RESUMO
Raising plasma free fatty acid (FFA) levels reduces muscle glucose uptake, but the effect of FFAs on splanchnic glucose uptake, total glucose output, and glucose cycling may also be critical to producing lipid-induced glucose intolerance. In eight normal volunteers, we measured glucose turnover and cycling rates ([2H7]glucose infusion) during a moderately hyperglycemic (7.7 mmol/l) hyperinsulinemic clamp, before and after ingestion of a labeled (dideuterated) oral glucose load (700 mg/kg). Each test was performed twice, with either a lipid or a saline infusion; four subjects also had a third test with a glycerol infusion. As shown by similar rates of exogenous glucose appearance, the lipid infusion did not reduce first-pass splanchnic glucose uptake (saline 1.48+/-0.18, lipid 1.69+/-0.17, and glycerol 1.88+/-0.17 mmol/kg per 180 min; NS), but it reduced peripheral glucose uptake by 40% (P < 0.01 vs. both saline and glycerol infusions). Before oral ingestion of glucose, total glucose output was similarly increased by the lipid and glycerol infusions. Total glucose output was significantly increased by FFAs after oral ingestion of glucose (saline 3.68+/-1.15, glycerol 3.68+/-1.70, and lipid 7.92+/-0.88 micromol x kg(-1) x min(-1); P < 0.01 vs. saline and P < 0.05 vs. glycerol). The glucose cycling rate was approximately 2.7 micromol x kg(-1) x min(-1) with the three infusions and tended to decrease all along the lipid infusion, which argues against a stimulation of glucose-6-phosphatase by FFAs. It is concluded that in situations of moderate hyperinsulinemia-hyperglycemia, FFAs reduce peripheral but not splanchnic glucose uptake. Total glucose output is increased by FFAs, by a mechanism that does not seem to involve stimulation of glucose-6-phosphatase.
Assuntos
Ácidos Graxos não Esterificados/sangue , Glucose/farmacocinética , Músculo Esquelético/metabolismo , Vísceras/metabolismo , Adulto , Gorduras/farmacologia , Ácidos Graxos não Esterificados/farmacologia , Glicerol/farmacologia , Hormônios/sangue , Humanos , Masculino , Valores de Referência , Distribuição TecidualRESUMO
BACKGROUND: Conversion of glucose into lipid (de novo lipogenesis; DNL) is a possible fate of carbohydrate administered during nutritional support. It cannot be detected by conventional methods such as indirect calorimetry if it does not exceed lipid oxidation. OBJECTIVE: The objective was to evaluate the effects of carbohydrate administered as part of continuous enteral nutrition in critically ill patients. DESIGN: This was a prospective, open study including 25 patients nonconsecutively admitted to a medicosurgical intensive care unit. Glucose metabolism and hepatic DNL were measured in the fasting state or after 3 d of continuous isoenergetic enteral feeding providing 28%, 53%, or 75% carbohydrate. RESULTS: DNL increased with increasing carbohydrate intake (f1.gif" BORDER="0"> +/- SEM: 7.5 +/- 1.2% with 28% carbohydrate, 9.2 +/- 1.5% with 53% carbohydrate, and 19.4 +/- 3.8% with 75% carbohydrate) and was nearly zero in a group of patients who had fasted for an average of 28 h (1.0 +/- 0.2%). In multiple regression analysis, DNL was correlated with carbohydrate intake, but not with body weight or plasma insulin concentrations. Endogenous glucose production, assessed with a dual-isotope technique, was not significantly different between the 3 groups of patients (13.7-15.3 micromol * kg(-1) * min(-1)), indicating impaired suppression by carbohydrate feeding. Gluconeogenesis was measured with [(13)C]bicarbonate, and increased as the carbohydrate intake increased (from 2.1 +/- 0.5 micromol * kg(-1) * min(-1) with 28% carbohydrate intake to 3.7 +/- 0.3 micromol * kg(-1) * min(-1) with 75% carbohydrate intake, P: < 0. 05). CONCLUSION: Carbohydrate feeding fails to suppress endogenous glucose production and gluconeogenesis, but stimulates DNL in critically ill patients.
