

Figure 6

Combination use of Toraymyxin and continuous hemodiafiltration (CHDF). (A) Survival of patients receiving combination therapy of Toraymyxin and CHDF (Both). (Reproduced from Suzuki et al. 2002.30) Combination therapy of Toraymyxin and CHDF significantly improved survival rate in patients with sepsis and acute renal failure. (B) Schematic of the combination of PMX and CHDF in a series‐parallel circuit. (Reproduced from Yonekawa et al. 2006.32) PMX, direct hemoperfusion with Toraymyxin