Effects of hypercaloric glucose infusion on lipid metabolism in injury and sepsis.

Lipolysis was studied by measuring glycerol turnover (GTO) in injured and infected patients. GTO was elevated two to three times the normal values in five injured and four infected patients during D5W infusion. No correlation was found between GTO and plasma glycerol concentration in the two patient groups. GTO showed similar levels when measured during TPN in five injured and three infected patients. During TPN, plasma FFA levels remained unchanged in injured but decreased by 48% in septic patients. B-OH butyrate concentrations were high during D5W and dropped in both groups during TPN. Norepinephrine urinary output was high in both groups during D5W and TPN. Conclusions: 1) GTO was elevated two to three times the normal range in injury and infection; plasma glycerol concentration was not related to GTO. 2) In face of high catecholamine output, the insulin response to TPN did not inhibit TG breakdown but did decrease plasma ketone body concentrations.     

Influence of total parenteral nutrition on tissue lipoprotein lipase activity during chronic and acute illness.

This study examines the influence of total parenteral nutrition (TPN) compared with 5% dextrose (D5) infusion on skeletal muscle and adipose tissue lipoprotein lipase (LPL) activity in nutritionally depleted, injured and infected patients. The plasma concentrations of glucose, free fatty acid (FFA), triglyceride and insulin were also measured. During TPN, nutritionally depleted subjects showed an increase in adipose tissue LPL activity, "fat cell size," and plasma insulin concentration. Skeletal muscle LPL activity and plasma FFA concentration decreased. In comparison, trauma patients showed a less marked rise in adipose tissue LPL activity and skeletal muscle LPL activity increased. Infected patients had a much smaller rise in adipose tissue LPL activity than either of the other groups, and muscle activity rose. The depleted and injured patients showed a linear relationship between adipose tissue LPL activity and plasma insulin concentration and an inverse hyperbolic relationship between adipose tissue LPL activity and plasma FFA concentration.     

Fatty acid kinetics in man during chronic and acute illness

Eight nutritionally depleted and five injured patients were studied prior to and during total parenteral nutrition (TPN). Five additional injured patients were studied at intervals while receiving only 5% dextrose. Fatty acid kinetics and oxidation were determined using an infusion of [1-14C]palmitate. Net substrate oxidation was calculated by indirect calorimetry. During TPN, resting energy expenditure rose from 109 to 119% and from 89 to 103% of predicted in injured and depleted patients, respectively. Free fatty acid (FFA) flux was unaffected, FFA oxidation and net fat oxidation (NFO) decreased by 60%. However NFO began higher in injured subjects (20.7 +/- 2.8 vs 14.6 +/- 0.9 kcal/kg/day, P less than 0.05) and remained higher during TPN (8.3 +/- 1.2 vs 5.6 +/- 0.9 kcal/kg/day, P less than 0.05). The proportion of NFO derived from immediate oxidation of circulating FFA was approximately 35%. The results indicate that, with glucose-based TPN, there is a discrepancy between suppression of FFA production and oxidation. We further conclude that sources of fatty acid which are not in rapid equilibrium with circulating plasma FFA contribute substantially to whole body fat oxidation.     

Evaluation of free fatty acid kinetics during TPN feeding of healthy rats

Free fatty acid (FFA) kinetics were evaluated in TPN-fed healthy rats using a single fatty acid tracer. Rats were divided into three groups according to the nonprotein energetic substrate infused: glucose (A), monoacetoacetin-glucose (B), and lipid emulsion-glucose (C). Fat kinetics were measured by continuous infusion of [1-14C]palmitate. Total FFA and individual FFA concentrations were measured and turnover and oxidation were determined for the total pool of FFA and for palmitate. Groups A and B were similar in all parameters. Group C had increased total and individual FFA concentrations. Group C appeared to have decreased total plasma FFA turnover and unchanged oxidation compared to groups A and B. Palmitate appeared to have a 400% increase in oxidation and a 50% increase in turnover for rats in Group C when compared to Groups A and B. It is concluded that a single tracer does not accurately reflect plasma FFA during TPN using lipid emulsion.     

