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Biomedical subjects

Andrea Kurz

Publications and source records attributed to Andrea Kurz.

At least 19 recordsLinked to original sources

Mild hypercapnia increases subcutaneous and colonic oxygen tension in patients given 80% inspired oxygen during abdominal surgery.

BACKGROUND: Supplemental perioperative oxygen increases tissue oxygen tension and decreases incidence of wound infection in colorectal surgery patients. Mild intraoperative hypercapnia also increases subcutaneous tissue oxygen tension. However, the effect of hypercapnia in patients already receiving supplemental oxygen is unknown, as is the effect of mild hypercapnia on intestinal oxygenation in humans-although the intestines are presumably the tissue of interest for colon surgeries. The authors tested the hypothesis that mild intraoperative hypercapnia increases both subcutaneous tissue and intramural intestinal oxygen tension in patients given supplemental oxygen. METHODS: Patients undergoing elective colon resection were randomly assigned to normocapnia (n = 15, end-tidal carbon dioxide tension 35 mmHg) or mild hypercapnia (n = 15, end-tidal carbon dioxide tension 50 mmHg). Intraoperative inspired oxygen concentration was 80%. The authors measured subcutaneous tissue oxygen tension in the right upper arm and intramural oxygen tension in the left colon. Measurements were averaged over time within each patient and, subsequently, among patients. Data were compared with chi-square, unpaired t, or Mann-Whitney rank sum tests; P < 0.05 was significant. RESULTS: Morphometric characteristics and other possible confounding factors were similar in the groups. Intraoperative tissue oxygen tension in hypercapnic patients was significantly greater in the arm (mean +/- SD: 116 +/- 29 mmHg vs. 84 +/- 25 mmHg; P = 0.006) and colon (median [interquartile range]: 107 [81-129] vs. 53 [41-104] mmHg; P = 0.020). CONCLUSIONS: During supplemental oxygen administration, mild intraoperative hypercapnia increased tissue oxygen tension in the arm and colon. Previous work suggests that improved tissue oxygenation will reduce infection risk via the proposed pathomechanism, although only an outcome study can confirm this.

Abdomen↗

Optimal perioperative oxygen administration.

PURPOSE OF REVIEW: During anesthesia and surgery oxygen is routinely administered to all patients. Inspired oxygen concentrations, however, vary between 30 and 100%, and oxygen is often administered in a seemingly random manner. During the last decade it has been shown in several randomized trials that perioperative supplemental oxygen administration might improve outcome after certain surgical procedures. The purpose of this review is to provide an overview about the benefits and risks of supplemental oxygen administration in the perioperative period. RECENT FINDINGS: Supplemental oxygen improves immune function. Furthermore, 80% inspired oxygen fraction almost doubles subcutaneous tissue oxygen tension and halves the rate of postoperative wound infections. Some studies have shown that supplemental oxygen also decreases the rate of postoperative nausea and vomiting after laparoscopic and open abdominal surgical procedures. Preconditioning with oxygen might improve organ function after liver transplantation and outcome after spinal ischemic insults. Supplemental perioperative oxygen administration is not associated with clinically important side effects. SUMMARY: Supplemental oxygen administration during the perioperative period might be a simple, inexpensive and well-tolerated treatment option to improve patient outcome. The optimal inspired oxygen concentration still needs to be evaluated.

Hemodynamics↗

Hypercapnia improves tissue oxygenation in morbidly obese surgical patients.

Risk of wound infection is increased in morbidly obese surgical patients, in part because a major determinant of wound infection risk, tissue oxygenation, is marginal. Unlike in lean patients, supplemental inspired oxygen (Fio2) only slightly improves tissue oxygenation in obese patients. Mild hypercapnia improves tissue oxygenation in lean patients but has not been evaluated in obese patients. We thus tested the hypothesis that mild hypercapnia markedly improves tissue oxygenation in morbidly obese patients given Fio2 80% during major abdominal surgery. Thirty obese patients (body mass index 61.5 +/- 17 kg/m2) scheduled for open gastric bypass were randomly assigned to normocapnia (n = 15, end-tidal Pco2 35 mm Hg) or hypercapnia (n = 15, end-tidal Pco2 50 mm Hg); Fio2 was 80%. Anesthetic management and other confounding factors were controlled. Tissue oxygen tension was measured subcutaneously at the upper arm using a polarographic probe in a silastic tonometer. Demographic characteristics, cardiovascular measurements, and Pao2 (222 +/- 48 versus 230 +/- 68 mm Hg in normocapnic versus hypercapnic; mean +/- sd; P = 0.705) were comparable in the groups. Tissue oxygen tension, however, was greater in hypercapnic than in normocapnic patients (78 +/- 31 versus 56 +/- 13 mm Hg; P = 0.029). Mild hypercapnia increased tissue oxygenation by an amount believed to be clinically important and could potentially reduce the risk of surgical wound infection in morbidly obese patients.

