European Journal of Cardiovascular Medicine

Sepsis remains a major cause of morbidity and mortality worldwide and continues to pose a significant challenge to health-care systems, particularly in intensive care units (ICUs). Defined as life-threatening organ dysfunction resulting from a dysregulated host response to infection, sepsis represents the severe end of a spectrum that begins with infection and progresses to multi-organ failure if not recognized and treated promptly.¹ Despite advances in critical care, sepsis is associated with substantial mortality, prolonged hospital stay, and long-term functional impairment among survivors.²

Globally, sepsis affects millions of individuals each year and accounts for a considerable proportion of ICU admissions. Mortality rates in severe sepsis and septic shock frequently exceed 30–40%, even in well-resourced settings.² In low- and middle-income countries, including India, the burden of sepsis is particularly high due to delayed presentation, limited access to intensive care facilities, high prevalence of infectious diseases, and comorbid conditions such as malnutrition, diabetes mellitus, and chronic kidney disease.³ Beyond its clinical consequences, sepsis imposes a significant economic burden on patients and health systems and is associated with long-term psychological and cognitive sequelae among survivors, underscoring the importance of early risk stratification and timely intervention.⁴

Current management strategies for sepsis emphasize early recognition, prompt administration of antimicrobials, adequate fluid resuscitation, and organ support when required.⁵ While clinical severity scores such as the Sequential Organ Failure Assessment (SOFA) score are widely used to quantify organ dysfunction and predict outcomes, their application may be limited by the need for multiple laboratory parameters and dynamic reassessment.⁶ Similarly, individual biochemical markers such as serum lactate are commonly employed as indicators of tissue hypoperfusion and illness severity, but their prognostic accuracy can be influenced by factors unrelated to sepsis, including liver dysfunction and adrenergic stimulation.⁷

Serum albumin reflects the host’s inflammatory state, nutritional reserve, and vascular permeability, all of which play important roles in the pathophysiology of sepsis. Hypoalbuminemia has consistently been associated with worse outcomes in critically ill patients.⁸ The lactate–albumin ratio (LAR), which integrates these two routinely available biomarkers, has therefore been proposed as a composite indicator that may better capture both metabolic stress and systemic inflammation than either parameter alone. Recent studies have suggested that LAR has superior prognostic value compared with lactate or albumin individually, with utility in predicting mortality and organ failure in septic patients.⁹–¹¹

However, most available evidence on LAR is derived from retrospective analyses or heterogeneous patient populations, and prospective data evaluating its role in predicting clinically relevant ICU outcomes remain limited, particularly in the Indian context.¹² There is a need for simple, cost-effective, and readily available tools that can assist clinicians in early identification of septic patients at high risk for deterioration and intensive organ support.

Study Design and Setting

This prospective observational cohort study was conducted in the intensive care unit of Krishna Rajendra Hospital, a tertiary care teaching hospital affiliated with Mysore Medical College and Research Institute, Mysuru. The study was carried out over a three-month period from November 2025 to January 2026.

Participants

Adult patients (aged ≥18 years) admitted to the ICU with a diagnosis of sepsis, as defined by the Sepsis-3 criteria, were consecutively enrolled during the study period. Sepsis was identified based on the presence of suspected or confirmed infection along with acute organ dysfunction, quantified by an increase in the Sequential Organ Failure Assessment (SOFA) score.

Inclusion and Exclusion Criteria  

Patients aged 18 years or older fulfilling Sepsis-3 diagnostic criteria were eligible for inclusion. Patients were excluded if they had chronic liver disease classified as Child–Pugh class C, chronic kidney disease stage 4 or higher, known malignancy, HIV infection, or were receiving chemotherapy. Patients or legally authorised representatives who declined consent were also excluded.

Data Collection and Variables

After obtaining institutional ethical clearance, informed written consent was obtained from all patients or their legally authorised representatives prior to enrolment. Baseline demographic data, clinical characteristics, and source of sepsis were recorded at ICU admission.

The requirement for intensive care interventions and ICU outcome were recorded as binary categorical variables for analysis. Mechanical ventilation requirement was coded as 1 for patients who required ventilator support and 2 for those who did not. Vasopressor or inotrope requirement was coded as 1 for patients who did not require support and 2 for those who required support. Similarly, renal replacement therapy was coded as 1 for patients who did not require therapy and 2 for those who required renal replacement therapy. ICU outcome was classified as 1 for survivors and 2 for non-survivors.

Outcome Measures

The primary outcome was a composite adverse outcome defined as ICU mortality or the requirement for mechanical ventilation, vasopressor or inotrope support, or renal replacement therapy during the ICU stay. Secondary outcomes included the individual components of the composite outcome and the correlation between admission LAR and SOFA score.

