Yamakawa Kazuma, Umemura Yutaka, Hayakawa Mineji, Kudo Daisuke, Sanui Masamitsu, Takahashi Hiroki, Yoshikawa Yoshiaki, Hamasaki Toshimitsu, Fujimi Satoshi
Department of Emergency and Critical Care, Osaka General Medical Center, 3-1-56 Bandai-Higashi, Sumiyoshi-ku, Osaka, 558-8558, Japan.
Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, 2-15 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Crit Care. 2016 Jul 29;20(1):229. doi: 10.1186/s13054-016-1415-1.
Little evidence supports anticoagulant therapy as effective adjuvant therapy to reduce mortality overall in sepsis. However, several studies suggest that anticoagulant therapy may reduce mortality in specific patients. This study aimed to identify a subset of patients with high benefit profiles for anticoagulant therapy against sepsis.
This post hoc subgroup analysis of a nationwide multicentre retrospective registry was conducted in 42 intensive care units in Japan. Consecutive adult patients with sepsis were included. Treatment effects of anticoagulants, e.g. antithrombin, recombinant thrombomodulin, heparin, and protease inhibitors, were evaluated by stratifying patients according to disseminated intravascular coagulation (DIC) and Sequential Organ Failure Assessment (SOFA) score. Intervention effects of anticoagulant therapy on in-hospital mortality and bleeding complications were analysed using Cox regression analysis stratified by propensity scores.
Participants comprised 2663 consecutive patients with sepsis; 1247 patients received anticoagulants and 1416 received none. After adjustment for imbalances, anticoagulant administration was significantly associated with reduced mortality only in subsets of patients diagnosed with DIC, whereas similar mortality rates were observed in non-DIC subsets with anticoagulant therapy. Favourable associations between anticoagulant therapy and mortality were observed only in the high-risk subset (SOFA score 13-17; adjusted hazard ratio 0.601; 95 % confidence interval 0.451, 0.800) but not in the subsets of patients with sepsis with low to moderate risk. Although the differences were not statistically significant, there was a consistent tendency towards an increase in bleeding-related transfusions in all SOFA score subsets.
The analysis of this large database indicates anticoagulant therapy may be associated with a survival benefit in patients with sepsis-induced coagulopathy and/or very severe disease.
University Hospital Medical Information Network Clinical Trial Registry (UMIN-CTR ID: UMIN000012543 ). Registered on 10 December 2013.
几乎没有证据支持抗凝治疗作为降低脓毒症总体死亡率的有效辅助治疗方法。然而，多项研究表明抗凝治疗可能降低特定患者的死亡率。本研究旨在确定对抗凝治疗脓毒症获益较高的患者亚组。
在日本42个重症监护病房进行了这项对全国多中心回顾性登记的事后亚组分析。纳入连续的成年脓毒症患者。通过根据弥散性血管内凝血（DIC）和序贯器官衰竭评估（SOFA）评分对患者进行分层，评估抗凝血剂（如抗凝血酶、重组血栓调节蛋白、肝素和蛋白酶抑制剂）的治疗效果。使用倾向评分分层的Cox回归分析，分析抗凝治疗对住院死亡率和出血并发症的干预效果。
参与者包括2663例连续的脓毒症患者；1247例患者接受了抗凝治疗，1416例未接受。在调整不平衡因素后，仅在诊断为DIC的患者亚组中，抗凝治疗与死亡率降低显著相关，而在接受抗凝治疗的非DIC亚组中观察到相似的死亡率。仅在高危亚组（SOFA评分13 - 17；调整后的风险比0.601；95%置信区间0.451, 0.800）中观察到抗凝治疗与死亡率之间的有利关联，而在低至中度风险的脓毒症患者亚组中未观察到。尽管差异无统计学意义，但在所有SOFA评分亚组中，出血相关输血均有持续增加的趋势。
对这个大型数据库的分析表明，抗凝治疗可能与脓毒症诱导的凝血病和/或非常严重疾病患者的生存获益相关。
大学医院医学信息网络临床试验注册中心（UMIN - CTR ID：UMIN000012543）。于2013年12月10日注册。
