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  • 351.
    Sharma, Hari S.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Ali, Syed F.
    Hussain, Saber M.
    Schlager, John J.
    Sharma, Aruna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Influence of Engineered Nanoparticles from Metals on the Blood-Brain Barrier Permeability, Cerebral Blood Flow, Brain Edema and Neurotoxicity: An Experimental Study in the Rat and Mice Using Biochemical and Morphological Approaches2009Ingår i: Journal of Nanoscience and Nanotechnology, ISSN 1533-4880, E-ISSN 1533-4899, Vol. 9, nr 8, s. 5055-5072Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Influence of nanoparticles on brain function following in vivo exposures is not well known. Depending on the magnitude and intensity of nanoparticle exposure from the environment, food and/or water source, neuronal function could be affected and may lead to neurotoxicity and neuropathology. This hypothesis was examined in present investigation using systemic or intracerebroventricular administration of engineered nanoparticles from metals, i.e., Al, Ag and Cu (approximate to 50 to 60 nm) on neurotoxicity in rats and mice. Intraperitoneal (50 mg/kg), intravenous (30 mg/kg), intracarotid (2.5 mg/kg) or intracerebroventricular administration (20 mu g) of nanoparticles significantly altered the blood-brain barrier (BBB) function to Evans blue and radioiodine in several regions of the brain and spinal cord at 24 h after their administration. Marked decreases in local cerebral blood flow (CBF) and pronounced brain edema was seen in regional areas associated with BBB leakage. Neuronal cell injuries, glial cell activation, heat shock protein (HSP) upregulation and loss of myelinated fibers are quite common in effected brain areas. The observed pathological changes were most pronounced in mice compared to rats. Exposures to Cu and Ag nanoparticles showed most marked effects on brain pathology when administered into systemic circulation or into the brain ventricular spaces as compared to Al nanoparticles. Our results are the first to show that nanoparticles from metals are able to induce selective and specific neurotoxicity that depends on the type of metals, route of administration and the species used.

  • 352.
    Sharma, Hari Shanker
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    A combination of tumor necrosis factor-α and neuronal nitric oxide synthase antibodies applied topically over the traumatized spinal cord enhances neuroprotection and functional recovery in the rat2010Ingår i: Annals of the New York Academy of Sciences, ISSN 0077-8923, E-ISSN 1749-6632, Vol. 1199, s. 175-185Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The possibility that neutralization of nitric oxide synthase and tumor necrosis factor alpha (TNF-alpha) in the cord using their antiserum will induce neuroprotection and improve functional outcome following spinal cord injury (SCI) was examined in a rat model. The SCI was induced in rats by a unilateral incision of the right dorsal horn at the T10-11 segments under equithesin anesthesia. TNF-alpha and/or neuronal nitric oxide synthase (nNOS) antibodies were applied over the traumatized spinal cord at 10-90 minutes after injury and functional recovery and cord pathophysiology were examined at five hours. Topical application of TNF-alpha antiserum at 10 min followed by NOS antiserum at 20 min after SCI significantly improved functional recovery and attenuated blood-spinal cord barrier (BSCB) disturbances, edema formation, and cord pathology. These neuroprotective effects were also seen when the NOS antiserum was applied 10 min after injury followed by TNF-alpha antiserum at 30 min after trauma. However, when TNF-alpha antiserum was applied 1 h after injury and NOS antiserum was given either before or after TNF-alpha antiserum, no neuroprotective effects were observed. Interestingly, neuronal injury was tightly correlated with nNOS expression in the cord in antibody treated groups. These novel observations suggest that early blockade of TNF-alpha and nNOS expression within 20-30 min after SCI is beneficial in nature. This indicates that TNF-alpha. and nitric oxide play synergistic roles in the pathophysiology of SCI and combined antibodies therapy has added neuroprotective values in spinal trauma.

  • 353.
    Sharma, Hari Shanker
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Ali, Syed F.
    Tian, Z. Ryan
    Hussain, Saber M.
    Schlager, John J.
    Sjöquist, Per-Ove
    Sharma, Aruna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Muresanu, Datin F.
    Chronic Treatment with Nanoparticles Exacerbate Hyperthermia Induced Blood-Brain Barrier Breakdown, Cognitive Dysfunction and Brain Pathology in the Rat: Neuroprotective Effects of Nanowired-Antioxidant Compound H-290/512009Ingår i: Journal of Nanoscience and Nanotechnology, ISSN 1533-4880, E-ISSN 1533-4899, Vol. 9, nr 8, s. 5073-5090Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The possibility that chronic exposure of nanoparticles may alter stress reaction and brain pathology following hyperthermia was examined in a rat model. Engineered nanoparticles from Ag or M Cu (approximate to 50-60 nm) were administered (30 mg/kg, i.p.) once daily for 1 week in young male rats. M On the 8th day these animals were subjected to 4 h heat stress at 38 degrees C in a BOD incubator. In these animals stress symptoms, blood-brain barrier (BBB) permeability, cognitive and motor functions and brain pathology were examined. Subjection of nanoparticle treated rats to heat stress showed exacerbation of stress symptoms i.e., hyperthermia, salivation and prostration and exhibited greater BBB disruption, brain edema formation, impairment of cognitive and motor functions M and brain damage compared to normal animals. This enhanced brain pathology in heat stress was most marked in animals that received Ag nanoparticles compared to Cu treatment. Treatment with antioxidant compound H-290/51 either 30 min or 60 min after heat stress did not alter hyperthermia M induce brain pathology in nanoparticle treated rats. Whereas, administration of nanowired-H-290/51 after 30 min or 60 min heat stress markedly attenuated BBB disruption, sensory motor function and brain pathology. These results suggest that chronic nanoparticles treatment exacerbate hyperthermia induced brain pathology that is significantly attenuated by nanowired but not normal H-290/51 compound. Taken together, our observations suggest that nano-wired drug delivery of H-290/51 is a promising approach to induce neuroprotection in hyperthermia induced brain pathology, not reported earlier.

  • 354.
    Sharma, Hari Shanker
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Hussain, Saber
    Schlager, John
    Ali, Syed F.
    Sharma, Aruna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Influence of Nanoparticles on Blood-Brain Barrier Permeability and Brain Edema Formation in Rats2010Ingår i: Brain Edema XIV / [ed] Zbigniew Czernicki et al., Vienna: Springer , 2010, Vol. 106, s. 359-364Konferensbidrag (Refereegranskat)
    Abstract [en]

    Nanoparticles are small sized (1-100 nm) particles derived from transition metals, silver, copper, aluminum, silicon, carbon and metal oxides that can easily cross the blood-brain barrier (BBB) and/or produce damage to the barrier integrity by altering endothelial cell membrane permeability. However, the influence of nanoparticles on BBB integrity is still not well-known. In this investigation, effect of nanoparticles derived from Ag, Al and Cu (50-60 nm) on BBB permeability in relation to brain edema formation was examined in a rat model. Intravenous (30 mg/kg), intraperitoneal (50 mg/kg) or intracerebral (20 mu g in 10 mu L) administration of Ag, Cu or AI nanoparticles disrupted the BBB function to Evans blue albumin (EBA) and radioiodine in rats 24 h after administration and induced brain edema formation. The leakage of Evans blue dye was observed largely in the ventral surface of brain and in the proximal frontal cortex. The dorsal surfaces of cerebellum showed mild to moderate EBA staining. These effects were most pronounced in animals that received Ag or Cu nanoparticles compared to Al nanoparticles through intravenous routes. These observations are the first to suggest that nanoparticles can induce brain edema formation by influencing BBB breakdown in vivo.

  • 355.
    Sharma, Hari Shanker
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Kiyatkin, Eugene A.
    NIDA, Vivo Electrophysiol Unit, Behav Neurosci Branch, IRP,NIH, Baltimore, MD USA..
    Patnaik, Ranjana
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Lafuente, Jose Vicente
    Univ Basque Country, Dept Neurosci, Bilbao, Spain..
    Muresanu, Dafin F.
    Univ Med & Pharm, Univ Hosp, Dept Clin Neurosci, Cluj Napoca, Romania..
    Sjoquist, Per-Ove
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Div Cardiol, Stockholm, Sweden..
    Sharma, Aruna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Exacerbation of Methamphetamine Neurotoxicity in Cold and Hot Environments: Neuroprotective Effects of an Antioxidant Compound H-290/512015Ingår i: Molecular Neurobiology, ISSN 0893-7648, E-ISSN 1559-1182, Vol. 52, nr 2, s. 1023-1033Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In this study, we examined the influence of cold and hot environments on methamphetamine (METH) neurotoxicity in both drug-naive rats and animals previously exposed to different types of nanoparticles (NPs). Since METH induces oxidative stress, we also examined how a potential chain-breaking antioxidant H-290/51 (Astra-Zeneca, Molndal, Sweden) affects METH-induced neurotoxicity. Exposure of drug-naive rats to METH (9 mg/kg, s.c.) at 4, 21, or 34 A degrees C for 3 h resulted in breakdown of the blood-brain barrier (BBB), brain edema, and neuronal injuries, which all differed in severity depending upon ambient temperatures. The changes were moderate at 21 A degrees C, 120-180 % larger at 34 A degrees C, and almost absent at 4 A degrees C. In rats chronically treated with NPs (SiO2, Cu, or Ag; 50-60 nm, 50 mg/kg, i.p. for 7 days), METH-induced brain alterations showed a two- to fourfold increase at 21 A degrees C, a four- to sixfold increase at 34 A degrees C, and three- to fourfold increase at 4 A degrees C. SiO2 exposure showed the most pronounced METH-induced brain pathology at all temperatures followed by Ag and Cu NPs. Pretreatment with a potent antioxidant compound H-290/51 (50 mg/kg, p.o., 30 min before METH) significantly reduced brain pathology in naive animals exposed to METH at 21 and 34 A degrees C. In NPs-treated animals, however, attenuation of METH-induced brain pathology occurred only after repeated exposure of H-290/51 (-30 min, 0 min, and +30 min). These observations are the first to show that NPs exacerbate METH-induced brain pathology in both cold and hot environments and demonstrate that timely intervention with antioxidant H-290/51 could have neuroprotective effects.

  • 356.
    Sharma, Hari Shanker
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Muresanu, D.
    Nozari, A.
    Patnaik, R.
    Moessler, H.
    Sharma, Aruna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Nanoparticles Aggravate Cardiac Arrest-Induced Blood-Brain Barrier Breakdown, Edema Formation, and Neuronal Injuries: Neuroprotective Effects of a Multimodal Drug Cerebrolysin2014Ingår i: Cell Transplantation, ISSN 0963-6897, E-ISSN 1555-3892, Vol. 23, nr 6, s. 782-783Artikel i tidskrift (Övrigt vetenskapligt)
  • 357.
    Sharma, Hari Shanker
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Muresanu, Dafin F.
    Univ Med & Pharm Cluj Napoca, Univ Hosp, Dept Clin Neurosci, Cluj Napoca, Romania.;RoNeuro Inst Neurol Res & Diagnost, Cluj Napoca 400364, Romania..
    Lafuente, Jose V.
    Univ Basque Country, Dept Neurosci, LaNCE, Bilbao, Spain.;Univ Autonoma Chile, Fac Hlth Sci, Santiago, Chile..
    Sjoquist, Per-Ove
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Div Cardiol, Stockholm, Sweden..
    Patnaik, Ranjana
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Banaras Hindu Univ, Indian Inst Technol, Sch Biomed Engn, Dept Biomat, Varanasi 221005, Uttar Pradesh, India..
    Sharma, Aruna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Nanoparticles Exacerbate Both Ubiquitin and Heat Shock Protein Expressions in Spinal Cord Injury: Neuroprotective Effects of the Proteasome Inhibitor Carfilzomib and the Antioxidant Compound H-290/512015Ingår i: Molecular Neurobiology, ISSN 0893-7648, E-ISSN 1559-1182, Vol. 52, nr 2, s. 882-898Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Increased levels of ubiquitin and heat shock protein (HSP) 72 kD are often seen in spinal cord injury (SCI). However, their roles in cell injury or survival are not well known. Thus, we have investigated the possible relationship between ubiquitin and HSP expressions in relation to cell injury in healthy animals, or following nanoparticle (NP) intoxication in SCI animals. A focal SCI was inflicted on the T10-11 segments over the right dorsal horn; animals were allowed to survive from 5 to 8 h after trauma. Separate groups of rats were exposed to SiO2, Ag, or Cu NPs for 7 days and subjected to SCI on the eighth day. A marked increase in ubiquitin or HSP immunoreactive cells occurred in the T9 to T12 segments 5 h after the injury, which further extended to the T4 and L5 after 8 h of survival. At this time, a marked increase in blood-spinal cord barrier (BSCB) permeability to Evans blue and radioiodine, accompanied by an intense edema formation, was observed. Changes were further exacerbated in NP-treated traumatized rats. The most marked expressions of ubiquitin and HSP in SCI were seen in rats treated with SiO2, followed by Ag, and Cu NPs. Treatment with H-290/51 (50 mg/kg p.o., 30 to 60 min after injury) or carfilzomib (1 mg/kg, i.v., 30 to 60 min after trauma) significantly reduced the ubiquitin or HSP expressions, as well as the BSCB breakdown, the edema formation, and the cell injury in the cord both 5 and 8 h after the injury, in normal animals. However, a double dose of H-290/51 (100 mg/kg) or carfilzomib (2 mg/kg) is needed to reduce cord pathology or ubiquitin and HSP expressions in traumatized animals treated with NPs. H-290/51 showed superior beneficial effects in reducing cord pathology in SCI than carfilzomib. These observations are the first to demonstrate that (i) NP-treated traumatized animals induce a widespread BSCB leakage, edema formation, and cord pathology as well as an overexpression of ubiquitin and HSP, (ii) high doses of antioxidant compounds or proteasome inhibitors are required for neuroprotection in the NP-exposed traumatized group, and (iii) ubiquitin and HSP expressions play a key role in neuronal injury in SCI, not reported earlier.

