Mortality is greater in septic patients with hyperlactatemia than with refractory hypotension

Background: In septic patients, it is uncertain whether isolated hyperlactatemia (lactate ≥4 mmol/L without refractory hypotension) can be used to diagnose septic shock and whether mortality rate differs from that of isolated refractory hypotension (refractory to 1000 mL or greater fluid bolus). Aims: To compare baseline characteristics, treatments, and outcomes of participants enrolled into the Australian Resuscitation in Sepsis Evaluation (ARISE) trial according to the presence of isolated hyperlactatemia or isolated refractory hypotension. Patients: Cohort of 1,332 ARISE participants with sepsis and either isolated hyperlactatemia or isolated refractory hypotension. Methods: We performed a secondary analysis of the ARISE data, constructing a propensity score model to discriminate between hyperlactatemia and isolated refractory hypotension. We analyzed 90-day all-cause mortality using a generalized linear model and inverse propensity score weighting. We modeled length of intensive care unit (ICU) and hospital stay using time to event analyses incorporating mortality as a competing risk. Results: There were 478 participants (35.9%) with isolated hyperlactatemia and 854 (64.1%) with isolated refractory hypotension. They had similar median (interquartile range) ages (66.2 [54.2, 76.3] years vs. 65.2 [50.9, 75.5] years) and similar sources of infection. However, isolated hyperlactatemia participants had higher mean (standard deviation) baseline APACHE II scores (isolated hyperlactatemia 16.2 [6.4]) vs. 14.5 [6.4] for isolated refractory hypotension; P < 0.001). Isolated hyperlactatemia participants had a 1.7 times higher risk of 90-day mortality (propensity-weighted risk ratio; 95% confidence intervals [CI] 1.2, 2.5, P = 0.003). They were less likely to be discharged alive from ICU and hospital (propensity weighted sub-hazard ratio 0.77 (95% CI 0.64, 0.92; P < 0.005) and 0.79 (95% CI 0.66, 0.95; P = 0.01), respectively). Conclusions: ARISE trial participants with isolated hyperlactatemia had worse adjusted 90-day mortality than those with isolated refractory hypotension. In septic patients, isolated hyperlactatemia may define greater illness severity and worse outcomes than isolated refractory hypotension.