There were 46,476 patients who were first admitted to the ICU, and 3512 had diagnoses of sepsis (ICD 995.91), severe sepsis (ICD 995.92), or septic shock (ICD 785.52; Figure 1). After exclusion of 5 patients who were younger than 18 years-old, 309 patients who were discharged from the ICU within 24 h, 4 patients who did not have chart event data, and 710 patients whose initial lactate levels were not measured, there were 2482 patients. Among these 2482 patients, 1100 were younger than 65 years and 1382 were 65 years or older.
Table 1 shows the baseline clinical and demographic characteristics of the 2482 patients overall and of the elderly and non-elderly groups. The overall 28-day mortality rate was 30.9%, and the rate in elderly patients was 64.8%. Most patients in the non-elderly and elderly groups were male. The average duration in the ICU was 126.07 h for the non-elderly and 101.80 h for the elderly. There were significant differences in the racial composition of the two age groups. In particular, there were higher percentages of black and Hispanic/Latino patients in the non-elderly group. The two age groups also had significant differences in many clinical characteristics, including multiple vital signs, mortality prediction scores, major comorbidities, and major source of infection.
Analysis of major complications indicated the incidence of hypertension, congestive heart failure, chronic renal insufficiency, cerebrovascular disease, and diabetes were greater in elderly patients, but the incidence of cirrhosis was greater in non-elderly patients. The elderly group had more respiratory tract infections (34.2% vs. 29.7%), but the non-elderly group had a greater incidence of skin and soft tissue infections (10.9% vs. 6.9%). The 28-day mortality was significantly greater in the non-elderly group (36.0% vs. 24.5%). The two groups had no significant difference in plasma lactate level.
Analysis of survivors and non-survivors (Table 2) indicated the mortality rate increased with patient age within each age group, and that time in the ICU had a positive association with survivorship only in the non-elderly group. Sex and race had no significant effect in either age group. The incidence of cirrhosis, chronic renal insufficiency, malignancy, and lactate level were significantly greater among non-survivors in each age group. There were significant differences in mortality prediction scores (SOFA and SAPS) of the two age groups. Further analysis (Table 3) showed that the lactate level was similar for elderly and non-elderly survivors (1.8 vs. 1.8 mmol/L, P = 0.571), but was greater in non-elderly non-survivors than elderly non-survivors (2.2 vs. 3.1 mmol/L, P < 0.001).
We initially used univariate logistic regression analysis to identify variables related to 28-day mortality. The subsequent multivariate logistic regression analysis, in which patients with normal levels of lactate (<2 mmol/L) were used as the reference group, indicated multiple factors were significantly and independently associated with 28-day mortality: age, SOFA, SAPS, SpO2, and malignancy (Table 4). The crude and adjusted ORs indicated the risk of death at 28 days in the non-elderly group increased with increased lactate level, but there was no such correlation in the elderly group.
We also used multivariate analysis to determine the impact of other clinical factors on mortality among patients overall (Figure 2), the non-elderly group (Figure 3), and the elderly group (Figure 4). The stepwise logistic regression analysis indicated that 28-day mortality correlated with age, lactate level, SOFA score, SAPS score, SpO2, and malignancy among all patients; with lactate level, SOFA score, and malignancy in the non-elderly group; and with SOFA score, SAPS score, SpO2, and malignancy in the elderly group. Table 5 shows the regression equations and Homser-Lemeshow test results for each group.
We performed ROC analysis to evaluate the diagnostic performance of the logistic regression models for the three different groups (Table 6). The AUROC for 28-day mortality was 0.752 for all patients, 0.793 for the non-elderly group, and 0.711 for the elderly group (Figure 5). For all patients, based on the maximal value of Youden’s index (J) for identification of the cut-off point (P = 0.315), the prediction of 28-day mortality had a sensitivity of 65.71% and a specificity of 71.86%. The cut-off point was 0.274 (sensitivity = 66.42%, specificity = 78.93%) in the non-elderly group and 0.389 in the elderly group (sensitivity = 56.05%, specificity = 74.20%).