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 [mu]mol[middle dot]kg-1[middle dot]min-1, P < 0.05; postoperative, epidural blockade 8.5 +/- 1.8 vs. control 10.5 +/- 1.2 [mu]mol[middle dot]kg-1[middle dot]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.     

Perioperative glucose infusion and the catabolic response to surgery: the effect of epidural block

Although the nitrogen-sparing properties of epidural block and i.v. glucose on the days after surgical trauma have been well established, their metabolic effects during the acute phase of the stress response remain unclear. Therefore, in this study we investigated the effect of epidural block on glucose and protein kinetics during and immediately after surgery in patients receiving i.v. glucose at 2 mg x kg(-1) x min(-1). Sixteen patients undergoing colorectal surgery received either general anesthesia with epidural block with bupivacaine (EDA; n = 8) or general anesthesia alone (control; n = 8). Glucose and protein kinetics were determined during and 2 h after the operation by stable isotope tracers [6,6-(2)H(2)]glucose and L-[1-(13)C]leucine. Plasma concentrations of glucose, insulin, cortisol, and glucagon were also determined. Epidural block attenuated the perioperative increase in plasma glucose concentration (P < 0.05). The rate of appearance of glucose (R(a) glucose) and endogenous glucose production (EGP) were slower in the EDA group than in control subjects during (R(a) glucose, EDA 13.2 +/- 1.0 versus control 15.3 +/- 1.8 micromol x kg(-1) x min(-1); P < 0.05; EGP, EDA 1.2 +/- 1.2 versus control 3.8 +/- 1.7 micromol x kg(-1) x min(-1); P < 0.05) and after the operation (P > 0.05). Whereas protein breakdown and amino acid oxidation decreased in both groups (P < 0.05), whole-body protein synthesis remained unchanged. Insulin levels increased with both anesthetic techniques (P < 0.05). Intraoperative plasma concentrations of cortisol and glucagon were smaller in the EDA group (P < 0.05). The intraoperative suppression of EGP by exogenous glucose was more pronounced in the presence of epidural block. However, epidural block failed to exert a protein-sparing effect during the acute phase of the stress response in patients receiving i.v. glucose.     

Understanding the mechanisms by which isoflurane modifies the hyperglycemic response to surgery.

We studied the effect of anesthesia on the kinetics of perioperative glucose metabolism by using stable isotope tracers. Twenty-three patients undergoing cystoprostatectomy were randomly assigned to receive epidural analgesia combined with general anesthesia (n = 8), fentanyl and midazolam anesthesia (n = 8), or inhaled anesthesia with isoflurane (n = 7). Whole-body glucose production and glucose clearance were measured before and during surgery. Glucose clearance significantly decreased during surgery independent of the type of anesthesia. Epidural analgesia caused a significant decrease in glucose production from 10.2 +/- 0.4 to 9.0 +/- 0.4 micromol. kg(-1). min(-1) (P < 0.05), whereas the plasma glucose concentration was not altered (before surgery, 5.0 +/- 0.2 mmol/L; during surgery, 5.2 +/- 0.1 mmol/L). Glucose production did not significantly change during fentanyl/midazolam anesthesia (before surgery, 10.5 +/- 0.5 micromol. kg(-1). min(-1); during surgery, 10.1 +/- 0.5 micromol. kg(-1). min(-1)), but plasma glucose concentration significantly increased from 4.8 +/- 0.1 mmol/L to 5.3 +/- 0.2 mmol/L during surgery (P < 0.05). Isoflurane anesthesia caused a significant increase in plasma glucose concentration (from 5.2 +/- 0.1 mmol/L to 7.2 +/- 0.5 mmol/L) and glucose production (from 10.8 +/- 0.5 micromol. kg(-1). min(-1) to 12.4 +/- 1.0 micromol. kg(-1). min(-1)) (P < 0.05). Epidural analgesia prevented the hyperglycemic response to surgery by a decrease in glucose production. The increased glucose plasma concentration during fentanyl/midazolam anesthesia was caused by a decrease in whole-body glucose clearance. The hyperglycemic response observed during isoflurane anesthesia was a consequence of both impaired glucose clearance and increased glucose production. Implications: Epidural analgesia combined with general anesthesia prevented the hyperglycemic response to surgery by decreasing endogenous glucose production.The increased glucose plasma concentration in patients receiving fentanyl/midazolam anesthesia was caused by a decrease in whole-body glucose clearance. The hyperglycemic response observed during inhaled anesthesia with isoflurane was a consequence of both impaired glucose clearance and increased glucose production.     

