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Biomedical subjects

G Kleinberger

Publications and source records attributed to G Kleinberger.

At least 19 recordsLinked to original sources
PubMed2001

Amino acid kinetics in patients with sepsis.

BACKGROUND: In patients with sepsis and systemic inflammatory response syndrome, amino acid extraction by the liver is enhanced, resulting in decreased plasma amino acid concentrations. Systematic investigations of the elimination of intravenously infused amino acids have not been performed. OBJECTIVE: The objective of this study was to compare the elimination of 17 amino acids in patients with sepsis and in healthy control subjects. DESIGN: Elimination of amino acids was evaluated in 9 patients with sepsis and in 8 healthy control subjects by using a combined loading and maintenance infusion of 375 mg amino acids/kg body wt for 60 min. Pharmacokinetic variables were analyzed from plasma curves. RESULTS: With the exception of lysine, methionine, glutamate, ornithine, phenylalanine, and tyrosine, plasma concentrations of amino acids were lower in the patients with sepsis than in the control subjects; phenylalanine was the only amino acid whose plasma concentration increased (P < 0.001). In patients with sepsis, whole-body clearance (Cl(tot)) of total amino acids was 74% higher than in control subjects (x +/- SEM: 13,161 +/- 1659 and 7566 +/- 91 mL/min, respectively; P < 0.01), the Cl(tot) of essential amino acids was 64% higher (P < 0.02), that of nonessential amino acids was 82% higher (P < 0.01), and that of both branched-chain amino acids and glucogenic amino acids was 97% higher (P < 0.001). With the exception of phenylalanine, ornithine, proline, and glutamate, the Cl(tot) of all amino acids was elevated. The Cl(tot) of phenylalanine and ornithine decreased slightly (NS). CONCLUSIONS: In patients with sepsis, plasma concentrations of most amino acids are greatly decreased and the elimination of amino acids from the intravascular space during intravenous infusion is greatly enhanced.

Adult↗
PubMed1997

Influence of a novel amino acid solution (enriched with the dipeptide glycyl-tyrosine) on plasma amino acid concentration of patients with acute renal failure.

In this randomized, double-blind controlled study we compared the effect of parenteralnutrition with two different amino acid solutions on the plasma concentration of amino acids in 27 patients with acute renal failure. Fourteen patients received the new dipeptide-containing (glycyl-tyrosine) amino acid solution (AADI) in combination with glucose (60%) and fat (10%) as an 'all-in-one' solution over 120 h continuously via a central venous catheter. In the control group (AAST), parenteral nutrition with a standard amino acid solution in isonitrogenous and isocaloric form (0.7 g amino acids/kg BW/day and 25 kcal/kg BW/day) was administered to 13 patients over the same period of time. The administration of the dipeptide-containing amino acid solution caused a return to within the normal range of most of the amino acid concentrations which were decreased at the onset. A significant difference could be found between the AADI and AAST group for the achieved plasma concentrations of threonine (P < 0.01), phenylalanine (P<0.05), isoleucine (P<0.05), tryptophan (P<0.01) and ornithine (P<0.05), The phenylalanine/tyrosine ratio, did not change in the AADI group, while a marked increase was observed in the AAST group. (152.7 +/- 23.5 - 159.8 +/- 37.6 vs 172.6 +/- 24.6 - 310.6 +/- 136.7, respectively). The plasma concentration of glycyl-tyrosine was at the limit of detectability indicating rapid hydrolysis of the dipeptide in acute renal failure. These data suggest that the new dipeptide-containing amino acid solution offers a clear advantage over a standard amino acid formulation in correcting the amino acid imbalances in plasma of patients with ARF and is able to maintain normal tyrosine concentrations and phenylalanine/tyrosine ratio.

Journal Article↗
PubMed1990

Energy metabolism in patients with acute and chronic liver disease.

