Prognostic utility of the lactate-to-albumin ratio for predicting 28-day all-cause mortality in critically Ill cases with acute sepsis: A retrospective study on the basis of MIMIC-IV critical care database

Lactate-to-Albumin Ratio and 28-Day Mortality in Sepsis

  • Jiaqi Cheng Department of surgical intensive care unit, Beijing Shijitan Hospital, affiliated to Capital Medical University
  • Jiatong Hou Department of surgical intensive care unit, Beijing Shijitan Hospital, affiliated to Capital Medical University
  • Yuefu Wang Department of surgical intensive care unit, Beijing Shijitan Hospital, affiliated to Capital Medical University
Keywords: Sepsis, lactate-to-albumin ratio, all-cause mortality, MIMIC-IV database

Abstract


Background: Sepsis constitutes a systemic dysregulated host response to infection and remains a predominant cause of ICU mortality globally. Given the limitations of conventional prognostic models (e.g., SOFA and APACHE II), incorporating variably subjective parameters, there is a pressing need to identify robust, objective biomarkers for early mortality risk stratification. This investigation delineated the prognostic significance of the lactate-to-albumin ratio (LAR) in predicting 28-day all-cause mortality (28-DACM) among critically ill septic cases.

Methods: It was attempted to undertake a retrospective analysis utilizing the MIMIC-IV database (2008–2019), comprising 5,398 adult cases who met Sepsis-3 diagnostic criteria. Clinical and laboratory data within the initial 24-h post-ICU admission were extracted. The LASSO regression algorithm was implemented as a regularization technique to mitigate multicollinearity, enhance model generalizability, and facilitate high-dimensional feature selection. It was attempted to evaluate the prognostic utility of LAR through Kaplan-Meier (KM) survival estimation, receiver operating characteristic (ROC) curve analysis, and multivariate logistic regression modeling.

Results: LAR values were remarkably escalated in non-survivors relative to survivors (median, 0.9 vs. 0.6; P < 0.001). ROC curve analysis unveiled that LAR outperformed lactate (AUC: 63.52%), albumin (AUC: 43.34%), and the SOFA score (AUC: 59.87%), achieving the highest discriminatory capacity (AUC: 64.71%; 95% CI: 62.85–66.58%). An optimal LAR threshold of 1.032 was identified, attaining sensitivity and specificity of 45.1% and 76.6%, respectively. KM analysis uncovered remarkably attenuated 28-day survival in cases with LAR ≥1.032 (P < 0.001). Multivariate logistic regression confirmed LAR as an independent predictor of 28-DACM (OR = 1.32; P < 0.001), following adjusting for confounding variables.

Conclusions: The LAR serves as a clinically accessible, objective biomarker with superior prognostic performance relative to established indicators in association with sepsis. Its integration into early risk assessment algorithms may enhance prognostication and inform timely therapeutic decision-making. Prospective, multicenter investigations are warranted to validate its external generalizability and clinical utility.