Adult↗

Perioperative hypothermia does not enhance the risk of cancer dissemination.

BACKGROUND: Resistance to cancer metastasis is mediated by host immunity, and mild perioperative hypothermia impairs immune function. We tested the hypothesis that mild perioperative hypothermia increases the risk of cancer recurrence and subsequent mortality METHODS: In a 5- to 9-year follow-up of 140 cancer patients enrolled in a study demonstrating that 2 degrees C mild perioperative hypothermia triples wound infection risk, tumor characteristics likely to influence recurrence, patient outcome, and current health status were determined. Primary outcomes were tumor recurrence and all-cause mortality. RESULTS: Tumor status in the groups was similar and included Duke's and TNM classifications, preoperative carcinoembryonic antigen concentration, histologic differentiation, numbers of nodes biopsied and positive nodes, blood vessel invasion, and adhesion of tumor to adjacent organs. Cancer-free and overall survival rates were similar in normothermic and hypothermic patients. These data provide 80% power for detecting a 25% difference between the groups. CONCLUSIONS: Mild perioperative hypothermia did not increase recurrent tumors, cancer death, or all-cause mortality.

Aged↗

Hypothermia--it's more than a toy.

PURPOSE OF REVIEW: Perioperative hypothermia triples the incidence of adverse myocardial outcomes in high-risk patients; it significantly increases blood loss and augments allogeneic transfusion requirements. Even mild hypothermia increases the incidence of surgical wound infection following colon resection and therefore the duration of hospitalization. Hypothermia adversely affects antibody- and cell-mediated immune defenses, as well as the oxygen availability in the peripheral wound tissues. Mild perioperative hypothermia changes the kinetics and action of various anesthetic and paralyzing agents, increases thermal discomfort, and is associated with delayed postanesthetic recovery. RECENT FINDINGS: On the other hand however, therapeutic hypothermia may be an interesting approach in various settings. Lowering core temperature to 32-34 degrees C may reduce cell injury by suppressing excitotoxins and oxygen radicals, stabilizing cell membranes, and reducing the number of abnormal electrical depolarizations. Evidence in animals indicates that even mild hypothermia provides substantial protection against cerebral ischemia and myocardial infarction. Mild hypothermia has been shown to improve outcome after cardiac arrest in humans. Randomized trials are in progress to evaluate the potential benefits of mild hypothermia during aneurysm clipping and after stroke or acute myocardial infarction. SUMMARY: This article reviews recent publications in the field of accidental as well as therapeutic hypothermia, and tries to assess what evidence is available at the present time.

Journal Article↗

Thermal management of the patient: where does the patient lose and/or gain temperature?

PURPOSE OF REVIEW: Anesthesia inhibits normal thermoregulatory control, leading to perioperative hypothermia or allowing therapeutic hypothermia. During the last decade many studies have shown the effects of anesthesia on thermoregulation. As a consequence many active warming and cooling devices are available to manipulate patients' core temperature. This review focuses on new findings in the field of temperature management. RECENT FINDINGS: Thermal management of patients has improved tremendously in recent years. Many outcome studies have shown adverse effects of perioperative hypothermia, as well as beneficial effects of therapeutic hypothermia after out-of-hospital cardiac arrest and brain trauma. However, inducing hypothermia is limited by physiologic thermoregulatory responses. Small reductions in core temperature lead to vasoconstriction and shivering, effectively hindering hypothermia. Thus prevention of vasoconstriction and shivering have become major goals during induction of therapeutic hypothermia. All anesthetics, opioids and sedatives lower the vasoconstriction and shivering threshold, thus allowing hypothermia. However, these drugs have side effects, such as respiratory depression, sedation and nausea. Several drugs, alone or in combination, lower the shivering threshold while causing minimal or no side effects. SUMMARY: Anesthesia affects thermoregulatory control and leads to perioperative hypothermia. The prevention of perioperative hypothermia improves patient's outcome. Therapeutic hypothermia can be induced and also improves outcome in certain conditions.

