Prognostic accuracy of the serum lactate level, the SOFA score and the qSOFA score for mortality among adults with Sepsis

Sepsis is a life-threatening complication of infection and characterized by physiologic, pathologic, and biochemical abnormalities [1, 2]. It is the tenth-most-common cause of death globally [3] and the most common cause of death in patients with infections, especially when sepsis is not identified and treated promptly. Early treatment of sepsis improves patients’ mortality and outcome [1].

Serum lactate level is a sensitive but nonspecific indicator of metabolic stress [4]. As a product of anaerobic glycolysis, lactate is increased during hypoxia, stress and many critical illnesses [5]. Recent research presents a positive association between higher levels of lactate and increased mortality [6]; the higher the lactate level, the worse the outcome [7]. Different lactate thresholds have been recommended in some studies as an early aggressive resuscitation predictor [7–12]. Based on this, early identification of elevated serum lactate levels can potentially lead to early identification of patients who are in danger of poor outcomes. Sequential Organ Failure Assessment (SOFA) [13] and quick SOFA (qSOFA) [1, 14] were designed to measure organ dysfunction in patients admitted to intensive care units (ICU). We further explored the prognostic accuracy of the serum lactate level, the SOFA and the qSOFA in predicting mortality in patients with sepsis.

Multiple studies have explored the association between lactate levels and prognosis in critically ill patients. Lower lactate levels, and even levels in the normal range, were reported to be related to lower severity of sepsis [12]. Wacharasint et al demonstrated that patients with lactate levels in the normal-range (between 1.4 and 2.3 mmol/L) had markedly increasing risk of organ failure and higher mortality compared with patients who had lactate levels less than 1.4 mmol/L in two cohorts [12]. Sepsis-3 recommended serum lactate level > 2 mmol/L as a major criterion for the clinically identification of septic shock [1]. A lactate concentration greater than 4 mmol/L was described as having a specificity of 96% in predicting hospital mortality in non-hypotensive patients [20]. A retrospective study that included 7155 ICU patients showed that a significant association between lactate concentration and increased hospital mortality was first detectable at the time weighted lactate concentration was greater than 0.75 mmol/L [7]. Lactate has also used to guide resuscitation efficacy [21]. At the same time, the use of qSOFA and SOFA has been endorsed by professional societies worldwide.

Recently, Simpson raised concerns that reliance on qSOFA or SOFA criteria may lead to delayed diagnosis and intervention in cases of serious infection [22]. Furthermore, a systematic review and meta-analysis demonstrated that qSOFA was poorly sensitive and moderately specific for the risk of death [23]. Ho [24] found that qSOFA had modest mortality predictive ability in both septic and non-septic patients in a prospective study. When combined with lactate, qSOFA showed predictive ability comparable to that of SOFA. An observational cohort study that included patients with infection who were admitted in the emergency department demonstrated poor performance of qSOFA in predicting mortality [25]. Therefore, we compared mortality prediction by serum lactate to mortality prediction by SOFA and qSOFA. First, we found that lactate was positively associated with qSOFA/SOFA scores (Fig. 3) and prognosis (Fig. 2). Next, lactate was shown to be an independent prognostic predictor by Cox regression model analysis (Table 2). Lactate showed superior prognostic accuracy for short-term and long-term mortality compared to qSOFA, and the predictive validity of lactate was similar to that of SOFA (Table 3). The AUROC of SOFA and of qSOFA combined with lactate was similar to the AUROC reported in a previous study in septic patients [24]. However, in our cohort, qSOFA showed a capacity to predict mortality in patients with an AUROC lower than that found in Ho’s study [24]. qSOFA had far less sensitivity, but similar specificity to lactate and SOFA (Table 4). Combining lactate with qSOFA yielded a predictive ability close to that of the SOFA score alone (Table 3).

Some studies revealed that the qSOFA score is associated with hospital mortality and that it present higher prognostic accuracy than the SIRS score in adults with suspected infection [14, 26]. The task force of Sepsis-3 suggested using qSOFA to assess organ dysfunction due to its convenience, rapid performance and repeatability. Lactate was not included as an indicator of illness severity. However, a recent study suggested that lactate reduction in the first day of ICU admission is correlated with improved outcome of septic patients regardless of the haemodynamic status [27]. Our study revealed that the sensitivity of qSOFA was low, although it showed relatively high specificity. Lactate testing is a simple, inexpensive, and reasonably sensitive tool for predicting mortality and is more stable than qSOFA when sedation is used. Lactate levels correlated significantly with the SOFA scores. This is consistent with existing studies [28–30]. High lactate can be considered a warning signal for organ dysfunction and is a signal for urgent medical intervention. In fact, high sensitivity may be superior to specificity in the context of fatal sepsis.

Although lactate was reported to guide resuscitation efficacy [21], multicentre, randomized trials indicated that fluid resuscitation was not beneficial to septic shock patients with or without hyperlactataemia [31, 32]. Moreover, fluid resuscitation and lactate clearance might be harmful when hyperlactataemia is not caused by hypoperfusion [5]. However, high lactate levels should be interpreted in accordance with the patient’s specific circumstances.

Our study has several limitations. This study is not prospective but retrospective. The inherent bias of retrospective studies could not be avoided. Lactate demonstrated low sensitivity and moderate specificity for short- and long-term mortality in septic patients. Lactate alone would not be a good predictive test of mortality. Approximately half of the adult sepsis patients in the database were excluded due to lack of laboratory testing; the significant number of excluded patients may affect our conclusion. In addition, because the data were collected from different types of ICUs, the heterogeneity of treatment further complicates the interpretation of the results. Previous studies have established that early lactate levels are associated with organ dysfunctions and mortality in the ICU and emergency departments [10, 33–35]. Delays in lactate measurement are correlated with increased mortality of septic patients [36]. However, in our cohort, the time that elapsed between the first lactate measurement and the onset of sepsis was inconsistent, and the time at which the patient’s lactate was measured in the first 24 h was also inconsistent. Although we used the 24-h average lactate levels to eliminate the bias, the levels might be influenced by resuscitation of the patients, and the average lactate levels may not reflect the true resuscitation state of the patients. Additionally, interventions that might affect SOFA scores, qSOFA scores and prognosis were not included in the study, and lack of these data may affect the analysis. It is difficult to assess the impact of the change in the definition of sepsis on our results due to the de-identification process of the data in the database. Prospective studies need to be conducted, and better outcome predictors need to be further explored.

In addition to its simplicity and accuracy, lactate is a better prognostic factor than qSOFA and SOFA in adult patients with sepsis. Further study is needed given that this work is based on retrospective data and that the timing of lactate determination in this study may affect results obtained.