Characteristics of study subjects: from June to September 2020, we screened all the patients admitted to the ED during convenient hours with symptoms suggesting potential sepsis. Among all 124,702 ED patients, 709 met the inclusion criteria, however, 307 patients were excluded because of exclusion criteria. The algorithm is shown in Fig. 1. We enrolled 402 patients for data analysis (Table 1). Two hundred and one patients (50%) were male, and the mean patient age was 63.7 ± 18.9 years. Vital signs at the triage presented with mean were: body temperature 37.7 ± 1.3 ℃, respiratory rate (RR) 20.0 ± 4.0/min, and heart rate (HR) 105.0 ± 21.1/min. Systolic and diastolic blood pressure at arrival were 130.3 ± 29.5 and 75.0 ± 17.1 mmHg and 26.4% and 38.1% of patients had diabetes and hypertension, respectively. In addition, 29.6% of the patients had known malignancy. Pneumonia (lower respiratory tract infection) was the most common infection focus (26.7%), followed by urinary tract infection (16.2%), intra-abdominal infection (11.5%), and soft tissue infection (4.2%). WBC count and monocyte distribution width were 11.5 ± 17.9/µL and 22.6 ± 5.3, respectively. The average serum lactate and procalcitonin were 20.3 ± 16.3 mg/dL and 2.5 ± 11.1 ng/mL, respectively. Blood culture was positive in 59 patients (14.7%), and overall mortality was 9.4%.
Table 1
Baseline characteristics of the patients
| ALL |
Total patient number | 402 |
Age (yrs) | 63.7 ± 18.9 |
Gender, Male N(%) | 201(50) |
Body temperature () | 37.7 ± 1.3 |
Respiratory rate (/min) | 20.0 ± 4.0 |
Heart rate (/min) | 105.0 ± 21.1 |
Systolic blood pressure (mmHg) | 130.3 ± 29.5 |
Diastolic blood pressure (mmHg) | 75.0 ± 17.1 |
White blood cell count (1,000/uL) | 11.5 ± 17.9 |
Platelet (1,000/uL) | 234.7 ± 121.8 |
Segment (%) | 78.1 ± 12.3 |
Lymphocyte (%) | 13.2 ± 9.8 |
Monocyte (%) | 6.7 ± 5.2 |
Cr (mg/dL) | 1.5 ± 1.8 |
ALT(U/L) | 41.4 ± 60.9 |
Total bilirubin (mg/dL) | 1.3 ± 1.1 |
PT (sec) | 14.0 ± 3.2 |
INR | 1.3 ± 0.3 |
aPTT (sec) | 27.9 ± 6.8 |
Lactate (mg/dL) | 20.3 ± 16.3 |
MDW | 22.6 ± 5.3 |
Procalcitonin (ng/mL) | 2.5 ± 11.1 |
Comorbidities N(%) | |
Diabetes | 106(26.4) |
Hypertension | 153(38.1) |
Chronic obstructive pulmonary disease | 17(4.2) |
Chronic kidney disease | 47(11.7) |
Congestive heart failure | 13(3.2) |
Malignancy | 119(29.6) |
Stroke | 25(6.5) |
Infection Focus N(%) | |
Respiratory tract infection | 107(26.7) |
Urinary tract infection | 65(16.2) |
Intra-abdominal infection | 46(11.5) |
Soft tissue infection | 17(4.2) |
Others | 166(41.4) |
Bacteremia, N(%) | 59(14.7) |
In-hospital mortality, N(%) | 35(9.4) |
Main results: Based on the chart review by two separate emergency physicians blinded to both MDW and PCT results, we assigned the patients to four distinct groups as follows (Table 2), the "non-infection" group (n = 64, 15.9%), the "infection" group (n = 82, 20.4%), the "sepsis" group (n = 202, 50.2%), and the "sepsis-3" group (n = 54, 13.4%).
