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

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Title: Lactate clearance as a prognostic marker of mortality in severely ill febrile children in East Africa
Author(s): Aramburo, A
Todd, J
George, EC
Kiguli, S
Olupot-Olupot, P
Opoka, RO
Engoru, C
Akech, SO
Nyeko, R
Gibb, DM
Babiker, AG
Maitland, K
Item Type: Journal Article
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). t 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.
Publication Date: 9-Mar-2018
Date of Acceptance: 26-Jan-2018
URI: http://hdl.handle.net/10044/1/56454
DOI: https://dx.doi.org/10.1186/s12916-018-1014-x
ISSN: 1741-7015
Publisher: BioMed Central
Journal / Book Title: BMC Medicine
Volume: 16
Sponsor/Funder: Medical Research Council (MRC)
Medical Research Council (MRC)
Wellcome Trust
Funder's Grant Number: G0601027
G0801439
100693/Z/12/Z
Copyright Statement: © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/ ), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/ ) applies to the data made available in this article, unless otherwise stated.
Keywords: Children
Clinical trials
East Africa
Hospital admission
Hyperlactataemia
Lactate clearance
Malaria
Mortality
Randomised
Sepsis
11 Medical And Health Sciences
General & Internal Medicine
Publication Status: Published
Article Number: ARTN 37
Appears in Collections:Department of Medicine
Faculty of Medicine



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