Background and Objectives: This is the first study to examine the role of monocyte distribution width (MDW) in predicting sepsis after cardiovascular surgery. Methods: This study included 43 consecutive patients who had undergone cardiovascular surgery between July 2021 and July 2022. All patients were examined at the following three time points (TPs): preoperative period (TP1), postoperative at 24 h (TP2), and discharge (TP3). SOFA score, leukocyte count, neutrophil-to-lymphocyte ratio (NLR), MDW, C-reactive protein (CRP), and procalcitonin (PCT) levels were tested at each TPs. The Sepsis-3 criteria were used to diagnose patients with sepsis. Results: The mean values of all variables (leukocyte count, NLR, MDW, CRP, and PCT levels) were significantly higher at TP2 and TP3 than at TP1 (p < 0.05). All these values were significantly higher at TP2 than at TP3 (p < 0.05). Patients with sepsis had significantly higher mean values for leukocyte count, NLR, MDW, CRP, and PCT levels than those without sepsis (p < 0.05). There was a significant correlation between MDW and inflammatory markers (CRP, PCT, and NLR) during the three time periods (p < 0.05). According to the ROC analysis, the optimal MDW cutoff value with the highest sensitivity and specificity for predicting sepsis in the postoperative period was 20.5. Conclusions: Our findings indicate that elevated MDW levels may be a valuable predictor of sepsis in patients following cardiovascular surgery.
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