Metformin restores insulin secretion altered by chronic exposure to free fatty acids or high glucose: a direct metformin effect on pancreatic beta-cells

Because metformin affects glucose and free fatty acid (FFA) metabolism in peripheral insulin target tissues, we investigated the effect of this drug in restoring a normal secretory pattern in rat pancreatic islets whose function has been impaired by chronic exposure to elevated FFA or glucose concentrations. We cultured rat pancreatic islets with or without FFA (2 mmol/l oleate/palmitate 2:1) or high glucose (16.7 mmol/l) concentrations in the presence or absence of metformin (0.25-12.5 microg/ml) and then measured insulin release, glucose utilization, glucose, and FFA oxidation. When compared with control islets, islets exposed to high FFA or glucose concentrations showed an increased basal and a decreased glucose-induced insulin release. In islets cultured for an additional 24 h with FFA or glucose in the presence of metformin (2.5 microg/ml), both basal and glucose-induced insulin secretions were restored. Both glucose utilization and glucose oxidation were altered in islets pre-exposed to high FFA or glucose concentrations. In particular, regarding control islets, glucose utilization was increased at 2.8 mmol/l glucose and decreased at 16.7 mmol/l glucose; glucose oxidation was similar to control islets at 2.8 mmol/l glucose but decreased at 16.7 mmol/l glucose. In contrast, oleate oxidation was increased in islets pre-exposed to FFA. All of these abnormalities were reversed in islets cultured for an additional 24 h with high FFA or glucose concentrations in the presence of metformin (2.5 microg/ml). In conclusion, our data show that metformin is able to restore the intracellular abnormalities of glucose and FFA metabolism and to restore a normal secretory pattern in rat pancreatic islets whose secretory function has been impaired by chronic exposure to elevated FFA or glucose levels. These data raise the possibility that, in diabetic patients, metformin (in addition to its peripheral effects) may have a direct beneficial effect on the beta-cell secretory function.     

Defective free-fatty acid and oxidative glucose metabolism in IDDM during hypoglycemia. Influence of glycemic control

To examine the impact of diabetes and its treatment on plasma free-fatty acid (FFA) and oxidative fuel metabolism during hypoglycemia, we combined indirect calorimetry with [3-3H]glucose during a 4-h low-dose insulin infusion (plasma insulin approximately 2-fold above basal) in six poorly controlled and nine well-controlled insulin-dependent diabetes mellitus (IDDM) patients and in six healthy subjects. Diabetic subjects received insulin overnight to maintain euglycemia before study. Although free-insulin levels and counterregulatory hormone responses were similar, the plasma glucose fall was more pronounced in well-controlled diabetic subjects. In well-controlled diabetic and healthy subjects, the small increment in insulin rapidly suppressed plasma FFA and fat oxidation by approximately 50% and stimulated carbohydrate oxidation by approximately 80%. In contrast, plasma FFA levels did not fall in poorly controlled diabetic subjects, and glucose oxidation was not stimulated. To determine whether this resistance to the antilipolytic effect of insulin occurs in the absence of hypoglycemic counterregulation, we used a sequential low-dose euglycemic insulin clamp (0.2, 0.3, and 0.5 mU.kg-1.min-1). In healthy subjects, plasma FFA was nearly maximally suppressed at the lowest insulin dose. In contrast, plasma FFA remained persistently elevated in poorly controlled diabetic subjects at each insulin dose. However, the insulin dose-response curve for suppression of plasma FFA was near normal in well-controlled subjects. We conclude that poorly controlled IDDM diabetic patients are resistant to the antilipolytic effects of insulin and show impaired stimulation of glucose oxidation during insulin-induced hypoglycemia. Amelioration of these defects in well-controlled patients may be another factor contributing to the higher risk of hypoglycemia during intensified insulin therapy.     

