Plasma fibronectin concentration in suspected septicaemia is related to severity of sepsis.

Low plasma fibronectin levels have been reported in patients with septic complications following surgery, major trauma or burn injury. Our purpose was to evaluate fibronectin in suspected septicaemia and its relationship to severity of infection and clinical outcome. In 51 consecutive patients with infection classified as mild (group A), severe (group B) or severe complicated by septic shock, disseminated intravascular coagulation or multiple organ failure (group C), the respective mean initial fibronectin concentrations were 85% +/- 10 (SD), 55% +/- 15 and 44% +/- 13 of the reference mean (0.35 g/l). In statistical analysis the groups differed significantly from each other and from controls. All 11 patients with mild infection had fibronectin values above the lower reference limit, which was 60%, whereas in 15 of 16 group C patients and all seven fatal cases in that group the initial fibronectin values were below 60%. Plasma fibronectin rose with clinical improvement, but remained low in patients with persisting septicaemia. The results confirmed earlier reports of low fibronectin levels in septic states, and indicate that low concentration is of prognostic value and is related to the severity of the disease.

A hemodynamic profile diagram and its application in septic patients.

A physiologic profile is presented in the form of a circular diagram, in which hemodynamic parameters, oxygen uptake and arterial lactate are displayed on 12 radial spokes. Results are presented as per cent of reference values. In the normal state the profile will be evenly circular, while different circulatory disturbances present typical patterns. This is shown in serial measurements on 12 septic patients, who displayed increases in cardiac output, oxygen metabolism, stroke volume, heart rate, pulmonary artery pressure, right atrial pressure, pulmonary capillary wedge pressure and arterial lactate, while pulmonary and systemic vascular resistances were decreased. Stepwise multiple regression analysis indicated that systemic vascular resistance was the best early discriminator between survivors and non-survivors. The hemodynamogram offers a compact and easily understood presentation of data, which makes it possible to follow the course of the disease and provides a diagnostic and didactic tool.

Metabolic effects of amino acid solutions in severely burned patients: with emphasis on sulfur amino acid metabolism and protein breakdown.

The metabolic effects of TPN containing high amounts of amino acids (18 gm N) was evaluated with respect to sulfur amino acid metabolism and protein breakdown in nine severely burned patients. The results were compared to corresponding data from burned patients receiving more moderate amounts of amino acids (9.2 gm N) or isocaloric amounts of carbohydrate and fat. Significantly increased urinary excretion and intracellular muscle tissue concentrations of methionine were found in patients receiving the concentrated amino acid solution, probably reflecting a combined effect of the injury and an increased load of the compound. These patients also showed a reduced oxidation of sulfur amino acids to inorganic sulfate, which may reflect an increased protein synthesis during treatment. A significantly decreased urinary excretion of 3-methyl-histidine and mercaptolactate was found in patients receiving the concentrated amino acid solution, probably reflecting a decreased breakdown of body protein. The findings favor the hypothesis of an anabolic effect of the new amino acid solution in burned patients during the early catabolic phase, but also emphasize the importance of monitoring the amounts of amino acids, e.g., methionine, given.

Changes in nutritional assessment variables caused by total parenteral nutrition in anorexia nervosa.

Nutritional assessment variables were measured weekly in 10 young women with severe anorexia nervosa during treatment with total parenteral nutrition (TPN) for a 5 week period. Before the start of treatment the patients had lost 25-53% of their habitual weight, triceps skin fold (TSF) and arm muscle circumference (AMC) measurements were below the 5th percentile and all were anergic in the delayed hypersensitivity (DH) response. Plasma protein levels were normal except in fibronectin and prealbumin where levels below the reference interval was found in five patients. During TPN the body weight increased most likely due to rehydration and increase in lean body mass. Significant increases were seen in body weight weekly, but in TSF and AMC only after 4 and 3 weeks respectively. TSF and AMC were still below or at the 5th percentile after 5 weeks of TPN. DH response as well as fibronectin and prealbumin levels normalised in all patients. Despite only partial recovery in body cell mass the clinical picture had changed markedly so that the patients now were amenable to psychotherapy and had an adequate intake of food orally, enabling further nutritional therapy to be completed without parenteral support.

Severe anorexia nervosa treated with total parenteral nutrition. Clinical course and influence on clinical chemical analyses.

