50 patients with diagnosis of severe sepsis or septic shock were included in the study. Median (IQR) age was 67 (52–75) years, APACHE-II on ICU admission was 19 (14–25) points, and SOFA score was 7 (5–11) points (Table 1). 28-day mortality was 42%. The empiric antibiotic treatment was adequate according to culture results from samples taken on admission in 45 patients (90%), and inappropriate in 5 (10%). In the five-patients group with inappropriate antibiotic treatment, mortality during first day of admission was 60%, versus (vs.) 40% in the rest (p = 0.390).
Table 1
Relationship between 28-day mortality and rest of variables (age expressed in years, APACHE-II and SOFA in points)
Variables | Total (n = 50) | Survivors (n = 29) | Non-survivors (n = 21) | P values |
Age | 67 (52,75) | 66 ( 48,74) | 71 (63,78) | 0.115 |
APACHE-II | 19 (14,25) | 18 (14,22) | 19 (14,25) | 0.333 |
SOFA | 7 (5,11) | 7 (5,10) | 7 (4,11) | 0.534 |
Lactate (mmol) | 2.1 (1.4,3.6) | 1.9 (1.4,3.4) | 2.1 (1.4,3.7) | 0.616 |
CRP (mg/l) | 221 (109,280) | 246 (136,285) | 158 (86,240) | 0.066 |
PCT (ng/ml) | 2 (0.5,21) | 8 (0.7,29) | 1 (0.4,9) | 0.092 |
Male gender * | 72 | 75.9 | 66.7 | 0.475 |
Risk factors of infection * Absent | 28 | 41.4 | 9.5 | 0.013 |
COPD | 18 | 10.3 | 28.6 | 0.098 |
DM | 22 | 20.7 | 23.8 | 0.793 |
Neoplasia | 4 | 6.9 | 0 | 0.219 |
Bladder catheter | 30 | 24.1 | 38.1 | 0.288 |
Central venous catheter | 14 | 6.9 | 23.8 | 0.089 |
Number of risk factors of infection* 0 | 28 | 41.4 | 9.5 | 0.013 |
> 1 | 42 | 31 | 57.1 | 0.065 |
Site of infection * | | | | 0.266 |
Respiratory | 34 | 27.6 | 42.9 | |
Urinary | 8 | 10.3 | 4.8 | |
Abdominal | 48 | 55.2 | 38.1 | |
Central nervous system | 2 | 3.4 | 0 | |
Cardiovascular | 2 | 0 | 4.8 | |
Soft tissues and bone | 2 | 3.4 | 0 | |
Unknown | 4 | 0 | 9.5 | |
Nosocomial origin* | 30 | 20.7 | 42.9 | 0.123 |
Previous antibiotic therapy * | 34 | 34.5 | 33.3 | 1 |
Septic shock * | 66 | 65.5 | 66.7 | 1 |
Urgent surgery | 30 | 34.5 | 23.8 | 0.537 |
Mechanical ventilation * | 52 | 48.3 | 57.1 | 0.578 |
Cathecolamine therapy * | 72 | 65.5 | 81.1 | 0.341 |
Quantitative variables are expressed as median and 25th–75th percentiles interval. |
*Qualitative variables are expressed as percentages (%) |
APACHE-II, Acute Physiology and Chronic Health Evaluation II; SOFA, Sepsis-related Organ Failure Assesment; CRP, C-Reactive Protein; PCT, Procalcitonine; COPD, chronic obstructive pulmonary disease; DM, diabetes mellitus |
Patients in the non-survival group scored higher on admission in APACHE-II: 19 (14–25) vs. 18 (14–22) points, and in SOFA: 7 (4–11) vs. 7 (5–10) points, with no significant statistical difference (n.s.) observed for both scores. Values of analyzed inflammatory biomarkers were lower in the non-survival group, being CRP 158 (86–240) vs. 246 (136–285), p = 0.066 (n.s.); and PCT 1 (0.4-9) vs. 8 (0.7–29), p = 0.092 (n.s.). Changes between recorded values on admission and the day after, and their relationship with mortality were analyzed. Patients in the survival group showed a more noticeable decrease in CRP : -3 (-48,18) vs. -9 (-53,36) and PCT: 0 (-1,1) vs. 0 (-6, 2), with no significant statistical difference (n.s.) observed for both decreases.
Variations in PSs between first and second day of admission (Value day of admission – Value second day) showed a significant statistical difference for both scores, with a variation in APACHE-II of 2 (-2, 4) points in the non-survivors group, and an observed decline in the survivals of -3 (-6,0) points, (p = 0.001), with similar observed findings in SOFA, increasing this in the non-survivals 1 (-1,3) points, and − 1(-2,0) points in the survival group, (p = 0.002) (Table 2).
Table 2
Relationship between 28-day mortality and changes in main studied variables from admission to day after (Parameter Value of admission day – Parameter Value of second day). APACHE-II and SOFA are expressed in points.