EFFECTS OF NEUROLEPTANAESTHESIA ON PLASMA LEVELS OF GROWTH HORMONE AND INSULIN

The effects of neuroleptanaesthesia and surgery on carbohydrateand fat metabolism were studied in twenty-five patients by determiningplasma human growth hormone (HGH), insulin, blood glucose andfree fatty acids (FFA). The neuroleptanaesthesia consisted ofdroperidol, pethidine and nitrous oxide alone for 45 minutesand surgery increased significantly plasma HGH, insulin andblood glucose levels. Plasma FFA levels were insignificantlyelevated. The clinical significance of this temporary stateof glucose intolerance is also discussed.     

Effect of desflurane/remifentanil anaesthesia on glucose metabolism during surgery: a comparison with desflurane/epidural anaesthesia

BACKGROUND: The aim of this study was to investigate the effect of general anaesthesia combined with remifentanil or epidural blockade on glucose metabolism during surgery. METHODS: We randomly assigned patients undergoing elective colorectal surgery to receive either desflurane anaesthesia supplemented with intravenous remifentanil (n = 7) or desflurane anaesthesia supplemented with epidural bupivacaine (n = 7). Plasma concentrations of glucose, lactate, free fatty acids (FFA), insulin, glucagon and cortisol were measured before and after 2 h of surgery. Pre- and intraoperative whole body glucose production and glucose clearance, an indicator of glucose uptake, were determined by an isotope dilution technique using [6,6-2H2]glucose. RESULTS: In both groups intraoperative glucose production ( P< 0.05) and uptake ( P< 0.05) decreased. Plasma glucose concentrations ( P< 0.05) increased during surgery but did not exceed the normal range (remifentanil group: 5.7 +/- 0.7 mmol l-1, epidural group: 5.8 +/- 0.4 mmol l-1). The plasma concentrations of lactate, FFA, insulin and glucagon remained unchanged during the operation. The plasma cortisol concentration in both groups increased intraoperatively (P< 0.05). CONCLUSION: Both desflurane/remifentanil and desflurane/epidural anaesthesia decrease the intraoperative rate of whole body glucose production, thereby attenuating the hyperglycaemic response to colorectal surgery.     

Metabolic utilization of intravenous fat emulsion during total parenteral nutrition

The effect of nutritional therapy on the utilization of an intravenous fat emulsion was studied in patients with injury, infection, and nutritional depletion using I-14C-trioleate labeled Intralipid. The plasma fractional removal rate and 14C-Intralipid oxidation rate was 55% ad 25% higher, respectively, in patients following trauma and during periods of infection receiving 5% dextrose than in healthy control subjects. Total parenteral nutrition (TPN) was administered as either 1) nonprotein calories given as glucose (Glucose System) or 2) equal proportions of glucose and intravenous fat emulsion (Lipid System). In comparison to TPN with the Lipid System, administration using the Glucose System resulted in higher plasma clearance rates and lower oxidation rates in both acutely ill and depleted patients. There was no correlation between the rates of plasma removal and oxidation of the intravenous fat emulsion (r = -0.04; NS) indicating that the removal of exogenous fat from plasma cannot be used as an indicator of oxidation. A negative linear relationship was seen between the oxidation rate of intravenous fat and carbohydrate intake (r = -0.92; p less than 0.001). Glucose intakes exceeding energy expenditure did not totally inhibit oxidation of the fat emulsion. The oxidation rate of 14C-Intralipid was linearly related to net whole body fat oxidation calculated using indirect calorimetry (r = -0.90; p less than 0.001) suggesting that the fat emulsion was oxidized in a similar manner to endogenous lipids. This study suggests that intravenous fat emulsions are utilized as an energy substrate in patients with major injury, infection or nutritional depletion. This observation, along with a relative unresponsiveness to glucose in surgical patients suggests that fat emulsions may be useful as a calorie source in patients receiving parenteral nutrition.     

