[show abstract][hide abstract] ABSTRACT: OBJECTIVE:: We tested the hypothesis that the anabolic effect of hypocaloric, isonitrogenous nutrition in patients undergoing colorectal surgery depends on the patient's preoperative catabolic state. BACKGROUND:: Although there is evidence to suggest that total parenteral nutrition more effectively spares protein in depleted than in nondepleted cancer patients, the influence of preoperative catabolism on the anabolic effects of hypocaloric nutrition in patients undergoing elective surgery is unknown. METHODS:: Seventeen patients undergoing colorectal surgery received intravenous infusion of glucose with amino acids. Feeding was administered over 72 hours, from 24 hours before until 48 hours after surgery. Glucose provided 50% of the patient's measured resting energy expenditure. Amino acids provided 20% of the resting energy expenditure. Whole-body leucine balance (difference between the incorporation of leucine into protein = protein synthesis and endogenous leucine release = proteolysis) was determined using L-[1-C]leucine kinetics before and 2 days after surgery. We analyzed the association between the postoperative increase in leucine balance and the following factors: preoperative leucine balance, protein breakdown, weight loss, oxygen consumption, circulating concentrations of glucose, free fatty acids, insulin, glucagon, cortisol, albumin, age, duration of surgery, and blood loss. RESULTS:: Of 6 potentially relevant variables, 4 (weight loss, protein breakdown, albumin, and cortisol) were removed because they were not significant during the stepwise linear regression procedure. Leucine balance and age were the remaining 2 factors that remained with the final regression model: Δleucine balance = 19.1 - (0.20 × age [years]) - (0.58) × leucine balancepreOP). CONCLUSIONS:: We demonstrate a significant association between the degree of preoperative catabolism, the patient's age, and the anabolic effect of hypocaloric nutrition (ClinicalTrials.gov registration ID: NCT01414946).
[show abstract][hide abstract] ABSTRACT: An exaggerated inflammatory response in patients undergoing major liver resection coupled with poor nutrition diminishes liver regenerative capacity and increases the risk of postoperative complications.
Our objective was to evaluate the biological context leading to better clinical outcomes in patients undergoing liver resection coupled with hyperinsulinemic-normoglycemic clamp vs. standard care (insulin sliding care).
This study was a fundamental research analysis of a patient subset from a randomized-controlled study at the McGill University Health Center.
Thirty consenting patients participating in a randomized clinical trial for liver resection received either hyperinsulinemic-normoglycemic clamp technique with 24-h preoperative carbohydrate load (intervention) or standard glucose control through insulin sliding scale treatment (control).
Liver biopsies and plasma samples were taken at various time points before and after surgery. Primary measures included mRNA quantitation for genes related to insulin signaling, inflammation, and proliferation; proinflammatory cytokines at various time points; and liver function markers. These measurements were associated with clinical outcomes.
The hyperinsulinemic-normoglycemic clamp technique reduced postoperative liver dysfunction, infections, and complications. Markers of energy stores indicated higher substrate availability. Cytokine expression pattern was altered (TNF-α, IL-8, monocyte chemoattractant protein-1, IL-6, IL-10, and C-reactive protein). Apoptosis was markedly reduced, whereas the complement system was unaltered.
The hyperinsulinemic-normoglycemic clamp technique reduced postoperative negative outcomes by suppressing apoptosis. This phenomenon appears to be linked with higher substrate availability and altered cytokine secretion profile and may provide a long-term benefit of this therapy on liver resection patients.
