Sepsis represents a complex clinical syndrome characterized by a dysregulated host response to infection, resulting in life-threatening organ dysfunction. The revised definition proposed by the Sepsis-3 consensus emphasizes the central role of immune dysregulation rather than systemic inflammation, offering improved diagnostic clarity and prognostic precision.¹

Despite substantial advances in our understanding of the immunopathogenesis of sepsis, including the interplay of pro-inflammatory and anti-inflammatory pathways, therapeutic progress has remained limited. Early recognition and timely initiation of evidence-based interventions, such as fluid resuscitation and broad-spectrum antibiotics, remain the cornerstone of sepsis management. However, identifying reliable prognostic markers that reflect underlying tissue hypoperfusion and predict outcomes with accuracy is critical to optimizing clinical decision-making in these patients.^2,3

Among the biochemical parameters under investigation, serum lactate has emerged as a robust indicator of global tissue hypoxia and impaired perfusion. Elevated lactate levels in sepsis indicate anaerobic metabolism due to reduced oxygen delivery and cellular utilization, hepatic dysfunction, or increased metabolic demand. Lactate is a surrogate marker for disease severity and has been incorporated into diagnostic criteria and therapeutic targets in recent sepsis guidelines.^4,5

Studies have shown that persistent hyperlactatemia is associated with increased mortality, even in the absence of hypotension, suggesting its role as a sensitive predictor of adverse outcomes. The Surviving Sepsis Campaign now recommends early lactate measurement as part of the resuscitation bundle, highlighting its relevance in guiding diagnosis and therapeutic response.^7,8

Although global data supports lactate levels as a prognostic marker, Indian literature on its independent predictive value in sepsis remains sparse. The unique burden of sepsis in India, compounded by late presentation, antimicrobial resistance, and variable access to critical care, necessitates context-specific validation of biomarkers.^9,10 In addition, although comprehensive, widely used scoring systems such as APACHE II may not be feasible for rapid bedside decision-making in all settings. In this context, evaluating serum lactate as a simple, accessible, and cost-effective tool for risk stratification gains particular relevance. Incorporating lactate trends over time, especially within the first 72 hours, may further refine prognostic accuracy and assist in timely escalation or de-escalation of care.^11,12

The present study aimed to assess the prognostic value of baseline and 72-hour serum lactate levels in predicting in-hospital mortality among sepsis patients admitted to a tertiary care center. It also evaluated the correlation between lactate levels and APACHE II scores to determine whether lactate could serve as an independent or complementary biomarker for early risk stratification and outcome prediction in sepsis.

Study Design and Setting: This study was a prospective, observational, non-interventional cohort study conducted in the Department of General Medicine at GMERS Medical College and General Hospital, Himmatnagar, Gujarat, India. The hospital is a tertiary care teaching facility catering to a wide catchment area and regularly managing critically ill patients with sepsis. The study was carried out over one year, from August 2022 to August 2023.

Study Population: The study population consisted of adult patients admitted to the emergency or general wards who were shifted to the Intensive Care Unit (ICU) after initial screening. Patients were eligible for inclusion if they were 18 years or older and presented with a suspected or confirmed infection and an acute change in SOFA (Sequential Organ Failure Assessment) score by ≥2 points, fulfilling Sepsis-3 diagnostic criteria. Written informed consent was obtained from each patient or their legally authorized representative before inclusion.

Inclusion and Exclusion Criteria: Patients were included if they were 18 years or older, diagnosed clinically with sepsis, and exhibited an acute SOFA score elevation of 2 or more. Patients unwilling to participate or those with conditions that could confound lactate levels were excluded. These included individuals with recent surgery or trauma, extensive burns, known malignancies, HIV infection, and chronic liver disease, including cirrhosis.

Sample Size and Sampling Technique: The sample size was calculated based on an anticipated in-hospital mortality rate of 35% among ICU-admitted sepsis patients. Using a confidence level of 95% and an absolute margin of error of 10%, the estimated sample size was determined using the formula N = Z² × p × (1-p) / E², yielding a minimum sample size of 87. A consecutive sampling method was employed to enroll eligible patients who met the inclusion criteria during the study period until the required sample size was achieved.