  • 358.
    Sharma, Hari Shanker
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Muresanu, Dafin Fior
    Tian, Z. Ryan
    Ozkizlicik, Asya
    Lafuente, Jose Vicente
    Moessler, Herbert
    Sharma, Aruna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    TiO2 Nanowired Cerebrolysin Attenuates Overexpression of Ubiquitin and Nitric Oxide Synthase and Induces Neuroprotection Following Spinal Cord Trauma2015Ingår i: The journal of head trauma rehabilitation, ISSN 0885-9701, E-ISSN 1550-509X, Vol. 30, nr 3, s. E80-E81Artikel i tidskrift (Övrigt vetenskapligt)
  • 359.
    Sharma, Hari Shanker
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Muresanu, Dafin
    Sharma, Aruna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Zimmermann-Meinzingen, Sibilla
    Cerebrolysin treatment attenuates heat shock protein overexpression in the brain following heat stress: An experimental study using immunohistochemistry at light and electron microscopy in the rat2010Ingår i: Annals of the New York Academy of Sciences, ISSN 0077-8923, E-ISSN 1749-6632, Vol. 1199, s. 138-148Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The possibility that overexpression of heat shock proteins (HSPs) in the CNS represents a neurodestructive signal following hyperthermia was examined in a rat model using a potent neuroprotective drug, Cerebrolysin (Ebewe Pharma, Austria). Rats subjected to four hours of heat stress in a biological oxygen demand incubator at 38 degrees C developed profound hyperthermia (41.23 +/- 0.14 degrees C) and overexpressed HSP 72 kD in several brain regions: cerebral cortex, hippocampus, cerebellum, thalamus, hypothalamus, brain stem, and spinal cord compared to controls. This HSP overexpression closely correlated with the leakage of blood-brain barrier permeability and vasogenic edema formation in these brain areas. HSP positive cells are largely confined in the edematous brain regions showing Evans blue leakage. Pretreatment with Cerebrolysin (5 mL/kg, i.v.) 30 minutes before heat stress markedly attenuated hyperthermia (39.48 +/- 0.23 degrees C, P < 0.01) and the induction of HSP to all the brain regions examined. Leakage of Evans blue albumin and increase in brain water content in these brain areas are also markedly reduced with Cerebrolysin pretreatment. These results are the first to show that Cerebrolysin, if administered before heat stress, attenuates hyperthermia induced stress reaction and HSP 72 kD induction. Taken together, these novel observations suggest that upregulation of HSP 72 kD in brain represents neurodestructive signals and a reduction in cellular stress mechanisms leading to decline in HSP expression is neuroprotective in nature.

  • 360.
    Sharma, Hari Shanker
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Patnaik, Ranjana
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Sharma, Aruna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Vicente Lafuente, Jose
    Univ Basque Country, Dept Neurosci, Bilbao, Spain..
    Miclescu, Adriana
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala Univ, Dept Surg Sci Anesthesiol & Intens Care Med, Lab Cerebrovasc Res, S-75185 Uppsala, Sweden..
    Wiklund, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Cardiac Arrest Alters Regional Ubiquitin Levels in Association with the Blood-Brain Barrier Breakdown and Neuronal Damages in the Porcine Brain2015Ingår i: Molecular Neurobiology, ISSN 0893-7648, E-ISSN 1559-1182, Vol. 52, nr 2, s. 1043-1053Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The possibility that ubiquitin expression is altered in cardiac arrest-associated neuropathology was examined in a porcine model using immunohistochemical and biochemical methods. Our observations show that cardiac arrest induces progressive increase in ubiquitin expression in the cortex and hippocampus in a selective and specific manner as compared to corresponding control brains using enzyme-linked immunoassay technique (enzyme-linked immunosorbent assay (ELISA)). Furthermore, immunohistochemical studies showed ubiquitin expression in the neurons exhibiting immunoreaction in the cytoplasm and karyoplasm of distorted or damaged cells. Separate Nissl and ubiquitin staining showed damaged and distorted neurons and in the same cortical region ubiquitin expression indicating that ubiquitin expression after cardiac arrest represents dying neurons. The finding that methylene blue treatment markedly induced neuroprotection following identical cardiac arrest and reduced ubiquitin expression strengthens this view. Taken together, our observations are the first to show that cardiac arrest enhanced ubiquitin expression in the brain that is related to the magnitude of neuronal injury and the finding that methylene blue reduced ubiquitin expression points to its role in cell damage, not reported earlier.

  • 361.
    Sharma, Hari Shanker
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Patnaik, Ranjana
    Sharma, Aruna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Wiklund, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    The contribution of glial cells and water channel aquaporin-4 in the neuropathology of cardiac arrest is still ignored2013Ingår i: CNS & Neurological Disorders: Drug Targets, ISSN 1871-5273, E-ISSN 1996-3181, Vol. 12, nr 1, s. 3-3Artikel i tidskrift (Refereegranskat)
  • 362.
    Sharma, Hari Shanker
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Ponten, Emma
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Gordh, Torsten
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Eriksson, P
    Fredriksson, A
    Sharma, Aruna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Propofol Promotes Blood-Brain Barrier Breakdown and Heat Shock Protein (HSP 72 kd) Activation in the Developing Mouse Brain2014Ingår i: CNS & Neurological Disorders: Drug Targets, ISSN 1871-5273, E-ISSN 1996-3181, Vol. 13, nr 9, s. 1595-1603Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Anesthetic agents induce cellular stress and affect blood-brain barrier permeability in the developing brain causing brain dysfunction. In this investigation, effects of Propofol on the inducible heat shock protein (HSP72) and albumin immunoreactivity in the mouse brain was examined. Propofol was administered to postnatal day 10 mice once (10 mg/kg or 60 mg/kg subcutaneously). On the 75th day, 3 µm paraffin sections of midbrain were processed for HSP72 and albumin immunostaining. Saline-treated and age-matched mice served as controls. Propofol dose-dependently produced a significant increase the number of HSP72 and albumin-positive cells in cortex, hippocampus, thalamus and hypothalamus, a feature not seen in the saline-treated group. HSP72 and albumin activity in the propofol-treated group was largely confined to neurons and often localized to their cell cytoplasm and/or nucleus. HSP72 and albumin expression was most prominent in the cerebral cortex and in hippocampus, followed by hypothalamus and thalamus. These novel observations suggest that anesthetic agents, by inducing cellular stress in the developing brain and disruption of blood-brain barrier function, may have long lasting effects on adult brain function.

  • 363.
    Sharma, Hari Shanker
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Sharma, Aruna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    The American Association for the Advancement of Science (AAAS), 180th Annual Meeting Chicago, IL, USA Feb 13-17, 2014 "Meeting Global Challenges Discoveries & Innovation"2014Ingår i: CNS & Neurological Disorders: Drug Targets, ISSN 1871-5273, E-ISSN 1996-3181, Vol. 13, nr 4, s. 553-555Artikel i tidskrift (Övrigt vetenskapligt)
  • 364.
    Sharma, Hari Shanker
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Sharma, Aruna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Hussain, Saber
    Schlager, John
    Sjöquist, Per-Ove
    Muresanu, Daffin
    A New Antioxidant Compound H-290/51 Attenuates Nanoparticle Induced Neurotoxicity and Enhances Neurorepair in Hyperthermia2010Ingår i: Brain Edema XIV / [ed] Zbigniew Czernicki et al., Vienna: Springer , 2010, Vol. 106, s. 351-357Konferensbidrag (Refereegranskat)
    Abstract [en]

    Previous reports from our laboratory show that animals treated with engineered nanoparticles derived from metals for 1 week and subjected to hyperthermia showed enhanced neurotoxicity in teens of blood-brain barrier (BBB) disruption, brain edema formation and cell injury. It appears that nano-particle induced enhanced oxidative stress leads to increased lipid peroxidation and over-production of hydroxyl radicals are responsible for exacerbation of neurotoxicity in hyperthermia. Therefore, in this investigation, rats (after 1 week administration of Ag or Cu nanoparticles) were treated with a new antioxidant compound H-290/51 (an inhibitor of lipid peroxidation, 50 mg/kg, p.o.) before subjecting them to hyperthermia. One group of nanoparticle treated rat received H-290/51 and were kept at room temperature for comparison. Our results show that H-290/51 significantly attenuated heat stress induced BBB impairment, brain edema formation and neurotoxicity in nanoparticle treated rats. However, no significant diminution of nanoparticle induced BBB breakdown, or neurotoxicity was observed in H-290/51 treated rats kept at room temperature. These observations suggest that nanoparticles aggravate oxidative stress following hyperthermia leading to exacerbation of neurotoxicity through oxidative stress-related mechanisms, not reported earlier.

  • 365.
    Sharma, Hari Shanker
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Skaper, Stephen D.
    Sharma, Aruna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    181st Annual Meeting of the American Association for the Advancement of Science (AAAS), San Jose Convention Center, San Jose, CA, USA February 12-16, 20152015Ingår i: CNS & Neurological Disorders: Drug Targets, ISSN 1871-5273, E-ISSN 1996-3181, Vol. 14, nr 4, s. 434-436Artikel i tidskrift (Övrigt vetenskapligt)
  • 366.
    Sharma, Hari Shanker
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Skaper, Stephen D.
    Sharma, Aruna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    7th Clinical Trials on Alzheimer's Disease Annual Conference, Philadelphia, PA, USA Nov 20-22, 20142015Ingår i: CNS & Neurological Disorders: Drug Targets, ISSN 1871-5273, E-ISSN 1996-3181, Vol. 14, nr 1, s. 7-10Artikel i tidskrift (Refereegranskat)
  • 367.
    Sharma, Hari Shanker
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Zimmermann-Meinzingen, Sibilla
    Johanson, Conrad E.
    Cerebrolysin reduces blood-cerebrospinal fluid barrier permeability change, brain pathology, and functional deficits following traumatic brain injury in the rat2010Ingår i: Annals of the New York Academy of Sciences, ISSN 0077-8923, E-ISSN 1749-6632, Vol. 1199, s. 125-137Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Traumatic brain injuries (TBIs) induce profound breakdown of the blood-brain and blood-cerebrospinal fluid barriers (BCSFB), brain pathology/edema, and sensory-motor disturbances. Because neurotrophic factors, such as brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), and glial cell-derived neurotrophic factor (GDNF), are neuroprotective in models of brain and spinal cord injuries, we hypothesized that a combination of neurotrophic factors would enhance neuroprotective efficacy. In the present investigation, we examined the effects of Cerebrolysin, a mixture of different neurotrophic factors (Ebewe Neuro Pharma, Austria) on the brain pathology and functional outcome in a rat model of TBI. TBI was produced under Equithesin (3 mL/kg, i.p.) anesthesia by making a longitudinal incision into the right parietal cerebral cortex. Untreated injured rats developed profound disruption of the blood-brain barrier (BBB) to proteins, edema/cell injury, and marked sensory-motor dysfunctions on rota-rod and grid-walking tests at 5 h TBI. Intracerebroventricular administration of Cerebrolysin (10 or 30 mu L) either 5 min or 1 h after TBI significantly reduced leakage of Evans blue and radioiodine tracers across the BBB and BCSFB, and attenuated brain edema formation/neuronal damage in the cortex as well as underlying subcortical regions. Cerebrolysin-treated animals also had improved sensory-motor functions. However, administration of Cerebrolysin 2 h after TBI did not affect these parameters significantly. These observations in TBI demonstrate that early intervention with Cerebrolysin reduces BBB and BCSFB permeability changes, attenuates brain pathology and brain edema, and mitigates functional deficits. Taken together, our observations suggest that Cerebrolysin has potential therapeutic value in TBI.

  • 368.
    Siegel, Tomasz
    et al.
    Czerniakowski Hosp, Dept Anaesthesiol & Intens Therapy, PL-00739 Warsaw, Poland..
    Adamski, Jan
    Satakunta Dist Hosp, Dept Anaesthesiol Intens Care, Pori, Finland..
    Nowakowski, Piotr
    Czerniakowski Hosp, Dept Anaesthesiol & Intens Therapy, PL-00739 Warsaw, Poland..
    Onichimowski, Dariusz
    Reg Hosp Olsztyn, Dept Anaesthesiol & Intens Therapy, Olsztyn, Poland..
    Weigl, Wojciech
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Prospective assessment of the standardized mortality ratio (SMR) as a measure of quality of care in an intensive care unit - a single-centre study2015Ingår i: ANAESTHESIOLOGY INTENSIVE THERAPY, ISSN 1642-5758, Vol. 47, nr 4, s. 328-332Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The standardized mortality ratio (SMR) is a recognized indicator of critical care quality. This ratio is used to compare actual hospital mortality of all patients treated in an Intensive Care Unit (ICU) with predicted mortality. The aim of this study was a prospective analysis of SMR as a measure of the quality of care in a single ICU. Methods: A prospective study was performed during a 12-month period in the ICU of the Czerniakowski Hospital in Warsaw. Predicted hospital mortality was calculated using the SAPS 3 model. The value of the SMR was evaluated in three risk groups (low, moderate, and high risk) and included the surgical status of patients (nonoperative, after elective or emergency surgery). Results: A total of 341 patients were included. The SMR in the general population was 0.98 (95% CI 0.74-1.28). In the low-and high-risk groups, the value of the SMR did not differ significantly from 1. In the average risk group, as well as among patients undergoing elective surgery, the value of the SMR tended to exceed 1. Conclusions: In groups of patients with low and high risk, the values of the SMR indicated a favourable quality of care. Study results should prompt a detailed analysis of the course of treatment for patients with an average risk of death. Analysis of the treatment course and qualification criteria for surgery in patients undergoing elective surgery is also indicated.

