Glucose and lactate kinetics in children with severe malaria

Children with severe malaria often present with lactic acidosis and hypogly cemia. Although both complications independently predict mortality, mechani sms underlying their development are poorly understood. To study these meta bolic derangements we sequentially allocated 21 children with falciparum ma laria and capillary lactate concentrations of 5 mmol/L or more to receive e ither quinine or artesunate as antimalarial therapy, and dichloroacetate or saline placebo for lactic acidosis. We then administered a primed infusion (90 min) of L-[3-C-13(1)]sodium lactate and D-[6,6-D-2]glucose to determin e the kinetics of these substrates. The mean (SD) glucose disposal rate in all patients was 56 (16) mu mol/kg.min, and the geometric mean (range) lact ate disposal rate was 100 (66-177) mu mol/kg.min. Glucose and lactate dispo sal rates were positively correlated (r = 0.62; P = 0.005). Artesunate was associated with faster parasite clearance, lower insulin/glucose ratios, an d higher glucose disposal rates than quinine. Lactate disposal was positive ly correlated with plasma lactate concentrations (r = 0.66; P = 0.002) and time to recovery from coma (r = 0.82; P < 0.001; n = 15). Basal lactate dis posal rates increased with dichloroacetate treatment. Elevated glucose turn over in severe malaria mainly results from enhanced anaerobic glycolysis. Q uinine differs from artesunate in its effects on glucose kinetics. Increase d lactate production is the most important determinant of lactic acidosis.