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.

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.

Bedside estimation of extravascular lung water in critically ill patients: comparison of the chest radiograph and the thermal dye technique.

Extravascular lung water (EVLW) was estimated in 53 critically ill patients by the chest radiograph (CXR) and the thermal dye technique. The comparison between these two methods revealed a direct and positive correlation (r = 0.83, p less than 0.001). However, EVLW-values obtained by the thermal dye technique showed considerable overlap between cases of radiographic low grade pulmonary edema and we were able to identify several reasons for radiographic over- or underestimation of EVLW. In these patients EVLW-measurement by the thermal dye technique provides additional information, thereby probably influencing further treatment.

Lipid metabolism in acute renal failure.

Plasma lipid and lipoprotein composition was investigated in acute renal failure (ARF). Forty-seven percent of the patients showed hypertriglyceridemia, whereas serum cholesterol was slightly reduced. Triglyceride (TG) content, predominantly of LDL and to a lesser degree of VLDL, was elevated. Cholesterol concentrations of HDL and LDL fractions were markedly reduced. HDL-TG and VLDL-cholesterol were in the normal range. Forty percent of the patients had a type IV hyperlipoproteinemia. Post-heparin lipolytic activity (PHLA) was reduced owing to an inhibition of hepatic-TG-lipase (HTGL) activity, whereas protamine-inactivated LPL was in the normal range. Fractional elimination (K2) of parenterally administered fat emulsions, determined by an intravenous fat tolerance test (IVFTT) was reduced to 2.44% min, about half of normal. The fat elimination rate increased but did not normalize during parenteral nutrition with amino acids and glucose, suggesting enhanced lipid deposition. Alterations of lipid metabolism develop early in ARF (by 4 days) and, in general, are not influenced by residual renal function, urinary output, or duration of renal failure.

Oral and parenteral nutrition with L-Valine: mode of action.

The intravenous application of the branched chain amino acid L-valine to patients with hepatic coma resulted in a specific drop of tryptophan, serotonin and 5-hydroxyindole acetic acid. Clinical improvement of hepatic encephalopathy and of the underlying neurotransmitter (serotonin) and ammonia derangements by administration of L-valine suggest a possible role of this competitive amino acid on intermediary metabolism and ammonia detoxification.

Human cerebral free amino acids in hepatic coma.

Free amino acids and some related compounds in autopsy specimens of different human brain areas have been determined by column chromatography. Only in patients with hepatic coma could a significant difference in the contents of tyrosine and lysine between caudate nucleus and N. amygdalae be found. In comparison with control subjects the brains of patients with hepatic coma contained significantly higher concentrations of glutamine, isoleucine, histidine and ammonia. In patients with hepatic coma after complete parenteral nutrition plus L-valine administration, dying from other causes, the brain levels of alanine and valine were decreased, while the content of taurine was significantly increased. However, most of the amino acid levels in brain tended toward lower levels. A very significant reduction after treatment with L-valine could be observed in glutamine and ammonia concentration. It is suggested that L-valine has some beneficial action on ammonia detoxification and has also a competing action on amino acid uptake mechanism (specially with the large neutral amino acids).

General properties of 14C-L-Valine-binding to human brain tissue.

L-Valine (VAL) binding is saturable, reversible, linear within a protein concentration of 0.2 to 0.8 mg prot./ml, pH dependent (pH-optimum 7.1 to 7.4), temperature dependent with extremely low binding at 0-4 degrees C; the assay runs at 37 degrees C; it is ion dependent (Bmax:CaCl2 (5mM): + 100%; NaCl (5 mM): -50%); very sensitive to TRITON X-100 (Bmax at 0.01%; -70%); N-ethylmaleimide (0.5 mM): Competitive inhibition; no change in non-specific binding; there are no effects by puromycin plus GTP; VAL binds to synaptic membranes of human frontal cortex with KD-values several fold lower than that observed with homogenates, the distribution of VAL-binding is different in various human brain areas and can be inhibited by L-leucine, L-isoleucine, L-serine, DL-threonine, glycine and D-valine, while aromatic amino acids, beta-alanine, GABA, taurine, glutamate, proline and gamma-glutamyltaurine have no effects of 10(-3) M.