Assuntos
Metabolismo dos Carboidratos , Nutrição Enteral/métodos , Lipídeos/biossíntese , Adulto , Idoso , Glicemia/análise , Calorimetria Indireta , Carboidratos/administração & dosagem , Cromatografia Líquida de Alta Pressão , Cuidados Críticos/métodos , Ácidos Graxos/sangue , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Glucagon/sangue , Gluconeogênese , Glucose/biossíntese , Glucose/metabolismo , Humanos , Hidrocortisona/sangue , Insulina/análise , Cinética , Fígado/metabolismo , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Prospectivos , Radioimunoensaio , Distribuição Aleatória , Análise de Regressão , Triglicerídeos/sangueRESUMO
OBJECTIVES: To assess the hemodynamic and metabolic adaptations to enteral nutrition (EN) in patients with hemodynamic compromise. DESIGN AND SETTING: Prospective study in a university hospital surgical ICU, comparing baseline (fasted) with continuous EN condition. PATIENTS: Nine patients requiring hemodynamic support by catecholamines (dobutamine and/or norepinephrine) 1 day after cardiac surgery under cardiopulmonary bypass. INTERVENTION: Isoenergetic EN via a postpyloric tube while catecholamine treatment remained constant. Baseline (fasted) condition was compared to continuous EN condition. MEASUREMENTS AND MAIN RESULTS: Cardiac index (CI), mean arterial pressure (MAP), pulmonary and wedge pressures, indocyanine green (ICG) clearance, gastric tonometry, plasma glucose and insulin, and glucose turnover (6,62H2-glucose infusion) were determined repetitively every 60 min during 2 h of baseline fasting condition and 3 h of EN. During EN CI increased (from 2.9 +/- 0.5 to 3.3 +/- 0.5 l min-1 m-2), MAP decreased transiently (from 78 +/- 7 to 70 +/- 11 mmHg), ICG clearance increased (from 527 +/- 396 to 690 +/- 548 ml/min), and gastric tonometry remained unchanged, while there were increases in glucose (158 +/- 23 to 216 +/- 62 mg/dl), insulin (29 +/- 23 to 181 +/- 200 mU/l), and glucose rate of appearance (2.4 +/- 0.2 to 3.3 +/- 0.2 mg min-1 kg-1). CONCLUSIONS: The introduction of EN in these postoperative patients increased CI and splanchnic blood flow, while the metabolic response indicated that nutrients were utilized. These preliminary results suggest that the hemodynamic response to early EN may be adequate after cardiac surgery even in patients requiring inotropes.
Assuntos
Baixo Débito Cardíaco/etiologia , Baixo Débito Cardíaco/fisiopatologia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Metabolismo Energético , Nutrição Enteral , Hipotensão/etiologia , Hipotensão/fisiopatologia , Circulação Esplâncnica , Adaptação Fisiológica , Idoso , Velocidade do Fluxo Sanguíneo , Glicemia/análise , Pressão Sanguínea , Baixo Débito Cardíaco/tratamento farmacológico , Baixo Débito Cardíaco/metabolismo , Dobutamina/uso terapêutico , Nutrição Enteral/métodos , Jejum , Feminino , Hemodinâmica , Humanos , Hipotensão/tratamento farmacológico , Hipotensão/metabolismo , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Norepinefrina/uso terapêutico , Período Pós-Operatório , Estudos Prospectivos , Pressão Propulsora Pulmonar , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVE: To investigate whether early selenium (Se) supplementation can modify the post-traumatic alterations of thyroid hormone metabolism, since the first week after trauma is characterised by low plasma Se and negative Se balances. DESIGN: Prospective, placebo-controlled randomised supplementation trial. SETTING: Surgical ICU in a tertiary university hospital. PATIENTS: Thirty-one critically ill trauma patients aged 42 +/- 16 years (mean +/- SD), with severe multiple injury (Injury Severity Score 30 +/- 7). INTERVENTION: Supplementation during the first 5 days after injury with either Se or placebo. The selenium group was further randomised to receive daily 500 microg Se, with or without 150 mg alpha-tocopherol (AT) and 13 mg zinc supplements. The placebo group received the vehicle. Circulating Se, AT, zinc, and thyroid hormones were determined on D0 (= day 0, admission), D1, D2, D5, D10, and D20. RESULTS: Plasma Se, low on D0, normalised from D1 in the selenium group; total T4 and T3 increased more and faster after D2 (P = 0.04 and 0.08), reverse T3 rising less between D0 and D2 (P = 0.05). CONCLUSIONS: Selenium supplements increased the circulating Se levels. Supplementation was associated with modest changes in thyroid hormones, with an earlier normalisation of T4 and reverse T3 plasma levels. The addition of AT and zinc did not produce any additional change.
