The frequent occurrence of pesticide poisoning and its associated high fatality rate pose a serious threat to the health of rural residents [1]. Rural hospitals admit hundreds of patients annually for pesticide poisoning, with a mortality rate as high as 15–30% [2, 3]. This alarming situation not only threatens the lives of farmers but also places immense pressure on the rural healthcare system. Patients poisoned with pesticides, especially paraquat and diquat, experience severe pain accompanied by symptoms such as nausea, vomiting, abdominal pain, and diarrhea. Additionally, the respiratory system is severely affected. Following pesticide poisoning, patients may develop progressive respiratory distress and cyanosis due to pesticide-induced damage to the structural and functional integrity of the lungs, leading to pulmonary edema, fibrosis, and respiratory failure. In severe cases, mechanical ventilation may be required within a short period to sustain life [4, 5].

Management of pesticide poisoning involves the rapid removal of toxic substances, including the removal of contaminated clothing and skin decontamination. In cases of oral ingestion, vomiting and gastric lavage are necessary. Specific antidotes, such as atropine and tripralidoxime, should be administered according to the poisoning agent, for organophosphorus poisoning, while closely monitoring and supporting vital signs. Blood purification therapy should be considered when clinically indicated.

In this study, pesticide poisoning detection and analysis were performed using Agilent 6495 high-performance liquid chromatography-tandem triple quadrupole mass spectrometer (Agilent Technologies, Santa Clara, CA, USA). Plasma samples were pretreated with methanol protein precipitation. An acetonitrile-water gradient mobile phase was employed with a flow rate of 0.4 mL$\cdot$min^-1. Sample separation was achieved using a Waters XBridge BEH HILIC column XP (100 mm long, 2.1 mm inner diameter, 2.5 µm particle diameter) (Part No. 186006079, Waters Corporation, Milford, MA, USA). Mass spectrometric analysis was conducted in electrospray ionization (ESI) positive ion mode using multiple reaction monitoring (MRM) for quantification of paraquat (m/z 186.1$\to$171.1) and diquat (m/z 183.1$\to$157.1). This method was applied to detect clinical plasma concentrations of paraquat and diquat, with a 5 µL injection volume used for high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) system analysis.

The albumin-corrected anion gap (ACAG), a clinical indicator reflecting renal function and acid-base balance status, has garnered increasing attention in recent years. The anion gap, defined as the difference between unmeasured cations and anions in the blood, is widely used to assess acid-base imbalances [6]. As albumin is a negatively charged protein, fluctuations in its concentration can influence the anion gap calculation. Therefore, correcting the anion gap for albumin levels yields more accurate diagnostic insights and better informs clinical management. Several studies have explored the use of ACAG in cardiac-related conditions [7, 8]. However, research on the predictive value of ACAG for myocardial injury due to pesticide poisoning remains limited. This study aimed to investigate the relationship between ACAG and secondary myocardial injury and to evaluate its predictive performance. The goal was to uncover potential associations between ACAG and acute myocardial injury, thereby providing new insights and methods for early intervention and prognostic assessment in patients with pesticide poisoning.

In this study, clinical data from 205 patients with acute pesticide poisoning were analyzed to investigate the predictive value of ACAG for secondary acute myocardial injury. The results indicate that ACAG is a valuable indicator for predicting secondary acute myocardial injury in such patients, demonstrating high sensitivity and specificity.

Significant differences were observed between the two groups in ACAG, respiratory failure, APACHE II score, and poisoning severity. Binary logistic regression analysis confirmed that ACAG, respiratory failure, APACHE II score, and severity of poisoning are independent influencing factors for the development of secondary acute myocardial injury in patients with acute pesticide poisoning. A previous study by Aydın and Aksakal [16] also indicated a significant association between elevated ACAG and increased mortality rate in hospitalized heart failure patients. These findings are consistent with the current study, providing additional validation for the current research. These findings suggest that ACAG, respiratory failure, APACHE II score, and poisoning severity are key factors contributing to the risk of secondary acute myocardial injury following pesticide poisoning. Several potential mechanisms may explain these associations. First, ACAG reflects electrolyte balance. Pesticide poisoning often leads to electrolyte imbalances, particularly acid-base disturbances. As a sensitive indicator of these imbalances, changes in ACAG may reflect variations in intracellular and extracellular ion concentrations in myocardial cells, contributing to myocardial injury.

