Baseline characteristics
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 346 patients whose initial lactate levels were not measured, there were 2848 patients. Among these 2848 patients, 1249 were younger than 65 years and 1599 were 65 years or older.
The average age of 2848 patients was 68.01 years old, and about 55.40% of them were male. The overall 28-day mortality rate was 30.4%, and the rate in elderly patients was 65.82%. Most patients in the non-elderly and elderly groups were male. The non-elderly patients stayed in ICU for more days, but the 28-day mortality was significantly greater in the elderly group. The baseline clinical and demographic characteristics of the survivors were compared to the non-survivors in each age group (Table 1). Analysis indicated the mortality rate increased with age within each age group, and that time in the ICU had a negative association with survivorship only in the elderly group. The non-survivors had a higher score of SAPSII, SOFA, LODS, OASIS, and lactate (p<0.001 for all). Analysis of major complications indicated the incidence of liver cirrhosis, chronic renal insufficiency and malignancy were significantly greater among non-survivors in each age group. Further analysis (Table 2) showed that the lactate was similar for elderly and non-elderly survivors (2.20 vs. 2.10 mmol/L, P = 0.062), but was greater in non-elderly non-survivors than elderly non-survivors (3.20 vs. 2.40 mmol/L, P < 0.001).
Predictive values of lactate and some severity scoring systems for 28-day mortality
nDferencetTable 3 lists the predictive values of lactate and some severity scoring systems in the two age groups for 28-day mortality. Their ROC curves are shown in Fig.2 and Fig.3. The predictive value of lactate for 28-day mortality was 0.661 for the non-elderly group, and 0.553 for the elderly group. The predictive performance of QSOFA and SIRS for 28-day mortality increased after lactate was added, but there was no significant difference in the AUROC values of SAPSII、SOFA and LODS before and after lactate addition in the two age groups.
Association of lactate with 28-day mortality for each age group
In our study, there were 296 dead patients in the non-elderly group and 570 dead patients in the elderly group. We developed different models to examine the independent predicting value of lactate for 28-day mortality and used multivariate analysis to determine the impact of lactate on mortality in each group. The adjusted ORs (95%CIs) for lactate were 1.16 (1.09-1.23) and 1.03 (0.98-1.08) for 28-day mortality in the non-elderly and elderly group, respectively.
To test the nonlinear trend between lactate and 28-day mortality in septic patients of each age group, we converted the continuous variable of lactate into a categorical variable according to tri-segment quantile in the models and divided lactate into three levels. Lactate levels in the non-elderly group were probably consistent with those in the elderly group. 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 low level of lactate were used as the reference group, indicated increased lactate level was associated with 28-day mortality. A significant trend in higher mortality was observed in patients with elevated lactate level compared to patients with less level of lactate in the non-elderly group (p < 0.05 for all). Lactate level was positively associated with risk of death at 28 days in the non-elderly group (p for trend < 0.001), but there was no such correlation in the elderly group (p for trend = 0.830).
Subgroup Analyses
A stratified analysis was conducted by baseline characteristics. In the subgroup analyses, we used sex, ethnicity, first care unit, severity scoring systems, comorbidities and major source of infection as the stratified variables to examined the associations between lactate and 28-day mortality (Table 5). There was no significant difference in relationship between lactate and risk of 28-day mortality in the elderly group in the subgroup analyses. We observed significant changes in SAPSII, SOFA, liver cirrhosis and intra-peritoneal infection (p < 0.05 for all) (Fig.4). It was worth mentioning that we found significant inverse association of liver cirrhosis with 28-day mortality among the non-elderly sepsis patients. The lactate of the non-elderly patients without liver cirrhosis had a higher risk of 28-day mortality (OR 1.28, p < 0.0001). The association between lactate and 28-day mortality for sepsis patients without liver cirrhosis was stronger than for sepsis patients with liver cirrhosis in non-elderly group (OR 1.28 vs. OR 1.10, P =0.027 for the interaction lactate* liver cirrhosis for 28-day mortality).