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).     

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.     

Acute Pain Induces Insulin Resistance in Humans

Background: Painful trauma results in a disturbed metabolic state with impaired insulin sensitivity, which is related to the magnitude of the trauma. The authors explored whether pain per se influences hepatic and extrahepatic actions of insulin.

Methods: Ten healthy male volunteers underwent two randomly sequenced hyperinsulinemic-euglycemic (insulin infusion rate, 0.6 mU [middle dot] kg-1 [middle dot] min-1 for 180 min) clamp studies 4 weeks apart. Self-controlled painful electrical stimulation was applied to the abdominal skin for 30 min, to a pain intensity of 8 on a visual analog scale of 0-10, just before the clamp procedure (study P). In the other study, no pain was inflicted (study C).

Results: Pain reduced whole-body insulin-stimulated glucose uptake from 6.37 +/- 1.87 mg [middle dot] kg-1 [middle dot] min-1 (mean +/- SD) in study C to 4.97 +/- 1.38 mg [middle dot] kg-1 [middle dot] min-1 in study P (P < 0.01) because of a decrease in nonoxidative glucose disposal, as determined by indirect calorimetry (2.47 +/- 0.88 mg [middle dot] kg-1 [middle dot] min-1 in study P vs. 3.41 +/- 1.03 mg [middle dot] kg-1 [middle dot] min-1 in study C;P < 0.05). Differences in glucose oxidation rates were not statistically significant. The suppression of isotopically determined endogenous glucose output during hyperinsulinemia tended to be decreased after pain (1.67 +/- 0.48 mg [middle dot] kg-1 [middle dot] min-1 in study P vs. 2.04 +/- 0.45 mg [middle dot] kg-1 [middle dot] min-1 in study C;P = 0.06). Pain elicited a twofold to threefold increase in serum cortisol (P < 0.01), plasma epinephrine (P < 0.05), and serum free fatty acids (P < 0.05). Similarly, circulating concentrations of glucagon and growth hormone tended to increase during pain.     

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.     

Remifentanil Requirements during Sevoflurane Administration to Block Somatic and Cardiovascular Responses to Skin Incision in Children and Adults

Background: The authors found no studies comparing intraoperative requirements of opioids between children and adults, so they determined the infusion rate of remifentanil to block somatic (IR50) and autonomic response (IRBAR50) to skin incision in children and adults.

Methods: Forty-one adults (aged 20-60 yr) and 24 children (aged 2-10 yr) undergoing lower abdominal surgery were studied. In adults, anesthesia induction was with sevoflurane during remifentanil infusion, whereas in children remifentanil administration was started after induction with sevoflurane. After intubation, sevoflurane was administered in 100% O2 and was adjusted to an ET% of 1 MAC-awake corrected for age at least 15 min before surgery. Patients were randomized to receive remifentanil at a rate ranging from 0.05 to 0.35 [mu]g [middle dot] kg-1 [middle dot] min-1 for at least 20 min before surgery. At the beginning of surgery, only the skin incision was performed, and the somatic and autonomic responses were observed. The somatic response was defined as positive with any gross movement of extremity, and the autonomic response was deemed positive with any increase in heart rate or mean arterial pressure equal to or more than 10% of preincision values. Using logistic regression, the IR50 and IRBAR50 were determined in both groups of patients and compared with unpaired Student t test. A P value less than 0.05 was considered significant.

Results: The IR50 +/- SD was 0.10 +/- 0.02 [mu]g [middle dot] kg-1 [middle dot] min-1 in adults and 0.22 +/- 0.03 [mu]g [middle dot] kg-1 [middle dot] min-1 in children (P < 0.001). The IRBAR50 +/- SD was 0.11 +/- 0.02 [mu]g [middle dot] kg-1 [middle dot] min-1 in adults and 0.27 +/- 0.06 [mu]g [middle dot] kg-1 [middle dot] min-1 in children (P < 0.001).     

