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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); P0.001). 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.

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.

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 H 2 ]glucose. Circulating concentrations of glucose, cortisol, insulin, and glucagon were determined. The administration of amino acids increased protein balance from −16 ± 4 μ mol · kg −1 · h −1 in the fasted state to 16 ± 3 μ mol · kg −1 · h −1 . Combined infusion of amino acids and glucose increased protein balance from −17 ± 7 to 7 ± 5 μ mol · 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 μ mol/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.

Background The authors tested the hypothesis that the catabolic responses to colorectal surgery are amplified in the presence of type 2 diabetes mellitus. Methods Seven nondiabetic and seven diabetic patients underwent a 6-h stable isotope infusion study (3 h fasted, 3-h glucose infusion at 4 mg . kg . min) on the second postoperative day. Leucine rate of appearance (Ra), leucine oxidation, nonoxidative leucine disposal, and glucose Ra were assessed by L-[1-C]leucine and [6,6-H2]glucose. Circulating concentrations of glucose, lactate, insulin, glucagon, and cortisol also were determined. Results Diabetic patients had a higher leucine oxidation than nondiabetic patients (P = 0.0003), whereas leucine Ra and nonoxidative leucine disposal were not different. Administration of glucose did not affect leucine kinetics regardless of whether patients were diabetic. In diabetic patients, glucose Ra was greater than in the nondiabetic group (P = 0.0032). Glucose infusion suppressed the endogenous glucose Ra to a lesser extent in diabetic than in nondiabetic patients (P = 0.0048). Plasma glucose concentrations were higher in diabetic than in nondiabetic patients (P = 0.0203), both in the postabsorptive and the fed state. Circulating concentrations of glucagon were higher (P = 0.0065) and concentrations of insulin were lower (P = 0.0146) in the presence of diabetes, resulting in a lower insulin/glucagon ratio (P = 0.0002). In diabetic patients, the insulin/glucagon ratio increased during glucose infusion to a lesser extent than in the nondiabetic group (P = 0.0014). Conclusion Protein catabolism after colorectal surgery is increased in patients with type 2 diabetes mellitus as reflected by an increased oxidative protein loss.

Purpose: To determine the effect of epidural analgesia on biochemical markers of stress, plasma oxytocin concentrations and frequency of uterine contractions during the first stage of labour. Methods: Nine nulliparous women, in spontaneous labour, with a singleton fetus and cervical dilatation < 5 cm were enrolled. Epidural bupivacaine 0.25% (range I 0 - 14 ml) was administered and bilateral sensory blockade to ice 0-8 - L4) achieved. Blood samples were collected before the epidermal block and every I0 min for one hour after the block was achieved for the measurement of plasma beta-endorphin, cortical, glucose, lactate and oxytocin concentrations. No exogenous oxytocin was given. Intensity of pain was assessed at the time of the blood sampling using a I0 cm visual analogue scale (VAS). The frequency of uterine contractions was recorded for 60 rain before and after the epidural block. Results: There was a decrease in plasma beta-endorphin and cortisol concentrations after epidural block (P < 0.01). There were no changes in plasma glucose and lactate concentrations. The mean VAS for pain decreased I0 rain after epidural block was achieved and remained < 2 throughout the study period (P < 0.001 ). Mean plasma oxytocin concentrations did not change. The frequency of uterine contractions before and after the epidural block was similar. Condusions: The metabolic stress response to the pain of labour was attenuated by epidural analgesia. In contrast, plasma oxytocin concentration and frequency of uterine contractions were unaffected by the attenuation of metabolic stress response. Object~ : D&erminer reffet de l'analg&ie p&idurale sur les marqueurs biochimiques de stress, les concentrations plasmatiques d'oxytocine et la frdquence des contractions ut&ines pendant le premier stade du travail.

Background The authors examined the hypothesis that continuous thoracic epidural blockade with local anesthetic and opioid, in contrast to patient-controlled intravenous analgesia with morphine, stimulates postoperative whole body protein synthesis during combined provision of energy (4 mg x kg(-1) x min(-1) glucose) and amino acids (0.02 ml x kg(-1) x min(-1) Travasol 10%, equivalent to approximately 2.9 g x kg(-1) x day(-1)). Methods Sixteen patients were randomly assigned to undergo a 6-h stable isotope infusion study (3 h fasted, 3 h feeding) on the second day after colorectal surgery performed with or without perioperative epidural blockade. Protein synthesis, breakdown and oxidation, glucose production, and clearance were measured by L-[1-(13)C]leucine and [6,6-(2)H(2) ]glucose. Results Epidural blockade did not affect protein and glucose metabolism in the fasted state. Parenteral alimentation decreased endogenous protein breakdown and glucose production to the same extent in both groups. Administration of glucose and amino acids was associated with an increase in whole body protein synthesis that was modified by the type of analgesia, i.e., protein synthesis increased by 13% in the epidural group (from 93.3 +/- 16.6 to 104.5 +/- 11.1 micromol x kg(-1) x h(-1) ) and by 4% in the patient-controlled analgesia group (from 90.0 +/- 27.1 to 92.9 +/- 14.8 micromol x kg(-1) x h(-1);P = 0.054). Conclusions Epidural blockade accentuates the stimulating effect of parenteral alimentation on whole body protein synthesis.

Background Mild hypothermia is accompanied by metabolic changes. Epidural local anesthetic agents attenuate the surgical stress response, but it is not known whether they modulate thermal stress. Methods Thirty patients undergoing colorectal surgery, performed by one surgical team, received epidural 0.5% bupivacaine to achieve T3-S5 sensory block. They were then assigned randomly to two groups of 15 patients each. The control or unwarmed group was left to cool during surgery, whereas active warming was used in the warmed group. General anesthesia was induced by thiopentone, vecuronium, fentanyl, nitrous oxide in oxygen, and enflurane. At the end of surgery, both groups received epidural 0.25% bupivacaine to maintain a T5-L3 sensory block. Aural canal (core) and skin surface (15 sites) temperatures; oxygen consumption; pain visual analogue score; and concentrations of epinephrine, norepinephrine, glucose, cortisol, lactate, and free fatty acids in plasma were measured before epidural blockade, 30 min after epidural blockade, at the end of surgery, and for 4 h after surgery. Patients and those measuring the outcomes were unaware of group allocation. Results Core and mean skin temperatures decreased significantly in the control group (P < 0.001) but not in the warmed group. Catecholamine concentrations in plasma decreased significantly after epidural block, and although concentration of epinephrine in plasma increased from baseline sharply in the control group at the end of surgery (P = 0.004), it decreased in the warmed group (P = 0.007). During recovery, there was no difference between the two groups for norepinephrine concentrations in plasma, body weight-adjusted oxygen consumption, pain visual analogue score, and metabolites. Conclusions The postoperative metabolic changes obtained with epidural block were similar except for an attenuated concentration of epinephrine in normothermic patients compared with those who were mildly hypothermic.