Stress hyperglycemia (SHG) refers to a temporary increase in blood glucose levels under high-stress conditions, such as major trauma, severe infection, or cardiovascular incidents, in patients with no prior history of diabetes [1, 2]. According to the American Diabetes Association (ADA) consensus, SHG is defined as a fasting blood glucose level $\ge$7.0 mmol/L or random blood glucose values $\ge$11.1 mmol/L on two or more occasions [3]. The common complications of cardiac surgery include SHG [2], pulmonary infection [4], anemia [5], ischemic cerebrovascular disease [6], postoperative neurocognitive dysfunction [7], arrhythmias [8], and seizures [9]. The incidence of SHG post-cardiac surgery is approximately 75%. Hyperglycemia is prevalent among postoperative cardiac patients, with early postoperative peak blood glucose levels persisting for an extended period, adversely affecting prognosis. Furthermore, the occurrence of SHG can lead to osmotic diuresis, causing disturbances in water, electrolytes, and acid-base balance, thereby posing a threat to the health of cardiac surgery patients [10]. Although studies [11, 12] have investigated risk factors for SHG in patients without diabetes after cardiac surgery, the inconsistency in the factors included in these studies necessitates a comprehensive analysis to minimize potential biases from different research methodologies and measurement tools. This study aimed to investigate risk factors for SHG in patients without diabetes after cardiac surgery through a literature review and meta-analysis. Currently, research on SHG in patients without diabetes undergoing cardiac surgery is largely limited to analyzing the influencing factors. The innovation of this study lies in its focus on patients without diabetes, an area often overlooked in research, as most studies primarily address postoperative glycemic management in diabetic patients. The risk and impact of SHG in patients without diabetes following surgery are frequently underestimated. Research [13] has shown that perioperative stress hyperglycemia in cardiac surgery not only increases the incidence of postoperative complications and adverse cardiac events but also prolongs intensive care unit (ICU) stays, extends total hospitalization time, and increases postoperative mortality rates. However, no comprehensive systematic review or meta-analysis has specifically addressed SHG in patients without diabetes after cardiac surgery. This study provides a more comprehensive exploration through a systematic review and meta-analysis, incorporating rigorous evidence-based methods. By searching relevant databases and conducting a strict quality assessment of the literature, this study synthesized and interpreted the findings. It not only offers guidance for clinical practice but also provides evidence to support early perioperative interventions and supportive treatments and enables clinicians to more accurately identify high-risk patients during perioperative evaluations in cardiac surgery. By uncovering the complexity of various influencing factors, this systematic review and meta-analysis emphasized the importance of multidisciplinary collaboration in postoperative management. These research findings encourage cardiac surgeons, endocrinologists, and anesthesiologists to work together to create and implement perioperative management plans, ultimately improving overall patient outcomes.