  • 369.
    Sigmundsson, Thorir Svavar
    et al.
    Karolinska Univ Hosp, Dept Perioperat Med & Intens Care, Stockholm, Sweden.;Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Öhman, Tomas
    Karolinska Univ Hosp, Dept Perioperat Med & Intens Care, Stockholm, Sweden.;Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Hallbäck, Magnus
    Maquet Crit Care AB, Solna, Sweden..
    Redondo, Eider
    Hosp Navarra, Dept Intens Care Med, Pamplona, Spain..
    Suarez-Sipmann, Fernando
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain..
    Wallin, Mats
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.;Maquet Crit Care AB, Solna, Sweden..
    Oldner, Anders
    Karolinska Univ Hosp, Dept Perioperat Med & Intens Care, Stockholm, Sweden.;Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Sander, Caroline Hällsjö
    Karolinska Univ Hosp, Dept Perioperat Med & Intens Care, Stockholm, Sweden.;Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Björne, Håkan
    Karolinska Univ Hosp, Dept Perioperat Med & Intens Care, Stockholm, Sweden.;Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Performance of a capnodynamic method estimating effective pulmonary blood flow during transient and sustained hypercapnia2018Ingår i: Journal of clinical monitoring and computing, ISSN 1387-1307, E-ISSN 1573-2614, Vol. 32, nr 2, s. 311-319Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The capnodynamic method is a minimally invasive method continuously calculating effective pulmonary blood flow (COEPBF), equivalent to cardiac output when intra pulmonary shunt flow is low. The capnodynamic equation joined with a ventilator pattern containing cyclic reoccurring expiratory holds, provides breath to breath hemodynamic monitoring in the anesthetized patient. Its performance however, might be affected by changes in the mixed venous content of carbon dioxide (CvCO2). The aim of the current study was to evaluate COEPBF during rapid measurable changes in mixed venous carbon dioxide partial pressure (PvCO2) following ischemia-reperfusion and during sustained hypercapnia in a porcine model. Sixteen pigs were submitted to either ischemia-reperfusion (n = 8) after the release of an aortic balloon inflated during 30 min or to prolonged hypercapnia (n = 8) induced by adding an instrumental dead space. Reference cardiac output (CO) was measured by an ultrasonic flow probe placed around the pulmonary artery trunk (COTS). Hemodynamic measurements were obtained at baseline, end of ischemia and during the first 5 min of reperfusion as well as during prolonged hypercapnia at high and low CO states. Ischemia-reperfusion resulted in large changes in PvCO2, hemodynamics and lactate. Bias (limits of agreement) was 0.7 (-0.4 to 1.8) L/min with a mean error of 28% at baseline. COEPBF was impaired during reperfusion but agreement was restored within 5 min. During prolonged hypercapnia, agreement remained good during changes in CO. The mean polar angle was -4.19A degrees (-8.8A degrees to 0.42A degrees). Capnodynamic COEPBF is affected but recovers rapidly after transient large changes in PvCO2 and preserves good agreement and trending ability during states of prolonged hypercapnia at different levels of CO.

  • 370.
    Simm, Mikael
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Söderberg, Ewa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Castegren, Markus
    Department of Anaesthesia, Intensive Care & Surgical Services, Karolinska University Hospital, Huddinge, Stockholm, Sweden..
    Nilsen, Tom
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Eriksson, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Performance of plasma calprotectin as a biomarker of early sepsis: a pilot study2016Ingår i: Biomarkers in Medicine, ISSN 1752-0363, E-ISSN 1752-0371, Vol. 10, nr 8, s. 811-818Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIM: To determine the performance of plasma calprotectin as a marker of sepsis on intensive care unit (ICU) admission and as a marker of mortality day 30 post-ICU admission.

    MATERIALS & METHODS: Consecutive ICU patients were allocated to: sepsis (n = 15), postoperative inflammation (n = 23) and intoxication without inflammation (n = 7) groups.

    RESULTS: Calprotectin was 4.3 (2.6-8.2; mg/l; median [interquartile range]) in the sepsis, 2.8 (1.6-4.4) in the postoperative and 0.7 (0.4-1.6) in the intoxication groups. Area under the receiver operating characteristic curve for sepsis versus intoxication group was: 0.95, for sepsis versus postoperative groups: 0.65 and for survivors versus nonsurvivors: 0.70.

    CONCLUSION: Calprotectin was a sensitive marker of systemic inflammation, is a potential sepsis marker and performed well as mortality predictor in this pilot study.

  • 371.
    Simonis, Fabienne D.
    et al.
    Acad Med Ctr, Dept Intens Care, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands;Acad Med Ctr, LEICA, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands.
    Barbas, Carmen S. V.
    Hosp Israelita Albert Einstein, Dept Intens Care Med, Sao Paulo, Brazil;Univ Sao Paulo, Fac Med, Dept Pulmonol, Sao Paulo, Brazil.
    Artigas-Raventos, Antonio
    Corporacio Sanitaria Univ Parc Tauli, Hosp Sabadell, Dept Intens Care Med, Sabadell, Spain;Corporacio Sanitaria Univ Parc Tauli, Hosp Sabadell, CIBER Enfermedades Resp, Sabadell, Spain.
    Canet, Jaume
    Univ Hosp Germans Trias I Pujol, Dept Anesthesiol, Barcelona, Spain.
    Determann, Rogier M.
    Westfriesgasthuis, Dept Crit Care, Hoorn, Netherlands.
    Anstey, James
    St Vincents Hosp, Dept Intens Care, Melbourne, Vic, Australia.
    Hedenstierna, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi.
    Hemmes, Sabrine N. T.
    Acad Med Ctr, Dept Anesthesiol, Amsterdam, Netherlands.
    Hermans, Greet
    Univ Hosp Leuven, Div Gen Internal Med, Med Intens Care Unit, Louvain, Belgium;Katholieke Univ Leuven, Dept Cellular & Mol Med, Lab Intens Care Med, Louvain, Belgium.
    Hiesmayr, Michael
    Med Univ Vienna, Div Cardiac Thorac & Vasc Anesthesia & Intens Car, Vienna, Austria.
    Hollmann, Markus W.
    Acad Med Ctr, Dept Anesthesiol, Amsterdam, Netherlands.
    Jaber, Samir
    St Eloi Univ Hosp, Dept Crit Care Med & Anesthesiol SAR B, Montpellier, France.
    Martin-Loeches, Ignacio
    St Jamess Univ, Hosp Dublin, HRB Clin Res, Welcome Trust,MICRO,Trinity Ctr Hlth Sci,Dept Cli, Dublin, Ireland;ICVB, Dublin, Ireland.
    Mills, Gary H.
    Sheffield Teaching Hosp, Dept Anaesthesia & Crit Care Med, Sheffield, S Yorkshire, England.
    Pearse, Rupert M.
    Queen Mary Univ London, Barts & London Sch Med & Dent, London, England.
    Putensen, Christian
    Univ Hosp Bonn, Dept Anesthesiol & Intens Care Med, Bonn, Germany.
    Schmid, Werner
    Med Univ Vienna, Div Cardiac Thorac & Vasc Anesthesia & Intens Car, Vienna, Austria.
    Severgnini, Paolo
    Insubria Univ, Dept Biotechnol & Sci Life, Varese, Italy.
    Smith, Roger
    St Vincents Hosp, Dept Intens Care, Melbourne, Vic, Australia.
    Treschan, Tanja A.
    Med Univ Vienna, Div Cardiac Thorac & Vasc Anesthesia & Intens Car, Vienna, Austria;Dusseldorf Univ Hosp, Dept Anaesthesiol, Dusseldorf, Germany.
    Tschernko, Edda M.
    Melo, Marcos F. Vidal
    Harvard Med Sch, Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA.
    Wrigge, Hermann
    Univ Leipzig, Dept Anesthesiol & Intens Care Med, Leipzig, Germany.
    de Abreu, Marcelo Gama
    Univ Hosp Carl Gustav Carus, Dept Anesthesiol & Intens Care Med, Pulm Engn Grp, Dresden, Germany;Tech Univ Dresden, Dept Anesthesiol & Intens Care Med, Pulm Engn Grp, Dresden, Germany.
    Pelosi, Paolo
    Univ Genoa, IRCCS Oncol, Osped Policlin Oncol, Dept Surg Sci & Integrated Diagnost, Genoa, Italy.
    Schultz, Marcus J.
    Acad Med Ctr, Dept Intens Care, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands;Acad Med Ctr, LEICA, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands;Mahidol Univ, MORU, Bangkok, Thailand.
    Serpa Neto, Ary
    Acad Med Ctr, Dept Intens Care, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands;Acad Med Ctr, LEICA, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands;Hosp Israelita Albert Einstein, Dept Intens Care Med, Sao Paulo, Brazil.
    Potentially modifiable respiratory variables contributing to outcome in ICU patients without ARDS: a secondary analysis of PRoVENT2018Ingår i: Annals of Intensive Care, ISSN 2110-5820, E-ISSN 2110-5820, Vol. 8, artikel-id 39Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The majority of critically ill patients do not suffer from acute respiratory distress syndrome (ARDS). To improve the treatment of these patients, we aimed to identify potentially modifiable factors associated with outcome of these patients. Methods: The PRoVENT was an international, multicenter, prospective cohort study of consecutive patients under invasive mechanical ventilatory support. A predefined secondary analysis was to examine factors associated with mortality. The primary endpoint was all-cause in-hospital mortality. Results: 935 Patients were included. In-hospital mortality was 21%. Compared to patients who died, patients who survived had a lower risk of ARDS according to the 'Lung Injury Prediction Score' and received lower maximum airway pressure (P-max), driving pressure (Delta P), positive end-expiratory pressure, and FiO(2) levels. Tidal volume size was similar between the groups. Higher P-max was a potentially modifiable ventilatory variable associated with in-hospital mortality in multivariable analyses. Delta P was not independently associated with in-hospital mortality, but reliable values for Delta P were available for 343 patients only. Non-modifiable factors associated with in-hospital mortality were older age, presence of immunosuppression, higher non-pulmonary sequential organ failure assessment scores, lower pulse oximetry readings, higher heart rates, and functional dependence. Conclusions: Higher P-max was independently associated with higher in-hospital mortality in mechanically ventilated critically ill patients under mechanical ventilatory support for reasons other than ARDS.

  • 372.
    Sjöberg, Folke
    et al.
    Inst för Experimentell och Klinisk medicin, Linköping.
    Larsen, Robert
    Inst för Experimentell och Klinisk medicin, Linköping.
    Bak, Zoltan
    Inst för Experimentell och Klinisk medicin, Linköping.
    Samuelsson, Anders
    Inst för Experimentell och Klinisk medicin, Linköping.
    Iredahl, Fredrik
    Inst för Experimentell och Klinisk medicin, Linköping.
    Thorfinn, Johan
    Inst för Experimentell och Klinisk medicin, Linköping.
    Huss, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Plastikkirurgi.
    Rousseau, Andréas
    Inst för Experimentell och Klinisk medicin, Linköping.
    Hyperbar syrgasbehandling kan vara skadlig vid kolmonoxidförgiftning: [Hyperbaric oxygen therapy can be harmful in carbon monoxide poisoning]2011Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 108, nr 32, s. 1506-1506Artikel i tidskrift (Refereegranskat)
  • 373.
    Sjödin, Marcus O.D.
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Lind, Anne-Li
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Katila, Lenka
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Gordh, Torsten
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Wetterhall, Magnus
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Proteomic analysis of cerebrospinal fluid from neuropathic pain patients reveals proteins with potential role in spinal cord stimulationManuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Spinal cord stimulation (SCS) is a widely used mode of therapy in neuropathic pain of peripheral origin. Despite its well-established clinical use, the underlying physiological mechanisms behind the beneficial analgesic effects of SCS still remain only partially known.  In this study, a proteomic approach was used to compare the protein concentration in cerebrospinal fluid (CSF) from responsive human patients (n=12). The comparison was made between samples taken during at two different timepoints. The first sample was taken when the stimulator had been off for 48 h, the second sample was taken after the stimulator had been used for three weeks. In total, 419 proteins could be identified (P<0.05) and relatively quantified using a shotgun proteomic approach based on immunoaffinity fractionation, multiplexed dimethyl labeling and reversed phase nanoliquid chromatography in combination with electrospray ionization high resolution tandem mass spectrometry. Statistical analysis (P<0.01) revealed two significantly down-regulated proteins; Co2 (P=0.0046), Ibp6 (P=0.0071) and five up-regulated proteins; Lynx1 (P=0.000048), Klk6 (P=0.00058), Angt (P=0.00057), A4 (P=0.0052) and Sap3 (P=0.0076) during the on state. Lynx1was the most significantly and consistently increased protein in all patients. Lynx1 is a modulator of the nicotinic acetylcholine receptor activity in the central nervous system previously described in mice. This study reports for the first time the possible involvement of Lynx1 in SCS-induced analgesia in humans.

  • 374.
    Skorup, Paul
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Antibacterial Effect and Inflammatory Response in Relation to Antibiotic Treatment of Sepsis2019Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Sepsis defines as life-threatening organ dysfunction caused by a dysregulated host response to infection. The importance of early administration of antibiotics in septic shock is undisputed, but the optimal antibiotic choice remains uncertain. Some national guidelines advocate single β-lactam antibiotic treatment while others recommend a combination of β-lactam and aminoglycoside. This thesis aimed to investigate the anti-bacterial properties and antibiotic-induced inflammatory responses of ß-lactam antibiotic compared with effects of the addition of an aminoglycoside in clinically relevant E. coli porcine intensive care sepsis/septic shock models. We also studied the host's antibacterial capacities in primary and secondary sepsis.

    In Paper I the addition of an aminoglycoside, in comparison with single β-lactam antibiotic treatment,  caused decreased bacterial growth in the liver and greater antibiotic-induced blood killing activity ex vivo. The results thereby constitute possible mechanisms to the previously reported improved survival in the most critically ill sepsis patients receiving the β-lactam/aminoglycoside combination. Also observed in this paper was that individual blood bactericidal capacity may have significant effects on antimicrobial outcome.  

    In Paper II we investigated endotoxin release in vivo after antibiotic treatment in comparison with no treatment. There were no differences, however, antibiotics did increase an inflammatory IL-6 response that was associated with leukocyte activation and pulmonary organ dysfunction. A secondary finding was that the addition of an aminoglycoside to a β-lactam induced trends towards less inflammation compared with β-lactam alone.

    Paper III compared how challenge with different pre-killed E. coli activates the inflammatory response, resulting in higher cytokine responses, more leucocyte activation and inflammatory capillary leakage after single β-lactam compared with live or heat-killed bacteria. The addition of an aminoglycoside lowered the β-lactam-induced responses.

    Paper IV demonstrated that animals with secondary sepsis exhibited an attenuated inflammatory response as expected; however, contrary to our hypothesis, the animals’ antibacterial capacities were intact and partly enhanced.

    We conclude that there are likely several beneficial effects of the addition of an aminoglycoside to a β-lactam therapy regimen in septic shock. Because host antibacterial capacities in secondary sepsis are enhanced, the need for bactericidal antibiotic combinations is not greater in secondary than in primary sepsis.