Journal Article↗

Supplemental intravenous crystalloid administration does not reduce the risk of surgical wound infection.

Wound perfusion and oxygenation are important determinants of the development of postoperative wound infections. Supplemental fluid administration significantly increases tissue oxygenation in surrogate wounds in the subcutaneous tissue of the upper arm in perioperative surgical patients. We tested the hypothesis that supplemental fluid administration during and after elective colon resections decreases the incidence of postoperative wound infections. Patients undergoing open colon resection were randomly assigned to small-volume (n = 124, 8 mL.kg(-1).h(-1)) or large-volume (n = 129, 16-18 mL.kg(-1).h(-1)) fluid management. Our major outcomes were two distinct criteria for diagnosis of surgical wound infections: 1) purulent exudate combined with a culture positive for pathogenic bacteria, and 2) Center for Disease Control criteria for diagnosis of surgical wound infections. All wound infections diagnosed using either criterion by a blinded observer in the 15 days after surgery were considered in the analysis. Wound healing was evaluated with the ASEPSIS scoring system. Of the patients given small fluid administration, 14 had surgical wound infections; 11 given large fluid therapy had infections, P = 0.46. ASEPSIS wound-healing scores were similar in both groups: 7 +/- 16 (small volume) versus 8 +/- 14 (large volume), P = 0.70. Our results suggest that supplemental hydration in the range tested does not impact wound infection rate.

Crystalloid Solutions↗

Compartmental pharmacokinetics of dantrolene in adults: do malignant hyperthermia association dosing guidelines work?

Dantrolene is the only drug proven effective for prevention and treatment of malignant hyperthermia (MH). Current dosing recommendations are based on noncompartmental analyses and are largely empiric. They are also divergent, as evidenced by differing recommendations from the Malignant Hyperthermia Association of the United States (MHAUS) and European Sources. We determined the compartmental pharmacokinetics of dantrolene, simulated the concentration time course based on currently recommended dosing, and suggest an optimal regimen. Nine volunteers (55-89 kg) received IV infusions of dantrolene (5 mg/kg over 30 min followed by 0.05 mg.kg(-1) . h(-1) for 5 h). Venous blood samples were drawn for up to 60 h, and dantrolene plasma concentrations were determined by reverse phase, high-performance liquid chromatography. One, two, and three compartmental models were fitted to the data, and a covariate analysis was performed. All calculations were performed with NONMEM using the population approach. The data were adequately described by a two-compartment model with the following typical variable values (median +/- se): volumes of distribution V1= 3.24 +/- 0.61 L; V2= 22.9 +/- 1.53 L; plasma clearance CL el= 0.03 +/- 0.003 L/min; and distributional clearance CL dist= 1.24 +/- 0.22 L/min. All parameters were scaled linearly with weight. Simulations of European recommendations for treatment of MH lead to plasma concentrations converging to 14-18 mg/L within 24 h. Simulating MHAUS guidelines (intermittent bolus administration) yielded peak and trough plasma concentrations ranging from 6.7-22.6 mg/L. Based on our findings, we propose an infusion regimen adjusted to the initial bolus dose(s) required to control symptoms. This strategy maintains the individualized therapeutic concentrations and improves stability of plasma concentrations.

Adult↗

Obesity decreases perioperative tissue oxygenation.

