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  • 1.
    Aahlin, Eirik K
    et al.
    Department of GI and HPB Surgery, University Hospital Northern Norway, Breivika, Tromsø, Norway; Institute of Clinical Medicine, University of Tromsø, Tromsø, Norway .
    von Meyenfeldt, Maarten
    Department of Surgery, University Hospital Maastricht, Maastricht, The Netherlands; NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University, Maastricht, The Netherlands.
    Dejong, Cornelius Hc
    Department of Surgery, University Hospital Maastricht, Maastricht, The Netherlands; NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University, Maastricht, The Netherlands.
    Ljungqvist, Olle
    Örebro University, School of Medicine, Örebro University, Sweden. Department of Surgery, Örebro University Hospital, Örebro; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Fearon, Kenneth C
    Clinical Surgery, University of Edinburgh, Royal Infirmary of Edinburgh, Edinburgh, UK .
    Lobo, Dileep N
    Division of Gastrointestinal Surgery, Nottingham Digestive Diseases Centre, National Institute for Health Research, Biomedical Research Unit, Nottingham University Hospitals, Queen's Medical Centre, Nottingham, UK .
    Demartines, Nicolas
    Hospital of Lausanne (CHUV), Lausanne, Switzerland .
    Revhaug, Arthur
    Department of GI and HPB Surgery, University Hospital Northern Norway, Breivika, Tromsø, Norway; Institute of Clinical Medicine, University of Tromsø, Tromsø, Norway .
    Wigmore, Stephen J
    Clinical Surgery, University of Edinburgh, Royal Infirmary of Edinburgh, Edinburgh, UK .
    Lassen, Kristoffer
    Department of GI and HPB Surgery, University Hospital Northern Norway, Breivika, Tromsø, Norway; Institute of Clinical Medicine, University of Tromsø, Tromsø, Norway .
    Functional recovery is considered the most important target: a survey of dedicated professionals2014In: Perioperative medicine, ISSN 2047-0525, Vol. 3, article id 3:5Article in journal (Refereed)
    Abstract [en]

    Background: The aim of this study was to survey the relative importance of postoperative recovery targets and perioperative care items, as perceived by a large group of international dedicated professionals.

    Methods: A questionnaire with eight postoperative recovery targets and 13 perioperative care items was mailed to participants of the first international Enhanced Recovery After Surgery (ERAS) congress and to authors of papers with a clear relevance to ERAS in abdominal surgery. The responders were divided into categories according to profession and region.

    Results: The recovery targets 'To be completely free of nausea', 'To be independently mobile' and 'To be able to eat and drink as soon as possible' received the highest score irrespective of the responder's profession or region of origin. Equally, the care items 'Optimizing fluid balance', 'Preoperative counselling' and 'Promoting early and scheduled mobilisation' received the highest score across all groups.

    Conclusions: Functional recovery, as in tolerance of food without nausea and regained mobility, was considered the most important target of recovery. There was a consistent uniformity in the way international dedicated professionals scored the relative importance of recovery targets and care items. The relative rating of the perioperative care items was not dependent on the strength of evidence supporting the items.

  • 2.
    Ahl, R.
    et al.
    Department of Surgery, Karolinska University Hospital, Stockholm, Sweden; School of Medical Sciences, Örebro University, Örebro, Sweden.
    Matthiessen, P.
    School of Medical Sciences, Örebro University, Örebro, Sweden; Department of Surgery, Örebro University Hospital, Örebro, Sweden.
    Fang, X.
    Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Cao, Yang
    Örebro University, School of Medical Sciences. Örebro University Hospital. Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; .
    Sjölin, Gabriel
    Örebro University, School of Medical Sciences. Department of Surgery.
    Lindgren, R.
    Department of Surgery, Örebro University Hospital, Örebro, Sweden.
    Ljungqvist, Olle
    Örebro University, School of Medical Sciences. Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Mohseni, Shahin
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Surgery.
    Effect of beta-blocker therapy on early mortality after emergency colonic cancer surgery2018In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Emergency colorectal cancer surgery is associated with significant mortality. Induced adrenergic hyperactivity is thought to be an important contributor. Downregulating the effects of circulating catecholamines may reduce the risk of adverse outcomes. This study assessed whether regular preoperative beta-blockade reduced mortality after emergency colonic cancer surgery.

    METHODS: This cohort study used the prospectively collected Swedish Colorectal Cancer Registry to recruit all adult patients requiring emergency colonic cancer surgery between 2011 and 2016. Patients were subdivided into those receiving regular beta-blocker therapy before surgery and those who were not (control). Demographics and clinical outcomes were compared. Risk factors for 30-day mortality were evaluated using Poisson regression analysis.

    RESULTS: A total of 3187 patients were included, of whom 685 (21·5 per cent) used regular beta-blocker therapy before surgery. The overall 30-day mortality rate was significantly reduced in the beta-blocker group compared with controls: 3·1 (95 per cent c.i. 1·9 to 4·7) versus 8·6 (7·6 to 9·8) per cent respectively (P < 0·001). Beta-blocker therapy was the only modifiable protective factor identified in multivariable analysis of 30-day all-cause mortality (incidence rate ratio 0·31, 95 per cent c.i. 0·20 to 0·47; P < 0·001) and was associated with a significant reduction in death of cardiovascular, respiratory, sepsis and multiple organ failure origin.

    CONCLUSION: Preoperative beta-blocker therapy may be associated with a reduction in 30-day mortality following emergency colonic cancer surgery.

  • 3.
    Ahl, Rebecka
    et al.
    Örebro University, School of Medical Sciences. Division of Trauma and Emergency Surgery, Department of Surgery, Karolinska University Hospital, Stockholm, Sweden.
    Barmparas, Galinos
    Division of Acute Care Surgery and Surgical Critical Care, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, USA.
    Riddez, Louis
    Division of Trauma and Emergency Surgery, Department of Surgery, Karolinska University Hospital, Stockholm, Sweden.
    Ley, Eric J
    Division of Acute Care Surgery and Surgical Critical Care, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, USA.
    Wallin, Göran
    Örebro University, School of Medical Sciences. Division of Trauma and Emergency Surgery, Department of Surgery, Örebro University Hospital, Örebro, Sweden.
    Ljungqvist, Olle
    Örebro University, School of Medical Sciences. Division of Trauma and Emergency Surgery, Department of Surgery, Örebro University Hospital, Örebro, Sweden.
    Mohseni, Shahin
    Örebro University, School of Medical Sciences. Örebro University Hospital. Division of Trauma and Emergency Surgery, Department of Surgery, Örebro University Hospital, Örebro, Sweden; Division of Trauma and Emergency Surgery, Department of Surgery, Karolinska University Hospital, Stockholm, Sweden.
    Does beta-blockade reduce the risk of depression in patients with isolated severe extracranial injuries?2017In: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 41, no 7, p. 1801-1806Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Approximately half of trauma patients develop post-traumatic depression. It is suggested that beta-blockade impairs trauma memory recollection, reducing depressive symptoms. This study investigates the effect of early beta-blockade on depression following severe traumatic injuries in patients without significant brain injury.

    METHODS: Patients were identified by retrospectively reviewing the trauma registry at an urban university hospital between 2007 and 2011. Severe extracranial injuries were defined as extracranial injuries with Abbreviated Injury Scale score ≥3, intracranial Abbreviated Injury Scale score <3 and an Injury Severity Score ≥16. In-hospital deaths and patients prescribed antidepressant therapy ≤1 year prior to admission were excluded. Patients were stratified into groups based on pre-admission beta-blocker status. The primary outcome was post-traumatic depression, defined as receiving antidepressants ≤1 year following trauma.

    RESULTS: Five hundred and ninety-six patients met the inclusion criteria with 11.4% prescribed pre-admission beta-blockade. Patients receiving beta-blockers were significantly older (57 ± 18 vs. 42 ± 17 years, p < 0.001) with lower Glasgow Coma Scale score (12 ± 3 vs. 14 ± 2, p < 0.001). The beta-blocked cohort spent significantly longer in hospital (21 ± 20 vs. 15 ± 17 days, p < 0.01) and intensive care (4 ± 7 vs. 3 ± 5 days, p = 0.01). A forward logistic regression model was applied and predicted lack of beta-blockade to be associated with increased risk of depression (OR 2.7, 95% CI 1.1-7.2, p = 0.04). After adjusting for group differences, patients lacking beta-blockers demonstrated an increased risk of depression (AOR 3.3, 95% CI 1.2-8.6, p = 0.02).

    CONCLUSIONS: Pre-admission beta-blockade is associated with a significantly reduced risk of depression following severe traumatic injury. Further investigation is needed to determine the beneficial effects of beta-blockade in these instances.

  • 4.
    Ahlman, B.
    et al.
    Department of Surgery, Karolinska Hospital, Stockholm, Sweden; Metabolic Research Laboratory, St Göran's Hospital, Stockholm, Sweden.
    Andersson, K.
    Metabolic Research Laboratory, St Göran's Hospital, Stockholm, Sweden.
    Leijonmarck, C. E.
    Department of Surgery, St Göran's Hospital, Stockholm, Sweden.
    Ljungqvist, Olle
    Department of Surgery, Karolinska Hospital, Stockholm, Sweden.
    Hedenborg, L.
    Department of Pathology, St Göran's Hospital, Stockholm, Sweden.
    Wernerman, J.
    St Göran's Hospital, Stockholm, Sweden.
    Short-term starvation alters the free amino acid content of human intestinal mucosa1994In: Clinical Science, ISSN 0143-5221, E-ISSN 1470-8736, Vol. 86, no 6, p. 653-662Article in journal (Refereed)
    Abstract [en]

    1. The effects of short-term starvation and refeeding on the free amino acid concentrations of the intestinal mucosa were characterized in male subjects (n=6), using endoscopically obtained biopsy specimens from the duodenum and from all four segments of the colon.

    2. The alterations in the amino acid concentrations in response to short-term starvation were overall uniform in both duodenal and colonic mucosa as well as in plasma. Most amino acids decreased, whereas branched-chain amino acids increased.

    3. In the colon, glutamic acid and glutamine decreased during the starvation period, whereas they remained unaltered in the duodenum. This was the major difference in response to short-term starvation between the amino acid concentrations in the intestinal mucosa of the duodenum and colon.

    4. Refeeding for 3 days normalized the amino acid concentrations except for glutamic acid, asparagine and histidine, which remained low in the colon, and threonine, which showed an overshoot in both parts of the intestine. S. The changes in mucosal amino acid concentrations seen in response to starvation and refeeding were uniform in the four segments of the colon. This suggests that sampling from the rectum/sigmoid colon will give representative values for the free amino acid concentrations of the entire large intestine.

  • 5.
    Ahlman, B.
    et al.
    Department of Surgery, Karolinska Hospital, Sweden.
    Andersson, K.
    Ljungqvist, Olle
    Persson, B.
    Wernerman, J.
    Elective abdominal surgery alters the free amino acid content of the human intestinal mucosa1995In: European Journal of Surgery, ISSN 1102-4151, E-ISSN 1741-9271, Vol. 161, no 8, p. 593-601Article in journal (Refereed)
    Abstract [en]

    Objective: To assess the impact of a standard moderately severe surgical operation on the mucosal amino acid content of the duodenum and the colon.

    Design: Open study.

    Setting: University hospital, Sweden.

    Subjects: Nine patients who were to undergo elective open cholecystectomy.

    Interventions: Endoscopically obtained biopsy specimens from the intestinal mucosa. Main outcome measures: Changes in the content of free amino acids in the duodenum and colon at three days postoperatively.

    Results: The concentration of glutamine in the duodenum increased by 27% and that of glutamic acid by 34% after operation, whereas their content in colon remained unaltered. The concentration of branched chain amino acids increased by 26% in the duodenal mucosa after operation and by 24% in the colonic mucosa. The total concentration of amino acids (excluding taurine) increased by 9% in the duodenum, but remained unaltered in the colon.

    Conclusion: This study shows characteristic and consistent alterations in the free amino acid content of the intestinal tract after a moderately severe operation.

  • 6.
    Ahlman, B.
    et al.
    Department of Surgery, Karolinska Hospital and Metabolic Research Laboratory, St Göran's Hospital, Stockholm, Sweden.
    Ljungqvist, Olle
    Department of Surgery, Karolinska Hospital and Metabolic Research Laboratory, St Göran's Hospital, Stockholm, Sweden.
    Andersson, K.
    Department of Surgery, Karolinska Hospital and Metabolic Research Laboratory, St Göran's Hospital, Stockholm, Sweden.
    Wernerman, J.
    Department of Surgery, Karolinska Hospital and Metabolic Research Laboratory, St Göran's Hospital, Stockholm, Sweden.
    Free amino acids in the human intestinal mucosa: Impact of surgical trauma and critical illness1995In: Clinical Nutrition, ISSN 0261-5614, E-ISSN 1532-1983, Vol. 14, no 1, p. 54-55Article in journal (Refereed)
  • 7.
    Ahlman, B.
    et al.
    Department of Surgery, Karolinska Hospital, Metabolic Research Laboratory, St Göran's Hospital, Stockholm, Sweden.
    Ljungqvist, Olle
    Department of Surgery, Karolinska Hospital, Stockholm, Sweden.
    Persson, B.
    cDepartment of Radiology, Karolinska Hospital, Stockholm, Sweden.
    Bindslev, L.
    Department of Anesthesiology and Intensive Care, Karolinska Hospital, Department of Anesthesiology and Intensive Care, St Göran's Hospital, Stockholm, Sweden.
    Wernerman, J.
    Metabolic Research Laboratory, St Göran's Hospital, Stockholm, Sweden.
    Intestinal amino acid content in critically ill patients1995In: JPEN - Journal of Parenteral and Enteral Nutrition, ISSN 0148-6071, E-ISSN 1941-2444, Vol. 19, no 4, p. 272-278Article in journal (Refereed)
    Abstract [en]

    Background: The purpose of the study was to determine the concentrations of free amino acids and the total protein content of the human intestinal mucosa during critical illness. Methods: The free amino acid and protein concentrations in endoscopically obtained biopsy specimens from the duodenum and the distal colonic segments were determined on 19 critically ill patients. The free amino acids were separated by ion exchange chromatography and detected by fluorescence, and the protein content was quantified by the method of Lowry. Results: In general, the typical amino acid pattern of the intestinal mucosa was seen, with very high levels of taurine, aspartate and glutamic acid. The main difference, as compared to a reference series of healthy subjects, was the elevated glutamine concentration of the duodenal mucosa. This amino acid was unaltered in the descending colon and depressed in the rectum. At the same time, the glutamatic acid concentrations were unaltered, suggesting that the degradation of glutamine was not increased in the septic state of the majority of the patients studied. Phenylalanine and the two branched-chain amino acids, valine and leucine, were elevated in the duodenal mucosa, and in the colonic mucosa, methionine and phenylalanine were elevated; otherwise, all the other individual amino acids were unaltered or depressed. Conclusions: The alterations seen in mucosal free amino acid and protein concentrations in connection with critical illness are different in many respects and contrast with the findings seen after starvation or moderate surgical trauma.