Energy expenditure and substrate oxidation rate for fat, glucose and protein were evaluated by indirect calorimetry in 20 normal individuals, 35 patients with acute hepatitis and 22 patients with biopsy-proven alcoholic cirrhosis in the postabsorptive state. Measurements were done in the resting state after an overnight fast (10 to 12 hr). Oxygen consumption (ml/min/1.73 m2) in normal subjects, in patients with acute hepatitis and in patients with cirrhosis was 206.5 +/- 4.0 (mean +/- S.E.M.), 216.4 +/- 4.7 and 228.8 +/- 7.1 (p less than 0.05 vs. controls), respectively. When related to body surface area (kcal/min/1.73 m2), resting energy expenditure did not differ between normal subjects (0.98 +/- 0.02), patients with acute hepatitis (1.03 +/- 0.02) and cirrhotic patients (1.06 +/- 0.03). However, when related to 24-hr urinary creatinine excretion as an estimate of lean body mass, energy expenditure was increased in cirrhosis (p less than 0.0001). In cirrhosis an inverse association between the severity of liver disease according to Pugh and oxygen consumption and resting energy expenditure was found. In cirrhotic patients the percentages of total calories derived from fat (86% +/- 5%), carbohydrate (2% +/- 4%) and protein (12% +/- 1%) were different from those of normal controls who metabolized 45% +/- 4%, 38% +/- 4%, 17% +/- 1%, respectively. In acute hepatitis no alterations in metabolism could be found apart from a decreased protein oxidation rate. In conclusion no appreciable changes in energy metabolism exist in acute hepatitis. The pattern of fuel use in cirrhosis resembles that in starvation.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1989

Assessment of oxygen-consumption by use of reverse Fick-principle and indirect calorimetry in critically ill patients.

Oxygen consumption was measured simultaneously by the reverse Fick-principle (V02FICK) and by indirect calorimetry ("Metabolic Measurement Cart Horizon") (V02MMC) in 31 critically ill patients; 24 men and 7 women. Seventeen patients were breathing spontaneously, 14 patients were on mechanical ventilation. The fractional inspiratory oxygen concentration (FI02) in ventilated patients ranged from 0.21 to 0.4 (mean 0.302). Total oxygen consumption as measured by indirect calorimetry was 286.7 +/- 59.7 ml/min (mean +/- SD), and measured by reverse Fick-principle 258.9 +/- 52.2 ml/min (mean +/- SD). The coefficient of correlation between the two methods was r = 0.873. The absolute difference of oxygen consumption between reverse Fick-method and indirect calorimetry was 11.3%. Regression analysis according to Theil revealed a similar regression between spontaneously breathing and mechanically ventilated patients for the studied FI02 values below 0.4. It is concluded that indirect calorimetry is a reliable method for measuring oxygen consumption in spontaneously breathing as well as mechanically ventilated critically ill patients.

Journal Article↗
PubMed1989

Beneficial effect of 8-ornithin vasopressin on renal dysfunction in decompensated cirrhosis.

In nine patients with decompensated alcoholic cirrhosis of the liver and impaired renal function the effect of 8-ornithin vasopressin (ornipressin) on renal function and haemodynamic parameters was studied. Ornipressin was infused at a dose of 6 IU/h over a period of four hours. During ornipressin infusion an improvement of renal function was achieved as indicated by an increase of creatinine clearance (76 (15)%; p less than 0.01), urine volume (108 (29)%; p less than 0.05) and sodium excretion (168 (30)%; p less than 0.05). The hyperdynamic circulation of hepatic failure, as characterised by increased cardiac index and heart rate as well as decreased systemic vascular resistance was reversed to a nearly normal circulatory state during ornipressin infusion. The raised noradrenaline plasma concentration (1.74 (0.31) ng/ml) and plasma renin activity (13.5 (3.9) ng/ml/h) were lowered during ornipressin infusion to 0.87 (0.21) ng/ml and 5.9 (2.1) ng/ml/h, respectively (p less than 0.01). The efficacy of a vasoconstrictor agent in reverting a hyperdynamic state and improving renal function provides evidence for the substantial role of accumulation of vasodilator substances and subsequent activation of sympathetic nervous system and renin-angiotensin-axis in the pathogenesis of renal dysfunction in hepatic failure. Values are expressed as mean (SE).

