Sepsis is the dysfunction of an organ resulting from an infection induced by the pathogen’s disease (Evans et al., 2021). Every year, approximately 48 million patients worldwide are diagnosed with sepsis, which is responsible for as many as 11 million deaths; sepsis has emerged as the primary cause of death among critically ill patients (Rudd et al., 2020). In the past two decades, sepsis mortality has decreased progressively due to the prompt administration of antibiotics, fluids for resuscitation, and multiple organ support therapies. Still substantial mortality exists, and there is scope for enhancement (Seymour et al., 2019; Kempker and Martin, 2020; Fleischmann-Struzek et al., 2020). Survivors of sepsis who are readmitted to the intensive care unit experience substantial functional impairment and a decline in their quality of life (Cheung et al., 2006). Both conditions impose substantial personal and financial burdens on families and society due to the necessity for personal care expenses and employment loss (Rudd et al., 2020; GBD, 2016 Causes of Death Collaborators, 2017).

Despite the progress made in the field of critical care, the fundamental aspects of sepsis management continue to revolve around organ support and infection control (Dellinger et al., 2012). The investigation of the correlation between thrombus, inflammation, and platelets, as well as the potential therapeutic advantages of antiplatelet medications in sepsis, has emerged as a prominent subject of scholarly inquiry (Toner et al., 2015). Acetylsalicylic acid (ASA), often known as aspirin, is a medication that shows promise in treating sepsis. Aspirin exhibits anti-inflammatory and antiplatelet properties, and has been suggested as a potential antisepsis drug due to its direct inhibition of bacterial growth (Menter and Bresalier, 2023; Van Oosterom et al., 2022; Patrono, 2023). The clinical evidence on the efficacy of aspirin in sepsis is inconclusive. Aspirin has been observed to decrease serum levels of inflammatory markers, sepsis-related multiorgan failure (MOF), and mortality in clinical investigations (Hsu et al., 2022; Boyle et al., 2015). A comprehensive cohort research employing propensity-matched design revealed a significant association between prehospital antiplatelet medication and reduced fatality rates (Chow et al., 2022). One randomized clinical investigation, however, revealed that the utilization of aspirin, in comparison to a placebo, did not result in a reduction in the likelihood of developing acute respiratory distress syndrome (ARDS) (Kor et al., 2016). The study’s findings may be constrained by a restricted sample size and may be influenced by uncontrolled confounding variables, such as pre-existing problems, additional life support interventions, and the timing of aspirin administration.

Propensity score matching (PSM) approaches are employed in order to mitigate the influence of sample selection bias and replicate the randomization process (Ryan, 2021; Narduzzi et al., 2014; Austin and Stuart, 2015). The objective of this study is to ascertain whether the early utilization of aspirin is a standalone indicator of mortality in individuals with sepsis. The current study utilized the PSM to examine the influence of early aspirin administration on the 90-day mortality of patients with sepsis.

The main aim of this study was to assess the potential association between early treatment of aspirin and enhanced survival outcomes in individuals with sepsis. The justification for investigating aspirin as a novel therapeutic intervention arises from its extensively documented anti-inflammatory and antiplatelet characteristics. In the present study, it was observed that those who were administered aspirin during the initial phases of sepsis demonstrated a notably reduced mortality rate during a 90-day period in comparison to those who did not get aspirin. This observation necessitates additional examination of the potential of aspirin in alleviating the systemic ramifications of sepsis. The results of our study provide valuable insights that contribute to the continuing scholarly conversation on the management of sepsis.

Previous research examining the impact of aspirin on the vulnerability to sepsis and its resulting effects has yielded diverse findings. Using a nested cohort study, Al Harbi, et al. found that aspirin use in ICU patients was associated with increased rates of severe sepsis and length of stay (Al Harbi et al., 2016). The findings of a population-based cohort analysis indicate that there is no significant association between baseline aspirin use and long-term incidence of sepsis (Hsu et al., 2018). In a retrospective population-based cohort analysis, it was observed that the administration of aspirin before to hospital admission is linked to a decreased mortality rate within a 90-day period among patients diagnosed with sepsis (Hsu et al., 2022). These findings align with the outcomes of our research. Our data differed from previous research in that they were not restricted to ICU admission and encompassed data on various baseline participant characteristics. After accounting for demographics and chronic medical disorders, we saw that the strongest reduction in the connection between early aspirin usage and 90-day mortality occurred. This indicates that aspirin use could potentially serve as an indicator of the burden of other medical conditions.

The correlation established between the early initiation of aspirin usage and a decrease in mortality rates presents thought-provoking inquiries on the fundamental mechanisms involved. However, the precise role of aspirin in sepsis remains uncertain, particularly with respect to the dosage and the reasons for its prescription. The vast majority of sepsis patients in this study received low-dose aspirin (e.g., 75 mg per day), which is commonly used for secondary prevention post-myocardial infarction (MI), primarily acting by inhibiting platelet cyclooxygenase (COX-1), which reduces platelet aggregation. This mechanism may offer a plausible explanation for its potential benefit in sepsis, given the recognized role of platelets in the pathogenesis of sepsis-related thrombosis and microvascular dysfunction (Cox, 2023; Yang et al., 2023). Moreover, while anti-platelet agents are not a cure for sepsis, they have shown promise in stabilizing patients by preventing progression to disseminated intravascular coagulation (DIC). This can provide clinicians with valuable time to address the underlying infection, particularly in cases where sepsis is culture-negative, a scenario in which antibiotics may be ineffective in the absence of an identified pathogen. Sepsis is known to induce endothelial dysfunction, leading to vascular leakage and contributing to organ failure (Joffre et al., 2020; Zhang et al., 2023). In this context, the potential protective effects of aspirin on the endothelium have been proposed (Dzeshka et al., 2016; Liu et al., 2023). By modulating the balance between vasoconstrictive and vasodilatory chemicals, aspirin may help preserve endothelial integrity, potentially counteracting the vascular damage seen in sepsis. Furthermore, The immunomodulatory effects of aspirin have been demonstrated, encompassing the modification of immune cell function (Schieffer and Drexler, 2003). This has the potential to impact the equilibrium between pro-inflammatory and anti-inflammatory reactions in sepsis, thereby promoting a more regulated and harmonious immune response.

Despite the importance of our findings, several limitations should be acknowledged. First, the retrospective nature of the study design introduces potential selection bias, although we employed the PSM approach to mitigate this. Additionally, we lacked information on whether patients were on aspirin prior to admission and the specific reasons for its use, which limits our understanding of its mechanisms in sepsis outcomes. Future research should focus on prospectively documenting patients’ medication history, including aspirin use and the clinical indications for its prescription, to better assess its impact on disease progression and treatment outcomes. Furthermore, since our study is based on an observational database, the findings should be interpreted as preliminary. Therefore, future prospective studies, particularly randomized controlled trials comparing aspirin with a placebo in sepsis patients, are necessary to more conclusively determine the causal relationship between aspirin use and mortality.

In conclusion, early aspirin use was associated with decreased 90-day mortality in septic patients, emphasizing the significance of early aspirin use strategy in the ICU.