Lactate clearance as a prognostic marker of mortality in severely ill febrile children in East Africa

Abstract

BackgroundHyperlactataemia (HL) is a biomarker of disease severity that predicts mortality in patients with sepsis and malaria. Lactate clearance (LC) during resuscitation has been shown to be a prognostic factor of survival in critically ill adults, but little data exist for African children living in malaria-endemic areas.MethodsIn a secondary data analysis of severely ill febrile children included in the Fluid Expansion as Supportive Therapy (FEAST) resuscitation trial, we assessed the association between lactate levels at admission and LC at 8 h with all-cause mortality at 72 h (d72). LC was defined as a relative lactate decline ≥ 40% and/or lactate normalisation (lactate < 2.5 mmol/L).ResultsOf 3170 children in the FEAST trial, including 1719 children (57%) with Plasmodium falciparum malaria, 3008 (95%) had a baseline lactate measurement, 2127 (71%) had HL (lactate ≥ 2.5 mmol/L), and 1179 (39%) had severe HL (≥ 5 mmol/L). Within 72 h, 309 children (10.3%) died, of whom 284 (92%) had baseline HL. After adjustment for potential confounders, severe HL was strongly associated with mortality (Odds Ratio (OR) 6.96; 95% CI 3.52, 13.76, p < 0.001). This association was not modified by malaria status, despite children with malaria having a higher baseline lactate (median 4.6 mmol/L vs 3 mmol/L; p < 0.001) and a lower mortality rate (OR = 0.42; p < 0.001) compared to non-malarial cases. Sensitivity and specificity analysis identified a higher lactate on admission cut-off value predictive of d72 for children with malaria (5.2 mmol/L) than for those with other febrile illnesses (3.4 mmol/L).At 8 h, 2748/3008 survivors (91%) had a lactate measured, 1906 (63%) of whom had HL on admission, of whom 1014 (53%) fulfilled pre-defined LC criteria. After adjustment for confounders, LC independently predicted survival after 8 h (OR 0.24; 95% CI 0.14, 0.42; p < 0.001). Absence of LC (< 10%) at 8 h was strongly associated with death at 72 h (OR 4.62; 95% CI 2.7, 8.0; p < 0.001).ConclusionsIndependently of the underlying diagnosis, HL is a strong risk factor for death at 72 h in children admitted with severe febrile illnesses in Africa. Children able to clear lactate within 8 h had an improved chance of survival. These findings prompt the more widespread use of lactate and LC to identify children with severe disease and monitor response to treatment.Trial registrationISRCTN69856593 Registered 21 January 2009.Electronic supplementary materialThe online version of this article (10.1186/s12916-018-1014-x) contains supplementary material, which is available to authorized users.

Handheld Point-of-Care Lactate Measurement at Admission Predicts Mortality in Ugandan Children Hospitalized with Pneumonia: A Prospective Cohort Study

“…Following the method of Aramburo et al, 28 slow lactate clearance predicted subsequent mortality. Among 75 children with elevated initial lactate (³ 2.5 mmol/L) and at least two lactate measurements, 7/22 (32%) with slow lactate clearance had a fatal outcome compared with 6/53 (11%) patients with efficient lactate clearance (P = 0.046).…”

“…27 Children were treated according to WHO guidelines. 19 The definition of lactate clearance was adapted from a recent study by Aramburo et al 28 Slow lactate clearance among patients with elevated lactate at baseline (³ 2.5 mmol/L) was defined as failure to normalize lactate and clearance half-life of ³ 10.8 hours (corresponding to clearance of least 40% of baseline lactate by 8 hours, assuming first-order clearance kinetics). 28 Ethical approval and consent to participate.…”

“…19 The definition of lactate clearance was adapted from a recent study by Aramburo et al 28 Slow lactate clearance among patients with elevated lactate at baseline (³ 2.5 mmol/L) was defined as failure to normalize lactate and clearance half-life of ³ 10.8 hours (corresponding to clearance of least 40% of baseline lactate by 8 hours, assuming first-order clearance kinetics). 28 Ethical approval and consent to participate. Ethics approval for this study was obtained from the University Health Network, University of Toronto (Toronto, Canada), and the Uganda National Council for Science and Technology, Makerere University Research Ethics Committee (Kampala, Uganda).…”

Lactate indices as predictors of in-hospital mortality or 90-day survival after admission to an intensive care unit in unselected critically ill patients

“…Several dynamic lactate indices have been shown as effective predictors of outcome in ICU patients. ΔLac, also called lactate clearance in some articles, has been extensively studied [7][8][9][10][11]. However, use of the term "clearance" has been criticized because of its general meaning of elimination and the need for intravenous injection of radiolabeled lactate to directly measure clearance [2,12].…”

“…Dynamic indices based on serial lactate changes may be more informative than static ones. In particular, changes in lactate concentrations (Δ Lac) have been extensively studied [7][8][9][10][11]. However, adequate time intervals or optimal cut-off values for Δ Lac have varied considerably among studies [7][8][9][10][11][12].…”