Influence of pre- and intra- operative factors on the occurrence of postoperative fatigue

Subjective feeling of fatigue was assessed before and 10, 20 and 30 days after uncomplicated abdominal surgery in 52 patients and after minor otological surgery in 15 patients. In major surgery fatigue increased from 3.0 +/- 0.2 (mean +/- s.e.m.) arbitrary units pre-operatively to 6.1 +/- 0.3, 5.3 +/- 0.3 and 4.1 +/- 0.3 on day 10, 20 and 30, respectively (P less than 0.001). In contrast, after minor surgery fatigue did not change from before surgery (2.1 +/- 0.3) to day 7 (2.9 +/- 0.5) (P greater than 0.05), day 20 (2.3 +/- 0.4) (P greater than 0.4), or day 30 after surgery (2.1 +/- 0.3) (P greater than 0.9). Differences in fatigue between groups were significant postoperatively (P less than 0.001), but not preoperatively (P greater than 0.05). Mean duration of surgery was similar in the two groups. In the abdominal group an increase in postoperative fatigue did not correlate with age, sex, pre-operative degree of fatigue, actual body weight, triceps skinfold thickness (TSF), arm muscle circumference (AMC), anthropometric index (body weight X TSF X AMC) or serum-transferrin, but did slightly with pre-operative body weight related to ideal body weight (r = -0.3, P less than 0.05). Thus, the magnitude of the trauma and not the duration of anaesthesia may be important for occurrence of postoperative fatigue. Furthermore, fatigue after elective abdominal surgery seems to be unpredictable from the pre-operative status of the patient.     

Skeletal muscle fiber composition, nutritional status and subjective fatigue during surgical convalescence

Samples from the lateral vastus femoris muscle were obtained by needle biopsy from 12 patients before and 20 days after elective abdominal surgery. The content of fast and slow twitch muscle fibers and their lesser diameter were determined and related to subjective degree of fatigue and changes in nutritional parameters. Fatigue increased from a mean preoperative level of 2.2 +/- 0.4 arbitrary units to 4.3 +/- 0.5 (p less than 0.001) on postoperative day 20. Body weight, triceps skin fold and slow twitch fiber diameter decreased postoperatively (p less than 0.05). There was no significant postoperative change in the distribution of muscle fiber types. Fatigue increase correlated to weight loss and reduction of triceps skin fold (r = 0.50 and 0.54, p = 0.08 and 0.06, respectively). Postoperative changes in slow and fast twitch fiber diameter correlated to loss of body weight (r = 0.60 and 0.74, p less than 0.05 and less than 0.01, respectively), but correlation was not found between postoperative fatigue and changes in fiber-type distribution (r = 0.34 and 0.29).     

Long-term changes in muscle free amino acid levels after elective abdominal surgery.

Characteristic changes in the pattern of muscle free amino acids are seen on the third day after elective surgery. The time course of the restoration to normal levels in uncomplicated cases has not been established before. Seven metabolically healthy patients undergoing cholecystectomy were studied. Muscle biopsy specimens and plasma samples were taken before operation and on days 3, 10, 20 and 30 after surgery. The level of total free amino acids in skeletal muscle decreased and the concentrations of branched chain and aromatic amino acids increased on day 3. The original levels were found to be restored on day 10 after surgery. A decrease in glutamine of 38 per cent (P less than 0.001) was seen on day 3, of 20 per cent (P less than 0.05) on day 10 and of 22 per cent (P less than 0.05) on day 30, compared with preoperative values. These results constitute a baseline for future studies in which the impact of nutritional and pharmacological therapies is to be evaluated beyond the immediate postoperative period.     

Elective laparoscopic cholecystectomy nearly abolishes the postoperative hepatic catabolic stress response.

