Open AccessArticle Prognostic Value of Serial Lactate Dehydrogenase Measurements for Determining Early Mortality in ICU Patients: A Retrospective Cohort Study by Hasan Göze Hasan Göze SciProfiles Scilit Preprints.org Google Scholar 1,* Türkay Akbaş Türkay Akbaş SciProfiles Scilit Preprints.org Google Scholar 2 1 Department of Hematology, Basaksehir Cam and Sakura City Hospital, University of Health Sciences, Istanbul 34480, Türkiye 2 Division of Intensive Care, Department of Internal Medicine, Düzce University Faculty of Medicine, Düzce 34295, Türkiye * Author to whom correspondence should be addressed. J. Clin. Med. 2026, 15(12), 4404; https://doi.org/10.3390/jcm15124404 (registering DOI) Submission received: 22 April 2026 / Revised: 4 June 2026 / Accepted: 4 June 2026 / Published: 6 June 2026 Background: This study investigated whether lactate dehydrogenase (LDH) levels measured at ICU admission predict early in-hospital mortality among critically ill medical patients in a single-center retrospective cohort study conducted in Turkey. Specifically, we aimed to (i) determine an optimal LDH threshold; (ii) examine the temporal trajectory of discriminatory performance over 72 h; and (iii) assess LDH as an independent predictor beyond established severity scores. Methods: In this single-center retrospective cohort study, 681 adults admitted to a medical ICU between January 2015 and January 2025 were analyzed. Serial LDH measurements were obtained at 0, 24, 48, and 72 h after ICU admission. This study was approved by the Institutional Ethics Committee (Decision No.: 2025/99). ROC analysis was performed under a predefined sensitivity constraint (≥0.70), and time-to-event outcomes were examined using Kaplan–Meier methods and Cox proportional hazards regression. Determinants of maximum LDH were assessed using a GLM with Gamma distribution and log link. Results: The 28-day mortality rate was 39.1%. ROC analysis identified an optimal 24-h LDH cut-off of approximately 275 U/L (AUC = 0.650; sensitivity = 0.70). Discriminatory performance improved progressively over time (AUC of 0.632 at baseline to 0.690 at 72 h), suggesting that serial measurements may capture evolving prognostic information more effectively than single-time-point measurements. Kaplan–Meier analyses demonstrated a stepwise decline in survival with increasing LDH across all categorization approaches (all log-rank p 3) and cases with missing 24-h LDH values were excluded, yielding an analytic sample of 618 patients. LDH was operationalized in three distinct ways: (i) a prognostic threshold for 24-h LDH was derived using ROC analysis under a predefined sensitivity constraint (≥0.70); (ii) percentile-based categories were defined using empirical quartiles (220, 288, and 411 U/L) for Kaplan–Meier survival comparisons; and (iii) clinically anchored categories were constructed based on the local laboratory reference range (upper limit of normal: 225 U/L), with further stratification in approximately 200 U/L increments (225–475, 475–675, and ≥675 U/L). Time-to-event outcomes were analyzed using Kaplan–Meier methods, with survival distributions compared using the log-rank (Mantel–Cox) test as the primary comparison, supplemented by Breslow and Tarone–Ware tests. Discriminative performance for mortality was assessed using ROC curves with paired comparisons of area under the curve (AUC) across time points. Associations with mortality were examined using Cox proportional hazards regression, with LDH exposure defined as the logarithm of the maximum LDH measured within the first 72 h. Models were adjusted for age and baseline severity indices (APACHE II and SOFA), and the proportional hazards assumption was evaluated. Variable selection was guided by clinical relevance and prior literature. Multicollinearity was assessed using variance inflation factors; SOFA and APACHE II, although correlated with each other, were retained as they capture distinct dimensions of organ dysfunction and chronic health reserve. Given the event-to-variable ratio in the fully adjusted model, overfitting