Date Published: October 19, 2004
Publisher: Public Library of Science
Author(s): Timothy Planche, Myriam Onanga, Achim Schwenk, Arnaud Dzeing, Steffen Borrmann, Jean-François Faucher, Antony Wright, Les Bluck, Leigh Ward, Maryvonne Kombila, Peter G Kremsner, Sanjeev Krishna, Nicholas J White
Abstract: AbstractBackgroundThe degree of volume depletion in severe malaria is currently unknown, although knowledge of fluid compartment volumes can guide therapy. To assist management of severely ill children, and to test the hypothesis that volume changes in fluid compartments reflect disease severity, we measured body compartment volumes in Gabonese children with malaria.Methods and FindingsTotal body water volume (TBW) and extracellular water volume (ECW) were estimated in children with severe or moderate malaria and in convalescence by tracer dilution with heavy water and bromide, respectively. Intracellular water volume (ICW) was derived from these parameters. Bioelectrical impedance analysis estimates of TBW and ECW were calibrated against dilution methods, and bioelectrical impedance analysis measurements were taken daily until discharge. Sixteen children had severe and 19 moderate malaria. Severe childhood malaria was associated with depletion of TBW (mean [SD] of 37  ml/kg, or 6.7% [6.0%]) relative to measurement at discharge. This is defined as mild dehydration in other conditions. ECW measurements were normal on admission in children with severe malaria and did not rise in the first few days of admission. Volumes in different compartments (TBW, ECW, and ICW) were not related to hyperlactataemia or other clinical and laboratory markers of disease severity. Moderate malaria was not associated with a depletion of TBW.ConclusionsSignificant hypovolaemia does not exacerbate complications of severe or moderate malaria. As rapid rehydration of children with malaria may have risks, we suggest that fluid replacement regimens should aim to correct fluid losses over 12–24 h.
Partial Text: Malaria claims one million lives annually, with more than 90% of these being those of children in sub-Saharan Africa . Most deaths of hospitalised children occur in the first 24 h after admission. Even modest improvements in management during this time may improve survival . There is considerable disagreement about the degree to which children with severe malaria become hypovolemic. In east African studies, clinical signs of severe malaria (such as tachycardia, prolonged capillary refill times, and decreased urine volume) have been interpreted as evidence for volume depletion [2,3,4,5,6]. However, determining fluid compartment volumes is the first and most critical step in optimising fluid replacement therapy for children with malaria because clinical assessment of fluid status is difficult and imprecise . Our study was designed to measure total body water volume (TBW) and extracellular water volume (ECW) using nonradioactive tracer dilution techniques and to derive intracellular water volume (ICW). Bromide distributes in the extracellular space so that concentrations measured 2–4 h after administration safely and reliably estimate ECW. Heavy water (2H2O) space represents TBW. ICW is calculated by subtraction of the ECW from the TBW.
The study was conducted at the Albert Schweitzer Hospital, Lambaréné, Gabon, and Centre Hospitalier de Libreville, Gabon. It was approved by the ethics committees of the International Foundation of the Albert Schweitzer Hospital, the Gabonese Ministry of Health, and the University of Tübingen.
Between October 1999 and March 2000, 205 children who were judged ill enough to be hospitalised were referred to the study team. One hundred and thirty-two children had malaria, 20 with severe and 35 with moderate disease. Ten children with moderate and two with severe malaria were ineligible for study because of their age, and for seven children (one with severe malaria) consent could not be obtained. One child died before inclusion into the study, leaving nineteen children with moderate and sixteen with severe malaria admitted to this study. The median (interquartile range [IQR]) time from admission to administration of tracers was 54 (37–84) min, during which complications such as convulsions or hypoglycaemia were treated. The baseline characteristics of children are given in Table 1. Those with severe malaria had significantly higher pulse rates, mean arterial pressure and blood lactate concentrations, and a longer capillary refill time (p < 0.001), compared to children with moderate malaria. Capillary refill time and blood lactate concentrations were correlated with each other (adjusted r2 [adj r2] = 0.25, p = 0.031). We have shown that severe childhood malaria is associated with mild dehydration in most cases, with a mean (SD) depletion of TBW of 37 (33) ml/kg, or 6.7% (6.0%). Only 3/16 children (19%) in our study had moderate volume depletion (> 60–90 ml/kg), and none were severely dehydrated (> 100 ml/kg) . Moderate malaria was not associated with any significant changes in TBW. Consistent with a lower TBW in severe disease, ICW was depleted in children with severe malaria by a mean (SD) of 40 (22) ml/kg, an 11.7% (11.0%) difference. However, we found no relationship between TBW, ECW, and ICW and clinical and laboratory markers of disease severity, in particular the two most important prognostic indicators of fatal outcome: hyperlactataemia and Blantyre coma score .