Second, ACAG is related to inflammatory responses. Pesticide exposure triggers systemic inflammation, and changes in albumin levels may indicate the severity and duration of this response [17]. Since ACAG adjusts the anion gap corrected for albumin, it may indirectly reflect the inflammatory response status of the body, thereby affecting myocardial outcomes [18]. Third, ACAG is linked to renal function. Pesticide-induced nephrotoxicity may impair acid-base balance. By correcting for albumin levels, ACAG offers a more accurate reflection of the renal function status on the anion gap, which is closely associated with myocardial injury [19, 20]. Lastly, ACAG directly correlates with the severity of poisoning. Patients with severe poisoning show significantly higher ACAG values than those with mild poisoning, indicating that ACAG may serve as a sensitive marker for identifying patients at higher risk of myocardial injury.

Further correlation analysis revealed that ACAG is negatively correlated with albumin (r = –0.528) and positively correlated with anion gap (AG), APACHE II score and severe Poisoning (r = 0.974, 0.365, 0.230). These correlation results suggest that variations in ACAG are closely related to the overall severity of the patient’s condition, with a particularly strong correlation with the APACHE II score, which reflects the clinical severity. This further supports the feasibility of using ACAG as a predictive indicator for secondary acute myocardial injury in patients with acute pesticide poisoning. Although ACAG demonstrates high specificity and may help reduce unnecessary medical interventions, its sensitivity is relatively low. This may be due to its stronger emphasis on accurately identifying patients without acute myocardial injury, which may limit its potential to capture certain characteristics of patients with acute myocardial injury. Consequently, some cases may be missed during screening, which limits its effectiveness as a universal clinical screening tool.

To evaluate the predictive value of ACAG for acute myocardial injury, this study employed ROC curve analysis. The findings indicate that ACAG has the highest predictive value, with an AUC of 0.859 (95% CI: 0.809–0.909), a standard error of 0.025, and a Youden index of 0.55. At this threshold, the sensitivity was 59.26%, and the specificity was 95.97%. A previous study by Lu et al. [21] also demonstrated that ACAG performs well in predicting in-hospital mortality in patients with acute myocardial infarction, which is consistent with the results of this study. These findings suggest that ACAG not only exhibits high predictive accuracy but also excels in specificity. High specificity indicates that, in clinical practice, ACAG can accurately identify patients without acute myocardial injury, thereby helping avoid unnecessary medical interventions and optimizing the use of medical resources.

Furthermore, this study compared the survival probability and post-treatment cardiac function indicators of patients across different ACAG levels. The results showed that the survival probability in the ACAG $\le$24.54 group was significantly higher than in the ACAG $>$24.54 group. Additionally, post-treatment cardiac function indicators in the ACAG $\le$24.54 group were significantly superior to those in the ACAG $>$24.54 group. These findings further underscore the value of ACAG in predicting prognosis and cardiac function in patients with acute pesticide poisoning. In clinical practice, physicians can formulate more personalized treatment strategies by considering the patient’s ACAG level in conjunction with other clinical indicators. For patients with elevated ACAG levels, closer monitoring and earlier intervention may help reduce the risk of acute myocardial injury, improve prognosis, and enhance quality of life. Previous research by Xu et al. [22] showed that incorporating ACAG into clinical decision-making for atrial fibrillation could improve treatment outcomes, which is consistent with the findings of this study and further supports the predictive value of ACAG in prognosis.

Based on the findings of this study, several clinical implications can be proposed. First, in patients with elevated ACAG, more intensive cardioprotective interventions, such as optimizing electrolyte balance or administering antioxidant therapy, may yield significant benefits. For example, dynamic monitoring of ACAG levels may guide the targeted use of antioxidants (e.g., N-acetylcysteine) or inform the application of mechanical ventilation to improve oxygenation in patients with respiratory failure, thereby reducing the risk of myocardial injury. Moreover, emerging therapeutic approaches such as exome-delivered circular RNAs (circRNAs) offer promising new directions for myocardial protection. Hu et al. [23] reported that adipose-derived exosomal circ-0008302 could mitigate oxidative stress-induced myocardial damage by targeting the Mir-466i-5p/MStrA pathway, suggesting that RNA-based exosome therapy may represent a novel treatment strategy for patients with elevated ACAG.