  • 8. Alibegovic, A.
    et al.
    Gannerdahl, P.
    Debeer, L.
    Ljungqvist, Olle
    Department of Surgery, Karolinska Hospital, Sweden.
    The effect of alpha 2 receptor agonists on central haemodynamic and blood glucose during hemorrhagic stress in the rat1998In: Surgical Research Communications, ISSN 0882-9233, Vol. 9, no 2-4, p. 151-164Article in journal (Refereed)
    Abstract [en]

    The effect of the selective alpha 2 agonist Mivazerol on catecholamine levels in plasma, and on central hemodynamics and blood glucose levels developments during hemorrhagic stress in rats was investigated. The animals were randomly given either saline, low dose of Mivazerol (0.6 μg/ml) or high dose (2.0 μg/ml) at a rate of 30 μl/100 g/min, beginning the infusions intravenously 30 min before onset and throughout 60 min of hemorrhagic stress. Before hemorrhage, Mivazerol raised mean arterial pressure, and reduced heart rate, adrenaline and noradrenaline levels in a dose dependent fashion. High dose infusion also resulted in an elevation in blood glucose. During hemorrhage, the high dose effectively dampened the catecholamine response. Simultaneously, the same group maintained better mean arterial pressure in response to hemorrhage. Blood glucose levels were elevated to similar levels regardless of treatment. These data indicate that Mivazerol effectively reduced the catecholamine response to severe hemorrhagic stress, while central hemodynamic and blood glucose responses were maintained or improved.

  • 9.
    Alibegovic, A.
    et al.
    Department of Surgery, Karolinska Hospital, Stockholm, Sweden.
    Ljungqvist, Olle
    Department of Surgery, Karolinska Hospital, Stockholm, Sweden.
    Pretreatment with glucose infusion prevents fatal outcome after hemorrhage in food deprived rats1993In: Circulatory Shock, ISSN 0092-6213, Vol. 39, no 1, p. 1-6Article in journal (Refereed)
    Abstract [en]

    Twenty-four hour food deprivation increases mortality after experimental hemorrhage. Survival after hemorrhage is closely related to the capacity of the animal to develop hyperglycemia. In this study, 24 hr food deprived rats were given a 3-hr infusion of either 0.3 ml/100 g b.wt./h 30% glucose iv (n = 10) or the same volume of 0.9% NaCl (n = 10) prior to 60 min of standardized hemorrhage. Glucose infusion resulted in a transient hyperglycemia, and 600% greater hepatic glycogen content compared to saline (P < 0.001). During hemorrhage, glucose-treated rats developed substantial hyperglycemia while glucose levels fell in saline treated (P < 0.001). Concomitant developments in hematocrits indicated improved plasma refill in glucose treated animals (P < 0.01). While saline treated rats developed irreversible shock and died within 3 hr of bleeding, glucose treated rats had a MAP of 52 ± 2 (mean ± SEM) mm Hg by the end of hemorrhage (P < 0.01). All glucose-treated rats recovered and survived the seven-day observation period. It is concluded that glucose infusion leading to hepatic glycogen repletion alters outcome after experimental hemorrhage in food deprived animals. These experimental results may be of clinical relevance, since elective surgery is generally performed after overnight fasting, which substantially reduces the hepatic glycogen reserve.

  • 10.
    Alston-Smith, J.
    et al.
    Department of Clinical Immunology and Transfusion Medicine, University Hospital, Uppsala, Sweden.
    Ljungqvist, Olle
    Boija, P.-O.
    Ware, J.
    Nilsson Ekdahl, K.
    Endotoxin, epinephrine, glucagon, insulin and calcium ionophore A23187 modulation of kinese activity in cultured rat hepatocytes1990In: Acta Chirurgica Scandinavica, ISSN 0001-5482, p. 677-681Article in journal (Refereed)
    Abstract [en]

    Altered glucose metabolism is one of the commonly observed sequelae of sepsis and septic shock. The present investigation was undertaken to determine the role of endotoxin (ET) upon hepatocyte glucoregulation, by measuring the activity of pyruvate kinase (PK), a key glycolytic enzyme. Hepatocytes were exposed to endotoxin concentrations known to occur in vivo during sepsis, i.e., from 1 X 10(-14) to 1 X 10(-8) g/ml. The alteration of the enzyme activities after addition of epinephrine, glucagon, insulin and calcium ionophore A23187 with and without ET preincubation were also examined. ET alone decreased the PK activity by 12% at all concentrations tested. The basal inhibition of the enzyme caused by epinephrine (-48%) was partially blocked by ET preincubation above 1 X 10(-10) g/ml. There were no ET-(glucagon, calcium ionophore, insulin) interaction. These in vitro results do not support pyruvate kinase as a site of hepatic enzyme regulation defect in endotoxaemia.

  • 11.
    Alston-Smith, J.
    et al.
    Uppsala University, Biomedical Center, Department of Medicine, Sweden.
    Ljungqvist, Olle
    Ware, J.
    Nilsson Ekdahl, K. N.
    Regulation of rat hepatocyte fructose 1,6-diphosphatase activity during endotoxemia1991In: Surgical Research Communication, ISSN 0882-9233, Vol. 11, no 1-2, p. 67-75Article in journal (Refereed)
  • 12.
    Aronson, D.
    et al.
    Research Division, Joslin Diabetes Center, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
    Wojtaszewski, J.
    Copenhagen Muscle Research Center, August Krogh Institute, University of Copenhagen, Copenhagen, Denmark.
    Thorell, A.
    Department of Surgery, Karolinska Hospital and Institute, Stockholm, Sweden.
    Nygren, J.
    Department of Surgery, Karolinska Hospital and Institute, Stockholm, Sweden.
    Zangen, A.
    Research Division, Joslin Diabetes Center, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
    Richter, E. A.
    Copenhagen Muscle Research Center, August Krogh Institute, University of Copenhagen, Copenhagen, Denmark.
    Ljungqvist, Olle
    Department of Surgery, Karolinska Hospital and Institute, Stockholm, Sweden.
    Fielding, R. A.
    Department of Health Sciences, Sargent Coll. All. Hlth. Professions, Boston University, Boston, MA , United States.
    Goodyear, L. J.
    Research Division, Joslin Diabetes Center, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA; Joslin Diabetes Center, One Joslin Place, Boston, MA, United States.
    Extracellular-regulated protein kinase cascades are activated in response to injury in human skeletal muscle1998In: American Journal of Physiology, ISSN 0002-9513, E-ISSN 2163-5773, Vol. 275, no 2, p. C555-C561Article in journal (Refereed)
    Abstract [en]

    The mitogen-activated protein (MAP) kinase signaling pathways are believed to act as critical signal transducers between stress stimuli and transcriptional responses in mammalian cells. However, it is not known whether these signaling cascades also participate in the response to injury in human tissues. To determine whether injury to the vastus lateralis muscle activates MAP kinase signaling in human subjects, two needle biopsies or open muscle biopsies were taken from the same incision site 30-60 min apart. The muscle biopsy procedures resulted in striking increases in dual phosphorylation of the extracellular-regulated kinases (ERK1 and ERK2) and in activity of the downstream substrate, the p90 ribosomal S6 kinase. Raf-1 kinase and MAP kinase kinase, upstream activators of ERK, were also markedly stimulated in all subjects. In addition, c-Jun NH2-terminal kinase and p38 kinase, components of two parallel MAP kinase pathways, were activated following muscle injury. The stimulation of the three MAP kinase cascades was present only in the immediate vicinity of the injury, a finding consistent with a local rather than systemic activation of these signaling cascades in response to injury. These data demonstrate that muscle injury induces the stimulation of the three MAP kinase cascades in human skeletal muscle, suggesting a physiological relevance of these protein kinases in the immediate response to tissue injury and possibly in the initiation of wound healing.

  • 13. Awad, Sherif
    et al.
    Varadhan, Krishna K.
    Ljungqvist, Olle
    Örebro University Hospital. Institution for Surgery & Molecular Medicine, Karolinska Institute, Stockholm, Sweden.
    Lobo, Dileep N
    A meta-analysis of randomised controlled trials on preoperative oral carbohydrate treatment in elective surgery2013In: Clinical Nutrition, ISSN 0261-5614, E-ISSN 1532-1983, Vol. 32, no 1, p. 34-44Article in journal (Refereed)
    Abstract [en]

    BACKGROUND & AIMS: Whilst preoperative carbohydrate treatment (PCT) results in beneficial physiological effects, the effects on postoperative clinical outcomes remain unclear and were studied in this meta-analysis.

    METHODS: Prospective studies that randomised adult non-diabetic patients to either PCT (≥50 g oral carbohydrates 2-4 h pre-anaesthesia) or control (fasted/placebo) were included. The primary outcome was length of hospital stay. Secondary outcomes included development of postoperative insulin resistance, complications, nausea and vomiting. Methodological quality was assessed using GRADEpro(®) software.

    RESULTS: Twenty-one randomised studies of 1685 patients (733 PCT: 952 control) were included. No overall difference in length of stay was noted for analysis of all studies or subgroups of patients undergoing surgery with an expected hospital stay ≤2 days or orthopaedic procedures. However, patients undergoing major abdominal surgery following PCT had reduced length of stay [mean difference, 95% confidence interval: -1.08 (-1.87 to -0.29); I(2) = 60%, p = 0.007]. PCT reduced postoperative insulin resistance with no effects on in-hospital complications over control (risk ratio, 95% confidence interval, 0.88 (0.50-1.53), I(2) = 41%; p = 0.640). There was significant heterogeneity amongst studies and, therefore, quality of evidence was low to moderate.

    CONCLUSIONS: PCT may be associated with reduced length of stay in patients undergoing major abdominal surgery, however, the included studies were of low to moderate quality.

  • 14.
    Baban, Bayar
    et al.
    Örebro University, School of Medical Sciences. Department of Surgery, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Ljungqvist, Olle
    Örebro University, School of Medical Sciences. Department of Surgery, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Särndahl, Eva
    Örebro University, School of Medical Sciences. iRiSC – Inflammatory Response and Infection Susceptibility Centre, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Inflammasome activation, colonic cancer and glucose metabolism2016In: Clinical Nutrition ESPEN, ISSN 2405-4577, Vol. 12, article id e37Article in journal (Refereed)
    Abstract [en]

    Objectives: To study the association between inflammasome activation (a potent initiator of inflammation acting via caspase-1 and maturation of interleukin-1β), colonic cancer and glucose metabolism.

    Methods: Five patients with colon cancer and ten matched controls without cancer were measured for insulin sensitivity using the hyperinsulinemic euglycemic clamp. For detection of inflammasome activation the caspase-1 activity, determined by detecting FLICA using flow cytometry, was measured in both monocytes and granulocytes at the start of, and at 120 minutes into the clamp. Descriptive and analytical statistics were performed using nonparametric methods by SPSS.

    Results: There was no difference in levels of insulin sensitivity between the two groups (p=0.09). The cancer patients had significantly lower levels of caspase-1 both in monocytes (p<0.05) and granulocytes (p<0.05) compared with the controls. However both patients and controls had significantly higher levels of both mono- and granulocyte caspase-1 activity at 120 minutes into the clamp as compared to at start (p<0.05). Patients showed an overall higher relative increase in caspase-1 during the clamp, however this finding did not reach statistical significance (monocytes; p=0.27, granulocytes; p=0.22).

  • 15.
    Baban, Bayar
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Dept of Surgery, Örebro University Hospital, Örebro, Sweden.
    Thorell, Anders
    Department of Clinical Science, Danderyds Hospital, Karolinska Institutet, Stockholm, Sweden; Dept of Surgery, Ersta Hospital, Stockholm, Sweden.
    Nygren, Jonas
    Department of Clinical Science, Danderyds Hospital, Karolinska Institutet, Stockholm, Sweden; Dept of Surgery, Ersta Hospital, Stockholm, Sweden.
    Bratt, Anette
    Department of Clinical Science, Danderyds Hospital, Karolinska Institutet, Stockholm, Sweden; Dept of Surgery, Ersta Hospital, Stockholm, Sweden.
    Ljungqvist, Olle
    Örebro University, School of Medicine, Örebro University, Sweden. Örebro University Hospital. Dept of Surgery, Örebro University Hospital, Örebro, Sweden; Institution for Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Determination of insulin resistance in surgery: the choice of method is crucial2015In: Clinical Nutrition, ISSN 0261-5614, E-ISSN 1532-1983, Vol. 34, no 1, p. 123-128Article in journal (Refereed)
    Abstract [en]

    BACKGROUND & AIMS: In elective surgery, postoperative hyperglycaemia and insulin resistance are independent risk factors for complications. Since the simpler HOMA method has been used as an alternative to the hyperinsulinemic normoglycemic clamp in studies of surgery induced insulin resistance, we compared the two methods in patients undergoing elective surgery.

