We enrolled 650/652 patients with suspected infection from the SPICE-ICU database, after excluding 2 patients who had missing data on frailty. The median age of the patients was 72 years (IQR 60 − 81), and 369 (56.8%) were men. The median CFS score was 3 (IQR 3–5). There were 337 (51.8%) fit patients, 109 (16.8%) vulnerable patients, and 204 (31.4%) frail patients (Table 1 and Fig. 1). The age of patients increased with increasing frailty: fit 67 years (IQR 54 − 78); vulnerable 73 years (IQR 64 − 81); and frail 77 years (IQR 69 − 84), p < 0.01. Comorbidities including congestive heart failure, cerebrovascular diseases, dementia, and chronic obstructive pulmonary disease (COPD) were more common in vulnerable and frail patients than in fit patients (p < 0.01). The SOFA scores of fit, vulnerable, and frail patients were 7 (4–10), 8 (5–11), and 7 (5–10), respectively (p = 0.59). The patients' median body temperatures were as follows: fit 37.5 (36.5–38.5)℃; vulnerable 37.5 (36.4–38.6)℃; and frail 37.0 (36.3–38.1)℃, p < 0.01. C-reactive protein levels in fit, vulnerable, and frail patients were 13.6 (4.6–24.5) mg/dL, 12.1 (3.9–24.9) mg/dL, 10.5 (3.0–21.0) mg/dL, respectively (p < 0.01).
Table 1
Characteristics of patients with suspected infection
| | Fit (CFS 1–3) | Vulnerable (CFS 4) | Frail (CFS 5–9) | |
| | n = 337 (51.8) | n = 109 (16.8) | n = 204 (31.4) | p-value |
Age at admission (years old) | | 67 (54–78) | 73 (64–81) | 77 (69–84) | < 0.01 |
Sex, male | | 199 (59.1) | 68 (62.4) | 102 (50.0) | 0.05 |
BMI (kg/m2) | | 22.4 (20.0–25.0) | 22.5 (19.6–24.9) | 20.8 (17.8–23.6) | < 0.01 |
Coexisting conditions | Myocardial infarction | 11 (3.3) | 7 (6.4) | 7 (3.4) | 0.33 |
Congestive heart failure | 20 (5.9) | 11 (10.1) | 28 (13.7) | < 0.01 |
Peripheral vascular disease | 9 (2.7) | 7 (6.4) | 7 (3.4) | 0.17 |
Cerebrovascular disease | 20 (5.9) | 9 (8.3) | 30 (14.7) | < 0.01 |
Dementia | 12 (3.6) | 15 (13.8) | 48 (23.5) | < 0.01 |
COPD | 12 (3.6) | 13 (11.9) | 30 (14.7) | < 0.01 |
Connective tissue disease | 14 (4.2) | 13 (11.9) | 19 (9.3) | < 0.01 |
Peptic ulcer disease | 13 (3.9) | 1 (0.9) | 10 (4.9) | 0.19 |
Diabetes mellitus without organ damage | 47 (13.9) | 22 (20.2) | 42 (20.6) | 0.09 |
Diabetes mellitus with organ damage | 28 (8.3) | 19 (17.4) | 14 (6.9) | < 0.01 |
Chronic kidney disease | 19 (5.6) | 20 (18.3) | 16 (7.8) | < 0.01 |
Hemiplegia | 3 (0.9) | 3 (2.8) | 25 (12.3) | < 0.01 |
Malignancy (solid) | 30 (8.9) | 19 (17.4) | 28 (13.7) | 0.03 |
Malignancy (blood) | 6 (1.8) | 0 | 1 (0.5) | 0.18 |
Metastatic tumor | 6 (1.8) | 4 (3.7) | 5 (2.5) | 0.46 |
Mild liver disease | 8 (2.4) | 11 (10.1) | 9 (4.4) | < 0.01 |
Moderate to severe liver disease | 13 (3.9) | 1 (0.9) | 9 (4.4) | 0.26 |
AIDS | 0 | 0 | 0 | |
CCI | | 1 (0–2) | 2 (1–4) | 2 (1–3) | < 0.01 |
SOFA score | | 7 (4–10) | 8 (5–11) | 7 (5–10) | 0.59 |
APACHE II score | | 18 (12–25) | 22 (17–28) | 21 (15–27) | < 0.01 |
Septic shock | | 60 (17.8) | 23 (21.1) | 28 (13.7) | 0.22 |
Mechanical ventilation | | 132 (39.3) | 46 (43.4) | 74 (36.5) | 0.49 |