References

1. Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). Jama-J Am Med Assoc 2016; 315(8): 801-10.
2. Rudd KE, Johnson SC, Agesa KM, Shackelford KA, Tsoi D, Kievlan DR, et al. Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the Global Burden of Disease Study. Lancet 2020; 395(10219): 200-11.
3. Liu D, Huang SY, Sun JH, Zhang HC, Cai QL, Gao C, et al. Sepsis-induced immunosuppression: mechanisms, diagnosis and current treatment options. Military Med Res 2022; 9(1): 56.
4. Vincent JL, Jones G, David S, Olariu E, Cadwell KK. Frequency and mortality of septic shock in Europe and North America: a systematic review and meta-analysis. Crit Care 2019; 23(1): 196.
5. McBride MA, Patil TK, Bohannon JK, Hernandez A, Sherwood ER, Patil NK. Immune Checkpoints: Novel Therapeutic Targets to Attenuate Sepsis-Induced Immunosuppression. Front Immunol 2020; 11: 624272.
6. Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Intens Care Med 2017; 43(3): 304-77.
7. Liu Q, Zheng HL, Wu MM, Wang QZ, Yan SJ, Wang M, et al. Association between lactate-to-albumin ratio and 28-days all-cause mortality in patients with acute pancreatitis: A retrospective analysis of the MIMIC-IV database. Front Immunol 2022; 13: 1076121.
8. Haas SA, Lange T, Saugel B, Petzoldt M, Fuhrmann V, Metschke M, et al. Severe hyperlactatemia, lactate clearance and mortality in unselected critically ill patients. Intens Care Med 2016; 42(2): 202-10.
9. Katopodis P, Pappas EM, Katopodis KP. Acid-base abnormalities and liver dysfunction. Ann Hepatol 2022; 27(2): 100675.
10. Kendall H, Abreu E, Cheng AL. Serum Albumin Trend Is a Predictor of Mortality in ICU Patients With Sepsis. Biol Res Nurs 2019; 21(3): 237-44.
11. Yoon SH, Choi B, Eun S, Bae GE, Koo CM, Kim MK. Using the lactate-to-albumin ratio to predict mortality in patients with sepsis or septic shock: a systematic review and meta-analysis. Eur Rev Med Pharmaco 2022; 26(5): 1743-52.
12. Johnson A, Bulgarelli L, Shen L, Gayles A, Shammout A, Horng S, et al. MIMIC-IV, a freely accessible electronic health record dataset. Sci Data 2023; 10(1): 1.
13. Guo W, Zhao L, Zhao H, Zeng F, Peng C, Guo W, et al. The value of lactate/albumin ratio for predicting the clinical outcomes of critically ill patients with heart failure. Ann Transl Med 2021; 9(2): 118.
14. Lu Y, Guo H, Chen X, Zhang Q. Association between lactate/albumin ratio and all-cause mortality in patients with acute respiratory failure: A retrospective analysis. Plos One 2021; 16(8): e0255744.
15. Garcia-Alvarez M, Marik P, Bellomo R. Sepsis-associated hyperlactatemia. Crit Care 2014; 18(5): 503.
16. Smith ZR, Horng M, Rech MA. Medication-Induced Hyperlactatemia and Lactic Acidosis: A Systematic Review of the Literature. Pharmacotherapy 2019; 39(9): 946-63.
17. Sterling SA, Puskarich MA, Jones AE. The effect of liver disease on lactate normalization in severe sepsis and septic shock: a cohort study. Clin Exp Emerg Med 2015; 2(4): 197-202.
18. Schouten M, Wiersinga WJ, Levi M, van der Poll T. Inflammation, endothelium, and coagulation in sepsis. J Leukocyte Biol 2008; 83(3): 536-45.
19. Arnau-Barres I, Guerri-Fernandez R, Luque S, Sorli L, Vazquez O, Miralles R. Serum albumin is a strong predictor of sepsis outcome in elderly patients. Eur J Clin Microbiol 2019; 38(4): 743-6.
20. Gharipour A, Razavi R, Gharipour M, Mukasa D. Lactate/albumin ratio: An early prognostic marker in critically ill patients. Am J Emerg Med 2020; 38(10): 2088-95.
21. Cakir E, Turan IO. Lactate/albumin ratio is more effective than lactate or albumin alone in predicting clinical outcomes in intensive care patients with sepsis. Scand J Clin Lab Inv 2021; 81(3): 225-9.
22. Shin J, Hwang SY, Jo IJ, Kim WY, Ryoo SM, Kang GH, et al. Prognostic Value of The Lactate/Albumin Ratio for Predicting 28-Day Mortality in Critically ILL Sepsis Patients. Shock 2018; 50(5): 545-50.
23. Li Y, Li D, Yuan X, Nazila H, Yang L, Xu R, et al. [Predictive value of early lactate/albumin ratio in the prognosis of sepsis]. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2023; 35(1): 61-5.
24. Moustafa AA, Antonios MA, Abdellatif EM, Hussain AH. Association of lactate/albumin ratio level to organ failure and mortality in severe sepsis in a pediatric intensive care unit in Egypt. Turkish J Pediatr 2018; 60(6): 691-701.
Published
2025/07/22
Section
Original paper