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

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dc.contributor.author Aramburo, A.
dc.contributor.author Todd, Jim
dc.contributor.author George, Elizabeth C.
dc.contributor.author Kiguli, Sarah
dc.contributor.author Olupot-Olupot, Peter
dc.contributor.author Opoka, Robert O.
dc.contributor.author Engoru, Charles
dc.contributor.author Akech, Samuel
dc.contributor.author Nyeko, Richard
dc.contributor.author Mtove, George
dc.contributor.author Gibb, Diana M.
dc.contributor.author Babiker, Abdel G.
dc.contributor.author Maitland, Kathryn
dc.date.accessioned 2019-02-14T12:20:09Z
dc.date.available 2019-02-14T12:20:09Z
dc.date.issued 2018
dc.identifier.issn 1741-7015
dc.identifier.uri http://hdl.handle.net/20.500.12283/220
dc.description.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 exist for African children living in malaria-endemic areas. Methods: In 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). Results: Of 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). Conclusions: Independently 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 registration: ISRCTN69856593 Registered 21 January 2009. en_US
dc.description.sponsorship Medical Research Council (MRC), UK, Department for International Development (DFID), Centres for Global Health Research, Imperial College Centre for Global Health Research, UK, Wellcome Trust en_US
dc.language.iso en en_US
dc.publisher BMC en_US
dc.subject Hyperlactataemia en_US
dc.subject Children en_US
dc.subject Lactate clearance en_US
dc.subject East Africa en_US
dc.subject Mortality en_US
dc.subject Hospital admission en_US
dc.subject Clinical trials en_US
dc.subject Randomised en_US
dc.subject Malaria en_US
dc.subject Sepsis en_US
dc.title Lactate clearance as a prognostic marker of mortality in severely ill febrile children in East Africa en_US
dc.type Article en_US


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