Study Tools and Data Collection Procedure: Data collection was initiated after approval from the Institutional Ethics Committee. A pre-designed, pre-tested structured proforma was utilized to capture relevant data across three domains: epidemiological characteristics, clinical findings, and outcome measures. Information such as age, sex, presenting symptoms, vital parameters, and systemic examination findings were documented. Investigations included routine blood work, renal and liver function tests, arterial blood gas analysis, lactate measurements, and imaging studies such as chest radiography and ultrasonography, wherever clinically indicated. The APACHE II score was calculated at admission based on physiological and laboratory parameters.

Measurement of Serum Lactate and APACHE II Score: Serum lactate levels were measured at two time points: within the first 3 hours of admission and after 72 hours. Blood samples were drawn under sterile conditions and analyzed using the hospital’s central laboratory autoanalyzer. A serum lactate level ≥2 mmol/L was considered elevated. The APACHE II (Acute Physiology and Chronic Health Evaluation II) scoring system was calculated at admission to assess disease severity, incorporating age, vital signs, laboratory values, and the Glasgow Coma Scale. Higher scores indicated greater predicted mortality risk.

Outcome Assessment: Patients were followed until discharge or in-hospital death. The primary outcome was all-cause in-hospital mortality. Secondary outcomes included the correlation of admission and 72-hour serum lactate levels with mortality and their association with APACHE II scores.

Statistical Analysis: Data were compiled in Microsoft Excel and analyzed using IBM SPSS Statistics version 20. Continuous variables were summarized using means and standard deviations, and categorical variables were presented as frequencies and percentages. The independent Student’s t-test was applied to compare means between survivors and non-survivors, while the chi-square test was used for categorical comparisons. Pearson correlation was used to analyze the association between serum lactate and APACHE II score. A p-value <0.05 was considered statistically significant.

Ethical Considerations: Before initiation, ethical approval for the study was obtained from the Institutional Ethics Committee of GMERS Medical College and Hospital, Himmatnagar. Confidentiality and privacy of the participants were maintained throughout the study. All procedures adhered to the principles of the Declaration of Helsinki.

As shown in Table 1, Patients who died had a higher mean age (54.2 years vs. 47.3 years, p = 0.046) and elevated APACHE II scores (21.7 vs. 19.0, p = 0.013). Notably, non-survivors also had significantly lower Glasgow Coma Scale scores and higher white blood cell counts and serum creatinine levels, indicating more severe physiological derangement at presentation.

Table 1: Baseline Characteristics of Study Participants (n = 87)

*Statistically significant

Table 2 details the serum lactate levels at two time points and their association with mortality. Mean lactate levels at admission and 72 hours were significantly elevated among non-survivors compared to survivors (6.4 vs. 3.5 mmol/L and 6.1 vs. 3.0 mmol/L, respectively; p < 0.001). These findings underscore the strong correlation between persistently raised lactate levels and adverse outcomes in sepsis.

Table 2: Serum Lactate Levels and Their Association with Mortality

*Statistically significant

Table 3: Distribution of Patients by Serum Lactate Categories and Outcome

*Statistically significant

Table 3 categorizes patients based on admission lactate levels and shows a clear trend in mortality. Among patients with lactate <2.5 mmol/L, mortality was only 25%, while it increased to 31.6% in those with levels between 2.5–4.0 mmol/L and peaked at 70.3% in those with levels exceeding 4 mmol/L (p = 0.007). This stratification highlights the prognostic threshold value of ≥4 mmol/L as clinically significant for predicting death.

Table 4: Correlation of Serum Lactate and APACHE II Score with Mortality

*Statistically significant

Table 4 compares the predictive accuracy of serum lactate and APACHE II scores. Lactate levels >4 mmol/L showed better sensitivity (63.4%) and specificity (76.1%) than APACHE II scores ≥20. The area under the curve (AUC) for lactate at 72 hours was the highest (0.745), suggesting superior prognostic performance compared to admission lactate or APACHE II. Combining lactate with APACHE II did not enhance prediction, reaffirming lactate’s standalone utility in sepsis prognosis.

The present study explored the role of serum lactate levels, measured at admission and 72 hours, as predictors of in-hospital mortality in sepsis patients and compared their prognostic value with APACHE II scoring. Sepsis, characterized by an uncontrolled inflammatory response to infection, is associated with high morbidity and mortality. Lactate, a byproduct of anaerobic glycolysis, is known to rise in tissue hypoxia—a hallmark of sepsis-related organ dysfunction. This study demonstrated that elevated serum lactate levels, particularly when persisting beyond 72 hours, were significantly associated with mortality, underlining their value as a prognostic biomarker.