Female↗
PubMed1988

Influence of fluid replacement on extravascular lung water (EVLW) in patients with diabetic ketoacidosis.

Fluid replacement is a major issue in the treatment of patients with diabetic ketoacidosis. During this therapy, development of pulmonary edema has been reported and attributed to an increase in pulmonary microvascular pressure and a decrease in colloid-osmotic pressure (COP). Because clinically apparent pulmonary edema is associated with an increase in extravascular lung water (EVLW) and impairment of pulmonary gas exchange, we studied the effect of fluid replacement on EVLW, COP, pulmonary hemodynamics and gas exchange parameters in 8 patients with diabetic ketoacidosis (blood glucose greater than 300 mg/dl, pH less than 7.1). EVLW was estimated by the thermal-dye technique. All variables were successively determined upon admission (A), after initial fluid replacement (IFR), when glucose had fallen below 180 mg/dl, after 8 h of intravenous glucose treatment (G), and after 24 h of total parenteral nutrition (TPN). Despite a total net fluid intake of 6.0 +/- 1.61, a significant decrease (p less than 0.001) in COP from 29.6 +/- 5.5 at A to 18.8 +/- 2.2 mmHg after TPE and a significant increase (p less than 0.001) in PCWP from 4 +/- 2 at A to 10 +/- 3 mmHg after TPE, EVLW remained almost unchanged. EVLW was 5.1 +/- 2.8 at A, 5.3 +/- 2.1 after IFR, 4.8 +/- 1.4 after G, and 5.3 +/- 1.7 ml/kg after TPN. However, PaO2 decreased from 137 +/- 17 at A to 87 +/- 10 mmHg after TPE (p less than 0.001), while Qs/Qt increased significantly (p less than 0.05). The alterations in gas exchange may be indicative of pulmonary dysfunction but as they were not associated with accumulation of EVLW, they may as well reflect the compensation of metabolic derangements in diabetic ketoacidosis.

Adult↗
PubMed1987

[Energy metabolism in patients with severe heart failure].

Resting energy expenditure was measured by indirect calorimetry in 11 patients (8 men, 3 women) with severe heart failure. The study was done after an over night fast (10-12 h). 5 patients suffered from idiopathic cardiomyopathy, 5 patients from coronary heart disease and 1 patient from congestive heart failure following from viral myocarditis. The cardiac index was 2.09 +/- 0.5 l/min/m2, the pulmonary capillary wedge pressure 24.6 +/- 8.0 mm Hg. Resting energy expenditure was 1.175 +/- 0.176 kcal/min/1.73 m2. The basal energy expenditure calculated according to Harris and Benedict was 1.008 +/- 0.055 kcal/min/1.73 m2. The difference was statistically significant (p less than 0.05). Respiratory quotient was 0.775 +/- 0.06 as a result of a high oxidation rate for fat (64.8% of total energy expenditure). These results show that after an overnight fast the caloric requirements of patients with severe heart failure are increased. This increased energy expenditure could be an explanation for the malnutrition often found in patients with severe chronic heart failure.

Adult↗
PubMed1987

[Effect of high-dose prednisolone on lung fluid in patients with non-cardiogenic lung edema].

