Nishita Yoshihiro, Taga Masatoshi, Sakurai Masaru, Iinuma Yoshitsugu, Masauji Togen
Department of Pharmacy, Kanazawa Medical University Hospital, 1-1 Daigaku, Uchinada-cho, Kahoku-gun, Ishikawa, 920-0293, Japan.
Department of Social and Environmental Medicine, Kanazawa Medical University, 1-1 Daigaku, Uchinada-cho, Kahoku-gun, Ishikawa, 920-0293, Japan.
J Pharm Health Care Sci. 2022 Dec 12;8(1):32. doi: 10.1186/s40780-022-00264-9.
Human soluble recombinant thrombomodulin (TM alfa), a treatment for septic Disseminated intravascular coagulation (DIC), is recommended for patients with severe renal dysfunction in reduced doses. However, no studies have examined yet how dose reduction affects clinical efficacy. In this study, we investigated the significance of the TM alfa dose as a prognostic factor in clarifying the clinical background factors related to the clinical effect of TM alfa in patients with septic DIC.
This study involved 102 patients with septic DIC admitted to a single-center intensive care unit between April 2013 and March 2020, receiving TM alfa. The following factors were retrospectively collected from the medical records of the target patients: (1) patient background, (2) sequential organ failure assessment (SOFA) score, (3) Japanese Association for Acute Medicine DIC diagnostic criteria score, (4) DIC treatment information, (5) TM alfa dose per bodyweight (normal dose: 0.06 mg/kg or reduced dose: 0.02 mg/kg), (6) DIC resolution within 7 days after the start of TM alfa administration (DIC resolution), (7) all deaths within 30 days after the start of TM alfa administration (30-days-all-cause mortality), (8) presence or absence of new hemorrhagic side effects after the start of TM alfa administration. Multiple logistic regression analysis was used to assess factors associated with DIC resolution and 30-days-all-cause mortality.
The SOFA score (odds ratio: 95% confidence interval, 0.76: 0.66-0.89), pneumonia (0.24: 0.08-0.75), and reduced dose administration of TM alfa (0.23: 0.08-0.66) were independent of and negatively related to the DIC resolution. For the 30-days-all-cause mortality, the SOFA score (1.66: 1.31-2.09), pneumonia (9.50: 2.49-36.25), and TM alfa dose reduction (3.52: 1.06-11.69) were independent, poor prognostic factors. We found no association between the hemorrhagic side effects and the TM alfa dose per bodyweight.
The reduced dose of TM alfa for patients with severe renal dysfunction was observed to be an influential factor for DIC resolution and 30-day all-cause mortality, as were SOFA scores and pneumonia. Further studies are required in the future to verify this finding.
人可溶性重组血栓调节蛋白（TMα）是治疗脓毒症弥散性血管内凝血（DIC）的药物，对于严重肾功能不全患者，建议降低剂量使用。然而，尚无研究探讨剂量降低如何影响临床疗效。在本研究中，我们调查了TMα剂量作为预后因素在阐明脓毒症DIC患者中与TMα临床疗效相关的临床背景因素方面的意义。
本研究纳入了2013年4月至2020年3月期间在单中心重症监护病房收治的102例接受TMα治疗的脓毒症DIC患者。从目标患者的病历中回顾性收集以下因素：（1）患者背景，（2）序贯器官衰竭评估（SOFA）评分，（3）日本急性医学协会DIC诊断标准评分，（4）DIC治疗信息，（5）每体重TMα剂量（正常剂量：0.06mg/kg或降低剂量：0.02mg/kg），（6）TMα给药开始后7天内DIC的缓解情况（DIC缓解），（7）TMα给药开始后30天内的所有死亡情况（30天全因死亡率），（8）TMα给药开始后是否出现新的出血性副作用。采用多因素logistic回归分析评估与DIC缓解和30天全因死亡率相关的因素。
SOFA评分（比值比：95%置信区间，0.76：0.66 - 0.89）、肺炎（0.24：0.08 - 0.75）以及TMα降低剂量给药（0.23：0.08 - 0.66）与DIC缓解独立且呈负相关。对于30天全因死亡率，SOFA评分（1.66：1.31 - 2.09）、肺炎（9.50：2.49 - 36.25）以及TMα剂量降低（3.52：1.06 - 11.69）是独立的不良预后因素。我们发现出血性副作用与每体重TMα剂量之间无关联。
观察到严重肾功能不全患者TMα剂量降低是影响DIC缓解和30天全因死亡率的因素，SOFA评分和肺炎也是如此。未来需要进一步研究来验证这一发现。