Plasma adiponectin concentrations predict insulin sensitivity of both glucose and lipid metabolism

In animals, the adipocyte-derived hormone adiponectin has been shown to improve insulin sensitivity, a key factor in the pathogenesis of type 2 diabetes. In Pima Indians, high plasma adiponectin levels are associated with increased insulin sensitivity and reduced risk of type 2 diabetes. It is unclear whether this is also the case in white individuals and whether an additional beneficial effect on lipid metabolism exists. We therefore analyzed in nondiabetic individuals the associations between plasma adiponectin concentrations and insulin sensitivity measured by a euglycemic-hyperinsulinemic clamp (n = 262) and estimated by an oral glucose tolerance test (OGTT; n = 636) and serum lipid parameters using correlational analysis. Plasma adiponectin concentrations were positively correlated with insulin sensitivity, both measured with the clamp (r = 0.28, P = 0.0015 in women; r = 0.42, P < 0.0001 in men) and estimated from the OGTT (r = 0.37, P < 0.0001 in women; r = 0.41, P < 0.0001 in men) before and after adjusting for sex and percentage of body fat (all P < 0.001). Fasting triglycerides and the free fatty acid (FFA) concentrations during the OGTT (area under the curve) and at 120 min were negatively correlated in both women and men, whereas HDL was positively correlated with plasma adiponectin concentrations (all P < 0.004). Most notable, these relationships remained significant after adjusting for insulin sensitivity of glucose disposal in addition to sex and percentage of body fat (all P < 0.05). In conclusion, high adiponectin predicts increased insulin sensitivity. This relationship is independent of low body fat mass and affects not only insulin-stimulated glucose disposal but also lipoprotein metabolism and insulin-mediated suppression of postprandial FFA release. This suggests pleiotropic insulin sensitizing effects of adiponectin in humans.     

Glucose, fatty acid, and urea kinetics in patients with severe pancreatitis. The response to substrate infusion and total parenteral nutrition.

Rates of glucose turnover and oxidation in normal volunteers (N = 16) and in severely ill patients with pancreatitis (N = 9) were isotopically determined. Glucose turnover was determined using primed constant infusions of either 6-3H-glucose or 6-d2-glucose, and glucose oxidation with either U-14C-glucose or U-13C-glucose after appropriate priming of the bicarbonate pool. Urea kinetics were determined using primed constant infusions of either (15N2)-urea or U-14C-urea, whereas free fatty acid (FFA) kinetics were determined by the constant infusion of 1,2-13C palmitate. Basal rates of glucose production and plasma glucose clearance were significantly higher in the patients than in the volunteers. During glucose infusion (4 mg/kg/min) endogenous glucose production was virtually totally suppressed in the volunteers (94 +/- 4%). There was significantly less suppression in the patients, however (44 +/- 1%). In addition, the percentage of available glucose oxidized (i.e., percentage of uptake oxidized) was significantly less in the patients than in the volunteers. The basal rate of urea production was significantly higher in the patients; however, in both patients and volunteers, glucose infusion resulted in a significant decrease. The rate of FFA turnover was similar in the patients and volunteers, and the patients and volunteers were equally sensitive to the suppressive effects of glucose infusion. When the patients were studied during total parenteral nutrition (TPN), there was no further suppression of endogenous glucose turnover than that seen during 2 hours of glucose infusion, and the mean rate of urea turnover measured during TPN (7.0 +/- 1.9 mumol/kg/min) was also not significantly different than the value determined during glucose infusion (8.9 +/- 1.8 mumol/kg/min). It was concluded from these studies that patients with pancreatitis are metabolically similar to septic patients, have an impairment in their ability to oxidize infused glucose when compared with normal volunteers, have an elevated rate of net protein catabolism, and have FFA kinetics similar to those seen in normal humans.     

Total parenteral nutrition in ex vivo lung perfusion: Addressing metabolism improves both inflammation and oxygenation