Assuntos
Síndromes do Eutireóideo Doente/prevenção & controle , Selênio/deficiência , Selênio/uso terapêutico , Ferimentos e Lesões/tratamento farmacológico , Adulto , Análise de Variância , Antioxidantes/uso terapêutico , Quimioterapia Combinada , Síndromes do Eutireóideo Doente/etiologia , Humanos , Estudos Prospectivos , Tiroxina/sangue , Tri-Iodotironina Reversa/sangue , Vitamina E/uso terapêutico , Ferimentos e Lesões/sangue , Ferimentos e Lesões/complicações , Zinco/uso terapêuticoRESUMO
BACKGROUND: Hyperglycemia and an increased ventilatory demand secondary to an increased CO2 production are frequent undesirable effects of total parenteral nutrition (TPN) in critically ill patients. This study was performed to assess whether sodium lactate as a metabolic substrate may affect these variables. METHODS: Five male patients with multiple trauma during the flow phase were studied during two consecutive 3-hour periods of isocaloric (1.1 x resting energy expenditure) TPN. Sixty-five percent of total calories was provided as carbohydrate, 15% as lipids, and 20% as amino acids during the first period (TPN-glucose), whereas 35% carbohydrate, 30% lactate, 20% lipids, and 15% amino acids (TPN-lactate) were substituted during the second period. Respiratory gas exchanges and net substrate oxidation were assessed by means of indirect calorimetry. Glucose kinetics was determined by primed-constant infusion of U-13C glucose. RESULTS: Compared with TPN-glucose, TPN-lactate decreased glycemia by 20%, insulinemia by 43%, net carbohydrate oxidation (assessed from indirect calorimetry) by 34%, and plasma glucose oxidation (assessed from 13CO2) by 54%. Respiratory oxygen exchange were increased by 3.7% due to a 20% thermic effect of lactate, but respiratory CO2 exchanges did not change. Pao2 decreased by 11.3 mm Hg, indicating that the increased O2 consumption was not matched by an appropriate increase in spontaneous ventilation. Arterial pH increased from 7.41 +/- 0.04 to 7.46 +/- 0.05. CONCLUSION: Sodium lactate as a metabolic substrate limits hyperglycemia but induces metabolic alkalosis and does not spare the ventilatory demand.
Assuntos
Glucose/administração & dosagem , Traumatismo Múltiplo/terapia , Nutrição Parenteral , Lactato de Sódio/administração & dosagem , Adulto , Calorimetria Indireta , Cuidados Críticos , Glucose/metabolismo , Glucose/farmacologia , Humanos , Escala de Gravidade do Ferimento , Masculino , Pessoa de Meia-Idade , Troca Gasosa Pulmonar/efeitos dos fármacos , Respiração Artificial , Lactato de Sódio/metabolismo , Lactato de Sódio/farmacologiaRESUMO
The effects of the sympathetic activation elicited by a mental stress on insulin sensitivity and energy expenditure (VO(2)) were studied in 11 lean and 8 obese women during a hyperinsulinemic-euglycemic clamp. Six lean women were restudied under nonselective beta-adrenergic blockade with propranolol to determine the role of beta-adrenoceptors in the metabolic response to mental stress. In lean women, mental stress increased VO(2) by 20%, whole body glucose utilization ([6,6-(2)H(2)]glucose) by 34%, and cardiac index (thoracic bioimpedance) by 25%, whereas systemic vascular resistance decreased by 24%. In obese women, mental stress increased energy expenditure as in lean subjects, but it neither stimulated glucose uptake nor decreased systemic vascular resistance. In the six lean women who were restudied under propranolol, the rise in VO(2), glucose uptake, and cardiac output and the decrease in systemic vascular resistance during mental stress were all abolished. It is concluded that 1) in lean subjects, mental stress stimulates glucose uptake and energy expenditure and produces vasodilation; activation of beta-adrenoceptors is involved in these responses; and 2) in obese patients, the effects of mental stress on glucose uptake and systemic vascular resistance, but not on energy expenditure, are blunted.
