High-dose selenium reduces ventilator-associated pneumonia and illness severity in critically ill patients with systemic inflammation
High-dose selenium reduces ventilator-associated pneumonia and illness severity in critically ill patients with systemic inflammation
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DOI：
10.1007/s00134-011-2212-6
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发表时间：
2011-07-01
影响因子：
38.9
通讯作者：
Hardy, Gil
中科院分区：
文献类型：
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作者：
Manzanares, William;Biestro, Alberto;Hardy, Gil
为证实亚硒酸盐初始负荷推注后持续输注大剂量硒（Se）对全身炎症反应综合征（SIRS）危重患者临床结局的药效学和疗效，在多学科大学医院重症监护室（ICU）进行了前瞻性、安慰剂对照、随机、单盲II期研究。两组SIRS患者，年龄> 18岁，急性生理学和慢性健康评估（APACHE）II a份/千日元15（n = 35），随机接受安慰剂或静脉注射亚硒酸盐，作为2,000 μ g Se的大剂量，随后每天连续输注1,600 μ g Se，持续10天。在随机化前（第0天），然后在第3、7和10天分析血样。采用序贯器官衰竭评估（SOFA）评分评估临床结局。医院获得性肺炎（包括呼吸机相关肺炎（VAP））、不良事件和其他安全参数作为次要终点进行监测。第10天，亚硒酸盐组的SOFA评分显着下降（1.3 +/-A1.2 vs 4.6 +/-A2.0，p = 0.0001）。亚硒酸盐组的早期VAP发生率较低（6.7%对37.5%，p = 0.04），ICU出院后医院获得性肺炎较低（p = 0.03）。谷胱甘肽过氧化物酶-3（GPx-3）活性在两组中均增加，在亚硒酸盐组中在第7天达到最大值（0.62 +/- A 0.24 vs 0.28 +/- A 0.14 U/mL，p = 0.001）。没有观察到可归因于亚硒酸盐的不良事件。每日输注1，600 μ g硒（以亚硒酸盐计），初始推注量为2，000 μ g，是新颖的，没有短期不良事件。大剂量静脉注射亚硒酸盐可显著增加ICU SIRS患者的硒状态，改善病情严重程度，降低医院获得性肺炎（包括早期VAP）的发生率。
To confirm the pharmacodynamics and evaluate the efficacy of high-dose selenium (Se) administered by continuous infusion, following an initial loading bolus of selenite, on clinical outcome in critically ill patients with systemic inflammatory response syndrome (SIRS).Prospective, placebo-controlled, randomized, single-blinded phase II study in a multidisciplinary university hospital intensive care unit (ICU). Two groups of patients with SIRS, age > 18 years, and Acute Physiology and Chronic Health Evaluation (APACHE) II a parts per thousand yen15 (n = 35) were randomized to receive either placebo or intravenous selenite as a bolus-loading dose of 2,000 mu g Se followed by continuous infusion of 1,600 mu g Se per day for 10 days. Blood samples were analyzed before randomization (day 0) then at days 3, 7, and 10. Clinical outcome was assessed by Sequential Organ Failure Assessment (SOFA) score. Hospital-acquired pneumonia including ventilator-associated pneumonia (VAP), adverse events, and other safety parameters were monitored as secondary endpoints.SOFA score decreased significantly in the selenite group at day 10 (1.3 +/- A 1.2 versus 4.6 +/- A 2.0, p = 0.0001). Early VAP rate was lower in the selenite group (6.7% versus 37.5%, p = 0.04), and hospital-acquired pneumonia was lower after ICU discharge (p = 0.03). Glutathione peroxidase-3 (GPx-3) activity increased in both groups, reaching a maximum at day 7 (0.62 +/- A 0.24 versus 0.28 +/- A 0.14 U/mL, p = 0.001) in the selenite group. No adverse events attributable to selenite were observed.Daily infusion of 1,600 mu g Se (as selenite), following an initial bolus of 2,000 mu g, is novel and without short-term adverse events. High-dose parenteral selenite significantly increases Se status, improves illness severity, and lowers incidence of hospital-acquired pneumonia including early VAP for SIRS patients in ICU.