Patients in the SHG group were more likely to be over 65 years old than those in the non-SHG group, making age an independent risk factor for SHG after cardiac surgery, which aligns with the findings of Xie Huihui [24]. This study showed a significant association between age and SHG in non-diabetic patients after cardiac surgery, with the severity of SHG increasing with age [25]. Elderly patients often have weakened immune responses and poorer stress responses due to underlying conditions and declining organ function; however, the impact of sex on stress hyperglycemia remains controversial. This study found that female sex is a relevant risk factor for SHG in non-diabetic patients after cardiac surgery, suggesting that older women with poorer cardiac function are more prone to SHG. The release of stress hormones and insulin resistance in response to surgical stress can lead to SHG. Although the mechanism related to female hormones requires further investigation, this study underscores the importance of early prediction and management of SHG in female patients during the perioperative period [26, 27]. Research by ME Ertorer et al. [28] on 494 ICU patients with coronary artery disease confirmed sex differences in SHG. Sharma et al. [29] also demonstrated a sex-related association with SHG levels. Stress conditions prolong the elevation of hormone levels, contributing to SHG in patients without diabetes post-cardiac surgery. The traumatic nature of surgery, particularly complex procedures like combined valve and coronary artery bypass surgeries, increases the risk of SHG compared to standard cardiac surgeries [30]. Patients with a history of cardiac surgery often experience physiological and metabolic changes, including SHG, consistent with the results of Christos Kourek et al. [31]. In patients with a history of heart surgery [32], unique cardiovascular characteristics lead to a more pronounced response to SHG risk factors. Reduced ejection fraction is a significant risk factor for SHG, as declining cardiac function leads to decreased myocardial contractility, a sharp drop in cardiac output, worsening microcirculation, and further exacerbation of myocardial injury, which is consistent with the findings of Stalikas N et al. [33]. This meta-analysis also identified hypertension as a risk factor for SHG in patients post-cardiac surgery. Izzo R et al. [34] and Conen D [35] found that at admission, systolic blood pressure is an independent risk factor for SHG. Retrospective studies [29] have shown that prehypertensive individuals have higher fasting blood glucose levels than those with ideal blood pressure, indicating that while abnormal blood pressure may not directly cause glucose abnormalities, it does affect blood glucose levels. A study [36] has shown that effective blood pressure control in hypertensive patients helps reduce the incidence of stress-induced hyperglycemia and the development of new-onset diabetes. These mechanisms include hypertension and significant fluctuations in blood pressure, which lead to insulin resistance, sympathetic nervous system activation, Renin-angiotensin-aldosterone system (RAAS) activation, oxidative stress, and inflammation [17], ultimately resulting in stress-induced hyperglycemia [37]. After acute myocardial infarction, the sympathetic nervous system activation increases the levels of glucagon, growth hormones, glucocorticoids, and catecholamines. Research has shown that glucagon is a key factor in gluconeogenesis, promoting hepatic glycogen breakdown, and inducing hyperglycemia. These hormones and cytokines also have complex feedback mechanisms, such as tumor necrosis factor (TNF)-$\alpha$ accelerating gluconeogenesis by stimulating glucagon production [38]. Studies indicate that dyslipidemia affects oxidative stress, impairs $\beta$-cell function, and reduces insulin secretion, leading to elevated blood glucose levels [39], with similar findings by Xie Huihui [24] and Abbasi F et al. [40]. This study [41] found that preoperative anticoagulant use is closely related to postoperative SHG and is a significant risk factor for SHG, suggesting that patients in a hypercoagulable state or those taking long-term anticoagulants should have their coagulation function closely monitored to ensure normal blood glucose levels preoperatively. Irregular use of warfarin before surgery can lead to stress hyperglycemia and bleeding complications, with irregular warfarin use accounting for 75% of postoperative complications, highlighting its significant impact on SHG in patients without diabetes; extracorporeal circulation time greater than 2 hours [42] was identified as a risk factor for SHG in patients without diabetes. Hormonal secretion of glucagon, glucocorticoids, catecholamines, and growth hormones is affected during surgery, with a decrease in insulin secretion contributing to elevated blood glucose levels. SHG is common in patients undergoing cardiac surgery with extracorporeal circulation time and the likelihood of SHG increases with prolonged extracorporeal circulation time. Extracorporeal circulation increases glucose production, and a prolonged extracorporeal circulation time significantly increases surgical trauma and stress responses, promoting glycogen breakdown and gluconeogenesis. Exogenous glucocorticoids administered during surgery also contribute to perioperative hyperglycemia, making longer extracorporeal circulation times more likely to result in SHG [43, 44]. Low temperatures and high oxygen levels during extracorporeal circulation in cardiac surgery, promote catecholamine release, which inhibits insulin secretion and stimulates glucose production. Low temperatures can directly suppress insulin secretion, potentially causing hypokalemia, which exacerbates insulin resistance [45]. Some researchers believe that high oxygen levels increase hepatic receptor responsiveness to glucagon, thereby elevating blood glucose. Thus, cardiopulmonary bypass and extended bypass duration, low temperatures, and high oxygen states have increasingly pronounced effects on the body. The following criteria can be used to assess high-risk SHG patients after cardiac surgery: Clinical characteristics such as age $>$65 and gender: Age 65 is considered a threshold, as older patients tend to experience more significant blood glucose fluctuations [24]. Women are at a higher risk of developing stress hyperglycemia after cardiac surgery, possibly because of hormonal changes and differences in metabolic mechanisms [29]. Surgical type and preoperative condition: Combined valve and coronary artery bypass surgery intensifies the postoperative stress response [30]. A reduced ejection fraction indicates weakened heart function, making patients more susceptible to surgical stress, leading to a greater metabolic burden and impaired blood glucose regulation [33]. Patients with a history of cardiac surgery experience increased stress during repeat procedures [31], which increases the risk of SHG. A history of myocardial infarction [38], hyperlipidemia [37], and hypertension [34, 35] may contribute to postoperative metabolic disorders, making blood glucose control challenging. Perioperative anticoagulant use [41], cardiopulmonary bypass and bypass duration $>$2 hours [43, 44] can also be used as criteria to identify high-risk SHG patients after cardiac surgery, even in patients without diabetes. For patients with identified risk factors, healthcare professionals should implement the following measures during the perioperative period to adjust treatment plans and reduce the incidence of SHG, thereby enhancing the practicality of this study: Preoperative Assessment and Optimization: Conduct a comprehensive evaluation of the patient’s age, gender, type of cardiac surgery, history of cardiac surgery, fasting blood glucose, HbA1c, insulin resistance status, and baseline metabolic level. Preoperative Assessment and Optimization: Conduct a comprehensive evaluation of the patient’s cardiac function before surgery, optimize left ventricular function, and manage heart failure or other cardiac conditions. For patients with impaired cardiac function, preoperative pharmacological treatment may be administered, such as early monitoring and intervention by closely tracking perioperative blood glucose levels, especially in high-risk patients. Effective intraoperative and postoperative insulin management ensures effective insulin management during and after surgery to control blood glucose levels. Preoperative assessment and adjustment of anticoagulant therapy include tailoring the type and dosage of anticoagulant medications based on the patient’s specific circumstances, such as history of thromboembolism or bleeding risk. Use of medications that may cause fluctuations in blood glucose levels. Choosing the appropriate anticoagulants during the perioperative period. Managing Comorbidities: Patients with comorbid conditions such as myocardial infarction, dyslipidemia, and hypertension should be closely monitored. Surgical indicators were adjusted for these patients to ensure that they were within normal ranges before surgery. Extra attention should be paid postoperatively to prevent changes in the patient’s condition and complications. Preoperative blood pressure should be adjusted to normal or within the target range appropriate for surgery. Management During Extracorporeal Circulation: Blood glucose levels were regularly monitored before, during, and after circulation. Continuous infusion of short-acting insulin allows more flexible glucose control during extracorporeal circulation. Additionally, using low-temperature extracorporeal circulation techniques (such as mild or moderate hypothermia) can help reduce the metabolic rate and inflammatory responses; however, the limitations of this study include the variability in the types of studies included and the bias in the selection of risk factors across different studies. To improve the accuracy of the included literature and enhance the reliability of the findings, we applied strict inclusion and exclusion criteria, categorized the studies based on their type, and used different quality assessment tools to reduce bias and heterogeneity in the analysis. In cases where bias and heterogeneity arose from the included studies on risk factors, we employed a stepwise exclusion method to remove studies with high heterogeneity, thereby reducing its impact on the results. We also updated and expanded the literature database, incorporating studies in Chinese, English, non-English languages, and grey literature. In the future, we plan to collaborate with language experts or translation services and design studies in multicenter hospitals specializing in cardiac surgery and endocrinology. This will allow us to handle larger datasets and multilingual literature, ensuring the representativeness of case numbers and the reliability of the data.