The influence of high-dose prednisolone on extravascular lung water (EVLW) was studied in a randomized trial in patients with noncardiac pulmonary edema. The patients were treated every 6 hours for 48 hours with 2 g of prednisolone-hemisuccinate or placebo. In the prednisolone-group (n = 7) EVLW decreased from 16.4 +/- 6.2 before to 11.8 +/- 5.1 ml/kg after treatment (p less than 0.05). Additionally alveolar-arterial oxygen gradient (AaDO2/FiO2), pulmonary vascular resistance and heart rate decreased, while arterial oxygen tension (PaO2/FiO2) and mean arterial pressure increased (p less than 0.05). In the placebo-group (n = 7) EVLW increased slightly from 17.5 +/- 3.1 before to 19.3 +/- 10.3 ml/kg after treatment. Additionally all other parameters did not change significantly in this group. Although no statistical significant difference was found between the two groups of treatment, a decrease in EVLW was observed in all prednisolone-treated patients, whereas a pronounced increase in EVLW was found in 3 placebo-treated patients. Probably, those patients would have benefited from high-dose prednisolone treatment. High-dose prednisolone reduced EVLW and improved hemodynamics and gas exchange in patients with noncardiac pulmonary edema, whereas placebo did not achieve comparable effects. Therefore, high-dose prednisolone appears beneficial in noncardiac pulmonary edema in respect of EVLW, hemodynamics, and gas exchange.

Adult↗
PubMed1987

Reproducibility of thermal-dye lung water measurements by a lung water computer in critically ill patients.

Reproducibility of thermal-dye extravascular lung water (EVLW) estimation by a lung water computer was studied by performing ten consecutive measurements in 45 critically ill patients. EVLW ranged over a wide spectrum from 187 to 1163 ml (2.4 to 18.6 ml/kg). The mean coefficient of variation of ten consecutive measurements was 13.6%. Spontaneously breathing patients showed significantly (p less than .05) higher coefficients of variation (16.1 +/- 6.8%) than patients on mechanical ventilation (10.8 +/- 4.2%). Other factors affecting reproducibility could not be clearly identified. Because in lung water estimation mean values of consecutive measurements are compared, we defined an EVLW determination as the mean value of three consecutive EVLW measurements. When comparing consecutive EVLW determinations in hemodynamically stable patients, we found in many that consecutive EVLW determinations varied no more than +/- 15%. These differences probably have to be attributed to the reproducibility of EVLW measurements and have to be considered, when changes in thermal-dye lung water measured by a lung water computer are discussed.

Adolescent↗
PubMed1987

Loading and maintenance dose for the determination of amino acid kinetics in plasma.

Intravenous bolus kinetics of amino acids and calculation of the kinetic parameters with an 1-compartment model revealed weak spots. Therefore, a new study design with a loading and maintenance dose and description of the plasma concentration time data with a 2-compartment model was created and studied in 9 healthy volunteers. After an over night fast the amino acid mixture Thomaeamin n 10% was infused with a loading dose of 20 mg AA/kg-1 X min-1 for 5 min and a maintenance dose of 5 mg AA/g-1 X min-1 for 55 min. The postinfusion period lasted 120 min. The PAA was determined with a Biotronic LC 6001 and the kinetic parameters were calculated by a Wang 2200 computer with the TOPFIT program package. The results showed mean values (means +/- SE) of the volume distribution between 4.7 +/- 0.6 till 9.4 +/- 1.8 liters, an elimination rate constant of 1.7 +/- 0.5 till 11.0 +/- 2.0 h-1, a total clearance of 186 +/- 37 till 846 +/- 66 ml X min-1 and transfer or endogenous production rate between 12 +/- 0.8 till 135 +/- 16 mumol kg-1 X h-1. The total transfer amounts to 17.6 mmol kg-1 X d-1 (= 2.2 g AA/kg-1 X d-1). It can be concluded that an optimal study design for the investigation of AA kinetics should increase the PAA levels 2-3 fold above basal during the infusion period.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Pharmacokinetics of ceftazidime and netilmicin in patients with sepsis.