Vital signs | Glasgow coma scale | 13 (8–15) | 11 (8–15) | 12 (7–14) | < 0.01 |
| Systolic blood pressure (mmHg) | 107 (87–128) | 105 (80–137) | 109 (86–128) | 0.97 |
| Heat rate (/min) | 105 (88–125) | 108 (90–120) | 103 (86–118) | 0.18 |
| Respiratory rate (/min) | 24 (19–29) | 22 (18–27) | 23 (19–30) | 0.42 |
| Body temperature (℃) | 37.5 (36.5–38.5) | 37.5 (36.4–38.6) | 37.0 (36.3–38.1) | 0.03 |
Laboratory data | White blood cells (/µL) | 11000 (5780–15580) | 10520 (6700–16000) | 11780 (7450–17200) | 0.32 |
| Hematocrit (%) | 35.4 (29.3–40.8) | 33.1 (26.8–39.1) | 34.4 (29.4–39.9) | 0.07 |
| Platelet (/µL) | 16.3 (9.8–24.4) | 18.0 (11.2–24.3) | 18.1 (12.9–25.5) | 0.16 |
| PT-INR | 1.2 (1.1–1.4) | 1.2 (1.1–1.4) | 1.2 (1.1–1.4) | 0.83 |
| Lactate (mmol/L) | 2.6 (1.4–4.4) | 2.7 (1.6–5.7) | 2.5 (1.4–4.4) | 0.27 |
| Glucose (mg/dL) | 142 (112–205) | 150 (109–210) | 138 (103–194) | 0.39 |
| Sodium (mEq/L) | 138 (134–141) | 138 (135–141) | 138 (134–141) | 0.94 |
| Potassium (mEq/L) | 4.0 (3.6–4.5) | 4.0 (3.4–4.7) | 4.1 (3.6–4.6) | 0.40 |
| Creatinine (mg/dL) | 1.5 (0.8–2.6) | 1.6 (0.9–2.9) | 1.2 (0.7–2.1) | 0.02 |
| Total bilirubin (mg/dL) | 0.8 (0.5–1.5) | 0.8 (0.5–1.5) | 0.7 (0.5–1.1) | 0.02 |
| C-reactive protein (mg/dL) | 13.6 (4.6–24.5) | 12.1 (3.9–24.9) | 10.5 (3.0–21.0) | 0.04 |
Positive blood cultures | | 141 (44.2) | 49 (47.6) | 85 (44.5) | 0.84 |
Site of infection at final diagnosis | Lung | 103 (30.6) | 39 (35.8) | 81 (39.7) | < 0.01 |
Abdomen | 74 (22.0) | 21 (19.3) | 35 (17.2) |
Urinary tract | 49 (14.5) | 13 (11.9) | 44 (21.6) |
Soft Tissue | 43 (12.8) | 18 (16.5) | 20 (9.8) |
Others | 35 (10.4) | 9 (8.3) | 7 (3.4) |
Reported counts (proportions) for categorical and median (interquartile range) for continuous variables. |
Continuous variables were compared using the Mann–Whitney U test. Categorical variables were compared using the Fisher’s exact test or chi square test, where appropriately. |
Missing data: BMI = 5; Metastatic tumor = 1; Mechanical ventilation = 2; Systolic blood pressure = 2; Heart rate = 1; Temperature = 1; Hematocrit = 1; PT–INR = 5; Lactate = 15; Glucose = 6; Total bilirubin = 1; C-reactive protein = 2; Positive blood cultures = 37 |
CFS: Clinical frailty scale, BMI: Body mass index, COPD: Chronic obstructive pulmonary disease, AIDS: Acquired immunodeficiency syndrome, CCI: Charlson comorbidity index, SOFA: Sequential organ failure assessment, APACHE: Acute physiology and chronic health evaluation, PT-INR: International normalized ratio of prothrombin time |
Table 2 shows the outcomes among fit, vulnerable, and frail patients. There was no statistically significant difference in in-hospital mortality between the three frailty groups: fit 55/335 (16.4%); vulnerable 23/107 (21.5%); and frail 45/203 (22.2%), p = 0.19. There were no significant differences in IFDs, VFDs, or LOS between the three frailty groups. Frailty was associated with disposition after discharge (discharge to home: fit 125/280 [44.6%]; vulnerable 36/84 [42.9%]; and frail 40/158 [25.3%], p < 0.01).
