Removing endocannabinoids and reducing oxidative stress with polymyxin-B-immobilized fibers in patients with septic shock

Introduction

Arachidonylethanolamide (AEA) and 2-arachidonyl-glycerol (2-AG) are endocannabinoids involved in septic shock, and 8-epi prostaglandin F2α (F2-isoprostane) is a biomarker of oxidative stress. Because the antibiotic polymyxin-B binds to endotoxins and endocannabinoids, direct hemoperfusion therapy with polymyxin-B-immobilized fibers (PMX-DHP) decreases serum levels of endocannabinoids. To investigate the features of sepsis and to determine the proper usage of PMX-DHP, we compared perioperative changes in levels of endocannabinoids and F2-isoprostane in patients with septic shock

Methods

Twenty-four patients with septic shock induced by peritonitis underwent laparotomy for drainage. Endocannabinoid absorption with PMX-DHP was examined in two groups of patients: patients in whom systolic arterial BP had increased more than 20 mmHg (BP elevation group; n = 12) and patients in whom BP did not increase or had increased no more than 20 mmHg (BP constant group; n = 12).

Results

Levels of AEA did not change after PMX-DHP in the either the BP constant group or the BP elevation group, whereas levels of 2-AG decreased significantly after PMX-DHP in the BP elevation group but not in the BP constant group (Figure 1). F2-isoprostane gradually increased after PMX-DHP. On the other hand, levels of F2-isoprostane remained constant in the BP elevation group (Figure 2).

Figure 1

Abstract P119

Figure 2

Abstract P119

Conclusion

Patients with septic shock are under considerable oxidative stress, and 2-AG plays an important role in the cardiovascular status of these patients. The removal of 2-AG by PMX-DHP benefits patients with septic shock by stabilizing cardiovascular status and decreasing long-term oxidative stress.