To the best of our knowledge, this study represents the first investigation into the association between the RDW and ill patients with SIC.The pathogenesis of SIC is complex and diverse. According to current relevant research, abnormal calcium signaling[20,21], mitochondrial dysfunction[22,23], inflammatory damage to cardiomyocytes[6] and abnormal energy metabolism[24] can all lead to the activation of intracellular apoptosis signal transduction pathways. This ultimately leads to cell apoptosis and damage tomyocardial cells, resulting in myocardial dysfunction. The presence of myocardial dysfunction is strongly associated with a poor prognosis in sepsis patients and is also a significant contributor to sepsis-related mortality[3].
This study constructed a highly efficient model for predicting the 28-day mortality rate in patients with SIC. The model's performance was enhanced by the inclusion of the RDW. Additionally, the PSM method was used to adjust for other potential factors that may impact the RDW of SIC patients. By using a matched cohort, the model effectively tackled the endogeneity issues caused by the descriptive variables. The study also ensured an ample selection of SIC patients from the MIMIC-IV database.
The assessment of disease incidence and progression utilizing RDW can impact clinical decision-making concerning treatment. As the patients' conditions in the ICU incessantly vary[25], reducing perplexity stemming from additional variables can facilitate harnessing the advantages provided by the RDW. In this study, the focus was on selecting patients with SIC based on stricter inclusion criteria. By narrowing down the patient pool to those who developed myocardial damage following the diagnosis of sepsis, the researchers aimed to gather more specific and relevant data. This approach allows for a more targeted analysis and interpretation of the findings, potentially leading to more accurate conclusions and the development of better strategies for managing SIC.
The findings from this study suggested that a higher RDW(>15.7%) was significantly correlated with increased ICU mortality rates among patients with SIC. Notably, this association remained statistically significant even after adjusting for potential confounding risk factors. Consequently, these results indicated that the high RDW holds promise as a valuable decision-making tool for clinicians and may serve as an independent prognostic factor.
Inflammatory states have a strong association with ineffective erythropoiesis. Previous studies have shown that inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, reduce the sensitivity of bone marrow erythroid progenitors to erythropoiesis[26]. Additionally, these cytokines hinder the maturation of red blood cells (RBCs), leading to an increase in anisocytosis. Falk and Fahey conducted a study showing that sepsis has a negative impact on the functions of the hematopoietic system. They also found that sepsis leads to an increase in erythrocyte heterogeneity[27]. This suggested that inflammation plays a significant role in disrupting normal erythropoiesis and promoting abnormal RBC development[28].
In our study, high RDW was independently associated with 28-day mortality, with a prevalence of 25.2% in patients with SIC(after PSM). Among the 6 selected variables, RDW accounted for the largest weight in the simplified model (HR=3.3; 95% CI, 2.30–4.70). Our study also found that administration of β-blocker was associated with lower risk of 28-day mortality (HR = 0.25, 95%CI: 0.2–0.3, P<0.001). This demonstrated the importance of early use of β-blockers in patients with sepsis to improve cardiac function.
The survival curve demonstrated that patients with high-level RDW have a lower 28-day survival rate compared to those with low-level RDW. This suggested that the detection of RDW is highly valuable in clinically assessing severity among patients with SIC. It is speculated that this phenomenon is attributed to the release of various neuroendocrine hormones following infection, which stimulates the synthesis of erythropoietin[29]. Consequently, there is a significant proliferation of red blood cells and an increase in RDW which, in turn, leads to cell membrane instability and a lack of nutrients in the blood, ultimately resulting in multiple organ dysfunction[30]. It's worth noting, Gong et al found that it was not the baseline RDW had a significant relationship with mortality, but the change in RDW over time might be a more reliable indicator of prognosis in sepsis patients[31]. Further research is needed to investigate the underlying mechanisms and potential clinical implications of these findings.
However, it is important to acknowledge certain limitations of this study. One limitation is the presence of selection bias due to its retrospective cohort study design. This means that the researchers relied on pre-existing data and medical records, which can introduce errors and biases. Another limitation is the potential effect of unadjusted potential confounders on the results. Despite efforts to match participants and control for variables, there may still be factors that were not taken into account. Furthermore, it is important to note that this study did not evaluate the long-term outcomes of the patients. Therefore, it is crucial to keep caution when extrapolating these findings as a predictive factor for long-term prognosis. Future research should consider assessing long-term outcomes to obtain a more comprehensive understanding of the subject matter.