European Journal of Cardiovascular Medicine

Sepsis is a life-threatening condition caused by a dysregulated host response to infection, leading to organ dysfunction and high mortality worldwide [1]. Despite advances in critical care and antimicrobials, sepsis remains a leading cause of ICU deaths [2]. Early identification of patients at high risk of poor outcomes is crucial to improve survival. While scoring systems such as SOFA and APACHE II are widely used, they are often complex, resource-intensive, and less feasible in resource-limited settings [3].

Recent research has focused on identifying simple, inexpensive prognostic markers that are routinely available. Red cell distribution width (RDW), a measure of variability in red blood cell size, traditionally used for anemia evaluation, has emerged as a potential predictor of outcomes in sepsis [4,5]. Elevated RDW has been associated with increased inflammation, oxidative stress, and impaired erythropoiesis—all of which are central to sepsis pathophysiology [6]. Several studies have demonstrated that higher RDW correlates with increased mortality and prolonged ICU stay in septic patients [7].

For example, Loureiro et al. found that elevated RDW at ICU admission was significantly higher in non-survivors of sepsis, independently predicting mortality. Similarly, Balta et al. reported that RDW was a strong independent predictor of death in patients with severe sepsis and septic shock. In an Indian ICU setting, Krishna et al. demonstrated that RDW could stratify sepsis patients by risk, showing a positive correlation with disease severity scores [8]. Meta-analyses have confirmed these findings, with Zhang et al. reporting that higher RDW values were consistently associated with increased mortality across multiple populations. Wang and Hsu further showed that combining RDW with lactate levels enhanced prognostic accuracy in septic patients [9].

The underlying mechanism linking RDW to poor outcomes in sepsis likely involves systemic inflammation, oxidative stress, and bone marrow dysfunction, resulting in anisocytosis. RDW may also reflect nutritional deficiencies, chronic comorbidities, or other physiological stresses that worsen prognosis. Its main advantage lies in its simplicity and availability as part of a routine complete blood count, making it a practical tool for early risk stratification even in resource-constrained hospitals [10]

The primary aim of this study is to evaluate the prognostic value of red cell distribution width (RDW) in patients with sepsis admitted to a tertiary care center in Eastern India. Specifically, the study seeks to determine whether elevated RDW at the time of hospital admission is associated with increased in-hospital mortality. Secondary objectives include assessing the relationship between RDW and other clinical outcomes such as the duration of intensive care unit (ICU) stay, the requirement for mechanical ventilation, and correlation with established severity scores like SOFA and APACHE II. Additionally, the study aims to explore whether RDW, as a simple and inexpensive laboratory parameter, can serve as a practical tool for early risk stratification in septic patients, particularly in resource-constrained healthcare settings.

Study Type: Retrospective study Study place: Nalanda Medical College and Hospital, Patna, Bihar Study duration: 9 months (1st February 2025 to 31st October 2025) Study Population : The study will include adult patients (≥18 years) diagnosed with sepsis and admitted to Nalanda Medical College and Hospital , Eastern India, between 1st February 2025 and 31st October 2025. Patients with hematological disorders, chronic liver disease, malignancy, or recent blood transfusions will be excluded. Data including demographics, RDW at admission, comorbidities, and clinical outcomes will be collected retrospectively from hospital records. Sample size: 200 patients diagnosed with sepsis. Study Variables: • Baseline Demographic Characteristics of Patients • Clinical Outcomes According to RDW Levels • Laboratory Parameters at Admission Inclusion Criteria: 1. Adult patients aged ≥18 years. 2. Patients diagnosed with sepsis according to Sepsis-3 criteria. 3. Patients admitted to the ICU or general ward during the study period. 4. Availability of complete medical records, including RDW values at admission. Exclusion Criteria: 1. Patients with pre-existing hematological disorders Patients who received blood transfusions within the past 3 months. 2. Patients with chronic liver disease or malignancy. 3. Pregnant women. 4. Patients with incomplete medical records or missing RDW data. Statistical analysis: Data from the study were analyzed using SPSS software, with continuous variables (e.g., age, liver enzyme levels) expressed as mean ± SD and compared using t-tests or Mann–Whitney U tests. Categorical variables (e.g., gender, CBD stones, and complications) were presented as frequencies and percentages, and compared using Chi-square or Fisher’s exact tests. Diagnostic accuracy (sensitivity, specificity, PPV, NPV, and accuracy) was calculated for MRCP-first and EUS-first strategies, using ERCP/intraoperative findings as the reference. Kaplan-Meier analysis may be used for time-to-intervention comparisons. A p-value < 0.05 was considered significant.

