Krishna S, Agbenyega T, Angus B J, Bedu-Addo G, Ofori-Amanfo G, Henderson G, Szwandt I S, O'Brien R, Stacpoole P W
Division of Communicable Diseases, St George's Hospital Medical School, London, UK.
QJM. 1995 May;88(5):341-9.
Lactic acidosis frequently complicates severe malaria in African children, and is a strong independent predictor of mortality. We tested the hypothesis that sodium dichloroacetate (DCA), an activator of pyruvate dehydrogenase, rapidly reduces hyperlactataemia in this patient population. Eighteen children with severe malaria and capillary plasma lactate > or = 5 mM were randomized to receive either intramuscular quinine plus a single 50 mg/kg intravenous infusion of DCA in saline, or quinine plus intravenous saline alone. Two patients in each treatment group died following randomization. Thirty minutes after treatment, the mean plasma lactate was 28% below pretreatment baseline values in the DCA group, but was unchanged in the placebo group. Throughout the first 4 h after treatment, mean plasma lactate in the DCA-treated patients was significantly less than that in controls (p = 0.003). Thereafter, mean plasma lactate declined in both groups and was < 2 mM 10 h after treatment. DCA was well tolerated and did not alter quinine pharmacokinetics. A single intravenous dose of DCA rapidly improved lactic acidosis in African children with severe malaria, suggesting that DCA may be a useful adjunct in the initial treatment of these patients, and may increase their chance of survival by improving a major complication of their illness.
乳酸性酸中毒常使非洲儿童的重症疟疾病情复杂化，且是死亡率的一个强有力的独立预测指标。我们检验了如下假设：二氯乙酸钠（DCA）作为丙酮酸脱氢酶的激活剂，能迅速降低该患者群体的高乳酸血症。18名患有重症疟疾且毛细血管血浆乳酸水平≥5 mM的儿童被随机分组，分别接受肌肉注射奎宁加单次50 mg/kg的DCA静脉注射生理盐水，或仅接受奎宁加静脉注射生理盐水。每个治疗组各有两名患者在随机分组后死亡。治疗30分钟后，DCA组的平均血浆乳酸水平比治疗前基线值低28%，而安慰剂组则无变化。在治疗后的前4小时内，接受DCA治疗的患者的平均血浆乳酸水平显著低于对照组（p = 0.003）。此后，两组的平均血浆乳酸水平均下降，且在治疗10小时后<2 mM。DCA耐受性良好，且未改变奎宁的药代动力学。单次静脉注射DCA能迅速改善患有重症疟疾的非洲儿童的乳酸性酸中毒，这表明DCA可能是这些患者初始治疗中的一种有用辅助药物，并且可能通过改善其疾病的一种主要并发症来增加他们的生存机会。
