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  • 151.
    Steinvall, Ingrid
    et al.
    Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Plastic Surgery, Hand surgery UHL. Linköping University, Department of Clinical and Experimental Medicine, Plastic Surgery, Hand Surgery and Burns.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Bak, Zoltan
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Burn Center. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Plastic Surgery, Hand surgery UHL. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Mortality After Thermal Injury: No Sex-Related Difference2011In: JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE, ISSN 0022-5282, Vol. 70, no 4, p. 959-964Article in journal (Refereed)
    Abstract [en]

    Background: Young women have been reported to be more likely to survive than men after severe trauma. Girls also have less inflammation and hypermetabolism after major burns. Yet burned women have been found to have a twofold greater risk of death than men. Our aim was to find out if there is a sex-related difference in mortality after thermal injury, particularly in the age group between 16 years and 49 years, when hormonal differences would be most influential. Methods: All patients admitted to the Linkoping University Hospital Burn Unit with thermal injuries during the years 1993-2008 were included and the variables percentage burned total body surface area (TBSA%), age, type of burn, mechanical ventilation, and year were included in a multiple regression (Poisson log) model. Results: Of 1,119 patients with thermal injury, 792 (71%) were men. Crude mortality was 5% among men, and 8% among women (p = 0.04). After adjustment for age and TBSA%, there was no correlation between mortality and sex, in any age group. Eight men and four women died in the group of young adults (16-49 years) in which TBSA% correlated with mortality (p andlt; 0.01) but age did not. Mortality was 14% (32 of 221) among the men and 23% (23 of 102) of women in the group of older adults (50 years and older), and both age and TBSA% correlated with mortality (p andlt; 0.001). Conclusions: There is no relevant sex-related difference in survival after thermal injury. The conclusion is, however, tempered by the few deaths, particularly among younger adults.

  • 152.
    Szabó, Zoltan
    et al.
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Andersson, Rolf
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
    Arnqvist, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Intraoperative muscle and fat metabolism in diabetic patients during coronary artery bypass grafting surgery: a parallel microdialysis and organ balance study2009In: British Journal of Anaesthesia, ISSN 0007-0912, E-ISSN 1471-6771, Vol. 103, no 2, p. 166-172Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Surgical trauma causes stress and inflammatory reactions with elevated serum free fatty acids (FFA) and glucose levels characteristic of intraoperative insulin resistance. Our aim was to compare microdialysis findings with those using the classical organ balance technique and to test the clinical feasibility of microdialysis during cardiac surgery. METHODS: Nine diabetic and nine non-diabetic patients, undergoing routine coronary artery bypass grafting surgery, were studied using both microdialysis and the organ balance technique in the brachio-radial muscle of the forearm, and microdialysis in the pre-pectoral fat tissue. Glucose, lactate, and glycerol were measured in arterial and venous plasma and in the microdialysate before administration of heparin, at the release of the aortic cross-clamp, and before transfer to the intensive care unit. RESULTS: Glucose release from the diabetic muscle at the last sampling time was detected. This was confirmed by a negative glucose A-I (arterial-interstitial difference) in the muscle. No differences were observed regarding lipolysis in the fat tissue in terms of A-I of glycerol. Intergroup differences were detected at the first sampling time, where arterial plasma glucose and plasma insulin levels were higher and muscle interstitial glucose lower in the diabetic patients. Plasma insulin was higher in the diabetic patients even at the final measurement time. CONCLUSIONS: In terms of lipolysis in the fat tissue and glucose transport in the muscle, the non-diabetic patients were metabolically 'diabetics' during surgery. Despite strict blood glucose control, disturbances in glucose homeostasis in the diabetic muscle persist. Microdialysis was easy to use during cardiac surgery.

  • 153.
    Tchou Folkesson, Kim
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Samuelsson, Anders
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Intensive Care UHL.
    Tesselaar, Erik
    Linköping University, Department of Clinical and Experimental Medicine, Burn Center. Linköping University, Faculty of Health Sciences.
    Dahlström, Bengt
    AB Biopharmacon, Uppsala.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Burn Center. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Plastic Surgery, Hand surgery UHL. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    A Human Vascular Model Based on Microdialysis for the Assessment of the Vasoconstrictive Dose-Response Effects of Norepinephrine and Vasopressin in Skin2012In: Microcirculation, ISSN 1073-9688, E-ISSN 1549-8719, Vol. 19, no 4, p. 352-359Article in journal (Refereed)
    Abstract [en]

    Abstract Objective: Microdialysis enables drug delivery in the skin and simultaneous measurement of their effects. The present study aimed to evaluate dose-dependent changes in blood flow and metabolism during microdialysis of norepinephrine and vasopressin. Methods: We investigated whether increasing concentrations of norepinephrine (NE, 1.859 mu mol/L) and vasopressin (VP, 1100 nmol/L), delivered sequentially in one catheter or simultaneously through four catheters, yield dose-dependent changes in blood flow (as measured using urea clearance) and metabolism (glucose and lactate). Results: We found a significant dose-dependent vasoconstriction with both drugs. Responses were characterized by a sigmoid dose response model. Urea in the dialysate increased from a baseline of 7.9 +/- 1.7 to 10.9 +/- 0.9 mmol/L for the highest concentration of NE (p andlt; 0.001) and from 8.1 +/- 1.4 to 10.0 +/- 1.7 mmol/L for the highest concentration of VP (p = 0.037). Glucose decreased from 2.3 +/- 0.7 to 0.41 +/- 0.18 mmol/L for NE (p = 0.001) and from 2.7 +/- 0.6 to 1.3 +/- 0.5 mmol/L for VP (p andlt; 0.001). Lactate increased from 1.1 +/- 0.4 to 2.6 +/- 0.5 mmol/L for NE (p = 0.005) and from 1.1 +/- 0.4 to 2.6 +/- 0.5 mmol/L for VP (p = 0.008). There were no significant differences between responses from a single catheter and from those obtained simultaneously using multiple catheters. Conclusions: Microdialysis in the skin, either with a single catheter or using multiple catheters, offers a useful tool for studying dose response effects of vasoactive drugs on local blood flow and metabolism without inducing any systemic effects.