Ex vivo lung perfusion (EVLP) protocols generally limit metabolic supplementation to insulin and glucose. We sought to determine whether the addition of total parenteral nutrition (TPN) would improve lung function in EVLP. Ten porcine lungs were perfused using EVLP for 24 hours and supplemented with insulin and glucose. In the treatment group (n = 5), the perfusate was also supplemented with a continuous infusion of TPN containing lipids, amino acids, essential vitamins, and cofactors. Physiologic parameters and perfusate electrolytes were continuously evaluated. Perfusate lactate, lipid and branch chain amino acid (BCAA) concentrations were also analyzed to elucidate how substrates were being utilized over time. Lungs in the TPN group exhibited significantly better oxygenation. Perfusate sodium was more stable in the TPN group. In the control group, free fatty acids (FFA) were quickly depleted, reaching negligible levels early in the perfusion. Alternatively, BCAA in the control group rose continually over the perfusion demonstrating a shift toward proteolysis for energy substrate. In the TPN group, both FFA and BCAA concentrations remained stable at in vivo levels after initial stabilization. TNF‐α concentrations were lower in the TPN group. The addition of TPN in EVLP allows for better electrolyte composition, decreased inflammation, and improved graft performance.     

The inefficiency of total parenteral nutrition to stimulate protein synthesis in moderately malnourished patients.

The acute whole-body and peripheral tissue protein response to total parenteral nutrition (TPN) was evaluated before surgery in moderately malnourished patients with stable disease. A primed constant infusion of (U-14C) tyrosine was used in combination with simultaneous measurements of the leg exchange of amino acids, glucose, glycerol, and free fatty acids (FFA). Energy expenditure was measured by indirect calorimetry. Sixteen patients with stable disease and in need of nutritional support were randomized to receive TPN at rates either corresponding to resting requirements (nonprotein calories at 120% of REE with 0.2 g of N/kg/d) or at increased rates (200% of REE with 0.33 g of N/kg/d). Energy expenditure was not affected by the low rate of TPN, but increased with the high rate, with a thermic effect corresponding to 16% of basal levels. Tyrosine flux and incorporation rate into whole-body proteins (protein synthesis) were not altered by the low TPN rate, but increased with the high rate. Estimates of protein breakdown decreased, and tyrosine oxidation increased significantly with both rates of TPN. Protein synthesis was stimulated at the high dose rate only. However, a positive whole-body tyrosine balance (net protein synthesis) measured by the 14C tyrosine technique was associated with a continued negative tyrosine balance across the skeletal muscle compartment in the leg. The results demonstrate that TPN given at rates corresponding to resting needs of 0.2 g of N/kg/day is insufficient to promote protein synthesis in the majority of body proteins. Skeletal muscles may remain in negative protein balance even at high TPN loads. Our results reflect the difficulties of expanding lean body mass through intravenous nutrition in moderately malnourished patients--even those with stable disease.     

Changes in Intermediary Metabolism in Severe Surgical Illness

Under normal circumstances there is a reciprocal relation between the availability of free fatty acids (FFAs) and glucose in plasma. In the fasted state, FFAs predominate in both availability and the relative contribution to energy production, whereas the same is true for glucose in the fed state. The extent of glucose oxidation is directly determined by its availability, whereas FFAs are normally available well in excess of their rate of oxidation. The rate of FFA oxidation is determined by the rate of transfer into the mitochondria via the carnitine palmitoyltransferase (CPT) enzyme system, which in turn is regulated by the metabolism of glucose. With critical illness the stress response involves mobilization of both plasma glucose and FFAs simultaneously in both the fed and fasted states. In the situation of excess availability of substrates, the metabolism of glucose limits the oxidation of FFAs, thereby channeling those fatty acids into triglyceride (TG) stores in the muscle and the liver. The high FFA concentrations and increased tissue TG stores can limit glucose clearance from the blood, thereby contributing to the development of hyperglycemia. Also, the excessive metabolism of glucose can result in lacticacidemia and can contribute to the depletion of muscle glutamine. The nutritional treatment of such patients must account for these underlying metabolic responses to avoid amplifying potentially detrimental responses to the excess availability of substrates already present in the fasting state.     

