Anandamide absorption by direct hemoperfusion with polymixin B-immobilized fiber improves the prognosis and organ failure assessment score in patients with sepsis.
OBJECTIVE
Direct hemoperfusion (DHP) with polymixin B-immobilized fiber (PMX) has been reported to be effective for patients with septic shock. The aim of this study was to clarify the mechanism of PMX-DHP effect on septic shock.


METHODS
The following parameters were measured in septic shock patients who were treated with PMX-DHP: survival rate, sepsis-related organ failure assessment (SOFA) score, acute physiology and chronic health evaluation II (APACHE-II) score, and plasma concentrations of cannabinoids [anandamide (ANA) and 2-arachidonyl glyceride (2-AG)], cytokines [interleukin (IL)-6, IL-8, IL-10], transforming growth factor beta (TGF-beta), and calcitonin gene-related peptide (CGRP)]. The primary end point was mortality from all causes at day 28 after intensive care unit (ICU) admission or discharge.


RESULTS
The survival rate of all patients at 28 days after ICU admission was 37.5% (9/24). The survival group showed significantly lower SOFA and APACHE-II scores than the nonsurvival group after PMX-DHP treatment (P = 0.008 and 0.028, respectively). The improved SOFA score group showed a better survival rate than the nonimproved SOFA score group (71.4% versus 23.5%, P = 0.028). Plasma ANA level significantly decreased after PMX-DHP treatment both in the improved SOFA score group and in the survival group. The level of 2-AG, however, showed no significant change in either group.


CONCLUSIONS
ANA, an intrinsic cannabinoid that induces hypotension in septic shock, is inferred to be the main mechanism of the PMX-DHP effect. Removal of ANA by PMX-DHP could be key to successful septic shock treatment.
Kohro
Shinji
S
Department of Anesthesiology, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo 060-8543, Japan.
Imaizumi
Hitoshi
H
Yamakage
Michiaki
M
Masuda
Yoshiki
Y
Namiki
Akiyoshi
A
Asai
Yasuhumi
Y
Maruyama
Ikuo
I
D018806:APACHE; D000328:Adult; D000368:Aged; D001095:Arachidonic Acids / Q000097:blood / Q000302:isolation & purification*; D015740:Calcitonin Gene-Related Peptide / Q000097:blood; D063388:Endocannabinoids; D005260:Female; D006464:Hemoperfusion / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000401:mortality / Q000628:therapy*; D011112:Polymyxin B / Q000008:administration & dosage*; D053284:Polyunsaturated Alkamides; D011379:Prognosis; D011446:Prospective Studies; D012772:Shock, Septic / Q000401:mortality / Q000628:therapy*; D015996:Survival Rate; D016212:Transforming Growth Factor beta / Q000097:blood
D001095:Arachidonic Acids; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; D016212:Transforming Growth Factor beta; D011112:Polymyxin B; D015740:Calcitonin Gene-Related Peptide; C078814:anandamide