Comparison of Adenosine and Remifentanil Infusions as Adjuvants to Desflurane Anesthesia

Background: Because adenosine has been alleged to produce both anesthetic and analgesic sparing effects, a randomized, double-blinded study was designed to compare the perioperative effects of adenosine and remifentanil when administered as intravenous adjuvants during general anesthesia for major gynecologic procedures.

Methods: Thirty-two women were assigned randomly to one of two drug treatment groups. After premedication with 0.04 mg/kg intravenous midazolam, anesthesia was induced with 2 [micro sign]g/kg intravenous fentanyl, 1.5 mg/kg intravenous propofol, and 0.6 mg/kg intravenous rocuronium, and maintained with desflurane, 2%, and nitrous oxide, 65%, in oxygen. Before skin incision, an infusion of either remifentanil (0.02 [micro sign]g [middle dot] kg-1 [middle dot] min-1) or adenosine (25 [micro sign]g [middle dot] kg-1 [middle dot] min-1) was started and subsequently titrated to maintain systolic blood pressure, heart rate, or both within 10-15% of the preincision values.

Results: Adenosine and remifentanil infusions were effective anesthetic adjuvants during lower abdominal surgery. Use of adenosine (mean +/- SEM, 166 +/- 17 [micro sign]g [middle dot] kg-1 [middle dot] min-1) was associated with a significantly greater decrease in systolic blood pressure and higher heart rate values compared with remifentanil (mean +/- SEM, 0.2 +/- 0.03 [micro sign]g [middle dot] kg-1 [middle dot] min-1). Total postoperative opioid analgesic use was 45% and 27% lower in the adenosine group at 0-2 h and 2-24 h after surgery, respectively.     

Narcotrend Monitoring Allows Faster Emergence and a Reduction of Drug Consumption in Propofol-Remifentanil Anesthesia

Background: The Narcotrend is a new electroencephalographic monitor designed to measure depth of anesthesia, based on a six-letter classification from A (awake) to F (increasing burst suppression) including 14 substages. This study was designed to investigate the impact of Narcotrend monitoring on recovery times and propofol consumption in comparison to Bispectral Index(R) (BIS(R)) monitoring or standard anesthetic practice.

Methods: With institutional review board approval and written informed consent, 120 adult patients scheduled to undergo minor orthopedic surgery were randomized to receive a propofol-remifentanil anesthetic controlled by Narcotrend, by BIS(R), or solely by clinical parameters. Anesthesia was induced with 0.4 [mu]g [middle dot] kg-1 [middle dot] min-1 remifentanil and a propofol target-controlled infusion at 3.5 [mu]g/ml. After intubation, remifentanil was reduced to 0.2 [mu]g [middle dot] kg-1 [middle dot] min-1, whereas the propofol infusion was adjusted according to clinical parameters or to the following target values: during maintenance to D0 (Narcotrend) or 50 (BIS(R)); 15 min before the end of surgery to C1 (Narcotrend) or 60 (BIS(R)). Recovery times were recorded by a blinded investigator, and average normalized propofol consumption was calculated from induction and maintenance doses.

Results: The groups were comparable for demographic data, duration of anesthesia, and mean remifentanil dosages. Compared with standard practice, patients with Narcotrend or BIS(R) monitoring needed significantly less propofol (standard practice, 6.8 +/- 1.2 mg [middle dot] kg-1 [middle dot] h-1vs. Narcotrend, 4.5 +/- 1.1 mg [middle dot] kg-1 [middle dot] h-1 or BIS(R), 4.8 +/- 1.0 mg [middle dot] kg-1 [middle dot] h-1;P < 0.001), opened their eyes earlier (9.3 +/- 5.2 vs. 3.4 +/- 2.2 or 3.5 +/- 2.9 min), and were extubated sooner (9.7 +/- 5.3 vs. 3.7 +/- 2.2 or 4.1 +/- 2.9 min).     