    METHODS: Data from 113 non-diabetic patients undergoing elective surgery were used. Insulin sensitivity, both before and after surgery, was quantified by the clamp and HOMA. Pre- and postoperatively, the results of the clamp were compared to HOMA using regression- and correlation analysis. Degree of agreement between the methods was studied using weighted linear kappa and the Bland-Altman test.

    RESULTS: Both the clamp and HOMA recorded a mean relative reduction in insulin sensitivity of 39 ± 24% and 39 ± 61% respectively after surgery; with significant correlations (p < 0.01) for pre- and post-operative measures as well as for relative changes. However r(2) values were low: 0.04, 0.07 and 0.03 respectively. The degree of agreement for the relative change in insulin sensitivity using the Bland-Altman test gave a mean of difference 0% but "limits of agreement" (±2SD) was ±125%. This poor inter-method agreement was consolidated by a weighted linear kappa value of 0.18.

    CONCLUSION: While the hyperinsulinemic euglycemic clamp measures the postoperative changes in insulin sensitivity, HOMA measures something different. Data using the HOMA method must therefore be interpreted cautiously and is not interchangeable with data obtained from the clamp.

  • 16. Balagopal, P.
    et al.
    Ljungqvist, Olle
    Dept. of Surgery, Karolinska Institute and Hospital, Stockholm, Sweden.
    Nair, K. S.
    Endocrine Research Unit, Mayo Clinic and Foundation, Rochester, MN, United States.
    Skeletal muscle heavy-chain synthesis rate in healthy humans1997In: American Journal of Physiology, ISSN 0002-9513, E-ISSN 2163-5773, Vol. 272, no 1, p. 45-50Article in journal (Refereed)
    Abstract [en]

    Mixed muscle protein synthetic rate has been measured in humans. These measurements represent the average of synthetic rates of all muscle proteins with variable rates. We determined to what extent the synthesis rate of mixed muscle protein in humans reflects that of myosin heavy chain (MHC), the main contractile protein responsible for the conversion of ATP to mechanical energy as muscle contraction. Fractional synthetic rates of MHC and mixed muscle protein were measured from the increment of [C-13]leucine in these proteins in vastus lateralis biopsy samples taken at 5 and 10 h during a primed continuous infusion of L-[1-C-13]leucine in 10 young healthy subjects. Calculations were done by use of plasma [C-13]ketoisocaproate (KIC) and muscle tissue fluid [C-13]leucine as surrogate measures of leucyl-tRNA. Fractional synthetic rate of MHC with plasma KIC (0.0299 +/- 0.0043%/h) and tissue fluid leucine (0.0443 +/- 0.0056%/h) were only 72 +/- 3% of that of mixed muscle protein (0.0408 +/- 0.0032 and 0.0603 +/- 0.0059%/h, respectively, with KIC and tissue fluid leucine). Contribution of MHC (7 +/- 1 mg . kg(-1) . h(-1)) to synthetic rates of whole body mixed muscle protein (36 +/- 5 mg . kg(-1) . h(-1)) and whole body protein (127 +/- 4 mg . kg(-1) . h(-1)) is only 18 +/- 1 and 5 +/- 1%, respectively. This relatively low contribution of MHC to whole body and mixed muscle protein synthesis warrants direct measurement of synthesis rate of MHC in conditions involving abnormalities of muscle contractile function.

  • 17.
    Bang, P.
    et al.
    Pediatric Endocrinology Unit, Department of Woman and Child Health, Karolinska Institute and Hospital, Stockholm, Sweden.
    Nygren, J.
    Department of Surgery, Karolinska Institute and Hospital, Stockholm, Sweden.
    Carlsson-Skwirut, C.
    Pediatric Endocrinology Unit, Department of Woman and Child Health, Karolinska Institute and Hospital, Stockholm, Sweden.
    Thorell, A.
    Department of Surgery, Karolinska Institute and Hospital, Stockholm, Sweden.
    Ljungqvist, Olle
    Department of Surgery, Karolinska Institute and Hospital, Stockholm, Sweden.
    Postoperative induction of insulin-like growth factor binding protein-3 proteolytic activity: relation to insulin and insulin sensitivity1998In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 83, no 7, p. 2509-2515Article in journal (Refereed)
    Abstract [en]

    Increased serum insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) proteolytic activity (IGFBP-3-PA) has been demonstrated in a number of clinical states of insulin resistance, including severe illness, after surgery, and in noninsulin-dependent diabetes mellitus. In the present study we assessed the role of insulin sensitivity in expression of IGFBP-3-PA in serum. In 18 patients studied, a significant increase in IGFBP-3-PA (P < 0.005) was demonstrated after cole-rectal surgery. Eight patients receiving an oral glucose load before surgery demonstrated a significant greater relative increase in IGFBP-3-PA compared with 10 patients not receiving glucose (32.9 +/- 7.1% vs. 8.6 +/- 6.7%, respectively; P < 0.05). Both groups had reduced insulin sensitivity after surgery(-58 +/- 4%; P < 0.0001; n = 18), as determined by hyperinsulinemic, normoglycemic clamps; however, the group not receiving glucose displayed 18% less insulin sensitivity than the oral glucose load group (P < 0.05). Multiple regression analysis demonstrated that the relative changes in IGFBP-3-PA and C peptide levels were inversely correlated (P < 0.05), suggesting that increased IGFBP-3-PA, presumably increasing IGF bioavailability, may be associated with decreased insulin demands. Interestingly, insulin infusion during the 4-h hyperinsulinemic, normoglycemic clamp performed 24 h after surgery (post-op) resulted in a further increase in IGFBP-3-PA in both groups (P < 0.005), whereas no significant responses could be demonstrated during the pre-op clamp. The expression of increased IGFBP-3-PA was accompanied by conversion of endogenous intact 39/42-kDa IGFBP-3 into its 30-kDa fragmented form as determined by Western immunoblotting, and this conversion was virtually complete after the 4-h post-op clamp in patients displaying marked increases in IGFBP-3-PA. Characterization of the IGFBP-3-PA demonstrated that it was specific for IGFBP-3, as no degradation of IGFBP-1 and -2 was detected, and the use of various protease inhibitors demonstrated that serine proteases and possibly matrix metalloproteinases contribute to the increased IGFBP-3-PA level after surgery. We propose that IGF bioavailability may be increased by the induction of IGFBP-3-PA in insulin-resistant subjects, and that insulin regulates IGFBP-3-PA in this state.

  • 18.
    Barazzoni, R.
    et al.
    Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy.
    Deutz, N. E. P.
    Center for Translational Research in Aging & Longevity, Department of Health and Kinesiology, Texas A & M University, College Station TX, USA.
    Biolo, G.
    Department of Medical, Surgical and Health Sciences, Internal Medicine, University of Trieste, Trieste, Italy.
    Bischoff, S.
    Department of Nutritional Medicine/Prevention, University of Hohenheim, Stuttgart, Germany.
    Boirie, Y.
    Department of Clinical Nutrition, CHU de Clermont-Ferrand, CRNH, Université d'Auvergne, Clermont-Ferrand, France.
    Cederholm, T.
    Clinical Nutrition and Metabolism, Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden; Department of Geriatric Medicine, Uppsala University Hospital, Uppsala, Sweden.
    Cuerda, C.
    Nutrition Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
    Delzenne, N.
    Department, Université Catholique de Louvain, Brussels, Belgium.
    Leon Sanz, M.
    Department of Medicine, Complutense University, Madrid, Spain.
    Ljungqvist, Olle
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Surgery.
    Muscaritoli, M.
    Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy.
    Pichard, C.
    Nutrition Unit, Geneva University Hospital, Geneva, Switzerland.
    Preiser, J. C.
    Department of Intensive Care, Erasme University Hospital, Brussels, Belgium.
    Sbraccia, R.
    Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.
    Singer, P.
    Department of Intensive Care, Institute for Nutrition Research, Rabin Medical Center, Beilinson Hospital, Sackler School of Medicine, Tel Aviv University, Israel.
    Tappy, L.
    Department of Physiology, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.
    Thorens, B.
    Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.
    Van Gossum, A.
    Gastroenterology Service, Hospital Erasme, Brussels, Belgium.
    Vettor, R.
    Internal Medicine Unit and Center for the Study and Integrated Treatment of Obesity, Department of Medicine, Padua University, Padua, Italy.
    Calder, P. C.
    Faculty of Medicine, University of Southampton, Southampton, United Kingdom; NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom; University of Southampton, Southampton, United Kingdom.
    Carbohydrates and insulin resistance in clinical nutrition: Recommendations from the ESPEN expert group2017In: Clinical Nutrition, ISSN 0261-5614, E-ISSN 1532-1983, Vol. 36, no 2, p. 355-363Article, review/survey (Refereed)
    Abstract [en]

    Growing evidence underscores the important role of glycemic control in health and recovery from illness. Carbohydrate ingestion in the diet or administration in nutritional support is mandatory, but carbohydrate intake can adversely affect major body organs and tissues if resulting plasma glucose becomes too high, too low, or highly variable. Plasma glucose control is especially important for patients with conditions such as diabetes or metabolic stress resulting from critical illness or surgery. These patients are particularly in need of glycemic management to help lessen glycemic variability and its negative health consequences when nutritional support is administered. Here we report on recent findings and emerging trends in the field based on an ESPEN workshop held in Venice, Italy, 8-9 November 2015. Evidence was discussed on pathophysiology, clinical impact, and nutritional recommendations for carbohydrate utilization and management in nutritional support. The main conclusions were: a) excess glucose and fructose availability may exacerbate metabolic complications in skeletal muscle, adipose tissue, and liver and can result in negative clinical impact; b) low-glycemic index and high-fiber diets, including specialty products for nutritional support, may provide metabolic and clinical benefits in individuals with obesity, insulin resistance, and diabetes; c) in acute conditions such as surgery and critical illness, insulin resistance and elevated circulating glucose levels have a negative impact on patient outcomes and should be prevented through nutritional and/or pharmacological intervention. In such acute settings, efforts should be implemented towards defining optimal plasma glucose targets, avoiding excessive plasma glucose variability, and optimizing glucose control relative to nutritional support. (C) 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism.

  • 19.
    Bark, Tor
    et al.
    Department of Surgery and Medicine, Karolinska Hospital, Stockholm, sweden.
    Engervall, Per A.
    Department of Surgery and Medicine, Karolinska Hospital, Stockholm, Sweden.
    Katouli, Mohammad
    Center for Microbiology and Tumorbiology, Karolinska Institute, Stockholm, Sweden.
    Ljungqvist, Olle
    Örebro University, School of Medical Sciences. Department of Oral Diagnostic Sciences, Karolinska Institute, Huddinge, Sweden.
    Loftenius, Annika
    Department of Oral Diagnostic Sciences, Karolinska Institute, Huddinge, Sweden.
    Möllby, Roland
    Center for Microbiology and Tumorbiology, Karolinska Institute, Stockholm, Sweden.
    Svenberg, Torgny E.
    Center for Microbiology and Tumorbiology, Karolinska Institute, Stockholm, Sweden.
    Oral arginine supplementation does not prevent bacterial translocation afterhemorrhagic stress in the rat1998In: Surgical Research Communications, ISSN 0882-9233, Vol. 19, p. 269-277Article in journal (Refereed)
  • 20.
    Bark, Tor
    et al.
    Department of Surgery, Karolinska Hospital, Stockholm, Sweden.
    Katouli, Mohammad
    Department of Surgery, Karolinska Hospital, Stockholm, Sweden.
    Ljungqvist, Olle
    Örebro University, School of Medical Sciences. Department of Surgery, Karolinska Hospital, Stockholm, Sweden.
    Möllby, R.
    Department of Surgery, Karolinska Hospital, Stockholm, Sweden.
    Svenberg, Torgny E.
    Department of Surgery, Karolinska Hospital, Stockholm, Sweden.
    Bacterial translocation after non-lethal hemorrhage in the rat1993In: Circulatory Shock, ISSN 0092-6213, Vol. 41, no 1, p. 60-65Article in journal (Refereed)
    Abstract [en]

    Translocation of enteric bacteria has been suggested to compromise patients in severe catabolic stress. Mechanisms for this route of infection are not known. In this study, ratswere subjected to hemorrhage without reinfusion during 60 min, total blood loss was 3.28 +/- 0.14 ml/100 g BW. Control groups consisted of sham-operated animals without bleeding, and rats not operated at all. The mean number of viable bacteria found in mesenteric lymph nodes (MLN) of bled animals was 168 +/- 45 colony forming units (c.f.u./MLN), significantly higher compared to sham operated (5 +/- 3 c.f.u./MLN) and not operated (0 +/- 0 c.f.u./MLN) controls (P < 0.01). Cultures from MLN were positive in 7/9 rats after bleeding, in 3/9 of sham operated, and in 0/6 of non-instrumented control animals. No positive blood cultures were isolated. Escherichia coli was the dominant species found in MLN. A biochemical fingerprinting method (the PhP system) was used to identify translocating strains of E. coli among strains found in cecum. The method was also used to compare translocating strains between different animals. Our findings reveal that bacteria translocate to MLN after hemorrhage. Some phenotypes of E. coli strains translocate more frequently than others, suggesting that they have properties facilitating translocation.