    Delarbeten
    1. Beneficial Antimicrobial Effect of the Addition of an Aminoglycoside to a β-Lactam Antibiotic in an E. coli Porcine Intensive Care Severe Sepsis Model.
    Öppna denna publikation i ny flik eller fönster >>Beneficial Antimicrobial Effect of the Addition of an Aminoglycoside to a β-Lactam Antibiotic in an E. coli Porcine Intensive Care Severe Sepsis Model.
    Visa övriga...
    2014 (Engelska)Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 2, s. e90441-Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    This study aimed to determine whether the addition of an aminoglycoside to a ß-lactam antibiotic increases the antimicrobial effect during the early phase of Gram-negative severe sepsis/septic shock. A porcine model was selected that considered each animal's individual blood bactericidal capacity. Escherichia coli, susceptible to both antibiotics, was given to healthy pigs intravenously during 3 h. At 2 h, the animals were randomized to a 20-min infusion with either cefuroxime alone (n = 9), a combination of cefuroxime+tobramycin (n = 9), or saline (control, n = 9). Blood samples were collected hourly for cultures and quantitative polymerase chain reaction (PCR). Bacterial growth in the organs after 6 h was chosen as the primary endpoint. A blood sample was obtained at baseline before start of bacterial infusion for ex vivo investigation of the blood bactericidal capacity. At 1 h after the administration of the antibiotics, a second blood sample was taken for ex vivo investigation of the antibiotic-induced blood killing activity. All animals developed severe sepsis/septic shock. Blood cultures and PCR rapidly became negative after completed bacterial infusion. Antibiotic-induced blood killing activity was significantly greater in the combination group than in the cefuroxime group (p<0.001). Growth of bacteria in the spleen was reduced in the two antibiotic groups compared with the controls (p<0.01); no difference was noted between the two antibiotic groups. Bacterial growth in the liver was significantly less in the combination group than in the cefuroxime group (p<0.05). High blood bactericidal capacity at baseline was associated with decreased growth in the blood and spleen (p<0.05). The addition of tobramycin to cefuroxime results in increased antibiotic-induced blood killing activity and less bacteria in the liver than cefuroxime alone. Individual blood bactericidal capacity may have a significant effect on antimicrobial outcome.

    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-220397 (URN)10.1371/journal.pone.0090441 (DOI)000332396200200 ()24587365 (PubMedID)
    Tillgänglig från: 2014-03-13 Skapad: 2014-03-13 Senast uppdaterad: 2018-12-12Bibliografiskt granskad
    2. Dynamics of Endotoxin, Inflammatory Variables, and Organ Dysfunction After Treatment With Antibiotics in an Escherichia coli Porcine Intensive Care Sepsis Model
    Öppna denna publikation i ny flik eller fönster >>Dynamics of Endotoxin, Inflammatory Variables, and Organ Dysfunction After Treatment With Antibiotics in an Escherichia coli Porcine Intensive Care Sepsis Model
    Visa övriga...
    2018 (Engelska)Ingår i: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 46, nr 7, s. e634-e641Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    OBJECTIVES: To investigate the dynamics of antibiotic-induced endotoxin liberation and inflammatory response in vivo in a clinically relevant large animal intensive care sepsis model and whether the addition of an aminoglycoside to a β-lactam antibiotic affects these responses.

    DESIGN: Prospective, placebo-controlled interventional experimental study.

    SETTING: University research unit.

    SUBJECTS: Thirty-six healthy pigs administered Escherichia coli as a 3-hour infusion.

    INTERVENTIONS: After 2 hours, during E. coli infusion, the animals were exposed to cefuroxime alone, the combination of cefuroxime and tobramycin, or saline.

    MEASUREMENTS AND MAIN RESULTS: Plasma endotoxin, interleukin-6, tumor necrosis factor-α, leucocytes, and organ dysfunction were recorded for 4 hours after antibiotic treatment, and differences to the values before treatment were calculated. In vitro experiments were performed to ascertain whether endotoxin is released during antibiotic-induced bacterial killing of this E. coli strain. Despite differences between the treatment arms in vitro, no differences in plasma endotoxin were observed in vivo. Antibiotic-treated animals demonstrated a higher interleukin-6 response (p < 0.001), greater leucocyte activation (p < 0.001), and more pronounced deterioration in pulmonary static compliance (p < 0.01) over time than controls. Animals treated with the combination showed a trend toward less inflammation.

    CONCLUSIONS: Treatment with antibiotics may elicit an increased inflammatory interleukin-6 response that is associated with leucocyte activation and pulmonary organ dysfunction. No observable differences were detected in plasma endotoxin concentrations. The reduction in cefuroxime-induced endotoxin release after the addition of an aminoglycoside in vitro could not be reproduced in this model.

    Nationell ämneskategori
    Infektionsmedicin
    Identifikatorer
    urn:nbn:se:uu:diva-349226 (URN)10.1097/CCM.0000000000003139 (DOI)000435290400002 ()29595561 (PubMedID)
    Tillgänglig från: 2018-04-23 Skapad: 2018-04-23 Senast uppdaterad: 2018-12-12Bibliografiskt granskad
    3. Mode of Bacterial Killing Affects the Inflammatory Response and Associated Organ Dysfunctions in a Porcine E. coli Intensive Care Sepsis Model
    Öppna denna publikation i ny flik eller fönster >>Mode of Bacterial Killing Affects the Inflammatory Response and Associated Organ Dysfunctions in a Porcine E. coli Intensive Care Sepsis Model
    Visa övriga...
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Nyckelord
    Antibiotics, Bacteria, Sepsis, Cytokines, Inflammation, Porcine
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-366974 (URN)
    Tillgänglig från: 2018-11-27 Skapad: 2018-11-27 Senast uppdaterad: 2018-12-12Bibliografiskt granskad
    4. Enhanced Bacterial Clearance at a Secondary Sepsis Challenge in an Endotoxin-tolerant Porcine Intensive Care Model
    Öppna denna publikation i ny flik eller fönster >>Enhanced Bacterial Clearance at a Secondary Sepsis Challenge in an Endotoxin-tolerant Porcine Intensive Care Model
    Visa övriga...
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Nyckelord
    Secondary sepsis, Endotoxin-tolerance, Bacteria, E. coli, Porcine, ICU
    Nationell ämneskategori
    Medicin och hälsovetenskap Infektionsmedicin
    Identifikatorer
    urn:nbn:se:uu:diva-366977 (URN)
    Anmärkning

    P Skorup and F Wilske contributed equally to this work.

    Tillgänglig från: 2018-11-27 Skapad: 2018-11-27 Senast uppdaterad: 2018-12-12Bibliografiskt granskad
  • 375.
    Soe, Jesper Langager
    et al.
    Univ Copenhagen, Hvidovre Hosp, Dept Anaesthesiol & Intens Care, Copenhagen, Denmark..
    Hansen, Magna
    Univ Hosp North Norway, Dept Anaesthesiol, Tromso, Norway..
    Tjessem, Marius
    Ullevaal Univ Hosp, Dept Anaesthesiol, Oslo, Norway..
    Ohlen, David
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Suominen, Pertti
    Univ Helsinki, Cent Hosp, Childrens Hosp, Dept Anesthesiol, Helsinki, Finland..
    Interhospital transport of critically ill children and neonates in the Nordic countries. How and by whom?2017Ingår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 61, nr 8, s. 996-996Artikel i tidskrift (Övrigt vetenskapligt)
  • 376.
    Solheim, N.
    et al.
    Lovisenberg Diakonal Hosp, Oslo, Norway;Univ Oslo, Inst Clin Med, Fac Med, Oslo, Norway.
    Gregersen, I.
    Univ Oslo, Inst Clin Med, Fac Med, Oslo, Norway;Oslo Univ Hosp, Res Inst Internal Med, Oslo, Norway.
    Halvorsen, B.
    Univ Oslo, Inst Clin Med, Fac Med, Oslo, Norway;Oslo Univ Hosp, Res Inst Internal Med, Oslo, Norway.
    Bjerkeli, V.
    Univ Oslo, Inst Clin Med, Fac Med, Oslo, Norway;Oslo Univ Hosp, Res Inst Internal Med, Oslo, Norway.
    Stubhaug, A.
    Univ Oslo, Inst Clin Med, Fac Med, Oslo, Norway;Oslo Univ Hosp, Div Emergencies & Crit Care, Dept Pain Med & Res, Oslo, Norway.
    Gordh, T
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Rosseland, L. A.
    Univ Oslo, Inst Clin Med, Fac Med, Oslo, Norway;Oslo Univ Hosp, Div Emergencies & Crit Care, Dept Res & Dev, Oslo, Norway.
    Randomized controlled trial of intra-articular ketorolac on pain and inflammation after minor arthroscopic knee surgery2018Ingår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 62, nr 6, s. 829-838Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Ketorolac is an effective non-steroidal anti-inflammatory drug, commonly used with local anaesthetics as part of local infiltration analgesia protocols following orthopaedic surgery. However, systemic uptake and drug action may be the major mechanism after local infiltration. The aims of this project were to study the effects of a small, systemically ineffective dose of ketorolac given intra-articularly for post-operative pain and also to study synovial inflammatory biomarkers. We investigated whether ketorolac affects pro-inflammatory biomarkers in an invitro model, as well.

    Methods: In this placebo-controlled, blind, randomized study, we analysed intra-articular ketorolac (5mg) in ambulatory minor knee surgery patients with moderate or severe pain (n=44). We assessed post-operative pain intensity (n=44) and analysed microdialysis samples taken from knee synovial tissue every 20min (n=34). We also tested cyclooxygenase-independent effects of ketorolac in synovial cells stimulated by prostaglandin E-2 and chondroitin sulphate invitro.

    Results: Intra-articular ketorolac (5mg) administration did not reduce pain or synovial pro-inflammatory cytokines CXCL1, IL-8, and MCP-1, 0-120min after knee arthroscopy. Female gender was a risk factor for moderate or severe pain (relative risk 1.45, 95% confidence interval 1.04-2.01). Paradoxically, ketorolac increased the release of CXCL1 and IL-8 in prostaglandin E-2 and chondroitin sulphate-stimulated synovial cells invitro.

    Conclusion: Ketorolac prescribed at a low dose intra-articularly does not produce any detectable analgesic effect after minor knee surgery.

  • 377.
    Sommar, Pehr
    et al.
    Inst för Experimentell och Klinisk medicin, Linköping.
    Huss, Fredrik
    [Burns].2008Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 105, nr 48-49, s. 3547-52Artikel i tidskrift (Refereegranskat)
  • 378.
    Sperber, Jesper
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Protective Mechanical Ventilation in Inflammatory and Ventilator-Associated Pneumonia Models2016Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Severe infections, trauma or major surgery can each cause a state of systemic inflammation. These causes for systemic inflammation often coexist and complicate each other. Mechanical ventilation is commonly used during major surgical procedures and when respiratory functions are failing in the intensive care setting. Although necessary, the use of mechanical ventilation can cause injury to the lungs and other organs especially under states of systemic inflammation. Moreover, a course of mechanical ventilator therapy can be complicated by ventilator-associated pneumonia, a factor greatly influencing mortality. The efforts to avoid additional ventilator-induced injury to patients are embodied in the expression ‘protective ventilation’.

    With the use of pig models we have examined the impact of protective ventilation on systemic inflammation, on organ-specific inflammation and on bacterial growth during pneumonia. Additionally, with a 30-hour ventilator-associated pneumonia model we examined the influence of mechanical ventilation and systemic inflammation on bacterial growth. Systemic inflammation was initiated with surgery and enhanced with endotoxin. The bacterium used was Pseudomonas aeruginosa.

    We found that protective ventilation during systemic inflammation attenuated the systemic inflammatory cytokine responses and reduced secondary organ damage. Moreover, the attenuated inflammatory responses were seen on the organ specific level, most clearly as reduced counts of inflammatory cytokines from the liver. Protective ventilation entailed lower bacterial counts in lung tissue after 6 hours of pneumonia. Mechanical ventilation for 24 h, before a bacterial challenge into the lungs, increased bacterial counts in lung tissue after 6 h. The addition of systemic inflammation by endotoxin during 24 h increased the bacterial counts even more. For comparison, these experiments used control groups with clinically common ventilator settings.

    Summarily, these results support the use of protective ventilation as a means to reduce systemic inflammation and organ injury, and to optimize bacterial clearance in states of systemic inflammation and pneumonia.

    Delarbeten
    1. Lung protective ventilation induces immunotolerance and nitric oxide metabolites in porcine experimental postoperative sepsis
    Öppna denna publikation i ny flik eller fönster >>Lung protective ventilation induces immunotolerance and nitric oxide metabolites in porcine experimental postoperative sepsis
    Visa övriga...
    2013 (Engelska)Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 12, s. e83182-Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Low tidal volume ventilation is beneficial in patients with severe pulmonary dysfunction and would, in theory, reduce postoperative complications if implemented during routine surgery. The study aimed to investigate whether low tidal volume ventilation and high positive end-expiratory pressure (PEEP) in a large animal model of postoperative sepsis would attenuate the systemic inflammatory response and organ dysfunction. Thirty healthy pigs were randomized to three groups: Group Prot-7h, i.e. protective ventilation for 7 h, was ventilated with a tidal volume of 6 mL x kg-1 for 7 h; group Prot-5h, i.e. protective ventilation for 5 h, was ventilated with a tidal volume of 10 mL x kg-1 for 2 h, after which the group was ventilated with a tidal volume of 6 mL x kg-1; and a control group that was ventilated with a tidal volume of 10 mL x kg-1 for 7 h. In groups Prot-7h and Prot-5h PEEP was 5 cmH2O for 2 h and 10 cmH2O for 5 h. In the control group PEEP was 5 cmH2O for the entire experiment. After surgery for 2 h, postoperative sepsis was simulated with an endotoxin infusion for 5 h. Low tidal volume ventilation combined with higher PEEP led to lower levels of interleukin 6 and 10 in plasma, higher PaO2/FiO2, better preserved functional residual capacity and lower plasma troponin I as compared with animals ventilated with a medium high tidal volume and lower PEEP. The beneficial effects of protective ventilation were seen despite greater reductions in cardiac index and oxygen delivery index. In the immediate postoperative phase low VT ventilation with higher PEEP was associated with reduced ex vivo plasma capacity to produce TNF-α upon endotoxin stimulation and higher nitrite levels in urine. These findings might represent mechanistic explanations for the attenuation of systemic inflammation and inflammatory-induced organ dysfunction.