The Journal of clinical endocrinology and metabolism 01/2012; 97(1):217-26. · 6.50 Impact Factor
[show abstract][hide abstract] ABSTRACT: Loss of body protein and hyperglycaemia represent typical features of the stress response to surgery and anaesthesia. This appears to be particularly pronounced in patients with diabetes mellitus type 2. The aim of the present study was to highlight the greater benefit of amino acids (AA) as represented by positive protein balance and maintenance of blood glucose homoeostasis compared with dextrose (DEX) in diabetic patients after colorectal surgery. A total of thirteen patients underwent a 5 h stable isotope infusion study (2 h fasted, 3 h fed with an infusion of AA (n 6) or DEX (n 7)) on the second post-operative day. Glucose and protein kinetics were assessed by using the stable isotopes l-[1-¹³C]leucine and [6,6-²H₂]glucose. The transition from fasted to fed state decreased endogenous glucose production (P < 0·001) in both groups, with a more profound effect in the DEX group (P = 0·031). In contrast, total glucose production was increased by the provision of DEX while being lowered by AA (P = 0·021). Feeding decreased protein oxidation (P = 0·009) and protein synthesis in the AA group, whereas DEX infusion did not affect oxidation and even decreased protein synthesis. Therefore, only AA shifted protein balance to a positive value, while patients in the DEX group remained in a catabolic state (P < 0·001). Parenteral nutritional support with AA rather than with DEX is an effective strategy to achieve a positive protein balance while maintaining normoglycaemia in diabetic patients after colorectal surgery.
The British journal of nutrition 08/2011; 107(4):573-80. · 3.45 Impact Factor
[show abstract][hide abstract] ABSTRACT: Although the effects of insulin on glucose homeostasis are well recognized in surgical patients, its effect on perioperative protein metabolism has received little attention. The purpose of this study was to examine the effect of high-dose insulin therapy on the plasma concentrations of amino acids (AAs) in patients undergoing coronary artery bypass grafting surgery. We studied 20 nondiabetic patients scheduled for elective coronary artery bypass grafting surgery. Patients were randomly allocated to receive either standard metabolic care (target glycemia 6.0-10.0 mmol/L, control group, n = 10) or high-dose insulin therapy (insulin group, n = 10). Insulin was administered at 5 mU·kg(-1)·min(-1) beginning at skin incision. Simultaneously, 20% dextrose was infused at a variable rate adjusted to maintain glycemia between 4.0 and 6.0 mmol/L. Plasma AAs, glucose, cortisol, and insulin were measured immediately before surgery and at sternal closure. Differences in mean values were assessed by Student t test. Plasma concentrations of all AAs decreased in the insulin group, with 15 of 22 AAs, including all branched-chain AAs, being significantly lower at sternal closure when compared with the control group. At the end of surgery, plasma glucose concentration was significantly lower in the insulin group (4.2 ± 0.6 vs 7.3 ± 1.0 mmol/L, P = .0001), whereas plasma cortisol levels did not show any difference between groups. High-dose insulin therapy resulted in a significant reduction in plasma AAs, particularly branched-chain AAs, during cardiac surgery.
Metabolism: clinical and experimental 05/2011; 60(10):1392-7. · 2.59 Impact Factor
[show abstract][hide abstract] ABSTRACT: Hypermetabolism, abnormal plasma amino acid profiles, increased gluconeogenesis, and changes in liver and muscle protein turnover are well-described undesirable effects in patients with cancer and diabetes mellitus type 2 (DM2) The aim of the present study was to analyze the specific impact and interaction of these 2 disease patterns on patients' preoperative glucose and protein metabolism. Eight nondiabetic and 8 diabetic patients devoid of cachexia underwent a stable isotope infusion study on the day before surgery for colorectal cancer or adenoma with high-grade dysplasia. Protein and glucose kinetics were assessed in a fasted state by L-[1-(13)C]leucine and [6,6(2)H(2)]glucose. In diabetic patients, glucose metabolism was found to be elevated as the plasma glucose level increased (P = 0.013) and endogenous rate of appearance of glucose tended to be higher compared to nondiabetic patients (P = 0.083). Protein metabolism was not affected by the metabolic state of the 2 groups. Resting energy expenditure was higher in diabetic patients (P = 0.028). Under postabsorptive conditions, noncachectic patients with DM2 suffering from colorectal tumors showed an elevated turnover in glucose metabolism whereas the nondiabetic counterparts failed to demonstrate any metabolic changes due solely to malignancy.
