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

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. In total, 106 patients with confirmed sepsis were enrolled in this study. The patients were divided into groups according to mortality outcome (survival, =53; nonsurvival, =53), IMV requirement (IMV group, =26; non-IMV group, =80), and LOS (LOS <10 days, =59; LOS ≥10 days, =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. 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], =0.043, and 5.68 μg/L [2.30-8.60] and 9.58 μg/L [4.83-40.05], =0.002, respectively). The 2-AG showed the best performance for IMV requirement prediction, with both sensitivity and specificity of 69% (<0.001). Endocannabinoid AEA was an independent risk factor of LOS ≥10 days (odds ratio [OR] 23.59; 95% CI 3.03-183.83; =0.003) and IMV requirement in sepsis (OR 0.79; 95% CI, 0.67-0.93; =0.004). 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.