    Nationell ämneskategori
    Medicinska och farmaceutiska grundvetenskaper
    Identifikatorer
    urn:nbn:se:uu:diva-213610 (URN)10.1371/journal.pone.0083182 (DOI)000328731800101 ()24349457 (PubMedID)
    Tillgänglig från: 2013-12-30 Skapad: 2013-12-30 Senast uppdaterad: 2018-01-11Bibliografiskt granskad
    2. Evaluating the effects of protective ventilation on organ-specific cytokine production in porcine experimental postoperative sepsis
    Öppna denna publikation i ny flik eller fönster >>Evaluating the effects of protective ventilation on organ-specific cytokine production in porcine experimental postoperative sepsis
    Visa övriga...
    2015 (Engelska)Ingår i: BMC Pulmonary Medicine, ISSN 1471-2466, E-ISSN 1471-2466, Vol. 15, artikel-id 60Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    BACKGROUND: Protective ventilation with lower tidal volume (VT) and higher positive end-expiratory pressure (PEEP) reduces the negative additive effects of mechanical ventilation during systemic inflammatory response syndrome. We hypothesised that protective ventilation during surgery would affect the organ-specific immune response in an experimental animal model of endotoxin-induced sepsis-like syndrome.

    METHODS: 30 pigs were laparotomised for 2 hours (h), after which a continuous endotoxin infusion was started at 0.25 micrograms × kg(-1) × h(-1) for 5 h. Catheters were placed in the carotid artery, hepatic vein, portal vein and jugular bulb. Animals were randomised to two protective ventilation groups (n = 10 each): one group was ventilated with VT 6 mL × kg(-1) during the whole experiment while the other group was ventilated during the surgical phase with VT of 10 mL × kg(-1). In both groups PEEP was 5 cmH2O during surgery and increased to 10 cmH2O at the start of endotoxin infusion. A control group (n = 10) was ventilated with VT of 10 mL × kg(-1) and PEEP 5 cm H20 throughout the experiment. In four sample locations we a) simultaneously compared cytokine levels, b) studied the effect of protective ventilation initiated before and during endotoxemia and c) evaluated protective ventilation on organ-specific cytokine levels.

    RESULTS: TNF-alpha levels were highest in the hepatic vein, IL-6 levels highest in the artery and jugular bulb and IL-10 levels lowest in the artery. Protective ventilation initiated before and during endotoxemia did not differ in organ-specific cytokine levels. Protective ventilation led to lower levels of TNF-alpha in the hepatic vein compared with the control group, whereas no significant differences were seen in the artery, portal vein or jugular bulb.

    CONCLUSIONS: Variation between organs in cytokine output was observed during experimental sepsis. We see no implication from cytokine levels for initiating protective ventilation before endotoxemia. However, during endotoxemia protective ventilation attenuates hepatic inflammatory cytokine output contributing to a reduced total inflammatory burden.

    Nationell ämneskategori
    Anestesi och intensivvård
    Identifikatorer
    urn:nbn:se:uu:diva-253174 (URN)10.1186/s12890-015-0052-9 (DOI)000354840700001 ()25958003 (PubMedID)
    Tillgänglig från: 2015-05-23 Skapad: 2015-05-23 Senast uppdaterad: 2017-12-04Bibliografiskt granskad
    3. Protective Ventilation Reduces Pseudomonas Aeruginosa Growth in a Porcine Pneumonia Model
    Öppna denna publikation i ny flik eller fönster >>Protective Ventilation Reduces Pseudomonas Aeruginosa Growth in a Porcine Pneumonia Model
    Visa övriga...
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Nationell ämneskategori
    Anestesi och intensivvård
    Identifikatorer
    urn:nbn:se:uu:diva-282600 (URN)
    Tillgänglig från: 2016-04-05 Skapad: 2016-04-05 Senast uppdaterad: 2016-05-12
    4. Exposure to Mechanical Ventilation and Endotoxin for 24 Hours Before Infection Influences Pseudomonas Aeruginosa Growth During Experimental Porcine Ventilator-Associated Pneumonia
    Öppna denna publikation i ny flik eller fönster >>Exposure to Mechanical Ventilation and Endotoxin for 24 Hours Before Infection Influences Pseudomonas Aeruginosa Growth During Experimental Porcine Ventilator-Associated Pneumonia
    Visa övriga...
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Nationell ämneskategori
    Anestesi och intensivvård
    Identifikatorer
    urn:nbn:se:uu:diva-282601 (URN)
    Tillgänglig från: 2016-04-05 Skapad: 2016-04-05 Senast uppdaterad: 2016-05-12
  • 379.
    Sperber, Jesper
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Castegren, Markus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Evaluating the effects of protective ventilation on organ-specific cytokine production in porcine experimental postoperative sepsis2015Ingår i: BMC Pulmonary Medicine, ISSN 1471-2466, E-ISSN 1471-2466, Vol. 15, artikel-id 60Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Protective ventilation with lower tidal volume (VT) and higher positive end-expiratory pressure (PEEP) reduces the negative additive effects of mechanical ventilation during systemic inflammatory response syndrome. We hypothesised that protective ventilation during surgery would affect the organ-specific immune response in an experimental animal model of endotoxin-induced sepsis-like syndrome.

    METHODS: 30 pigs were laparotomised for 2 hours (h), after which a continuous endotoxin infusion was started at 0.25 micrograms × kg(-1) × h(-1) for 5 h. Catheters were placed in the carotid artery, hepatic vein, portal vein and jugular bulb. Animals were randomised to two protective ventilation groups (n = 10 each): one group was ventilated with VT 6 mL × kg(-1) during the whole experiment while the other group was ventilated during the surgical phase with VT of 10 mL × kg(-1). In both groups PEEP was 5 cmH2O during surgery and increased to 10 cmH2O at the start of endotoxin infusion. A control group (n = 10) was ventilated with VT of 10 mL × kg(-1) and PEEP 5 cm H20 throughout the experiment. In four sample locations we a) simultaneously compared cytokine levels, b) studied the effect of protective ventilation initiated before and during endotoxemia and c) evaluated protective ventilation on organ-specific cytokine levels.

    RESULTS: TNF-alpha levels were highest in the hepatic vein, IL-6 levels highest in the artery and jugular bulb and IL-10 levels lowest in the artery. Protective ventilation initiated before and during endotoxemia did not differ in organ-specific cytokine levels. Protective ventilation led to lower levels of TNF-alpha in the hepatic vein compared with the control group, whereas no significant differences were seen in the artery, portal vein or jugular bulb.

    CONCLUSIONS: Variation between organs in cytokine output was observed during experimental sepsis. We see no implication from cytokine levels for initiating protective ventilation before endotoxemia. However, during endotoxemia protective ventilation attenuates hepatic inflammatory cytokine output contributing to a reduced total inflammatory burden.

  • 380.
    Sperber, Jesper
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Nyberg, Axel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Castegren, Markus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Exposure to Mechanical Ventilation and Endotoxin for 24 Hours Before Infection Influences Pseudomonas Aeruginosa Growth During Experimental Porcine Ventilator-Associated PneumoniaManuskript (preprint) (Övrigt vetenskapligt)
  • 381.
    Sperber, Jesper
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Nyberg, Axel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Melhus, Åsa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi och infektionsmedicin.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Castegren, Markus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Protective Ventilation Reduces Pseudomonas Aeruginosa Growth in a Porcine Pneumonia ModelManuskript (preprint) (Övrigt vetenskapligt)
  • 382.
    Sperber, Jesper
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Centre for Clinical Research Sörmland, Department of Anesthesiology & Intensive Care Mälarsjukhuset, SE-631 88 Eskilstuna, Sweden.
    Nyberg, Axel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Centre for Clinical Research Sörmland, Department of Anesthesiology & Intensive Care Mälarsjukhuset, SE-631 88 Eskilstuna, Sweden.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Melhus, Åsa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Castegren, Markus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Perioperative Medicine and Intensive Care, Karolinska University Hospital and CLINTEC, Karolinska Institute, Stockholm, Sweden.
    Protective ventilation reduces Pseudomonas aeruginosa growth in lung tissue in a porcine pneumonia model2017Ingår i: Intensive & Critical Care Nursing, ISSN 0964-3397, E-ISSN 1532-4036, Vol. 5, artikel-id 40Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Mechanical ventilation with positive end expiratory pressure and low tidal volume, i.e. protective ventilation, is recommended in patients with acute respiratory distress syndrome. However, the effect of protective ventilation on bacterial growth during early pneumonia in non-injured lungs is not extensively studied. The main objectives were to compare two different ventilator settings on Pseudomonas aeruginosa growth in lung tissue and the development of lung injury.

    METHODS: A porcine model of severe pneumonia was used. The protective group (n = 10) had an end expiratory pressure of 10 cm H2O and a tidal volume of 6 ml x kg-1. The control group (n = 10) had an end expiratory pressure of 5 cm H2O and a tidal volume of 10 ml x kg-1. 1011 colony forming units of Pseudomonas aeruginosa were inoculated intra-tracheally at baseline, after which the experiment continued for 6 h. Two animals from each group received only saline, and served as sham animals. Lung tissue samples from each animal were used for bacterial cultures and wet-to-dry weight ratio measurements.

    RESULTS: The protective group displayed lower numbers of Pseudomonas aeruginosa (p < 0.05) in the lung tissue, and a lower wet-to-dry ratio (p < 0.01) than the control group. The control group deteriorated in arterial oxygen tension/inspired oxygen fraction, whereas the protective group was unchanged (p < 0.01).

    CONCLUSIONS: In early phase pneumonia, protective ventilation with lower tidal volume and higher end expiratory pressure has the potential to reduce the pulmonary bacterial burden and the development of lung injury.

  • 383. Stenqvist, Ola
    et al.
    Hallén, Börje
    Lennmarken, Claes
    Lindahl, Sten
    Zetterström, Henrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Guidelines for increased safety in anaesthesiology1991Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 88, s. 242-243Artikel i tidskrift (Refereegranskat)
  • 384.
    Strandberg, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Experimental Studies on Diagnostic and Therapeutic Aspects of Intraosseous Access2017Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Reliable access to the circulation is paramount in most medical and surgical emergencies. When venous access cannot be expediently established, intraosseous (IO) access is indicated. This method has a high success rate even in relatively inexperienced hands and there is considerable clinical experience of IO administration of drugs and fluids. There is however limited evidence on the use of IO samples for laboratory analysis. Also, uptake of drugs during shock has not been extensively studied. Further, there have been concerns that analysis of IO samples may damage laboratory equipment. We have studied, in a porcine model, the use of IO samples for point of care analysis of blood gases, acid base parameters and blood chemistries in stable circulation, in experimental septic shock, and in hypovolemia after major hemorrhage, comparing IO samples with arterial and venous samples, and comparing IO samples from different sites. We have also studied coagulation assays on IO samples in stable circulation and after major hemorrhage. Furthermore, we have compared IO and intravenous administration of antibiotics in experimental sepsis.

    Average differences between IO and arterial/venous samples varied between the studied analytes. During stable circulation, average IO levels of blood gases, acid-base parameters, hemoglobin/hematocrit and several blood chemistries approximated venous levels relatively well. Differences in acid-base and blood gas parameters, and lactate, were more pronounced in hypovolemia, as well as in sepsis. The dispersion of the differences was often relatively large, indicating limited precision. Average differences between two intraosseous sites were small.

    Intraosseous samples were clinically hypercoagulable with a strong tendency to clot in vitro, and thromboelastography demonstrated shortened reaction times compared with venous samples. Major bleeding and hemodilution moderately affected the studied coagulation parameters.

    In endotoxemic animals with circulatory instability, concentrations of cefotaxime and gentamicin in samples from the pulmonary artery were comparable at 5 minutes after intraosseous and intravenous administration, and during a 3 hour observation period.

    In summary, agreement between analytes in intraosseous and conventional blood samples was variable and often unpredictable, especially during circulatory compromise. Intraosseous samples clinically appeared hypercoagulable, and thromboelastography confirmed this. High and comparable concentrations of cefotaxime and gentamicin were found after intraosseous and intravenous administration of equivalent doses, suggesting that uptake is acceptable during septic instability.  

    Delarbeten
    1. Analysis of intraosseous samples using point of care technology: an experimental study in the anaesthetised pig
    Öppna denna publikation i ny flik eller fönster >>Analysis of intraosseous samples using point of care technology: an experimental study in the anaesthetised pig
    Visa övriga...
    2012 (Engelska)Ingår i: Resuscitation, ISSN 0300-9572, E-ISSN 1873-1570, Vol. 83, nr 11, s. 1381-1385Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    BACKGROUND:

    Intraosseous access is an essential method in emergency medicine when other forms of vascular access are unavailable and there is an urgent need for fluid or drug therapy. A number of publications have discussed the suitability of using intraosseous access for laboratory testing. We aimed to further evaluate this issue and to study the accuracy and precision of intraosseous measurements.

    METHODS:

    Five healthy, anaesthetised pigs were instrumented with bilateral tibial intraosseous cannulae and an arterial catheter. Samples were collected hourly for 6h and analysed for blood gases, acid base status, haemoglobin and electrolytes using an I-Stat(®) point of care analyser.

    RESULTS:

    There was no clinically relevant difference between results from left and right intraosseous sites. The variability of the intraosseous sample values, measured as the coefficient of variance (CV), was maximally 11%, and smaller than for the arterial sample values for all variables except SO(2). For most variables, there seems to be some degree of systematic difference between intraosseous and arterial results. However, the direction of this difference seems to be predictable.

    CONCLUSION:

    Based on our findings in this animal model, cartridge based point of care instruments appear suitable for the analysis of intraosseous samples. The agreement between intraosseous and arterial analysis seems to be good enough for the method to be clinically useful. The precision, quantified in terms of CV, is at least as good for intraosseous as for arterial analysis. There is no clinically important difference between samples from left and right tibia, indicating a good reproducibility.

    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-181455 (URN)10.1016/j.resuscitation.2012.04.007 (DOI)000311793100023 ()22542768 (PubMedID)
    Tillgänglig från: 2012-09-24 Skapad: 2012-09-24 Senast uppdaterad: 2017-12-07Bibliografiskt granskad
    2. Analysis of intraosseous samples in endotoxemic shock: an experimental study in the anaesthetised pig
    Öppna denna publikation i ny flik eller fönster >>Analysis of intraosseous samples in endotoxemic shock: an experimental study in the anaesthetised pig
    Visa övriga...
    2014 (Engelska)Ingår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 58, nr 3, s. 337-344Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Background

    Intraosseous (IO) access is used in emergency situations to allow rapid initiation of treatment. IO access is also sometimes used for blood sampling, although data on accuracy of such sampling in critical illness are limited. There is also a potential risk that bone marrow fragments in IO samples may damage laboratory equipment. It is ethically questionable to perform a simultaneous comparison between IO and arterial/venous sampling in critically ill humans. We have, thus, studied the analytical performance of IO sampling in a porcine septic shock model using a cartridge-based analyser.

