Cardiac arrest (CA), defined as the sudden cessation of the myocardium, leads to the interruption of blood circulation in the whole body, and then, progresses to sudden cardiac death. CA is a primary public health problem, with high levels of morbidity and mortality worldwide [1, 2]. In recent years, the management and treatment of post-CA patients has made progress, yet the overall prognosis is still poor due to the onset of pathological changes, such as severe systemic ischemia hypoxia–reperfusion injury [3], systemic inflammation response, and multiple organ dysfunction [4]. In the intensive care unit (ICU), about 0.5 percent to 5 percent of critically ill patients will experience a CA, and although approximately 50 percent will recover spontaneous circulation, only 15 percent survive until hospital discharge [5]. Therefore, it is of great significance to further strengthen and carry out research concerning CA.

Lactate dehydrogenase (LDH), a marker of tissue and organ hypoperfusion, is a key enzyme in glycolysis, by catalyzing the transformation of pyruvate to lactate. Elevated LDH levels in critically ill patients have been reported in the literature to indicate a poor outcome [6, 7]. Albumin is synthesized by the liver and has important physiological functions, such as anti-inflammatory and antioxidant activities, scavenging free radicals, and maintaining plasma osmolality. When the body is infected or hit, the consumption of albumin increases, and studies have shown that lower albumin levels are associated with increased mortality in patients with various diseases [8, 9, 10]. In addition, multiple studies have shown that elevated LDH and decreased albumin levels are associated with poor outcomes in CA patients [10, 11, 12]. The lactate dehydrogenase to albumin ratio (LAR) is a novel disease prognostic marker, which reflects the balance between LDH and albumin. Previous research has revealed that the LAR provides a high predictive effect for disease severity and poor prognosis in tumors [13], pneumonia [14], sepsis [15], and other diseases.

However, to date, no reports have linked the LAR to the prognosis of CA patients. Therefore, we investigated whether there was an association between the LAR levels at ICU admission and mortality in CA patients, to determine a simple and effective prognostic indicator to guide the clinical management of these patients.

Based on the fact that high LDH and low albumin levels are associated with poor prognosis in CA patients, this study investigated the effects of using the LAR on the prognosis of patients after a CA. In our research, the LAR was higher in the non-survivors than in the survivors. The all-cause mortality risk during ICU hospitalization and 30 days increased accordingly as the LAR increased. The cumulative survival rates during ICU hospitalization and 30 days were lower in the high LAR group (p 0.001). Furthermore, elevated LAR ($\ge$15.50) was an independent risk factor for all-cause mortality during ICU hospitalization and 30 days (p 0.005). The results may help to identify high-risk patients and assist with their clinical management.

CA is a global health problem. Thus, assessing the prognosis of patients with CA is a very complex task that requires a comprehensive judgment based on clinical, biochemical, neurophysiological, and imaging studies [17]. However, the detection of relative serological indicators is expensive, time-consuming, and difficult to promote in clinical practice. As a new disease prognostic marker, the LAR is easy to obtain, low in cost, strong in applicability, and easy to apply in clinical practice. Recently, several studies have shown that a high LAR was associated with increased mortality in many critical illnesses. A study found that the LAR was an independent prognostic indicator for patients with nasopharyngeal carcinoma, which was more predictive than using LDH or albumin and more accurate than the current staging system for nasopharyngeal carcinoma [13]. Meanwhile, Jeon found that the LAR could predict in-hospital mortality earlier in critical infection patients (odds ratio (OR) = 1.001, 95% CI: 1.000–1.002) [15]. In addition, the LAR serves as a new index to measure systemic inflammation and nutritional status, whereby a higher LAR ($\ge$5.93) was correlated with the occurrence of cognitive dysfunction after ischemic stroke (OR = 2.003, 95% CI: 1.305–3.074) [18]. However, the LAR is rarely reported in CA patients. Therefore, we analyzed the association between the LAR and the prognosis of patients after a CA and confirmed that an elevated LAR could be used to predict short-term mortality risk.

The mechanism of the association between the LAR and poor prognosis in patients after a CA has not been fully elucidated. However, it is well known that systemic ischemia–hypoxic reperfusion injury is the link between the occurrence and development of post-CA patients [19, 20]. LDH is a cytoplasmic enzyme that is expressed in blood cells, the heart, the brain, muscle, and other body tissues. It is one of the key enzymes in the glycolysis pathway and converts pyruvate into lactic acid during hypoxic injury [21]. LDH is rapidly released into the peripheral blood after tissue cell ischemia–hypoxia injury and is a useful biomarker of cell damage [22]. Park et al. [6] showed that at each time point after post-cardiopulmonary resuscitation, the median LDH in the group with poor neurological prognosis was significantly higher than in the group with good neurological prognosis; thus, the inhibition of LDH was considered to have neuroprotective effects in ischemic stroke [23]. Human serum albumin has anti-inflammatory properties and protective effects in reducing ischemia–reperfusion injury [24]. Systemic ischemia–hypoxia–reperfusion injuries after CA resuscitation produce a variety of endotoxins and free radicals, while albumin can act as a scavenger for oxygen free radicals and reactive nitrogen through its binding and transport capacity to reduce organ damage [25]. In addition, albumin levels are a biochemical indicator of nutritional status, and malnutrition is considered to be one of the factors associated with a poor prognosis in seriously ill patients [26]. Several studies have shown that decreased albumin levels after cardiopulmonary resuscitation were independently associated with increased mortality [10, 12, 27].