OBJECTIVE: Surgery results in a catabolic state of postoperative stress, where the efficiency of the liver to convert amino acids to urea is increased. This study measured the metabolic consequences of the less traumatic laparoscopic surgery in elective cholecystectomy compared with traditional open surgery technique. SUMMARY BACKGROUND DATA: The authors previously have shown that open cholecystectomy doubles the urea synthesis measured by the means of the functional hepatic nitrogen clearance. Glucagon and cortisol increased by 50% (p < 0.05) and 75% (p < 0.05), respectively, after open cholecystectomy. METHODS: Patients undergoing uncomplicated elective laparoscopic cholecystectomies were included. Preoperatively and on the first postoperative day, blood and urine samples were drawn every hour under basal conditions and during amino acid infusion. The urea synthesis rate was calculated from the urea excreted in urine and accumulated in total body water. Functional hepatic nitrogen clearance was quantified as the slope of the linear relation between blood amino-N concentration and the urea synthesis rate. The results were compared with an historic matched group of patients who underwent open cholecystectomies and were studied by the same protocol. RESULTS: The laparoscopic cholecystectomy increased the functional hepatic nitrogen clearance by only 25% (from 8.7 +/- 0.9 to 11.1 +/- 1.5 mL/sec [mean +/- SEM; p < 0.05]), compared with a doubling after open cholecystectomy (from 9.4 +/- 0.9 to 17.6 +/- 3.3 mL/sec [p < 0.05]). The difference between the groups was significant (p < 0.05). Neither glucagon nor cortisol increased significantly after laparoscopic cholecystectomy. CONCLUSIONS: The laparoscopic technique results in a much smaller postoperative hepatic catabolic stress response and probably reduced tissue loss of amino-N. This may be important for the more rapid convalescence and reduced postoperative fatigue.     

Postoperative fatigue and changes in nutritional status

Subjective feeling of fatigue was quantified before and 10, 20 and 30 days after elective uncomplicated abdominal surgery in 36 otherwise healthy patients, using a constructed fatigue scale model. One third of the patients had a remarkable increase in fatigue which continued throughout the first postoperative month. The fatigued patients showed a more pronounced postoperative loss in weight (P less than 0.001), triceps skinfold caliper (P less than 0.001) and arm muscle circumference (n.s.) and had lower levels in serum transferrin (P less than 0.02). No correlation was found between postoperative fatigue and postoperative changes in blood haemoglobin, lymphocyte count, plasma albumin, electrolytes and various minerals. Development of late postoperative fatigue was unpredictable from pre-operative nutritional status, serum transferrin, albumin, electrolytes, haemoglobin, lymphocyte count and various minerals, as well as from age, sex and duration of surgery. These results suggest future therapeutic measures against the postoperative fatigue syndrome.     

Minor role of ketone bodies in energy metabolism by skeletal muscle tissue during the postoperative course.

To evaluate changes of peripheral ketone body (KB) metabolism after operation, muscle metabolism in postsurgical patients was studied at 3 hours (SI) and 24 hours (SII) after surgery by the forearm catheter technique. Data were compared to those of equivalent fasted controls (CI, CII). In a manner consistent with enhanced mobilization of endogenous substrate stores, arterial concentrations of free fatty acids (FFA), 3-hydroxybutyrate (3-HOB), and acetoacetate (AcAc) were markedly elevated immediately after surgery. This increase was accompanied by a rise in muscular utilization of AcAc (SI: 0.21 +/- 0.05 mumol/100 g/min; CI: 0.08 +/- 0.05, p less than 0.05) and 3-HOB (SI: 0.24 +/- 0.06 mumol/100 g/min; CI: 0.11 +/- 0.01, p less than 0.05). Surprisingly, on the first postoperative day, concentrations of AcAc and 3-HOB fell below those of fasting controls. Concomitantly, the utilization rate of AcAc by muscle (SII: 0.07 +/- 0.03 mumol/100 g/min; CII: 0.27 +/- 0.04, p less than 0.05) was significantly lower in patients than in controls. Reduction of the fractional extraction rate of AcAc (SI: 38.4 +/- 3.8%; SII: 24.0 +/- 6.1%, p less than 0.05), as well as a net production of 3-HOB by muscle (SII: -0.08 +/- 0.05 mumol/100 g/min; CII: 0.49 +/- 0.13, p less than 0.05) 24 hours after surgery indicated a reduced peripheral capacity for KB removal. Since this finding was related to a significantly higher rate of muscular glycerol production (SII: -0.13 +/- 0.03 mumol/100 g/min; CII: -0.06 +/- 0.02, p less than 0.05), one may suggest that increased intramuscular availability of FFA from triglyceride hydrolysis was responsible for the impairment of peripheral KB utilization. These results indicate that KBs contribute little to energy metabolism in skeletal muscle tissue in the late postoperative phase.     