    Methods

    Eight pigs with endotoxin-induced septic shock were sampled hourly for 6 h, and analysed for blood gases, acid base status, haemoglobin, glucose and lactate using point of care instruments. Samples were taken from three IO cannulae (tibia bilaterally, one with infusion, and humerus), one arterial and one venous. An interaction test was used to assess changes in agreement between methods over time. Bland–Altman plots were constructed to study bias between methods.

    Results

    There were, to a varying extent, differences between IO and arterial/venous levels for all studied variables, but agreement did not change significantly during the experiment. A general finding was a large dispersion of differences between methods.

    Conclusions

    IO sample values should be treated with caution in this setting but may add useful information to the clinical picture. The tibia or humerus may be used for sampling. IO infusion decreases agreement, thus sampling during infusion should be avoided.

    Nationell ämneskategori
    Anestesi och intensivvård
    Identifikatorer
    urn:nbn:se:uu:diva-220973 (URN)10.1111/aas.12274 (DOI)000331406500011 ()
    Tillgänglig från: 2014-03-25 Skapad: 2014-03-24 Senast uppdaterad: 2017-12-05Bibliografiskt granskad
    3. Intraosseous and intravenous administration of antibiotics yields comparable plasma concentrations during experimental septic shock
    Öppna denna publikation i ny flik eller fönster >>Intraosseous and intravenous administration of antibiotics yields comparable plasma concentrations during experimental septic shock
    Visa övriga...
    2015 (Engelska)Ingår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 59, nr 3, s. 346-353Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    BACKGROUND: We aimed to investigate whether comparable antibiotic concentrations could be reached with intraosseous and intravenous administration during septic shock.

    METHODS: In this randomized, prospective experimental study conducted at an animal research laboratory at the University Hospital of Uppsala, eight anesthetized pigs, weighing 21.2 to 29.1 kg (mean: 25.2 ± 2.3 kg), received endotoxin infusion at 4 μg/kg/h for 6 h. At the onset of clinical shock, alternatively after 3 h of endotoxemia, they received 75 mg/kg of cefotaxime and 7 mg/kg of gentamicin either in a proximal tibial intraosseous catheter or in a peripheral intravenous catheter. Mixed venous samples were taken after 5, 15, 30, 60, 120 and 180 min and analyzed for antibiotic concentrations.

    RESULTS: For both antibiotics, plasma concentrations after intraosseous and intravenous administration followed similar curves throughout the observation period, and peak concentrations were comparable. Mean concentration area under the curve (AUC mg × h/l) for cefotaxime was 108.1 ± 19.5 after intraosseous and 116.5 ± 11.1 after intravenous administration; ratio 0.93, (95% CI 0.71-1.19). Mean AUC for gentamicin was 28.1 ± 6.8 for intraosseous and 32.2 ± 3.5 for intravenous administration; ratio 0.87 (95% CI 0.62-1.19).

    CONCLUSIONS: In this porcine septic shock model, intraosseous and intravenous administration of gentamicin and cefotaxime yielded comparable concentrations. In an emergency, intraosseous administration of these antibiotics may be considered in severe infections when venous access is difficult.

    Nationell ämneskategori
    Anestesi och intensivvård
    Identifikatorer
    urn:nbn:se:uu:diva-240273 (URN)10.1111/aas.12454 (DOI)000349604000009 ()25557933 (PubMedID)
    Tillgänglig från: 2015-01-06 Skapad: 2015-01-06 Senast uppdaterad: 2017-12-05Bibliografiskt granskad
    4. Analysis of Thromboelastography, PT, APTT and Fibrinogen in Intraosseous and Venous Samples: An Experimental Study
    Öppna denna publikation i ny flik eller fönster >>Analysis of Thromboelastography, PT, APTT and Fibrinogen in Intraosseous and Venous Samples: An Experimental Study
    Visa övriga...
    2016 (Engelska)Ingår i: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine, ISSN 1757-7241, E-ISSN 1757-7241, Vol. 24, artikel-id 131Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Background:Laboratory analysis of coagulation is often important in emergencies. If vascular access is challenging,intraosseous catheterization may be necessary for treatment. We studied the analysis of coagulation parameters inintraosseous aspirate during stable conditions and after major haemorrhage in a porcine model.Methods:Ten anesthetized pigs received central venous and intraosseous catheters and samples were taken foranalysis of thromboelastography (TEG), prothrombin time (PT), activated partial thromboplastin time (APTT) andfibrinogen concentration. Analyses were repeated after removal of 50 % of the calculated blood volume andresuscitation with crystalloid. Intraosseous and venous values were compared.Results:Bleeding and resuscitation resulted in haemodilution and hypotension. Median TEG reaction time wasshorter in intraosseous than in venous samples before (1.6 vs 4.6 min) and after (1.6 vs 4.7 min) haemodilution.Median maximal amplitude was smaller in intraosseous samples at baseline (68.3 vs 76.4 mm). No major differenceswere demonstrated for the other TEG parameters. The intraosseous samples often coagulated in vitro, makinganalysis of PT, APTT and fibrinogen difficult. After haemodilution, TEG maximal amplitude andα-angle, andfibrinogen concentration, were decreased and PT increased.Discussion:The intraosseous samples were clinically hypercoagulable and the TEG demonstrated a shortenedreaction time. The reason for this may hypothetically be found in the composition of the IO aspirate or in thesampling technique. After 50 % haemorrhage and haemodilution, a clinically relevant decrease in fibrinogenconcentration and a lower TEG maximal amplitude were observed.Conclusions:Although the sample is small, these data indicate that intraosseous samples are hypercoagulable,which may limit their usefulness for coagulation studies. Major haemodilution only moderately affected the studied parameters.

    Nyckelord
    Blood coagulation; Haemorrhage; Infusions; Intraosseous; Thrombelastography
    Nationell ämneskategori
    Anestesi och intensivvård
    Identifikatorer
    urn:nbn:se:uu:diva-306587 (URN)10.1186/s13049-016-0318-0 (DOI)000386860300001 ()
    Tillgänglig från: 2016-10-29 Skapad: 2016-10-29 Senast uppdaterad: 2017-11-29Bibliografiskt granskad
    5. Comparison of Intraosseous, Arterial, and Venous Blood Sampling for Laboratory Analysis in Hemorrhagic Shock
    Öppna denna publikation i ny flik eller fönster >>Comparison of Intraosseous, Arterial, and Venous Blood Sampling for Laboratory Analysis in Hemorrhagic Shock
    2019 (Engelska)Ingår i: Clinical Laboratory, ISSN 1433-6510, Vol. 65, nr 7, s. 1169-1177Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Background: Intraosseous (IO) access is often indicated for administration of drugs and fluids in emergencies when venous access is challenging. There is no consensus regarding whether and which laboratory analyses may be performed on IO aspirates, and research on hemodynamically unstable subjects is limited.

    Methods: Twelve anesthetized pigs were sampled from IO, venous, and arterial accesses during stable circulation and after hemorrhage corresponding to 20% and 40% of the blood volume. Samples were analyzed for blood gases and acid-base status, electrolytes, hematocrit, creatinine, glucose, alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase (γ-GT), alkaline phosphatase (ALP), and creatine kinase (CK).

    Results: Average differences of blood gases and acid-base parameters, sodium, creatinine, hematocrit, ALT, and γ-GT and between IO and venous samples were small at baseline and after hemorrhage while differences for lactate and glucose increased with hypovolemia. Both IO-arterial and venoarterial differences in acid-base parameters increased with hypovolemia. Dispersions of differences were often large.

    Conclusions: Average levels of blood gases, acid base parameters, hematocrit, CK, AST, γ-GT, creatinine, and ALT, but not lactate and glucose, were similar in IO and venous samples in hypovolemia. However, precision was limited, indicating that IO test results should be confirmed when other vascular access is established, and that analysis of IO samples should be limited to acute situations and not used for detailed diagnostics in this setting.

    Nyckelord
    analysis, blood drawing, intraosseous sampling, laboratory, precision, shock
    Nationell ämneskategori
    Anestesi och intensivvård
    Forskningsämne
    Anestesiologi och intensivvård
    Identifikatorer
    urn:nbn:se:uu:diva-321402 (URN)10.7754/Clin.Lab.2019.181214 (DOI)000475700400006 ()31307157 (PubMedID)
    Anmärkning

    Title in thesis list of papers: Comparison of Intraosseous, Arterial and Venous Blood Sampling for Laboratory Analysis in Haemorrhagic Shock

    Tillgänglig från: 2017-05-04 Skapad: 2017-05-04 Senast uppdaterad: 2019-08-26Bibliografiskt granskad
  • 385.
    Strandberg, Gunnar
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Eriksson, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Lipcsey, Miklos
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Intraosseous Samples Can Be Used for CreatinineMeasurements - An Experimental Study in the Anaesthetised Pig2014Ingår i: Clinical Laboratory, ISSN 1433-6510, Vol. 60, nr 10, s. 1587-1591Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Intraosseous (IO) access is a valuable tool in prehospital locations and in emergency departments when other forms of vascular access are unavailable. Creatinine is often used for dose adjustment of drugs that may be administered through intraosseous cannulae. We aimed to study the possibility of analysing creatinine in intraosseous samples and study the accuracy and precision of such measurements.

    Methods: Eight pigs with endotoxin induced septic shock were sampled hourly for six hours and analysed for plasma creatinine. Samples were collected from arterial, venous, and IO cannulae.

    Results: There was an increase in creatinine values during the later part of the experiment. The coefficients of variation between the three sampling sites were less than 10% at all sampling times.

    Conclusions: Based on our findings intraosseous samples can be used for creatinine determination in emergency settings.

  • 386.
    Strandberg, Gunnar
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Lipcsey, Miklos
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Berglund, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Eriksson, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Analysis of intraosseous samples in endotoxemic shock: an experimental study in the anaesthetised pig2014Ingår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 58, nr 3, s. 337-344Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background

    Intraosseous (IO) access is used in emergency situations to allow rapid initiation of treatment. IO access is also sometimes used for blood sampling, although data on accuracy of such sampling in critical illness are limited. There is also a potential risk that bone marrow fragments in IO samples may damage laboratory equipment. It is ethically questionable to perform a simultaneous comparison between IO and arterial/venous sampling in critically ill humans. We have, thus, studied the analytical performance of IO sampling in a porcine septic shock model using a cartridge-based analyser.

    Methods

    Eight pigs with endotoxin-induced septic shock were sampled hourly for 6 h, and analysed for blood gases, acid base status, haemoglobin, glucose and lactate using point of care instruments. Samples were taken from three IO cannulae (tibia bilaterally, one with infusion, and humerus), one arterial and one venous. An interaction test was used to assess changes in agreement between methods over time. Bland–Altman plots were constructed to study bias between methods.

    Results

    There were, to a varying extent, differences between IO and arterial/venous levels for all studied variables, but agreement did not change significantly during the experiment. A general finding was a large dispersion of differences between methods.

    Conclusions

    IO sample values should be treated with caution in this setting but may add useful information to the clinical picture. The tibia or humerus may be used for sampling. IO infusion decreases agreement, thus sampling during infusion should be avoided.

  • 387.
    Strandberg, Gunnar
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Lipcsey, Miklos
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Eriksson, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Intraosseous blood aspirates analysed by a portable cartridge-based device2011Ingår i: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 15, nr Suppl 1, s. 49-49Artikel i tidskrift (Refereegranskat)
  • 388.
    Strandberg, Gunnar
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Lipcsey, Miklos
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Michalek, J
    Eriksson, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Intraosseous and intravenous administration of antibiotics yields comparable plasma concentrations during experimental septic shock2015Ingår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 59, nr 3, s. 346-353Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: We aimed to investigate whether comparable antibiotic concentrations could be reached with intraosseous and intravenous administration during septic shock.

    METHODS: In this randomized, prospective experimental study conducted at an animal research laboratory at the University Hospital of Uppsala, eight anesthetized pigs, weighing 21.2 to 29.1 kg (mean: 25.2 ± 2.3 kg), received endotoxin infusion at 4 μg/kg/h for 6 h. At the onset of clinical shock, alternatively after 3 h of endotoxemia, they received 75 mg/kg of cefotaxime and 7 mg/kg of gentamicin either in a proximal tibial intraosseous catheter or in a peripheral intravenous catheter. Mixed venous samples were taken after 5, 15, 30, 60, 120 and 180 min and analyzed for antibiotic concentrations.

    RESULTS: For both antibiotics, plasma concentrations after intraosseous and intravenous administration followed similar curves throughout the observation period, and peak concentrations were comparable. Mean concentration area under the curve (AUC mg × h/l) for cefotaxime was 108.1 ± 19.5 after intraosseous and 116.5 ± 11.1 after intravenous administration; ratio 0.93, (95% CI 0.71-1.19). Mean AUC for gentamicin was 28.1 ± 6.8 for intraosseous and 32.2 ± 3.5 for intravenous administration; ratio 0.87 (95% CI 0.62-1.19).

    CONCLUSIONS: In this porcine septic shock model, intraosseous and intravenous administration of gentamicin and cefotaxime yielded comparable concentrations. In an emergency, intraosseous administration of these antibiotics may be considered in severe infections when venous access is difficult.

  • 389.
    Strandberg, Gunnar
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Eriksson, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Comparison of Intraosseous, Arterial, and Venous Blood Sampling for Laboratory Analysis in Hemorrhagic Shock2019Ingår i: Clinical Laboratory, ISSN 1433-6510, Vol. 65, nr 7, s. 1169-1177Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Intraosseous (IO) access is often indicated for administration of drugs and fluids in emergencies when venous access is challenging. There is no consensus regarding whether and which laboratory analyses may be performed on IO aspirates, and research on hemodynamically unstable subjects is limited.

    Methods: Twelve anesthetized pigs were sampled from IO, venous, and arterial accesses during stable circulation and after hemorrhage corresponding to 20% and 40% of the blood volume. Samples were analyzed for blood gases and acid-base status, electrolytes, hematocrit, creatinine, glucose, alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase (γ-GT), alkaline phosphatase (ALP), and creatine kinase (CK).