BACKGROUND: Obesity is an important risk factor for surgical site infections. The incidence of surgical wound infections is directly related to tissue perfusion and oxygenation. Fat tissue mass expands without a concomitant increase in blood flow per cell, which might result in a relative hypoperfusion with decreased tissue oxygenation. Consequently, the authors tested the hypotheses that perioperative tissue oxygen tension is reduced in obese surgical patients. Furthermore, they compared the effect of supplemental oxygen administration on tissue oxygenation in obese and nonobese patients. METHODS: Forty-six patients undergoing major abdominal surgery were assigned to one of two groups according to their body mass index: body mass index less than 30 kg/m2 (nonobese) or 30 kg/m2 or greater (obese). Intraoperative oxygen administration was adjusted to arterial oxygen tensions of approximately 150 mmHg and approximately 300 mmHg in random order. Anesthesia technique and perioperative fluid management were standardized. Subcutaneous tissue oxygen tension was measured with a polarographic electrode positioned within a subcutaneous tonometer in the lateral upper arm during surgery, in the recovery room, and on the first postoperative day. Postoperative tissue oxygen was also measured adjacent to the wound. Data were compared with unpaired two-tailed t tests and Wilcoxon rank sum test; P < 0.05 was considered statistically significant. RESULTS: Intraoperative subcutaneous tissue oxygen tension was significantly less in the obese patients at baseline (36 vs. 57 mmHg; P = 0.002) and with supplemental oxygen administration (47 vs. 76 mmHg; P = 0.014). Immediate postoperative tissue oxygen tension was also significantly less in subcutaneous tissue of the upper arm (43 vs. 54 mmHg; P = 0.011) as well as near the incision (42 vs. 62 mmHg; P = 0.012) in obese patients. In contrast, tissue oxygen tension was comparable in each group on the first postoperative morning. CONCLUSION: Wound and tissue hypoxia were common in obese patients in the perioperative period and most pronounced during surgery. Even with supplemental oxygen tissue, oxygen tension in obese patients was reduced to levels that are associated with a substantial increase in infection risk.

Abdomen↗

Effects of a circulating-water garment and forced-air warming on body heat content and core temperature.

BACKGROUND: Forced-air warming is sometimes unable to maintain perioperative normothermia. Therefore, the authors compared heat transfer, regional heat distribution, and core rewarming of forced-air warming with a novel circulating-water garment. METHODS: Nine volunteers were each evaluated on two randomly ordered study days. They were anesthetized and cooled to a core temperature near 34 degrees C. The volunteers were subsequently warmed for 2.5 h with either a circulating-water garment or a forced-air cover. Overall, heat balance was determined from the difference between cutaneous heat loss (thermal flux transducers) and metabolic heat production (oxygen consumption). Average arm and leg (peripheral) tissue temperatures were determined from 18 intramuscular needle thermocouples, 15 skin thermal flux transducers, and "deep" hand and foot thermometers. RESULTS: Heat production (approximately 60 kcal/h) and loss (approximately 45 kcal/h) were similar with each treatment before warming. The increases in heat transfer across anterior portions of the skin surface were similar with each warming system (approximately 65 kcal/h). Forced-air warming had no effect on posterior heat transfer, whereas circulating-water transferred 21+/-9 kcal/h through the posterior skin surface after a half hour of warming. Over 2.5 h, circulating water thus increased body heat content 56% more than forced air. Core temperatures thus increased faster than with circulating water than forced air, especially during the first hour, with the result that core temperature was 1.1 degrees +/- 0.7 degrees C greater after 2.5 h (P < 0.001). Peripheral tissue heat content increased twice as much as core heat content with each device, but the core-to-peripheral tissue temperature gradient remained positive throughout the study. CONCLUSIONS: The circulating-water system transferred more heat than forced air, with the difference resulting largely from posterior heating. Circulating water rewarmed patients 0.4 degrees C/h faster than forced air. A substantial peripheral-to-core tissue temperature gradient with each device indicated that peripheral tissues insulated the core, thus slowing heat transfer.

Body Temperature↗

Dantrolene reduces the threshold and gain for shivering.

