Critical Care Research Laboratories, Institute for Heart + Lung Health, University of British Columbia, Vancouver, British Columbia, Canada.
Am J Respir Crit Care Med. 2013 Jun 15;187(12):1303-7. doi: 10.1164/rccm.201303-0567UP.
Pivotal sepsis clinical trials and preclinical research in 2012 are reviewed. For interventions ranging from synthetic complex starch solutions to recombinant human activated protein C, large multicenter randomized controlled trials generally failed to show benefit and some even demonstrated harm in the intervention group. In smaller innovative clinical trials simple interventions such as external cooling to control fever and biomarker-guided weaning from mechanical ventilation found potential benefit. Biomarkers for sepsis, including multimarker panels, are increasingly showing promise for clinical application. Breakthroughs in basic research in sepsis continue to highlight the complexity of the systemic inflammatory response and its consequences. A series of publications in AJRCCM follow the septic inflammatory response starting from intracellular structures and organelles to mitochondria and the cytoskeleton. Additional publications explore the key leukocyte subsets acting in sepsis, highlighting the underappreciated role of helper T-cell type 2-related pathways. Cellular remnants in the form of microparticles contribute to coagulopathy and further organ dysfunction. As a consequence, we suggest that sepsis may be the paradigm disease or condition requiring personalized care first to discover and validate new therapies and second to increase survival.
回顾了 2012 年关键性脓毒症临床试验和临床前研究。对于从合成复杂淀粉溶液到重组人活化蛋白 C 的各种干预措施，大型多中心随机对照试验通常未能显示出益处，甚至有些试验显示干预组存在危害。在较小的创新性临床试验中，一些简单的干预措施，如外部冷却以控制发热和基于生物标志物的机械通气脱机，显示出了潜在的益处。脓毒症的生物标志物，包括多标志物组合，越来越多地显示出临床应用的前景。脓毒症基础研究的突破继续强调全身炎症反应及其后果的复杂性。一系列发表在 AJRCCM 的文章从细胞内结构和细胞器到线粒体和细胞骨架，跟踪了脓毒症的炎症反应。其他出版物则探讨了在脓毒症中起关键作用的白细胞亚群，强调了辅助性 T 细胞 2 型相关途径被低估的作用。以微颗粒形式存在的细胞残余物导致凝血功能障碍和进一步的器官功能障碍。因此，我们认为脓毒症可能是需要个性化治疗的范例疾病或病症，首先是发现和验证新的治疗方法，其次是提高生存率。
