Sepsis is a life-threatening syndrome arising from a dysregulated host response to infection and remains a major cause of preventable death, prolonged critical illness, and healthcare use. Global estimates indicate that sepsis accounts for a substantial proportion of deaths across all age groups and regions [1]. Contemporary Sepsis-3 terminology defines sepsis through infection-associated organ dysfunction and identifies septic shock as a high-risk subset with persistent circulatory and metabolic abnormalities [2,3]. Although the term severe sepsis has been removed from current definitions, it remains present in many clinical datasets and institutional protocols. Timely recognition, antimicrobial treatment, source control, haemodynamic support, and repeated assessment are central to modern sepsis management [4].

Lactate is produced continuously during glycolysis and is cleared predominantly by the liver, with additional renal contribution. In sepsis, hyperlactataemia cannot be attributed solely to anaerobic metabolism. Reduced tissue oxygen delivery, impaired oxygen utilisation, accelerated aerobic glycolysis from adrenergic stimulation, mitochondrial dysfunction, diminished pyruvate oxidation, and reduced hepatic or renal clearance can coexist. Consequently, lactate is best interpreted as an integrated marker of metabolic stress rather than a direct measurement of tissue hypoxia. Its practical strengths are rapid availability, low sample volume, and responsiveness to changes in perfusion and cellular metabolism. Elevated lactate can also disclose occult hypoperfusion in patients without overt hypotension.

Observational studies have consistently linked increasing lactate concentrations with mortality in infected emergency-department and intensive-care populations [5-7]. Early lactate reduction has likewise been associated with improved survival [5], and lactate clearance has been tested as a resuscitation endpoint in randomised and observational studies [8,9]. Nevertheless, prognostic performance varies with sampling time, initial concentration, illness severity, treatment exposure, and the formula used to calculate clearance. Suggested mortality thresholds range from modest elevations to concentrations of 4 mmol/L or higher [6,7,10]. Subsequent lactate values can outperform the initial measurement, while some investigations have found absolute concentrations more informative than calculated clearance [11,12]. Even lactate values near the conventional reference range have been associated with increased risk in critically ill populations [13]. These findings support serial interpretation but also underline the need for setting-specific evaluation.

Evidence from Indian emergency-care populations remains comparatively limited, particularly for heterogeneous medical and surgical sepsis presenting at first contact. The present study therefore aimed to evaluate arterial lactate as a predictive marker in patients with sepsis or septic shock presenting to the emergency department. The primary objective was to measure arterial lactate early after presentation. The secondary objectives were to examine serial lactate concentrations at 24, 48, and 72 hours, compare lactate and the recorded clearance index between survivors and non-survivors, assess associations with haemodynamic variables, and determine mortality discrimination using receiver operating characteristic analysis.