UNLABELLED: Dantrolene is used for treatment of life-threatening hyperthermia, yet its thermoregulatory effects are unknown. We tested the hypothesis that dantrolene reduces the threshold (triggering core temperature) and gain (incremental increase) of shivering. Healthy volunteers were evaluated on 2 random days: control and dantrolene (approximately 2.5 mg/kg plus a continuous infusion). In Study 1, 9 men were warmed until sweating was provoked and then cooled until arteriovenous shunt constriction and shivering occurred. Sweating was quantified on the chest using a ventilated capsule. Absolute right middle fingertip blood flow was quantified using venous-occlusion volume plethysmography. A sustained increase in oxygen consumption identified the shivering threshold. In Study 2, 9 men were given cold lactated Ringer's solution i.v. to reduce core temperature approximately 2 degrees C/h. Cooling was stopped when shivering intensity no longer increased with further core cooling. The gain of shivering was the slope of oxygen consumption versus core temperature regression. In Study 1, sweating and vasoconstriction thresholds were similar on both days. In contrast, shivering threshold decreased 0.3 +/- 0.3 degrees C, P = 0.004, on the dantrolene day. In Study 2, dantrolene decreased the shivering threshold from 36.7 +/- 0.2 to 36.3 +/- 0.3 degrees C, P = 0.01 and systemic gain from 353 +/- 144 to 211 +/- 93 mL.min(-1).degrees C(-1), P = 0.02. Thus, dantrolene substantially decreased the gain of shivering, but produced little central thermoregulatory inhibition. IMPLICATIONS: Dantrolene substantially decreases the gain of shivering but produces relatively little central thermoregulatory inhibition. It thus seems unlikely to prove more effective than conventional muscle relaxants for treatment of life-threatening hyperthermia.

Adolescent↗

Supplemental oxygen and carbon dioxide each increase subcutaneous and intestinal intramural oxygenation.

Oxidative killing by neutrophils, a primary defense against surgical pathogens, is directly related to tissue oxygenation. We tested the hypothesis that supplemental inspired oxygen or mild hypercapnia (end-tidal PCO2 of 50 mm Hg) improves intestinal oxygenation. Pigs (25 +/- 2.5 kg) were used in 2 studies in random order: 1) Oxygen Study: 30% versus 100% inspired oxygen concentration at an end-tidal PCO2 of 40 mm Hg, and 2) Carbon Dioxide Study: end-tidal PCO2 of 30 mm Hg versus 50 mm Hg with 30% oxygen. Within each study, treatment order was randomized. Treatments were maintained for 1.5 h; measurements were averaged over the final hour. A tonometer inserted in the subcutaneous tissue of the left upper foreleg measured subcutaneous oxygen tension. Tonometers inserted into the intestinal wall measured intestinal intramural oxygen tension from the small and large intestines. Oxygen 100% administration doubled subcutaneous oxygen partial pressure (PO2) (57 +/- 10 to 107 +/- 48 mm Hg, P = 0.006) and large intestine intramural PO2 (53 +/- 14 to 118 +/- 72 mm Hg, P = 0.014); intramural PO2 increased 40% in the small intestine (37 +/- 10 to 52 +/- 25 mm Hg, P = 0.004). An end-tidal PCO2 of 50 mm Hg increased large intestinal PO2 approximately 16% (49 +/- 10 to 57 +/- 12 mm Hg, P = 0.039), whereas intramural PO2 increased by 45% in the small intestine (31 +/- 12 to 44 +/- 16 mm Hg, P = 0.002). Supplemental oxygen and mild hypercapnia each increased subcutaneous and intramural tissue PO2, with supplemental oxygen being most effective.

Administration, Inhalation↗

Supplemental perioperative fluid administration increases tissue oxygen pressure.

BACKGROUND: Wound infections are common and serious surgical complications. Wound perfusion delivers oxygen, inflammatory cells, growth factors, and cytokines to injured tissues. Hypoperfused regions experience low oxygen tensions that do not support adequate oxidative killing or wound healing. Clinicians may fail to recognize clinically important hypovolemia because hemodynamic stability and urine output are maintained after peripheral perfusion is compromised. We tested the hypothesis that supplemental fluid administration during and after elective colon resection increases tissue perfusion and tissue oxygen pressure. METHODS: Fifty-six patients undergoing colon resection were randomly assigned to conservative (8 mL x kg(-1) x h(-1), n = 26) or aggressive (16 to 18 mL x kg(-1) x h(-1), n = 30) fluid management. Anesthetic technique was standardized. We used 60% nitrous oxide in 40% oxygen. During surgery and postanesthetic recovery, subcutaneous oxygen tension (P(sq)O(2)) was measured by using a polarographic sensor implanted subcutaneously into 1 upper arm. Capillary blood flow was evaluated postoperatively with a thermal diffusion system. Data were analyzed with 2-tailed t tests; P value less than.05 was considered statistically significant. RESULTS: Hemodynamic and renal responses were similar in the groups. Intraoperative tissue oxygen tension was significantly greater in patients given supplemental fluid: 81 +/- 26 vs 67 +/- 18 mm Hg, P =.03. Postoperative P(sq)O(2) (77 +/- 26 vs 59 +/- 15 mm Hg, P =.009) and capillary blood flow (69 +/- 12 vs 53 +/- 12, P <.001) were also greater in the supplemental fluid patients. CONCLUSIONS: Supplemental perioperative fluid administration significantly increases tissue perfusion and tissue oxygen partial pressure. Optimizing tissue perfusion will require providing more fluid than indicated by normal clinical criteria or use of invasive monitoring to guide treatment. The actual effect of supplemental fluid administration on incidence of wound infection requires further investigation.