Assuntos
Glucose/metabolismo , Insulina/sangue , Obesidade/sangue , Estresse Psicológico/sangue , Magreza/sangue , Antagonistas Adrenérgicos beta/administração & dosagem , Adulto , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Débito Cardíaco/efeitos dos fármacos , Débito Cardíaco/fisiologia , Metabolismo Energético/fisiologia , Epinefrina/sangue , Feminino , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Humanos , Infusões Intravenosas , Ácido Láctico/sangue , Norepinefrina/sangue , Consumo de Oxigênio/efeitos dos fármacos , Consumo de Oxigênio/fisiologia , Propranolol/administração & dosagem , Sistema Nervoso Simpático/metabolismo , Resistência Vascular/efeitos dos fármacos , Resistência Vascular/fisiologiaRESUMO
This study aimed to compare O2 consumption (VO2) determination by the gas-exchange (VO2GE) and Fick (VO2F) methods in cardiac surgical patients. A total of 10 mechanically ventilated postoperative patients were studied prospectively. Thermodilution was performed using three randomly applied techniques: room temperature saline injected at end expiration, room temperature saline randomly injected in the respiratory cycle, and iced saline injected at end expiration. The influence of the number of thermodilution determinations was assessed by comparing results from 2 and 10 injections. The variability of VO2F was greater than that of VO2GE. There was no bias between VO2GE and VO2F values using injectate at room temperature. Accuracy and precision were not improved by increasing the number of cardiac output determinations from 2 to 10. A significant bias was observed using ice-cold injectate, VO2F being 18.0 +/- 15.4 ml/min/m2 lower than VO2GE (p = 0.001). Published results when comparing VO2F and VO2GE are discrepant. However, a significant bias was found in all studies using cold injectate, with lower VO2F values. We conclude that iced injectate should not be used to assess VO2 in critically ill patients.
Assuntos
Consumo de Oxigênio , Adulto , Idoso , Calorimetria Indireta , Débito Cardíaco , Ponte de Artéria Coronária , Estado Terminal , Feminino , Humanos , Masculino , Métodos , Pessoa de Meia-Idade , Cuidados Pós-Operatórios , Estudos Prospectivos , Troca Gasosa Pulmonar , Respiração Artificial , TermodiluiçãoRESUMO
Acute ethanol administration stimulates sympathetic nervous system activity. The present study was designed to determine whether this sympathetic activation affects glycogenolysis and total hepatic glucose production (HGP) during ethanol-induced inhibition of gluconeogenesis. Nineteen volunteers participated in four protocols. Two protocols aimed to study--using combined infusion of [6,6-2H2]glucose and [U-13C]glucose, VCO2 and 13CO2 measurements--the effects of ethanol infusion alone (n = 10) or with propranolol (n = 6) or phentolamine infusion (n = 4) on HGP, glucose disposal (Rd), glucose oxidation [13C]Glcox and non-oxidative glucose disposal (NOGD = Rd - [13C]Glcox). The fourth protocol assessed the effects of saline infusion alone on HGP. Using ethanol, HGP decreased by 23%, Rd by 20% and glycaemia by 9% (all P < 0.001); heart rate increased by 10%, whereas blood pressure remained unchanged. The effects were not observed with saline, except a slight (10%) decrease in HGP (P < 0.01 vs. ethanol). Ethanol did not affect [13C]Glcox but decreased NOGD by 73% (P < 0.001). Propranolol or phentolamine did not alter any of the effects of ethanol on glucose metabolism, but decreased mean arterial pressure. Propranolol prevented the ethanol-induced increase in heart rate. In conclusion, ethanol decreased blood glucose by decreasing HGP, presumably by inhibiting gluconeogenesis. Sympathetic activation prevented the decrease in blood pressure produced by ethanol but did not stimulate glycogenolysis.
