This case-control study included a total of 85 IHCA patients and retrospectively analyzed demographics, clinical characteristics and relevant laboratory indicators within 72 h after ROSC. The results of the linear mixed model showed that within 72 h after ROSC, inflammatory markers showed different patterns: the AMC showed no significant change trend, the ALC showed an overall upward trend, and the ANC, WBC, PLT, NLR, PLR and SII showed an overall downward trend. After adjusting for confounding variables by Cox multivariate regression, PLR within 72 h after ROSC was an independent risk factor for 30-day mortality in IHCA patients. When PLR ≥ 180, the risk of 30-day mortality of IHCA patients increased by 199.3% (HR = 2.993, 95% CI (1.442, 6.214)). The inflammatory biomarker PLR can be used as a predictor of 30-day mortality in IHCA patients with ROSC, and it can be a reference for early prognostication.
Early organ failure is a main cause of short-term mortality in IHCA patients, and its potential pathological process is the development of PCAS. In particular, the comprehensive activation of the immune system and coagulation pathway within 72 h can lead to coagulation disorders and multiorgan failure and eventually to the death of patients. Many studies have pointed out that the systemic inflammatory response plays an important role in the pathophysiological development of early PCAS and affects the prognosis of IHCA patients [6, 12]. Neutrophils are early determinants of the development of the systemic inflammatory response. Whole-body ischemia and reperfusion during CPR can activate neutrophils to release inflammatory mediators, such as elastase and heparin binding protein, which can lead to inflammatory tissue damage and therefore affect the prognosis of patients [21, 22]. Villois et al. [23] reported that a low ALC on admission is an independent predictor of poor prognosis in OHCA patients. In a large retrospective cohort study of > 1,000 OHCA patients, Weiser et al. [24] further showed that NLR on admission was a predictor of long-term mortality of patients with cardiogenic OHCA. OHCA patients with NLR ≥ 6 had a higher risk of mortality. Additionally, PLTs have been proven to play an important immune role in the systemic inflammatory response and have an important impact on the prognosis of patients [20, 25]. Kim et al. [26] identified that a continuously decreased PLT count within 7 days is associated with a poor neurologic outcome and mortality at 6 months. Therefore, the early dynamic changes in routine inflammatory markers may reflect the immunopathological process of PCAS, which is closely related to the prognosis of cardiac arrest. Therefore, these dynamic changes could be used as an important index for prognosis assessment.
This study analyzed the dynamic changes of inflammatory markers within 72 h after ROSC in 85 IHCA patients, and found that the AMC trend did not significantly change, the ALC showed an overall upward trend, and the ANC, WBC count, PLT count, NLR, PLR and SII showed an overall downward trend; in addition, the PLR and SII tended to be stable with time. Kim et al. [26] found that in OHCA patients treated with targeted temperature management, the PLT count continuously decreased within 72 h after cardiac arrest. Many recent studies on sepsis and other severe diseases [27–29] have shown that the NLR, PLR and SII can continue to decrease in the early stage of disease, which is consistent with the conclusion of our study. However, Ryzhov et al. [30] showed that the AMC increases briefly within 6 h after ROSC, the ALC shows a persistent decrease 6–72 h after ROSC, and the ANC and WBC count increase significantly within 48 h and 72–168 h after ROSC. These findings are inconsistent with the results of our study. First, these discrepancies can be explained by the heterogeneity of the study population; 80% of the patients had OHCA in Ryzhov’s study [30], while the target population of our study was IHCA patients. In addition, the use of drugs in the early stage after cardiac arrest may affect the dynamic changes of related indicators; for example, corticosteroids can lead to lymphopenia after cardiac arrest [23]. Therefore, our study excluded patients using immunosuppressants, and these controversial results still need further verification.
Through analysis of the association of inflammatory markers within 72 h with prognosis, this study further found that only the PLR was associated with 30-day mortality. The PLR can be quickly calculated by obtaining the PLT count and ALC from routine clinical blood examinations. The PLR reveals changes in both the PLT count and the ALC caused by acute inflammation and a prethrombotic state. As a novel, simple and inexpensive routine composite inflammatory marker, the PLR has been proven to have value for predicting the prognosis of various disorders in recent years [31, 32]. A study on dynamic changes in the PLR in breast cancer patients identified that patients with a persistently low PLR after initial treatment have a significantly better prognosis in terms of late metastasis than other patients [31]. Shen et al. [33] showed that a high PLR on admission (PLR > 200) was significantly associated with increased mortality in patients with sepsis (OR = 1.0002, 95% CI [1.0001–1.0004]). Additionally, studies have also shown that a high PLR can be used to predict poor prognosis in relation to cardiovascular events [34]. In this study, when PLR ≥ 180, the risk of 30-day mortality of IHCA patients increased by 199.3% (HR = 2.993, 95% CI (1.442, 6.214)). The reason for this pattern may be that PLTs play an important role in both the immunomodulatory and inflammatory processes in IHCA patients. They can contribute to the initiation or exacerbation of the inflammatory process by inducing the release of inflammatory cytokines and interacting with different kinds of bacteria and immune cells, including neutrophils, T lymphocytes, natural killer cells and macrophages. Higher PLT counts, to a certain extent, are associated with increased systemic inflammation [25], and a low ALC may represent a suppressed immune and inflammatory response [28, 35]. Therefore, a higher PLR reflects a more severe systemic inflammatory immune response in IHCA patients, which is closely related to the development of PCAS and death.
We acknowledge several limitations in our study. 1. This study is a single-center retrospective case-control study, and the sample size is relatively small, so it is necessary to verify the conclusions in a prospective study with an expanded sample size. 2. Since 0–72 h after ROSC is an important period for determining the prognosis of patients, we focused on the association of the dynamic changes in inflammatory markers in this period with the 30-day mortality of IHCA patients to identify routine inflammatory markers that can predict prognosis early. However, according to the results of our study, the median survival time of patients was 13 days, so future studies should include routine inflammatory marker data after 72 h to provide a clearer picture of the progression of PCAS and the association of the change trends of inflammatory markers with mortality. 3. This study didn’t conduct combined analysis of inflammatory markers. In a future study, we will combine related inflammatory markers, such as the PLR and NLR, to further explore the relationship between the severity of inflammation and the mortality of IHCA patients.