  • 154.
    Turina, Dean
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Propofol changes the cytoskeletal function in neurons: An experimental study in cortical cultures2012Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Every day, general anaesthetics are given to a large number of patients around the world but the cellular mechanisms of how anaesthetics act are still not clear. General anaesthetics cause the intended unconsciousness, amnesia and immobility in patients, but also side effects such as a decrease in mean arterial pressure and arrhythmia, both of which contribute to complications such as heart damage and stroke. With more knowledge of the mechanism of anaesthetic drugs, these complications could be reduced.

    It has been shown that anaesthetics cause a disruption of the thalamocortical connectivity and brain network connectivity. How the network communication is disrupted however is not known. Propofol and thiopental are both intravenous anaesthetic drugs used widely in clinical anaesthesia. They bind to the GABAA receptor and enhance its function.

    The cytoskeleton helps the cell to maintain its shape and participate in cellular movement and transport. Cellular transport to and from a neuron’s cell body and periphery is performed by motor proteins that move vesicles, organelles and proteins along cytoskeletal tracks. We have previously shown that propofol causes a reorganisation of the cytoskeleton protein actin in neurons, but we were further interested to study the effects of propofol and thiopental on the cytoskeletal function of cultured cortical rat neurons.

    Our results show that propofol and thiopental cause neurite (axon and dendrite) retraction. Propofol’s effects were time- and dose-dependent, and can be reversed when propofol is removed. We were able to inhibit propofolinduced neurite retraction if we stabilised actin by blocking either the motor protein myosin II or the GABAA receptor. We have previously shown that a small GTP-binding protein, RhoA, inhibits propofol-caused actin reorganisation. Propofol-induced neurite retraction was mediated via a downstream effector of RhoA, ROK, which induces phosphorylation of the myosin light chain and increases contractility. Furthermore, we have shown that propofol causes a switch from anterograde to retrograde transport and increases the average velocity of the moving vesicles in neurites. The propofol induced retrograde vesicle transport was GABAA receptor-mediated.

    Orexin A is a neuropeptide which regulates the sleep/awake cycle and has also been shown to reduce anaesthesia in animals when given intracerebroventricularly. We found that orexin A reverses propofol and thiopental-induced neurite retraction and actin reorganisation. Moreover, we have shown that the orexin A inhibition of propofol-induced neurite retraction is mediated via the PLD/PKC intracellular signalling pathway. Propofol and thiopental decreased the tyrosine phosphorilation of the intermediate cytoskeletal protein vimentin which is reversed by orexin A.

    Taken together, these results suggest that propofol causes a time- and dose-dependent, reversible and GABAAreceptor-mediated neurite retraction in cultured cortical rat neurons. Propofol also causes a switch from anterograde to retrograde vesicle transport in neurites. Orexin A reverses propofol and thiopental-induced neurite retraction and cytoskeletal reorganisation. Orexin A inhibits propofol-induced neurite retraction via the PLD/PKC intracellular signalling pathway.

    List of papers
    1. Propofol causes neurite retraction in neurons
    Open this publication in new window or tab >>Propofol causes neurite retraction in neurons
    Show others...
    2008 (English)In: British Journal of Anaesthesia, ISSN 0007-0912, E-ISSN 1471-6771, Vol. 101, no 3, p. 374-379Article in journal (Refereed) Published
    Abstract [en]

    Background The mechanism by which anaesthetic agents produce general anaesthesia is not yet fully understood. Retraction of neurites is an important function of individual neurones and neural plexuses during normal and pathological conditions, and it has been shown that such a retraction pathway exists in developing and mature neurones. We hypothesized that propofol decreases neuronal activity by causing retraction of neuronal neurites.

    Methods Primary cultures of rat cortical neurones were exposed in concentration– and time–response experiments to 0.02, 0.2, 2, and 20 µM propofol or lipid vehicle. Neurones were pretreated with the GABAA receptor (GABAAR) antagonist, bicuculline, the myosin II ATPase activity inhibitor, blebbistatin, and the F-actin stabilizing agent, phalloidin, followed by administration of propofol (20 µM). Changes in neurite retraction were evaluated using time-lapse light microscopy.

    Results Propofol caused a concentration- and time-dependent reversible retraction of cultured cortical neurone neurites. Bicuculline, blebbistatin, and phalloidin completely inhibited propofol-induced neurite retraction. Images of retracted neurites were characterized by a retraction bulb and a thin trailing membrane remnant.

    Conclusions Cultured cortical rat neurones retract their neurites after exposure to propofol in a concentration- and time-dependent manner. This retraction is GABAAR mediated, reversible, and dependent on actin and myosin II. Furthermore, the concentrations and times to full retraction and recovery correspond to those observed during propofol anaesthesia.