    Results: Average differences of blood gases and acid-base parameters, sodium, creatinine, hematocrit, ALT, and γ-GT and between IO and venous samples were small at baseline and after hemorrhage while differences for lactate and glucose increased with hypovolemia. Both IO-arterial and venoarterial differences in acid-base parameters increased with hypovolemia. Dispersions of differences were often large.

    Conclusions: Average levels of blood gases, acid base parameters, hematocrit, CK, AST, γ-GT, creatinine, and ALT, but not lactate and glucose, were similar in IO and venous samples in hypovolemia. However, precision was limited, indicating that IO test results should be confirmed when other vascular access is established, and that analysis of IO samples should be limited to acute situations and not used for detailed diagnostics in this setting.

  • 390.
    Strandberg, Gunnar
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Eriksson, Mats B.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Lubenow, Norbert
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Analysis of Thromboelastography, PT, APTT and Fibrinogen in Intraosseous and Venous Samples: An Experimental Study2016Ingår i: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine, ISSN 1757-7241, E-ISSN 1757-7241, Vol. 24, artikel-id 131Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background:Laboratory analysis of coagulation is often important in emergencies. If vascular access is challenging,intraosseous catheterization may be necessary for treatment. We studied the analysis of coagulation parameters inintraosseous aspirate during stable conditions and after major haemorrhage in a porcine model.Methods:Ten anesthetized pigs received central venous and intraosseous catheters and samples were taken foranalysis of thromboelastography (TEG), prothrombin time (PT), activated partial thromboplastin time (APTT) andfibrinogen concentration. Analyses were repeated after removal of 50 % of the calculated blood volume andresuscitation with crystalloid. Intraosseous and venous values were compared.Results:Bleeding and resuscitation resulted in haemodilution and hypotension. Median TEG reaction time wasshorter in intraosseous than in venous samples before (1.6 vs 4.6 min) and after (1.6 vs 4.7 min) haemodilution.Median maximal amplitude was smaller in intraosseous samples at baseline (68.3 vs 76.4 mm). No major differenceswere demonstrated for the other TEG parameters. The intraosseous samples often coagulated in vitro, makinganalysis of PT, APTT and fibrinogen difficult. After haemodilution, TEG maximal amplitude andα-angle, andfibrinogen concentration, were decreased and PT increased.Discussion:The intraosseous samples were clinically hypercoagulable and the TEG demonstrated a shortenedreaction time. The reason for this may hypothetically be found in the composition of the IO aspirate or in thesampling technique. After 50 % haemorrhage and haemodilution, a clinically relevant decrease in fibrinogenconcentration and a lower TEG maximal amplitude were observed.Conclusions:Although the sample is small, these data indicate that intraosseous samples are hypercoagulable,which may limit their usefulness for coagulation studies. Major haemodilution only moderately affected the studied parameters.

  • 391.
    Strandberg, Gunnar
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Walther, Sten
    Uppsala Univ, Uppsala, Sweden..
    Öhman, Christina Agvald
    Uppsala Univ, Uppsala, Sweden..
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Long-term mortality after severe sepsis and septic shock in Swedish intensive care units 2005-20152017Ingår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 61, nr 8, s. 1039-1039Artikel i tidskrift (Övrigt vetenskapligt)
  • 392.
    Strang, Christof M.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi.
    Fredén, Filip
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Maripuu, E.
    Ebmeyer, U.
    Hachenberg, T.
    Hedenstierna, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi.
    Improved ventilation-perfusion matching with increasing abdominal pressure during CO(2)-pneumoperitoneum in pigs2011Ingår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 55, nr 7, s. 887-896Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: CO(2)-pneumoperitoneum (PP) is performed at varying abdominal pressures. We studied in an animal preparation the effect of increasing abdominal pressures on gas exchange during PP. Methods: Eighteen anaesthetized pigs were studied. Three abdominal pressures (8, 12 and 16mmHg) were randomly selected in each animal. In six pigs, single-photon emission computed tomography (SPECT) was used for the analysis of V / Q distributions; in another six pigs, multiple inert gas elimination technique (MIGET) was used for assessing V / Q matching. In further six pigs, computed tomography (CT) was performed for the analysis of regional aeration. MIGET, CT and central haemodynamics and pulmonary gas exchange were recorded during anaesthesia and after 60min on each of the three abdominal pressures. SPECT was performed three times, corresponding to each PP level. Results: Atelectasis, as assessed by CT, increased during PP and in proportion to abdominal pressure [from 9 +/- 2% (mean +/- standard deviation) at 8mmHg to 15 +/- 2% at 16mmHg, P <0.05]. SPECT during increasing abdominal CO(2) pressures showed a shift of blood flow towards better ventilated areas. V / Q analysis by MIGET showed no change in shunt during 8 mmHg PP (9 +/- 1.9% compared with baseline 9 +/- 1.2%) but a decrease during 12mmHg PP (7 +/- 0.9%, P <0.05) and 16mmHg PP (5 +/- 1%, P <0.01). PaO(2) increased from 39 +/- 10 to 52 +/- 9 kPa (baseline to 16 mmHg PP, P <0.01). Arterial carbon dioxide (PCO(2)) increased during PP and increased further with increasing abdominal pressures. Conclusion: With increasing abdominal pressure during PP perfusion was redistributed more than ventilation away from dorsal, collapsed lung regions. This resulted in a better V / Q match. A possible mechanism is enhanced hypoxic pulmonary vasoconstriction mediated by increasing PCO(2).

  • 393.
    Strassmann, Stephan
    et al.
    Witten Herdecke Univ Hosp, Cologne Merheim Hosp, Dept Pneumol & Crit Care Med, ARDS & ECMO Ctr,Kliniken Stadt Koln gGmbH, Ostmerheimer Str 200, D-51109 Cologne, Germany.
    Merten, Michaela
    Witten Herdecke Univ Hosp, Cologne Merheim Hosp, Dept Pneumol & Crit Care Med, ARDS & ECMO Ctr,Kliniken Stadt Koln gGmbH, Ostmerheimer Str 200, D-51109 Cologne, Germany.
    Schäfer, Simone
    Witten Herdecke Univ Hosp, Cologne Merheim Hosp, Dept Pneumol & Crit Care Med, ARDS & ECMO Ctr,Kliniken Stadt Koln gGmbH, Ostmerheimer Str 200, D-51109 Cologne, Germany.
    de Moll, Jonas
    Witten Herdecke Univ Hosp, Cologne Merheim Hosp, Dept Pneumol & Crit Care Med, ARDS & ECMO Ctr,Kliniken Stadt Koln gGmbH, Ostmerheimer Str 200, D-51109 Cologne, Germany.
    Brodie, Daniel
    Columbia Univ Coll Phys & Surg, Div Pulm Allergy & Crit Care, New York Presbyterian Hosp, 630 W 168th St, New York, NY 10032 USA.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Windisch, Wolfram
    Witten Herdecke Univ Hosp, Cologne Merheim Hosp, Dept Pneumol & Crit Care Med, ARDS & ECMO Ctr,Kliniken Stadt Koln gGmbH, Ostmerheimer Str 200, D-51109 Cologne, Germany.
    Karagiannidis, Christian
    Witten Herdecke Univ Hosp, Cologne Merheim Hosp, Dept Pneumol & Crit Care Med, ARDS & ECMO Ctr,Kliniken Stadt Koln gGmbH, Ostmerheimer Str 200, D-51109 Cologne, Germany.
    Impact of sweep gas flow on extracorporeal CO2 removal (ECCO2R)2019Ingår i: Intensive Care Medicine Experimental, ISSN 1646-2335, E-ISSN 2197-425X, Vol. 7, artikel-id 17Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Veno-venous extracorporeal carbon dioxide (CO2) removal (vv-ECCO2R) is increasingly being used in the setting of acute respiratory failure. Blood flow rates range in clinical practice from 200mL/min to more than 1500mL/min, and sweep gas flow rates range from less than 1 to more than 10L/min. The present porcine model study was aimed at determining the impact of varying sweep gas flow rates on CO2 removal under different blood flow conditions and membrane lung surface areas.

    Methods: Two different membrane lungs, with surface areas of 0.4 and 0.8m(2), were used in nine pigs with experimentally-induced hypercapnia. During each experiment, the blood flow was increased stepwise from 300 to 900 mL/min, with further increases up to 1800 mL/min with the larger membrane lung in steps of 300 mL/min. Sweep gas was titrated under each condition from 2 to 8L/min in steps of 2 L/min. Extracorporeal CO2 elimination was normalized to a PaCO2 of 45 mmHg before the membrane lung.

    Results: Reversal of hypercapnia was only feasible when blood flow rates above 900mL/min were used with a membrane lung surface area of at least 0.8m(2). The membrane lung with a surface of 0.4m(2) allowed a maximum normalized CO2 elimination rate of 416mL/min with 8L/min sweep gas flow and 900mLbloodflow/min. The increase in sweep gas flow from 2 to 8L/min increased normalized CO2 elimination from 35 +/- 5 to 41 +/- 6 with 900mLbloodflow/min, whereas with lower blood flow rates, any increase was less effective, levelling out at 4Lsweepgasflow/min. The membrane lung with a surface area of 0.8 m(2) allowed a maximum normalized CO2 elimination rate of 101 +/- 12 mL/min with increasing influence of sweep gas flow. The delta of normalized CO2 elimination increased from 4 +/- 2 to 26 +/- 7 mL/min with blood flow rates being increased from 300 to 1800 mL/min, respectively.

    Conclusions: The influence of sweep gas flow on the CO2 removal capacity of ECCO2R systems depends predominantly on blood flow rate and membrane lung surface area. In this model, considerable CO2 removal occurred only with the larger membrane lung surface of 0.8m(2) and when blood flow rates of >= 900mL/min were used.

  • 394. Stromskag, Kjell Erik
    et al.
    Brock-Utne, Johan G.
    Eklund, Jan
    Holmdahl, Martin H:son
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    A history of nordic anesthesia2014Ingår i: The Wondrous Story of Anesthesia, Springer-Verlag New York, 2014, Vol. 9781461484417, s. 417-428Kapitel i bok, del av antologi (Refereegranskat)
    Abstract [en]

    News of anesthesia's discovery came via Great Britain and France, and ether was given by February 1847. Chloroform quickly followed, but its lethality caused a reversion to ether by 1900. During the last half of the nineteenth Century, surgeons directed delivery of anesthesia by nurses and non-medical persons. Operations were few in number, and infections remained the dominant surgical risk. Surgeons introduced local and regional anesthesia after Koller's 1884 demonstration of the anesthetic effects of cocaine. Until the 1930s, nurse anesthetists, directed by surgeons, continued to provide most anesthesia. Surgeons persuaded a few colleagues like Gordh (Sweden) to pursue a career in anesthesia. Gordh returned home in 1940 after 2 years training in the US. World War II delayed the training of other Nordic pioneers. Swedish scientists synthesized lidocaine, and Gordh clinically tested it in 1943. In 1950, Thesleff, and von Dardel in Sweden studied succinylcholine in patients.

  • 395.
    Sundblom, Jimmy
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Melberg, Atle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Rücker, Franz
    Department of Medicine, Visby Hospital.
    Smits, Anja
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Islander, Gunilla
    MH Unit, Department of Intensive- and perioperative care, Lund University Hospital.
    A family with discordance between Malignant hyperthermia susceptibility and Rippling muscle disease2013Ingår i: Journal of Anesthesia, ISSN 0913-8668, E-ISSN 1438-8359, Vol. 27, nr 1, s. 128-131Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Rippling muscle disease (RMD) is a benign disorder affecting striated muscle.Malignant hyperthermia (MH) susceptibility is a potentially lethal disorder in which otherwise healthy individuals can develop an extreme hypermetabolism and muscle rigidity/rhabdomyolysis during anesthesia with potent inhalational agents and/or succinylcholine. Disturbed calcium homeostasis has been suggested as the cause of RMD symptoms. Uncontrolled increase in intracellular calcium concentration starts a MH reaction.

    Purpose

    To investigate if there is a relation between RMD and MH susceptibility in a family with both RMD and MH susceptibility.

    Materials and methods

    Ten members of a family segregating RMD had, prior to RMD diagnosis, been investigated for MH susceptibility. Results from MH and RMD investigations and anesthesia outcomes were cross-referenced and evaluated to find connections or phenotype variations predicted by in vitro contracture test results.

    Results

    There was no relation between RMD and MH susceptibility. There were no adverse anesthesia reactions recorded in this family.

    Conclusions

    RMD and MH susceptibility did not co-segregate. RMD patients should probably not be considered at risk for MH reactions.

  • 396. Suzuki, Satoshi
    et al.
    Woinarski, Nicholas C. Z.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Candal, Cristina Lluch
    Schneider, Antoine G.
    Glassford, Neil J.
    Eastwood, Glenn M.
    Bellomo, Rinaldo
    Pulse pressure variation-guided fluid therapy after cardiac surgery: A pilot before-and-after trial2014Ingår i: Journal of critical care, ISSN 0883-9441, E-ISSN 1557-8615, Vol. 29, nr 6, s. 992-996Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: The aim of this study is to study the feasibility, safety, and physiological effects of pulse pressure variation (PPV)-guided fluid therapy in patients after cardiac surgery. Materials and methods: We conducted a pilot prospective before-and-after study during mandatory ventilation after cardiac surgery in a tertiary intensive care unit. We introduced a protocol to deliver a fluid bolus for a PPV >= 13% for at least >10 minutes during the intervention period. Results: We studied 45 control patients and 53 intervention patients. During the intervention period, clinicians administered a fluid bolus on 79% of the defined PPV trigger episodes. Median total fluid intake was similar between 2 groups during mandatory ventilation (1297 mL[interquartile range 549-1968] vs 1481 mL [807-2563]; P =. 17) and the first 24 hours (3046 mL [interquartile range 2317-3982] vs 3017 mL [2192-4028]; P = .73). After adjusting for several baseline factors, PPV-guided fluid management significantly increased fluid intake during mandatory ventilation (P = .004) but not during the first 24 hours (P = .47). Pulse pressure variation-guided fluid therapy, however, did not significantly affect hemodynamic, renal, and metabolic variables. No serious adverse events were noted. Conclusions: Pulse pressure variation-guided fluid management was feasible and safe during mandatory ventilation after cardiac surgery. However, its advantages may be clinically small.