Adult↗

The effects of epidural and general anesthesia on tissue oxygenation.

UNLABELLED: The risk of wound infections is inversely related to subcutaneous tissue oxygen tension. General anesthesia increases local blood flow by direct vasodilation and central inhibition of thermoregulatory vasoconstriction. Epidural anesthesia can increase perfusion in blocked regions by decreasing sympathetic tone. We therefore tested the hypothesis that epidural anesthesia increases tissue oxygen tension in awake and anesthetized subjects. Fifteen healthy volunteers underwent epidural, general, and combined epidural and general anesthesia. Subcutaneous tissue oxygen tension was measured using tonometers in the lateral upper arm and the lateral thigh. Epidural anesthesia to a T10 level was maintained with 0.75% mepivacaine. General anesthesia was maintained with 1.5% sevoflurane in 30% oxygen; 30% inspired oxygen was given via a sealed facemask during baseline and epidural anesthesia. Baseline subcutaneous tissue oxygen tensions for arm and thigh were 57 +/- 11 and 54 +/- 8 mm Hg, respectively. Epidural anesthesia significantly increased tissue oxygenation in the thigh by 9 mm Hg, to 63 +/- 7 mm Hg, without increasing arm oxygenation. Tissue oxygenation in the arm and thigh were similar during general anesthesia alone, 58 +/- 11 and 63 +/- 12 mm Hg. Arm oxygenation remained unchanged with the addition of epidural anesthesia; however, thigh subcutaneous oxygen partial pressure increased 8 +/- 3 mm Hg, from 63 +/- 12 to 71 +/- 9 mm Hg. Although epidural anesthesia increased tissue oxygenation significantly with and without general anesthesia, the magnitude of this increase might be of marginal clinical importance in regard to surgical wound infections. IMPLICATIONS: Epidural anesthesia significantly increased subcutaneous tissue oxygenation in the thigh both with and without general anesthesia. Although each increase was statistically significant, previous work suggests that the magnitude of these changes is unlikely to markedly reduce the risk of surgical wound infection.

Adult↗

Thoracic epidural anesthesia increases tissue oxygenation during major abdominal surgery.

UNLABELLED: Intraoperative surgical stress may markedly increase adrenergic nerve activity and plasma catecholamine concentrations, which causes peripheral vasoconstriction and decreased tissue oxygen partial pressure possibly leading to tissue hypoxia. Tissue hypoxia is associated with an increased incidence of surgical wound infections. Thoracic epidural anesthesia blocks afferent neural stimuli and inhibits efferent sympathetic outflow in response to painful stimuli. Consequently, we tested the hypothesis that supplemental thoracic epidural anesthesia during major abdominal surgery improves tissue perfusion and subcutaneous oxygen tension. Thirty patients were randomly assigned to two groups: general (n = 15) or combined general and epidural anesthesia (n = 15). Anesthesia technique and fluid management were standardized. Subcutaneous tissue oxygen tension was measured continuously in the upper arm with a Clark type electrode. Data were compared with unpaired, two-tailed t-tests, Wilcoxon's ranked sum test, or repeated-measures analysis of variance and Scheffé F tests as appropriate; P < 0.05 was considered statistically significant. After 60 min, intraoperative tissue oxygen tension was significantly larger during combined anesthesia than during general anesthesia (54.3 +/- 7.4 mm Hg versus 42.1 +/- 8.6 mm Hg; P = 0.0002). Subcutaneous tissue oxygen tension remained significantly higher in the combined general/epidural anesthesia group throughout the observation period. Hemodynamic responses and global oxygen variables were similar in the groups. Thoracic epidural anesthesia improved intraoperative tissue oxygen tension outside the area of the epidural block. Thus, our results give evidence that supplemental neural nociceptive block blunts generalized vasoconstriction caused by surgical stress and adrenergic responses. IMPLICATIONS: Thoracic epidural anesthesia blunts the decrease of subcutaneous tissue oxygen tension caused by surgical stress and adrenergic vasoconstriction during major abdominal surgery. Consequently, combined general and epidural anesthesia helps to provide sufficient tissue oxygenation.

