Randomized controlled trial of inhaled nitric oxide for the treatment of microcirculatory dysfunction in patients with sepsis*.
Randomized controlled trial of inhaled nitric oxide for the treatment of microcirculatory dysfunction in patients with sepsis*.
复制标题
吸入一氧化氮治疗脓毒症患者微循环功能障碍的随机对照试验*。
DOI：
10.1097/ccm.0000000000000549
复制
发表时间：
2014
影响因子：
8.8
通讯作者：
Hollenberg,StevenM
中科院分区：
文献类型：
--
作者：
Trzeciak,Stephen;Glaspey,LindseyJ;Dellinger,RPhillip;Durflinger,Paige;Anderson,Keith;Dezfulian,Cameron;Roberts,BrianW;Chansky,MichaelE;Parrillo,JosephE;Hollenberg,StevenM
目的：脓毒症治疗指南推荐大循环血流动力学优化；然而，微循环功能障碍是脓毒症发病机制的组成部分。我们旨在验证以下假设：在大循环优化后，吸入一氧化氮可以改善败血症患者的微循环，而微循环的改善可以改善乳酸清除和多器官功能障碍。设计：随机、假对照临床试验。环境：单一的城市学术医疗中心。患者：成年严重脓毒症患者，尽管血管内体积扩张和/或血清乳酸大于或等于4.0 mmol/L，收缩压小于90 mm Hg。干预措施：在实现大循环复苏目标后，我们将患者随机分为6小时吸入一氧化氮（40 ppm）或假吸入一氧化氮。我们通过一种特殊的给药装置给药，该装置隐藏了治疗分配，使研究人员和临床工作人员保持盲法。测量和主要结果：我们在研究药物开始前和开始后2小时对舌下微循环进行了侧流暗场视频显微镜检查。主要观察指标为微循环流量指数的变化。次要结果是乳酸清除率和序贯器官衰竭评估评分的变化。我们招募了50例患者（50例中有28例（56%）需要血管加压药物；50例中有15例（30%）死亡）。虽然吸入一氧化氮能显著提高血浆亚硝酸盐水平，但不能改善微循环流量、乳酸清除率或器官功能障碍。与之前在复苏早期进行的研究相反，我们发现微循环流量的变化与乳酸清除或器官功能障碍之间没有关联。结论：在大循环优化后，吸入40 ppm的一氧化氮不会增加败血症患者的微循环灌注。此外，我们发现初始复苏后微循环灌注与多器官功能障碍之间没有关联。
Objectives:Sepsis treatment guidelines recommend macrocirculatory hemodynamic optimization; however, microcirculatory dysfunction is integral to sepsis pathogenesis. We aimed to test the hypothesis that following macrocirculatory optimization, inhaled nitric oxide would improve microcirculation in patients with sepsis and that improved microcirculation would improve lactate clearance and multiple organ dysfunction.Design:Randomized, sham-controlled clinical trial.Setting:Single urban academic medical center.Patients:Adult patients with severe sepsis and systolic blood pressure less than 90 mm Hg despite intravascular volume expansion and/or serum lactate greater than or equal to 4.0 mmol/L.Interventions:After achievement of macrocirculatory resuscitation goals, we randomized patients to 6 hours of inhaled nitric oxide (40 ppm) or sham inhaled nitric oxide administration. We administered study drug via a specialized delivery device that concealed treatment allocation so that investigators and clinical staff remained blinded.Measurements and Main Results:We performed sidestream dark-field videomicroscopy of the sublingual microcirculation prior to and 2 hours after study drug initiation. The primary outcome measure was the change in microcirculatory flow index. Secondary outcomes were lactate clearance and change in Sequential Organ Failure Assessment score. We enrolled 50 patients (28 of 50 [56%] requiring vasopressor agents; 15 of 50 [30%] died). Although inhaled nitric oxide significantly raised plasma nitrite levels, it did not improve microcirculatory flow, lactate clearance, or organ dysfunction. In contrast to previous studies conducted during the earliest phase of resuscitation, we found no association between changes in microcirculatory flow and lactate clearance or organ dysfunction.Conclusions:Following macrocirculatory optimization, inhaled nitric oxide at 40 ppm did not augment microcirculatory perfusion in patients with sepsis. Further, we found no association between microcirculatory perfusion and multiple organ dysfunction after initial resuscitation.