Fluid volume, lactate values, and mortality in sepsis patients with intermediate lactate values

Abstract

Rationale: Patients with severe sepsis without shock or tissue hypoperfusion face substantial mortality; however, treatment guidelines are lacking.

Objectives: To evaluate the association between intravenous fluid resuscitation, lactate clearance, and mortality in patients with "intermediate" lactate values of 2 mmol/L or greater and less than 4 mmol/L.

Measurements and main results: This was a retrospective study of 9,190 patients with sepsis with intermediate lactate values. Interval changes between index lactate values and those at 4, 8, and 12 hours were calculated with corresponding weight-based fluid volumes. Outcomes included lactate change and mortality. Repeat lactate tests were completed in 94.7% of patients within 12 hours. Hospital and 30-day mortality were 8.2 and 13.3%, respectively, for patients with lactate clearance; they were 18.7 and 24.7%, respectively, for those without lactate clearance. Each 10% increase in repeat lactate values was associated with a 9.4% (95% confidence interval [CI] = 7.8-11.1%) increase in the odds of hospital death. Within 4 hours, patients received 32 (± 18) ml/kg of fluid. Each 7.5 ml/kg increase was associated with a 1.3% (95% CI = 0.6-2.1%) decrease in repeat lactate. Across an unrestricted range, increased fluid was not associated with improved mortality. However, when limited to less than 45 ml/kg, additional fluid was associated with a trend toward improved survival (odds ratio = 0.92; 95% CI = 0.82-1.03) that was statistically significant among patients with highly concordant fluid records.

Conclusions: Early fluid administration, below 45 ml/kg, was associated with modest improvements in lactate clearance and potential improvements in mortality. Further study is needed to define treatment strategies in this prevalent and morbid group of patients with sepsis.

Figure 1.

Mean hospital mortality (solid line) and 95% confidence interval (dotted lines) based on the magnitude of lactate change within 12 hours compared with index values. Patients with decreased lactate (across percentage strata) are represented toward the right of the figure, whereas those with increased lactate are toward the left. The vertical line demarcates increased and decreased repeat lactate values.

Figure 2.

Frequency of changes in lactate levels within 4 hours stratified by total fluid volume and magnitude of change. Changes are represented by shading of bars based on whether lactate levels increased (white), decreased (gray), or were unchanged (black).

Figure 3.

Mean hospital mortality among patients with decreased lactate within 8 hours of index test, stratified by total fluid received in increments of 7.5 ml/kg based on medication administration record.