    Place, publisher, year, edition, pages
    Oxford, UK: Oxford University Press, 2008
    Keywords
    Anaesthetics i.v., propofol; brain, GABA rat; theories of anaesthetic action, cellular mechanisms
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-78010 (URN)10.1093/bja/aen185 (DOI)000259093300014 ()
    Available from: 2012-06-04 Created: 2012-06-04 Last updated: 2017-12-07Bibliographically approved
    2. Propofol alters vesicular transport in rat cortical neuronalcultures
    Open this publication in new window or tab >>Propofol alters vesicular transport in rat cortical neuronalcultures
    2011 (English)In: Journal of Physiology and Pharmacology, ISSN 0867-5910, E-ISSN 1899-1505, Vol. 62, no 1, p. 119-124Article in journal (Refereed) Published
    Abstract [en]

    Neuronal intracellular transport is performed by motor proteins, which deliver vesicles, organelles and proteins along cytoskeletal tracks inside the neuron. We have previously shown that the anesthetic propofol causes dose- and time-dependent, reversible retraction of neuronal neurites. We hypothesize that propofol alters the vesicular transport of cortical neurons due to this neurite retraction. Primary cultures of co-cultivated rat cortical neurons and glial cells were exposed to either 2 mu M propofol, control medium or the lipid vehicle, in time-response experiments. Reversibility was tested by washing propofol off the cells. The role of the GABA(A) receptor (GABA(A)R) was assessed with the GABA(A)R antagonist gabazine. Vesicles were tracked using differential interference contrast video microscopy. Propofol caused a retrograde movement in 83.4 +/- 5.2% (mean +/- S.E.M.) of vesicles, which accelerated over the observed time course (0.025 +/- 0.012 mu m.s(-1)). In control medium, vesicles moved predominantly anterograde (84.6 +/- 11.1%) with lower velocity (0.011 +/- 0.004 mu m.s(-1)). Cells exposed to the lipid vehicle showed the same dynamic characteristics as cells in control medium. The propofol-induced effect on vesicle transport was reversible and blocked by the GABA(A)R antagonist gabazine in low concentration. Our results show that propofol causes a reversible, accelerating vesicle movement toward the neuronal cell body that is mediated via synaptic GABA(A)R. We have previously reported that propofol initiates neurite retraction, and we propose that propofol causes vesicle movement by retrograde flow of cytoplasm from the narrowed neurite.

    Place, publisher, year, edition, pages
    Polish Physiological Society, 2011
    Keywords
    anesthetics intravenously, brain, cellular mechanism, cerebral cortex, neurotransmission effects, pharmacology, propofol, theories of anesthetic action, vesicular transport
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-67967 (URN)000289542300014 ()
    Available from: 2011-05-04 Created: 2011-05-04 Last updated: 2017-12-11Bibliographically approved
    3. Orexin A reverses propofol and thiopental induced cytoskeletal rearrangement in primary cortical neuronal culture
    Open this publication in new window or tab >>Orexin A reverses propofol and thiopental induced cytoskeletal rearrangement in primary cortical neuronal culture
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Background: Orexin A (OA) is an endogenous peptide regulating awakeness. It is a potential reversing agent of anaesthetics, shown to reduce anaesthesia in animals, but on cellular level its mechanisms are unknown.

    Methods: Primary cortical cell cultures from newborn rat brains are used, and live cell light microscopy is performed to measure 1) neurite retraction after propofol, thiopental, barbituric acid and ketamine exposure and 2) the effect of OA application either before or after anaesthetics. Cytoskeletal reorganization of vimentin and actin is evaluated with fluorescence microscopy, protein changes detected with Western blot and proteins identified with mass spectrometry after treatment with anaesthetics and/or OA.

    Results: Orexin A reverses and inhibits neurite retraction and the actin ring formation induced by propofol and thiopental. No effect on retraction or actin rings was seen for ketamine (not active on GABAA receptors), the non-anaesthetic barbituric acid, OA or solvents used. OA increases tyrosine phosphorylation of a 50 kDa protein, identified as vimentin. Propofol treatment induces a granular appearance of vimentin, which OA reverses to a smooth distribution throughout the cell.

    Conclusions: OA reverses cellular effects known to be mediated via the GABAA receptor of both propofol and thiopental in cultured rat brain cells. The morphologic changes of actin and vimentin caused by propofol and thiopental, and the subsequent reversal by OA, deepens our understanding of the mechanisms of anaesthesia. In the future, an OA agonist could be used to reverse the effects of GABAA receptor dependent anaesthetic drugs.

    Keywords
    orexin A, propofol, thiopental
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-77167 (URN)
    Available from: 2012-05-07 Created: 2012-05-07 Last updated: 2012-06-04Bibliographically approved
    4. Orexin A inhibits propofol-induced neurite retraction by a PLD-dependent mechanism in neurons
    Open this publication in new window or tab >>Orexin A inhibits propofol-induced neurite retraction by a PLD-dependent mechanism in neurons
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Background: Propofol retracts neurites and reverses the transport of vesicles in rat cortical neurons in a γ-aminobutyric acid type A (GABAA) receptor dependent manner. Orexin A (OA) is an endogenous peptide regulating wakefulness, and is known to interact with anaesthetics. We aim to investigate whether OA inhibits propofol-induced neurite retraction and elucidate the intracellular signalling involved.

    Methods: In primary cortical cell cultures from newborn rat brains, live cell light microscopy was used to measure neurite retraction after propofol (2 μM) with or without OA (10 nM) application after preincubation with the Rhokinase inhibitor (HA-1077), phospholipase D (PLD) inhibitor [5-fluoro-2- indolyl des-chlorohalopemide (FIPI)], protein kinase C (PKC) inhibitor (staurosporine) or PKC activator phorbol 12-myristate 13-acetate (PMA).

    Results: The neurite retraction induced by propofol is blocked by HA-1077 and PMA. OA blocks neurite retraction induced by propofol, and this inhibitory effect could be prevented by FIPI, as well as staurosporine.

    Conclusions: Rho-kinase is essential for propofol-induced neurite retraction in cortical neuronal cells. Activation of PKC plays an inhibitive role during neurite retraction caused by propofol. OA blocks propofol-induced neurite retraction by a PLD/PKC-mediated pathway.