  • 397.
    Svensson, Anna-Lena
    Högskolan på Gotland, Institutionen för humaniora och samhällsvetenskap.
    Lokalbedövning: ett förbättringsprojekt på Hallands sjukhus Varberg2011Självständigt arbete på grundnivå (kandidatexamen), 10 poäng / 15 hpStudentuppsats (Examensarbete)
    Abstract [sv]

    Operationsavdelningen på Hallands sjukhus Varberg har genomfört ett förbättringsprojekt för att se hur flödet med att ge lokalbedövning (blockad) inför operation kan optimeras. Projektets mål var att spara tid på operationssalen genom snabbare byten, förbättra miljön för patienter och personal och samtidigt säkerställa fortsatt god patientsäkerhet och gott bemötande.

    Jag har valt att göra en fallstudie av projektet för att se hur förbättringsarbetet fungerat och hur gruppens förståelse utvecklats. Jag har gjort en deskriptiv undersökning och utgått från ett kvalitativt angreppssätt. Informationen har samlats in genom deltagande observationer av gruppens arbete och utvärdering av dokumentation.

    Som lösningsmetod har jag utgått från PDSA-hjulet, (Plan, Do, Study, Act) och tillämpat ett antal olika förbättringsverktyg för att analysera och beskriva verksamheten.

    I projektplaneringen har jag använt Tonnquists projektmodell. Resultatet har utvärderats genom tidmätningar, en loggbok som förts under testperioden och en enkät för att samla in medarbetarnas synpunkter. Tidsplanen fick revideras eftersom vi hade svårt att få fram resurser och testen fick skjutas fram en månad.

    Arbetsgruppen har bestått av ett multiprofessionellt team med en enhetschef, anestesiläkare, sjuksköterskor och undersköterskor. Samarbetet har fungerat väl och engagemanget har varit stort, trots att det har varit svårt att avsätta tid, särskilt för läkaren.

    Det nya arbetssättet har testats under maj och vi har börjat utvärdera resultatet. Mätningen av bytestiderna har inte visat något tydligt resultat. Den loggbok som förts i sänghallen under testtiden visade att det fungerade bra att lägga blockaderna i sänghallen och att patientsäkerheten inte påverkats. Enligt enkäten ansåg en anestesiläkare att miljön var lugnare i sänghallen, medan ett par anestesisjuksköterskor hade invändningar mot att inte samma person följer patienten hela vägen från det att blockaden lagts. De ansåg också att resursen i sänghallen skulle kunnat utnyttjas bättre på operationssalarna.

    Min rekommendation är att detaljerna kring arbetsfördelningen ses över för att skapa en bättre balans mellan de olika uppgifterna i sänghallen respektive på operationssalen. Vi behöver också se över mätningen av bytestiderna. En allmän reflektion är att det är svårt att få loss resurser till förbättringsprojekt. Det har också varit bra att prova i mindre skala först, då vi fick många idéer under resans gång. Vi har även insett vikten av tydlighet kring projektets omfattning och mätmetoder. Det är också viktigt att förändringar kommuniceras ordentligt och fungerar bra för alla inblandade, för att de ska gå att införa.

  • 398.
    Söderberg, Ewa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Anestesi och intensivvård.
    Experimental septic shock – Effects of endotoxemia with special reference to pathophysiological responses in the pig2016Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Sepsis and septic shock are conditions, with severe outcome or in many cases death. Sepsis is a systemic inflammatory response trigger by bacteraemia but systemic inflammatory response can also be triggered by major trauma, major surgery, pancreatitis, severe burns etc.

    The systemic inflammatory reaction initiating the evolvement of septic organ dysfunction can be modelled using endotoxin, a Gram-negative bacterial lipopolysaccharide. This thesis used a porcine experimental sepsis model to examine timing of the inflammatory response due to endotoxin infusion (Paper I) and the influence of steroid treatment on the inflammatory response in endotoxemic pigs (Paper II). Timing of steroid treatment and the role of neutrophil granulocyte activation was evaluated with pig specific NGAL assessing neutrophil activation (Paper III). A clinical observational study was performed with the aim to differentiate between sepsis and other inflammatory conditions (e.g. trauma due to major surgery) evaluated by calprotectin as a marker of neutrophil activation (Paper IV).

    There was a dose-dependency in endotoxin tolerance which was measured with TNF-a. Pre-exposure to endotoxin did not reduce the pulmonary response to endotoxemic challenge. In fact, both PaO2 / FiO2 and static pulmonary compliance were reduced in this group when pre-treated with endotoxin at low dose.

    Endotoxemic animals treated with hydrocortisone were more stable in circulatory variables than those without such treatment. This was not explained by an ability of steroids to modulate the production of NO (Nitric oxide), which has been suggested to be a mechanism of steroids in this aspect.

    Pre-treatment with hydrocortisone attenuated the neutrophil granulocyte response and consequently diminished the release of NGAL in plasma. Circulatory derangement was associated with high plasma NGAL levels. Urine NGAL levels did not differ among the four groups.

    Plasma calprotectin levels on ICU admission is a sensitive marker of systemic inflammation and are markedly increased in patients with sepsis and patients with systemic inflammatory response. Plasma Calprotectin performed better than any of the other inflammatory variables in predicting mortality at 30 days, except from the composite mortality prediction score, SAPS 3.

    Delarbeten
    1. Differences in Organ Dysfunction in Endotoxin Tolerant Pigs Under Intensive Care Exposed to a Second Hit of Endotoxin
    Öppna denna publikation i ny flik eller fönster >>Differences in Organ Dysfunction in Endotoxin Tolerant Pigs Under Intensive Care Exposed to a Second Hit of Endotoxin
    Visa övriga...
    2012 (Engelska)Ingår i: Shock, ISSN 1073-2322, E-ISSN 1540-0514, Vol. 37, nr 5, s. 501-510Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Endotoxin tolerance is a well-studied phenomenon associated with a reduced inflammatory response. In the switch from an inflammatory to an anti-inflammatory response in clinical sepsis the concept of endotoxin tolerance is of obvious interest. However, only limited data exist regarding the effect of endotoxin tolerance on organ dysfunction and, therefore, this was investigated in a porcine intensive care sepsis model. Twenty-seven healthy pigs, including nine control animals, were included in the study. Twelve pigs pre-exposed to 24 h of intravenous endotoxin infusion and intensive care and six unexposed pigs were given either a high- or low-dose endotoxin challenge for 6 h. Inflammatory, circulatory, hypoperfusion and organ dysfunction parameters were followed. The inflammatory responses as well as parameters representing circulation, hypoperfusion, cardiac and renal function were all markedly attenuated in animals pre-exposed to endotoxin and intensive care as compared with animals not pre-exposed. In animals pre-exposed to endotoxin and given the high-dose of endotoxin challenge, deterioration in pulmonary function was equal to or even worse than in animals not pre-exposed.In contrast to the overall protective effect of endotoxin tolerance observed in other organ systems, the lungs of endotoxin tolerant animals demonstrated an increased responsiveness to high-dose endotoxin challenge.

    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-168692 (URN)10.1097/SHK.0b013e318249bb0d (DOI)000303010000009 ()22266970 (PubMedID)
    Anmärkning

    Previous title as submitted: "Compartmentalization of organ endotoxin tolerance in a porcine model of secondary sepsis"

    Tillgänglig från: 2012-02-15 Skapad: 2012-02-15 Senast uppdaterad: 2017-12-07Bibliografiskt granskad
    2. Counteraction of early circulatory derangement by administration of low dose steroid treatment at the onset of established endotoxemic shock is not directly mediated by TNF-α and IL-6
    Öppna denna publikation i ny flik eller fönster >>Counteraction of early circulatory derangement by administration of low dose steroid treatment at the onset of established endotoxemic shock is not directly mediated by TNF-α and IL-6
    Visa övriga...
    2012 (Engelska)Ingår i: Steroids, ISSN 0039-128X, E-ISSN 1878-5867, Vol. 77, nr 11, s. 1101-1106Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    BACKGROUND:

    Once a septic condition is progressing, administration of steroids in the pro-inflammatory phase of septic shock ought to yield maximal effect on the subsequent, devastating inflammatory response. Recently, a retrospective study showed that early initiation of corticosteroid therapy improved survival in septic shock. We aimed to prospectively evaluate effects of early administrated hydrocortisone therapy on physiologic variables in a porcine model of septic shock.

    EXPERIMENT:

    Eight anesthetized pigs were given a continuous infusion of endotoxin during this 6h prospective, randomized, parallel-grouped placebo-controlled experimental study. At the onset of endotoxemic shock, defined as the moment when the mean pulmonary arterial pressure reached the double baseline value, the pigs were either given a single intravenous dose of hydrocortisone (5 mg kg−1) or the corresponding volume of saline.

    RESULTS:

    Mean arterial pressure and systemic vascular resistance index were significantly higher (both p<0.05), and heart rate was significantly lower (p<0.05), in the endotoxin+hydrocortisone group as compared to the endotoxin+saline group. Body temperature and blood hemoglobin levels increased significantly in the endotoxin+saline group (both p<0.05). Urinary hydrocortisone increased significantly in both groups (p<0.05). There were no significant differences in the plasma levels of TNF-alpha, IL-6 or nitrite/nitrate between the groups.

    CONCLUSION:

    Early treatment with hydrocortisone ameliorates some endotoxin mediated circulatory derangements, fever response and microvascular outflow. Our results suggest that these effects are not directly mediated by the pro-inflammatory cytokines TNF-alpha or IL-6, nor by NO.

    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-181444 (URN)10.1016/j.steroids.2012.06.001 (DOI)000309021700010 ()22705410 (PubMedID)
    Tillgänglig från: 2012-09-24 Skapad: 2012-09-24 Senast uppdaterad: 2017-12-07Bibliografiskt granskad
    3. The impact of hydrocortisone on neutrophil granulocyte activation in porcine endotoxemic shock
    Öppna denna publikation i ny flik eller fönster >>The impact of hydrocortisone on neutrophil granulocyte activation in porcine endotoxemic shock
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Nationell ämneskategori
    Anestesi och intensivvård
    Identifikatorer
    urn:nbn:se:uu:diva-303801 (URN)
    Tillgänglig från: 2016-09-24 Skapad: 2016-09-23 Senast uppdaterad: 2016-09-24
    4. Performance of plasma calprotectin as a biomarker of early sepsis: a pilot study
    Öppna denna publikation i ny flik eller fönster >>Performance of plasma calprotectin as a biomarker of early sepsis: a pilot study
    Visa övriga...
    2016 (Engelska)Ingår i: Biomarkers in Medicine, ISSN 1752-0363, E-ISSN 1752-0371, Vol. 10, nr 8, s. 811-818Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    AIM: To determine the performance of plasma calprotectin as a marker of sepsis on intensive care unit (ICU) admission and as a marker of mortality day 30 post-ICU admission.

    MATERIALS & METHODS: Consecutive ICU patients were allocated to: sepsis (n = 15), postoperative inflammation (n = 23) and intoxication without inflammation (n = 7) groups.

    RESULTS: Calprotectin was 4.3 (2.6-8.2; mg/l; median [interquartile range]) in the sepsis, 2.8 (1.6-4.4) in the postoperative and 0.7 (0.4-1.6) in the intoxication groups. Area under the receiver operating characteristic curve for sepsis versus intoxication group was: 0.95, for sepsis versus postoperative groups: 0.65 and for survivors versus nonsurvivors: 0.70.

    CONCLUSION: Calprotectin was a sensitive marker of systemic inflammation, is a potential sepsis marker and performed well as mortality predictor in this pilot study.

    Nyckelord
    calprotectin; sepsis; systemic inflammatory response syndrome
    Nationell ämneskategori
    Anestesi och intensivvård
    Identifikatorer
    urn:nbn:se:uu:diva-299540 (URN)10.2217/bmm-2016-0032 (DOI)000383776800003 ()27414210 (PubMedID)
    Tillgänglig från: 2016-07-22 Skapad: 2016-07-22 Senast uppdaterad: 2017-11-28Bibliografiskt granskad
  • 399.
    Söderberg, Ewa
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper. Anestesi och intensivvård.
    Eriksson, Mats B
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper. Anestesi och intensivvård.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper. Anestesi och intensivvård.
    The impact of hydrocortisone on neutrophil granulocyte activation in porcine endotoxemic shockManuskript (preprint) (Övrigt vetenskapligt)
  • 400.
    Söderberg, Ewa
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Eriksson, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Lipcsey, Miklos
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    The impact of hydrocortisone treatment on neutrophil gelatinase-associated lipocalin release in porcine endotoxemic shock2017Ingår i: Intensive Care Medicine Experimental, ISSN 1646-2335, E-ISSN 2197-425X, Vol. 5, artikel-id 4Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: A key feature of sepsis is systemic inflammatory activation that could be counteracted by steroids. In this experimental model of systemic inflammation, we sought to investigate whether septic neutrophil activation, evaluated by the plasma levels of neutrophil gelatinase-associated protein (NGAL), is modulated by the timing of hydrocortisone treatment.

    METHODS: Sixteen anesthetized pigs were allocated to one of four equally sized groups. Three of these groups received endotoxin at 2 μg × kg(-1) × h(-1) for 6 h so as to induce endotoxemic shock. Hydrocortisone (5 mg × kg(-1)) was administered intravenously before endotoxemic challenge, or at the onset of endotoxemic shock. Endotoxemic pigs not receiving hydrocortisone and non-endotoxemic pigs served as control groups. Physiologic variables, hematology, and biochemistry, including plasma NGAL, were measured repeatedly.

    RESULTS: Hydrocortisone treatment prior to endotoxemia attenuated some inflammatory, hematological, circulatory, and metabolic manifestations of shock (i.e., higher white blood cell count, higher mean arterial pressure, lower heart rate and mean pulmonary arterial pressure, higher left ventricular stroke work index, higher base excess). Endotoxemic shock increased plasma NGAL (p < 0.001). In pigs given hydrocortisone before the endotoxin infusion, plasma NGAL was lower as compared to those given hydrocortisone at endotoxemic shock (p < 0.05). Plasma NGAL levels correlated inversely to neutrophil granulocyte counts (rho = -0.65) but not to urine output (rho = -0.10) at the end of the experiment.

    CONCLUSIONS: The increase in plasma NGAL is counteracted by hydrocortisone administration prior to endotoxemia; concomitantly, this treatment was associated with less expressed circulatory derangement. Urine NGAL did not differ between the groups, suggesting that the NGAL response was not primarily related to kidney injury.

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