Nutrition and Cancer 01/2011; 63(6):924-9. · 2.70 Impact Factor
[show abstract][hide abstract] ABSTRACT: Surgical injury provokes a stress response that leads to a catabolic state and, when prolonged, interferes with the postoperative recovery process. This study tests the impact of 2 nutrition support regimens on protein and glucose metabolism as part of an integrated approach in the perioperative period incorporating epidural analgesia in 18 nondiabetic patients undergoing colorectal surgery. To test the hypothesis that parenteral amino acid infusion (amino acid group, n = 9) maintains glucose homeostasis while maintaining normoglycemia and reduces proteolysis compared with infusion of dextrose alone (DEX group, n = 9), glucose and protein kinetics were measured before and on the second day after surgery using a stable isotope tracer technique. Postoperatively, the rate of appearance of glucose was higher (P < .001) and blood glucose increased more (P < .001) in the DEX group than in the amino acid group. The postoperative increase in the appearance of leucine from protein breakdown tended to be greater (P = .077) in the DEX group. We conclude that perioperative infusion of a nutrition support regimen delivering amino acids alone maintains blood glucose homeostasis and normoglycemia and tends to have a suppressive effect on protein breakdown compared with infusion of dextrose alone.
Metabolism: clinical and experimental 11/2010; 59(11):1649-55. · 2.59 Impact Factor
[show abstract][hide abstract] ABSTRACT: Surgical injury provokes a stress response that is thought to be pronounced in patients with diabetes mellitus type 2 (DM2) leading to intensified catabolism. The aim of this study was to compare the effects of perioperative epidural analgesia (EDA) versus patient controlled analgesia (PCA) and amino acid infusion on postoperative metabolism in patients with and without DM2.
For this study, 12 nondiabetic patients and 12 diabetic patients undergoing colorectal surgery were randomly assigned to 4 groups (n = 6 per group) receiving either EDA (nondiabetic EDA and diabetic EDA [DEDA group]) or PCA with morphine (nondiabetic PCA and diabetic PCA) for perioperative pain control. Protein and glucose kinetics were measured on the second postoperative day using L-[1-13C]leucine and [6,6-2H2]glucose infusion during a fasted state and a 3-hr fed state with amino acid infusion.
The transition from the fasted to fed state suppressed endogenous rate of appearance (Ra) of glucose (P G 0.001) with a distinct effect for the DEDA group (P G 0.001). The Ra of leucine and the endogenous rate of appearance of leucine tended to be lower in the DEDA group(P = 0.056 and P = 0.07). Leucine oxidation was more suppressed in the DEDA group (P = 0.02) and when receiving amino acids(P = 0.001). Diabetic patients achieved a higher protein balance than nondiabetic patients (P = 0.032) and when receiving EDA instead of PCA (P = 0.012) or infusion of amino acids (P = 0.014).
A short-term infusion of amino acids reduced protein breakdown, increased protein synthesis, and rendered protein balance positive. This anabolic effect was pronounced in diabetic patients with EDA compared with nondiabetic patients or PCA, respectively, and prevented an undesirable hyperglycemia.
Regional anesthesia and pain medicine 01/2010; 35(4):355-60. · 4.16 Impact Factor
[show abstract][hide abstract] ABSTRACT: Malnutrition and cytokine-induced catabolism are pervasive in children with inflammatory bowel diseases (IBD), however, the benefits of aggressive nutrition support or of probiotics on nutrient and functional deficiencies and growth remain unclear. Piglets with dextran sulfate (DS)-induced colitis consuming a 50% macronutrient restricted diet (C-MR) were compared with those receiving probiotics (C-MRP) or adequate nutrition (C-WN) and with healthy well-nourished controls (REF). C-WN versus REF had reduced growth (-34% chest circumference and -22% snout-to-rump length gain) and a tendency toward lesser weight gain, but no differences in skeletal muscle protein fractional synthesis rates (FSR) or initiation of translation via the mTOR pathway were observed. Compared with C-WN, the C-MR and C-MRP piglets had lower weight gain, growth, and skeletal muscle FSR, and lower phosphorylated p70S6K1 with higher eIF4E*4E-BP1, indicative of reduced initiation of protein translation. Finally, plasma leucine concentrations were positively correlated with weight and phosphorylated p70S6K1, whereas negatively correlated with eIF4E*4E-BP1. In conclusion, reductions in weight gain, growth, protein turnover, skeletal muscle FSR, and initiation of protein translation with moderate macronutrient restriction in colitis are not ameliorated by probiotic supplementation. However, maintaining adequate nutrient intake during colitis preserves whole body protein metabolism, but growth remains compromised.