was considered unlikely. Determinants of LDH burden were evaluated using a generalized linear model (GLM) with Gamma distribution and log link, with maximum LDH as the dependent variable and sex and ICU length of stay as covariates. These covariates were selected based on evidence linking sex hormones to LDH expression and the physiological rationale that prolonged ICU stay reflects ongoing tissue injury or recovery. We acknowledge that treatment-related variables (e.g., vasopressor use, renal replacement therapy, and mechanical ventilation) were not available as structured data fields in the registry and therefore could not be included as covariates; this represents a limitation, which is discussed below. Parameter estimates were obtained using 1000 bootstrap resamples. Separate univariable binary logistic regression analyses were performed to evaluate LDH quartiles and age groups with 28-day mortality. No formal a priori sample size calculation was performed, as this study utilized a consecutive sample of all eligible patients admitted during the 10-year study period. Two-sided p-values 275 U/L at 24 h may benefit from escalated monitoring, earlier multidisciplinary review, or goals-of-care discussions. Serial measurement over 72 h may additionally support the dynamic reassessment of mortality risk. Prospective multicenter studies are warranted to validate these thresholds and to evaluate whether LDH-guided management strategies can improve ICU outcomes. Author Contributions Conceptualization, H.G. and T.A.; methodology, H.G. and T.A.; software, H.G. and T.A.; validation, H.G. and T.A.; formal analysis, H.G. and T.A.; investigation, H.G. and T.A.; resources, H.G. and T.A.; data curation, H.G. and T.A.; writing—original draft preparation, H.G. and T.A.; writing—review and editing, H.G. and T.A.; visualization, H.G. and T.A.; supervision, H.G. and T.A.; project administration, H.G. and T.A. All authors have read and agreed to the published version of the manuscript. Funding The authors received no financial support for the research and/or authorship of this article. Institutional Review Board Statement The study was conducted in accordance with the Declaration of Helsinki and ethical approval for the study was obtained from the Non-Interventional Research Ethics Committee of Duzce University (Approval Date: 7 April 2025, Decision No: 2025/99). The confidentiality of patient data was fully protected. Informed Consent Statement Informed consent was waived due to the retrospective nature of the study. Data Availability Statement The raw data supporting the conclusions of this article will be made available by the authors on request. Conflicts of Interest The authors declare no conflicts of interest. Abbreviations APACHE II Acute Physiology and Chronic Health Evaluation II AUC Area Under the Curve CI Confidence Interval CKD Chronic Kidney Disease CRP C-Reactive Protein GLM Generalized Linear Model HR Hazard Ratio ICU Intensive Care Unit IQR Interquartile Range LDH Lactate Dehydrogenase OR Odds Ratio ROC Receiver Operating Characteristic SD Standard Deviation SOFA Sequential Organ Failure Assessment References Cresti, A.; Baratta, P.; De Sensi, F.; Aloia, E.; Sposato, B.; Limbruno, U. Clinical features and mortality rate of infective endocarditis in intensive care unit: A large-scale study and literature review. Anatol. J. Cardiol. 2024, 28, 44. [ Google Scholar] [ CrossRef] Pu, Z.C.; Wei, X.L.; Zhou, Y.; Liu, X.L.; Fang, Z.J.; Li, L.L.; Jia, P. Systematic review and meta-analysis of prediction models for multidrug-resistant organism infections in comprehensive intensive care units. J. Glob. Antimicrob. Resist. 2025, 44, 139–145. 