Skeletal muscle enzyme activities and metabolic substrates during exercise in patients with postoperative fatigue

Subjective fatigue was quantified before and 20 days after uncomplicated elective abdominal surgery in 12 patients and compared with changes in heart rate, enzyme activities and skeletal muscle substrates before and after bicycle exercise for 10 min at 65 per cent of patients' preoperative maximum work capacity. Fatigue increased from a mean(s.e.m.) preoperative level of 2.5(0.5) arbitrary units to 4.6(0.5) on postoperative day 20 (P less than 0.01). Body-weight, triceps skinfold thickness and arm circumference decreased postoperatively (P less than 0.02). Postoperative values of muscle enzyme activities indicative of oxidative phosphorylation capacity (citrate synthase and 3-OH-acyl coenzyme A dehydrogenase) were lower than preoperative values (P less than 0.05). Lactate dehydrogenase was unaltered and resting values of muscle glycogen and adenosine triphosphate were higher after operation (P less than 0.05). In response to exercise, heart rate, muscle glucose, glucose-6-phosphate and lactate increased (P less than 0.05), while muscle glycogen and creatine phosphate decreased (P less than 0.05). Increase in postoperative fatigue correlated with the increase in heart rate (P less than 0.05), while no significant correlations were found between fatigue and muscle parameters. Our results suggest that lack of exercise and malnutrition may be of importance in the decrease in work capacity and in fatigue after operation.     

Glutamine-containing dipeptides as infusion substrates in the septic state

Recently a relationship has been postulated between lowered intracellular glutamine concentrations in the skeletal muscle and the rate of protein synthesis. We investigated the effect of 48 hours of parenteral nutrition supplemented with a solution containing glutamine in free or dipeptide form (alanylglutamine or glycylglutamine) on the intracellular glutamine pool in skeletal muscle and on the hind limb exchange of glutamine in dogs with sepsis after surgery. Before surgery, dogs were fasted for 48 hours. We used glutamine dipeptides as sources because they remain stable in an aqueous solution. Nutrition solutions were isocaloric (17.8 kcal/kg body weight/day on day 1 and 35.6 kcal/kg on day 2) and isonitrogenous (0.33 gm nitrogen/kg body weight/day), providing 2.6 mmol/kg body weight/day as glutamine source. During starvation, muscular free glutamine levels decreased by 41% to 10.4 mmol/L (p less than 0.001). On the second postoperative day the dogs had lowered plasma protein levels, a sharp drop in platelet count, an increase in the leukocyte count, and positive blood cultures. None of the solutions investigated in this study was effective in repleting the glutamine pool during 2 days of postoperative nutrition (11 +/- 2.0 mmol/L without glutamine, 10.3 +/- 2.2 mmol/L with glutamine plus alanine, 9.9 +/- 1.6 mmol/L with alanylglutamine, 7.5 +/- 1.1 mmol/L with glutamine plus glycine, and 7.2 +/- 1.2 mmol/L with glycylglutamine, respectively). The release of glutamine from the hindquarter was 631 +/- 38 nmol/kg body weight/min in the control group and decreased significantly in dogs receiving alanylglutamine (13.5 +/- 45 nmol/kg body weight/min; p less than 0.001) or the constituent amino acids (265 +/- 66 nmol/kg body weight/min; p less than 0.01) but was unchanged in dogs receiving glycylglutamine or glutamine plus glycine. We conclude that the duration and dosage of glutamine administration (equivalent to 26 gm glutamine per day in a patient weighing 70 kg) used in this study are not sufficient to restore glutamine deficiency of the skeletal muscle in the depleted state.     

Electrical activity and arm muscle force in postoperative fatigue

Muscle force of elbow flexors and quantitative electromyographic analyses were assessed before and 10 and 20 days after uncomplicated elective abdominal surgery in 20 patients. The findings were compared with subjective fatigue. Fatigue increased significantly from a mean preoperative level of 3.4 +/- 0.4 arbitrary units to 7.0 +/- 0.5 and 6.1 +/- 0.5 on postoperative days 10 and 20. Muscle force decreased by about 10% postoperatively. The duration of sustained contraction (endurance) at a force adjusted to 30% of maximum fell from 426 +/- 64 sec preoperatively to 301 +/- 22 sec 20 days after surgery (all differences significant). Postoperative increase in fatigue correlated significantly to decrease in maximum force (r = 0.45) and to decrease in endurance (r = 0.5). The electromyographic findings at a force of 2 kg and at 30% of maximum suggested activation of fewer motor units during short contraction in the early postoperative period. During sustained contraction there was more pronounced increase in mean amplitude 20 days postoperatively than before surgery. This may suggest that the decreased muscle performance in the late postoperative period was secondary to muscle fatigue.     