Statistical Analysis

Data were analysed using SPSS software version 22.0. Continuous variables were expressed as mean ± standard deviation, and categorical variables as frequencies and percentages. The association between lactate–albumin ratio and SOFA score was assessed using Pearson’s correlation coefficient. Unadjusted logistic regression analysis was performed to estimate odds ratios with 95% confidence intervals for the association between lactate–albumin ratio and binary outcomes. All categorical outcome variables were analysed as binary variables using the predefined coding scheme.

Ethical Considerations

The study was approved by the Institutional Ethics Committee of Mysore Medical College and Research Institute, Mysuru. The study involved no interventions beyond standard clinical care. All procedures were conducted in accordance with the principles of the Declaration of Helsinki.

Study Population and Baseline Characteristics A total of 75 adult patients with sepsis admitted to the intensive care unit were included in the final analysis. The mean age of the study population was 56.72 ± 18.30 years (range: 18–85 years). Male patients constituted 57.3% of the cohort, while females accounted for 42.7%. The majority of patients were aged above 60 years, with 38.7% in the 61–75 year age group. The mean SOFA score at ICU admission was 7.13 ± 3.65, indicating moderate to severe organ dysfunction. Serum lactate levels at admission were elevated (mean 3.37 ± 2.40 mmol/L), while serum albumin levels were reduced (mean 3.69 ± 0.49 g/dL), resulting in a mean lactate–albumin ratio of 1.18 ± 1.00. (Table1) Table 1. Baseline Demographic and Clinical Characteristics of the Study Population (n = 75) Variable Mean ± SD / n (%) Age (years) 56.72 ± 18.30 Male 43 (57.3) Female 32 (42.7) SOFA score at admission 7.13 ± 3.65 Serum lactate (mmol/L) 3.37 ± 2.40 Serum albumin (g/dL) 3.69 ± 0.49 Lactate–albumin ratio 1.18 ± 1.00 Distribution of Age Groups and Source of Sepsis Most patients were elderly, with individuals aged ≥61 years comprising over half of the study population. Respiratory tract infections were the most common source of sepsis (50.7%), followed by urosepsis (16.0%) and abdominal infections (14.7%). Central nervous system, bloodstream, and skin or soft tissue infections accounted for a smaller proportion of cases. (Table 2) Table 2. Age Group Distribution and Source of Sepsis Variable n (%) Age group (years) 18–30 9 (12.0) 31–45 13 (17.3) 46–60 14 (18.7) 61–75 29 (38.7) >75 10 (13.3) Source of sepsis Respiratory 38 (50.7) Urosepsis 12 (16.0) Abdominal 11 (14.7) Central nervous system 8 (10.7) Bloodstream 4 (5.3) Skin and soft tissue 2 (2.7) ICU Interventions and Clinical Outcomes Mechanical ventilation was required in 33 patients (44.0%), while vasopressor or inotrope support was administered to 32 patients (42.7%). Renal replacement therapy was required in few patients. Most patients who required ventilator or inotrope support received these interventions for five days or less. Overall ICU mortality was 33.3%, with 25 patients classified as non-survivors. (Table3) Table 3. ICU Interventions and Outcomes Outcome n (%) Mechanical ventilation required 33 (44.0) Vasopressor/Inotrope support required 32 (42.7) Renal replacement therapy required 9 (12.0) ICU survivors 50 (66.7) ICU non-survivors 25 (33.3) Lactate Dynamics and Lactate Clearance The mean lactate level at ICU admission was 3.37 ± 2.40 mmol/L, which decreased to 2.46 ± 2.27 mmol/L at 4 hours. The mean lactate clearance was 30.55 ± 22.78%, although wide inter-individual variability was observed, with values ranging from −64.00% to 66.67%. (Table 4) Table 4. Lactate Parameters and Lactate Clearance Parameter Mean ± SD Range Lactate at 0 hour (mmol/L) 3.37 ± 2.40 0.20–12.10 Lactate at 4 hours (mmol/L) 2.46 ± 2.27 0.10–12.90 Lactate clearance (%) 30.55 ± 22.78 −64.00–66.67 Correlation Between Lactate–Albumin Ratio and Disease Severity A statistically significant moderate positive correlation was observed between admission lactate–albumin ratio and SOFA score (r = 0.569, p < 0.001), indicating that higher LAR values were associated with greater severity of organ dysfunction. (Table5) Table 5. Correlation Between Lactate–Albumin Ratio and SOFA Score Variables Pearson r p-value LAR vs SOFA score 0.569 <0.001 Association of Lactate–Albumin Ratio With ICU Interventions and Mortality On unadjusted logistic regression analysis, lactate–albumin ratio was significantly associated with the requirement for mechanical ventilation and vasopressor or inotrope support. Higher LAR values were also strongly associated with ICU mortality. No significant association was observed between LAR and the requirement for renal replacement therapy. (Table 6) Table 6. Association Between Lactate–Albumin Ratio and ICU Outcomes (Unadjusted Logistic Regression) Outcome Odds Ratio (95% CI) p-value Mechanical ventilation 0.231 (0.095–0.562) <0.001 Vasopressor/Inotrope support 0.133 (0.043–0.413) <0.001 Renal replacement therapy 1.271 (0.693–2.329) 0.439 ICU mortality 8.240 (2.713–25.025) <0.001 Predictive Performance of Lactate–Albumin Ratio Receiver operating characteristic curve analysis demonstrated good discriminative ability of the lactate–albumin ratio in predicting adverse ICU outcomes, with an area under the curve of 0.84 (95% CI 0.75–0.93; p < 0.001). (Table 7) Table 7. Receiver Operating Characteristic Analysis of Lactate–Albumin Ratio Parameter Value Area under the curve (AUC) 0.840 Standard error 0.045 95% confidence interval 0.751–0.929 p-value <0.001