The anabolic effect of epidural blockade requires energy and substrate supply

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.     

Effect of epidural blockade on protein, glucose, and lipid metabolism in the fasted state and during dextrose infusion in volunteers

BACKGROUND: To interpret correctly the results from studies performed during surgery and anesthesia it is necessary to dissect the separate effect of the anesthetic technique itself. The purpose of this study was to investigate the metabolic effects of epidural blockade (T7-S1) with bupivacaine 0.25% after 12 h fasting and during administration of 4 mg x kg(-1) x min(-1) dextrose in six healthy volunteers. METHODS: Each volunteer was assigned to randomly undergo a 6-h multiple stable isotope infusion study (3 h fasted, 3 h dextrose infusion) with or without epidural blockade. L-[1-13C]leucine, [6,6-2H2]glucose, and [1,1,2,3,3-2H5]glycerol were infused to measure protein synthesis, breakdown, and amino acid oxidation; glucose production and clearance; and lipolysis. Plasma concentrations of glucose, lactate, glycerol, free fatty acids, insulin, and glucagon were determined. RESULTS: Epidural blockade with bupivacaine had no influence on protein oxidation, breakdown and synthesis, glucose production, glucose clearance and lipolysis in the fasted state. Plasma concentrations of metabolic substrates and hormones also were not affected. Dextrose infusion significantly increased glucose clearance and plasma concentrations of glucose and insulin, while endogenous glucose production and lipolysis decreased to a similar degree in both groups. Protein synthesis, breakdown, and oxidation did not change during dextrose infusion. CONCLUSIONS: Epidural blockade with bupivacaine in the absence of surgery has no effect on fasting protein, glucose, and lipid metabolism. Epidural blockade does not modify the inhibitory influence of dextrose administration on endogenous glucose production and lipolysis.     

Epidural blockade suppresses lipolysis during major abdominal surgery

BACKGROUND AND OBJECTIVES: The purpose of the study was to investigate the effect of thoracic epidural administration of local anesthetic, i.e., epidural block on perioperative lipolysis. METHODS: Fourteen patients undergoing elective colorectal surgery were randomly assigned to receive either general anesthesia combined with epidural block (EDA, n = 7) or general anesthesia alone (control, n = 7). The rates of glycerol appearance (R(a) glycerol), i.e., lipolysis, were assessed by the stable isotope tracer [1,1,2,3,3-(2)H(5)]glycerol before, during, and 2 hours after the operation. Plasma concentrations of metabolic substrates (glycerol, free fatty acids [FFA], lactate) and hormones (insulin, glucagon, cortisol) were also determined. RESULTS: In the EDA group, R(a) glycerol decreased to lower intra- and postoperative values than in the control group (P <.05). Perioperative plasma concentrations of glycerol, FFA, lactate, and insulin remained unaltered with both anesthetic techniques. Intraoperative plasma glucagon and cortisol concentrations were lower in the EDA group than in the control group (P <.05). CONCLUSIONS: Epidural block suppresses lipolysis during and 2 hours after major abdominal surgery without affecting plasma glycerol or FFA concentrations.     

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.     

The Anabolic Effect of Epidural Blockade Requires Energy and Substrate Supply

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 [middle dot] kg-1 [middle dot] min-1 glucose) and amino acids (0.02 ml [middle dot] kg-1 [middle dot] min-1 Travasol(TM) 10%, equivalent to approximately 2.9 g [middle dot] kg-1 [middle dot] 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-[1-13C]leucine and [6,6-2H2]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 [mu]mol [middle dot] kg-1 [middle dot] h-1) and by 4% in the patient-controlled analgesia group (from 90.0 +/- 27.1 to 92.9 +/- 14.8 [mu]mol [middle dot] kg-1 [middle dot] h-1;P = 0.054).     