Fat elimination in acute renal failure.

Lipid metabolism and elimination of parenterally administered fat were investigated in 15 patients with acute renal failure (ARF). The mean triglyceride level was elevated to 2.56 +/- 1.43 mmol/l and the mean cholesterol level was 3.32 +/- 0.66 mmol/l, which is slightly below the normal range. A type IV hyperlipoproteinaemia was present in 47 per cent of the patients. The triglyceride content of LDL and VLDL was elevated and the cholesterol concentration of HDL and of LDL was reduced markedly. The fractional removal rate of triglycerides (K2) evaluated by an intravenous fat tolerance test using a bolus technique was reduced to 2.44 +/- 1.56 per cent/min which is about half of normal and correspondingly the elimination half life was prolonged to 28.4 min. No correlation could be demonstrated between the impairment of fat elimination and residual renal function, basal and VLDL triglyceride concentration or HDL cholesterol content.

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.

Lung perforation by nasogastric feeding tubes.

Endotracheal misdirection of narrow bore nasogastric feeding tubes resulted in perforation of the lung, pneumothorax and hydrothorax in two intensive care patients. Both were intubated with cuffed endotracheal low pressure tubes, one patient was on respirator therapy with neuromuscular relaxation. Feeding tubes were inserted by experienced personnel with the assistance of a steel stylet without difficulties. Aspiration of fluid was misinterpreted as proof of correct positioning, the liquid being however pleural effusion and not gastric juice. Similarly auscultation of gurgling sounds in the upper epigastrium was not a reliable sign of intragastric position. Insertion of nasoenteric feeding tubes may be complicated by perforation of the upper gastrointestinal tract and lung in poorly responsive patients with cuffed endotracheal devices during neuromuscular blockage. In these patients a laryngoscope and forceps should be used to ensure free passage of the tube into the oesophagus. Röntgenographic confirmation of correct positioning of the tube immediately after insertion is mandatory.

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.

Post-heparin lipolytic activity in acute renal failure.

Total post-heparin lipolytic activity (PHLA), hepatic triglyceride lipase (HTGL) and protamine inactivated lipoprotein lipase (LPL) and plasma lipoprotein pattern were investigated in 8 patients with acute renal failure (ARF). PHLA was determined at 5, 10, 15, 30, 45 and 60 minutes after heparin administration (100 U/kg b.w.). Maximal PHLA in ARF was 6.12 +/- 1.56 mumol FFA/ml/h at 10 minutes versus 14.62 +/- 4.29 at 45 min in controls (= 42%, p less than 0.001). PHLA was reduced in ARF throughout the study period (p less than 0.001). Maximal HTGL activity (3.06 +/- 0.84 mumol FFA/ml/h) was obtained at 10 min in ARF versus 8.97 +/- 3.11 after 15 min in controls (= 34%, p less than 0.001). HTGL in ARF differed from controls at all points of determination (p less than 0.001). LPL maximum was 3.12 +/- 1.93 mumol FFA/ml/h at 15 min in ARF and 7.65 +/- 3.44 at 45 min in controls (= 40%, p less than 0.001). LPL activity was different from controls at 30, 45 and 60 min (p less than 0.001) but not at 5, 10 and 15 min after heparin injection. Due to a rapid decrease of LPL activity (half maximal activity after 34 min in ARF versus 94 min in controls, p less than 0.05) activity half life of PHLA was diminished in ARF (49 min in ARF versus 112 min in controls, p less than 0.01). Thus both the activity of HTGL and LPL is impaired in ARF. Because of the different activation kinetics of the two PHLA fractions no conclusions concerning maximal enzyme activities can be drawn from single determinations as suggested in previous studies on chronic renal failure.

[Bedside chest x-rays and extravascular lung water determination in intensive care patients]. / Die Thoraxbettaufnahme und extravaskuläre Lungenwasserbestimmung bei Intensivpatienten.