Critical Oxygen Delivery in Conscious Humans Is Less Than 7.3 ml O2 · kg-1 · min-1

Background: The "critical" level of oxygen delivery (DO2) is the value below which DO2 fails to satisfy the metabolic need for oxygen. No prospective data in healthy, conscious humans define this value. The authors reduced DO2 in healthy volunteers in an attempt to determine the critical DO2.

Methods: With Institutional Review Board approval and informed consent, the authors studied eight healthy, conscious volunteers, aged 19-25 yr. Hemodynamic measurements were obtained at steady state before and after profound acute isovolemic hemodilution with 5% albumin and autologous plasma, and again at the reduced hemoglobin concentration after additional reduction of DO2 by an infusion of a [beta]-adrenergic antagonist, esmolol.

Results: Reduction of hemoglobin from 12.5 +/- 0.8 g/dl to 4.8 +/- 0.2 g/dl (mean +/- SD) increased heart rate, stroke volume index, and cardiac index, and reduced DO2 (14.0 +/- 2.9 to 9.9 +/- 2.0 ml O2 [middle dot] kg-1 [middle dot] min-1; all P < 0.001). Oxygen consumption (VO2; 3.0 +/- 0.5 to 3.4 +/- 0.6 ml O2 [middle dot] kg-1 [middle dot] min-1;P < 0.05) and plasma lactate concentration (0.50 +/- 0.10 to 0.62 +/- 0.16 mM;P < 0.05; n = 7) increased slightly. Esmolol decreased heart rate, stroke volume index, and cardiac index, and further decreased DO2 (to 7.3 +/- 1.4 ml O2 [middle dot] kg-1 [middle dot] min-1; all P < 0.01 vs. before esmolol). VO2 (3.2 +/- 0.6 ml O2 [middle dot] kg-1 [middle dot] min-1;P > 0.05) and plasma lactate (0.66 +/- 0.14 mM;P > 0.05) did not change further. No value of plasma lactate exceeded the normal range.     

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.     

Cerebral Blood Flow and CO2 Reactivity Is Similar during Remifentanil/N2 O and Fentanyl/N2 O Anesthesia

Background: Remifentanil, a rapidly metabolized [micro sign]-opioid agonist, may offer advantages for neurosurgical procedures in which prolonged anesthetic effects can delay assessment of the patient. This study compared the effects of remifentanil-nitrous oxide on cerebral blood flow (CBF) and carbon dioxide reactivity with those of fentanyl-nitrous oxide anesthesia during craniotomy.

Methods: After institutional approval and informed patient consent were obtained, 23 patients scheduled to undergo supratentorial tumor surgery were randomly assigned to remifentanil or fentanyl infusion groups in a double-blinded manner. Midazolam, thiopental, and pancuronium induction was followed by equipotent narcotic loading infusions of remifentanil (1 [micro sign]g [middle dot] kg-1 [middle dot] min-1) or fentanyl (2 [micro sign]g [middle dot] kg-1 [middle dot] min-1) for 5-10 min. Patients were ventilated with 2:1 nitrous oxide-oxygen, and opioid rates were reduced and then titrated to a stable hemodynamic effect. After dural exposure, CBF was measured by the intravenous133 xenon technique at normocapnia and hypocapnia. Reactivity of CBF to carbon dioxide was calculated as the absolute increase in CBF per millimeters of mercury increase in the partial pressure of carbon dioxide (PaCO2). Data were analyzed by repeated-measures analysis of variance, unpaired Student's t tests, or contingency analysis.