Differential effects of prednisone and growth hormone on fuel metabolism and insulin antagonism in humans

Human growth hormone (hGH) and prednisone cause insulin resistance and glucose intolerance. However, it is unknown whether hGH and prednisone antagonize insulin action on protein, fat, and carbohydrate metabolism by a common or independent mechanism. Therefore, protein, fat, and carbohydrate metabolism was assessed simultaneously in four groups of eight subjects each after 7 days of placebo, recombinant DNA hGH (rhGH; 0.1 mg.kg-1.day-1), prednisone (0.8 mg.kg-1.day-1), or rhGH and prednisone administration after an 18-h fast and during gut infusion of glucose and amino acids (fed state). Fasting plasma glucose concentrations were similar during placebo and rhGH but elevated (P less than 0.001) during combined treatment, whereas plasma insulin concentrations were higher (237 +/- 57 pmol/ml, P less than 0.001) during combined than during placebo, rhGH, or prednisone treatment (34, 52, and 91 pM, respectively). In the fed state, plasma glucose concentrations were elevated only during combined treatment (11.3 +/- 2.1 mM, P less than 0.001). Plasma insulin concentrations were elevated during therapy with prednisone alone and rhGH alone (667 +/- 72 and 564 +/- 65 pmol/ml, respectively, P less than 0.001) compared with placebo (226 +/- 44 pmol/ml) but lower than with the combined rhGH and prednisone treatment (1249 +/- 54 pmol/ml, P less than 0.01). Protein oxidation [( 14C]leucine) increased (P less than 0.001) with prednisone therapy, decreased (P less than 0.001) with rhGH treatment, and was normal during the combined treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Additive hypoglycemic effects of drugs that modify free-fatty acid metabolism by different mechanisms in rats with streptozocin-induced diabetes

In this study the effect of two drugs [etomoxir and nicotinic acid (NA)] on plasma glucose, free-fatty acid (FFA), and triglyceride (TG) concentrations was determined in rats with streptozocin (STZ)-induced diabetes. The two compounds modify FFA metabolism by different mechanisms, etomoxir (ethyl-2-[6-(4-cholorophenoxyl)-hexyl]oxirane-2-carboxylate) by inhibiting hepatic fatty acid oxidation, and NA by inhibiting lipolysis in adipose tissue. Diabetes was induced in male Sprague-Dawley rats, weighing approximately 400 g, by STZ injection (30 mg/kg i.v.), and the metabolic effects of the two drugs were studied 7-10 days later. The acute administration of either etomoxir or NA lowered plasma glucose concentrations in diabetic rats by approximately 150 mg/dl (P less than .001) in 4 h. However, the two drugs differed dramatically in their effects on plasma FFA and TG concentrations. Specifically, etomoxir produced striking increases in plasma FFA and TG concentrations, whereas NA administration caused a marked decrease. However, when NA was given in conjunction with etomoxir, NA prevented the increase in plasma FFA and TG concentration seen with etomoxir; the combination of NA and etomoxir approximately doubled the decrease in plasma glucose concentration produced by NA or etomoxir when given alone. Because plasma insulin concentrations did not change in response to either drug, whether administered singly or in combination, these metabolic effects do not result from a change in insulin secretion. These results suggest that modulation of FFA metabolism at the level of the adipocyte or the liver can have dramatic effects on carbohydrate and lipid metabolism.     

Nutritional impact on the energy cost of fat fuel mobilization in polytrauma victims

In the "flow" phase of severe injury, mobilization of body fat and protein sources are accelerated to meet increased demands. Fat mobilization usually exceeds the need for oxidative substrates and the leftover fatty acids are re-esterified, resulting in a "futile" TG/FFA cycle. This contributes to increased energy expenditure and provision of nutrients may alter the activity of this cycle. We measured in nine adult (age 40 +/- 7 years, weight, 80 +/- 4 kg) severely traumatized (ISS 32 +/- 4) patients, the resting energy expenditure (REE) and net fat oxidation rate (NFO) by indirect calorimetry and whole body lipolysis rate (WBLR) by a two-stage, primed-constant infusion of glycerol. Fasting postinjury kinetic studies were performed within 48-96 hours after admission when the patients were receiving saline without calories or nitrogen. Glucose-based nutritional therapy was then started and continued for 5 to 7 days. The kinetic measurements were repeated after the nutritive solutions were replaced by normal saline for 12 to 15 hours to achieve a postabsorptive state. Trauma elicits an accelerated rate of fat mobilization with increased TG/FFA cycle activity. Adequate nutritional support for 5 to 7 days tends to reduce but cannot normalize the lipid metabolism. In acute trauma 47 +/- 7% of the mobilized fat was recycled to triglyceride and this is increased to 54 +/- 9% after providing nutrition. The energy cost of this cycling was 38 kcal/day, which is five times that seen in normals and corresponds to 1.34% REE.     

