Prognosis of patients excluded by the definition of septic shock based on their lactate levels after initial fluid resuscitation: a prospective multi-center observational study

Background: Septic shock can be defined both by the presence of hyperlactatemia and need of vasopressors. Lactate levels should be measured after volume resuscitation (as per the Sepsis-3 definition). However, currently, no studies have evaluated patients who have been excluded by the new criteria for septic shock. The aim of this study was to determine the clinical characteristics and prognosis of these patients, based on their lactate levels after initial fluid resuscitation. Methods: This observational study was performed using a prospective, multi-center registry of septic shock, with the participation of 10 hospitals in the Korean Shock Society, between October 2015 and February 2017. We compared the 28-day mortality between patients who were excluded from the new definition (defined as lactate level <2 mmol/L after volume resuscitation) and those who were not (>= 2 mmol/L after volume resuscitation), from among a cohort of patients with refractory hypotension, and requiring the use of vasopressors. Other outcome variables such as in-hospital mortality, intensive care unit (ICU) stay (days), Sequential Organ Failure Assessment (SOFA) scores and Acute Physiology and Chronic Health Evaluation (APACHE) II scores were also analyzed. Results: Of 567 patients with refractory hypotension, requiring the use of vasopressors, 435 had elevated lactate levels, while 83 did not have elevated lactate levels (either initially or after volume resuscitation), and 49 (8.2%) had elevated lactate levels initially, which normalized after fluid resuscitation. Thus, these 49 patients were excluded by the new definition of septic shock. These patients, in whom perfusion was restored, demonstrated significantly lower age, platelet count, and initial and subsequent lactate levels (all p < 0.01). Similarly, significantly lower 28-day mortality was observed in these patients than in those who had not been excluded (8.2% vs 25.5%, p = 0.02). In-hospital mortality and the maximum SOFA score were also significantly lower in the excluded patients group (p = 0.03, both). Conclusions: It seems reasonable for septic shock to be defined by the lactate levels after volume resuscitation. However, owing to the small number of patients in whom lactate levels were improved, further study is warranted