Results: In the remifentanil group (n = 10), CBF decreased from 36 +/- 11 to 27 +/- 8 ml [middle dot] 100 g-1 [middle dot] min-1 as PaCO2 decreased from 33 +/- 5 to 25 +/- 2 mmHg. In the fentanyl group (n = 8), CBF decreased from 37 +/- 11 to 25 +/- 6 ml [middle dot] 100 g-1 [middle dot] min-1 as PaCO2 decreased from 34 +/- 3 to 25 +/- 3 mmHg. Absolute carbon dioxide reactivity was preserved with both agents: 1 +/- 1.2 ml [middle dot] 100 g-1 [middle dot] min-1 [middle dot] mmHg-1 for remifentanil and 1.5 +/- 0.5 ml [middle dot] 100 g-1 [middle dot] min-1 [middle dot] mmHg-1 for fentanyl (P = 0.318).     

Epidural Ropivacaine versus Epidural Morphine and the Catabolic Response to Colonic Surgery: Stable Isotope Kinetic Studies in the Fasted State and during Infusion of Glucose

Background: The authors examined the hypothesis that epidural administration of local anesthetic, in contrast to epidural analgesia with morphine, inhibits postoperative protein oxidation during administration of glucose.

Methods: Fourteen patients were randomly assigned to undergo a 6-h stable isotope infusion study (3 h fasted, 3 h feeding with 4 mg [middle dot] kg-1 [middle dot] min-1 glucose) on the second day after colorectal surgery using epidural analgesia with either continuous ropivacaine or intermittent morphine. Protein synthesis, breakdown and oxidation, and glucose production were measured by l-[1-13C]leucine and [6,6-2H2]glucose. Substrate oxidation rates were determined by indirect calorimetry. Plasma concentrations of metabolic substrates and hormones were also measured.

Results: Whole body protein breakdown, oxidation, synthesis, and glucose production in the fasted state were similar between the two groups. Glucose administration decreased protein breakdown (P = 0.01), protein synthesis (P = 0.001), and glucose production (P = 0.001) to the same extent in both groups, whereas protein oxidation was not significantly affected. The type of epidural analgesia did not significantly influence the circulating concentrations of metabolic substrates and hormones in the fasted or in the fed state. Carbohydrate oxidation rate in the ropivacaine group was greater than in patients receiving morphine (P = 0.04), regardless of whether glucose was infused.     

Effects of Mild Hypothermia on Blood-Brain Barrier Disruption during Isoflurane or Pentobarbital Anesthesia

Background: This study was performed to determine whether mild hypothermia (32[degrees]C) could attenuate the degree of blood-brain barrier (BBB) disruption caused by a hyperosmolar solution and whether the degree of disruption would vary depending on anesthetic agents.

Methods: Rats were assigned to one of four groups: normothermic isoflurane, normothermic pentobarbital, hypothermic isoflurane, and hypothermic pentobarbital. During isoflurane (1.4%; normothermic or hypothermic) or pentobarbital (50 mg/kg administered intraperitoneally; normothermic or hypothermic) anesthesia, the external carotid artery and the femoral artery and vein were catheterized. Body temperature was maintained at 37 and 32[degrees]C for the normothermic and hypothermic groups, respectively. To open the BBB, 25% mannitol was infused through the right carotid artery at the rate of 0.25 ml [middle dot] kg-1 [middle dot] s-1 for 30 s. The transfer coefficient of 14C-[alpha]-aminoisobutyric acid was determined.

Results: Blood pressure was similar among the four groups of animals. The degree of the BBB disruption by hyperosmolar mannitol was less with isoflurane than pentobarbital anesthesia in the normothermic groups (transfer coefficient: 29.9 +/- 17.1 and 50.4 +/- 17.5 [mu]l [middle dot] g-1 [middle dot] min-1 for normothermic isoflurane and pentobarbital, respectively;P < 0.05). Mild hypothermia decreased the BBB disruption during anesthesia with both anesthetic agents (hypothermic isoflurane: 9.8 +/- 8.3 [mu]l [middle dot] g-1 [middle dot] min-1, P < 0.05 vs. normothermic isoflurane; hypothermic pentobarbital: 30.2 +/- 13.9 [mu]l [middle dot] g-1 [middle dot] min-1, P < 0.05 vs. normothermic pentobarbital), but the disruption was less during isoflurane anesthesia (hypothermic isoflurane vs. hypothermic pentobarbital, P < 0.005). In the contralateral cortex, there were no significant differences among these four experimental groups.     