The findings revealed that mean lactate levels at admission were significantly higher among non-survivors (6.4 ± 4.0 mmol/L) compared to survivors (3.5 ± 1.6 mmol/L), and this trend persisted at 72 hours (6.1 ± 4.5 vs. 3.0 ± 1.6 mmol/L, p < 0.001). These results align with those reported by Nguyen et al.,⁶ who observed mean lactate levels of 8.0 ± 4.7 mmol/L in non-survivors and 6.1 ± 4.4 mmol/L in survivors​. Similarly, Chaudhari et al.¹³ noted significantly higher lactate levels in non-survivors (8.3 ± 2.55 mmol/L) compared to survivors (5.21 ± 2.22 mmol/L)​. This consistent association reinforces the utility of serum lactate in early risk stratification. The present study further supports the assertion by Villar et al.¹⁴ that increasing lactate concentration is directly proportional to short-term mortality, with significantly higher mortality observed among patients whose lactate exceeded 4 mmol/L​.

A cut-off value of 4 mmol/L for serum lactate was identified as a critical prognostic threshold. Patients with lactate ≥4 mmol/L at admission had 3.68 times higher odds of death (p = 0.005), while the odds increased to 4.31 after 72 hours (p = 0.003). This concurs with the findings of Trzeciak et al.,^15, who demonstrated that lactate levels ≥4 mmol/L were associated with nearly six-fold increased risk of acute-phase mortality​. Furthermore, when analyzed in terms of predictive accuracy, the specificity of serum lactate improved over time—rising from 76.1% at admission to 80.4% at 72 hours—suggesting that persistently elevated lactate may reflect ongoing tissue hypoxia despite resuscitative efforts.

Although APACHE II remains a widely used scoring system to assess disease severity and predict outcomes, its performance was relatively modest in this study. The mean APACHE II score was significantly higher in non-survivors (21.7 ± 5.0) than survivors (19.0 ± 4.8; p = 0.013), indicating its predictive capability. However, when using a cut-off score of 17, the odds ratio for mortality was 1.63 and failed to achieve statistical significance (p = 0.343), echoing the findings of Sadaka et al.,¹⁶ who stated that while APACHE II has good discriminative capacity, it may not serve as a standalone predictor in all settings​. The ROC curve analysis also highlighted that lactate at 72 hours (AUC = 0.745) was a better discriminator of mortality than either admission lactate (AUC = 0.724) or APACHE II (AUC = 0.648), underscoring the superiority of dynamic lactate monitoring in prognostication.

When the predictive utility of combining APACHE II with either admission or Day 3 lactate levels was evaluated, no significant incremental benefit was noted. The AUC for these combinations dropped to 0.561 and 0.560, respectively, indicating that the added complexity did not enhance clinical utility. This suggests that serum lactate levels, particularly at 72 hours, can independently guide risk stratification and may be more practical in resource-limited settings than composite scoring systems.

In summary, this study substantiates the role of serum lactate—especially persistent elevation beyond 72 hours—as a robust and independent predictor of mortality in sepsis. The findings are well supported by global literature, including the work of Bou Chebl et al.,¹⁷ Cao et al.,¹⁸ and guidelines by the Surviving Sepsis Campaign,¹⁹ which advocate serial lactate monitoring as part of standard sepsis management​. Incorporating lactate measurement in the routine evaluation of sepsis patients may facilitate timely intervention, improved prognostication, and rational use of critical care resources.

LIMITATIONS

This was a single-center study with a limited sample size, which may affect the generalizability of the findings. Only ICU-admitted patients were included, introducing potential selection bias. Lactate was measured at only two-time points, and confounding factors such as comorbidities or infection sources were not fully controlled—the observational design limits causal inference.

The present study concludes that serum lactate, particularly when measured serially, is a strong independent predictor of in-hospital mortality among patients with sepsis. Elevated lactate levels at admission and persistent elevation after 72 hours were significantly associated with poor outcomes, with a threshold of ≥4 mmol/L demonstrating high prognostic value. While APACHE II scores were also higher in non-survivors, their predictive capacity was comparatively limited, and combining them with lactate measurements did not yield additional benefits. These findings emphasize the clinical relevance of lactate monitoring in guiding early risk stratification, prognostic assessment, and timely intervention in sepsis management, especially in resource-constrained settings.

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