Reclassifying the spectrum of septic patients using lactate: severe sepsis, cryptic shock, vasoplegic shock and dysoxic shock

Abstract

Objective: The current definition of severe sepsis and septic shock includes a heterogeneous profile of patients. Although the prognostic value of hyperlactatemia is well established, hyperlactatemia is observed in patients with and without shock. The present study aimed to compare the prognosis of septic patients by stratifying them according to two factors: hyperlactatemia and persistent hypotension.

Methods: The present study is a secondary analysis of an observational study conducted in ten hospitals in Brazil (Rede Amil - SP). Septic patients with initial lactate measurements in the first 6 hours of diagnosis were included and divided into 4 groups according to hyperlactatemia (lactate >4mmol/L) and persistent hypotension: (1) severe sepsis (without both criteria); (2) cryptic shock (hyperlactatemia without persistent hypotension); (3) vasoplegic shock (persistent hypotension without hyperlactatemia); and (4) dysoxic shock (both criteria).

Results: In total, 1,948 patients were analyzed, and the sepsis group represented 52% of the patients, followed by 28% with vasoplegic shock, 12% with dysoxic shock and 8% with cryptic shock. Survival at 28 days differed among the groups (p<0.001). Survival was highest among the severe sepsis group (69%, p<0.001 versus others), similar in the cryptic and vasoplegic shock groups (53%, p=0.39), and lowest in the dysoxic shock group (38%, p<0.001 versus others). In the adjusted analysis, the survival at 28 days remained different among the groups (p<0.001) and the dysoxic shock group exhibited the highest hazard ratio (HR=2.99, 95%CI 2.21-4.05).

Conclusion: The definition of sepsis includes four different profiles if we consider the presence of hyperlactatemia. Further studies are needed to better characterize septic patients, to understand the etiology and to design adequate targeted treatments.

Figure 1

Study diagram.

Figure 2

Survival curve 28 days after the sepsis diagnosis. A significant difference is observed among the four sepsis phenotypes (log-rank test, p<0.001). In post-hoc comparisons, the survival was different among the four groups, except for the comparison between the cryptic shock group and the vasoplegic shock group (p=0.387).

Figure 3

Adjusted survival curves 28 days after the sepsis diagnosis. Model A is adjusted for age, APACHE II, and SOFA, and model B is adjusted for age, APACHE II, SOFA, early use of antibiotics, place of sepsis diagnosis, and source hospital. In both models, the group with dysoxic shock exhibited a higher hazard ratio when compared with the group with severe sepsis without hyperlactatemia.

Figure 4

Role of intermediate lactate values in patients with severe sepsis and septic shock. An important increase in the risk of death can be observed from the 2 mmol/L value in both groups, although patients with septic shock exhibit a higher risk of death. The risk of death was adjusted by a nonlinear locally weighted function called Locally Weighted Scatterplot Smoothing (LOESS). The gray area corresponds to a confidence interval of 95%.