This study evaluated the prognostic utility of the lactate–albumin ratio (LAR) measured at ICU admission in patients with sepsis and examined its association with disease severity and clinically meaningful adverse outcomes. Early risk stratification remains a cornerstone of sepsis management, particularly in intensive care units in low- and middle-income countries, where delayed presentation and resource constraints are common. In this context, a simple biomarker derived from routinely available laboratory parameters may provide significant clinical value. Recent literature increasingly supports the role of LAR as a composite indicator that complements traditional severity scoring systems and improves early prognostication in sepsis.¹³,¹⁴

Lactate–Albumin Ratio and Disease Severity

In the present study, admission LAR demonstrated a significant positive correlation with SOFA score, indicating that higher LAR values were associated with greater severity of organ dysfunction. This finding is consistent with published evidence. Ponce-Orozco et al. reported that LAR independently correlated with established severity indices and adverse outcomes in critically ill septic patients, with proposed cut-off values showing good diagnostic accuracy.¹³ Similarly, Zhang et al., in a meta-analysis encompassing heterogeneous sepsis populations, demonstrated that elevated LAR was consistently associated with increased short-term mortality and greater disease severity.¹⁴ The pathophysiological basis for this association lies in the dual contribution of lactate, a marker of tissue hypo perfusion and metabolic stress, and albumin, a surrogate of systemic inflammation, endothelial dysfunction, and reduced physiological reserve. By integrating these two parameters, LAR provides a more comprehensive representation of the severity of sepsis than either biomarker alone.

Lactate–Albumin Ratio and ICU Interventions

A key objective of this study was to assess whether admission LAR could predict the requirement for major ICU interventions. Higher LAR values were significantly associated with the need for mechanical ventilation and vasopressor or inotrope support. These findings are supported by prior studies. Kim et al. demonstrated that elevated LAR at ICU admission was an independent predictor of progression to septic shock and the subsequent need for vasopressor therapy, with superior predictive performance compared to baseline lactate or albumin alone.¹⁵ Wu et al. further reported that LAR was a strong early predictor of acute respiratory distress syndrome (ARDS) and the requirement for mechanical ventilation in septic patients, often outperforming traditional inflammatory markers.¹⁸

In contrast, no statistically significant association was observed between LAR and the requirement for renal replacement therapy in the present study. This observation may reflect the multifactorial etiology of acute kidney injury in sepsis, which is influenced by factors such as baseline renal function, nephrotoxic exposure, and hemodynamic instability. Nevertheless, Liu et al. reported that higher admission LAR values were associated with increased risk of acute kidney injury and mortality in patients with septic shock, suggesting that the predictive value of LAR for renal outcomes may vary across populations and clinical contexts.¹⁷

Comparison With Established Prognostic Tools

Several studies have compared the prognostic performance of LAR with established clinical scoring systems. Abdou et al. demonstrated that LAR had superior predictive accuracy for ICU mortality compared with SOFA and qSOFA scores, particularly when assessed early in the disease course.¹⁶ Bajaj et al. similarly reported that combining LAR with SOFA score improved risk stratification compared with either parameter alone, supporting a complementary rather than substitutive role for LAR in clinical practice.²⁰ These findings reinforce the potential utility of LAR as an adjunctive tool that can be rapidly applied at ICU admission, even before complete clinical scoring is available.

Clinical Implications and Limitations

Overall, the findings of this study add to the growing evidence that LAR is a simple, cost-effective, and readily accessible biomarker for early risk stratification in sepsis. In high-burden ICU settings, LAR may assist clinicians in identifying patients at increased risk for deterioration, facilitating timely escalation of care and optimized allocation of critical care resources. Emerging evidence also suggests that dynamic changes in LAR during the early ICU course may provide additional prognostic information beyond admission values alone.²¹ The present study is limited by its single-center design, modest sample size, and follow-up restricted to the ICU stay. Additionally, serial LAR measurements were not evaluated. Despite these limitations, the consistency of the present findings with existing literature supports the clinical relevance of LAR as an adjunctive prognostic marker in critically ill patients with sepsis.