Addition of glutamine to total parenteral nutrition after elective abdominal surgery spares free glutamine in muscle, counteracts the fall in muscle protein synthesis, and improves nitrogen balance.

Twenty-two patients undergoing elective abdominal surgery were given total parenteral nutrition (TPN) after the operation. The TPN contained either a conventional amino acid solution supplemented with glutamine or a conventional amino acid solution without supplementation. To study amino acid and protein metabolism, muscle biopsy specimens were taken before surgery and on the third postoperative day. The postoperative decrease in the intracellular concentration of free glutamine was less pronounced in the glutamine group (21.8 +/- 5.5%) than in the control group (38.7 +/- 5.1%; p less than 0.05). The protein synthesis was reflected in the concentration and size distribution of ribosomes. No significant changes in these parameters were seen in the glutamine group after the operation. In the control group, the total concentration of ribosomes fell by 27.2 +/- 8.5% (p less than 0.05), and the relative proportion of polyribosomes fell by 10.6 +/- 2.9% (p less than 0.01). Although there were significant changes in the control group, no significant differences in the changes of these parameters between the two groups were detected. The cumulative nitrogen loss was significantly less in the glutamine group as compared to the control group during the period studied--2.3 +/- 1.4 g versus 8.5 +/- 1.5 g, respectively (p less than 0.01). Administration of glutamine to catabolic patients is advocated.     

Loss of insulin response to ingested amino acids after jejunoileal bypass surgery for morbid obesity

Amino acid tolerance tests were performed before and after jejunoileal bypass surgery for morbid obesity to determine whether an enteric factor(s) originating in the bypassed jejunum and/or ileum potentiates the insulin response to oral nitrogen loading. Preoperatively a 30-gm. mixture of amino acids given orally evoked a larger peak insulin than an intravenous load yielding comparable plasma amino acid elevations (82 +/- 17 muU./ml versus 38 +/- 8 muU./ml., p less than 0.05). Four months after operation, basal insulin concentrations were 46 per cent (p less than 0.001) of preoperative values. After surgery the response to intravenous amino acids was preserved when expressed as percentage increase above basal. In contrast, the peak increment and the percentage increase in insulin secretion after 30-gm. oral amino acid loading was significantly blunted (p less than 0.005). A smaller amino acid load (16.5 gm.) was given preoperatively to duplicate the plasma amino acid elevations seen postoperatively with the 30-gm. mixture given by mouth. The insulin response postoperatively was still significantly lower (167 +/- 33 per cent versus 98 +/- 16 per cent, p less than 0.05). After various explanations for the diminished postoperative insulin release following oral amino acid ingestion are considered, the results are best explained by the loss of an enteric insulinotrophic factor(s) normally released by the bypassed portions of jejunum or ileum in response to ingested protein.     

Effects of glucocorticoids on lung glutamine and alanine metabolism

The role of the glucocorticoid hormones as possible mediators of the accelerated lung glutamine and alanine release that occurs during critical illness was investigated. Studies were done in adult rats receiving dexamethasone (0.6 mg intramuscularly/100 gm body weight/day for 2 consecutive days; n = 24) or saline solution (controls; n = 20). Measurements were made in the postabsorptive state and amino acid flux was calculated by multiplying pulmonary blood flow by the right ventricular-arterial concentration difference for glutamine and alanine. Lung glutamine release was 703 +/- 184 nmol/100 gm body weight/min in control rats. This release rate doubled in the dexamethasone-treated rats (1476 +/- 256; p less than 0.05). The activity of the glutamine synthetase enzyme increased by 33% in the dexamethasone-treated animals and there was a 50% decrease in lung glutamine content (p less than 0.01). Likewise, dexamethasone accelerated the release of alanine by the lungs twofold (559 +/- 173 nmol/100 gm body weight/min in controls vs 1113 +/- 184 nmol/100 gm body weight/min in dexamethasone-treated rats; p less than 0.05). The increased release of both amino acids was caused by a significant increase in the concentration difference across the lungs and not a change in pulmonary blood flow. Glucocorticoids appear to be key mediators of the accelerated lung amino acid release that characterizes catabolic diseases.     

Hormonal and neural blockade prevents the postoperative increase in amino acid clearance and urea synthesis.