Study design and setting: This hospital-based prospective observational study was conducted over six months in the Departments of Emergency Medicine and Critical Care at KIMS Saveera Hospital, Anantapuramu, Andhra Pradesh, India. Study population: Consecutive patients presenting to the emergency department with a treating-team diagnosis of sepsis or septic shock, or with clinical features indicating a high risk of progression, were screened. Eligible features included suspected infection with hypotension, tachycardia, fever or hypothermia, reduced urine output, or reduced mean arterial pressure. Patients with relevant vulnerability, including diabetes mellitus or immunodeficiency, were also considered when infection-related systemic deterioration was suspected. Eligibility criteria: Patients diagnosed with sepsis or septic shock and those at risk of developing these conditions were included after consent. Patients with alternative disorders capable of independently increasing arterial lactate were excluded, including acute respiratory failure associated with chronic obstructive pulmonary disease, renal tubular acidosis, and diabetic ketoacidosis. The original protocol did not specify an age restriction. Sample size: A sample of 150 patients was planned. The calculation used an anticipated positive predictive value of lactate clearance of 54.7%, an absolute precision of 8%, and a 95% confidence level. The calculated value of 149 was rounded to 150. Data collection and measurements: Demographic characteristics, presenting symptoms, medical history, comorbidities, general and systemic examination findings, vital signs, and final clinical diagnoses were recorded in a pretested proforma. Arterial blood was obtained for blood-gas analysis and lactate estimation. Supportive investigations included total leukocyte count, blood culture, and antimicrobial susceptibility testing when clinically indicated. Arterial lactate and total leukocyte count were documented at baseline and at 24, 48, and 72 hours. Vital signs were monitored serially during the first 72 hours. The primary outcome was in-hospital mortality. The dataset reported lactate clearance as a signed change index rather than a conventional percentage; negative values denoted a follow-up concentration above the baseline value, and the recorded index was analysed without recalculation. Statistical analysis: Continuous variables were summarised as mean, standard deviation, and range; categorical variables were reported as frequency and percentage. Serial continuous measurements were compared across time, and survivor–non-survivor differences were expressed with 95% confidence intervals. Categorical associations were assessed using chi-square or Fisher’s exact test, as appropriate. Correlation coefficients described relationships between blood pressure and lactate. Receiver operating characteristic curves, areas under the curve, and Youden-index cut-offs were used to evaluate mortality discrimination. A two-sided p value below 0.05 indicated statistical significance. Ethical considerations: Institutional Ethics Committee approval was obtained before enrolment. Written informed consent was secured from each patient or authorised attendant. Data were handled confidentially, and clinical management remained under the treating team.

A total of 150 patients were included. The mean age was 46.60 ± 15.31 years (range, 19–86 years), and 98 patients (65.3%) were male. Diabetes mellitus was the most frequent comorbidity, followed by systemic hypertension and coronary artery disease. The study population represented a heterogeneous emergency sepsis cohort, with diabetic foot ulcer, grade 3 pressure sores, appendicitis, cellulitis, and lower respiratory tract infection forming the leading diagnostic groups. The baseline profile and complete diagnostic distribution are presented in Table 1.

Table 1. Baseline demographic, comorbidity, and diagnostic profile (N=150)

Values are mean ± standard deviation, range, or n (%). Percentages are based on 150 participants.

At presentation, tachycardia and tachypnoea were prominent. Mean pulse rate declined from 116.19 ± 5.69 beats/min at baseline to 73.91 ± 5.04 beats/min at 72 hours, whereas the respiratory rate decreased from 24.99 ± 2.99 to 14.44 ± 0.82 breaths/min. Peripheral oxygen saturation improved from 94.80 ± 1.30% to 97.79 ± 0.74%. Total leukocyte count fell progressively during follow-up. Arterial lactate increased from 1.067 ± 0.32 mmol/L at baseline to 2.642 ± 1.91 mmol/L at 24 hours, remained elevated at 48 hours, and declined to 1.190 ± 0.67 mmol/L at 72 hours. These serial clinical and laboratory measurements are summarised in Table 2.

Table 2. Serial vital signs and laboratory indices during the first 72 hours

Values are mean ± standard deviation, except baseline temperature, which is shown as mean (range). SBP: systolic blood pressure; DBP: diastolic blood pressure; SpO₂: peripheral oxygen saturation. The source standard deviation for baseline temperature was not interpretable.

Sixty patients died during hospitalisation, giving an in-hospital mortality of 40.0%, whereas 90 patients (60.0%) survived. Study-defined high lactate categories were strongly associated with mortality at 24, 48, and 72 hours. Baseline lactate did not differ between non-survivors and survivors; however, marked separation emerged at 24 hours and persisted at 48 hours. At 72 hours, the between-group difference remained statistically significant but was smaller. Mortality distributions and lactate values according to survival status are shown in Table 3.

Table 3. Mortality distribution and arterial lactate according to survival status

High and low lactate categories are reproduced from the source dataset; corresponding category thresholds were not stated in the source table. CI: confidence interval; SD: standard deviation.

The recorded signed lactate-clearance index was more negative among non-survivors at 24, 48, and 72 hours. In receiver operating characteristic analysis, baseline lactate showed no useful mortality discrimination. Discrimination was excellent at 24 hours (AUC, 0.925) and good at 48 hours (AUC, 0.876). A 24-hour lactate cut-off of 4.05 mmol/L yielded 93.2% sensitivity and 95.6% specificity. The signed clearance index produced AUC values below 0.5, indicating poor or directionally inverted discrimination in its recorded form (Table 4).