Pediatric Research 11/2009; 67(3):268-73. · 2.67 Impact Factor
[show abstract][hide abstract] ABSTRACT: We tested the hypothesis that the avoidance of preoperative fasting by hypocaloric nutrition attenuates protein catabolism after surgery.
Prolonged fasting before major abdominal procedures has been demonstrated to accentuate the catabolic response to surgery.
Twenty-two patients undergoing colorectal cancer surgery were randomly assigned to receive glucose and amino acids intravenously starting either 20 hours before the operation or with surgical skin incision. Nutrition was administered until the second postoperative day, with glucose providing 50% and amino acids 20% of each patient's measured resting energy expenditure. Whole body leucine and glucose kinetics were assessed by L-[1-(13)C]leucine and [6,6-(2)H(2)]glucose before and after surgery. Fractional synthesis rates of muscle protein, albumin, and fibrinogen were determined using primed continuous infusions of L-[(2)H(5)]phenylalanine postoperatively, whereas the expression of mRNA of proteolytic genes in muscle (Mafbx/atrogin-1, ubiquitin, Murf 1) was determined by quantitative RT-PCR. Circulating concentrations of glucose, lactate, amino acids, insulin, glucagon, and cortisol were also measured. This study has been registered at ClinicalTrials.gov (Identifier: NCT00614133).
Preoperative feeding inhibited endogenous protein breakdown (fasting group: 128 +/- 23 micromol . kg(-1) . h(-1); nutrition group: 96 +/- 22 micromol . kg(-1) . h(-1); P = 0.02) and blunted the increase in amino acid oxidation (fasting group: 27 +/- 5 micromol . kg(-1) . h(-1); nutrition group: 20 +/- 5 micromol . kg(-1) . h(-1); P = 0.03), resulting in positive whole-body protein balance after surgery (fasting group: -10 +/- 4 micromol . kg(-1) . h(-1); nutrition group: 1 +/- 3 micromol . kg(-1) . h(-1); P < 0.001). This anabolic response was associated with decreased muscle proteolytic gene expression and increased hepatic albumin synthesis. Total plasma protein, fibrinogen, and muscle protein synthesis were not affected.
Hypocaloric nutrition decreases protein catabolism, with a contribution from the ubiquitin pathway in muscle, and stimulates albumin synthesis after colorectal surgery if initiated 1 day before the operation.
Annals of surgery 12/2008; 248(6):1051-9. · 7.90 Impact Factor
[show abstract][hide abstract] ABSTRACT: It has been suggested that diabetes mellitus type 2 amplifies the endocrine-metabolic stress response to surgery, and patients become more catabolic during the postoperative period. The aim of this study, conducted in patients with diabetes mellitus type 2 scheduled to undergo elective colorectal surgery, was to determine whether the anabolic effects of intravenous amino acids are more pronounced when receiving perioperative epidural analgesia compared with patient-controlled analgesia with intravenous morphine.
Twelve patients were randomly assigned to receive either epidural analgesia or patient-controlled analgesia with intravenous morphine for perioperative pain control. Protein and glucose kinetics were measured before surgery and on the second postoperative day using L-[1-C]leucine and [6,6H2]glucose infusion during a fasted and a fed (amino acid infusion) state.
Preoperative parameters for glucose and protein kinetics were comparable in the fasted state for both groups. Postoperative amino acid infusion increased glucose concentration slightly (P = 0.124) and suppressed the endogenous rate of appearance of glucose (P < 0.0001) and glucose clearance (P < 0.0001) regardless of analgesia technique. The rate of appearance of leucine (P = 0.002), leucine oxidation (P < 0.0001), and protein synthesis (P = 0.026) increased, whereas net protein breakdown was decreased (P = 0.002), leading to a positive protein balance (P < 0.0001) in both groups. The increase in protein balance was greater in the epidural group compared with the patient-controlled analgesia group (P = 0.027).
Diabetic patients receiving an amino acid infusion after surgery achieved a positive protein balance without hyperglycemia. This anabolic effect was greater in patients receiving epidural analgesia compared with patient-controlled analgesia with intravenous morphine.