Table 2
Patient characteristics in different groups
| Non-infection | Infection | Sepsis | Sepsis-3 | p-value |
N (%) | 64 (15.9) | 82 (20.4) | 202 (50.2) | 54 (13.4) | |
Age (yrs) | 60.1 ± 17.8 | 62.3 ± 20.2 | 62.8 ± 18.9 | 73.2 ± 15.7 | 0.001 |
Gender, Male N(%) | 29(45.31) | 38(46.34) | 103(50.99) | 31(57.41) | 0.5191 |
Body temperature () | 37 ± 1.15 | 37.17 ± 0.93 | 38.2 ± 1.16 | 37.56 ± 1.46 | < 0.0001 |
Respiratory rate (/min) | 20 ± 3.72 | 17.94 ± 2.27 | 19.69 ± 3.59 | 24.59 ± 4.59 | < 0.0001 |
Heart rate (/min) | 96.63 ± 22.9 | 89.95 ± 15.39 | 112.43 ± 17.3 | 109.65 ± 24.2 | < 0.0001 |
Systolic blood pressure (mmHg) | 130.5 ± 29.46 | 128 ± 29.97 | 135.34 ± 27.57 | 114.8 ± 30.66 | 0.0005 |
Diastolic blood pressure (mmHg) | 76.27 ± 18.8 | 75.45 ± 16.55 | 76.3 ± 15.66 | 68.09 ± 19.49 | 0.0046 |
White blood cell count (1,000/uL) | 8.78 ± 4.99 | 7.93 ± 3.34 | 12.06 ± 5.95 | 18.25 ± 46.35 | < 0.0001 |
Platelet (1,000/uL) | 250.85 ± 113.13 | 229.24 ± 102.37 | 237.46 ± 127.41 | 214.59 ± 130.87 | 0.2594 |
Segment (%) | 74.01 ± 9.85 | 73.99 ± 12.36 | 80.4 ± 11.74 | 80.34 ± 14.13 | < 0.0001 |
Lymphocyte (%) | 17.39 ± 8.89 | 16.62 ± 9.15 | 10.99 ± 8.88 | 11.24 ± 11.74 | < 0.0001 |
Monocyte (%) | 6.5 ± 2.94 | 7.02 ± 5.14 | 7.07 ± 6.17 | 5.48 ± 3.12 | 0.142 |
Cr (mg/dL) | 1.65 ± 2.03 | 1.47 ± 1.7 | 1.43 ± 1.74 | 1.79 ± 1.65 | 0.1564 |
Total bilirubin (mg/dL) | 1.43 ± 1.5 | 0.93 ± 0.59 | 1.23 ± 1.01 | 1.66 ± 1.65 | 0.2965 |
INR | 1.33 ± 0.33 | 1.16 ± 0.12 | 1.25 ± 0.26 | 1.45 ± 0.32 | 0.0003 |
MDW | 18.54 ± 3.33 | 20.78 ± 3.98 | 23.46 ± 4.64 | 26.77 ± 6.98 | < 0.0001 |
Procalcitonin (ng/mL) | 0.2 ± 0.29 | 0.44 ± 1.5 | 1.93 ± 7.91 | 10.25 ± 24.56 | < 0.0001 |
Bacteremia, N(%) | 1(1.56) | 3(3.7) | 35(17.33) | 20(37.04) | < 0.0001 |
In-hospital mortality, N(%) | 1(1.85) | 2(2.63) | 13(6.81) | 19(36.54) | < 0.0001 |
Among the four groups, age and gender distribution were similar. Patients in the sepsis group had the highest initial body temperature (38.2 ± 1.2 ℃, p < 0.001). Patients in the sepsis-3 group had a higher respiratory rate (24.6 ± 4.6/min) and lower systolic blood pressure (114.8 ± 30.66 mmHg, p < 0.001). There was no difference regarding the underlying condition of the patients. Laboratory examinations, including BUN, sodium, potassium, total bilirubin, alanine aminotransferase, were not different between groups. Sepsis and Sepsis-3 groups had higher serum creatinine and INR (p < 0.05). WBC count in each group was 8.8 ± 5.0, 7.9 ± 3.3, 12.1 ± 6.0, and 18.3 ± 46.4 1,000/uL, respectively (Fig. 2A, p < 0.05). MDW in each group was measured to be 18.5 ± 3.3, 20.8 ± 4.0, 23.5 ± 4.6, and 26.8 ± 7.0, respectively (Fig. 2B, p < 0.05). The estimated PCT in each group was 0.2 ± 0.3, 0.4 ± 1.5, 1.9 ± 7.9, and 10.3 ± 24.6 ng/mL, respectively (Fig. 2C, p < 0.05).