Assuntos
Antagonistas Adrenérgicos/farmacologia , Etanol/toxicidade , Glucose/biossíntese , Fígado/efeitos dos fármacos , Fígado/metabolismo , Adulto , Glicemia/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Etanol/sangue , Ácidos Graxos não Esterificados/sangue , Glucagon/sangue , Gluconeogênese/efeitos dos fármacos , Glucose/metabolismo , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Humanos , Insulina/sangue , Glicogênio Hepático/metabolismo , Masculino , Fentolamina/farmacologia , Propranolol/farmacologia , Sistema Nervoso Simpático/efeitos dos fármacos , Sistema Nervoso Simpático/fisiologiaRESUMO
Plasma levels of lipoprotein(a) [Lp(a)], an atherogenic particle, vary widely between individuals and are highly genetically determined. Whether Lp(a) is a positive acute-phase reactant is debated. The present study was designed to evaluate the impact of major inflammatory responses on plasma Lp(a) levels. Plasma levels of C-reactive protein (CRP), low density lipoprotein cholesterol, Lp(a), and apolipoprotein(a) [apo(a)] fragments, as well as urinary apo(a), were measured serially in 9 patients admitted to the intensive care unit for sepsis and 4 patients with extensive burns. Sepsis and burns elicited a major increase in plasma CRP levels. In both conditions, plasma concentrations of Lp(a) declined abruptly and transiently in parallel with plasma low density lipoprotein cholesterol levels and closely mirrored plasma CRP levels. In 5 survivors, the nadir of plasma Lp(a) levels was 5- to 15-fold lower than levels 16 to 18 months after the study period. No change in plasma levels of apo(a) fragments or urinary apo(a) was noticed during the study period. Turnover studies in mice indicated that clearance of Lp(a) was retarded in lipopolysaccharide-treated animals. Taken together, these data demonstrate that Lp(a) behaves as a negative acute-phase reactant during major inflammatory response. Nongenetic factors have a major, acute, and unexpected impact on Lp(a) metabolism in burns and sepsis. Identification of these factors may provide new tools to lower elevated plasma Lp(a) levels.
Assuntos
Queimaduras/sangue , Lipoproteína(a)/sangue , Sepse/sangue , Adulto , Idoso , Animais , Proteína C-Reativa/metabolismo , LDL-Colesterol/sangue , Feminino , Humanos , Cinética , Masculino , Taxa de Depuração Metabólica , Camundongos , Pessoa de Meia-IdadeRESUMO
BACKGROUND: The liver plays an important role in glucose and lactate metabolism. Major hepatectomy may therefore be suspected to cause alterations of glucose and lactate homeostasis. METHODS: Thirteen subjects were studied: six patients after major hepatectomy and seven healthy subjects who had fasted overnight. Glucose turnover was measured with 6,6(2)H glucose. Lactate metabolism was assessed using two complementary approaches: 13C-glucose synthesis and 13CO2 production from an exogenous 13C-labeled lactate load infused over 15 minutes were measured, then the plasma lactate concentrations observed over 185 minutes after lactate load were fitted using a biexponential model to calculate lactate clearance, endogenous production, and half-lives. RESULTS: Three to five liver segments were excised. Compared to healthy controls, the following results were observed in the patients: 1) normal endogenous glucose production; 2) unchanged 13C-lactate oxidation and transformation into glucose; 3) similar basal plasma lactate concentration, lactate clearance, and lactate endogenous production; 4) decreased plasma lactate half-life 1 and increased half-life 2. CONCLUSIONS: Glucose and lactate metabolism are well maintained in patients after major hepatectomy, demonstrating a large liver functional reserve. Reduction in the size of normal liver parenchyma does not lead to hyperlactatemia. The use of a pharmacokinetic model, however, allows the detection of subtle alterations of lactate metabolism.
