In this study, we defined a nomogram based on routinely measured clinical variables that may reliably predict 90-day mortality among patients with sepsis. While our nomogram should be verified with other patient populations, it establishes the feasibility of accurate mortality prediction using relatively simple clinical tests. While several studies have identified risk factors associated with 90-day mortality in sepsis, our work suggests that certain risk factors may be particularly relevant for screening patients for mortality risk.
The 90-day mortality in our retrospective cohort of Chinese patients was 31.6%, which was higher than in previous studies [2, 3, 5]. Sepsis patients concluded in the present study had much higher APACHE II scores and had a longer follow-up (90-day mortality) than in previous reports,which could make an explaination of these differences[14].
We found that international normalized ratio was significantly higher among sepsis patients who died within 90 days of follow-up than among those who did not die, and it emerged as an independent predictor of 90-day mortality in multivariate analysis. Coagulopathy is frequently observed in sepsis [15], and it contributes to multiple organ dysfunction syndrome [16]. More severe coagulopathy has been linked to higher risk of mortality among patients with sepsis [17], and clinical parameters reflecting hemostasis can predict sepsis-related mortality [18–20]. Our results are consistent with this literature. Nevertheless, international normalized ratio alone cannot accurately predict sepsis outcomes [5], which our results suggest may be due to the need to take into account other independent predictors of mortality.
One of those predictors is lactate level, which was significantly higher among our patients who died within 90 days than among those who did not. Critically ill patients, particularly those with sepsis or septic shock, show elevated lactate [21], and the magnitude of the elevation correlates strongly and positively with sepsis severity and associated mortality [22–24]. Serum lactate levels are considered a marker of tissue hypoxia [19], and they have proven useful for guiding clinical treatment and predicting prognosis in various clinical contexts [25]. Our study supports the “Sepsis 3” recommendation that septic shock be defined as persistence of serum lactate > 2 mmol/L [10].
Another risk factor of 90-day mortality that emerged as particularly important for prediction was elevated thrombomodulin level. Thrombomodulin, an integral endothelial cell membrane protein, is cleaved and released into the bloodstream during sepsis and septic shock [26, 27], leading to elevated levels of serum thrombomodulin in pediatric and adult sepsis patients [28, 29]. Endothelium is the primary site of damage in sepsis due to massive production of proinflammatory cytokines [30]. Elevated serum thrombomodulin level is associated with sepsis severity and risk of death [31].
Our nomogram showed AUC values above 0.8 for the training and validation cohorts, suggesting good predictive ability. In addition, DCA suggested that treating our cohorts according to our nomogram’s predictions could be superior to treating all or none of them. The calibration curve also suggested good fit. Nevertheless, our model was generated based on retrospective analysis of a relatively small sample from a single medical center, so it should be validated in other patient populations. It may be possible to further improve the model by a multicenter study with external validation.