Radiological staging of pulmonary oedema was compared with the determination of extra-vascular lung water by means of a double indicator dilution technique. One hundred and forty-six ward chest radiographs were evaluated and compared with the results of simultaneous measurements of lung water. Seventy-seven cases could be evaluated statistically. Chest x-rays regarded as normal corresponded to extra-vascular lung water of 5 to 9 ml./kg. body weight. Interstitial oedema (radiological stage I and II) corresponded to extravascular lung water levels of 8 to 12 ml./kg. Differentiation of stages I and II was not possible. During stage III, extra-vascular lung water was 15 to 21 ml./kg. A comparative analyses of these findings revealed a discrepancy of 34%. The reasons for this are discussed.

Neuroleptanalgesia in acute myocardial infarction: effects of hemodynamic parameters and plasma catecholamines.

The use of neuroleptanalgesia in acute myocardial infarction offers the possibility of reducing pain and emotional stress. The influence of such treatment on hemodynamic parameters (heart rate, cardiac output, stroke volume, peripheral resistance, systemic blood pressure, and pulmonary pressure) and on the plasma level of adrenaline and noradrenaline has been studied in 6 patients with acute myocardial infarction. This results demonstrate that during neuroleptanalgesia the already elevated levels of noradrenaline and adrenaline further increase. This increase was most pronounced in the patients with the highest initial levels of catecholamines. Since the peripheral resistance and systolic and diastolic blood pressures decrease concomitantly, it is concluded that the increase in levels of noradrenaline and adrenaline further increase. This increase was most pronounced in the plasma catecholamines is due to a reaction of the sympathetic nervous system to the alpha-adrenergic receptor blocking activity of droperidol causing vasodilation. The data indicate that pain, emotional stress, and anxiety in the acute phase of myocardial infarction do not play the expected essential role for the activation of the sympathetic nervous system generally observed in acute myocardial infarction. Additionally, the data demonstrate that drugs producing a vasodilation can have a deteriorating effect on the hemodynamic situation and that a reduction of the afterload by vasodilating drugs can result in a further increase in the release of catecholamines.

[Influence of insulinfree rehydration on diabetic derangements (author's transl)]. / Einfluss der insulinfreien Rehydratation auf die diabetische Stoffwechselentgleisung.

In two groups of pts with diabetic derangements the effect of infusion therapy was investigated with regard to metabolic and endocrine functions. The rate of infusion was adapted to the height of the central venous pressure and the administration of electrolytes to their serum concentration. Insulin was withheld until no further decrease of blood glucose was noted. Group A consisted of 8 pts with severe diabetic ketoacidosis (blood glucose higher than 25 mmol/l, pH below 7.0 and/or bicarbonate below 10 mmol/l). The duration of insulinfree rehydration was 8.8 +/- 1.3 (x +/- SE) hrs and the fluid retention 4060 +/- 3 633 ml. The osmolality in serum decreased from 356 +/- 12 to 340 +/- 8 mosm/kg H2O and the blood glucose from 37.9 +/- 2.9 to 28.6 +/- 3.4 mmol/l. No correlation existed between the decrease of blood glucose and the expansion of the intravascular volume. Therefore, the decrease of blood glucose was not caused by a simple dilution effect. High renal glucose excreation was observed (408 +/- 83 mmol) but could not explain the decrease of blood glucose. The glucose clearance fell from 25.9 +/- 6.9 to 21.5 +/- 3.8 ml/min/1.73 m2 body surface from the first to the last 2-hr periods. It must be concluded that the initial rehydration deminished gluconeogeneses and/or increased tissue glucose utilization without exogenous insulin administration. This conclusion is supported by the decrease in the plasma concentration of the contrainsular hormons. Glucagon decreased 579 +/- 209 to 319 +/- 88 pg/ml (n.s.). Cortisol from 49.9 +/- 4.6 to 35.8 +/- 6.7 micrograms/100 ml (p < 0.05) and Adrenalin from 2.43 +/- 1.03 to 0.4 +/- 0.22 ng/ml (p < 0.05). Blood gas analysis revealed only minimal and ketobodies in serum no changes. Therefore, it can be concluded that rehydration and decrease of plasma concentration of contrainsular hormones do not influence the enhenced lipolyses in diabetic ketoacidosis. Group B consisted of 8 pts with nonacidotic diabetic derangements (blood glucose higher than 25 mmol/l, pH above 7.3 and/or bicarbonate above 18 mmol/l) and an acute weightloss of more than 3 kg. The insulinfree rehydration lasted 13 +/- 1.6 hrs and the fluid retention was 4620 +/- 380 ml. The serum osmolality decreased from 317 +/- 5.3 to 288 +/- 1.9 mmol/l. The decrease of blood glucose could not be explained by delution effect. The renal glucose excreation was 370 +/- 120 mmol/l in total and the glucose clearance decreased from 15.3 +/- 8.4 to 8.0 +/- 2.8 ml/min/1.73 m2 body surface (p < 0.01). Decrease of gluconeogenese and/or increase of glucose assimilation of the tissues can also be expected for the pts with nonacidotic diabetic derangements during plain rehydration.