1. Baseline Demographics and Comorbidities

A total of 200 patients with sepsis were included, divided equally into two groups based on RDW levels: ≤14% (n = 100) and >14% (n = 100). The mean age in the RDW >14% group was significantly higher at 56.7 ± 15.1 years compared to 52.3 ± 14.2 years in the RDW ≤14% group (p = 0.04). In terms of sex distribution, 62 patients (62%) were male and 38 patients (38%) were female in the RDW ≤14% group, while the RDW >14% group included 68 males (68%) and 32 females (32%) (p = 0.38), showing no significant difference. Regarding comorbidities, diabetes was present in 28 patients (28%) in the RDW ≤14% group and 35 patients (35%) in the RDW >14% group (p = 0.28); hypertension was observed in 30 patients (30%) versus 38 patients (38%) (p = 0.21); and chronic kidney disease occurred in 12 patients (12%) in the RDW ≤14% group compared to 18 patients (18%) in the RDW >14% group (p = 0.21). These results indicate that apart from age, there were no statistically significant differences in baseline demographics or comorbidities between the two RDW groups.

Table 1: Baseline Demographic Characteristics of Patients (n = 200)

Figure 1: Baseline Demographic Characteristics of Patients (n = 200)

2. Clinical Outcomes

Clinical outcomes were significantly worse in patients with elevated RDW. The mean ICU stay was longer in the RDW >14% group at 9.5 ± 3.4 days compared to 6.2 ± 2.8 days in the RDW ≤14% group (p < 0.001). The need for mechanical ventilation was also higher in the RDW >14% group, with 45 patients (45%) requiring ventilatory support versus 20 patients (20%) in the RDW ≤14% group (p < 0.001). In-hospital mortality was significantly greater in patients with RDW >14%, affecting 38 patients (38%) compared to 15 patients (15%) in the RDW ≤14% group (p < 0.001).

Table 2: Clinical Outcomes According to RDW Levels

Figure 2: Clinical Outcomes According to RDW Levels

3. Laboratory Parameters at Admission

Laboratory investigations revealed significant differences between the two RDW groups. As expected, RDW values were higher in the RDW >14% group (15.2 ± 0.8%) compared to the RDW ≤14% group (13.5 ± 0.3%, p < 0.001). Hemoglobin levels were lower in the RDW >14% group at 11.0 ± 1.6 g/dL versus 11.8 ± 1.5 g/dL in the RDW ≤14% group (p = 0.002). White blood cell (WBC) counts were elevated in patients with higher RDW (14.5 ± 5.0 ×10³/µL) compared to those with lower RDW (12.2 ± 4.1 ×10³/µL, p = 0.01). Serum creatinine levels were also significantly higher in the RDW >14% group (1.8 ± 0.9 mg/dL) versus the RDW ≤14% group (1.2 ± 0.5 mg/dL, p < 0.001).

Table 3: Laboratory Parameters at Admission

4. RDW with SOFA Score

Among the 200 patients studied, a clear gradient was observed between RDW categories and SOFA score severity. In the RDW <14% group (n = 100), 81 patients (81.0%) had SOFA scores ≤6, while 19 patients (19.0%) had SOFA scores >6. In contrast, among patients with RDW 14.1–16% (n = 60), 26 patients (43.3%) had SOFA scores ≤6 and 34 patients (56.7%) had SOFA scores >6. This pattern was most pronounced in the RDW >16% group (n = 40), where only 8 patients (20.0%) had SOFA scores ≤6, whereas 32 patients (80.0%) had SOFA scores >6.The association between RDW category and SOFA score was statistically significant (p = 0.001).

