The pathophysiological impact of CA on systemic internal environment homeostasis is complex and evolves throughout the resuscitation process[16]. This retrospective analysis of 270 CA patients revealed distinct characteristics in their blood internal environment before cardiac arrest, during CPR, and after ROSC. Further analysis of blood parameters during resuscitation showed that, compared to the non-ROSC group, the ROSC group had higher levels of WBC, neutrophils, lymphocytes, platelets, and PO2, while INR, D-dimer, and BE were lower. WBC, D-dimer, and PO2 were identified as independent factors influencing ROSC in CA patients.
The specific extent of damage caused by CA depends on the patient’s baseline organ function, the etiology of CA, and the duration of ischemia without reperfusion[17]. During CA, the body is in a state of complete ischemia and hypoxia with severe shock, where the transport of oxygen, glucose, and other metabolic substrates is blocked, leading to mitochondrial anaerobic metabolism and dysfunction of the electron transport chain. The reduced ATP production causes energy-dependent ion channels to cease functioning, resulting in sodium, potassium, and calcium ion retention, cellular edema, and decreased cytoplasmic enzyme activation[18–19]. As the duration of CA increases and hypoxia worsens, anaerobic metabolism produces excessive lactic acid, exacerbating metabolic acidosis. Inadequate ventilation can further lead to respiratory acidosis, with increased PCO2 and lactic acid levels, while PH and PO2 decrease. Patients in prolonged low blood flow or hypoperfusion states result massive production, release, and activated infiltration of inflammatory mediators, leading to widespread activation of the inflammatory response, eventually the development of systemic inflammatory response syndrome (SIRS). This induces vascular dysregulation, endothelial cell activation and injury, triggering a cascade of reperfusion-related damage. These effects manifest as microcirculatory dysfunction, increased vascular permeability, activation of leukocytes and platelets, activation of the coagulation pathway, and reduced fibrinolytic activity. This promotes microvascular thrombosis, leading to coagulation-fibrinolysis imbalance, and results in the progression of disseminated intravascular coagulation (DIC). As the condition worsens, tissue and organ no-reflow phenomena occur, exacerbating myocardial injury and multi-organ dysfunction, including liver, kidney, and brain damage[20–22]. Elevated levels of CN-T, CK, ALT, and AST are observed, increasing the patient’s risk of mortality. Although some patients exhibit normalized hemodynamic and respiratory parameters after early ROSC, acidosis and organ hypoperfusion often persist. In patients who fail to achieve ROSC or those with prolonged no-flow or low-flow periods, thrombin levels are higher compared to survivors and patients with shorter hypoperfusion durations[23–24], consistent with the findings of this study.
Previous studies[25] have investigated the association between pre-CA blood laboratory results and the risk of in-hospital cardiac arrest (IHCA), suggesting that rapid changes in the blood internal environment can serve as predictors of CA. Early monitoring and intervention could help reduce and prevent CA occurrences. Some researchers[26] have even developed predictive models for IHCA based on blood markers, although the findings are not always consistent. Certain specific blood internal environment indicators, such as lactate and potassium, can reflect the severity of the disease and may appear before clinical deterioration[27]. Our findings also indicate that disruptions in the body's internal environment occur before CA, manifesting as abnormal physiological and pathological states, such as acidosis and inflammation. Some markers, such as CN-T and BNP, were significantly elevated, even reaching critical levels.
However, not all patients exhibited significant changes in blood internal environment indicators prior to CA, and the cause and timing of CA are often unpredictable. Approximately two-thirds of patients lacked blood results before CA, so we further analyzed the blood samples collected during resuscitation. The results showed that WBC, D-dimer, and PO2 could serve as predictive indicators for ROSC, although the predictive efficacy of D-dimer was relatively low. One possible reason is that, due to the limitations of detection levels, the D-dimer values for some patients exceeded the measurement range, and we analyzed these values using the maximum detectable limits, which may have introduced some data bias. The primary goal of CPR is to restore spontaneous circulation and ensure adequate blood and oxygen supply to the body. Studies have shown that CA and resuscitation trigger widespread activation of non-specific systemic inflammation, with surviving patients exhibiting higher levels of neutrophils and lymphocytes compared to non-survivors[28–29]. Additionally, during CPR, hypoxic patients had lower survival rates compared to those who received normal or high oxygen levels[30], which is consistent with our findings. Currently, there is no unified international strategy for optimal ventilation during CA. Clinically, 100% oxygen is recommended to prevent hypoxia and reduce severe fluctuations in PaCO2[31]. However, excessive oxygen therapy and hyperventilation during and after resuscitation are common, and both hyperoxemia and hypercapnia have been associated with poor outcomes[32]. Research suggests that hyperoxia following ischemia/reperfusion injury may predict increased oxidative stress, myocardial injury, and inflammation[33]. Post-cardiac arrest ventilation with pure oxygen has been shown to result in worse neurological function scores and more severe brain injury[34]. After successful resuscitation and ROSC, it is equally important to maintain appropriate arterial oxygen and carbon dioxide levels to avoid further hypoxia and secondary injuries.
Blood biomarkers have decisive significance in clinical practice. Currently, interventions during the period of CA are often empirical, lacking guidance from patient-specific data. Blood analysis during CA remains extremely rare, especially in OHCA patients. Most studies focus on blood results obtained after ROSC or once the patient’s vital signs have stabilized. In some cases, the timing of blood sampling is overlooked, and there is a lack of standardized processes for collection, storage, analysis, and grouping of blood samples[12]. The collection of blood samples from CA patients is a challenge faced globally by clinicians, influenced by patient condition, environment, and physician decision-making. There are no standardized guidelines for the timing, frequency, or specific parameters of blood sampling in CA patients. Research[36] indicates that 87.7% of IHCA patients have at least one blood test within 24 hours of hospital admission, and 11.8% have more than three blood samples taken. Given the variability and challenges, relying solely on a single laboratory marker to predict CA occurrence and prognosis remains controversial and difficult. A multi-marker approach offers better predictive performance and provides a more comprehensive reflection of the patient’s overall condition. Therefore, in the future, a series of rigorous and relevant clinical studies are needed to clarify the status and dynamic changes of physiological internal environment indicators before and after resuscitation. The goal is to identify the optimal physiological ranges to fine-tune the resuscitation process, guide resuscitation management, improve blood-related therapies, and aid in decisions regarding medication, ventilation, and continued resuscitation. These efforts will ultimately enhance the success rate of CPR and improve the long-term post-resuscitation care of patients.
As a single-center retrospective study, our research has certain limitations. First, the small sample size may introduce some bias into the results. We analyzed routine and readily available blood laboratory tests in the emergency department, but due to the special nature of CA patients and clinical practice, the baseline levels of patients across different groups were not entirely consistent. Despite this, the results still reflect the characteristics and changes in the blood internal environment during resuscitation, providing some reference value. We must carefully consider whether these differences represent normal physiological and pathological changes during the resuscitation of CA patients, as this directly influences clinical decision-making. In the future, high-quality scientific research with larger sample sizes is necessary to clarify the dynamic changes in the blood internal environment of CA patients, continuously improving the entire process of physiological monitoring during cardiopulmonary resuscitation.