Aramburo, A; Todd, J; George, EC; Kiguli, S; Olupot- Olupot, P; Opoka, RO; Engoru, C; ... Maitland, K; + view all Aramburo, A; Todd, J; George, EC; Kiguli, S; Olupot- Olupot, P; Opoka, RO; Engoru, C; Akech, SO; Nyeko, R; Mtove, G; Gibb, DM; Babiker, AG; Maitland, K; - view fewer (2018) Lactate clearance as a prognostic marker of mortality in severely ill febrile children in East Africa. BMC Medicine , 16 (37) 10.1186/s12916-018-1014-x.

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Abstract

Background: Hyperlactataemia (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 exists in African children living in malaria-endemic areas. Methods: In a secondary data analysis of severely ill febrile children included in a fluid resuscitation trial (FEAST), we assessed the association between lactate levels at admission and LC at 8 hours with all-cause mortality at 72 hours (d72). LC was defined as a relative lactate decline ≥40% and/or lactate normalisation (lactate <2.5 mmol/L). Results: Of 3170 children in the FEAST trial, including 1719 (57%) children 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 hours 309 (10.3%) children 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). This association was not modified by malaria status, despite children with malaria having a higher baseline lactate (median 4.6mmol/L vs 3mmol/L; p<0.001) and a lower mortality rate (OR=0.42; p <0.001) compared to nonmalarial 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 those with other febrile illnesses (3.4 mmol/L). At 8 hours, 2748/3008 (91%) survivors 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 hours (OR 0.24; 95% CI 0.14, 4 0.42; p<0.001). Absence of LC (<10%) at 8 hours was strongly associated with death at 72 hours (OR 4.62; 95% CI 2.7, 8.0; p<0.001). Conclusion: Independently of the underlying diagnosis, HL is a strong risk factor for death at 72 hours in children admitted with severe febrile illnesses in Africa. Children able to clear lactate within 8 hours 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 registration: ISRCTN69856593

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