Table 4: Association between RDW with SOFA Score in Sepsis (n = 200)

5. Sepsis Etiology with Outcome

In the present study involving 200 patients with sepsis, gram-positive bacterial infections were identified in 70 patients, gram-negative bacterial infections in 80 patients, fungal infections in 20 patients, and viral infections in 20 patients. Among patients with gram-positive bacterial sepsis (n = 70), 45 patients (64.3%) had mild to moderate sepsis, while 25 patients (35.7%) developed severe sepsis or septic shock. In the gram-negative bacterial group (n = 80), 35 patients (43.8%) had mild to moderate sepsis and 45 patients (56.2%) progressed to severe sepsis or septic shock. Among patients with fungal sepsis (n = 20), 5 patients (25%) had mild to moderate sepsis, whereas 15 patients (75%) had severe sepsis or septic shock. In contrast, in the viral sepsis group (n = 20), 15 patients (75%) presented with mild to moderate sepsis and only 5 patients (25%) developed severe sepsis or septic shock. The association between etiology of sepsis and severity was found to be statistically significant (p = 0.01).

Table 5 : Association of Sepsis Etiology with Outcome (n = 200)

In the present retrospective study involving 200 patients with sepsis, elevated RDW (>14%) was found to be significantly associated with adverse clinical outcomes, including prolonged ICU stay, increased need for mechanical ventilation, and higher in-hospital mortality. These findings are in agreement with the Third International Consensus Definitions for Sepsis (Sepsis-3) described by Seymour et al. [11], which emphasize the importance of early risk stratification in septic patients.

The demographic analysis revealed that patients with elevated RDW were significantly older, a finding consistent with the observations of Lippi et al. [12], who demonstrated a strong association between RDW and inflammatory burden, particularly in elderly populations. However, sex distribution and major comorbidities such as diabetes, hypertension, and chronic kidney disease did not differ significantly between the two groups. Similar results were reported by Balta et al. [13] and Jo et al. [14], who showed that RDW predicts mortality independently of baseline comorbid conditions, suggesting that RDW reflects acute physiological stress rather than chronic disease alone.

Clinical outcomes in our study were notably worse among patients with RDW >14%. The longer ICU stay and higher requirement for mechanical ventilation observed in this group are consistent with findings by Kim et al. [15], who demonstrated that rising RDW levels during hospitalization were associated with increased disease severity and mortality in severe sepsis and septic shock. Likewise, Wang et al. [16] reported that elevated RDW was associated with increased mortality and poorer outcomes, particularly among elderly septic patients presenting to emergency departments.

Laboratory investigations in the present study showed that patients with elevated RDW had lower hemoglobin levels, higher WBC counts, and elevated serum creatinine, indicating greater inflammatory response and organ dysfunction. These findings support the work of Zhang et al. [17], who identified RDW as a marker of systemic inflammation and multi-organ dysfunction in critically ill patients. The biological plausibility of this association is further supported by experimental evidence from Pierce and Larson [18], who demonstrated that inflammatory cytokines impair erythropoiesis and alter red blood cell morphology, leading to increased RDW during systemic inflammatory states such as sepsis.

Importantly, multivariate logistic regression analysis in our study identified RDW >14% as an independent predictor of in-hospital mortality. This observation is strongly supported by the meta-analysis conducted by Zhang et al. [19], which included over 18,000 septic patients and confirmed that elevated RDW is consistently associated with increased mortality across diverse clinical settings. Furthermore, Hunziker et al. [20] demonstrated that RDW adds incremental prognostic value beyond conventional clinical and laboratory parameters in hospitalized patients.

This study demonstrates that elevated RDW is closely associated with increased severity and poorer clinical outcomes in patients with sepsis. Patients with higher RDW levels tended to be older and experienced a more complicated clinical course, characterized by prolonged intensive care stay, increased requirement for mechanical ventilation, and higher in-hospital mortality. Laboratory parameters at admission in patients with elevated RDW reflected greater systemic inflammation and organ dysfunction, including lower hemoglobin levels, higher leukocyte counts, and impaired renal function. A clear and progressive relationship was observed between increasing RDW categories and higher SOFA scores, underscoring the value of RDW as a marker of organ failure severity. Furthermore, the severity of sepsis varied with its underlying etiology, with gram-negative and fungal infections being associated with more severe disease compared to gram-positive and viral causes. Overall, RDW appears to be a simple, inexpensive, and readily available prognostic indicator that can aid in early risk stratification and guide clinical decision-making in patients with sepsis.