    Keywords
    Orexin A, propofol, PLD
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-77168 (URN)
    Available from: 2012-05-07 Created: 2012-05-07 Last updated: 2012-06-04Bibliographically approved
  • 155.
    Turina, Dean
    et al.
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Björnström, Karin
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Mechanisms of general anesthetic action: Focus on the cellular network2011In: TRANSLATIONAL NEUROSCIENCE, ISSN 2081-3856, Vol. 2, no 2, p. 168-175Article in journal (Refereed)
    Abstract [en]

    The discovery of general anesthetics had a tremendous impact on development of surgery and medicine in general, during the last century. Despite the widespread use of general anesthetics, the mechanisms by which they produce their effects in the central nervous system are still poorly understood. Over the past decade, several new findings have contributed significantly to a better understanding of general anesthetic mechanisms. The current review summarizes recent data on different anesthetic neuronal targets that might be involved in the mechanism of action of general anesthetics, giving special attention to the importance of binding pockets for anesthetics within transmembrane receptors and cellular signaling leading to morphological changes of neuronal cells. Several lines of evidence suggest that disruption in brain network connectivity is important for anaesthesia-induced loss of consciousness and this is discussed in relation to morphological changes.

  • 156.
    Turina, Dean
    et al.
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Björnström-Karlsson, Karin
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Sundqvist, Tommy
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Eintrei, Christina
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Intensive Care UHL.
    Propofol alters vesicular transport in rat cortical neuronalcultures2011In: Journal of Physiology and Pharmacology, ISSN 0867-5910, E-ISSN 1899-1505, Vol. 62, no 1, p. 119-124Article in journal (Refereed)
    Abstract [en]

    Neuronal intracellular transport is performed by motor proteins, which deliver vesicles, organelles and proteins along cytoskeletal tracks inside the neuron. We have previously shown that the anesthetic propofol causes dose- and time-dependent, reversible retraction of neuronal neurites. We hypothesize that propofol alters the vesicular transport of cortical neurons due to this neurite retraction. Primary cultures of co-cultivated rat cortical neurons and glial cells were exposed to either 2 mu M propofol, control medium or the lipid vehicle, in time-response experiments. Reversibility was tested by washing propofol off the cells. The role of the GABA(A) receptor (GABA(A)R) was assessed with the GABA(A)R antagonist gabazine. Vesicles were tracked using differential interference contrast video microscopy. Propofol caused a retrograde movement in 83.4 +/- 5.2% (mean +/- S.E.M.) of vesicles, which accelerated over the observed time course (0.025 +/- 0.012 mu m.s(-1)). In control medium, vesicles moved predominantly anterograde (84.6 +/- 11.1%) with lower velocity (0.011 +/- 0.004 mu m.s(-1)). Cells exposed to the lipid vehicle showed the same dynamic characteristics as cells in control medium. The propofol-induced effect on vesicle transport was reversible and blocked by the GABA(A)R antagonist gabazine in low concentration. Our results show that propofol causes a reversible, accelerating vesicle movement toward the neuronal cell body that is mediated via synaptic GABA(A)R. We have previously reported that propofol initiates neurite retraction, and we propose that propofol causes vesicle movement by retrograde flow of cytoplasm from the narrowed neurite.

  • 157.
    Turina, Dean
    et al.
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences.
    Glavas, Alenka
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences.
    Björnström, Karin
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences.
    Orexin A reverses propofol and thiopental induced cytoskeletal rearrangement in primary cortical neuronal cultureManuscript (preprint) (Other academic)
    Abstract [en]

    Background: Orexin A (OA) is an endogenous peptide regulating awakeness. It is a potential reversing agent of anaesthetics, shown to reduce anaesthesia in animals, but on cellular level its mechanisms are unknown.

    Methods: Primary cortical cell cultures from newborn rat brains are used, and live cell light microscopy is performed to measure 1) neurite retraction after propofol, thiopental, barbituric acid and ketamine exposure and 2) the effect of OA application either before or after anaesthetics. Cytoskeletal reorganization of vimentin and actin is evaluated with fluorescence microscopy, protein changes detected with Western blot and proteins identified with mass spectrometry after treatment with anaesthetics and/or OA.

    Results: Orexin A reverses and inhibits neurite retraction and the actin ring formation induced by propofol and thiopental. No effect on retraction or actin rings was seen for ketamine (not active on GABAA receptors), the non-anaesthetic barbituric acid, OA or solvents used. OA increases tyrosine phosphorylation of a 50 kDa protein, identified as vimentin. Propofol treatment induces a granular appearance of vimentin, which OA reverses to a smooth distribution throughout the cell.

    Conclusions: OA reverses cellular effects known to be mediated via the GABAA receptor of both propofol and thiopental in cultured rat brain cells. The morphologic changes of actin and vimentin caused by propofol and thiopental, and the subsequent reversal by OA, deepens our understanding of the mechanisms of anaesthesia. In the future, an OA agonist could be used to reverse the effects of GABAA receptor dependent anaesthetic drugs.

  • 158.
    Turina, Dean
    et al.
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences.
    Karin, Björnström Karlsson
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences.
    Sundqvist, Tommy
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Eintrei, Christina
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Intensive Care UHL.
    Orexin A inhibits propofol-induced neurite retraction by a PLD-dependent mechanism in neuronsManuscript (preprint) (Other academic)
    Abstract [en]

    Background: Propofol retracts neurites and reverses the transport of vesicles in rat cortical neurons in a γ-aminobutyric acid type A (GABAA) receptor dependent manner. Orexin A (OA) is an endogenous peptide regulating wakefulness, and is known to interact with anaesthetics. We aim to investigate whether OA inhibits propofol-induced neurite retraction and elucidate the intracellular signalling involved.

