COMPARATIVE EVALUATION OF PROCALCITONIN AND SERUM LACTATE AS PROGNOSTIC BIOMARKERS IN SEPSIS

Sepsis is characterized as a dangerous failure of organ systems resulting from a patient's irregular immune reaction to an infection. This medical condition encompasses a range of severity, from initial sepsis to septic shock, and continues to be a primary driver of Intensive Care Unit (ICU) admissions and global mortality. Pathophysiologically, a disruption in the equilibrium between pro-inflammatory and anti-inflammatory pathways triggers widespread cytokine release and the activation of coagulation and complement cascades, resulting in microcirculatory impairment and eventual multiorgan failure (1,2). During septic shock, impaired oxygen delivery relative to cellular demand forces tissues to switch from oxidative  phosphorylation to anaerobic glycolysis and subsequent lactate production. (3,4)

Historically, sepsis diagnosis relied on the Systemic Inflammatory Response Syndrome (SIRS) framework, which required ≥2 of the following abnormalities: temperature >38 °C or <36 °C, heart rate >90 beats/min, respiratory rate >20 breaths/min or PaCO₂ <32 mmHg, and deranged white blood cell count (>12,000/mm³, <4,000/mm³, or >10% immature forms). Despite its clinical utility, SIRS has limited specificity for outcome prediction. Subsequently, the Sepsis-3 consensus shifted focus to organ dysfunction, operationalized through a Sequential Organ Failure Assessment (SOFA) score increase of ≥2 points as the diagnostic threshold for sepsis. As a practical bedside adjunct, the quick SOFA (qSOFA) tool was introduced, comprising three parameters — reduced level of consciousness (GCS below 15), elevated respiratory rate (≥22/min), and low systolic blood pressure (≤100 mmHg) — with a score of ≥2 signalling heightened risk of adverse outcomes.(5)

Risk stratification systems such as the Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation II (APACHE II) are commonly employed to estimate disease severity and assess mortality risk. However, these scoring systems require multiple clinical and laboratory parameters and may not always be feasible in emergencies or resource- limited settings. (6)

Serum lactate functions as a sensitive, though non-specific, marker of tissue oxygen insufficiency and cellular metabolic disturbance. Elevated lactate levels typically arise from impaired oxygen consumption, enhanced anaerobic metabolic activity, and reduced hepatic and renal clearance.(3) Given that rising lactate concentrations correlate with increased mortality, repeated lactate monitoring has been incorporated into sepsis resuscitation bundles as a means of tracking treatment response.(3,4,6)

Additionally, procalcitonin (PCT), the biochemical precursor to calcitonin, rises during systemic bacterial infections and serves as a reflection of the severity of organ dysfunction and the inflammatory response (2,7,8). Furthermore, serial assessment of procalcitonin (PCT) levels during intensive care unit stay may offer valuable prognostic insights into patient outcomes. (9,10,11)

Notwithstanding their routine clinical application, the question of which biomarker holds superior prognostic value in sepsis remains unresolved. The present study was therefore designed to directly compare the prognostic utility of serum lactate and PCT, examining their temporal kinetics throughout the ICU stay, with the aim of identifying the more reliable marker for outcome prediction in critically ill sepsis patients.

OBJECTIVE

To compare the prognostic utility of serum lactate and procalcitonin levels in predicting disease severity in patients with sepsis

This retrospective, record-based cross-sectional study was conducted in the medical and surgical ICUs of Apollo General Hospital, Hyderabad, India. The study was initiated after approval by the Institutional Research Committee of AIMSR. As this was a record-based study, previously documented clinical and laboratory data were analyzed.

Study eligibility was assessed for 118 individuals aged ≥18 years who were hospitalized in medical or surgical ICUs with sepsis during the period from June 2024 to June 2025. Patients were categorized as having sepsis if they met the SIRS criteria in addition to having a presumed or documented infection.

Inclusion criteria for the study comprised adults aged 18 years or above, of any sex, admitted to the ICU with sepsis fulfilling SIRS parameters. To be eligible, patients also required documented assessments of specific serum biomarkers, namely lactate and procalcitonin, both at the point of ICU admission and throughout the duration of their hospitalization.

Exclusion criteria for the study comprises of patients with incomplete or missing clinical or laboratory data, those who had undergone recent major surgery, those with severe trauma, extensive burns, severe hepatic dysfunction, metabolic disorders, or seizures and those with conditions that could independently influence serum lactate and procalcitonin levels.

Of the 118 patients initially screened, 21 were subsequently excluded based on the predefined criteria. Thus, the final analysis comprised 97 patients.

At the point of admission, baseline clinical were recorded for each patient, encompassing  vital signs (including blood pressure, heart rate, respiratory rate, and body temperature), total leukocyte count, and Glasgow Coma Scale (GCS) values. Initial qSOFA scores were also determined at this stage. Laboratory evaluations for serum procalcitonin and lactate were completed within the first 24 hours of admission, followed by periodic reassessments of all clinical variables on hospital days 3, 5, and 7. All statistical computations were performed using IBM SSPS Statistics, version 24.0.