1. Zhang B, Dai H, Chen H, Wang X, Zhou X, Li Y. Prognostic role of red blood cell distribution width in patients with sepsis: a systematic review and meta‑analysis. BMC Immunol. 2020;21:18.
2. Balta S, Demirkol S, Hatipoglu M, Ardic S, Arslan Z, Celik T. Red cell distribution width is a prognostic factor in severe sepsis and septic shock. Am J Emerg Med. 2013;31(6):989‑990.
3. Association between red blood cell distribution width and 30‑day mortality in critically ill septic patients: a propensity score‑matched study. J Intensive Care. 2024;12:34.
4. Association Between Red Cell Distribution Width and Hospital Mortality in Patients with Sepsis. Crit Care Med. 2021;49(8):e820‑e828.
5. Honore PM, Redant S, Djimafo P, Blackman S, Bousbiat I, Perriens E, et al. Red blood cell distribution width as prognostic factor in sepsis: a new use for a classical parameter. J Crit Care. 2022;72:154134.
6. Krishna R, Kumar S, Nair A, et al. Red Cell Distribution Width as a Predictor of Mortality in Patients With Sepsis. Indian J Crit Care Med. 2021; (Article).
7. Red cell distribution width as a prognostic marker in severe sepsis and septic shock. Int J Adv Med. 2017;5(3): (Article).
8. Selvaraj S. Red cell distribution width in correlation with Sequential Organ Failure Assessment score as a prognostic marker of sepsis. Asian J Med Health. 2021;19(11):109‑113.
9. An increase in red blood cell distribution width from baseline predicts mortality in patients with severe sepsis or septic shock. Intensive Care Med. 2014;40(6):830‑838.
10. Assessing the Prognostic Accuracy of Red Cell Distribution Width for Predicting Mortality in Sepsis Patients: A Comparative Study With Serum Lactate and qSOFA Score. Crit Care Res. 2025; (Article).
11. Seymour CW, Liu VX, Iwashyna TJ, et al. Assessment of clinical criteria for sepsis: for the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315(8):762-774.
12. Lippi G, Targher G, Montagnana M, Salvagno GL, Zoppini G, Guidi GC. Relation between red blood cell distribution width and inflammatory biomarkers in a large cohort of unselected outpatients. Arch Pathol Lab Med. 2009;133(4):628-632.
13. Balta S, Demirkol S, Hatipoglu M, et al. Red cell distribution width is a prognostic factor in severe sepsis and septic shock. Am J Emerg Med. 2013;31(6):989-990.
14. Jo YH, Kim K, Lee JH, et al. Red cell distribution width is a prognostic factor in severe sepsis and septic shock. Am J Emerg Med. 2013;31(3):545-548.
15. Kim CH, Park JT, Kim EJ, et al. An increase in red blood cell distribution width from baseline predicts mortality in patients with severe sepsis or septic shock. Intensive Care Med. 2014;40(6):830-839.
16. Wang AY, Ma HP, Kao WF, Tsai SH, Chang CK. Red blood cell distribution width is associated with mortality in elderly patients with sepsis. Am J Emerg Med. 2018;36(6):949-953.
17. Zhang Z, Xu X, Ni H, Deng H. Red cell distribution width is associated with hospital mortality in unselected critically ill patients. J Thorac Dis. 2013;5(6):730-736.
18. Pierce CN, Larson DF. Inflammatory cytokine inhibition of erythropoiesis in patients with anemia of chronic disease. Exp Hematol. 2005;33(1):1-6.
19. Zhang B, Dai H, Chen H, et al. Prognostic role of red blood cell distribution width in patients with sepsis: a systematic review and meta-analysis. BMC Immunol. 2020;21:18.
20. Hunziker S, Stevens J, Howell MD. Red cell distribution width and mortality in newly hospitalized patients. Am J Med. 2012;125(3):283-291.