    Methods: In primary cortical cell cultures from newborn rat brains, live cell light microscopy was used to measure neurite retraction after propofol (2 μM) with or without OA (10 nM) application after preincubation with the Rhokinase inhibitor (HA-1077), phospholipase D (PLD) inhibitor [5-fluoro-2- indolyl des-chlorohalopemide (FIPI)], protein kinase C (PKC) inhibitor (staurosporine) or PKC activator phorbol 12-myristate 13-acetate (PMA).

    Results: The neurite retraction induced by propofol is blocked by HA-1077 and PMA. OA blocks neurite retraction induced by propofol, and this inhibitory effect could be prevented by FIPI, as well as staurosporine.

    Conclusions: Rho-kinase is essential for propofol-induced neurite retraction in cortical neuronal cells. Activation of PKC plays an inhibitive role during neurite retraction caused by propofol. OA blocks propofol-induced neurite retraction by a PLD/PKC-mediated pathway.

  • 159.
    Turina, Dean
    et al.
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Loitto, Vesa
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Björnström, Karin
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Sundqvist, Tommy
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Eintrei, Christina
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Propofol causes neurite retraction in neurons2008Conference paper (Refereed)
  • 160.
    Turina, Dean
    et al.
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Loitto, Vesa
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Björnström, Karin
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Sundqvist, Tommy
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Eintrei, Christina
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Propofol causes neurite retraction in neurons2008In: British Journal of Anaesthesia, ISSN 0007-0912, E-ISSN 1471-6771, Vol. 101, no 3, p. 374-379Article in journal (Refereed)
    Abstract [en]

    Background The mechanism by which anaesthetic agents produce general anaesthesia is not yet fully understood. Retraction of neurites is an important function of individual neurones and neural plexuses during normal and pathological conditions, and it has been shown that such a retraction pathway exists in developing and mature neurones. We hypothesized that propofol decreases neuronal activity by causing retraction of neuronal neurites.

    Methods Primary cultures of rat cortical neurones were exposed in concentration– and time–response experiments to 0.02, 0.2, 2, and 20 µM propofol or lipid vehicle. Neurones were pretreated with the GABAA receptor (GABAAR) antagonist, bicuculline, the myosin II ATPase activity inhibitor, blebbistatin, and the F-actin stabilizing agent, phalloidin, followed by administration of propofol (20 µM). Changes in neurite retraction were evaluated using time-lapse light microscopy.

    Results Propofol caused a concentration- and time-dependent reversible retraction of cultured cortical neurone neurites. Bicuculline, blebbistatin, and phalloidin completely inhibited propofol-induced neurite retraction. Images of retracted neurites were characterized by a retraction bulb and a thin trailing membrane remnant.

    Conclusions Cultured cortical rat neurones retract their neurites after exposure to propofol in a concentration- and time-dependent manner. This retraction is GABAAR mediated, reversible, and dependent on actin and myosin II. Furthermore, the concentrations and times to full retraction and recovery correspond to those observed during propofol anaesthesia.

  • 161.
    Unbeck, Maria
    et al.
    Danderyd Hospital.
    Schildmeijer, Kristina
    Linnaeus University.
    Henriksson, Peter
    Danderyd Hospital.
    Jurgensen, Urban
    Qulturum, Jönköping.
    Muren, Olav
    Danderyd Hospital.
    Nilsson, Lena
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping.
    Pukk Härenstam, Karin
    Karolinska Institute.
    Is detection of adverse events affected by record review methodology? An evaluation of the “Harvard Medical Practice Study” method and the “Global Trigger Tool”.2013In: Patient Safety in Surgery, ISSN 1754-9493, E-ISSN 1754-9493, Vol. 7, no 1, p. 10-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    There has been a theoretical debate as to which retrospective record review method is the most valid, reliable, cost efficient and feasible for detecting adverse events. The aim of the present study was to evaluate the feasibility and capability of two common retrospective record review methods, the "Harvard Medical Practice Study" method and the "Global Trigger Tool" in detecting adverse events in adult orthopaedic inpatients.

    METHODS:

    We performed a three-stage structured retrospective record review process in a random sample of 350 orthopaedic admissions during 2009 at a Swedish university hospital. Two teams comprised each of a registered nurse and two physicians were assigned, one to each method. All records were primarily reviewed by registered nurses. Records containing a potential adverse event were forwarded to physicians for review in stage 2. Physicians made an independent review regarding, for example, healthcare causation, preventability and severity. In the third review stage all adverse events that were found with the two methods together were compared and all discrepancies after review stage 2 were analysed. Events that had not been identified by one of the methods in the first two review stages were reviewed by the respective physicians.

    RESULTS:

    Altogether, 160 different adverse events were identified in 105 (30.0%) of the 350 records with both methods combined. The "Harvard Medical Practice Study" method identified 155 of the 160 (96.9%, 95% CI: 92.9-99.0) adverse events in 104 (29.7%) records compared with 137 (85.6%, 95% CI: 79.2-90.7) adverse events in 98 (28.0%) records using the "Global Trigger Tool". Adverse events "causing harm without permanent disability" accounted for most of the observed difference. The overall positive predictive value for criteria and triggers using the "Harvard Medical Practice Study" method and the "Global Trigger Tool" was 40.3% and 30.4%, respectively.

    CONCLUSIONS:

    More adverse events were identified using the "Harvard Medical Practice Study" method than using the "Global Trigger Tool". Differences in review methodology, perception of less severe adverse events and context knowledge may explain the observed difference between two expert review teams in the detection of adverse events.