Severe anorexia nervosa in which psychiatric treatment has failed is a life-threatening condition since the degree of emaciation can be profound. Nine young women with a weight loss of 25-50% of their habitual weights were given total parenteral nutrition (TPN) over 3-8 weeks through a tunneled central venous silicone catheter. They initially received a mean of 55 kcal/kg body weight/24 hours increasing to 65-70 kcal/kg body weight during the first week. The initial bradycardia and hypotension were normalized and body weight increased with a mean of 2.5 kg/week. All patients showed a general somato-psychic improvement after two weeks of TPN. The electrolyte disturbances seen at the beginning were normalized during the first weeks of treatment and the previously reported life-threatening electrolyte disturbances and dehydration in connection with TPN treatment were not seen. The only adverse effect registered was a rise in liver enzymes in two patients who were given greater than 80 kcal/kg and day. With a reduction of the caloric supply these changes normalized, and TPN could be continued. After 3-8 weeks the oral intake had normalized and TPN was discontinued. This study confirms that TPN can be used successfully and with minimal risk in severe anorexia nervosa until the patients have normalized their oral intake.

Kinetics of morphine in cerebrospinal fluid after epidural administration.

Forty patients undergoing arthroscopy were given an epidural dose of 0.05 mg morphine-HCl in 0.1 ml saline/kg body weight to study the disposition of morphine in the cerebrospinal fluid (CSF). In each patient one to three CSF samples were collected (86 samples in total). A mean peak concentration of 13 890 nmol/l was achieved 75 min after morphine administration. The compiled data show an elimination half-life of 162 min (r = 0.98). Individual half-lives in seven patients with three samples ranged from 61-172 min. Large interindividual variations were found in CSF-concentrations of morphine, 9- and 8-fold at 3 and 8 h, respectively, after the dose. However, 16 h after administration no patient had a concentration less than 81 nmol/l. At 8 h after the dose, CSF concentrations of morphine were significantly higher (P less than 0.05) in a group of patients (n = 5) kept uptilted (80 degrees), as compared to those in the supine position (n = 5). Such a difference was not observed 3 h after the dose. The sampling procedure and age also seemed to influence CSF concentrations of morphine. There was no correlation between the dose given in mg and the CSF concentrations achieved. Strict standardization is thus mandatory when studying the disposition of opiates in CSF after epidural or intrathecal administration. Since our calculated half-lives of morphine in CSF were similar to those reported in plasma, the long-lasting effect is probably related to the high initial morphine concentrations in CSF.

Influence of total parenteral nutrition on plasma fibronectin in malnourished subjects with or without inflammatory response.

Plasma fibronectin, which is an alpha 2-glycoprotein of importance for the immunodefence, has been reported to decrease after starvation and in severely ill patients with cancer. To evaluate the usefulness of fibronectin as an indicator of nutritional repletion, 18 patients with gastrointestinal disorders were studied over a 2-wk period of total parenteral nutrition (TPN). According to nutritional assessment on admission the patients were divided into well nourished (n = 6) and malnourished (n = 12). For comparison nine patients with anorexia nervosa were also studied over a 3-wk period of TPN. Before and after TPN fibronectin, albumin, prealbumin, transferrin, and two acute-phase reactants, haptoglobin and orosomucoid were measured in plasma. The majority of the malnourished patients had an inflammatory reaction in contrast to only a few of the well-nourished and anorexia nervosa patients. Of the proteins measured, only fibronectin rose significantly in the malnourished patients (malnourished and anorexia nervosa), but not in the well nourished patients during TPN. Our results may indicate the usefulness of fibronectin as an indicator of short-term TPN in malnourished subjects, irrespective of the presence or absence of inflammatory response.

Muscle and plasma carnitine levels and urinary carnitine excretion in multiply injured patients on total parenteral nutrition.

Carnitine is necessary for the transport of long-chain fatty acids across the mitochondrial membrane. Thirteen severely injured patients on total parenteral nutrition were studied during days 2-8 post injury. Initially plasma and skeletal muscle carnitine values were within the range earlier found for normal subjects, whereas the urinary carnitine excretion was markedly increased. On day 4 there was a simultaneous decrease in the carnitine concentration in plasma (alpha < 0.01) and urine (alpha < 0.05) as well as in skeletal muscle tissue (alpha < 0.05 using only the values that could be paired i.e. from eight subjects), whereas no difference was found between day 2 and 8. One explanation of this pattern might be that a redistribution of carnitine occurs to other organs not measured, for example the liver. In skeletal muscle tissue, statistically significant positive correlations were found between the carnitine level and ATP (alpha < 0.01) and phosphocreatine (alpha < 0.02) as well as between carnitine and glycogen (alpha < 0.05).