DATA ANALYSIS

Continuous variables are reported as mean ± standard deviation accompanied by 95% confidence intervals (CI), while categorical variables are presented as  frequencies and percentages. To evaluate the relationships between PCT, serum lactate, qSOFA scores, and total leukocyte count (TLC), the Pearson correlation coefficient was utilized. The prognostic accuracy of these biomarkers was measured through receiver operating characteristic (ROC) curve analysis. Furthermore, area under the curve (AUC) values were calculated, and the Youden index was applied to establish optimal diagnostic cut-off thresholds. Statistical significance was set at a two-tailed p-value of less than 0.05.

and no statistically significant results.

Overall, although both biomarkers declined over time, PCT demonstrated a stronger association with qSOFA scores and relatively better prognostic performance than serum lactate.

Sepsis is defined as a multifaceted pathological state where an aberrant host immune response to an infectious agent triggers widespread inflammation, reduced blood flow to tissues, and the failure of various organ systems. The early identification of reliable biomarkers capable of predicting disease severity and clinical outcomes is necessary for optimizing management strategies and improving survival. (1)

In the present study, both PCT and serum  lactate were evaluated as prognostic tools in individuals requiring intensive care due to sepsis. The findings demonstrated that PCT levels were significantly correlated with qSOFA scores during hospitalization, indicating that increasing PCT levels were associated with worsening clinical severity. However, the strength of this association was weak-to-moderate, suggesting a modest relationship between PCT levels and disease severity. The strongest correlation observed between PCT on day 5 and qSOFA score on day 7 suggests that procalcitonin levels may reflect impending clinical deterioration. Furthermore, serial measurements revealed a progressive decline in procalcitonin levels among patients who demonstrated clinical improvement, highlighting its utility in monitoring therapeutic response. These observations agree with prior studies reporting the rise in procalcitonin levels during systemic bacterial infection owing to the upregulation of the CALC-1 gene in response to microbial toxins and inflammatory cytokines. (2,7)

In contrast, although serum lactate levels showed a statistically significant overall decline over time, they failed to demonstrate clinically meaningful correlations with qSOFA scores or inflammatory markers across the study period. Only a weak and isolated association was observed, while most correlations remained non-significant. Furthermore, receiver operating characteristic (ROC) analysis revealed poor discriminative ability of serum lactate, with no statistically significant predictive performance, whereas procalcitonin showed a progressive improvement in diagnostic accuracy over time. Although sensitivity was high, specificity remained low, limiting procalcitonin’s standalone clinical utility. These findings indicate that, despite its established role as a marker of tissue hypoxia and metabolic stress, serum lactate may have limited prognostic reliability when used in isolation. Similar variability in serum lactate performance has been reported in previous studies, where its prognostic value was influenced by factors such as hepatic clearance, comorbid conditions, and heterogeneity in patient populations (4). Conversely, other investigators have reported serum lactate clearance as a useful predictor of mortality, suggesting that differences in study design, patient severity, and endpoints may account for the observed discrepancies (12).

An additional observation was the presence of a weak but statistically significant correlation between PCT and total leukocyte count at admission, suggesting a relationship with the early inflammatory response. However, this association was not sustained over time, reflecting the dynamic and heterogeneous nature of the immune response in sepsis. The absence of a consistent relationship between serum lactate and leukocyte count further supports the limited role of lactate as an inflammatory biomarker.

Overall, the results of the present study support the hypothesis that procalcitonin demonstrates comparatively better, though modest performance, than serum lactate as a biomarker for predicting outcomes in sepsis. The ability of PCT to demonstrate significant correlations with clinical severity, its dynamic decline with clinical improvement, and its relatively better performance in ROC analysis collectively establish its clinical relevance in risk stratification and monitoring. However, certain unexpected findings, such as the lack of strong correlation between serum lactate and qSOFA, may be attributed to factors such as early clinical intervention, variability in tissue perfusion states, and differences in serum lactate metabolism among individuals.

Serum procalcitonin and serum lactate levels measured during the ICU stay were evaluated for  their clinical prognostic relevance in patients with sepsis in correlation with the qSOFA score and total leukocyte count. The findings suggest that procalcitonin demonstrates relatively better,  though modest, prognostic performance than serum lactate; however, expanded multicenter trials are essential to corroborate the current observations.

LIMITATIONS

This study is subject to several constraints. As it was executed in a single institution, which may have introduced population bias and the findings may not be fully generalizable to other patient populations. The follow-up window was confined to seven days, which may be insufficient to capture the complete clinical evolution of sepsis over a longer observation period. Additionally, mortality outcomes were not analyzed due to incomplete longitudinal data on biomarker levels and qSOFA scores for all patients, which may have introduced attrition bias and limited the validity of outcome analysis. Furthermore, qSOFA was used as a surrogate marker of disease severity rather than a definitive clinical outcome such as mortality, which may limit the interpretation of prognostic accuracy. Therefore, further large-scale multicenter studies with longer follow-up durations are required to minimize potential confounding factors and better establish the prognostic significance of PCT and serum lactate levels in patients with sepsis.

ACKNOWLEDGEMENTS

The authors thank the Department of General Medicine, AIMSR, for permitting and supporting this study. We are grateful to the Institutional Research Committee for their approval and guidance. We also acknowledge the support of the Medical Records Department and ICU staff for their assistance in data collection. We extend our appreciation to the laboratory personnel for their cooperation in processing the investigations.

Funding: No Funding sources

Conflicts of interest: The authors have no conflicts of interest to declare.

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