[show abstract][hide abstract] ABSTRACT: Malnutrition in surgical patients is associated with higher rates of morbidity and mortality. Nutrition support for perioperative and critically ill patients is still considered as a challenge and remains a controversial topic. In the high-risk populations of obese, diabetic and geriatric patients these concerns are even more emphasized. To adapt to their special needs, the management of nutrition support must carefully integrate data from current trials and guidelines. Clinical expertise not only in nutrition support but also in the illness or injury treated and the patient's profile is paramount. This review article discusses current strategies of perioperative nutrition support with special regard to obese, diabetic and geriatric patients.
[show abstract][hide abstract] ABSTRACT: We tested the hypothesis that perioperative amino acid supplementation of hypocaloric dextrose would attenuate the inhibitory effect of glucose on endogenous glucose production after surgery. Sixteen patients undergoing colorectal cancer surgery were randomly assigned to receive intravenous glucose either with or without amino acids. Nutrition was administered over 48 hours from surgical skin incision until the second postoperative day. Glucose provided 50% and amino acids 20% of the patient's measured resting energy expenditure. Glucose rate of appearance was assessed by [6,6-2H2]glucose before and after surgery. Circulating concentrations of glucose, lactate, insulin, and glucagon were also determined. Hypocaloric glucose suppressed postoperative endogenous glucose production to a similar degree in both groups. The circulating concentrations of glucose increased to the same extent, whereas there was no significant change in plasma concentrations of lactate, glucagon, and cortisol. Postoperative plasma levels of insulin were significantly higher in patients receiving amino acids (P = .009). Perioperative amino acid administration does not mitigate the inhibitory effect of glucose on glucose production or aggravate hyperglycemia after colorectal surgery.
[show abstract][hide abstract] ABSTRACT: Although capable of inducing an anabolic state after surgery, parenteral nutrition, including glucose, leads to hyperglycemia. Even moderate increases in blood glucose are associated with poor surgical outcome. We examined the hypothesis that amino acids, in the absence of glucose supply, spare protein while preventing hyperglycemia. In this prospective study, 14 patients with colonic cancer were randomly assigned to undergo a 6-hour stable isotope infusion study (3 hours of fasting followed by 3-hour infusions of amino acids, Travasol [Baxter, Montreal, Canada] 10% at 0.02 mL.kg(-1).min(-1), with or without glucose at 4 mg.kg(-1).min(-1)) on the second day after colorectal surgery. Protein breakdown, protein oxidation, protein balance, and glucose production were assessed by stable isotope tracer kinetics using l-[1-(13)C]leucine and [6,6-(2)H2]glucose. Circulating concentrations of glucose, cortisol, insulin, and glucagon were determined. The administration of amino acids increased protein balance from -16+/-4 micromol.kg(-1).h(-1) in the fasted state to 16+/-3 micromol.kg(-1).h(-1). Combined infusion of amino acids and glucose increased protein balance from -17+/-7 to 7+/-5 micromol.kg(-1).h(-1). The increase in protein balance during nutrition was comparable in the 2 groups (P=.07). Combined administration of amino acids and glucose decreased endogenous glucose production (P=.001) and stimulated insulin secretion (P=.001) to a greater extent than the administration of amino acids alone. Hyperglycemia (blood glucose, 10.1+/-1.9 micromol/L) occurred only in the presence of glucose infusion. In summary, excluding glucose from a short-term feeding protocol does not diminish the protein-sparing effect of amino acids and avoids hyperglycemia.
[show abstract][hide abstract] ABSTRACT: Severe acute pancreatitis is associated with high mortality. Adequate nutrition support improves clinical outcome. Nevertheless, several recent trials have focused primarily on the route of nutrition support and neglected the role of nutrition status assessment in tailoring nutrition support to individual needs.
[show abstract][hide abstract] ABSTRACT: The infusion of dextrose in patients receiving epidural and light general anesthesia or general anesthesia alone failed to achieve a positive protein balance. We sought to verify the hypothesis that nutritional supplementation with i.v. amino acids induced a greater protein balance in patients receiving epidural blockade compared with those receiving general anesthesia.
Sixteen patients were randomly assigned to receive either general anesthesia with desflurane (control group) or general anesthesia combined with epidural analgesia (EDA group). A primed constant infusion of stable isotope tracers L-[1-(13)C]leucine and [6,6-(2)H2]glucose was started after a 32-h fast before surgery, (3 h of fasted state), and continued for 3 h during surgery during which amino acids were infused i.v. (fed state).