  • 21.
    Bark, Tor
    et al.
    Department of Surgery, Karolinska Hospital, Stockholm, Sweden.
    Katouli, Mohammad
    Department of Surgery, Karolinska Hospital, Stockholm, Sweden.
    Ljungqvist, Olle
    Örebro University, School of Medical Sciences. Department of Surgery, Karolinska Hospital, Stockholm, Sweden.
    Möllby, R.
    Department of Surgery, Karolinska Hospital, Stockholm, Sweden.
    Svenberg, Torgny E.
    Department of Surgery, Karolinska Hospital, Stockholm, Sweden.
    Glutamine supplementation does not prevent bacterial translocation after non-lethal haemorrhage in rats1995In: European Journal of Surgery, ISSN 1102-4151, E-ISSN 1741-9271, Vol. 161, no 1, p. 3-8Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    To find out whether supplementation of an enteral diet with glutamine would reduce translocation of bacteria to mesenteric lymph nodes or blood after major haemorrhage in rats.

    DESIGN:

    Open randomised study.

    SETTING:

    University departments of surgery and microbiology, Sweden.

    MATERIAL:

    49 Sprague-Dawley rats.

    INTERVENTIONS:

    Rats were fed enterally for 7 days on diets supplemented with either glutamine or an isonitrogenous amount of non-essential amino acids. After feeding, 8 experimental and 8 control rats underwent sham operation; 9 and 7, respectively, underwent moderate haemorrhage (to 65 mm Hg); and 9 and 8, respectively, underwent severe haemorrhage (50 mm Hg) without reinfusion.

    MAIN OUTCOME MEASURES:

    Microbiological analyses of samples of blood and mesenteric lymph nodes taken 24 hours after haemorrhage.

    RESULTS:

    The median (interquartile) number of colony forming units/mesenteric lymph nodes after moderate haemorrhage in animals who were given glutamine supplementation was 11 (0-34) and in control animals 20 (0-178). After severe haemorrhage the corresponding figures were 199 (10-310) and 22 (0-187). No pathogens were isolated from blood cultures.

    CONCLUSION:

    Glutamine supplementation before haemorrhage did not reduce bacterial translocation to mesenteric lymph nodes in this rat model.

  • 22.
    Bark, Tor
    et al.
    Department of Surgery, Karolinska Hospital, Stockholm, Sweden.
    Katouli, Mohammad
    Department of Surgery, Karolinska Hospital, Stockholm, Sweden.
    Svenberg, Torgny E.
    Department of Surgery, Karolinska Hospital, Stockholm, Sweden.
    Ljungqvist, Olle
    Örebro University, School of Medical Sciences. Department of Surgery, Karolinska Hospital, Stockholm, Sweden.
    Food deprivation increases bacterial translocation after non-lethal haemorrhage in rats1995In: European Journal of Surgery, ISSN 1102-4151, E-ISSN 1741-9271, Vol. 161, no 2, p. 67-71Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    To investigate whether brief fasting before the induction of hypotension by non-lethal haemorrhage may induce translocation of enteric bacteria to mesenteric lymph nodes or blood in rats.

    DESIGN:

    Laboratory experiment.

    SETTING:

    University departments of surgery and microbiology, Sweden.

    MATERIAL:

    39 Male Sprague-Dawley rats.

    INTERVENTIONS:

    20 animals were fasted for 24 hours, all 39 then underwent controlled haemorrhage for 60 minutes that reduced the blood pressure to 55 mm Hg.

    MAIN OUTCOME MEASURES:

    Differences in blood loss, blood glucose concentrations, and packed cell volume; and aerobic cultures of mesenteric lymph nodes and blood.

    RESULTS:

    Fasted rats (n = 20) lost 2.3% of blood volume compared with 2.8% in fed rats(p < 0.001). Packed cell volume dropped by 11.3% in fasted rats and 16.5% in fed rats (p < 0.001). Glucose concentrations rose by 7.0 mmol/l in fasted rats compared with 21.0 mmol/l in fed rats (p < 0.001). Mesenteric lymph nodes contained enteric bacteria in 14/20 fasted rats compared with 6/19 fed rats (p < 0.05). In 4 fasted rats blood cultures grew pathogenic bacteria compared with no fed rats (p = 0.11). The number of bacteria found in mesenteric lymph nodes was significantly greater in fasted than in fed rats (p = 0.01).

    CONCLUSIONS:

    Brief fasting before hypotension caused by non-lethal haemorrhage was associated with significantly increased bacterial translocation compared with fed animals. Increases in blood glucose concentrations and plasma refill may have had a protective effect in fed rats. These experiments may be of clinical relevance as elective operations are usually preceded by overnight fasting.

  • 23.
    Batchelor, Timothy J. P.
    et al.
    Department of Thoracic Surgery, University Hospitals Bristol NHS Foundation Trust, Bristol, UK.
    Rasburn, Neil J.
    Department of Anaesthesia, University Hospitals Bristol NHS Foundation Trust, Bristol, UK.
    Abdelnour-Berchtold, Etienne
    Division of Thoracic Surgery, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
    Brunelli, Alessandro
    Department of Thoracic Surgery, St. James’s University Hospital, Leeds, UK.
    Cerfolio, Robert J.
    Department of Cardiothoracic Surgery, New York University Langone Health, New York, NY, USA.
    Gonzalez, Michel
    Division of Thoracic Surgery, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
    Ljungqvist, Olle
    Örebro University, School of Medical Sciences. Department of Surgery.
    Petersen, René H.
    Department of Thoracic Surgery, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
    Popescu, Wanda M.
    Department of Anesthesiology, Yale University School of Medicine, New Haven, CT, USA.
    Slinger, Peter D.
    Department of Anesthesia, University Health Network – Toronto General Hospital, Toronto, ON, Canada.
    Naidu, Babu
    Department of Thoracic Surgery, Heart of England NHS Foundation Trust, Birmingham, UK.
    Guidelines for enhanced recovery after lung surgery: recommendations of the Enhanced Recovery After Surgery (ERAS®) Society and the European Society of Thoracic Surgeons (ESTS)2018In: European Journal of Cardio-Thoracic Surgery, ISSN 1010-7940, E-ISSN 1873-734XArticle in journal (Refereed)
    Abstract [en]

    Enhanced recovery after surgery is well established in specialties such as colorectal surgery. It is achieved through the introduction of multiple evidence-based perioperative measures that aim to diminish postoperative organ dysfunction while facilitating recovery. This review aims to present consensus recommendations for the optimal perioperative management of patients undergoing thoracic surgery (principally lung resection). A systematic review of meta-analyses, randomized controlled trials, large non-randomized studies and reviews was conducted for each protocol element. Smaller prospective and retrospective cohort studies were considered only when higher-level evidence was unavailable. The quality of the evidence base was graded by the authors and used to form consensus recommendations for each topic. Development of these recommendations was endorsed by the Enhanced Recovery after Surgery Society and the European Society for Thoracic Surgery. Recommendations were developed for a total of 45 enhanced recovery items covering topics related to preadmission, admission, intraoperative care and postoperative care. Most are based on good-quality studies. In some instances, good-quality data were not available, and subsequent recommendations are generic or based on data extrapolated from other specialties. In other cases, no recommendation can currently be made because either equipoise exists or there is a lack of available evidence. Recommendations are based not only on the quality of the evidence but also on the balance between desirable and undesirable effects. Key recommendations include preoperative counselling, nutritional screening, smoking cessation, prehabilitation for high-risk patients, avoidance of fasting, carbohydrate loading, avoidance of preoperative sedatives, venous thromboembolism prophylaxis, prevention of hypothermia, short-acting anaesthetics to facilitate early emergence, regional anaesthesia, nausea and vomiting control, opioid-sparing analgesia, euvolemic fluid management, minimally invasive surgery, early chest drain removal, avoidance of urinary catheters and early mobilization after surgery. These guidelines outline recommendations for the perioperative management of patients undergoing lung surgery based on the best available evidence. As the recommendation grade for most of the elements is strong, the use of a systematic perioperative care pathway has the potential to improve outcomes after surgery.

  • 24.
    Beverly, Anair
    et al.
    Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Boston MA, USA.
    Kaye, Alan D.
    Department of Anesthesiology and Pharmacology, Anesthesiology Services, LSU School of Medicine, University Medical Center Hospital, New Orleans LA, USA.
    Ljungqvist, Olle
    Örebro University, School of Medical Sciences. Department of Surgery, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Urman, Richard D.
    Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Boston MA, USA.
    Essential Elements of Multimodal Analgesia in Enhanced Recovery After Surgery (ERAS) Guidelines2017In: Anesthesiology Clinics, ISSN 1932-2275, Vol. 35, no 2, p. e115-e143Article in journal (Refereed)
    Abstract [en]

    Perioperative multimodal analgesia uses combinations of analgesic medications that act on different sites and pathways in an additive or synergistic manner to achieve pain relief with minimal or no opiate consumption. Although all medications have side effects, opiates have particularly concerning, multisystemic, long-term, and short-term side effects, which increase morbidity and prolong admissions. Enhanced recovery is a systematic process addressing each aspect affecting recovery. This article outlines the evidence base forming the current multimodal analgesia recommendations made by the Enhanced Recovery After Surgery Society (ERAS). We describe current evidence and important future directions for effective perioperative multimodal analgesia in enhanced recovery pathways.

  • 25.
    Blixt, Christina
    et al.
    Dept of Anaesthesia and Intensive Care, Karolinska University Hospital, Huddinge, Sweden; Dept of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Huddinge, Sweden.
    Ahlstedt, Christian
    Dept of Anaesthesia and Intensive Care, Karolinska University Hospital, Huddinge, Sweden; Dept of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Huddinge, Sweden.
    Ljungqvist, Olle
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Surgery, Örebro University Hospital, Örebro, Sweden.
    Isaksson, Bengt
    Dept of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Huddinge, Sweden; Division of Surgery, Karolinska University Hospital, Huddinge, Sweden.
    Kalman, Sigridur
    Dept of Anaesthesia and Intensive Care, Karolinska University Hospital, Huddinge, Sweden; Dept of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Huddinge, Sweden.
    Rooyackers, Olav
    Dept of Anaesthesia and Intensive Care, Karolinska University Hospital, Huddinge, Sweden; Dept of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Huddinge, Sweden.
    Corrigendum to ‘The effect of perioperative glucose control on postoperative insulin resistance’ [Clin Nutr 31 (5) (2012) 676–681]2018In: Clinical Nutrition, ISSN 0261-5614, E-ISSN 1532-1983, Vol. 37, no 3, p. 1091-1091Article in journal (Refereed)
  • 26. Blixt, Christina
    et al.
    Ahlstedt, Christian
    Ljungqvist, Olle
    Örebro University, School of Medicine, Örebro University, Sweden. Dept of Surgery, Örebro University Hospital, Örebro, Sweden.
    Isaksson, Bengt
    Kalman, Sigridur
    Rooyackers, Olav
    The effect of perioperative glucose control on postoperative insulin resistance2012In: Clinical Nutrition, ISSN 0261-5614, E-ISSN 1532-1983, Vol. 31, no 5, p. 676-681Article in journal (Refereed)
    Abstract [en]

    BACKGROUND & AIMS: Postoperative insulin resistance and the consequent hyperglycemia affects clinical outcome. Insulin sensitivity may be modulated by preoperative nutrition, adequate pain management and minimal invasive surgery. This study aims to disclose the impact of perioperative glucose control on postoperative insulin resistance.

    METHODS: Twenty patients scheduled for elective open hepatectomy were enrolled in this prospective, randomized study. In the treatment group (n = 9) insulin was administered intravenously to keep blood glucose between 6 and 8 mmol/l during surgery. The control group (n = 8) received insulin if blood glucose >14 mmol/l. Insulin sensitivity was measured by a hyperinsulinemic normoglycemic clamp (0.8 mU/kg/min), performed on all patients both on the day before surgery and immediately postoperatively. Plasma cortisol, insulin and C-peptide were measured.

    RESULTS: There was a significant difference in mean glucose value during surgery. In the control group 8.8 mmol/l (SD 1.5) vs. 6.9 mmol/l (SD 0.4) in the treated group, p = 0.003. In the control group insulin sensitivity decreased to 21.9% ± 16.2% of the preoperative value and in the insulin treated group to 46.8 ± 15.5%, p < 0.005. Insulin levels were significantly higher in the treatment group as well as consequently lower C-peptide levels.

    CONCLUSIONS: This trial revealed a significant difference in postoperative insulin resistance in the group treated with insulin during surgery.

  • 27.
    Boija, Per Olov
    et al.
    Department. of Surgery, Karolinska Hospital, Stockholm, Sweden.
    Ljungqvist, Olle
    Örebro University, School of Medical Sciences. Department. of Surgery, Karolinska Hospital, Stockholm, Sweden.
    Nylander, Gunnar
    Department. of Surgery, Karolinska Hospital, Stockholm, Sweden.
    Ware, James
    Department. of Surgery, Karolinska Hospital, Stockholm, Sweden.
    Hypovolaemic stress induced glycogenolysis, isolated liver perfusion study1987In: Research in experimental medicine, ISSN 0300-9130, E-ISSN 1433-8580, Vol. 187, no 5, p. 315-322Article in journal (Refereed)
    Abstract [en]

    Intrinsic hepatic glycogenolysis was examined after hypovolemic stress. Hemorrhagic hypotension of 70 (P70) and 40 mm Hg (P40) for 60 min was inflicted for two postprandial groups and of 70 mm Hg (S70) in a 24-h starved group. The results were compared with three control groups; one postprandial (Pc), one 24-h starved (Sc), and one starved for 9 h (Sc: 9) to mimic the glycogen depletion produced by 70 mm Hg hemorrhagic hypotension. Glucose output was studied in vitro using av recirculating isolated liver perfusion system with a perfusate free of glucose and endocrine stimulation. Liver glycogen determination was made before perfusion start. Although the glycogen stores were decreased after hemorrhage glucose yield was increased (P70) and unchanged (P40) as compared to controls (Pc and Sc: 9). Both starved groups delivered small amounts of glucose, but the released fraction of the S70 group was more than twice that from the Sc group. These data suggest a liver enzyme activation with increased velocity of the enzymesubstrate reactions responsible for glycogen degradation, induced during in vivo hemorrhage and persisting for at least 30 min in vitro perfusion.