Table 4. Recorded lactate-clearance index and receiver operating characteristic performance

The source dataset reported a signed change index rather than conventional percentage lactate clearance. More negative values corresponded to higher follow-up lactate relative to baseline. AUC: area under the receiver operating characteristic curve; CI: confidence interval. Cut-offs were derived using the Youden index.

Systolic blood pressure was inversely correlated with arterial lactate at baseline and at 24, 48, and 72 hours. The strongest relationship was observed at baseline (r=-0.301; p<0.001), whereas subsequent correlations were weaker but remained statistically significant. Diastolic blood pressure showed a weak positive correlation at baseline and no significant association at later time points (Table 5).

Table 5. Correlation of arterial lactate with systolic and diastolic blood pressure

DBP: diastolic blood pressure; SBP: systolic blood pressure.

This study demonstrates that serial arterial lactate concentrations, particularly at 24 and 48 hours, were substantially more informative than the baseline value for predicting in-hospital mortality. Mortality was 40%, and non-survivors showed marked lactate elevation at 24 and 48 hours despite nearly identical baseline concentrations. The 24-hour AUC of 0.925 and 48-hour AUC of 0.876 indicate strong discrimination. By contrast, baseline lactate had an AUC below 0.5, probably reflecting the narrow baseline range of 0.5–2.0 mmol/L and the timing of measurement before the full metabolic consequences of illness became apparent. These findings reinforce the principle that lactate kinetics provide information beyond a single measurement. Nguyen et al. reported that early lactate clearance was associated with improved outcome in severe sepsis and septic shock [5]. Trzeciak et al. and Howell et al. also demonstrated increasing mortality with higher lactate among emergency patients with infection, including normotensive patients with occult hypoperfusion [6,7]. In the present cohort, systolic blood pressure correlated inversely with lactate, supporting the complementary value of metabolic and haemodynamic assessment. However, the modest correlation coefficients indicate that lactate should not be treated as a surrogate for blood pressure alone. The optimal 24-hour threshold of 4.05 mmol/L yielded high sensitivity and specificity. This aligns with evidence that concentrations near or above 4 mmol/L identify a particularly high-risk group [6,7], although Rabello Filho et al. reported a lower optimum of 2.5 mmol/L in a different sepsis population [10]. Variation in thresholds is expected because case mix, treatment before sampling, organ dysfunction, and outcome timing differ across studies. Ryoo et al. found that the absolute 6-hour lactate concentration outperformed clearance in Sepsis-3 septic shock [11], while Lee et al. similarly showed important prognostic information from serial lactate levels in patients with initial hyperlactataemia [12]. The present data extend this pattern to later 24- and 48-hour measurements. An unexpected result was the poor ROC performance of the recorded clearance index, despite significantly more negative values among non-survivors. Conventional clearance is usually expressed as a percentage reduction from baseline, and higher clearance has predicted survival in several cohorts [5,14] and has been evaluated as a therapeutic target [8,9]. Here, the source dataset used a signed change measure, with negative values representing rising follow-up lactate. This reversed orientation explains part of the sub-0.5 AUC and limits direct comparison with standard percentage clearance. Absolute serial concentrations therefore provide the more interpretable prognostic signal in this dataset. Clinically, the results support repeated lactate measurement alongside examination, blood pressure, urine output, oxygenation, infection control, and organ-function assessment. Lactate should guide risk stratification and reassessment rather than trigger isolated fluid administration, because hyperlactataemia reflects several metabolic mechanisms. Patients with persistent elevation at 24 or 48 hours warrant urgent review for inadequate source control, unresolved hypoperfusion, organ dysfunction, or treatment failure. Limitations This single-centre study included a heterogeneous spectrum of medical and surgical infections, limiting external generalisability. Sepsis severity scores, organ-support requirements, microbiological profiles, treatment timing, and multivariable adjustment were not consistently available. The signed lactate-clearance index differed from conventional percentage clearance, complicating comparison with published studies. Baseline lactate values were narrowly distributed, and mortality was assessed only during the index hospitalisation without longer-term follow-up.