Amelioration of metabolic complications of conventional total parenteral nutrition. A prospective randomized study

The most common metabolic complications of total parenteral nutrition (TPN), glucose intolerance and abnormal liver function, can be significantly reduced when 30% of the glucose calories are replaced by fat. We gave 88 patients either conventional TPN (CON-TPN, 25% dextrose and 4.25% amino acids) or modified TPN (MOD-TPN, 15% dextrose, fat, and 5% amino acids). The treatment groups were as follows: group A, no surgery with TPN only; group B, postoperative TPN; and group C, preoperative and postoperative TPN. Serial blood samples were analyzed for glucose, albumin, triglycerides, and insulin, and for liver function values. Nine patients manifested hyperglycemia and were removed from the study; seven patients had received CON-TPN and two had received MOD-TPN. In group A, the insulin level rose 50% less with MOD-TPN. There was a 50% smaller rise in the triglyceride, SGOT, and SGPT levels in patients who received MOD-TPN. Replacing one third of the TPN glucose calories with fat leads to better glucose tolerance and fewer hepatic complications.     

EFFECTS OF SPINAL ANAESTHESIA AND SURGERY ON CARBOHYDRATE AND FAT METABOLISM IN MAN

The effects of spinal anaesthesia and surgery on carbohydrateand fat metabolism were studied in thirty patients by determiningplasma concentrations of human growth hormone (HGH), insulin,blood glucose and free fatty acids (FFA). Hyperbaric spinalanaesthesia with lignocaine or quatacaine alone and subsequentsurgery did not influence the plasma HGH, insulin or FFA levels.Mean blood glucose levels were elevated significantly duringspinal anaesthesia and surgery, but remained within the normalrange.     

Epidural blockade modifies perioperative glucose production without affecting protein catabolism

BACKGROUND: Epidural blockade with local anesthetic has been shown to blunt the increase in plasma glucose concentration during and after abdominal surgery. The aim of the study was to test the hypothesis that epidural blockade inhibits this hyperglycemic response by attenuating endogenous glucose production. The authors further examined if the modification of glucose production by epidural blockade has an impact on perioperative protein catabolism. METHODS: Sixteen patients undergoing colorectal surgery received either general anesthesia and epidural blockade with local anesthetic (n = 8) or general anesthesia alone (control, n = 8). Glucose and protein kinetics were assessed by stable isotope tracer technique ([6,6-2H2]glucose, L-[1-13C]leucine) during and 2 h after surgery. Plasma concentrations of glucose, lactate, free fatty acids (FFA), cortisol, glucagon, and insulin were also determined. RESULTS: Epidural blockade blunted the perioperative increase in the plasma concentration of glucose, cortisol, and glucagon when compared with the control group (P < 0.05). Plasma concentrations of lactate, FFA, and insulin did not change. Intra- and postoperative glucose production was lower in patients with epidural blockade than in control subjects (intraoperative, epidural blockade 8.2 +/- 1.9 vs. control 10.7 +/- 1.4 micromol x kg(-1) x min(-1), P < 0.05; postoperative, epidural blockade 8.5 +/- 1.8 vs. control 10.5 +/- 1.2 micromol x kg(-1) x min(-1), P < 0.05), whereas glucose clearance decreased to a comparable extent in both groups (P < 0.05). Protein breakdown (P < 0.05), protein synthesis (P < 0.05), and amino acid oxidation (P > 0.05) decreased with both anesthetic techniques. CONCLUSIONS: Epidural blockade attenuates the hyperglycemic response to surgery through modification of glucose production. The perioperative suppression of protein metabolism was not influenced by epidural blockade.