  • 28.
    Bowyer, A.
    et al.
    Department of Anaesthesia and Pain Management, Royal Melbourne Hospital, Parkville Vic, Australia.
    Jakobsson, J.
    Department for Anaesthesia and Intensive Care, Institution of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
    Ljungqvist, Olle
    Örebro University Hospital. Department of Surgery; Institution of Molecular medicine and Surgery, Karolinska Insitutet, Stockholm, Sweden.
    Royse, C.
    Department of Surgery, The University of Melbourne, Parkville Vic, Australia.
    A review of the scope and measurement of postoperative quality of recovery2014In: Anaesthesia, ISSN 0003-2409, E-ISSN 1365-2044, Vol. 69, no 11, p. 1266-1278Article, review/survey (Refereed)
    Abstract [en]

    To date, postoperative quality of recovery lacks a universally accepted definition and assessment technique. Current quality of recovery assessment tools vary in their development, breadth of assessment, validation, use of continuous vs dichotomous outcomes and focus on individual vs group recovery. They have progressed from identifying pure restitution of physiological parameters to multidimensional assessments of postoperative function and patient-focused outcomes. This review focuses on the progression of these tools towards an as yet unreached ideal that would provide multidimensional assessment of recovery over time at the individual and group level. A literature search identified 11 unique recovery assessment tools. The Postoperative Quality of Recovery Scale assesses recovery in multiple domains, including physiological, nociceptive, emotive, activities of daily living, cognition and patient satisfaction. It addresses recovery over time and compares individual patient data with base line, thus describing resumption of capacities and is an acceptable method for identification of individual patient recovery.

  • 29. Braga, M.
    et al.
    Ljungqvist, Olle
    Örebro University, School of Health and Medical Sciences.
    Soeters, P.
    Fearon, K.
    Weimann, A.
    Bozzetti, F.
    ESPEN Guidelines on Parenteral Nutrition: surgery2009In: Clinical Nutrition, ISSN 0261-5614, E-ISSN 1532-1983, Vol. 28, no 4, p. 378-386Article in journal (Refereed)
    Abstract [en]

    In modern surgical practice it is advisable to manage patients within an enhanced recovery protocol and thereby have them eating normal food within 1-3 days. Consequently, there is little room for routine perioperative artificial nutrition. Only a minority of patients may benefit from such therapy. These are predominantly patients who are at risk of developing complications after surgery. The main goals of perioperative nutritional support are to minimize negative protein balance by avoiding starvation, with the purpose of maintaining muscle, immune, and cognitive function and to enhance postoperative recovery. Several studies have demonstrated that 7-10 days of preoperative parenteral nutrition improves postoperative outcome in patients with severe undernutrition who cannot be adequately orally or enterally fed. Conversely, its use in well-nourished or mildly undernourished patients is associated with either no benefit or with increased morbidity. Postoperative parenteral nutrition is recommended in patients who cannot meet their caloric requirements within 7-10 days orally or enterally. In patients who require postoperative artificial nutrition, enteral feeding or a combination of enteral and supplementary parenteral feeding is the first choice. The main consideration when administering fat and carbohydrates in parenteral nutrition is not to overfeed the patient. The commonly used formula of 25 kcal/kg ideal body weight furnishes an approximate estimate of daily energy expenditure and requirements. Under conditions of severe stress requirements may approach 30 kcal/kg ideal body weights. In those patients who are unable to be fed via the enteral route after surgery, and in whom total or near total parenteral nutrition is required, a full range of vitamins and trace elements should be supplemented on a daily basis.

  • 30.
    Calles-Escandon, Jorge
    et al.
    Department of Medicine, Endocrine and Metabolism Section, University of Vermont, Burlington VT, United States; University of Vermont, College of Medicine, Burlington VT, United States.
    Sweet, Leigh M.
    Department of Medicine, Endocrine and Metabolism Section, University of Vermont, Burlington VT, United States.
    Ljungqvist, Olle
    Örebro University, School of Medical Sciences. Department of Surgery, Karolinska Institute, Stockholm, Sweden.
    Hirschman, Michael F.
    Joslin Diabetes Center, Boston, MA, United States.
    The membrane-associated 40 KD fatty acid binding protein(Berk's protein), a putative fatty acid transporter is present in human skeletal muscle1995In: Life Sciences, ISSN 0024-3205, E-ISSN 1879-0631, Vol. 58, no 1, p. 19-28Article in journal (Refereed)
    Abstract [en]

    Muscle tissue (1.1 +/- 0.1 grams) was obtained from seven healthy individuals (3 males, 4 females) using an open incision approach before and after ingestion of either 75 grams of dextrose (N=5) or water (N=2). Purified sarcolemmal membranes from the muscle were prepared using a sucrose step gradient. A polyclonal antibody raised against the purified (99%) rat hepatocyte 40 KD membrane fatty acid binding protein (mFABP-L) was used to probe for this putative transporter in the muscle membranes using Western blot. A single band at the 40 KD MW band was identified which reacted antigenically with the proteinpurified from rat livers. These response of Berk's protein 60-75 minutes after dextrose ingestion (or water) was erratic and no specific trend could be identified. Our data demonstrate that the 40 KD mFABP-L originally isolated from rat liver is also present in human skeletal muscle membrane. This protein may be involved in transport of fatty acids across the membrane of skeletal muscle, however its physiological role in human fatty acidmetabolism remains to be established.

  • 31.
    Cerantola, Yannick
    et al.
    University Hospital of Lausanne, Lausanne, Switzerland.
    Valerio, Massimo
    University Hospital of Lausanne, Lausanne, Switzerland.
    Persson, Beata
    University Hospital of Örebro, Örebro, Sweden.
    Jichlinski, Patrice
    University Hospital of Lausanne, Lausanne, Switzerland.
    Ljungqvist, Olle
    Örebro University, School of Medicine, Örebro University, Sweden. Örebro University Hospital.
    Hubner, Martin
    University Hospital of Lausanne, Lausanne, Switzerland.
    Kassouf, Wassim
    McGill University, Montreal, Canada.
    Muller, Stig
    Akershus University Hospital, Oslo, Norway.
    Baldini, Gabriele
    McGill University, Montreal, Canada.
    Carli, Francesco
    McGill University, Montreal, Canada.
    Naesheimh, Torvind
    University Hospital of Northern Norway, Tromsø, Norway.
    Ytrebo, Lars
    University Hospital of Northern Norway, Tromsø, Norway.
    Revhaug, Arthur
    University Hospital of Northern Norway, Tromsø, Norway.
    Lassen, Kristoffer
    University Hospital of Northern Norway, Tromsø, Norway.
    Knutsen, Tore
    University Hospital of Northern Norway, Tromsø, Norway.
    Aarsether, Erling
    University Hospital of Northern Norway, Tromsø, Norway.
    Wiklund, Peter
    Karolinska University Hospital, Stockholm, Sweden.
    Patel, Hitendra R H
    University Hospital of Northern Norway, Tromsø, Norway.
    Guidelines for perioperative care after radical cystectomy for bladder cancer: enhanced Recovery After Surgery (ERAS(®)) society recommendations2013In: Clinical Nutrition, ISSN 0261-5614, E-ISSN 1532-1983, Vol. 32, no 6, p. 879-887Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Enhanced recovery after surgery (ERAS) pathways have significantly reduced complications and length of hospital stay after colorectal procedures. This multimodal concept could probably be partially applied to major urological surgery.

    OBJECTIVES: The primary objective was to systematically assess the evidence of ERAS single items and protocols applied to cystectomy patients. The secondary objective was to address a grade of recommendation to each item, based on the evidence and, if lacking, on consensus opinion from our ERAS Society working group.

    EVIDENCE ACQUISITION: A systematic literature review was performed on ERAS for cystectomy by searching EMBASE and Medline. Relevant articles were selected and quality-assessed by two independent reviewers using the GRADE approach. If no study specific to cystectomy was available for any of the 22 given items, the authors evaluated whether colorectal guidelines could be extrapolated.

    EVIDENCE SYNTHESIS: Overall, 804 articles were retrieved from electronic databases. Fifteen articles were included in the present systematic review and 7 of 22 ERAS items were studied. Bowel preparation did not improve outcomes. Early nasogastric tube removal reduced morbidity, bowel recovery time and length of hospital stay. Doppler-guided fluid administration allowed for reduced morbidity. A quicker bowel recovery was observed with a multimodal prevention of ileus, including gum chewing, prevention of PONV and minimally invasive surgery.

    CONCLUSIONS: ERAS has not yet been widely implemented in urology and evidence for individual interventions is limited or unavailable. The experience in other surgical disciplines encourages the development of an ERAS protocol for cystectomy.

  • 32.
    Coenen Schimke, J. M.
    et al.
    Endocrine Research Unit, Division of Endocrinology and Metabolism, Mayo Clinic and Mayo Foundation, Rochester, MN, USA.
    Ljungqvist, Olle
    Department of Medicine, University of Vermont, Burlington, VT, USA.
    Sarkar, G.
    Department of Medicine, University of Vermont, Burlington, VT, USA.
    Conover, C. A.
    Endocrine Research Unit, Division of Endocrinology and Metabolism, Mayo Clinic and Mayo Foundation, Rochester, MN, USA.
    Nair, K. S.
    Endocrine Research Unit, Division of Endocrinology and Metabolism, Mayo Clinic and Mayo Foundation, Rochester, MN, USA.
    A quantitative PCR measurement of messenger RNA expression of IGF-I, IGF-II and IGFBP-5 in human skeletal muscle1999In: Growth Hormone & IGF Research, ISSN 1096-6374, E-ISSN 1532-2238, Vol. 9, no 3, p. 179-186Article in journal (Refereed)
    Abstract [en]

    Insulin-like growth factor-I and -II (IGF-I and IGF-II) and their binding proteins are important components in growth promotion and tissue maintenance. We determined the presence of IGF-I, -II, and binding protein 5 (IGFBP-5) gene expression in human skeletal muscle and that mRNA abundance is not altered by nutrients and insulin. In the first protocol, (control) subjects were given water. In the second protocol, half of these subjects drank Polycose (carbohydrate) and the remaining subjects drank equal calories as a mixed meal. Quadriceps muscle biopsies were taken at 10 h. A semi-quantitative polymerase chain reaction was designed to measure gene expression. IGF-I, IGF-II and IGFBP-5 mRNA are present in adult human skeletal muscle, but no significant changes between meal groups were observed for IGF-I, IGF-II or IGFBP-5 mRNA levels, indicating that the expression of these genes are not altered acutely by nutrients and insulin.

  • 33.
    Currie, Andrew
    et al.
    Department of Surgery, St Mark's Hospital, Academic Institute, Imperial College London, London, United Kingdom.
    Burch, Jennifer
    Department of Surgery, St Mark's Hospital, Academic Institute, Imperial College London, London, United Kingdom.
    Jenkins, John T.
    Department of Surgery, St Mark's Hospital, Academic Institute, Imperial College London, London, United Kingdom.
    Faiz, Omar
    Department of Surgery, St Mark's Hospital, Academic Institute, Imperial College London, London, United Kingdom.
    Kennedy, Robin H.
    Department of Surgery, St Mark's Hospital, Academic Institute, Imperial College London, London, United Kingdom.
    Ljungqvist, Olle
    Örebro University, School of Medicine, Örebro University, Sweden. Department of Surgery, Örebro University Hospital, Örebro, Sweden.
    Demartines, Nicolas
    CHUV Lausanne Surg, Lausanne, Switzerland.
    Hjern, Fredrik
    Danderyds Sjukhus, Danderyd, Sweden.
    Norderval, Stig
    University Hospital of North Norway, Tromsö, Norway.
    Lassen, Kristoffer
    University Hospital of North Norway, Tromsö, Norway.
    Revhaug, Andarthur
    University Hospital of North Norway, Tromsö, Norway.
    Koczkas, Tomas
    Östersunds Sjukhus, Östersund, Sweden.
    Nygren, Jonas
    Ersta Sjukhus, Stockholm, Sweden.
    Gustafsson, Ulf
    Ersta Sjukhus, Stockholm, Sweden.
    Kornfeld, Dan
    Kirurgkliniken St Göran, Stockholm, Sweden.
    Slim, Karem
    University Hospital, Clermont Ferrand, France.
    Hill, Andrew
    Middlemore Hospital, Auckland, New Zealand.
    Soop, Mattias
    North Shore Hospital, Auckland, New Zealand.
    Carlander, Johan
    Västerås Centrallasarett, Västerås, Sweden.
    Lundberg, Owe
    Kirurgkliniken Umeå, Umeå, Sweden.
    Fearon, Ken
    Western General Hospital, Edinburgh, United Kingdom.
    Kennedy, Robin
    St Marks Hospital, London, England..
    The Impact of Enhanced Recovery Protocol Compliance on Elective Colorectal Cancer Resection Results From an International Registry2015In: Annals of Surgery, ISSN 0003-4932, E-ISSN 1528-1140, Vol. 261, no 6, p. 1153-1159Article in journal (Refereed)
    Abstract [en]

    Background: The ERAS (enhanced recovery after surgery) care has been shown in randomized clinical trials to improve outcome after colorectal surgery compared to traditional care. The impact of different levels of compliance and specific elements, particularly out with a trial setting, is poorly understood.

