Endocannabinoids, Anandamide and 2-Arachidonoylglycerol, as Prognostic Markers of Sepsis Outcome and Complications

Abstract

Background: One of the major challenges in improving sepsis care is early prediction of sepsis complications. The endocannabinoid system has been intensely studied in recent years; however, little is known about its role in sepsis in humans. This study aimed to assess the prognostic role of endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), as early predictors of mortality, invasive mechanical ventilation (IMV) requirement, and length of stay (LOS) in patients with sepsis. Materials and Methods: In total, 106 patients with confirmed sepsis were enrolled in this study. The patients were divided into groups according to mortality outcome (survival, N =53; nonsurvival, N =53), IMV requirement (IMV group, N =26; non-IMV group, N =80), and LOS (LOS <10 days, N =59; LOS ≥10 days, N =47). Patients' clinical status was assessed along with laboratory biomarkers as well as AEA and 2-AG concentration measurements early on admission to emergency units. AEA and 2-AG levels were measured by enzyme-linked immunosorbent assay (ELISA) using an ELISA processor, EtiMax 3000 (DiaSorin, Saluggia, Italy). The predictive value of AEA and 2-AG for the studied sepsis outcomes and complications was analyzed using univariate and multivariate analyses and receiver operating characteristic (ROC) curve analysis. Results: Two endocannabinoids showed no significant difference between survivors and nonsurvivors, although an AEA concentration <7.16 μg/L predicted mortality outcome with a sensitivity of 57% (95% confidence interval [CI] 42–71) and specificity of 80% (95% CI 66–91). AEA concentrations ≤17.84 μg/L predicted LOS ≥10 days with sensitivity of 98% (95% CI 89–100) and specificity of 34% (95% CI 22–47). When analyzing IMV requirement, levels of AEA and 2-AG were significantly lower within the IMV group compared with the non-IMV group (5.94 μg/L [2.04–9.44] and 6.70 μg/L [3.50–27.04], p =0.043, and 5.68 μg/L [2.30–8.60] and 9.58 μg/L [4.83–40.05], p =0.002, respectively). The 2-AG showed the best performance for IMV requirement prediction, with both sensitivity and specificity of 69% ( p <0.001). Endocannabinoid AEA was an independent risk factor of LOS ≥10 days (odds ratio [OR] 23.59; 95% CI 3.03–183.83; p =0.003) and IMV requirement in sepsis (OR 0.79; 95% CI, 0.67–0.93; p =0.004). Conclusion: Low AEA concentration is a prognostic factor of hospital LOS longer than 10 days. Lower AEA and 2-AG concentrations obtained at the time of admission to the hospital are predictors of IMV requirement.

Investigating the impact of human blood metabolites on the Sepsis development and progression: a study utilizing two-sample Mendelian randomization

“…Recent research findings suggest that low baseline plasma AEA levels may serve as prognostic indicators for septic patients requiring prolonged mechanical ventilation. Furthermore, a lower concentration of AEA has been identified as a prognostic factor for hospital stays exceeding 10 days (30). In another study, AEA was found to attenuate acute respiratory distress syndrome induced by Staphylococcus Enterotoxin B by suppressing inflammation through the down-regulation of key miRNA that regulates immunosuppressive pathways (31).…”

Exploring the versatile roles of the endocannabinoid system and phytocannabinoids in modulating bacterial infections

“…Lastly, beyond the roles of CB 1 R and CB 2 R in immune and physiological regulation, researchers have explored the indicators of altered eCB production as potential markers for sepsis severity. A study encompassing 106 hospitalized sepsis patients showed that patients with diminished AEA and 2-AG levels necessitated extended hospital stays and invasive mechanical ventilation ( 159 ).…”