Effect of Dobutamine on Splanchnic Carbohydrate Metabolism and Amino Acid Balance after Cardiac Surgery

Background: As a predominant [beta]-adrenergic agonist, dobutamine may modify blood flow distribution and increase metabolic demands. The authors investigated the effect of a dobutamine-induced increase in cardiac output on splanchnic and femoral blood flow and metabolism in patients after cardiac surgery.

Methods: Seventeen stable patients were randomized to receive dobutamine or placebo (n = 8 per group, one dropout). After baseline measurement for systemic, splanchnic, and femoral blood flow (by dye dilution); oxygen consumption; gastric mucosal pressure of carbon dioxide (PCO2); total and splanchnic glucose production (by stable isotope tracer dilution); and regional lactate and amino acid balance, patients received either dobutamine, at a dosage (6 [mu]g [middle dot] kg-1min-1) sufficient to increase cardiac index by at least 25%, or placebo. A second set of measurements was performed 60 min after the start of dobutamine or placebo infusion.

Results: Dobutamine increased cardiac index (3.0 +/- 0.6 to 4.4 +/- 1.0 l [middle dot] min-1m-2, mean +/- SD;P< 0.05), splanchnic blood flow (from 0.8 +/- 0.2 to 1.0 +/- 0.2 l [middle dot] min-1m-2;P< 0.05), femoral blood flow (from 0.2 +/- 0.1 to 0.3 +/- 0.1 l [middle dot] min-1m-2;P< 0.05), and the arterial-gastric mucosal PCO2 gap (from 11.4 +/- 9.5 to 11.9 +/- 8.0 mmHg;P< 0.05). Dobutamine increased systemic oxygen consumption (from 132 +/- 14 to 146 +/- 13 ml [middle dot] min-1 [middle dot] m-2;P< 0.05) but not splanchnic or femoral oxygen consumption. Splanchnic glucose production and lactate and amino acid balance did not change.     

Low-dose Intravenous Ketamine Potentiates Epidural Analgesia after Thoracotomy

Background: Ketamine potentiates intravenous or epidural morphine analgesia. The authors hypothesized that very-low-dose ketamine infusion reduces acute and long-term postthoracotomy pain.

Methods: Forty-nine patients scheduled to undergo open thoracotomy were randomly assigned to receive one of two anesthesia regimens: continuous epidural infusion of ropivacaine and morphine, along with intravenous infusion of ketamine (0.05 mg [middle dot] kg-1 [middle dot] h-1 [approximately 3 mg/h], ketamine group, n = 24) or placebo (saline, control group, n = 25). Epidural analgesia was continued for 2 days after surgery, and infusion of ketamine or placebo was continued for 3 days. Pain was assessed at 6, 12, 24, and 48 h after surgery. Patients were asked about their pain, abnormal sensation on the wound, and inconvenience in daily life at 7 days and 1, 3, and 6 months after surgery.

Results: The visual analog scale scores for pain at rest and on coughing 24 and 48 h after thoracotomy were lower in the ketamine group than in the control group (pain at rest, 9 +/- 11 vs. 25 +/- 20 and 9 +/- 11 vs. 18 +/- 13; pain on coughing, 26 +/- 16 vs. 50 +/- 17 and 30 +/- 18 vs. 43 +/- 18, mean +/- SD; P = 0.002 and P = 0.01, P < 0.0001 and P = 0.02, respectively). The numerical rating scale scores for baseline pain 1 and 3 months after thoracotomy were significantly lower in the ketamine group (0.5 [0-4] vs. 2 [0-5] and 0 [0-5] vs. 1.5 [0-6], median [range], respectively; P = 0.02). Three months after surgery, a higher number of control patients were taking pain medication (2 vs. 9; P = 0.03).     