    Objective: This study evaluated the individual impact of specific patient factors and perioperative enhanced recovery protocol compliance on postoperative outcome after elective primary colorectal cancer resection.

    Methods: The international, multicenter ERAS registry data, collected between November 2008 and March 2013, was reviewed. Patient demographics, disease characteristics, and perioperative ERAS protocol compliance were assessed. Linear regression was undertaken for primary admission duration and logistic regression for the development of any postoperative complication.

    Findings: A total of 1509 colonic and 843 rectal resections were undertaken in 13 centers from 6 countries. Median length of stay for colorectal resections was 6 days, with readmissions in 216 (9.2%), complications in 948 (40%), and reoperation in 167 (7.1%) of 2352 patients. Laparoscopic surgery was associated with reduced complications [odds ratio (OR) = 0.68; P < 0.001] and length of stay (OR = 0.83, P < 0.001). Increasing ERAS compliance was correlated with fewer complications (OR = 0.69, P < 0.001) and shorter primary hospital admission (OR = 0.88, P < 0.001). Shorter hospital stay was associated with preoperative carbohydrate and fluid loading (OR = 0.89, P = 0.001), and totally intravenous anesthesia (OR= 0.86, P < 0.001); longer stay was associated with intraoperative epidural analgesia (OR = 1.07, P = 0.019). Reduced postoperative complications were associated with restrictive perioperative intravenous fluids (OR = 0.35, P < 0.001).

    Conclusions: This analysis has demonstrated that in a large, international cohort of patients, increasing compliance with an ERAS program and the use of laparoscopic surgery independently improve outcome.

  • 34.
    Degens, Hans
    et al.
    Department of Clinical Neuroscience, Karolinska Hospital, Stockholm, Sweden; Department of Anatomy, MDC Box 6, University of South Florida, Tampa FL, United States; Department of Anatomy, MDC 6, University of South Florida, Tampa, United States.
    Soop, Mattias
    Department of Surgery, Karolinska Hospital, Stockholm, Sweden.
    Höök, Peter
    Department of Clinical Neuroscience, Karolinska Hospital, Stockholm, Sweden; Department of Clinical Neuroscience, Karolinska Hospital, Stockholm, Sweden.
    Ljungqvist, Olle
    Örebro University, School of Medical Sciences. Department of Surgery, Huddinge University Hospital, Huddinge, Sweden.
    Larsson, Lars E.I.
    Department of Clinical Neuroscience, Karolinska Hospital, Stockholm, Sweden; Department of Clinical Neuroscience, Karolinska Hospital, Stockholm, Sweden.
    Post-operative effects on insulin resistance and specific tension of single skeletal muscle fibres1999In: Clinical Science, ISSN 0143-5221, E-ISSN 1470-8736, Vol. 97, no 4, p. 449-455Article in journal (Refereed)
    Abstract [en]

    Surgery and accidental trauma are associated with a transient period of insulin resistance, substrate catabolism and muscle weakness. In the present study, we evaluated the changes in the force-generating capacity of chemically skinned single muscle fibresfollowing abdominal surgery. Biopsies of the m. vastus lateralis were obtained in three patients 1 day before and 3 or 6 days after surgery. Part of the biopsy was frozen for histochemical analysis of the fibre cross-sectional area (FCSA) and myofibrillar protein content, and another part was used for single-fibre contractile measurements. All patients developed insulin resistance following surgery. The maximum velocity of unloaded shortening of single muscle fibres did not change following surgery. The FCSA did not decrease after surgery, as determined either from histochemical sections or from singlefibres measured at a fixed sarcomere length of 2.76+/-0.09 microm (mean+/-S.D.). Further, the force-generating capacity of the single fibres, measured as maximal Ca(2+)-activated force (P(0)) or as P(0) normalized to FCSA (specific tension), remained unchanged, as did the myofibrillar protein content of the muscle. In conclusion, the muscle weakness associated with post-operative insulin resistance is not related to a decreased specifictension or a loss of myofibrillar proteins. Other potential cellular mechanisms underlying post-operative weakness are discussed.

  • 35.
    Dort, Joseph C.
    et al.
    Section of Otolaryngology, Department of Surgery, Cumming School of Medicine, University of Calgary, Calgary AB, Canada; Cancer Strategic Clinical Network, Alberta Health Services, Calgary AB, Canada.
    Farwell, D. Gregory
    Department of Otolaryngology, Division of Head and Neck Surgery, University of California Davis, Sacramento, USA.
    Findlay, Merran
    Department of Nutrition and Dietetics, Royal Prince Alfred Hospital, Camperdown NSW, Australia.
    Huber, Gerhard F.
    ENT Clinic, University Hospital Zürich, Zürich, Switzerland .
    Kerr, Paul
    Department of Otolaryngology, Winnipeg MB, Canada.
    Shea-Budgell, Melissa A.
    Cancer Strategic Clinical Network, Alberta Health Services, Calgary AB, Canada; Department of Oncology, Cumming School of Medicine, University of Calgary, Calgary AB, Canada.
    Simon, Christian
    Department of Otolaryngology, Head and Neck Surgery, Centre hospitalier universitaire vaudois, University of Lausanne, Lausanne, Switzerland.
    Uppington, Jeffrey
    Davis Health System, University of California, Sacramento, USA.
    Zygun, David
    Division of Critical Care Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton AB, Canada.
    Ljungqvist, Olle
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Surgery, Örebro University Hospital, Örebro, Sweden.
    Harris, Jeffrey
    Division of Otolaryngology – Head and Neck Surgery, Department of Surgery, University of Alberta, Edmonton AB, Canada.
    Optimal Perioperative Care in Major Head and Neck Cancer Surgery With Free Flap Reconstruction: A Consensus Review and Recommendations From the Enhanced Recovery After Surgery Society2017In: JAMA Otolaryngology - Head and Neck Surgery, ISSN 2168-6181, E-ISSN 2168-619X, Vol. 143, no 3, p. 292-303Article, review/survey (Refereed)
    Abstract [en]

    Importance: Head and neck cancers often require complex, labor-intensive surgeries, especially when free flap reconstruction is required. Enhanced recovery is important in this patient population but evidence-based protocols on perioperative care for this population are lacking.

    Objective: To provide a consensus-based protocol for optimal perioperative care of patients undergoing head and neck cancer surgery with free flap reconstruction.

    Evidence Review: Following endorsement by the Enhanced Recovery After Surgery (ERAS) Society to develop this protocol, a systematic review was conducted for each topic. The PubMed and Cochrane databases were initially searched to identify relevant publications on head and neck cancer surgery from 1965 through April 2015. Consistent key words for each topic included "head and neck surgery," "pharyngectomy," "laryngectomy," "laryngopharyngectomy," "neck dissection," "parotid lymphadenectomy," "thyroidectomy," "oral cavity resection," "glossectomy," and "head and neck." The final selection of literature included meta-analyses and systematic reviews as well as randomized controlled trials where available. In the absence of high-level data, case series and nonrandomized studies in head and neck cancer surgery patients or randomized controlled trials and systematic reviews in non-head and neck cancer surgery patients, were considered. An international panel of experts in major head and neck cancer surgery and enhanced recovery after surgery reviewed and assessed the literature for quality and developed recommendations for each topic based on the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. All recommendations were graded following a consensus discussion among the expert panel.

    Findings: The literature search, including a hand search of reference lists, identified 215 relevant publications that were considered to be the best evidence for the topic areas. A total of 17 topic areas were identified for inclusion in the protocol for the perioperative care of patients undergoing major head and neck cancer surgery with free flap reconstruction. Best practice includes several elements of perioperative care. Among these elements are the provision of preoperative carbohydrate treatment, pharmacologic thromboprophylaxis, perioperative antibiotics in clean-contaminated procedures, corticosteroid and antiemetic medications, short acting anxiolytics, goal-directed fluid management, opioid-sparing multimodal analgesia, frequent flap monitoring, early mobilization, and the avoidance of preoperative fasting.

    Conclusions and Relevance: The evidence base for specific perioperative care elements in head and neck cancer surgery is variable and in many cases information from different surgerical procedures form the basis for these recommendations. Clinical evaluation of these recommendations is a logical next step and further research in this patient population is warranted.

  • 36.
    Elia, Marinos
    et al.
    Institute of Human Nutrition, University of Southampton, Southampton, UK.
    Ljungqvist, OlleDepartment of Surgery, Örebro University Hospital, Örebro, Sweden; Centre for Gastrointestinal Disease, Karolinska Institutet, Stockholm, Sweden.J Stratton, RebeccaInstitute of Human Nutrition, University of Southampton, Southampton, UK.Lanham-New, Susan A.Department of Nutritional Sciences, University of Surrey, Guildford, UK.
    Clinical Nutrition2013Collection (editor) (Refereed)
  • 37.
    Elias, Kevin M.
    et al.
    Brigham and Women’s Hospital, Harvard Medical School, Boston, USA.
    Stone, Alexander B.
    Brigham and Women’s Hospital, Harvard Medical School, Boston, USA.
    McGinigle, Katharine
    University of North Carolina School of Medicine, Chapel Hill, USA.
    Tankou, Jo'An I.
    Brigham and Women’s Hospital, Harvard Medical School, Boston, USA.
    Scott, Michael J.
    Virginia Commonwealth University Health System, Richmond, USA; Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA.
    Fawcett, William J.
    Royal Surrey County Hospital, Guilford, UK; University of Surrey, Guilford, UK.
    Demartines, Nicolas
    Lausanne University Hospital CHUV, Lausanne, Switzerland.
    Lobo, Dileep N
    Nottingham Digestive Diseases Centre, Nottingham, UK; National Institute for Health Research (NIHR), Nottingham, UK; Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust, Nottingham, UK; Queen’s Medical Centre, University of Nottingham, Nottingham, UK.
    Ljungqvist, Olle
    Örebro University, School of Medical Sciences.
    Urman, Richard D.
    Brigham and Women’s Hospital, Harvard Medical School, Boston, USA.
    Eras, Society
    The Reporting on ERAS Compliance, Outcomes, and Elements Research (RECOvER) Checklist: A Joint Statement by the ERAS® and ERAS® USA Societies2018In: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Enhanced recovery after surgery (ERAS) programs are multimodal care pathways designed to minimize the physiological and psychological impact of surgery for patients. Increased compliance with ERAS guidelines is associated with improved patient outcomes across surgical types. As ERAS programs have proliferated, an unintentional effect has been significant variation in how ERAS-related studies are reported in the literature.

    METHODS: Society launched an effort to create an instrument to assist authors in manuscript preparation. Criteria to include were selected by a combination of literature review and expert opinion. The final checklist was refined by group consensus.

    RESULTS: The Societies present the Reporting on ERAS Compliance, Outcomes, and Elements Research (RECOvER) Checklist. The tool contains 20 items including best practices for reporting clinical pathways, compliance auditing, and formatting guidelines.

    CONCLUSIONS: The RECOvER Checklist is intended to provide a standardized framework for the reporting of ERAS-related studies. The checklist can also assist reviewers in evaluating the quality of ERAS-related manuscripts. Authors are encouraged to include the RECOvER Checklist when submitting ERAS-related studies to peer-reviewed journals.

  • 38.
    Eliman, A.
    et al.
    Department of Paediatrics, Endocrine Research Unit, Huddinge University Hospital, Karolinska Institute, Huddinge, Sweden.
    Tjäder, I.
    Department of Anaesthesiology and Intensive Care, Huddinge University Hospital, Karolinska Institute, Huddinge, Sweden.
    Norgren, S.
    Department of Paediatrics, Endocrine Research Unit, Huddinge University Hospital, Karolinska Institute, Huddinge, Sweden.
    Wernerman, J.
    Department of Anaesthesiology and Intensive Care, Huddinge University Hospital, Karolinska Institute, Huddinge, Sweden.
    Essén, P.
    Department of Anaesthesiology and Intensive Care, Huddinge University Hospital, Karolinska Institute, Huddinge, Sweden.
    Ljungqvist, Olle
    Department of Surgery, Huddinge University Hospital, Karolinska Institute, Huddinge, Sweden.
    Marcus, C.
    Department of Paediatrics, Endocrine Research Unit, Huddinge University Hospital, Karolinska Institute, Huddinge, Sweden.
    Totalparenteral nutrition after surgery rapidly increases serum leptin levels2001In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 144, no 2, p. 123-128Article in journal (Refereed)
    Abstract [en]

    Objective: In humans, leptin is regulated by long-term changes in energy intake. However, short-term regulation of serum leptin by nutrients has been difficult to show. The aim of this study was to investigate whether short periods of fasting and stress sensitise the leptin response to nutrients.

    Subjects and experimental protocol: Fourteen patients of normal weight undergoing elective open cholecystectomy were randomised into two groups. One group received saline infusion during surgery and for 24 h postoperatively. The other group also received saline during the surgical procedure, but total parenteral (TPN) was started immediately after surgery. Blood samples were drawn before as well as 2, 4, 8, 16, and 24 h after the start of surgery to determine the serum levels of leptin and other hormones.

    Results: Postoperative TPN induced a significant rise in serum leptin within 6 h, reaching a more than fourfold increase within 14 h (P < 0.001). Serum glucose and insulin levels increased within 2 h. Growth hormone and IGF-1 serum levels also increased significantly in the group receiving TPN. Serum cortisol levels increased postoperatively in both groups, which may explain why no significant reduction in serum leptin was observed in the group receiving saline. Free tri-iodothyronine (T3) decreased in both groups, while catecholamines were similar in the groups.