  • 162.
    Waldreus, Nana
    et al.
    Linköping University, Department of Social and Welfare Studies, Division of Health, Activity and Care. Linköping University, Faculty of Health Sciences.
    Hahn, Robert G
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Surgery.
    Jaarsma, Tiny
    Linköping University, Department of Social and Welfare Studies, Division of Health, Activity and Care. Linköping University, Faculty of Health Sciences.
    Thirst in heart failure: a systematic literature review2013In: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 15, no 2, p. 141-149Article, review/survey (Refereed)
    Abstract [en]

    Although patients with heart failure (HF) may suffer from severe thirst, this has received little attention in scientific studies. A systematic literature review was conducted to identify and analyse data on thirst in HF. less thanbrgreater than less thanbrgreater thanPubmed, Cochrane, Cinahl, and Medline databases were searched for original studies on patients with HF with thirst as an outcome measure. Of 174 screened citations, nine articles were included, in which a total of 4375 HF patients had been studied. Four studies comprising 181 patients provided visual analogue scale (VAS) scores. Median thirst intensity ranged from 23 to 75 mm (VAS 0100 mm). One study showed 2 prevalence of thirst in a placebo group and another study showed that 46 of HF patients (n 25) experienced thirst distress. Thirst was described as annoying and as a cause of suffering. In most studies, the main results reflect a poor description of several dimensions of thirst. Factors that affected thirst were related to treatment, HF condition, demographics, and emotions. The consequences of thirst in HF were related to compliance, preoccupation with thirst, and a negative impact on quality of life. less thanbrgreater than less thanbrgreater thanThirst may be increased and experienced as distressing in patients with HF, but there is limited knowledge about the causative factors. More research is needed to study the effects of thirst and effective interventions in order to relieve troublesome thirst in HF patients.

  • 163.
    Waldreus, Nana
    et al.
    Department of Research, Södertälje Hospital, Södertälje, Sweden.
    Sjöstrand, Fredrik
    Linköping University, Department of Management and Engineering. Linköping University, The Institute of Technology.
    Hahn, Robert
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Surgery.
    Thirst in the elderly with and without heart failure2011In: Archives of gerontology and geriatrics (Print), ISSN 0167-4943, E-ISSN 1872-6976, Vol. 53, no 2, p. 174-178Article in journal (Refereed)
    Abstract [en]

    Elderly patients with heart failure (HF) may be troubled by thirst, despite the fact that elderly have an impaired ability to sense thirst. The present study was undertaken to compare the intensity of thirst in patients with and without HF and to evaluate how this symptom relates to the health-related quality of life and indices of the fluid balance. Forty-eight patients (mean age 80 years) admitted to hospital with worsening HF (n = 23) or with other acute illness (n = 25) graded their thirst and estimated their health-related quality of life (HRQoL). Serum sodium was measured and urine samples were assessed for color and electrolyte content. The HF patients reported significantly more intensive thirst (median = 75 mm) compared with those in the control group (median = 25 mm; p less than 0.0001). There was no statistically significant relationship between thirst and HRQoL, which was low overall. Serum sodium and urine color did not differ significantly between the groups, but the urine of the HF patients had a lower sodium concentration and osmolality. We conclude that elderly patients with worsening HF have considerably increased thirst and, hence, intense thirst should be regarded as a symptom of HF.

  • 164.
    Walldén, Jakob
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Anesthesiology .
    Thorn, SE
    Wattwil, Magnus
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care.
    The delay of gastric emptying induced by remifentanil is not influenced by posture2004In: Anesthesia and Analgesia, ISSN 0003-2999, E-ISSN 1526-7598, Vol. 99, no 2, p. 429-434Article in journal (Refereed)
    Abstract [en]

    Posture has an effect on gastric emptying. In this study, we investigated whether posture influences the delay in gastric emptying induced by opioid analgesics. Ten healthy male subjects underwent 4 gastric emptying studies with the acetaminophen method. On two occasions the subjects were given a continuous infusion of remifentanil (0.2 mug . kg(-1) . min(-1)) while lying either on the right lateral side in a 20degrees head-up position or on the left lateral side in a 20degrees head-down position. On two other occasions no infusion was given, and the subjects were studied lying in the two positions. When remifentanil was given, there were no significant differences between the two postures in maximal acetaminophen concentration (right side, 34 mumol . L-1, versus left side, 16 mumol . L-1), time taken to reach the maximal concentration (94 versus 109 min), or area under the serum acetaminophen concentration time curve from 0 to 60 min (962 versus 197 min . mumol - L-1). In the control situation, there were differences between the postures in maximal acetaminophen concentration (138 versus 94 mumol . L-1, P < 0.0001) and area under the serum acetaminophen concentration time curves from 0 to 60 min (5092 versus 3793 min . mumol . L-1, P < 0.0001), but there was no significant difference in time taken to reach the maximal concentration (25 versus 47 min). Compared with the control situation, remifentanil delayed gastric emptying in both postures. We conclude that remifentanil delays gastric emptying and that this delay is not influenced by posture.

  • 165.
    Widhe, Mona
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Ekerfelt, Christina
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Jarefors, Sara
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Hedin-Skogman, Barbro
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Peterson, E. M.
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences.
    Bergstrom, S.
    University of Umeå.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    T-Cell Epitope Mapping of the Borrelia garinii Outer Surface Protein A in Lyme Neuroborreliosis2009In: SCANDINAVIAN JOURNAL OF IMMUNOLOGY, ISSN 0300-9475, Vol. 70, no 2, p. 141-148Article in journal (Refereed)
    Abstract [en]

    We studied the T-cell reactivity to overlapping peptides of B. garinii OspA, in order to locate possible immunodominant T-cell epitopes in neuroborreliosis. Cells from cerebrospinal fluid (CSF) and blood from 39 patients with neuroborreliosis and 31 controls were stimulated with 31 overlapping peptides, and interferon-gamma secreting cells were detected by ELISPOT. The peptides OspA(17-36), OspA(49-68), OspA(105-124), OspA(137-156), OspA(193-212) and OspA(233-252) showed the highest frequency of positive responses, being positive in CSF from 38% to 50% of patients with neuroborreliosis. These peptides also elicited higher responses in CSF compared with controls (P = 0.004). CSF cells more often showed positive responses to these peptides than blood cells (P = 0.001), in line with a compartmentalization to the central nervous system. Thus, a set of potential T-cell epitopes were identified in CSF cells from patients with neuroborreliosis. Further studies may reveal whether these epitopes can be used diagnostically and studies involving HLA interactions may show their possible pathogenetic importance.