Sex Differences in Morphine-induced Ventilatory Depression Reside within the Peripheral Chemoreflex Loop

Background: This study gathers information in humans on the sites of sex-related differences in ventilatory depression caused by the [micro sign]-opioid receptor agonist morphine.

Methods: Experiments were performed in healthy young men (n = 9) and women (n = 7). Dynamic ventilatory responses to square-wave changes in end-tidal carbon dioxide tension (7.5-15 mmHg) and step decreases in end-tidal oxygen tension (step from 110 to 50 mmHg, duration of hypoxia 15 min) were obtained before and during morphine infusion (intravenous bolus dose 100 [micro sign]g/kg, followed by 30 [micro sign]g [middle dot] kg-1 [middle dot] h-1). Each hypercapnic response was separated into a fast peripheral and slow central component, which yield central (Gc) and peripheral (Gp) carbon dioxide sensitivities. Values are mean +/- SD.

Results: In carbon dioxide studies in men, morphine reduced Gc from 1.61 +/- 0.33 to 1.23 +/- 0.12 l [middle dot] mmHg-1 (P < 0.05) without affecting Gp (control, 0.41 +/- 0.16 and morphine, 0.49 +/- 0.12 l [middle dot] [middle dot] min-1 [middle dot] mmHg-1, not significant). In carbon dioxide studies in women, morphine reduced Gc, from 1.51 +/- 0.74 to 1.17 +/- 0.52 l [middle dot] min-1 [middle dot] mmHg-1 (P < 0.05), and Gp, from 0.54 +/- 0.19 to 0.39 +/- 0.22 l [middle dot] min-1 [middle dot] mmHg-1 (P < 0.05). Morphine-induced changes in Gc were equal in men and women; changes in Gp were greater in women. In hypoxic studies, morphine depressed the hyperventilatory response at the initiation of hypoxia more in women than in men (0.54 +/- 0.23 vs. 0.26 +/- 0.34 l [middle dot] min-1 [middle dot] %-1, respectively; P < 0.05). The ventilatory response to sustained hypoxia (i.e., 15 min) did not differ between men and women.     

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.     

Epidural Lidocaine Decreases Sevoflurane Requirement for Adequate Depth of Anesthesia as Measured by the Bispectral Index ® Monitor

Background: Epidural anesthesia potentiates sedative drug effects and decreases minimum alveolar concentration (MAC). The authors hypothesized that epidural anesthesia also decreases the general anesthetic requirements for adequate depth of anesthesia as measured by Bispectral Index (BIS).

Methods: After premedication with 0.02 mg/kg midazolam and 1 [mu]g/kg fentanyl, 30 patients aged 20-65 yr were randomized in a double-blinded fashion to receive general anesthesia with either intravenous saline placebo or intravenous lidocaine control (1-mg/kg bolus dose; 25 [mu]g [middle dot] kg-1 [middle dot] min-1). A matched group was prospectively assigned to receive epidural lidocaine (15 ml; 2%) with intravenous saline placebo. All patients received 4 mg/kg thiopental and 1 mg/kg rocuronium for tracheal intubation. After 10 min of a predetermined end-tidal sevoflurane concentration, BIS was measured. The ED50 of sevoflurane for each group was determined by up-down methodology based on BIS less than 50 (MACBIS50). Plasma lidocaine concentrations were measured.

Results: The MACBIS50 of sevoflurane (0.59% end tidal) was significantly decreased with lidocaine epidural anesthesia compared with general anesthesia alone (0.92%) or with intravenous lidocaine (1 %;P < 0.0001). Plasma lidocaine concentrations in the intravenous lidocaine group (1.9 [mu]g/ml) were similar to those in the epidural lidocaine group (2.0 [mu]g/ml).     