    Conclusion: During fasting and surgical stress, nutrients rapidly increased the serum leptin levels in humans in a manner similar to that previously reported in rodents. This may be mediated by increases in serum glucose, insulin and cortisol.

  • 39.
    El-Sharkawy, Ahmed M.
    et al.
    Gastrointestinal Surgery, National Institute for Health Research Nottingham Digestive Diseases Biomedical Research Unit, Nottingham University Hospitals and University of Nottingham, Queen’s Medical Centre, Nottingham, UK.
    Watson, Phillip
    School of Exercise and Health Sciences, Loughborough University, Loughborough, UK.
    Neal, Keith R.
    Division of Public Health and Epidemiology, University of Nottingham, Nottingham, UK.
    Ljungqvist, Olle
    Örebro University, School of Medicine, Örebro University, Sweden.
    Maughan, Ron J.
    School of Exercise and Health Sciences, Loughborough University, Loughborough, UK.
    Sahota, Opinder
    Department of Elderly Medicine, Nottingham University Hospitals, Queen’s Medical Centre, Nottingham, UK.
    Lobo, Dileep N.
    Gastrointestinal Surgery, National Institute for Health Research Nottingham Digestive Diseases Biomedical Research Unit, Nottingham University Hospitals and University of Nottingham, Queen’s Medical Centre, Nottingham, UK.
    Hydration and outcome in older patients admitted to hospital (The HOOP prospective cohort study)2015In: Age and Ageing, ISSN 0002-0729, E-ISSN 1468-2834, Vol. 44, no 6, p. 943-947Article in journal (Refereed)
    Abstract [en]

    Background: older adults are susceptible to dehydration due to age-related pathophysiological changes. We aimed to investigate the prevalence of hyperosmolar dehydration (HD) in hospitalised older adults, aged >= 65 years, admitted as an emergency and to assess the impact on short-term and long-term outcome.

    Methods: this prospective cohort study was performed on older adult participants who were admitted acutely to a large UK teaching hospital. Data collected included the Charlson comorbidity index (CCI), national early warning score (NEWS), Canadian Study of Health and Aging (CSHA) clinical frailty scale and Nutrition Risk Screening Tool (NRS) 2002. Admission bloods were used to measure serum osmolality. HD was defined as serum osmolality > 300 mOsmol/kg. Participants who were still in hospital 48 h after admission were reviewed, and the same measurements were repeated.

    Results: a total of 200 participants were recruited at admission to hospital, 37% of whom were dehydrated. Of those dehydrated, 62% were still dehydrated when reviewed at 48 h after admission. Overall, 7% of the participants died in hospital, 79% of whom were dehydrated at admission (P = 0.001). Cox regression analysis adjusted for age, gender, CCI, NEWS, CSHA and NRS demonstrated that participants dehydrated at admission were 6 times more likely to die in hospital than those euhydrated, hazards ratio (HR) 6.04 (1.64-22.25); P = 0.007.

    Conclusions: HD is common in hospitalised older adults and is associated with poor outcome. Coordinated efforts are necessary to develop comprehensive hydration assessment tools to implement and monitor a real change in culture and attitude towards hydration in hospitalised older adults.

  • 40.
    Esahili, A. H.
    et al.
    Department of Surgery, Karolinska Hospital, S-104 01 Stockholm, Sweden.
    Boija, Per Olov
    Department of Surgery, Karolinska Hospital, S-104 01 Stockholm, Sweden.
    Ljungqvist, Olle
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Surgery, Karolinska Hospital, S-104 01 Stockholm, Sweden.
    Rubio, Carlos Alberto
    Department of Surgery, Karolinska Hospital, S-104 01 Stockholm, Sweden.
    Ware, James
    Department of Surgery, Karolinska Hospital, S-104 01 Stockholm, Sweden.
    Twenty-four hour fasting increases endotoxin lethality in the rat1991In: European Journal of Surgery, ISSN 1102-4151, E-ISSN 1741-9271, Vol. 157, no 2, p. 89-95Article in journal (Refereed)
    Abstract [en]

    The effect of 24 h food deprivation on endotoxin (ET) lethality in SpD rats was studied. Fed and fasted animals received either 6 h i.v. infusions or i.p. boluses of ET at low, intermediate and high doses, and survival for seven days observed. Fasting was associated with 208-240% greater mortality when ET was infused i.v., and 87-200% when given i.p. ET doses LD10-LD80 gave a linear relationship with mortality. In non-fasted control rats liver glycogen content reduced by 1.28 mumols/min/g dry liver wt over the first post-prandial six hours, and increased by 65-99% in a dose dependent manner after ET (p less than 0.01). Evidence was also obtained relating both liver damage (assessed blind by histopathological scoring) and leucopenia with endotoxin dose, results which were modified by nutritional status. The evidence supports the role of liver glycogen as a protective substrate resource in endotoxic shock.

  • 41.
    Essén, Pia
    et al.
    Depts. of Anesth. and Intensive Care, Huddinge University Hospital, Stockholm, Sweden; Depts. of Anesth. and Intensive Care, Karolinska Institute, Stockholm, Sweden.
    Thorell, Anders
    Department of Surgery, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden.
    McNurlan, Margaret A.
    Rowett Research Institute, Aberdeen, United Kingdom.
    Anderson, Susan
    Rowett Research Institute, Aberdeen, United Kingdom.
    Ljungqvist, Olle
    Örebro University, School of Medical Sciences. Department of Surgery, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden.
    Wernerman, Jan
    Depts. of Anesth. and Intensive Care, Huddinge University Hospital, Stockholm, Sweden; Depts. of Anesth. and Intensive Care, Karolinska Institute, Stockholm, Sweden.
    Garlick, Peter J.
    Department of Surgery, State University of New York, Stony Brook NY, United States.
    Laparoscopic cholecystectomy does not prevent the postoperative protein catabolic response in muscle1995In: Annals of Surgery, ISSN 0003-4932, E-ISSN 1528-1140, Vol. 222, no 1, p. 36-42Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    The authors determined the effect of laparoscopic cholecystectomy on protein synthesis in skeletal muscle. In addition to a decrease in muscle protein synthesis, after open cholecystectomy, the authors previously demonstrated a decrease in insulin sensitivity. This study on patients undergoing laparoscopic and open surgery, therefore, included simultaneous measurements of protein synthesis and insulin sensitivity.

    SUMMARY BACKGROUND DATA:

    Laparoscopy has become a routine technique for several operations because of postoperative benefits that allow rapid recovery. However, its effect on postoperative protein catabolism has not been characterized. Conventional laparotomy induces a drop in muscle protein synthesis, whereas degradation is unaffected.

    METHODS:

    Patients were randomized to laparoscopic or open cholecystectomy, and the rate of protein synthesis in skeletal muscle was determined 24 hours postoperatively by the flooding technique using L-(2H5)phenylalanine, during a hyperinsulinemic normoglycemic clamp to assess insulin sensitivity.

    RESULTS:

    The protein synthesis rate decreased by 28% (1.77 +/- 0.11%/day vs. 1.26 +/- 0.08%/day, p < 0.01) in the laparoscopic group and by 20% (1.97 +/- 0.15%/day vs. 1.57 +/- 0.15%/day, p < 0.01) in the open cholecystectomy group. In contrast, the fall in insulin sensitivity after surgery was lower with laparoscopic (22 +/- 2%) compared with open surgery (49 +/- 5%).

    CONCLUSIONS:

    Laparoscopic cholecystectomy did not avoid a substantial decline in muscle protein synthesis, despite improved insulin sensitivity. The change in the two parameters occurred independently, indicating different mechanisms controlling insulin sensitivity and muscle protein synthesis.

  • 42.
    Fawcett, William J.
    et al.
    Consultant Anaesthetist, Royal Surrey County Hospital, Guildford, UK.
    Ljungqvist, Olle
    Örebro University, School of Medical Sciences. Department of Surgery, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Starvation, carbohydrate loading, and outcome after major surgery2017In: BJA Education, ISSN 2058-5349, Vol. 17, no 9, p. 312-316Article in journal (Refereed)
  • 43.
    Fearon, K C H
    et al.
    Clinical and Surgical Sciences (Surgery), School of Clinical Sciences and Community Health, The University of Edinburgh, Edinburgh, UK.
    Ljungqvist, Olle
    Centre of Gastrointestinal Disease, Ersta Hospital, Stockholm; Karolinska Institutet, Centre for Surgical Sciences, Karolinska University Hospital, Huddinge, Stockholm.
    Von Meyenfeldt, M
    Department of Surgery, University Hospital Maastricht, The Netherlands.
    Revhaug, A
    Department of Surgery, Tromso University Hospital, Tromso, Norway.
    Dejong, C H C
    Department of Surgery, University Hospital Maastricht, The Netherlands.
    Lassen, K
    Department of Surgery, Tromso University Hospital, Tromso, Norway.
    Nygren, J
    Centre of Gastrointestinal Disease, Ersta Hospital, Stockholm; Karolinska Institutet, Centre for Surgical Sciences, Karolinska University Hospital, Huddinge, Stockholm.
    Hausel, J
    Centre of Gastrointestinal Disease, Ersta Hospital, Stockholm; Karolinska Institutet, Centre for Surgical Sciences, Karolinska University Hospital, Huddinge, Stockholm.
    Soop, M
    Centre of Gastrointestinal Disease, Ersta Hospital, Stockholm; Karolinska Institutet, Centre for Surgical Sciences, Karolinska University Hospital, Huddinge, Stockholm.
    Andersen, J
    Department of Surgical Gastroenterology, Hvidovre University Hospital, Hvidovre, Denmark.
    Kehlet, H
    Department of Surgical Gastroenterology, Hvidovre University Hospital, Hvidovre, Denmark; fSection for Surgical Pathophysiology, Rigshospitalet, Copenhagen, Denmark.
    Enhanced recovery after surgery: a consensus review of clinical care for patients undergoing colonic resection2005In: Clinical Nutrition, ISSN 0261-5614, E-ISSN 1532-1983, Vol. 24, no 3, p. 466-77Article in journal (Refereed)
    Abstract [en]

    Background & aims: Clinical care of patients undergoing colonic surgery differs between hospitals and countries. In addition, there is considerable variation in rates of recovery and length of hospital stay following major abdominal surgery. There is a need to develop a consensus on key elements of perioperative care for inclusion in enhanced recovery programmes so that these can be widely adopted and refined further in future clinical trials.

    Methods: Medline database was searched for all clinical studies/trials relating to enhanced recovery after colorectal resection. Relevant papers from the reference lists of these articles and from the authors' personal collections were also reviewed. A combination of evidence-based and consensus methodology was used to develop the resulting enhanced recovery after surgery (ERAS) clinical care protocol.

    Results and conclusions: Within traditional perioperative practice there is considerable evidence supporting a range of manoeuvres which, in isolation, may improve individual aspects of recovery after colonic surgery. The present manuscript reviews these issues in detail. There is also growing evidence that an integrated multimodal approach to perioperative care can result in an overall enhancement of recovery. However, effects on major morbidity and mortality remain to be determined. A protocol is presented which is in current use by the ERAS Group and may provide a standard of care against which either current or future novel elements of an enhanced recovery approach can be tested for their effect on outcome.

  • 44.
    Feldheiser, A.
    et al.
    Department of Anesthesiology and Intensive Care Medicine Campus Charité, Mitte and Campus Virchow-Klinikum Charité, University Medicine, Berlin, Germany.
    Aziz, O.
    St. Mark’s Hospital, Harrow, UK.
    Baldini, G.
    Department of Anesthesia, McGill University Health Centre, Montreal General Hospital, Montreal QC, Canada.
    Cox, B. P. B. W.
    Department of Anesthesiology and Pain Therapy, University Hospital Maastricht (azM), Maastricht, The Netherlands.
    Fearon, K. C. H.
    Clinical Surgery, The Royal Infirmary, University of Edinburgh, Edinburgh, UK.
    Feldman, L. S.
    Department of Surgery, McGill University Health Centre, Montreal General Hospital, Montreal QC, Canada.
    Gan, T. J.
    Department of Anesthesiology, Duke University Medical Center, Durham NC, USA.
    Kennedy, R. H.
    St. Mark’s Imperial College, London, UK; St. Mark’s Hospital, Harrow, UK.
    Ljungqvist, Olle
    Örebro University, School of Medical Sciences. Department of Surgery.
    Lobo, D. N.
    Gastrointestinal Surgery, National Institute for Health Research Nottingham Digestive Diseases Biomedical Research Unit, Nottingham University Hospitals and University of Nottingham, Queen’s Medical Centre, Nottingham, UK.
    Miller, T.
    Department of Anesthesiology, Duke University Medical Center, Durham NC, USA.
    Radtke, F. F.
    Department of Anesthesiology and Intensive Care Medicine Campus Charité, Mitte and Campus Virchow-Klinikum Charité, University Medicine, Berlin, Germany.
    Ruiz Garces, T.
    Anestesiologa y Reanimacin, Hospital Clinico Lozano Blesa, Universidad de Zaragoza, Zaragoza, Spain.
    Schricker, T.
    Department of Anesthesia, McGill University Health Centre, Royal Victoria Hospital, Montreal QC, Canada.
    Scott, M. J.
    Royal Surrey County Hospital NHS Foundation Trust, University of Surrey, Guildford, UK.
    Thacker, J. K.
    Department of Surgery, Duke University Medical Center, Durham NC, USA.
    Ytrebø, L. M.
    Department of Anaesthesiology, University Hospital of North Norway, Tromsø, Norway.
    Carli, F.
    Department of Anesthesia, McGill University Health Centre, Montreal General Hospital, Montreal QC, Canada.
    Enhanced Recovery After Surgery (ERAS) for gastrointestinal surgery, part 2: consensus statement for anaesthesia practice2016In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 60, no 3, p. 289-334Article, review/survey (Refereed)
    Abstract [en]

    Background: The present interdisciplinary consensus review proposes clinical considerations and recommendations for anaesthetic practice in patients undergoing gastrointestinal surgery with an Enhanced Recovery after Surgery (ERAS) programme.