The combined effect of continuous blockade of glucagon and cortisol by somatostatin and etomidate and thoracic epidural analgesia on hepatic conversion of amino nitrogen was studied in eight patients who underwent elective cholecystectomy on day 1 after operation and was compared with 16 patients who underwent operation without blockade. Surgery increased the plasma clearance of total alpha-amino nitrogen from 5.2 +/- 0.3 to 6.6 +/- 0.3 ml/sec (mean +/- sem; p less than 0.05). This increase was due to increased elimination by the liver, because the hepatic effectiveness for amino nitrogen conversion measured by the functional hepatic nitrogen clearance increased from 9 +/- 2 to 16 +/- 4 ml/sec (p less than 0.05). In contrast, during the combined neural and hormonal blockade, surgery decreased the plasma clearance of amino nitrogen from 5.3 +/- 0.3 to 3.9 +/- 0.3 ml/sec (p less than 0.05), and the blockade prevented the postoperative increase in functional hepatic nitrogen clearance. The results suggest that glucagon, cortisol, and afferent neural reflexes are mediators of the hepatic contribution to catabolism after operation.     

Reduced amino acid transport in skeletal muscle caused by a circulating factor during endotoxemia.

The present study was designed to determine whether reduced amino acid uptake in skeletal muscle during endotoxemia is due to associated hypotension or is caused by a factor present in plasma. Three series of experiments were performed. In the first series of experiments, mean arterial pressure (MAP), heart rate, and amino acid uptake in incubated soleus muscles were measured after intravenous injection of endotoxin (1 mg/kg) in male Sprague-Dawley rats (40 to 60 g). Amino acid transport was measured by determining intracellular uptake of [3H]-alpha-amino-isobutyric acid (AIB) during 2 hours of incubation. In the second series of experiments, hypotension was induced by bleeding and muscle amino acid uptake was measured. In the third series of experiments, whole plasma or a low molecular weight fraction (less than 10,000 d) of plasma from endotoxin-injected rats was added in vitro to incubated muscles and amino acid uptake was determined. One hour after injection of endotoxin, MAP was reduced from 80 +/- 2 mmHg to 54 +/- 4 mmHg (p less than 0.05). AIB uptake was reduced by 20% (p less than 0.05) 2 hours after endotoxin injection. When MAP was maintained at 50 mmHg for 1 hour by bleeding, no changes in muscle AIB uptake were noted. When plasma obtained from rats 2 hours after endotoxin injection was added to incubated soleus muscles, AIB uptake was reduced by 22%. This effect was duplicated by a fraction of endotoxic plasma containing substances with a molecular weight less than 10,000 d. The present results suggest that reduced muscle amino acid uptake during endotoxemia is not due to associated hypotension, but may be caused by a circulating factor(s) with a molecular weight less than 10,000 d.     

Is skeletal muscle luxury perfusion the main hemodynamic effect of high-dose insulin in cardiac surgery?

Insulin, in combination with glucose and potassium (GIK), can be used in heart surgery to improve hemodynamic performance. This study evaluates the role of skeletal muscle vasodilation in hemodynamic effects of high-dose GIK therapy early after coronary surgery. Thirty-three male patients undergoing coronary artery bypass grafting were included in a prospective, randomized and controlled study. Eleven patients received infusions of mixed amino acids (11.4 g) and insulin solution (225 IU insulin, glucose with the glucose clamp technique, and potassium), 11 patients received infusions of mixed amino acids (11.4 g) and 11 patients served as control subjects. During combined insulin and amino acid infusion, cardiac output increased by 13+/-3% (+0.6+/-0.2 L x min(-1)) and systemic vascular resistance decreased by 24+/-3% (-320+/-46 dyn x s x cm(-5)). The changes differed from those in the control group (CO: -0.2+/-0.1 L x min(-1), p < 0.05; SVR: +136+/-42 dyn x s x cm(-5), p < 0.05). Changes in skeletal muscle perfusion and leg vascular resistance did not differ significantly among the groups. At most, changes in leg blood flow could explain 40% of the changes in cardiac output. Skeletal muscle luxury perfusion is not the main hemodynamic effect of high-dose insulin in the early postoperative period after coronary surgery.     

Nutritional status and amino acids in granulocytes and plasma in patients with chronic renal disease and varying residual renal function.

