Manzanares William, Langlois Pascal L, Heyland Daren K
Department of Critical Care, Intensive Care Unit-Hospital de Clínicas (University Hospital), Faculty of Medicine, Universidad de la República (UDELAR), Montevideo, Uruguay
Department of Anesthesia and Reanimation, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Centre Hospitalier Universitaire de Sherbrooke-Hôpital Fleurimont, Québec, Canada.
Nutr Clin Pract. 2015 Feb;30(1):34-43. doi: 10.1177/0884533614561794. Epub 2014 Dec 18.
Selenium is a component of selenoproteins with antioxidant, anti-inflammatory, and immunomodulatory properties. Systemic inflammatory response syndrome (SIRS), multiorgan dysfunction (MOD), and multiorgan failure (MOF) are associated with an early reduction in plasma selenium and glutathione peroxidase activity (GPx), and both parameters correlate inversely with the severity of illness and outcomes. Several randomized clinical trials (RCTs) evaluated selenium therapy as monotherapy or in antioxidant cocktails in intensive care unit (ICU) patient populations, and more recently several meta-analyses suggested benefits with selenium therapy in the most seriously ill patients. However, the largest RCT on pharmaconutrition with glutamine and antioxidants, the REducing Deaths due to Oxidative Stress (REDOXS) Study, was unable to find any improvement in clinical outcomes with antioxidants provided by the enteral and parenteral route and suggested harm in patients with renal dysfunction. Subsequently, the MetaPlus study demonstrated increased mortality in medical patients when provided extra glutamine and selenium enterally. The treatment effect of selenium may be dependent on the dose, the route of administration, and whether administered with other nutrients and the patient population studied. Currently, there are few small studies evaluating the pharmacokinetic profile of intravenous (IV) selenium in SIRS, and therefore more data are necessary, particularly in patients with MOD, including those with renal dysfunction. According to current knowledge, high-dose pentahydrate sodium selenite could be given as an IV bolus injection (1000-2000 µg), which causes transient pro-oxidant, cytotoxic, and anti-inflammatory effects, and then followed by a continuous infusion of 1000-1600 µg/d for up to 10-14 days. Nonetheless, the optimum dose and efficacy still remain controversial and need to be definitively established.
硒是具有抗氧化、抗炎和免疫调节特性的硒蛋白的组成部分。全身炎症反应综合征（SIRS）、多器官功能障碍（MOD）和多器官衰竭（MOF）与血浆硒和谷胱甘肽过氧化物酶活性（GPx）早期降低有关，且这两个参数均与疾病严重程度和预后呈负相关。多项随机临床试验（RCT）评估了在重症监护病房（ICU）患者群体中，硒疗法作为单一疗法或在抗氧化剂混合物中的应用，最近的几项荟萃分析表明，硒疗法对病情最严重的患者有益。然而，关于谷氨酰胺和抗氧化剂的最大规模的药物营养RCT，即降低氧化应激导致的死亡（REDOXS）研究，未能发现肠内和肠外途径提供的抗氧化剂在临床结局方面有任何改善，并提示对肾功能不全患者有危害。随后，MetaPlus研究表明，对内科患者经肠内补充额外的谷氨酰胺和硒会增加死亡率。硒的治疗效果可能取决于剂量、给药途径、是否与其他营养素一起给药以及所研究的患者群体。目前，很少有小型研究评估静脉注射（IV）硒在SIRS中的药代动力学特征，因此需要更多数据，特别是在MOD患者中，包括肾功能不全患者。根据目前的知识，高剂量的亚硒酸钠五水合物可静脉推注（1000 - 2000μg），这会产生短暂的促氧化、细胞毒性和抗炎作用，然后持续输注1000 - 1600μg/d，持续10 - 14天。尽管如此，最佳剂量和疗效仍存在争议且需要明确确定。