The anticatabolic effect of neuraxial blockade after hip surgery

Although the protein-sparing effect of neuraxial blockade after abdominal surgery is well established, its metabolic effect after operations on the lower extremities remains unclear. In this study, we tested the hypothesis that combined spinal and epidural blockade (CSE) inhibits amino acid oxidation after hip surgery. Sixteen patients undergoing hip replacement surgery received either general anesthesia followed by IV patient-controlled analgesia with piritramide (control; n = 8) or CSE using bupivacaine 0.5% for spinal anesthesia and ropivacaine 0.2% with 0.5 microg/mL of sufentanil for postoperative epidural analgesia (CSE; n = 8). Glucose and protein kinetics were assessed by stable isotope tracer technique ([6,6-2H2]glucose, L-[1-13C]leucine) on the day before and one day after surgery. Plasma concentrations of glucose, lactate, free fatty acids, cortisol, glucagon, and insulin were also determined. CSE prevented the increase in plasma glucose concentration during and immediately after the operation (60 min after skin incision: CSE 4.9 +/- 0.7 versus control 6.2 +/- 0.7 mmol/L; P < 0.05; postanesthesia care unit: CSE 5.0 +/- 0.9 versus control 7.3 +/- 1.1 mmol/L; P < 0.05). Intraoperative cortisol plasma concentrations were smaller in the CSE group than in the control group. One day after the operation, however, glucose plasma concentration, glucose production, and glucose clearance were comparable in both groups. CSE inhibited the postoperative increase in leucine oxidation rate (CSE 30 +/- 12 versus control 43 +/- 8 micromol.kg(-1).h(-1); P < 0.05). There were no differences between the groups in protein breakdown, whole body protein synthesis, and plasma concentrations of lactate, free fatty acids, insulin, and glucagon. In conclusion, CSE prevents hyperglycemia during hip surgery and inhibits protein catabolism thereafter. IMPLICATIONS: We studied the effect of combined spinal/epidural blockade (CSE) on protein and glucose metabolism during and after hip surgery. In comparison to general anesthesia followed by intravenous patient-controlled analgesia, CSE inhibits the increase in glucose plasma concentration during surgery and prevents protein loss on the first postoperative day.     

Intraoperative epidural blockade prevents the increase in protein breakdown after abdominal surgery

BACKGROUND: The aim of this study was to investigate the effect of epidural blockade with bupivacaine, restricted to the intraoperative period, on protein catabolism after major abdominal surgery. METHODS: Fourteen patients undergoing cystoprostatectomy were randomly assigned to receive either general anaesthesia with isoflurane (control group, n=7) or a combination of general anaesthesia and epidural blockade with bupivacaine from segment T4 to S5 (epidural group, n=7). Rates of urea (Ra urea) and glucose production (Ra glucose) were measured three days before and three days after the operation using stable isotope tracers ([15N2]urea, [6,6-2H2]glucose). Protein breakdown was calculated from the urea production rate. Plasma concentrations of metabolic substrates (urea, glucose, lactate, glycerol, amino acids) and hormones (insulin, glucagon, cortisol, adrenaline, noradrenaline) were also determined. RESULTS: Protein breakdown significantly increased after surgery in the control group (P<0.05), while it remained unaltered in the epidural group (control; 66 (54-76), epidural; 43 (29-58) mg x kg(-1) x h(-1), P<0.05, median (range)). Glucose plasma concentration and Ra glucose increased in both groups to a similar extent (P<0.05). Plasma concentration of branched chain amino acids decreased after epidural analgesia to a value significantly lower than in the control group (P<0.05). Glutamine plasma concentration decreased in the control group (P<0.05), but did not change in the epidural group. There were no differences in plasma concentrations of insulin, cortisol and catecholamines between the two groups. Glucagon plasma concentration in the epidural group was significantly lower than in the control group (P<0.05). CONCLUSION: Intraoperative epidural blockade inhibits the increase in protein breakdown after abdominal surgery.     