Effects of the extradural administration of morphine, or bupivacaine, on the endocrine response to upper abdominal surgery.

The endocrine response, and the relief of pain, following the extradural administration of morphine or a local anaesthetic agent bupivacaine (0.5%) were studied for 24h after abdominal surgery and compared with a control group given conventional i.v. morphine after operation. Samples were taken before and at 2, 4, 6, 12 and 24 h after skin incision. Pain relief in both extradural groups was significantly better when compared with the control group. In all three groups, the plasma concentration of cortisol was increased immediately after surgery. Thereafter, significantly lower values were seen in the extradural groups. Plasma adrenaline concentration was lower immediately after surgery only in the group given the extradural local anaesthetic. Plasma noradrenaline concentration remained unchanged after extradural local anaesthesia while an intermediate increase occurred after extradural morphine. Plasma noradrenaline concentration was significantly greater in the controls compared with both extradural groups. Our results indicate that extradural analgesia with a local anaesthetic drug can suppress the increases in the plasma concentrations of the catecholamines and cortisol after surgery. In contrast to extradural local anaesthetic extradural morphine cannot suppress the endocrine response immediately after surgery. However, later in the postoperative period, extradural morphine can suppress the endocrine response, thus indicating that postoperative pain is a factor involved in the stress response following surgery.

Low plasma fibronectin indicates septicaemia in major burns.

Plasma fibronectin was measured by laser nephelometry in 23 patients with 20--85% burns. Control measurements were made in 118 healthy blood donors aged 18--60 years. The reference level was significantly higher in the 72 males (mean +/- SD = 377 +/- 70 mg/l) than in the 46 females (327 +/- 55 mg/l). In the burn-injured patients the mean fibronectin concentration was significantly lower than the reference values for one week after the injury. All the patients had low concentrations, about 70% of their respective reference means, in the first 24 hours after the injury. When burn treatment was successful, the fibronectin thereafter increased, gradually exceeding the reference level. Patients with septic complications, by contrast, showed further reduction of fibronectin levels. In the patients who died, the fibronectin concentration 6--10 days after burn injury was significantly less than in the patients who survived. On the basis of these results, repeated analysis of plasma fibronectin in the early postburn period is recommended. Persistent fibronectin deficiency then is an indicator of imminent septicaemia, vital organ failure and risk of fatal outcome.

The effect of severe trauma on muscle energy metabolism in man.

Muscle energy metabolism after severe trauma was studied in four nutritionally isocaloric groups of patients, receiving different amounts of glucose, fat and nitrogen. Muscle biopsy was performed 2, 4, 8 and 30 days after trauma. The pattern of energy metabolites was similar in all groups. Adenosine triphosphate was decreased on day 8, with further fall on day 30. Phosphoryl-creatine was reduced from day 2 onwards. Concomitant creatine increase gave a constant total creatine pool up to day 8 post-trauma. Lactate was increased and glycogen moderately decreased. The single exception to the pattern was greater increment of lactate and maintenance of glycogen levels in the specimens from groups with high glucose intake. The reduction in high-energy phosphates could have resulted from impaired substrate utilization or rapid degradation of tissue energy stores. The glucose and the lipid system were equally effective in supporting the cellular energy status after severe trauma.

Thyroid hormones, catecholamine and cortisol concentrations after upper abdominal surgery.