Compared with the fasted state, the endogenous rate of appearance of leucine decreased to a similar extent in both groups, and protein synthesis increased, with no difference between the two groups. Leucine oxidation did not change in either group. After amino acids infusion, endogenous glucose production remained unchanged and glucose clearance decreased in both groups. Blood glucose, plasma cortisol, serum insulin, and glucagon concentrations increased to the same extent in both groups.
Epidural anesthesia provided no additional benefit beyond the anabolism obtained with amino acids.
Anesthesia and analgesia 01/2007; 103(6):1549-56. · 3.08 Impact Factor
[show abstract][hide abstract] ABSTRACT: The goal of the present study was to investigate whether epidural analgesia exerts a protein-sparing effect after colorectal surgery in the presence of hypocaloric glucose supply initiated with surgical skin incision.
We randomly allocated 10 patients to receive general anesthesia combined with epidural anesthesia with bupivacaine, followed by epidural analgesia using bupivacaine/fentanyl, and 10 patients to receive general anesthesia, followed by patient-controlled analgesia with intravenous morphine. All patients received a 48-hour infusion of glucose 10% from surgical skin incision until the second day after surgery. The glucose infusion rate provided 50% of the patient's resting energy expenditure. Kinetics of protein and glucose metabolism were assessed by a stable-isotope tracer technique (L-[1-(13)C]leucine and [6,6-(2)H(2)]glucose).
The rate of appearance of leucine increased in the intravenous-analgesia group (112 +/- 29 to 130 +/- 25 micromol/kg/h) 2 days after surgery, and this increase was more pronounced than in the epidural analgesia group (preoperative 120 +/- 24, postoperative 123 +/- 22 micromol/kg/h, P < .05). Leucine oxidation rate increased in the intravenous analgesia group from 17 +/- 8 to 23 +/- 8 micromol/kg/h and in the epidural group from 17 +/- 6 to 19 +/- 7 micromol/kg/h without the difference between the groups reaching statistical significance (P = .067). Nonoxidative leucine disposal remained unaltered in both groups. No differences in glucose metabolism were seen between the groups.
Epidural analgesia inhibits the increase in whole-body protein breakdown in patients receiving perioperative hypocaloric glucose infusion initiated with surgical skin incision. However, oxidative protein loss, protein synthesis, and glucose metabolism are not affected by epidural analgesia.
Regional Anesthesia and Pain Medicine 01/2007; 32(3):227-32. · 3.46 Impact Factor
[show abstract][hide abstract] ABSTRACT: Net loss of body protein is a prominent feature of the catabolic response to surgical tissue trauma. Epidural analgesia with hypocaloric dextrose has been demonstrated to attenuate leucine oxidation but was unable to make protein balance positive. The current study was set to determine whether an infusion of amino acids on the second day after colon surgery would revert the catabolic state and promote protein synthesis while maintaining glucose homeostasis in patients receiving epidural analgesia as compared with patient-controlled analgesia with morphine (PCA).
Sixteen patients undergoing colorectal surgery were randomly assigned to receive epidural blockade or PCA as analgesic techniques and underwent a 6-h stable isotope infusion study (3 h fasted, 3 h fed) on the second postoperative day. Whole body glucose kinetics and protein turnover were measured using [6,6-2H2]glucose and l-[1-13C]leucine as tracer.
The infusion of amino acids caused a decrease in endogenous glucose rate of appearance in both groups (P < 0.05), with greater changes in the PCA group (P < 0.05). Administration of amino acids suppressed the appearance of leucine from protein breakdown in both groups (P < 0.05), although the decrease was greater in the PCA group (P < 0.05). Leucine oxidation increased in both groups (P < 0.05), with greater change in the epidural group (P < 0.05). Protein synthesis increased to the same extent in both groups (P < 0.05). Protein balance became positive after the infusion of amino acids, and the effect was greater in the PCA group (P < 0.05).
Infusion of amino acids decreased the endogenous glucose production and induced a positive protein balance independent of the type of anesthesia provided, although such effects were greater in the PCA group.