Small-dose S(+)-ketamine reduces postoperative pain when applied with ropivacaine in epidural anesthesia for total knee arthroplasty

Reduction of nociceptive input through blockade of N-methyl-D-aspartate (NMDA) receptors has been reported. We compared the effects of epidural S(+)-ketamine versus placebo on postoperative pain in a randomized, double-blinded study in 37 patients undergoing unilateral knee arthroplasty. After lumbar epidural anesthesia with ropivacaine (10 mg/mL, 10-20 mL), 19 patients received 0.9% epidural saline, and 18 patients received 0.25 mg/kg epidural S(+)-ketamine 10 min before surgical incision. After surgery, patient-controlled epidural analgesia with ropivacaine was provided. During the first 8 h after surgery, visual analog scale pain rating was similar between groups. Twenty-four and 48 h after surgery, patients anesthetized with ropivacaine had higher visual analog scale ratings at rest and during movement (P < 0.05) than patients anesthetized with S(+)-ketamine and ropivacaine. Forty-eight hours after surgery, patients anesthetized with ropivacaine also consumed more ropivacaine (558 +/- 210 mg) (P < 0.01) than those anesthetized with S(+)-ketamine and ropivacaine (319 +/- 204 mg). Adverse events were similar between groups. Patients who received S(+)-ketamine and ropivacaine rated the quality of their pain therapy better than those who received ropivacaine alone (P < 0.05). We conclude that the combination of S(+)-ketamine and ropivacaine in epidural anesthesia increases postoperative pain relief when compared with ropivacaine. IMPLICATIONS: Epidural S(+)-ketamine applied with ropivacaine before surgery is a rational approach to decrease injury-induced pain sensitization. Epidural blockade with an N-methyl-D-aspartate receptor antagonist and a local anesthetic may provide better analgesia in the postoperative period than a local anesthetic alone.     

Laparoscopic-assisted vaginal hysterectomy and the hyperglycemic response to surgery: an observational study

PURPOSE: To test the hypothesis that laparoscopic-assisted vaginal hysterectomy (LAVH) attenuates the hyperglycemic response to surgery when compared to vaginal hysterectomy (VH). METHODS: Fourteen patients received either LAVH (n=7) or VH (n=7). Whole body glucose production was measured before and three hours after surgery using [6.6-2H2] glucose. Before, during and after the operation, plasma concentrations of glucose, insulin, glucagon, cortisol, epinephrine and norepinephrine were determined. RESULTS: Plasma glucose concentration increased in both groups during and after surgery showing a significantly higher value after VH than after LAVH (VH: 8.3 +/- 1.4 mmol x L(-1); LAVH: 6.6 +/- 0.9 mmol x L(-1), P <0.05). The postoperative increase in glucose production was comparable in both groups. While plasma concentrations of insulin and glucagon remained unchanged, intra- and postoperative plasma cortisol concentrations were significantly higher in the VH group than in the LAVH group. Plasma catecholamine concentrations significantly increased after both types of surgery to the same extent. CONCLUSION: In this observational study, LAVH appears to blunt the hyperglycemic and cortisol response to surgery when compared to VH.     

Effect of Epidural Blockade on Protein, Glucose, and Lipid Metabolism in the Fasted State and during Dextrose Infusion in Volunteers

Background: To interpret correctly the results from studies performed during surgery and anesthesia it is necessary to dissect the separate effect of the anesthetic technique itself. The purpose of this study was to investigate the metabolic effects of epidural blockade (T7-S1) with bupivacaine 0.25% after 12 h fasting and during administration of 4 mg [middle dot] kg-1 [middle dot] min-1 dextrose in six healthy volunteers.

Methods: Each volunteer was assigned to randomly undergo a 6-h multiple stable isotope infusion study (3 h fasted, 3 h dextrose infusion) with or without epidural blockade. L-[1-13C]leucine, [6,6-2H2]glucose, and [1,1,2,3,3-2H5]glycerol were infused to measure protein synthesis, breakdown, and amino acid oxidation; glucose production and clearance; and lipolysis. Plasma concentrations of glucose, lactate, glycerol, free fatty acids, insulin, and glucagon were determined.