Current standard treatments for acute myocardial injury, such as beta blockers and Angiotensin Converting Enzyme (ACE) inhibitors, are not yet stratified based on ACAG levels. Future studies should explore the potential value of ACAG as a treatment stratification biomarker. For instance, whether patients with ACAG $>$24.54 should receive prioritized intensive monitoring or early intervention, such as continuous Electrocardiogram (ECG) monitoring and dynamic myocardial enzyme profiling, remains an open question. Additionally, individualized treatment plans could incorporate ACAG measurements, especially in high-risk patients with significantly elevated ACAG levels. A comprehensive therapeutic approach combining antioxidant therapy, exosome-based interventions, and mechanical support, guided by dynamic ACAG trends, may enable precision myocardial protection and optimize clinical outcomes.

The results of this study suggest that ACAG holds promising potential for predicting secondary acute myocardial injury in patients with acute pesticide poisoning. However, certain limitations should be acknowledged. First, the sample size was relatively small, which may impact the accuracy and generalizability of the results. Future research should include larger-scale, multicenter studies for further validation. Second, this study did not assess the dynamic changes in ACAG over time. Continuous monitoring may better capture disease progression and treatment outcomes. Additionally, this study did not employ statistical methods such as the DeLong test to compare the AUC values of ACAG with other predictors (e.g., APACHE II score). Without such comparisons, it is challenging to determine whether the differences are statistically significant. The current results only suggest a certain degree of predictive value, and more conclusive evidence is needed. Future studies should focus on expanding the sample size and incorporating dynamic monitoring to enhance the predictive accuracy and clinical utility of ACAG in the management of patients with acute pesticide poisoning.

In conclusion, this study confirms the predictive value of ACAG for secondary acute myocardial injury in patients with acute pesticide poisoning through in-depth analysis of clinical data. ACAG is closely associated with the overall severity of the patient’s condition and demonstrates excellent specificity. Additionally, ACAG levels are strongly linked to patient prognosis. With continued research and advances in clinical practice, broader applications of ACAG in the management of acute pesticide poisoning are anticipated. Simultaneously, the ongoing development and refinement of other relevant indicators and diagnostic methods will be essential to further improve patient outcomes and enhance the overall quality of care for patients with acute pesticide poisoning.

$\bullet$ ACAG demonstrates significant predictive value for secondary acute myocardial injury in patients with acute pesticide poisoning, with the area under the ROC curve reaching 0.859 (sensitivity 59.26%, specificity 95.97%).

$\bullet$ Binary logistic regression analysis identified ACAG (OR = 1.586), respiratory failure (OR = 4.432), APACHE II score (OR = 1.242), and severe poisoning (OR = 3.472) as independent risk factors for secondary myocardial injury.

$\bullet$ Correlation analysis revealed that ACAG is negatively correlated with albumin (r = –0.528) and positively correlated with anion gap (AG), APACHE II score and severe Poisoning (r = 0.974, 0.365, 0.230).

$\bullet$ An ACAG cutoff value of 24.54 can effectively distinguish patients at high risk of pesticide poisoning.

The data used to support the findings of this study are available from the corresponding author upon request.

JW: conceptualization, methodology, validation, formal analysis, investigation, data curation, writing—original draft, writing—review & editing, visualization; BL: methodology, formal analysis. Both authors contributed to revising the manuscript critically for important intellectual content. Both authors read and approved the final manuscript. Both authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work.

This study was approved by the Clinical Research Ethics Committee of the First Affiliated Hospital, Zhejiang University School of Medicine (approval number: IIT20230383B-R1), which also granted a waiver of written informed consent. A retrospective analysis was conducted on the cases of paraquat and diquat poisoning from March 2017 to December 2024. The risk to the subjects in this study is no greater than the minimum risk. Waiving informed consent will not have an adverse impact on the rights and health of the subjects. All procedures were conducted following the principles outlined in the Declaration of Helsinki.

We thank the Department of Laboratory Medicine, the First Affiliated Hospital, Zhejiang University School of Medicine, and Zhejiang Key Laboratory of Clinical In Vitro Diagnostic Techniques for technical assistance.

This research received no external funding.

The authors declare no conflict of interest.