Lactate turnover and forearm lactate metabolism in severe falciparum malaria

Lactic acidosis is a serious but poorly understood sequelum of severe malaria. To characterize lactate kinetics in complicated Plasmodium falciparum infections, eight lean, non-hypoglycaemic Thais aged 17-37 years with coma, jaundice, anaemia and/or hyperparasitaemia were studied during [1-¹³C]lactate infusions before treatment, after initial quinine administration and in convalescence. Forearm muscle lactate balance was also determined serially from arterialized and deep venous blood samples, and plethysmographic blood flow estimates. Arterialized pH remained >7.30 in all patients. Plasma lactate concentrations were elevated at presentation (mean±SD; 3.4±1.8 vs 1.0±0.30 mmol/l at follow-up; P<0.001) but did not change significantly during quinine treatment (3.0±1.9 mmol/l end-infusion; P>0.9). Pre-treatment lactate turnover (91±64 μmol/kg/min) correlated with the simultaneous plasma lactate (r(s)=0.71; P=0.02) but was comparable to that after quinine (85±34 μmol/kg/min) and in convalescence (65±24 μmol/kg/min; P>0.2). Total lactate metabolic clearance was lower both before and after quinine (30±1 and 36±24 ml/kg/min) than at follow-up (78±40 ml/kg/min; P≤0.025). Forearm balance studies indicated net skeletal muscle lactate release which increased after quinine (-1.12±0.94 vs -2.14±1.26, P<0.05; vs 0.00±0.65 μmol/100 ml/min in convalescence, P<0.001). Impaired lactate clearance appears to contribute to moderate increases in plasma lactate in non-acidotic patients with severe malaria, while increased skeletal muscle lactate production does not increase overall lactate turnover. Quinine may augment forearm muscle lactate production.