The LAR reflects the ratio of LDH to albumin in peripheral blood, whereby an increase in the LAR is related to an increase in LDH or (and) a relative decrease in albumin, thereby indicating that the body is in an imbalanced state, which can simultaneously reflect tissue ischemia, hypoxia, and nutritional status. This may be more informative than the predictive value of LDH or albumin alone [28]. Our study showed that an elevated LAR might be linked to short-term mortality in CA patients and could be used as a supplementary prognostic factor. However, the specific mechanism needs further study.

The SOFA score has been successfully applied to assess the severity and predict the prognosis of critically ill patients. A study of 231 out-of-hospital CA patients with the return of spontaneous circulation found that an elevated SOFA score on admission was an independent predictor of 30-day all-cause mortality and poor neurological prognosis (OR = 0.68, 95% CI: 0.50–0.79; OR = 0.79, 95% CI: 0.69–0.90) [29]. This study compared the predictive efficacy of the LAR and SOFA score using the ROC curve and found that the LAR (AUC = 0.676, 95% CI: 0.629–0.723) was slightly better than the SOFA score (AUC = 0.619, 95% CI: 0.570–0.668). However, the evaluation of the SOFA score is complicated and difficult to obtain in real-time, while the LAR is simple to obtain clinically. Therefore, the LAR can be used as a predictive indicator for the prognosis of patients after a CA. The LAR, as a prognostic biomarker, can help identify high-risk patients and help clinicians make medical decisions to improve outcomes.

Based on the MIMIC database, this is a big sample study that reflects the real clinical world, while it might also be the first to evaluate the link between the LAR and the prognosis of CA patients. However, there were some limitations: First, this study was a single-center retrospective observational study, meaning several of the important prognostic indicators, such as cerebral performance category (CPC) and witnesses of CA were not available in the MIMIC database; thus, the introduction of potential bias was difficult to avoid. Second, the MIMIC-IV database does not provide data that distinguishes between in-hospital and out-of-hospital CA patients, meaning our study did not distinguish between these two populations. Furthermore, this paper only studied the LAR data at the time of admission to the ICU and did not dynamically observe the impact of the LAR levels on the mortality of patients after a CA, therefore, future studies are needed to verify our results. Finally, some comorbidities, such as cirrhosis, malignancy, and other confounding factors, may affect the results. To verify the reliability of our findings, we performed several sensitivity analyses and found that the findings were reliable. However, these findings are exploratory and multicenter prospective studies need to be designed to evaluate and confirm these data.

Elevated LAR ($\ge$15.50) was a predictor of mortality in patients during ICU hospitalization and 30 days after a CA. It has strong clinical practicability and can assist clinicians in evaluating the prognosis of patients after a CA.

CA, cardiac arrest; ICU, intensive care unit; LAR, lactate dehydrogenase to albumin ratio; MIMIC, Medical Information Mart for Intensive Care; RCS, restricted cubic splines; ROC, receiver operating characteristic curve; AUC, area under the curve; SOFA, sequential organ failure assessment; LDH, lactate dehydrogenase; WBC, white blood cell; HB, hemoglobin; PLT, platelet; TBI, total bilirubin; CRE, creatinine; RDW, red cell distribution width; PO${}_2$, oxygen partial pressure; ALT, alanine transaminase; AST, aspartate aminotransferase; BUN, blood urea nitrogen; PT, prothrombin time; MV, mechanical ventilation; CRRT, continuous renal replacement therapy; AMI, acute myocardial infarction; AKI, acute kidney injury; VF, ventricular fibrillation; IABP, intra-aortic balloon pump.

The data that support the findings of this study are available from MIMIC-IV (https://mimic-iv.mit.edu) database but restrictions apply to the availability of these data, which were used under license for the current study, and are not publicly available. However, data are available from the MIMIC-IV dataset with permission of Massachusetts Institute of Technology (MIT) and Beth Israel Deaconess Medical Center (BIDMC).

JFX, LLY, MY, JM and JHL conceived, designed the study, read and revised the manuscript. JFX, LLY and MY wrote the manuscript. LLY and LZ collected, managed, analyzed data and provided constructive suggestions for revision of the manuscript. All authors contributed to editorial changes in the manuscript. All authors have read and approved the final manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work.

MIMIC-IV is an anonymized public database. To apply for access to the database, two of the authors passed the Protecting Human Research Participants exam (No. 36142713, 51832843). The project was approved by the institutional review boards of the Massachusetts Institute of Technology (MIT) and Beth Israel Deaconess Medical Center (BIDMC) and was given a waiver of informed consent. All methods were carried out in accordance with the institutional guidelines and regulations and with the 2002 Helsinki declaration and its later amendments or comparable ethical standards.

Not applicable.

This work was supported by the Science and Technology Program of Huzhou [2022GY20].

The authors declare no conflict of interest.