Serum and plasma concentrations of thyroid hormones, catecholamines and cortisol as well as oxygen consumption were measured simultaneously in twenty patients in connection with cholecystectomy. Arterial blood samples were taken before surgery and at 2, 24, 48, 72 and 96 h after skin incision. A marked and prolonged decrease in T3 and free T3 concentrations was seen. A minor decrease in T4 was also observed but free T4 remained unchanged. TSH concentration was increased 2 h after skin incision, but at no other occasion. A marked increase in adrenaline and noradrenaline concentrations was observed 2 h after the start of surgery. This increase lasted 24 h for noradrenaline. There was a marked and prolonged rise in plasma cortisol after surgery. The oxygen uptake was higher than the preoperative value during the entire postoperative period. No correlations between thyroid hormones and catecholamines or cortisol or oxygen uptake were found. It is concluded that the most pronounced changes in thyroid hormones and TSH after upper abdominal surgery occur about 24 h postoperatively but catecholamines demonstrate their maximal increase immediately after surgery. The inverse correlation between T3 and catecholamines previously reported in burned patients, with their severe hypermetabolism, it is not present during the moderate hypermetabolism after abdominal surgery.

Nutritional assessment reflects muscle energy metabolism in gastric carcinoma.

Preoperative nutritional status and muscle energy metabolism were studied in 26 patients with gastric carcinoma. Fat stores were reduced in 30% and visceral proteins in 25% to 90% of the patients. According to the nutritional assessment, the patients were divided into well-nourished (group I, n = 8) with no or minor signs of malnutrition and malnourished (group II, n = 13) with signs of pronounced malnutrition. Group I had normal content of muscle energy metabolites despite their malignant disease. In group II, adenine nucleotides (p less than 0.001), phosphorylcreatine (p less than 0.01), creatine (p less than 0.05) and also glycogen (p less than 0.01) were markedly decreased. Weight loss, albumin, and fibronectin levels correlated significantly with adenosine-triphosphate, total adenine nucleotides, and glycogen levels. The most malnourished patients also had the poorest energy metabolite status in the muscle. These findings revive the interest in nutritional assessment.

Metabolic changes in a case of malignant hyperthermia.

A patient with fulminant MH is presented. The metabolic changes in muscle tissue, whole blood and plasma are compared with those obtained from the porcine model. The samples were taken 1 h after treatment (including dantrolene sodium) had been commenced. Increased concentrations of lactate, pyruvate and citrate were found in muscle, whereas the concentrations of potassium, free inorganic phosphate and glycogen were reduced. The ATP, ADP and phosphoryl creatine concentrations remained unchanged. In blood, increased concentrations of alanine, lactate and glycerol were observed. An increase in carbon dioxide production was found. These changes are similar to those found in the porcine model.

Urinary excretion of carnitine in multiply injured patients on different regimens of total parenteral nutrition.

Carnitine derives from intake of preformed exogenous carnitine and synthesis from lysine and methionine, but is absent in parenteral fluids. Urinary excretions of carnitine and its derivatives was measured in 30 patients 2-8 days after severe multiple injuries and compared with controls. The patients received five different isocaloric parenteral nutritional regimens;group 1 glucose and fat, group 2 glucose, fat and amino acids, group 3 glucose and insulin, group 4 glucose and amino acids, and group 5 branched-chain amino acids. The mean total carnitine excretion in healthy men was 420 mumol/24 h +/- 57 (SEM), and in women 266 mumol/24 h +/- 29, 41% of which was free carnitine. Mean excretion of total carnitine during days 2-8 after trauma for the five groups was: 900 +/- 100, 1169 +/- 112, 1251 +/- 102, 1023 +/- 117, and 668 +/- 128 mumol/24 h, being significantly higher in groups 1-4 than in healthy men. The free carnitine fraction in the patients was significantly higher than in controlled healthy subjects. Total carnitine excretion was unaffected by different nutritional regimens in the very first days. During days 6-8, group 5, receiving branched-chain amino acids had lower excretion of total carnitine (compared to groups 2-4) and free carnitine (compared to groups 3-4). Groups 3 and 4 excreted a higher percentage as free carnitine compared to the other groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Metabolic effects of four intravenous nutritional regimens in patients undergoing elective surgery II.--Muscle amino acids and energy-rich phosphates.

