RESUMO
Children with severe malaria often present with lactic acidosis and hypoglycemia. Although both complications independently predict mortality, mechanisms underlying their development are poorly understood. To study these metabolic derangements we sequentially allocated 21 children with falciparum malaria and capillary lactate concentrations of 5 mmol/L or more to receive either quinine or artesunate as antimalarial therapy, and dichloroacetate or saline placebo for lactic acidosis. We then administered a primed infusion (90 min) of L-[3-13C1]sodium lactate and D-[6,6-D2]glucose to determine the kinetics of these substrates. The mean (SD) glucose disposal rate in all patients was 56 (16) micromol/kg x min, and the geometric mean (range) lactate disposal rate was 100 (66-177) micromol/kg x min. Glucose and lactate disposal rates were positively correlated (r = 0.62; P = 0.005). Artesunate was associated with faster parasite clearance, lower insulin/glucose ratios, and higher glucose disposal rates than quinine. Lactate disposal was positively 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 disposal rates increased with dichloroacetate treatment. Elevated glucose turnover in severe malaria mainly results from enhanced anaerobic glycolysis. Quinine differs from artesunate in its effects on glucose kinetics. Increased lactate production is the most important determinant of lactic acidosis.
Assuntos
Artemisininas , Glicemia/metabolismo , Ácido Láctico/sangue , Malária Falciparum/sangue , Acidose Láctica/tratamento farmacológico , Antimaláricos/uso terapêutico , Artesunato , Criança , Pré-Escolar , Ácido Dicloroacético/uso terapêutico , Feminino , Humanos , Lactente , Insulina/sangue , Cinética , Malária Falciparum/tratamento farmacológico , Masculino , Quinina/uso terapêutico , Sesquiterpenos/uso terapêuticoRESUMO
BACKGROUND: Dysrhythmias and death occur in patients with acquired long QT syndrome (LQTS). Little information exists regarding interactions between anesthetics and drugs that prolong ventricular repolarization. Therefore the effects of three commonly used intravenous anesthetics on ventricular repolarization were investigated in the setting of drug-induced, long QT syndrome. METHODS: The effects of increasing concentrations (0, 10, 25, and 50 microM) of propofol, ketamine, and thiopental on ventricular repolarization were evaluated by measuring the monophasic action potential duration at 90% repolarization (MAPD90) in guinea pig Langendorff-perfused hearts in the absence or presence of erythromycin (100 microM). If an anesthetic enhanced erythromycin-induced prolongation of MAPD90, its effects on the delayed rectifier (I[K]) and inward rectifier (I[Kl]) potassium currents were measured using the whole-cell patch-clamp technique. RESULTS: At clinically relevant concentrations, only thiopental significantly modulated erythromycin's effect on MAPD90. Thiopental at 10, 25, and 50 microM prolonged MAPD90 from a control of 163 +/- 6 ms by 18 +/- 4, 30 +/- 3, and 31 +/- 4 ms, respectively. In a separate group, erythromycin prolonged MAPD90 from 155 +/- 2 ms to 171 +/- 2 ms (n = 21, P < 0.001). In the presence of erythromycin, thiopental at 10, 25, and 50 microM caused significantly greater prolongation from a control of 171 +/- 2 ms by 39 +/- 2, 58 +/- 3, and 72 +/- 6 ms, respectively. Whole-cell patch-clamp experiments indicated that thiopental inhibited I(K) and I(Kl). CONCLUSIONS: Intravenous anesthetics caused markedly different effects on ventricular repolarization. Thiopental, unlike propofol and ketamine, potentiated the effects of erythromycin on ventricular repolarization by inhibiting I(K) and I(Kl).
Assuntos
Anestésicos Intravenosos/farmacologia , Eritromicina/toxicidade , Coração/efeitos dos fármacos , Síndrome do QT Longo/induzido quimicamente , Potenciais de Ação/efeitos dos fármacos , Animais , Feminino , Cobaias , Coração/fisiologia , Ventrículos do Coração , Masculino , Canais de Potássio/efeitos dos fármacosAssuntos
Procedimentos Cirúrgicos Ambulatórios/economia , Anestésicos Inalatórios/normas , Anestésicos Intravenosos/normas , Farmacoeconomia/normas , Isoflurano/análogos & derivados , Isoflurano/normas , Propofol/normas , Adulto , Procedimentos Cirúrgicos Ambulatórios/métodos , Anestésicos Inalatórios/economia , Anestésicos Intravenosos/economia , Desflurano , Florida , Hospitais com mais de 500 Leitos , Hospitais Universitários , Humanos , Isoflurano/economia , Comitê de Farmácia e Terapêutica , Propofol/economiaRESUMO
Fetal plasma alanine disposal rate (DR) and decarboxylation rate were measured at 132 +/- 1 days gestation in nine fetal lambs infused with L-[1-14C]alanine via a brachial vein. In five experiments, L-[1-13C]alanine was added to the infusate. Using L-[1-14C]alanine, we found mean DR to be 15.5 +/- 1.8 mumol.min-1 . kg-1. DR was significantly correlated to both arterial plasma alanine and whole blood lactate concentrations. Placental uptake of fetal plasma alanine accounted for 19 +/- 4% of DR. Fetal and placental production of CO2 from the first carbon of alanine were 61 +/- 2 and 16 +/- 2% of DR, respectively, for a total uterine excretion of 77 +/- 3%. Net alanine flux from placenta to fetus was 5.2 +/- 0.5 mumol.min-1 x kg-1, which was less than fetal plasma alanine decarboxylation (9.4 +/- 1.2 mumol.min-1 x kg-1) plus fetal alanine accretion (2.4 mumol.min-1 x kg-1). Utilizing L-[1-13C]alanine, we found DR to be 14.2 +/- 0.8 mumol.min-1 x kg-1, not significantly different from the 14C data. We conclude that both the umbilical uptake of alanine from the placenta and fetal alanine synthesis contribute to fetal alanine supply and that oxidation is the main route of fetal plasma alanine disposal.