BACKGROUND: Protein metabolism changes with loss of renal function resulting in deterioration of nutritional status. Whether changes in macroscopic (anthropometry and subjective global nutritional assessment (SGNA)) and cellular (plasma and granulocyte free amino acid concentration) nutritional status with loss of residual renal function are related is not known. METHODS: Anthropometric variables, SGNA, and blood samples were measured after a night's fast in 43 patients (age 57 years, median (range 27-77), 32 males and 11 females) with chronic renal disease. A 24-hour urine sample was collected the day before the study for calculation of creatinine clearance and protein nitrogen appearance rate. The patients were stratified according to creatinine clearance (group I: >35 ml/min/1.73 m(2), group II 35-15 ml/min/1.73 m(2), group III <15 ml/min/1.73 m(2)). RESULTS: In males a significant lower body weight (p < 0.05) and upper mid-arm muscle area (p < 0.05) was found in group III compared to group I. SGNA indicated suboptimal nutritional status in 12 patients. In group I all had normal SGNA while in group II and group III, 26 and 57% respectively were malnourished. SGNA was significantly and negatively correlated to upper mid-arm muscle area (rho = -0.37, p < 0.05) and percent body fat mass (rho = -0.46, p < 0.01) and positively correlated to percent ideal body weight (rho = 0.48, p < 0.01). Nine patients with malnutrition (M) were compared with 9 well-nourished (N) patients. They were comparable with respect to creatinine clearance (M: 13 +/- 5 ml/min/1.73 m(2); N: 16 +/- 7 ml/min/1.73 m(2)), age and sex. In malnourished patients plasma concentration of nonessential amino acids was higher (23%, p < 0.05). The intracellular concentration was generally not affected except for sulfur amino acid methionine which was increased by a factor of 2.5 (p < 0.05) and taurine decreased by a factor of 1.6 (p < 0.05). CONCLUSION: Loss of renal residual function worsened both macroscopic and cellular nutritional status. SGNA correlated to objective measures of nutritional status and is clinically usable. In malnourished chronic renal patients, increased plasma concentration of nonessential amino acids was found which might indicate increased protein degradation.     

Alpha-ketoglutarate preserves protein synthesis and free glutamine in skeletal muscle after surgery

Serving as a reproducible human trauma model, patients (n = 21) undergoing elective cholecystectomy received postoperative total parenteral nutrition with (n = 9) or without (n = 12) alpha-ketoglutarate (AKG) supplementation. Skeletal muscle biopsy specimens were taken before surgery and on the third postoperative day. The postoperative decreases in the concentrations of free glutamine and basic amino acids seen in the control group were counteracted in the AKG group (p less than 0.05). Muscle protein synthesis was estimated by ribosome analysis. On the third postoperative day the control group showed a decline in the polyribosome concentration (25.8% +/- 4.5%; p less than 0.001). No significant change was observed in the AKG group. On each postoperative day the nitrogen balance was negative in the control group but not in the AKG group. In the control group the cumulative nitrogen balance amounted to -9.9 +/- 1.8 gm of nitrogen and in the AKG group -2.6 +/- 2.6 gm of nitrogen, which was significantly different (p less than 0.05). Administration of AKG, the carbon skeleton corresponding to glutamine, produced results similar to those seen when glutamine is added to postoperative total parental nutrition. The results suggest that the availability of precursors for glutamine synthesis in skeletal muscle is crucial for the degree of muscle protein catabolism after surgical trauma.     

Changes in blood glucose levels in relation to blood ketone body ratio following hypertonic glucose infusion in 70% hepatectomized rabbits

The effects of postoperative infusion of a hypertonic glucose solution on the blood glucose level, blood ketone body ratio (acetoacetate/beta-hydroxybutyrate), and plasma alanine and proline levels were studied in 70% hepatectomized rabbits (group A) and in rabbits 70% hepatectomized and, in addition, subjected to bile duct obstruction at 12 h after hepatectomy (group B). Glucose infusion was started at the end of hepatectomy and continued for 20 h. The blood glucose level in group A remained at approximately 300 mg/dl throughout the study; however, it reached 789 mg/dl in group B at 20 h. The blood ketone body ratio, which reflects hepatic mitochondrial redox potential, decreased from 0.90 +/- 0.09 in untreated rabbits to 0.38 +/- 0.05 in group A, and to 0.19 +/- 0.03 in group B at 20 h. As the blood ketone body ratio decreased, plasma proline and alanine levels increased rapidly (proline, r = -0.601, p less than 0.02; alanine, r = -0.640, p less than 0.001). In addition, the blood ketone body ratio was positively correlated with the hepatic energy charge level [(ATP + 0.5 ADP)/(ATP + ADP + AMP)] (r = 0.57, p less than 0.001). It is suggested that the entry of glucose and amino acids into the Krebs cycle is inhibited as the blood ketone body ratio decreases, and under such conditions the infused glucose tends to accumulate, resulting in severe hyperglycemia.     