Serial arterial lactate measurement provided prognostic information in patients with sepsis or septic shock presenting to the emergency department. Baseline lactate did not distinguish survivors from non-survivors, whereas concentrations measured at 24 and 48 hours showed strong mortality discrimination. A 24-hour lactate threshold of 4.05 mmol/L achieved high sensitivity and specificity. Persistent elevation was associated with lower systolic blood pressure and a markedly increased risk of death. The signed clearance index was less interpretable and performed poorly in ROC analysis. Arterial lactate should therefore be reassessed serially and interpreted with haemodynamic status, organ function, response to antimicrobial therapy, and adequacy of source control to support escalation of care.

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):200–211.

2. 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. 2016;315(8):801–810.
3. Shankar-Hari M, Phillips GS, Levy ML, Seymour CW, Liu VX, Deutschman CS, et al. Developing a new definition and assessing new clinical criteria for septic shock: for the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315(8):775–787.
4. Evans L, Rhodes A, Alhazzani W, Antonelli M, Coopersmith CM, French C, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock 2021. Intensive Care Med. 2021;47(11):1181–1247.
5. Nguyen HB, Rivers EP, Knoblich BP, Jacobsen G, Muzzin A, Ressler JA, et al. Early lactate clearance is associated with improved outcome in severe sepsis and septic shock. Crit Care Med. 2004;32(8):1637–1642.
6. Trzeciak S, Dellinger RP, Chansky ME, Arnold RC, Schorr C, Milcarek B, et al. Serum lactate as a predictor of mortality in patients with infection. Intensive Care Med. 2007;33(6):970–977.
7. Howell MD, Donnino M, Clardy P, Talmor D, Shapiro NI. Occult hypoperfusion and mortality in patients with suspected infection. Intensive Care Med. 2007;33(11):1892–1899.
8. Jones AE, Shapiro NI, Trzeciak S, Arnold RC, Claremont HA, Kline JA; Emergency Medicine Shock Research Network Investigators. Lactate clearance versus central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial. JAMA. 2010;303(8):739–746.
9. Jansen TC, van Bommel J, Schoonderbeek FJ, Sleeswijk Visser SJ, van der Klooster JM, Lima AP, et al. Early lactate-guided therapy in intensive care unit patients: a multicenter, open-label, randomized controlled trial. Am J Respir Crit Care Med. 2010;182(6):752–761.
10. Rabello Filho R, Rocha LL, Corrêa TD, Pessoa CM, Colombo G, Assuncao MS. Blood lactate levels cutoff and mortality prediction in sepsis—time for a reappraisal? A retrospective cohort study. Shock. 2016;46(5):480–485.
11. Ryoo SM, Lee J, Lee YS, Lee JH, Lim KS, Huh JW, et al. Lactate level versus lactate clearance for predicting mortality in patients with septic shock defined by Sepsis-3. Crit Care Med. 2018;46(6):e489–e495.
12. Lee SG, Song J, Park DW, Moon S, Cho HJ, Kim JY, et al. Prognostic value of lactate levels and lactate clearance in sepsis and septic shock with initial hyperlactatemia: a retrospective cohort study according to the Sepsis-3 definitions. Medicine (Baltimore). 2021;100(7):e24835.
13. Rishu AH, Khan R, Al-Dorzi HM, Tamim HM, Al-Qahtani S, Al-Ghamdi G, et al. Even mild hyperlactatemia is associated with increased mortality in critically ill patients. Crit Care. 2013;17(5):R197.
14. Marty P, Roquilly A, Vallée F, Luzi A, Ferré F, Fourcade O, et al. Lactate clearance for death prediction in severe sepsis or septic shock patients during the first 24 hours in intensive care unit: an observational study. Ann Intensive Care. 2013;3(1):3.