    Methods: Studies were selected with particular attention being paid to meta-analyses, randomized controlled trials and large prospective cohort studies. For each item of the perioperative treatment pathway, available English-language literature was examined and reviewed. The group reached a consensus recommendation after critical appraisal of the literature.

    Results: This consensus statement demonstrates that anaesthesiologists control several preoperative, intraoperative and postoperative ERAS elements. Further research is needed to verify the strength of these recommendations.

    Conclusions: Based on the evidence available for each element of perioperative care pathways, the Enhanced Recovery After Surgery (ERAS ((R))) Society presents a comprehensive consensus review, clinical considerations and recommendations for anaesthesia care in patients undergoing gastrointestinal surgery within an ERAS programme. This unified protocol facilitates involvement of anaesthesiologists in the implementation of the ERAS programmes and allows for comparison between centres and it eventually might facilitate the design of multi-institutional prospective and adequately powered randomized trials.

  • 45.
    Francis, Nader K.
    et al.
    Department of Colorectal Surgery, Yeovil District Hospital Foundation Trust, Higher Kingston, Yeovil, UK; Faculty of Science, University of Bath, Bath, UK.
    Walker, Thomas
    Department of Colorectal Surgery, Yeovil District Hospital Foundation Trust, Higher Kingston, Yeovil, UK.
    Carter, Fiona
    South West Surgical Training Network, ERAS-UK, Yeovil, UK.
    Hübner, Martin
    Department of Visceral Surgery, Lausanne University Hospital (CHUV), Lausanne, Switzerland.
    Balfour, Angela
    NHS Lothian Western General Hospital, Edinburgh, UK.
    Jakobsen, Dorthe Hjort
    Section of Surgical Pathophysiology, Rigshospitalet, Copenhagen, Denmark.
    Burch, Jennie
    Head of Gastrointestinal Nurse Education, Academic Institute, St Mark's Hospital, London, UK.
    Wasylak, Tracy
    Strategic Clinical Networks, Alberta Health Services, Edmonton AB, Canada; Faculty of Nursing, University of Calgary, Calgary AB, Canada.
    Demartines, Nicolas
    Department of Visceral Surgery, Lausanne University Hospital (CHUV), Lausanne, Switzerland.
    Lobo, Dileep N.
    Gastrointestinal Surgery, Nottingham Digestive Diseases Centre, Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust, Nottingham, UK; Queen's Medical Centre, University of Nottingham, Nottingham, UK; National Institute for Health Research (NIHR), London, UK.
    Addor, Valerie
    Department of Visceral Surgery, Lausanne University Hospital (CHUV), Lausanne, Switzerland.
    Ljungqvist, Olle
    Örebro University, School of Medical Sciences. Department of Surgery, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Consensus on Training and Implementation of Enhanced Recovery After Surgery: A Delphi Study2018In: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 42, no 7, p. 1919-1928Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Enhanced Recovery After Surgery (ERAS) is widely accepted in current surgical practice due to its positive impact on patient outcomes. The successful implementation of ERAS is challenging and compliance with protocols varies widely. Continual staff education is essential for successful ERAS programmes. Teaching modalities exist, but there remains no agreement regarding the optimal training curriculum or how its effectiveness is assessed. We aimed to draw consensus from an expert panel regarding the successful training and implementation of ERAS.

    METHODS: A modified Delphi technique was used; three rounds of questionnaires were sent to 58 selected international experts from 11 countries across multiple ERAS specialities and multidisciplinary teams (MDT) between January 2016 and February 2017. We interrogated opinion regarding four topics: (1) the components of a training curriculum and the structure of training courses; (2) the optimal framework for successful implementation and audit of ERAS including a guide for data collection; (3) a framework to assess the effectiveness of training; (4) criteria to define ERAS training centres of excellence.

    RESULTS: An ERAS training course must cover the evidence-based principles of ERAS with team-oriented training. Successful implementation requires strong leadership, an ERAS facilitator and an effective MDT. Effectiveness of training can be measured by improved compliance. A training centre of excellence should show a willingness to teach and demonstrable team working.

    CONCLUSIONS: We propose an international expert consensus providing an ERAS training curriculum, a framework for successful implementation, methods for assessing effectiveness of training and a definition of ERAS training centres of excellence.

  • 46. Frauche, P.
    et al.
    Hübner, M.
    Ljungqvist, Olle
    Örebro University, School of Medical Sciences.
    Fast-track and ERAS programs i Geriatric Surgery2018In: Perioperative Care of the Elderly: Clinical and Organizational Aspects / [ed] G. Bettelli, Cambridge, United Kingdom: Cambridge University Press, 2018, 1, p. 226-232Chapter in book (Refereed)
  • 47.
    Fredriksson, Katarina
    et al.
    Department of Anesthesiology and Intensive Care, Karolinska University Hospital, Huddinge, Stockholm.
    Hammarqvist, Folke
    Gastrocentrum, Department of Surgery, Karolinska University Hospital, Huddinge, Stockholm.
    Strigård, Karin
    Gastrocentrum, Department of Surgery, Karolinska University Hospital, Huddinge, Stockholm.
    Hultenby, Kjell
    Clinical Research Center, Karolinska University Hospital, Huddinge, Stockholm.
    Ljungqvist, Olle
    Center for Gastrointestinal Disease at Ersta Hospital, CLINTEC, Karolinska Institutet, Stockholm.
    Wernerman, Jan
    Department of Anesthesiology and Intensive Care, Karolinska University Hospital, Huddinge, Stockholm.
    Rooyackers, Olav
    Department of Anesthesiology and Intensive Care, Karolinska University Hospital, Huddinge, Stockholm.
    Derangements in mitochondrial metabolism in intercostal and leg muscle of critically ill patients with sepsis-induced multiple organ failure2006In: American Journal of Physiology. Endocrinology and Metabolism, ISSN 0193-1849, E-ISSN 1522-1555, Vol. 291, no 5, p. E1044-50Article in journal (Refereed)
    Abstract [en]

    Critically ill patients treated for multiple organ failure often develop muscle dysfunction. Here we test the hypothesis that mitochondrial and energy metabolism are deranged in leg and intercostal muscle of critically ill patients with sepsis-induced multiple organ failure. Ten critically ill patients suffering from sepsis-induced multiple organ failure and requiring mechanical ventilation were included in the study. A group (n = 10) of metabolically healthy age- and sex-matched patients undergoing elective surgery were used as controls. Muscle biopsies were obtained from the vastus lateralis (leg) and intercostal muscle. The activities of citrate synthase and mitochondrial respiratory chain complexes I and IV and concentrations of ATP, creatine phosphate, and lactate were analyzed. Morphological evaluation of mitochondria was performed by electron microscopy. Activities of citrate synthase and complex I were 53 and 60% lower, respectively, in intercostal muscle of the patients but not in leg muscle compared with controls. The activity of complex IV was 30% lower in leg muscle but not in intercostal muscle. Concentrations of ATP and creatine phosphate were, respectively, 40 and 34% lower, and lactate concentrations were 43% higher in leg muscle but not in intercostal muscle. We conclude that both leg and intercostal muscle show a twofold decrease in mitochondrial content in intensive care unit patients with multiple organ failure, which is associated with lower concentrations of energy-rich phosphates and an increased anaerobic energy production in leg muscle but not in intercostal muscle.

  • 48.
    Friberg, B.
    et al.
    Dept of Surgery, Karolinska Hospital, Stockholm, Sweden.
    Heilborn, Berit
    Dept of Surgery, Karolinska Hospital, Stockholm, Sweden.
    Häggmark, Tom
    Dept of Surgery, Karolinska Hospital, Stockholm, Sweden.
    Ljungqvist, Olle
    Örebro University, School of Medical Sciences. Dept of Surgery, Karolinska Hospital, Stockholm, Sweden.
    Food deprivation prior to stress reduces stimulated muscle force both before and after hemorrhage in the rat1994In: Journal of Surgical Research, ISSN 0022-4804, E-ISSN 1095-8673, Vol. 16, no 2, p. 131-137Article in journal (Refereed)
  • 49.
    Fujii, N.
    et al.
    Research Division, Joslin Diabetes Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
    Hayashi, T.
    Research Division, Joslin Diabetes Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
    Hirshman, M.
    Research Division, Joslin Diabetes Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
    Smith, J.
    Research Division, Joslin Diabetes Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
    Habonowski, S.
    Endocrine-Metabolism Division, Department of Medicine and Biochemistry, Dartmouth Medical School, Hanover, New Hampshire, USA.
    Kaijser, L.
    Department of Clinical Physiology, Huddinge University Hospital, Karolinska Institute, Huddinge, Sweden.
    Mu, J.
    Howard Hughes Medical Institute, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
    Ljungqvist, Olle
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Surgery, Huddinge University Hospital, Karolinska Institute, Huddinge, Sweden; Center of Gastrointestinal Disease, Ersta Hospital, Karolinska Institute, Stockholm, Sweden.
    Birnbaum, M.
    Howard Hughes Medical Institute, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
    Witters, L.
    Endocrine-Metabolism Division, Department of Medicine and Biochemistry, Dartmouth Medical School, Hanover, New Hampshire, USA.
    Thorell, A.
    Center of Gastrointestinal Disease, Ersta Hospital, Karolinska Institute, Stockholm, Sweden.
    Goodyear, L.
    Research Division, Joslin Diabetes Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
    Exercise induces isoform-specific increase in 5'AMP-activated protein kinase activity in human skeletal muscle2000In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 273, no 3, p. 1150-1155Article in journal (Refereed)
    Abstract [en]

    The 5'AMP-activated protein kinase (AMPK) is stimulated by contractile activity in rat skeletal muscle. AMPK has emerged as an important signaling intermediary in the regulation of cell metabolism being linked to exercise-induced changes in muscle glucose and fatty acid metabolism. In the present study, we determined the effects of exercise on isoform-specific AMPK activity (alpha1 and alpha2) in human skeletal muscle. Needle biopsies of vastus lateralis muscle were obtained from seven healthy subjects at rest, after 20 and 60 min of cycle ergometer exercise at 70% of VO(2)max, and 30 min following the 60 min exercise bout. In comparison to the resting state, AMPK alpha2 activity significantly increased at 20 and 60 min of exercise, and remained at a higher level with 30 min of recovery. AMPK alpha1 activity tended to slightly decrease with 20 min of exercise at 70%VO(2)max; however, the change was not statistically significant. AMPK alpha1 activities were at basal levels at 60 min of exercise and 30 min of recovery. On a separate day, the same subjects exercised for 20 min at 50% of VO(2)max. Exercise at this intensity did not change alpha2 activity, and similar to exercise at 70% of VO(2)max, there was no significant change in alpha1 activity. In conclusion, exercise at a higher intensity for only 20 min leads to increases in AMPK alpha2 activity but not alpha1 activity. These results suggest that the alpha2-containing AMPK complex, rather than alpha1, may be involved in the metabolic responses to exercise in human skeletal muscle.

  • 50.
    Gannedahl, P. E.
    et al.
    Dept. of Anesth. and Intensive Care, Karolinska Institute, Karolinska, Sweden; eDept. of Anesth. and Intensive Care, Karolinska Hospital, Stockholm, Sweden.
    Edner, M.
    Department of Cardiology, Karolinska Institute, Karolinska, Sweden; Danderyd Hospitals, Stockholm, Sweden.
    Ljungqvist, Olle
    Department of Surgery, Karolinska Institute, Karolinska, Sweden.
    Computerized vectorcardiography for improved perioperative cardiac monitoring in vascular surgery1996In: Journal of the American College of Surgeons, ISSN 1072-7515, E-ISSN 1879-1190, Vol. 182, no 6, p. 530-536Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Postoperative cardiac complications occur frequently after noncardiac operations in high-risk patients. Routine cardiac monitoring is usually done by electrocardiographic (ECG) methods. The present analysis shows that computerized vectorcardiography (VCG) is superior to traditional ECG monitoring in predicting postoperative cardiac complications.

    STUDY DESIGN: Thirty-eight patients scheduled for abdominal aortic operations were monitored intraoperatively and for 48 hours postoperatively using VCG. These data were analyzed in a blinded fashion, and compared to cardiac outcome and regularly calculated 12-lead ECGs.

    RESULTS: Thirteen patients suffered from cardiac events: myocardial infarction (n = 3), cardiac death (n = 1), recurrent myocardial ischemia (n = 1), arrhythmias (n = 2), congestive heart failure (n = 2), and arrhythmias combined with congestive heart failure (n = 4). Thirty of 38 patients had ischemia recorded on their VCG, including all 13 patients with cardiac events. Only seven of the 13 patients had ischemic changes on the V5-lead alone and ten on the three leads II, V4, V5, yielding a sensitivity of 54 percent (V5), 77 percent (II, V4, V5) and 100 percent (VCG). Signs of ischemia appeared 400 +/- 690 (mean plus or minus standard deviation) minutes earlier (median 78 minutes, with a range of zero to 2,284 minutes), and never later on the VCG compared to the three leads II, V4, V5.

    CONCLUSIONS: Vectorcardiography in this risk group shows increased sensitivity in predicting perioperative cardiac complications and earlier ischemia detection than the most sensitive scalar leads. Vectorcardiography substantially improves the possibility of earlier intervention, potentially reducing the incidence of postoperative cardiac complications.

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