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Mortality risk by medical history, disease categories, and clinical course: the forest plot of the study sample ( n = 681). Figure 1. Mortality risk by medical history, disease categories, and clinical course: the forest plot of the study sample ( n = 681). Figure 2. Interval plot of mean LDH values with 95% confidence intervals by mortality status (0/1) and time point. Figure 2. Interval plot of mean LDH values with 95% confidence intervals by mortality status (0/1) and time point. Figure 3. ROC curves for LDH at baseline and at 24, 48, and 72 h after ICU admission. Figure 3. ROC curves for LDH at baseline and at 24, 48, and 72 h after ICU admission. Figure 4. Three-dimensional plots illustrating the relationships between baseline SOFA score, APACHE II score, and 24-h LDH in relation to 28-day mortality outcomes. Figure 4. Three-dimensional plots illustrating the relationships between baseline SOFA score, APACHE II score, and 24-h LDH in relation to 28-day mortality outcomes. Figure 5. Kaplan–Meier survival curves according to laboratory-anchored 24-h LDH categories. Figure 5. Kaplan–Meier survival curves according to laboratory-anchored 24-h LDH categories. Figure 6. Kaplan–Meier survival curves according to percentile-based 24-h LDH quartiles. Figure 6. Kaplan–Meier survival curves according to percentile-based 24-h LDH quartiles. Figure 7. Kaplan–Meier survival curves stratified by percentile-based LDH cut-offs over the 28-day follow-up period. Figure 7. Kaplan–Meier survival curves stratified by percentile-based LDH cut-offs over the 28-day follow-up period. Figure 8. Cumulative hazard plots for log-transformed maximum LDH over the first 28 days of ICU stay. Figure 8. Cumulative hazard plots for log-transformed maximum LDH over the first 28 days of ICU stay. Figure 9. Proposed pathophysiological mechanisms linking serum lactate dehydrogenase (LDH) elevation to multi-organ dysfunction and early mortality in critically ill ICU patients. LDH release reflects cellular energy failure, tissue necrosis, and end-organ damage across hepatic, renal, hematologic, and pulmonary compartments. Abbreviations: LDH, lactate dehydrogenase; ICU, intensive care unit; SOFA, Sequential Organ Failure Assessment; APACHE II, Acute Physiology and Chronic Health Evaluation II; CKD, chronic kidney disease; mTOR, mechanistic target of rapamycin. Figure 9. Proposed pathophysiological mechanisms linking serum lactate dehydrogenase (LDH) elevation to multi-organ dysfunction and early mortality in critically ill ICU patients. LDH release reflects cellular energy failure, tissue necrosis, and end-organ damage across hepatic, renal, hematologic, and pulmonary compartments. Abbreviations: LDH, lactate dehydrogenase; ICU, intensive care unit; SOFA, Sequential Organ Failure Assessment; APACHE II, Acute Physiology and Chronic Health Evaluation II; CKD, chronic kidney disease; mTOR, mechanistic target of rapamycin. Table 1. Univariable binary logistic regression analysis of LDH quartiles and age groups for 28-day mortality. Table 1. Univariable binary logistic regression analysis of LDH quartiles and age groups for 28-day mortality. Predictor Category (vs. Reference) OR (Exp(B)) 95% CI p-Value LDH quartiles 220–287 vs. 410 vs. <220 5.66 3.48–9.22 <0.001 Age groups 63–72 vs. 18–62 1.41 0.91–2.20 0.126 ≥73 vs. 18–62 1.59 1.08–2.32 0.018 Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. © 2026 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license. Share and Cite Göze, H.; Akbaş, T. Prognostic Value of Serial Lactate Dehydrogenase Measurements for Determining Early Mortality in ICU Patients: A Retrospective Cohort Study. J. Clin. Med. 2026, 15, 4404. https://doi.org/10.3390/jcm15124404 Göze H, Akbaş T. Prognostic Value of Serial Lactate Dehydrogenase Measurements for Determining Early Mortality in ICU Patients: A Retrospective Cohort Study. Journal of Clinical Medicine. 2026; 15(12):4404. https://doi.org/10.3390/jcm15124404 Göze, Hasan, and Türkay Akbaş. 2026. "Prognostic Value of Serial Lactate Dehydrogenase Measurements for Determining Early Mortality in ICU Patients: A Retrospective Cohort Study" Journal of Clinical Medicine 15, no. 12: 4404. https://doi.org/10.3390/jcm15124404 Göze, H., & Akbaş, T. (2026). Prognostic Value of Serial Lactate Dehydrogenase Measurements for Determining Early Mortality in ICU Patients: A Retrospective Cohort Study. 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