Next, we evaluated the diagnostic accuracy of MDW, PCT and MDW + WBC with AUC analysis. For predicting sepsis, the AUC of MDW and PCT was 0.753 (0.701–0.804) and 0.704 (0.65–0.759), respectively (Table 3 and Fig. 3A). The best MDW cutoff values were estimated to be 19.3 and. Based on the earlier reports and our data, we defined normal WBC count in the range of 4,000 to 11,000/µL.[28] When normal WBC count and normal MDW were used as the cutoff, the AUC predicting sepsis and sepsis-3 was 0.784 (0.738–0.829), and 0.699 (0.631–0.768), respectively. The sensitivity, specificity, PPV, and NPV of MDW using 20 as the cutoff in predicting sepsis were 86.4%, 54.2%, 76.4%, and 70%, compared to 32.9%, 88%, 82.5%, and 43.4% using 0.5 ng/mL as the PCT cutoff value. On combing MDW and WBC count, the sensitivity and NPV further increased to 93.4% and 80.3%, respectively. In predicting sepsis-3, the AUC of MDW and PCT was 0.722 (0.652–0.792), and 0.733 (0.663–0.802), with the best MDW cutoff value of 23.4 and 0.31 ng/mL (Fig. 3B). When the WBC count was added to the model, the AUC was 0.700 (0.631–0.768). MDW, using 20 as cutoff, exhibited sensitivity, specificity, PPV, and NPV of 90.6%, 37.1%, 18.7%, and 96.1%, respectively, compared to 49.1%, 78.6%, 26.8%, and 90.6% when 0.5 ng/mL PCT was used as cutoff. When WBC count was combined with MDW, the sensitivity and NPV were 86.8% and 95.3%, respectively.
Table 3
Diagnostic accuracy of MDW and PCT in predicting sepsis and sepsis-3
| AUC | 95% C.I. | Cut-off | Sensitivity | Specificity | PPV | NPV |
MDW | 0.753 | (0.701,0.804) | 19.26 | 0.8642 | 0.5423 | 0.7636 | 0.7000 |
Procalcitonin | 0.704 | (0.650,0.759) | 0.10 | 0.7778 | 0.5634 | 0.7530 | 0.5970 |
WBC_N + MDW_N | 0.784 | (0.738,0.829) | - | 0.9342 | 0.4577 | 0.7467 | 0.8025 |
MDW | 0.753 | (0.701,0.804) | 20.00 | 0.8066 | 0.5634 | 0.7597 | 0.6299 |
Procalcitonin | 0.704 | (0.650,0.759) | 0.50 | 0.3292 | 0.8803 | 0.8247 | 0.4340 |
| AUC | 95% C.I. | Cut-off | Sensitivity | Specificity | PPV | NPV |
MDW | 0.722 | (0.652,0.792) | 23.41 | 0.6981 | 0.6747 | 0.2552 | 0.9333 |
Procalcitonin | 0.733 | (0.664,0.802) | 0.31 | 0.6792 | 0.6657 | 0.2449 | 0.9286 |
WBC_N + MDW_N | 0.700 | (0.631,0.768) | - | 0.8679 | 0.4277 | 0.1949 | 0.9530 |
MDW | 0.722 | (0.652,0.792) | 20.00 | 0.9057 | 0.3705 | 0.1868 | 0.9609 |
Procalcitonin | 0.733 | (0.664,0.802) | 0.50 | 0.4906 | 0.7861 | 0.2680 | 0.9063 |
AUC: Area under receiver operating characteristic (ROC) curve; PPV: positive predictive value; NPV: negative predictive value |