[Haemodynamic effects of depot zinc protamine glucagon in heart failure (author's transl)]. / Hämodynamische Wirkungen von Depot-Zink-Protamin-Glukagon bei kardialer Dekompensation.

In contrast to intravenously-administered crystallene glucagon, which acts for 20 minutes only, the depot form, zinc protamine glucagon, shows a prolonged haemodynamic action. Fourteen patients with pre-existing heart failure received a single dose of 20 mg Zn protamine glucagon intramuscularly. The stroke volume and cardiac output were increased, whereas the mean and end-diastolic pulmonary pressure were decreased, indicating a positive inotropic action of the administered drug. Heart rate and mean arterial pressure remained almost unchanged. The haemodynamic changes started 60 minutes after intramuscular administration of the drug, reached a maximum effect at 3 hours and started to decrease after the fourth hour. Zn protamine glucagon can, therefore, be considered a beneficial drug in the treatment of digitalis-resistant heart failure on the basis of its long duration of action and easy route of administration.

[Emergency treatment with a temporary balloon-floated pacemaker electrode (author's transl)]. / Notfalltherapie mit der temporären Schrittmacher-Ballonelektrode.

The "blind" insertion of a balloon-tipped pacemaker electrode is a suitable method when emergency pacing at the bedside is needed. The disadvantage of placement of the electrode without fluoroscopic control is counter-balanced by the saving of time and the lesser stress and risk involved for the patient, who is not required to be moved to a fluoroscopic room.

[Severe intoxication with leponex (author's transl)]. / Schwere Leponex-Vergftung und ihre Intensivbehandlung

The clinical picture and the therapeutic management of a severe case of self-poisoning with Leponex (clozapin) are presented. In particular, the grave complications, their possible aetiology and the value of the administration of cortisone are discussed. Forced diuresis or haemodialysis are ineffective measures on account of the low serum concentrations of Leponex.

[Angiotensin - a possible cause of acute renal failure (author's transl)]. / Angiotensin - mögliche Ursache eines akuten Niervenversagens

The hypertensive action of angiotensin is purely brought about by peripheral vasoconstriction and may, thus, lead to reduced perfusion of vital organs, especially the kidneys. The dangers of angiotensin in triggering off acute renal failure are illustrated by a case report in which this drug was administered to a comatose patient with hypovolaemic hypotension following barbiturate self-poisoning.

[Clinical results with dopamine in acute renal failure (author's transl)]. / Erfahrungen mit Dopamin beim akuten Nierenversagen

Dopamine possesses specific pharmacological actions which distinguish it from the other catecholamines. Apart from its positive inotropic effect, dopamine exerts a favourable influence on renal function with an increase in renal blood flow and alterations in intrarenal haemodynamics. The use of dopamine in the early stages of acute oliguric failure is recommended on the basis of the good therapeutic response achieved in a series of cases.