Department of Clinical Laboratory Diagnostics, University Hospital Osijek, Osijek, Croatia.
J.J. Strossmayer University of Osijek, Faculty of Medicine Osijek, Osijek, Croatia.
Cannabis Cannabinoid Res. 2023 Oct;8(5):802-811. doi: 10.1089/can.2022.0046. Epub 2022 Jun 1.
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.
在改善脓毒症护理方面，面临的主要挑战之一是早期预测脓毒症并发症。内源性大麻素系统在近年来受到了深入研究；然而，关于其在人类脓毒症中的作用，我们知之甚少。本研究旨在评估内源性大麻素（AEA 和 2-花生四烯酸甘油）作为死亡率、有创机械通气（IMV）需求和脓毒症患者住院时间（ LOS ）的早期预测指标的预后作用。共有 106 名确诊脓毒症的患者纳入本研究。根据死亡率结局（存活组，=53；非存活组，=53）、IMV 需求（IMV 组，=26；非 IMV 组，=80）和 LOS（<10 天，=59；≥10 天，=47）将患者分为不同的组。在入住急诊单元时，对患者的临床状况进行评估，并检测实验室生物标志物以及 AEA 和 2-AG 浓度。使用酶联免疫吸附测定（ELISA）通过 ELISA 处理器（DiaSorin，Saluggia，意大利）EtiMax 3000 测量 AEA 和 2-AG 水平。使用单变量和多变量分析以及接收者操作特征（ROC）曲线分析，分析 AEA 和 2-AG 对研究中脓毒症结局和并发症的预测价值。尽管 AEA 浓度<7.16μg/L 预测死亡率的敏感性为 57%（95%CI 42-71），特异性为 80%（95%CI 66-91），但在幸存者和非幸存者之间，两种内源性大麻素没有显著差异。AEA 浓度≤17.84μg/L 预测 LOS≥10 天的敏感性为 98%（95%CI 89-100），特异性为 34%（95%CI 22-47）。在分析 IMV 需求时，与非 IMV 组相比，AEA 和 2-AG 在 IMV 组中的水平显著降低（5.94μg/L [2.04-9.44] 和 6.70μg/L [3.50-27.04]，=0.043；5.68μg/L [2.30-8.60] 和 9.58μg/L [4.83-40.05]，=0.002）。2-AG 对 IMV 需求的预测具有最佳性能，敏感性和特异性均为 69%（<0.001）。内源性大麻素 AEA 是 LOS≥10 天（比值比[OR]23.59；95%CI 3.03-183.83；=0.003）和脓毒症中 IMV 需求（OR 0.79；95%CI，0.67-0.93；=0.004）的独立危险因素。低 AEA 浓度是住院 LOS 超过 10 天的预后因素。入院时获得的较低的 AEA 和 2-AG 浓度是 IMV 需求的预测指标。