Remifentanil-induced Postoperative Hyperalgesia and Its Prevention with Small-dose Ketamine

Background: Remifentanil-induced secondary hyperalgesia has been documented experimentally in both animals and healthy human volunteers, but never clinically. This study tested the hypotheses that increased pain sensitivity assessed by periincisional allodynia and hyperalgesia can occur after relatively large-dose intraoperative remifentanil and that small-dose ketamine prevents this hyperalgesia.

Methods: Seventy-five patients undergoing major abdominal surgery were randomly assigned to receive (1) intraoperative remifentanil at 0.05 [mu]g [middle dot]kg-1 [middle dot]min-1 (small-dose remifentanil); (2) intraoperative remifentanil at 0.40 [mu]g [middle dot]kg-1 [middle dot]min-1 (large-dose remifentanil); or (3) intraoperative remifentanil at 0.40 [mu]g [middle dot]kg-1 [middle dot]min-1 and 0.5 mg/kg ketamine just after the induction, followed by an intraoperative infusion of 5 [mu]g [middle dot] kg-1 [middle dot] min-1 until skin closure and then 2 [mu]g [middle dot]kg-1 [middle dot]min-1 for 48 h (large-dose remifentanil-ketamine). Pain scores and morphine consumption were recorded for 48 postoperative hours. Quantitative sensory tests, peak expiratory flow measures, and cognitive tests were performed at 24 and 48 h.

Results: Hyperalgesia to von Frey hair stimulation adjacent to the surgical wound and morphine requirements were larger (P < 0.05) and allodynia to von Frey hair stimulation was greater (P < 0.01) in the large-dose remifentanil group compared with the other two groups, which were comparable. There were no significant differences in pain, pressure pain detection threshold with an algometer, peak flow, cognitive tests, or side effects.     

Optimal Adrenergic Support in Septic Shock Due to Peritonitis

Background: The authors evaluated optimal adrenergic support using norepinephrine, dopamine, and dobutamine in a clinically relevant model of septic shock.

Methods: Twenty-eight mature, female, anesthetized sheep (weight, 30.5 +/- 3.6 kg) underwent cecal ligation and perforation and were randomized into four groups of seven animals to be treated with norepinephrine, dopamine-norepinephrine, dobutamine-norepinephrine, or no adrenergic agent. In all groups, lactated Ringer's solution was administered to restore cardiac filling pressures to baseline. In the norepinephrine group, norepinephrine (0.5-5 [mu]g [middle dot] kg-1 [middle dot] min-1) was titrated to maintain mean arterial pressure between 75-85 mmHg. In the dopamine-norepinephrine group, dopamine was given first, and norepinephrine was added only when mean arterial pressure remained below 75 mmHg despite the infusion of 20 [mu]g [middle dot] kg-1 [middle dot] min-1 dopamine. In the dobutamine-norepinephrine group, dobutamine was started at the same time as norepinephrine and titrated up to 20 [mu]g [middle dot] kg-1 [middle dot] min-1 to get a 15% increase in cardiac output.

Results: The dobutamine-norepinephrine group had greater cardiac output; superior mesenteric blood flow, oxygen delivery (Do2), and oxygen consumption ([latin capital V with dot above]o2); and lower blood lactate concentration and partial pressure of carbon dioxide (Pco2) gap than the controls did. Cumulative urine output was significantly higher in the dobutamine-norepinephrine group than in the other groups. Survival time was significantly longer in the dobutamine-norepinephrine (24 +/- 4 h), dopamine- norepinephrine (24 +/- 6 h), and norepinephrine (20 +/- 1 h) groups than the control group (17 +/- 2 h;P < 0.05 vs. other groups), and significantly longer in the combined dopamine-norepinephrine and dobutamine-norepinephrine groups (24 +/- 5 h) than in the norepinephrine alone group (P < 0.05). Histologic examination of lung biopsies revealed less severe lesions in the dobutamine-norepinephrine group than in the control and norepinephrine alone groups. Anatomic alterations in the lung, liver, and small intestine were less severe in the dobutamine-norepinephrine group than in the other groups.     

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.