Current evidence suggests that age $>$65 years, female gender, combined heart valve and coronary artery bypass surgery, ejection fraction40%, history of heart surgery, myocardial infarction, hyperlipidemia, hypertension, anticoagulant medication, cardiopulmonary bypass time $>$2 hours and history of cardiopulmonary bypass are key risk factors for postoperative stress hyperglycemia in patients without diabetes who have undergone cardiac surgery. These factors can help identify patients at a high risk of perioperative stress hyperglycemia during cardiac surgery. This evidence provides a basis for healthcare professionals to develop predictive management strategies for perioperative stress hyperglycemia in patients without diabetes period. However, more high-quality studies are required to address the limitations of the current research.

The dataset from this study has been provided as part of the submitted manuscript.

MLZ, YKW and ZYZ designed the research study. MLZ and YKW performed the research. NNZ and LLW provided help and advice on the Systematic review and meta-analysis. HH and FX analyzed the data. All authors contributed to editorial changes in the manuscript. All authors 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.

Not applicable.

We would like to express our gratitude to all those who helped us during the writing of this manuscript. Thanks to all the peer reviewers for their opinions and suggestions.

This research received no external funding.

The authors declare no conflict of interest.

Supplementary material associated with this article can be found, in the online version, at https://doi.org/10.31083/RCM25485.