The pharmacokinetics of ceftazidime and netilmicin were evaluated under septicemic conditions. In a longitudinal study, both drugs were administered simultaneously (ceftazidime 2.0 g 20 min constant i.v. infusion and netilmicin 150 mg i.v. bolus injection) every 12 hours to patients who had a positive blood culture and hyperdynamic circulatory functions. Twenty-four hours after the first period of this pharmacokinetic study, identical parameters were evaluated under dipyrone induced normothermic conditions. The mean residence time and the volume of distribution was significantly altered during septicemia compared to normal conditions. With respect to the relative distribution properties ceftazidime tended to be distributed to a greater extent to the tissue compartment, whereas netilmicin showed an opposite behaviour. Beside significant correlations of absolute values, i.e. blood volume vs. volume of distribution, and relative values, i.e. total peripheral resistance vs. extraction rate, all other attempts failed to show any meaningful correlation. Owing to the heterogenous alterations of metabolic and hemodynamic functions and pharmacokinetic parameters, respectively, the data gained from this study do not allow any statistically validated conclusion regarding the pathophysiological mechanisms involved, although these findings are in accordance with animal experiments.

Adolescent↗
PubMed1986

Fructose-induced hyperlactemia in hyperosmolar syndromes.

Severe hyperlactemia of 8.7, 8.6 and 7.9 mmol/l, respectively, developed in three patients with hyperosmolar syndromes (two hypernatremic, 417 and 415 mosmol/kg H2O; one hyperglycemic 437 mosmol/kg H2O) during rehydration treatment with 5% fructose in water (fructose dosage 0.5 g/kg body wt. per hour). After resolution of the electrolyte disturbances, the infusion of fructose at the same dosage increased the plasma lactate concentration in two of the patients to 4.9 and 4.0 mmol/l, indicating near normalization of hepatic lactate utilization. Thus, in addition to peripheral insulin resistance and decreased muscular glucose utilization, the hyperosmolar state is associated with a reduced tolerance to fructose. This is most likely due to an osmolality-dependent impairment of hepatic gluconeogenesis. In rehydration therapy for hyperosmolar syndromes, fructose-containing infusion solutions should no longer be used.

Acidosis↗
PubMed1986

[Parenteral nutrition in liver insufficiency].

In recent years various regimens for parenteral nutrition in liver insufficiency, containing glucose and fat for energy supply and a liver-adapted amino acid mixture for nitrogen supply, have been recommended. The substrates should be delivered in an all-in-one-solution which facilitates metabolic monitoring and decreases the risk of infections. For treatment of hepatic encephalopathy (HE), branched chain amino acids (BCAA) are recommended. The separation of parenteral nutrition from the treatment of HE makes it much easier to adapt the dosage of the BCAA to the clinical symptoms of the patients. In patients with a severe decrease of gluconeogenesis (spontaneous hypoglycemia below 3 mmol/l combined with a hyperlactemia above 7 mmol/l) or a decreased elimination rate of ammonia (production rate of urea nitrogen below 5 g/l combined with hyperammonemia above 100 mumol/l), an exogenous amino acid supply is not indicated.

Amino Acids, Branched-Chain↗
PubMed1986

[The effect of positive end-expiratory pressure (PEEP) on extravascular lung water in intensive care patients].

The use of positive end-expiratory pressure (PEEP) has been highly recommended because of its favourable effects on pulmonary gas exchange and circulation. It was the aim of this study to investigate the influence of PEEP on extravascular lung water (EVLW), which was estimated by the thermal-dye technique. In 12 intensive care patients PEEP was changed every 30 minutes from 0 to 5, 10, 15 and 0 cm H2O, thereby causing a non-significant increase in EVLW of 2, 10, 7 and 1%. Analysis of individual EVLW-dynamics revealed a more than 20% increase in 6 of 7 patients with normal EVLW (5.8 +/- 0.9 ml/kg), whereas this occurred in only one of the five patients with elevated EVLW (10.9 +/- 1.1 ml/kg). Intraindividual regression analysis between EVLW and PaO2/FiO2, AaDO2/FiO2, Qs/Qt, and CO revealed no correlation between these parameters. Therefore, shorttime application of PEEP did not affect EVLW. Patients with normal EVLW were more prone to show increased EVLW during PEEP than patients with elevated EVLW. PEEP-induced improvement of gas exchange and pulmonary shunt were not accompanied by changes in EVLW.

Adult↗