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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).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.Cohort of 1,332 ARISE participants with sepsis and either isolated hyperlactatemia or isolated refractory hypotension.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.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).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.