RESUMO
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
RESUMO
The lessons from the Great Hanshin-Awaji Earthquake and Chuuetsu Earthquake showed us how difficult it is to keep chronic disease management for survivors of such large-scale earthquakes, particularly for elderly people. To solve the problem, an ordinance for enforcement on exceptional practices was issued for the Pharmaceutical Affairs Law Article 49 Clause 1. The law allows selling prescription medicines for patients with chronic diseases who have difficulties to continue their medications due to a large-scale disaster. To make it work, the patient should demonstrate that he or she continuously received the medication by presenting either Medication Notebook or prescription book recorded by the pharmacist. However, the Separation Rate of Prescription and Dispensing in Japan is still low; in particular, that in Ishikawa prefecture, where the Noto Peninsula Earthquake (M 6.9) occurred on March 25, 20007, is very low. It means that few victims hold a Medication Notebook. In consideration of this situation, we conducted a questionnaire survey of elderly victims of the Noto Peninsula Earthquake with a key-informant-interview during the period from July through August, 2007. This study revealed that: 1) Only 16% (18/110) of respondents kept a Medication Notebook; 2) 75% (82/110) had chronic diseases and received medication regularly; 3) Of 81 who had chronic diseases, 42% (34/91) were dispensed at the same pharmacy always, (The rest received from either clinic or changing pharmacy according to clinic location); and 4) Diseases that the respondents had were hypertension, cardiovascular diseases, diabetes, and so on. Based on these results, we discuss the establishment of a pharmaceutical supply system that can effectively distribute appropriate medicines to patients under difficult situations following a large-scale disaster in Japan.