Results: Epidural blockade with bupivacaine had no influence on protein oxidation, breakdown and synthesis, glucose production, glucose clearance and lipolysis in the fasted state. Plasma concentrations of metabolic substrates and hormones also were not affected. Dextrose infusion significantly increased glucose clearance and plasma concentrations of glucose and insulin, while endogenous glucose production and lipolysis decreased to a similar degree in both groups. Protein synthesis, breakdown, and oxidation did not change during dextrose infusion.     

Regional postprandial fatty acid metabolism in different obesity phenotypes.

To examine if postprandial splanchnic/hepatic free fatty acid (FFA) delivery is increased in upper-body (UB) obesity, and to determine the adipose tissue depots responsible for the greater postprandial FFA availability, we measured systemic and regional uptake and release of FFAs ([1-(14)C]palmitate) before and during a 5-h frequent-feeding mixed meal in eight UB and eight lower-body (LB) obese women. Postabsorptive FFA flux and splanchnic FFA delivery were not different in UB and LB obese women; however, postprandial FFA concentrations (257 +/- 45 vs. 81 +/- 12 micromol/l, P < 0.0001), FFA flux (8.5 +/- 1.2 vs. 3.9 +/- 0.8 micromol x kg(-1) fat-free mass x min(-1), P < 0.0001), splanchnic FFA delivery (275 +/- 45 vs. 88 +/- 24 micromol/min, respectively, P < 0.005), and estimated hepatic FFA delivery were greater in UB than LB obese women. Nonsplanchnic UB adipose tissue FFA release was greater in UB than in LB obese women (276 +/- 71 vs. 97 +/- 37 micromol/min, respectively, P < 0.05) and accounted for the greater postprandial FFA availability in UB obesity. Postprandial leg glucose uptake was less in UB than in LB obese women (8.4 +/- 5.1 vs. 22.9 +/- 2.6 micromol x kg(-1) leg fat-free mass x min(-1), P < 0.05). We conclude that the elevated postprandial FFA release observed in UB obese women originates from the nonsplanchnic UB fat, not visceral fat. These results suggest that visceral fat may be a marker for, but not the source of, excess postprandial FFAs in obesity.     

A randomized controlled trial of the anticatabolic effect of epidural analgesia and hypocaloric glucose

BACKGROUND AND OBJECTIVES: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.     

Low dose clonidine premedication accentuates the hyperglycemic response to surgery

PURPOSE: To investigate the influence of low dose clonidine premedication on perioperative glucose homeostasis. METHODS: Sixteen patients undergoing abdominal hysterectomy for benign uterine myoma were randomly assigned to receive either iv clonidine (1 microg x kg(-1)) 30 min before induction of general anesthesia (clonidine, n=8) or saline (control, n=8). Plasma concentrations of glucose, insulin, cortisol, epinephrine and norepinephrine were measured before, during and two hours after surgery. At the same time heart rate, mean arterial pressure and cardiac output were recorded. RESULTS: In both groups, glucose concentrations significantly increased during and after surgery. Intraoperative glucose plasma concentration in the clonidine group was higher than in the control group (clonidine: 6.8 +/- 0.6 mmol x L(-1) vs control: 5.7 +/- 0.8 mmol x L(-1), P < 0.05). This was accompanied by a lower insulin plasma concentration (clonidine: 3.9 +/- 1.9 microU x mL(-1) vs control: 6.5 +/- 2.8 microU x mL(-1), P <0.05). Heart rate, mean arterial pressure and cardiac output remained unchanged throughout the study period without any differences between the groups. While norepinephrine plasma concentrations increased in the control group only (P <0.05), the plasma concentrations of epinephrine and cortisol increased in both groups (P <0.05). Clonidine significantly attenuated the cortisol response as reflected by lower intra- and postoperative cortisol plasma concentrations than in the control group (P <0.05). CONCLUSION: Premedication with clonidine 1 microg x kg(-1) accentuates the hyperglycemic response to lower abdominal surgery caused by the decrease in insulin plasma concentrations.     

Postoperative infusion of amino acids induces a positive protein balance independently of the type of analgesia used

BACKGROUND: 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). METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.     

