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BMC Med. 2018 Mar 9;16(1):37. doi: 10.1186/s12916-018-1014-x.

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

Author information

1
Royal Brompton & Harefield NHS Foundation Trust, Sydney Street, London, SW3 6NP, UK.
2
London School of Hygiene and Tropical Medicine, 15-17, Tavistock Place WC1H 9SH, London, WC1H 9SH, UK.
3
Medical Research Council Clinical Trials Unit (MRC CTU) at UCL, 125 Aviation House, Kingsway, London, WC2B 6NH, UK.
4
Department of Paediatrics, Mulago Hospital, Makerere College of Health Sciences, PO Box 7072, Kampala, Uganda.
5
Department of Paediatrics, Mbale Regional Referral Hospital, Pallisa Road, PO Box 291, Mbale, Uganda.
6
Mbale Clinical Research Institute (MCRI), Plot 29-33 Pallisa Rd, PO Box 1966, Mbale, Uganda.
7
Department of Paediatrics, Soroti Regional Referral Hospital, PO Box 289, Soroti, Uganda.
8
Kilifi Clinical Trials Facility, KEMRI-Wellcome Trust Research Programme, PO Box 203, Nairobi, Kenya.
9
St Mary's Hospital, Lacor, PO Box 180, Gulu, Uganda.
10
Teule Hospital, PO Box 81, Muheza, Tanzania.
11
Kilifi Clinical Trials Facility, KEMRI-Wellcome Trust Research Programme, PO Box 203, Nairobi, Kenya. k.maitland@imperial.ac.uk.
12
Department of Paediatrics, Faculty of Medicine, Imperial College, W2 1PG, London, UK. k.maitland@imperial.ac.uk.

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.

KEYWORDS:

Children; Clinical trials; East Africa; Hospital admission; Hyperlactataemia; Lactate clearance; Malaria; Mortality; Randomised; Sepsis

PMID:
29519240
PMCID:
PMC5844084
DOI:
10.1186/s12916-018-1014-x
[Indexed for MEDLINE]
Free PMC Article

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