  • 166.
    Yu-Hong, Li
    et al.
    Department of Anesthesia, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.
    Waldréus, Nana
    Section for Research, Department of Patient Safety and Quality, Södertälje Hospital, Södertälje, Sweden.
    Zdolsek, Joachim
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Hahn, Robert G
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Effects of tap water, electrolyte solution, and spontaneous and furosemide-stimulated urinary excretion on thirst2012In: World Journal of Experimental Medicine, ISSN 2220-315X, Vol. 2, no 1, p. 1-6Article in journal (Refereed)
    Abstract [en]

    AIM: To contrast the effects of various modifications of body fluid volumes on thirst as reported by healthy volunteers.

    METHODS: Ten male volunteers aged between 19 and 37 years (mean 22 years) underwent four experiments each, which comprised infusion of 400-800 mL of acetated Ringer’s solution and intake of 600 mL of tap water. Half of the experiments were preceded by volume depletion (median 1.7 L) with furosemide. A visual analogue scale (0-100 mm) was used to assess perceived thirst during each experiment.

    RESULTS: Volume depletion (P < 0.001) and tap water (P < 0.03) both affected thirst by 13 mm per L of fluid, whereas spontaneous diuresis and infusion of Ringer’s acetate did not significantly change the thirst rating (multiple regressions). More detailed analyses showed that the volume depletion increased the median (25th-75th percentiles) thirst rating from 28 mm (21-43) to 59 mm (46-72, P < 0.001) while no change occurred in those who were only slightly thirsty (< 30 mm) before the volume depletion began. Ringer’s solution alleviated thirst in those who were very thirsty, but tended to increase thirst in the volunteers who were not thirsty before the infusion. Similarly, hydration with tap water decreased thirst (by 24 mm, P < 0.04) in those who were thirsty (> 60 mm) while the others reported no change.

    CONCLUSION: The change in thirst rating during volume depletion, administration of Ringer’s acetate, and ingestion of tap water were all dependent on the thirst rating obtained when the manipulation of the body fluid volume was initiated.

  • 167.
    Zdolsek, Joachim
    et al.
    Östergötlands Läns Landsting, Anaesthesiology and Surgical Centre, Department of Intensive Care UHL.
    Holmgren, Susanna
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics.
    Wedenberg, K
    Department of Obstetrics and Gynaecology, Eskilstuna, Sweden.
    Lennmarken, Claes
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthesiology and Surgical Centre, Department of Intensive Care UHL.
    Circulatory arrest in late pregnancy: caesarean section a vital decision for both mother and child2009In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 53, no 6, p. 828-829Article in journal (Refereed)
    Abstract [en]

    Circulatory arrest during pregnancy is extremely rare and there should be a well-planned strategy for its management in all hospitals. To consider the priority of the mothers life over the childs and an unwarranted pre-term delivery may lead to hesitancy and uncertainty and jeopardize both of them. In these situations, speed is a priority. Cardiopulmonary resuscitation should commence immediately. The anaesthesiologist should be well aware of the possible advantage of a caesarean section. Even if the obstetrician is responsible for the decision to perform the operation, the anaesthesiologist should strongly support the action. An emergency caesarean kit with the essential surgical instruments should be immediately available in every labour ward and emergency department.

  • 168.
    Zdolsek, Joachim
    et al.
    Östergötlands Läns Landsting, Anaesthesiology and Surgical Centre, Department of Intensive Care UHL.
    Kågedal, Bertil
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Lisander, Björn
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthesiology and Surgical Centre, Department of Intensive Care UHL.
    Hahn, Robert
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthesiology and Surgical Centre, Department of Intensive Care UHL.
    Glomerular filtration rate is increased in burn patients2010In: Burns, ISSN 0305-4179, E-ISSN 1879-1409, Vol. 36, no 8, p. 1271-1276Article in journal (Refereed)
    Abstract [en]

    Urinary output a key parameter guiding fluid resuscitation in burn trauma is an inadequate measure of renal function In this study the clearance of iohexol (CL) was used to follow the glomerular filtration rate during the first week after burn Nineteen adults with major burns received an intravenous bolus injection of iohexol every other day Plasma concentration of iohexol was measured over 4 h and CL was calculated by a one compartment kinetic model The results were compared to the CL as obtained by a two compartment model and also to the CL measured in 10 healthy controls The results show that CL values for burn patients were high The first day after burn median CL was 155 mL/min/1 73 m(2) (range 46-237) which exceeded that for the controls (mean 117 mL/min/1 73 m(2) P less than 0 01) However on day 7 the CL approached the expected baseline (mean 122 mL/min/1 73 m(2)) CL was 10% lower when calculated from two compartment kinetics and a correction factor of 0 9 was applied to all results obtained by the one compartment calculations to give results comparable to those from the two compartment kinetics In conclusion CL is increased early after burn The mechanism is unclear but it parallels the period of vascular dysfunction and increased cardiac output

  • 169.
    Zdolsek, Joachim
    et al.
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Li, Yuhong
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences.
    Hahn, Robert G
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Detection of Dehydration by Using Volume Kinetics2012In: Anesthesia and Analgesia, ISSN 0003-2999, E-ISSN 1526-7598, Vol. 115, no 4, p. 814-822Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Patients admitted to surgery may be dehydrated, which is difficult to diagnose except when it is severe (>5% Gl116 of the body weight). We hypothesized that modest dehydration can be detected by kinetic analysis of the blood hemoglobin concentration after a bolus infusion of crystalloid fluid.