Direct and indirect effects of insulin on glucose uptake and storage by the liver

Studies were conducted in conscious 42-h-fasted dogs to determine how much of insulin's effect on hepatic glucose uptake arises from its direct hepatic action versus its indirect (extrahepatic) action. Each experiment consisted of equilibration, basal, and experimental periods. During the latter, somatostatin, basal intraportal glucagon, portal glucose (21.3 micromol x kg(-1) x min(-1)), and peripheral glucose (to double the hepatic glucose load) were infused. During the experimental period, insulin was infused intraportally at a basal rate (BI, n = 6), at a fourfold basal rate (PoI, n = 6), or via a peripheral vein to create a selective increase in the arterial insulin level similar to that in PoI (PeI, n = 6). Arterial and hepatic sinusoidal insulin levels (in picomoles per liter) during the experimental period were 31 +/- 5 and 113 +/- 15 in BI, 97 +/- 11 and 394 +/- 66 in PoI, and 111 +/- 13 and 96 +/- 9 in PeI, respectively. Net hepatic glucose uptake (NHGU) averaged 7.0 +/- 1.1 micromol x kg(-1) x min(-1), 15.7 +/- 2.7 micromol x kg(-1) x min(-1) (P < 0.05 vs. BI), and 12.0 +/- 2.4 micromol x kg(-1) x min(-1) (P < 0.05 vs. BI) in BI, PoI, and PeI, respectively. Net hepatic carbon retention was 4.4 +/- 1.2 micromol glucose equivalents. kg(-1) x min(-1), 12.3 +/- 2.5 micromol glucose equivalents x kg(-1) x min(-1) (P < 0.05 vs. BI, P < 0.05 vs. PeI), and 7.1 +/- 1.0 micromol glucose equivalents x kg(-1) x min(-1) (P < 0.05 vs. BI) in BI, PoI, and PeI, respectively. Both direct and indirect insulin actions increase NHGU, but the rise in hepatic sinusoidal insulin appears critical for efficient storage of glucose as hepatic glycogen.     

Time of peritoneal cavity exposure influences postoperative glucose production

PURPOSE: To examine the effect of the duration of peritoneal cavity exposure on glucose metabolism after abdominal surgery. METHODS: In eight otherwise healthy patients (ASA 1) with uterine myoma, endogenous glucose production (Ra glucose) was measured immediately before and two hours after abdominal hysterectomy by a stable isotope dilution technique using primed continuous infusions of [6,6-2H2]-glucose. Plasma concentrations of glucose, lactate, insulin, glucagon, cortisol, epinephrine and norepinephrine were determined before, during (5 and 60 min after peritoneal incision, skin closure) and two hours after surgery. Pre- and postoperative glucose clearance was calculated as Ra glucose divided by plasma glucose concentration. RESULTS: Ra glucose increased from 11.8 +/- 1.2 to 16.8 +/- 3.2 micromol x kg(-1) x min(-1) two hours after hysterectomy (P < 0.05) with a correlation between the degree of increase and the time of peritoneal cavity exposure (r = 0.859, P = 0.006). Plasma glucose concentration increased after surgery from 4.7 +/- 0.8 to 8.3 +/- 1.9 mmol x l(-1) (P < 0.05), while glucose clearance decreased from 2.6 +/- 0.4 to 2.1 +/- 0.4 ml x kg(-1) x min(-1) (P < 0.05). Plasma concentrations of cortisol and catecholamines increased after hysterectomy (cortisol from 6 +/- 2 to 31 +/- 7 microg x dl(-1), epinephrine from 25 +/- 14 to 205 +/- 132 pg x ml(-1), norepinephrine from 182 +/- 82 to 377 +/- 132 pg x ml(-1), P < 0.05), whereas plasma lactate, insulin and glucagon concentrations remained unchanged. CONCLUSION: The magnitude of increase of glucose production after abdominal hysterectomy is associated with the duration of peritoneal cavity exposure.     

Postoperative Infusion of Amino Acids Induces a Positive Protein Balance Independently of the Type of Analgesia Used

Background: 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).

Methods: 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.

Results: 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).