Variables | Total (n = 48) | Survivors (n = 29) | Non-survivors (n = 19) | P values |
APACHE-II | -1 (-5,2) | -3 (-6,0) | 2 (-2,4) | 0.001 |
SOFA | 0 (-1,1) | -1 (-2,0) | 1 (-1,3) | 0.002 |
Lactate (mmol) | 0 (-0.7,0.5) | 0 (-0.6,-0.3) | 0.1 (-0.6,1.3) | 0.499 |
CRP (mg/l) | -5 (-50,20) | -9 (-53,36) | -3 (-48,18) | 0.974 |
PCT (ng/ml) | 0 (-1,1) | 0 (-6,2) | 0 (-1,1) | 0.57 |
Quantitative variables are expressed as median and 25th–75th percentiles interval. |
APACHE-II, Acute Physiology and Chronic Health Evaluation II; SOFA, Sepsis-related Organ Failure Assesment; CRP, C-Reactive Protein; PCT, Procalcitonine. |
The area under the ROC curve was used to analyse discrimination of changes in values of parameters and scores between first and second day of admission in relation to mortality, being 0.77 (0.62–0.93) for APACHE-II changes, 0.68 (0.5–0.85) for SOFA score changes, and just 0.52 for CRP and 0.51 for PCT changes respectively.
We categorized APACHE II and SOFA scores variations between first and second day of admission and we analyzed its relationship with mortality. Patients were classified according to scores variations > 0 (deterioration) or ≤ 0 (improvement). 28-day mortality of 28 patients with APACHE II score variation ≤ 0 was 21.4% vs. 65% of 20 patients with score variation > 0 (p = 0.002). 28-day mortality of 35 patients with SOFA score variation ≤ 0 was 25.7% vs 76.9% of 13 patients with score variation > 0 (p = 0.001).
Table 3 shows variations of SOFA, APACHE-II, CRP, PCT and lactate between admission days 1st and 5th (Value day of admission – Value 5th day) and we analysed its relationship with mortality. Variations of the prognostic scores for clinical severity (APACHE-II and SOFA) between 1st and 5th day showed a significant statistical differences between survival and non-survival groups, with decreasing figures in the survival group, and mildly increasing in non-survivals. Variations of the laboratory parameters (CRP, PCT, lactate) showed a significant statistical differences between survival and non-survival groups for PCT and without statistical differences between survival and non-survival groups for CRP and lactate.
Table 3
Relationship between 28-day mortality and changes in main studied variables from admission to 5th day (Parameter Value admission day – Parameter Value day 5). APACHE-II and SOFA are expressed in points.
Variables | Total (n = 42) | Survivors (n = 28) | Non-survivors (n = 14) | P values |
APACHE II | -5 (-10,0) | -7 (-10,-3) | 2 (-5,6) | 0.002 |
SOFA | -1 (-5,1) | -4 (-6,-1) | 1 (-1,3) | < 0.001 |
Lactate (mmol) | -0.3 (-1.3,0.2) | -0.7 (-1.3,-0.19) | 0 (-0.58,0.33) | 0.325 |
CRP (mg/l) | -117 (-186,-2) | -140 (-205,-20) | -32 (-145,26) | 0.065 |
PCT (ng/ml) | -2 (-18,0) | -4.5 (-21,-0.4) | -0.3 (-2.4,0.4) | 0.012 |
Quantitative variables are expressed as median and 25th–75th percentiles interval. |
APACHE-II, Acute Physiology and Chronic Health Evaluation II; SOFA, Sepsis-related Organ Failure Assesment; CRP, C-Reactive Protein; PCT, Procalcitonine |
Multivariate analysis was performed using a multiple logistic regression model, showing that mortality was significantly related to changes in recorded APACHE-II scores between date of admission and second day, odds ratio (OR): 1.33 (1.1–1.63). In this model we did not include analyzed variables that showed high statistical significance in univariate analysis, as changes in SOFA scores between date of admission and first day after it, or presence of one or more risk factors, or changes in PCT and CRP.
According to the strong observed relationship between mortality and changes in SOFA scores between date of admission and second day, with similar discriminative values observed in comparison to APACHE-II score changes, a second multivariate analysis was performed, excluding this time APACHE-II score changes, trying to create an easier model to be used in the clinical practice, as SOFA score is easier to estimate than APACHE-II score. This second model showed that mortality was related to changes in SOFA score, OR: 2.13 (1.18–3.86), and to the presence of one or more risk factors, OR: 6.01 (1.01–35.78). The discrimination of this model, evaluated with the area under the ROC curve was 0.84 (0.72–0.95).
Simplifying and making even more intuitive the statistical model, a third multivariate analysis was performed classifying SOFA score evolution between admission and second day in worsening of the SOFA score, and improving or maintenance of its initial value, showing an OR: 12.26 (2.18–68.82), according to the presence of risk factors the OR was 8.19 (1.17–57.31). The area under the ROC curve for this model was 0.78 (0.65–0.91).