Table 2
Outcomes of patients with suspected infection
| | Fit (CFS 1–3) | Vulnerable (CFS 4) | Frail (CFS 5–9) | |
| | n = 337 (51.8) | n = 109 (16.8) | n = 204 (31.4) | p-value |
In-hospital mortality | | 55/335 (16.4) | 23/107 (21.5) | 45/203 (22.2) | 0.19 |
Dispositions | Home | 125/280 (44.6) | 36/84 (42.9) | 40/158 (25.3) | < 0.01 |
| Transfer | 155/280 (55.4) | 48/84 (57.1) | 118/158 (74.7) |
ICU-free days | | 16 (0–22) | 17 (0–22) | 15 (0–22) | 0.85 |
Ventilator–free days | | 21 (0–28) | 21 (8–28) | 20 (0–28) | 0.71 |
Length of hospital stay | | 22 (10–49) | 23 (14–41) | 23 (11–40) | 0.86 |
Reported counts (proportions) for categorical and median (interquartile range) for continuous variables. Continuous variables were compared using the Mann–Whitney U test. Categorical variables were compared using the Fisher’s exact test or chi square test, where appropriately. |
Missing data: In–hospital mortality = 5; ICU–free days = 41; Ventilator–free days = 41; Length of hospital stay = 5 |
CFS: Clinical frailty scale, ICU: Intensive care unit |
Figure 2 shows the Kaplan–Meier survival curves stratified by the three groups. There was little difference in in-hospital mortality between the groups during the acute disease phase. However, more vulnerable and frail patients died after the acute disease phase than did fit patients, although this difference was not statistically significant (p = 0.25). Cox proportional hazards regression analysis did not demonstrate an association between in-hospital mortality and frailty (vulnerable vs. fit: adjusted hazard ratio 1.16 [95% confidential interval, 0.70–1.92], p = 0.57, frail vs. fit: adjusted hazard ratio 1.13 [95% confidential interval 0.75–1.72], p = 0.56), and there were no interactions between frailty and age, frailty and the Charlson comorbidity index, and age and the Charlson comorbidity index (Table 3).
Table 3
Univariable and multivariable analysis for mortality associated with frailty in patients with suspected infection
Univariable analysis | | HR | 95% CI | p-value |
Frailty | Vulnerable vs fit | 1.33 | 0.82 | 2.16 | 0.25 |
| Frail vs fit | 1.36 | 0.92 | 2.01 | 0.13 |
Multivariable analysis | | HR | 95% CI | p-value |
Age | | 1.01 | 1.00 | 1.03 | 0.04 |
Sex, male | | 1.10 | 0.76 | 1.61 | 0.61 |
Charlson comorbidity index | | 1.04 | 0.95 | 1.15 | 0.39 |
SOFA score | | 1.18 | 1.14 | 1.24 | < 0.01 |
Frailty | Vulnerable vs fit | 1.16 | 0.70 | 1.92 | 0.57 |
| Frail vs fit | 1.13 | 0.75 | 1.72 | 0.56 |
HR: Hazard ratio, CI: Confidence Interval, SOFA: Sequential organ failure assessment |
Among patients with suspected infection, 599 (92.2%) patients were diagnosed with sepsis. The subgroup analysis of patients with sepsis gave similar results to the primary analysis (Supplementary Tables 1 and 2). Similarly, there was no association between in-hospital mortality and frailty in patients with sepsis (vulnerable vs. fit: adjusted hazard ratio 1.22 [95% confidential interval, 0.73–2.04], p = 0.45, frail vs. fit: adjusted hazard ratio 1.26 [95% confidential interval 0.82–1.93], p = 0.29 [Supplementary Table 3]).