Abstract
Introduction: Disseminated intravascular coagulation (DIC) and sepsis are both associated with high morbidity and mortality in the United States (U.S.). Sepsis is one of the most common causes of DIC. The presence of DIC in sepsis is associated with a higher mortality rate, compared to sepsis alone. Despite their clinical overlap, the compounded impact of DIC and sepsis on mortality is not well defined at the population level. Thus, the current retrospective analysis aims to evaluate their combined mortality burden among U.S. adults from 1999 to 2020.
Methods: We queried the CDC WONDER Multiple Cause of Death (MCOD) database to extract overall mortality data and age-adjusted mortality rates (AAMR) per 100,000 population for DIC (ICD-10 code: D65) and sepsis (ICD-10 code: A40-A41) among US adults whose death certificates listed both DIC and sepsis as causes of death. We stratified AAMRs by year, gender, age, race, and geographical distribution. Joinpoint regression software was used to calculate annual percentage change (APC) and average annual percentage change (AAPC), and the parametric method was applied to determine 95% confidence intervals (CI). A p-value < 0.05 was considered significant, indicated by *.
Results: From 1999 to 2020, a total of 29,664 adult deaths in the U.S. had both DIC and sepsis listed as causes of death. The overall AAMR decreased from 0.76 in 1999 to 0.62 in 2020, with an AAPC of -1.2495*. Notably, after a sharp decline from 1999 to 2004 (APC: -3.7631*), the trend stabilized until 2020 (APC: -0.4506). Overall AAMR in women superseded that in men (0.63 vs. 0.61), with the latter showing a more pronounced decline in trend (female AAPC: -0.157 vs. male AAPC: -1.8669*). Of particular concern is the upward spike seen in women between 2015 and 2020 (APC: 3.0933). Age-based analysis revealed a downward trend in AAMR in all age groups except the 25-34 (AAPC: 1.1283) and 35-44 age groups (AAPC: 0.046). The steepest decline was observed among individuals aged 85 and above (AAPC: -3.6174*). Among racial groups, the highest overall AAMR was exhibited by Non-Hispanic (NH) Blacks (1.32), followed by NH American Indians (1.03), Hispanics (0.75), NH Asians (0.62), and lastly, NH Whites (0.54). All races showed a declining overall trend. The steepest decline was observed in NH Asians (AAPC: -2.6566*). The recent reversal in trend seen in the African American population from 2014 to 2020 (APC: 2.4837) is a notable finding. Regional analysis demonstrated the highest overall mortality burden in the South (AAMR: 0.75) and the lowest in the Midwest (0.54); the Northeast and West regions showed comparable rates (0.6). The West was the only region that showed an overall upward trend (AAPC: 0.5433*). Moreover, upon Joinpoint analysis, the Northeast region exhibited a substantial increase in mortality rates (APC: 14.5022*) from 2017 to 2020, which deserves particular attention. Additionally, rural areas had slightly elevated rates compared to urban areas (0.64 vs. 0.6), with the former showing a slightly upward trend compared to the decline seen in the latter (rural AAPC: 0.3891 vs. urban AAPC: -1.2903*). Considerable statewide variation was seen, with the highest AAMR in the District of Columbia (1.33), Rhode Island (1.07), and South Carolina (1.03), and the lowest seen in Utah (0.29), Vermont (0.28), and Montana (0.25). The mortality burden was highest in inpatient facilities (94.77%).
Conclusion: Despite the overall decline in the combined DIC and sepsis-associated mortality rate from 1999 to 2020, the mortality burden remains disproportionately high among women, NH Blacks, and the South region. This disparity warrants a closer evaluation of the factors responsible for driving the susceptibility of the aforementioned groups to high mortality rates. Timely intervention strategies, like implementation of sepsis screening tools, utilization of a consistent scoring system for DIC across hospitals, and risk-adjusted diagnostic protocols to identify and treat DIC earlier in underserved groups can help address these disparities.
