Research Article: Lactate normalization within 6 hours of bundle therapy and 24 hours of delayed achievement were associated with 28-day mortality in septic shock patients

Date Published: June 3, 2019

Publisher: Public Library of Science

Author(s): Seung Mok Ryoo, Ryeok Ahn, Tae Gun Shin, You Hwan Jo, Sung Phil Chung, Jin Ho Beom, Sung-Hyuk Choi, Young -Hoon Yoon, Byuk Sung Ko, Hui Jai Lee, Gil Joon Suh, Won Young Kim, Chiara Lazzeri.


This study evaluated the prognostic ability of lactate normalization achieved within 6 and 24 h from septic shock recognition. Data from a septic shock registry from October 2015 to February 2017 were reviewed. The study included 2,102 eligible septic shock patients to analyze the prognostic ability of lactate normalization, defined as a follow-up lactate level <2 mmol/L within six hours of bundle therapy and within 24 hours of delayed normalization. The primary outcome was 28-day mortality. The overall 28-day mortality rate was 21.4%. The rates of lactate normalization within 6 and 24 h were significantly higher in the survivor groups than in the non-survivor group (42.4% vs. 23.4% and 60.2% vs. 31.2%; P<0.001, respectively). Multivariate logistic regression analysis showed that both 6- and 24-h lactate normalization were independent predictors (odds ratio [OR] 0.58, 95% confidence interval [CI] 0.45–0.75, p<0.001 and OR 0.42, 95% CI 0.33–0.54, p<0.001, respectively). When we could not achieve the lactate normalization, the sensitivity, specificity, positive, and negative predictive value to predict mortality were 76.6%, 42.4%, 26.5% and 87.0% respectively for 6-h normalization, and 68.8%, 60.2%, 32.0% and 87.7% respectively for 24-h normalization. Besides 6-h lactate normalization, 24-h delayed lactate normalization was associated with decreasing mortality in septic shock patients. Lactate normalization may have a role in early risk stratification and as a therapeutic target.

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Hyperlactatemia in sepsis and septic shock occurs as a result of tissue hypoxia, accelerated aerobic glycolysis driven by excess beta-adrenergic stimulation, or other cause. Regardless of the source, increased lactate levels are associated with a poor prognosis.[1] Lactic acidosis can cause reduced cardiac contractility and vascular hypo-responsiveness to vasopressors through various mechanisms.[1] Moreover, in normotensive patients with sepsis, lactate concentrations above 4 mmol/L were independently correlated with a higher mortality rate and, therefore, require urgent recognition and proper resuscitation.[2] Additionally, high initial lactate level as well as prolonged time to lactate normalization was also associated with increased mortality.[3] Previous reports have demonstrated improved outcomes in patients with severe sepsis and septic shock who achieved both lactate clearance and lactate normalization.[4–6] Since 2013, Surviving Sepsis Campaign (SSC) guidelines have recommended bundle therapy for patients with sepsis and septic shock, including measurements of lactate level within 3 h and re-measurement at 6 h in cases with elevated initial lactate level.[7]

During the study period, 2,264 eligible septic shock patients were enrolled in the registry. We excluded 162 patients with missing data, leaving 2,102 patients who were included in the present study. Of the included patients, 806 (38.3%) achieved lactate normalization within 6 h from recognition, with a mortality rate lower than that in the group that did not achieve normalization within 6 h (13.0% vs. 26.5%). In addition, 135 (1,135/2,102, 54.0%) patients achieved lactate normalization within 24 h from recognition; their mortality rate was also lower than that of the patients who did not achieve normalization within 24 h (12.3% vs. 32.0%) (Fig 1).

In this study, lactate normalization was an independent prognostic factor in septic shock patients. Achieving normalization within not only 6 h from shock recognition but also within 24 h (delayed achievement) were independently associated with decreased mortality. To our knowledge, this is the first report on delayed lactate normalization. This result may indicate that lactate normalization has roles as an early prognostic marker as well as a therapeutic target. Therefore, physicians managing septic shock patients should make efforts to achieve lactate normalization though prolonged resuscitation.

Early lactate normalization within 6 h as well as delayed lactate normalization within 24 h from shock recognition was also independently associated with mortality. Lactate normalization may have a role in early risk stratification as well as a therapeutic target.




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