Abdomen↗

Opioid-induced bowel dysfunction: pathophysiology and potential new therapies.

Opioid treatment for postoperative or chronic pain is frequently associated with adverse effects, the most common being dose-limiting and debilitating bowel dysfunction. Postoperative ileus, although attributable to surgical procedures, is often exacerbated by opioid use during and following surgery. Postoperative ileus is marked by increased inhibitory neural input, heightened inflammatory responses, decreased propulsive movements and increased fluid absorption in the gastrointestinal tract. The use of opioids for chronic pain is characterised by a constellation of symptoms including hard dry stools, straining, incomplete evacuation, bloating, abdominal distension and increased gastroesophageal reflux. The current management of opioid-induced bowel dysfunction among patients receiving opioid analgesics consists primarily of nonspecific ameliorative measures. Intensive investigations into the mode of action of opioids have characterised three opioid receptor classes -mu, delta and kappa- that mediate the myriad of peripheral and central actions of opioids. Activation of mu-opioid receptors in the gastrointestinal tract is responsible for inhibition of gut motility, whereas receptors in the central nervous system mediate the analgesic actions of opioids. Blocking peripheral opioid receptors in the gut is therefore a logical therapeutic target for managing opioid-induced bowel dysfunction. Available opioid antagonists such as naloxone are of limited use because they are readily absorbed, cross the blood-brain barrier, and act at central opioid receptors to reverse analgesia and elicit opioid withdrawal. Methylnaltrexone and alvimopan are recently developed opioid antagonists with activity that is restricted to peripheral receptors. Both have recently shown the ability to reverse opioid-induced bowel dysfunction without reversing analgesia or precipitating central nervous system withdrawal signs in non-surgical patients receiving opioids for chronic pain. In addition, recent clinical studies with alvimopan suggest that it may normalise bowel function without blocking opioid analgesia in abdominal laparotomy patients with opioid-related postoperative ileus.

Constipation↗

Nitrous oxide and risk of surgical wound infection: a randomised trial.

BACKGROUND: Nitrous oxide inactivates vitamin B12 and methionine synthase, thereby impairing DNA formation and, consequently, new cell formation. The gas also inhibits methionine production, which can reduce scar formation and depresses chemotactic migration by monocytes. Therefore, we assessed whether nitrous oxide increases the incidence of surgical wound infection. METHODS: We recruited 418 patients aged 18-80 years, scheduled for colon resection that was expected to last more than 2 h, at three hospitals in Austria and Hungary. Patients were randomly assigned 65% intraoperative nitrous oxide (n=208) or nitrogen (n=206), with remifentanil and isoflurane. The primary outcome was the incidence of clinical postoperative wound infection, analysed by intention to treat. FINDINGS: 206 patients in the nitrous oxide group and 202 in the nitrogen group were included in the final analysis. Duration of surgery was longer in the nitrogen group (3.4 h [1.5]) than in the nitrous oxide group (3.0 h [SD 1.3]) and arterial pressure (84 mm Hg [10] vs 81 mm Hg [9]), bispectral index values (53 [9] vs 44 [8]), and end-tidal isoflurane concentration (0.64% [0.14] vs 0.56% [0.13]) were greater in patients given nitrogen than in those given nitrous oxide. Infection rate was 15% (31/206) in patients given nitrous oxide and 20% (40/202) in those given nitrogen (p=0.205). Additionally, the ASEPSIS wound healing score, wound collagen deposition, number of patients admitted to critical care unit, time to first food ingestion, duration of hospital stay, and mortality did not differ between treatment groups. INTERPRETATION: Nitrous oxide does not increase the incidence of surgical wound infection.

Anesthetics, Inhalation↗