Relative hyperlactatemia and hospital mortality in critically ill patients: a retrospective multi-centre study

Abstract

Introduction: Higher lactate concentrations within the normal reference range (relative hyperlactatemia) are not considered clinically significant. We tested the hypothesis that relative hyperlactatemia is independently associated with an increased risk of hospital death.

Methods: This observational study examined a prospectively obtained intensive care database of 7,155 consecutive critically ill patients admitted to the Intensive Care Units (ICUs) of four Australian university hospitals. We assessed the relationship between ICU admission lactate, maximal lactate and time-weighted lactate levels and hospital outcome in all patients and also in those patients whose lactate concentrations (admission n = 3,964, maximal n = 2,511, and time-weighted n = 4,584) were under 2 mmol.L-1 (i.e. relative hyperlactatemia).

Results: We obtained 172,723 lactate measurements. Higher admission and time-weightedlactate concentration within the reference range was independently associated with increased hospital mortality (admission odds ratio (OR) 2.1, 95% confidence interval (CI) 1.3 to 3.5, P = 0.01; time-weighted OR 3.7, 95% CI 1.9 to 7.00, P < 0.0001). This significant association was first detectable at lactate concentrations > 0.75 mmol.L-1. Furthermore, in patients whose lactate ever exceeded 2 mmol.L-1, higher time-weighted lactate remained strongly associated with higher hospital mortality (OR 4.8, 95% CI 1.8 to 12.4, P < 0.001).

Conclusions: In critically ill patients, relative hyperlactataemia is independently associated with increased hospital mortality. Blood lactate concentrations > 0.75 mmol.L-1 can be used by clinicians to identify patients at higher risk of death. The current reference range for lactate in the critically ill may need to be re-assessed.

Figure 1

Relationship among the admission, maximal and time weighted blood lactate concentration and mortality. Relationship among the admission blood lactate concentration (Lac_ADM) Panel (a); maximal blood lactate concentration (Lac_MAX;) Panel (b); and time weighted blood lactate concentration (Lac_TW) Panel (c); and hospital and ICU mortality. The number of patients in each group is expressed as (n).

Figure 2

Relationship between the admission blood lactate concentration within the normal range and mortality rate. Relationship between the admission blood lactate (Lac_ADM) concentration within the normal range and ICU and hospital mortality rate (Panel (a)). The number of patients in each group is expressed as (n). Panel (b) displays the result (adjusted odds ratios (OR) with 95% Confidence Interval (CI)) of a multivariate analysis assessing the association between admission blood lactate (Lac_ADM) within the normal range and hospital mortality. (All ORs in the multivariate analysis are compared to the 0.00 to 0.75mmol.L^-1 group with the horizontal line representing an OR of 1.0.).

Figure 3

Relationship between time-weighted blood lactate concentration within the normal range and mortality rate. Relationship between time-weighted blood lactate (Lac_TW) concentration within the reference range and ICU and hospital mortality rate (Panel (a)). The number of patients in each group is expressed as (n). Panel (b) displays the result (adjusted odds ratios (OR) with 95% Confidence Interval (CI)) of a multivariate analysis assessing the association between time-weighted blood lactate concentration (Lac_TW) within the normal range and hospital mortality. Abbreviations: OR U95; odds ratio upper 95% CI; OR L95, odds ratios lower 95% CI. (All ORs in the multivariate analysis are compared to 0.00 to 0.75 mmol.L^-1 group with the horizontal line representing an OR of 1.0.).