Effect of amino acid based dialysis solution on peritoneal permeability and prostanoid generation in patients undergoing continuous ambulatory peritoneal dialysis.

The acute effect of amino acid based dialysis solution on peritoneal kinetics of amino acids and plasma proteins in comparison to conventional glucose-based dialysate was studied in 9 patients with end-stage renal failure on continuous ambulatory peritoneal dialysis. Instillation of 2.6% amino acid solution resulted in raised plasma concentrations of all essential amino acids included in the dialysis fluid (p less than 0.005). The amino acid solution induced an augmented leakage of plasma proteins into the dialysate at all dwell times investigated (1-8 h). After a dwell time at 8 h, the dialysate total protein increased from 2.62 +/- 0.45 g with glucose dialysate to 3.85 +/- 0.42 g with amino acid solution (p less than 0.05). Corresponding results were obtained for beta 2-microglobulin, albumin, transferrin, IgG, and for the non-essential amino acids alanine, citrulline, and glutamine (p less than 0.025) not included in the initial amino acid composition of the dialysis fluid. During the use of amino acid based dialysis fluid, the effluent prostaglandin E2 concentration increased by more than 80% in comparison to glucose dialysate (p less than 0.025). The augmented loss of proteins induced by the amino acid solution was positively correlated with increased dialysate prostaglandin E2 (r = 0.8894; p less than 0.001). Peritoneal ultrafiltration was not affected by the use of amino acid based dialysate fluid. The present results indicate that amino acid based dialysis fluid enhances the peritoneal permeability for plasma proteins and amino acids, probably mediated by locally generated prostanoids.     

Infusion of the Branched Chain Amino Acids in Postoperative Patients: Anticatabolic Properties

Postinjury metabolism is characterized by breakdown of muscle protein as substrate for energy production and gluconeogenesis and by the resultant loss of lean body mass and weight loss. The branched chain amino acids (BCAAs) which are principally oxidized by the skeletal muscle have been implicated in recent in vitro and in vivo studies as having special anticatabolic and regulating effects in skeletal muscle. We studied the anticatabolic effects of the BCAAs in 35 patients undergoing operative injury of moderate severity. In a prospective randomized and blinded manner patients were infused for five days starting immediately after surgery with either 5% dextrose or 5% dextrose with an amino acid solution containing 22, 35 or 100% BCAAs. All patients survived and there were no major postoperative complications. Mean hospital stay was 17 days for patients receiving amino acids and 19 days for patients receiving 5% dextrose only (p = ns). All three groups receiving amino acid solutions were in nitrogen equilibrium or in a slight positive nitrogen balance, while the group receiving 5% dextrose only was in a mean negative nitrogen balance of 6.6 +/- 0.6 gN/day. The differences between the three groups receiving amino acids were slight and not significant. Weight loss was 2 +/- 0.7 kg in the 5% dextrose group, 1 +/- 0.7 kg in the 22% BCAAs group, 0.5 +/- 0.5 kg in the 35% BCAAs group and the 100% BCAAs group gained 0.4 +/- 1.8 kg. Blood chemistries in the different groups and during the study period remained within normal limits except for ammonia levels rising significantly in the 5% dextrose group and SGOT levels rising in the 22% and 35% BCAA groups. With mild variations the plasma amino acid patterns in all groups were similar to the normal pattern, even in the 100% BCAAs group receiving an unbalanced amino acid solution, suggesting the complete cessation of amino acid efflux from muscle, the muscle depending solely on the exogenous supply of BCAAs to satisfy its metabolic requirements. The results suggest that early nutritional suppport in the postoperative period will result in nitrogen equilibrium and that the infusion of the three BCAAs only in the postoperative state is as effective in preventing muscle catabolism as other more balanced amino acid solutions. In the postinjury state balanced amino acid solutions rich in BCAA may prove beneficial.