    METHODS: Four series of experiments were performed on 10 conscious, healthy male volunteers. Separated by at least 2 days, they received 5 or 10 mL/kg acetated Ringer's solution over 15 minutes. Before starting half of the IV infusions, volume depletion amounting to 1.5 to 2.0 L (approximately 2% of body weight) was induced with furosemide. The elimination clearance and the half-life of the infused fluid were calculated based on blood hemoglobin over 120 minutes. The perfusion index and the pleth variability index were monitored by pulse oximetry after a change of body position.

    RESULTS: Dehydration decreased the elimination clearance of acetated Ringer's solution [median (25th-75th percentile)] from 1.84 (1.23-2.57) to 0.53 (0.41-0.79) mL/kg/min (Wilcoxon matched-pair test P < 0.001) and increased the half-life from 23 (12-37) to 76 (57-101) minutes (P < 0.001). The smaller infusion, 5 mL/kg, fully discriminated between experiments performed in the euhydrated and dehydrated states, whereas the urinary excretion provided a less-reliable indication of hydration status. Dehydration decreased the perfusion index but did not affect the pleth variability index.

    CONCLUSION: Dehydration amounting to 2% of the body weight could be detected from the elimination clearance and the half-life of an infusion of 5 mL/kg Ringer's solution.

  • 170.
    Zdolsek, Joachim
    et al.
    Östergötlands Läns Landsting, Anaesthesiology and Surgical Centre, Department of Intensive Care UHL.
    Lisander, Björn
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences.
    Hahn, Robert G.
    Department of Anesthesiology, Karolinska Institute, Stockholm, Sweden.
    Measuring the size of the extracellular fluid space using bromide, iohexol, and sodium dilution2005In: Anesthesia and Analgesia, ISSN 0003-2999, E-ISSN 1526-7598, Vol. 101, no 6, p. 1770-1777Article in journal (Refereed)
    Abstract [en]

    There is a need to find methods to assess the size of the extracellular fluid (ECF) volume without involving radioactive tracers. For this purpose, we applied 3 methods for measuring the ECF volume in 10 male volunteers (mean age, 34 yr). Steady-state plasma bromide concentration (control) was compared to the results of kinetic analysis of plasma iohexol and to kinetic analysis of the dilution of serum sodium after IV infusion of 1 L of isotonic mannitol. The volume of distribution of these tracers was used to indicate the ECF volume. The results disclosed statistically significant correlations between the results of all 3 methods, although the average sodium dilution showed 0.7 L lower values than iohexol and 1.4 L lower than bromide. All three methods correlated significantly with body weight. The percentage of the body weight indicated by the methods was 18.3% (3.1%) for sodium, 19.6% (1.0%) for iohexol, and 20.5% (1.1%) for bromide. We conclude that sodium dilution may be performed at bedside but iohexol and bromide showed less intersubject variability. Iohexol simultaneously measures the glomerular filtration rate and should be a viable clinical option if the hospital performs routine assessments of kidney function using this tracer. ©2005 by the International Anesthesia Research Society.

  • 171.
    Zdolsek, Joachim
    et al.
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL. Östergötlands Läns Landsting, Sinnescentrum, Department of Intensive Care UHL.
    Vegfors, Magnus
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Intensive Care VHN.
    Lindahl, Tomas
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Chemistry.
    Tornquist, T.
    Regional Hospital Motala.
    Bortnik, P.
    Regional Hospital Motala.
    Hahn, Robert
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Hydroxyethyl starches and dextran during hip replacement surgery: effects on blood volume and coagulation2011In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 55, no 6, p. 677-685Article in journal (Refereed)
    Abstract [en]

    Background: Colloid fluids influence the coagulation system by diluting the plasma and, potentially, by exerting other effects that are unique for each fluid product. We hypothesised that changes in the coagulation measured at the end of surgery would be mainly governed by differences in half-life between the colloid fluids. Methods: Eighty-four patients were randomised to receive one of four colloids: HES 130/0.42/6 : 1 (Venofundin (R)), 130/0.4/9 : 1 (Voluven (R)), 200/0.5/5 : 1 (Haes-steril (R)) and 6% dextran 70 (Macrodex (R)). Blood samples were taken just before and after a preoperative 500ml bolus, and also after subsequent elective hip replacement surgery. Volume expansion was estimated from the blood dilution and coagulation assessed by ROTEM, activated partial thromboplastin time, prothrombin international normalised ratio (PT-INR), D-dimer and thrombin-antithrombin complex (TAT). Results: The blood volume expansion amounted to approximately 600 ml for all four colloids directly after infusion. Voluven (R) and Haes-steril (R) prolonged the aPT time and Venofundin (R) increased TAT. Although all colloids increased PT-INR and D-dimer, the ROTEM analyses showed that they consistently shortened the clotting time and weakened the clot strength. These effects were mainly unchanged after surgery, during which the haemorrhage averaged 500-600 ml. Macrodex (R) produced a stronger volume support at the end of the surgery (91% of infused volume; Pless than0.001) than the three starch solutions (42-60%). Conclusions: All tested colloid fluids induced a mild hypercoagulable state with faster clotting, but with weaker clot strength. The additive influence of surgery was relatively small, and postoperative changes in coagulation were mainly due to differences in the half-life of each colloid.

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