Assuntos
Glucose/metabolismo , Hepatectomia , Ácido Láctico/metabolismo , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVES: We designed this study to assess intestinal absorption in patients with adequate or altered hemodynamic status after cardiac surgery and to test clinical tolerance to early enteral nutrition. DESIGN: Prospective, descriptive study. SETTING: Surgical intensive unit in a university teaching hospital. PATIENTS: Cardiac surgery patients, age 64+/-10 yrs (mean +/-SD) were subdivided into two groups according to hemodynamic status: group I, 16 patients with adequate hemodynamic status; group II, 23 patients with hemodynamic failure. These groups were compared with healthy controls (group III, n = 6). INTERVENTIONS: Paracetamol pharmacokinetic study on days 1 and 3 with nasogastric or postpyloric paracetamol administration. Early postpyloric or conventional gastric nutrition in group II. MEASUREMENTS AND MAIN RESULTS: Plasma concentrations were measured on days 1 and 3, and area under the curve (AUC) was calculated. Absorption was strongly reduced on day 1 in all patients after gastric administration (lower peak paracetamol and AUC), but normal after postpyloric delivery. Duration of anesthesia and of circulatory bypass did not affect paracetamol absorption. On day 3, AUC was close to normal in case of hemodynamic failure. Peak absorption on day 1 was negatively correlated with opiate dose (r2 = 0.176, p = .008). Hypocaloric enteral nutrition was well tolerated. CONCLUSIONS: The close-to-normal AUC, during low cardiac output, despite lower peak paracetamol, shows absorption was not suppressed, only delayed, because of decreased pyloric motility. The decrease on day 1 can be attributed to opiates, known to alter pyloric function and to slow down the intestinal transit.
Assuntos
Acetaminofen/farmacocinética , Cardiopatias/cirurgia , Hemodinâmica , Complicações Pós-Operatórias/metabolismo , APACHE , Acetaminofen/sangue , Idoso , Análise de Variância , Índice de Massa Corporal , Baixo Débito Cardíaco/metabolismo , Cuidados Críticos , Nutrição Enteral , Humanos , Absorção Intestinal , Tempo de Internação , Pessoa de Meia-Idade , Respiração ArtificialRESUMO
OBJECTIVE: To compare the effects of isocaloric, isonitrogenous carbohydrate nutrition vs. lipid-based total parenteral nutrition on respiratory gas exchange and intermediary metabolism in critically ill patients. DESIGN: Prospective, clinical trial. SETTING: Surgical intensive care unit in a major university hospital in Switzerland. PATIENTS: Sixteen patients admitted to the surgical intensive care unit. INTERVENTIONS: Patients were randomized to receive isocaloric isonitrogenous total parenteral nutrition (TPN) containing 75% (TPN-glucose) or 15% (TPN-lipid) glucose over a 5-day period. MEASUREMENTS AND MAIN RESULTS: Indirect glucose metabolism was assessed from plasma carbon-13 (13C)-labeled glucose and 13C-labeled CO2 production during a tracer infusion of uniformly 13C-labeled glucose, and de novo lipogenesis was estimated from the incorporation of 13C into palmitate-very low density lipoproteins (VLDL) during a tracer infusion of 1-(13)C acetate. Compared with TPN-lipid, TPN-glucose increased plasma glucose more (by 26% vs. 7%, p < .05), increased insulin more (by 284% vs. 40%, p < .01), and increased total CO2 more (by 15% vs. 0%, p < .01). Both nutrient mixtures failed to inhibit endogenous glucose production and net protein oxidation, suggesting absence of suppression of gluconeogenesis. Fractional de novo lipogenesis was markedly increased by TPN-glucose to 17.4% vs. 3.3% with TPN lipids. CONCLUSIONS: The rate of glucose administration commonly used during TPN of critically ill patients does not suppress endogenous glucose production or net protein loss, but markedly stimulates de novo lipogenesis and CO2 production. Increasing the proportion of fat may be beneficial, provided that lipid emulsion has no adverse effects.