Muscle amino acids and energy-rich phosphates have been determined in 28 patients before and after resection of a carcinoma of colon or rectum. Before operation the patients received a synthetic diet (Vivasorb for four days and postoperatively four different intravenous regimens with different amounts and proportions of amino acids were given for six days, the energy intake being the same for all groups. When compared with age-matched healthy controls the patients showed only slight increases in phenylalanine and isoleucine concentration in muscle and plasma with elevated plasma glutamate during the four days prior to the operation. Vivasorb treatment increased the concentration of alanine, glycine and methionine in both muscle and plasma while increases of threonine and histidine were seen only in muscle. Decreased concentrations of valine were found in muscle and plasma, while lysine and leucine decreased only in plasma. As an effect of operation, but independent of the nutritional regimen, muscle asparagine increased and muscle glutamine and glutamate decreased in all groups. The unique pattern of amino acid changes in postoperative trauma was confirmed in the present investigation but few differences in amino acid concentrations could be related to the various nutritional intakes. Alterations in the individual amino acid concentrations were not influenced by the intake of amino acids and seemed to have little relationship to the composition of any solution infused. Prior to operation there were low levels of ATP in muscle possibly due to immobilisation and chronic semistarvation but no changes in the energy rich phosphates could be attributed to trauma or nutrition. The content of muscle glycogen increased as a result of the Vivasorb supply indicating that the preoperative carbohydrate administration promotes muscle glycogen synthesis and postoperatively muscle glycogen was reduced significantly indicating enhanced glycogenolysis in the postoperative state. This finding emphasizes the importance of providing the patients with ample amount of glucose before and after surgery.

Delayed hypersensitivity. A critical evaluation of five recall antigens in a large reference population.

The reactivity to five recall antigens, candida, mumps, PPD, varidase and trichophyton and the corresponding diluents was tested in 840 healthy persons aged between 17 and 101 years. Candida antigen was tested in a lower (l) and a higher (h) dose. The size of reactions did not follow a Gaussian distribution and we therefore used the 10th and 5th percentiles instead of standard deviation to define the limits between positive, weak and negative reactions. The number of positive reactions to each of candida-h, mumps, PPD and varidase was between 80 and 95 per cent in patients less than 60 years of age and above this age it varied between 0 and 85 per cent. The number of positive reactions to candida-l and trichophytin was low in all ages. The reactivity was regarded as normal if there was a positive reaction i.e.sum of right angle diameters >10 mm to atl east one antigen, relatively anergic if there was only a weak reaction (7-9 mm) and anergic if there was a negative reaction (0-6 mm) to all antigens. A normal reaction was found in 100 per cent of subjects up to 60 years of age, and in 95 per cent up to 30 years. Among those with normal reactivity, positive results were found with candida-h alone in between 67-93 per cent, candida-h + mumps between 92-100 per cent and candida + mumps + PPD in 100 per cent irrespective of age.

Metabolic effects of four intravenous nutritional regimens after elective surgery. I. Clinical data and biochemistry.

Biochemical variables have been determined in 28 patients before and after resection of carcinoma of colon or rectum. A synthetic oral diet was given for four days before operation, (0.1 gN.kg/day and 165 kJ.kg/day) and four isocaloric intravenous regimens with different amounts and proportions of amino acids were given for six days after operation. During the preoperative diet the serum urea, glucose, urate, inorganic phosphate and cholesterol concentration decreased while those of triglyceride, iron and alanine amino-transferase increased. After operation the serum triglyceride, protein, albumin, iron, TIBC and urate concentrations decreased. The serum calcium fell in all groups receiving amino acids after operation while magnesium increased in all groups except the one receiving the highest amount of amino acids. The urea concentration decreased when no amino acids were given but increased when amino acids were administered whereas the reverse situation occurred with cholesterol. The highest increase in glucose level was observed when the highest amount of amino acids were given.

Nutritional assessment and clinical course in 112 elective surgical patients.

Recent Swedish reference values in anthropometry and delayed hypersensitivity (DH) were applied in the nutritional assessment of 112 surgical patients. The presence of three or more subnormal variables indicating malnutrition was found in 28% of all patients, and in 52% of those with malignant disease. The anthropometric variables revealed deficits in fat stores and muscle in 26 and 6%, respectively. Plasma protein determinations indicated malnutrition in 6-49%. DH skin testing revealed a subnormal response in 17% of the patients. Ten of the 79 operated patients had postoperative complications. Malnutrition was found preoperatively in six of these. The malnourished patients had a 5.5 times higher complication rate compared to the well-nourished (p less than 0.01). Subnormal values in albumin, prealbumin or DH were associated with a statistically significantly increased complication rate. Regression analysis showed correlations between the anthropometric measurements and plasma protein levels. Furthermore, DH correlated with triceps skin fold, albumin, prealbumin and cholinesterase.