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  • 201.
    Larsson, Ing-Marie
    et al.
    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, Sjuksköterskeutbildningar.
    Wallin, Ewa
    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, Sjuksköterskeutbildningar.
    Kristofferzon, Marja-Leena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Vårdvetenskap.
    Niessner, Maron
    Zetterberg, Henrik
    Rubertsson, Sten
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Post-cardiac arrest serum levels of glial fibrillary acidic protein for predicting neurological outcome2014Ingår i: Resuscitation, ISSN 0300-9572, E-ISSN 1873-1570, Vol. 85, nr 12, s. 1654-1661Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIM OF THE STUDY: To investigate serum levels of glial fibrillary acidic protein (GFAP) for evaluation of neurological outcome in cardiac arrest (CA) patients and compare GFAP sensitivity and specificity to that of more studied biomarkers neuron-specific enolas (NSE) and S100B.METHOD: A prospective observational study was performed in three hospitals in Sweden during 2008-2012. The participants were 125 CA patients treated with therapeutic hypothermia (TH) to 32-34°C for 24hours. Samples were collected from peripheral blood (n=125) and the jugular bulb (n=47) up to 108hours post-CA. GFAP serum levels were quantified using a novel, fully automated immunochemical method. Other biomarkers investigated were NSE and S100B. Neurological outcome was assessed using the Cerebral Performance Categories scale (CPC) and dichotomized into good and poor outcome.RESULTS: GFAP predicted poor neurological outcome with 100% specificity and 14-23% sensitivity at 24, 48 and 72hours post-CA. The corresponding values for NSE were 27-50% sensitivity and for S100B 21-30% sensitivity when specificity was set to 100%. A logistic regression with stepwise combination of the investigated biomarkers, GFAP, did not increase the ability to predict neurological outcome. No differences were found in GFAP, NSE and S100B levels when peripheral and jugular bulb blood samples were compared.CONCLUSION: Serum GFAP increase in patients with poor outcome but did not show sufficient sensitivity to predict neurological outcome after CA. Both NSE and S100B were shown to be better predictors. The ability to predict neurological outcome did not increased when combining the three biomarkers.

  • 202.
    Larsson, Ing-Marie
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Wallin, Ewa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Rubertsson, Sten
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Kristofferzon, Marja-Leena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Vårdvetenskap.
    Relatives' experiences during the next of kin's hospital stay after surviving cardiac arrest and therapeutic hypothermia2013Ingår i: European Journal of Cardiovascular Nursing, ISSN 1474-5151, E-ISSN 1873-1953, Vol. 12, nr 4, s. 353-359Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIM:

    To describe relatives' experiences during the next of kin's hospital stay after surviving a cardiac arrest (CA) treated with hypothermia at an intensive care unit (ICU).

    METHODS:

    Twenty relatives were interviewed when the person having suffered the CA was discharged from hospital, 1.5 to 6 weeks post-CA. Data were analysed using qualitative content analysis.

    RESULTS:

    Three themes are described: The first period of chaos, Feeling secure in a difficult situation, and Living in a changed existence. Relatives found it difficult to assimilate the medical information and wanted it in written form. They wanted honest and clear information about their next of kin's condition and prognosis. They lacked rehabilitation plans after discharge from the medical ward. Relatives felt a need to maintain telephone contact with family members and friends, which was time-consuming. They felt guilty and had a conscience about these feelings. Relatives felt uncertain about the future, but still hopeful.

    CONCLUSION:

    Relatives asked for more information and individual rehabilitation plans. Booklets describing CA, the ICU stay and continuing care and rehabilitation directed at both the patients and their relatives are needed. Follow-up visits to the ICU staff, for both patients and relatives, need to be arranged. Hospitals should consider having a rehabilitation plan for this group of patients, which is presented by a team of healthcare professionals and that focuses on the individual's situation, including the consequences of their heart disease and brain damage.

  • 203.
    Larsson, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Hälso- och sjukvårdsforskning. Univ Uppsala Hosp, Clin Anaesthesia & Intens Care, Uppsala, Sweden..
    Monitoring the anaesthetist in the operating theatre - professional competence and patient safety2017Ingår i: Anaesthesia, ISSN 0003-2409, E-ISSN 1365-2044, Vol. 72, s. 76-83Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    This article about competence and patient safety in anaesthesia was inspired by a statement in the 2015 AAGBI guidelines on monitoring during anaesthesia: the presence of an appropriately trained and experienced anaesthetist is important for patient safety during anaesthesia'. The review starts with a structured description of competence, presenting five dimensions of it; the first two dimensions are identical with the two classical attributes of competence, practical skills and theoretical knowledge. Concerning skills, the value of aiming for a high level of proficiency early in a traning programme is pointed out, and deliberate practice is given as an example of a pedagogical model where aiming for excellence is a core idea. For theoretical knowledge, the value of a deep approach to learning physiology and basic sciences is stressed. The third dimension (anaesthetists' non-technical skills), represents skills necessary for good team-work in the operating theatre. The two last dimensions of competence are the understanding of work and intuitive expert knowing. Understanding work means being aware of what the work is about, appreciating the different aspects of the anaesthetist's job. Intuitive expert knowing, lastly, concerns the tacit dimension of knowledge and skills, which enables professional experts to quickly find a working solution for most clinical problems. The final part of the review is about the when' and how' of competence assessment. The main message is the importance of assessing the competence of clinically active anaesthetists regularly during their whole career.

  • 204.
    Lattuada, Marco
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi.
    Effect of Ventilatory Support on Abdominal Fluid Balance in a Sepsis Model2013Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    In patients affected by acute respiratory failure or acute respiratory distress syndrome (ARDS) the leading cause of death is failure of different vital organs other than the lungs, so called multiple organ dysfunction syndrome (MODS). The abdominal organs have a crucial role in the pathogenesis of this syndrome.

    There is a lack of knowledge regarding the mechanisms by which mechanical ventilation can affect the abdominal compartment. One hypothesis is that mechanical ventilation can interfere with abdominal fluid balance causing edema and inflammation.

    We addressed the question whether different levels of ventilatory support (mechanical ventilation with different levels of positive end-expiratory pressure, PEEP, and spontaneous breathing with or without PEEP) can influence abdominal edema and inflammation in both healthy and endotoxin-exposed animals.

    The effect on lymphatic drainage from the abdomen exerted by different degrees of ventilatory support was evaluated (paper I). We demonstrated that endotoxin increases abdominal lymph production, that PEEP and mechanical ventilation increase lymph production but also impede lymphatic drainage; spontaneous breathing improves lymphatic drainage from the abdomen.

    By adapting a non-invasive nuclear medicine imaging technique and validating it (paper II), we have been able to evaluate extravascular fluid accumulation (edema formation) in the abdomen over time (paper III) demonstrating that edema increases during endotoxemia, mimicking a sepsis-like condition, and that spontaneous breathing, compared to mechanical ventilation, reduces extravascular fluid. Pro-inflammatory cytokines TNF-α and IL-6 in intestinal biopsies are reduced during spontaneous breathing compared to mechanical ventilation.

    Abdominal edema results in increased intra-abdominal pressure (IAP): in paper IV we analyzed the effect of increased intra-abdominal pressure on the respiratory system. Pulmonary shunt fraction increased with high IAP both in healthy and LPS animals, resulting in decreased level of oxygenation. These changes are only partially reversible by reducing IAP.

    In conclusion, mechanical ventilation is a life-saving tool but the possible side effect at the extra-pulmonary level should be considered, and the introduction of some degree of spontaneous breathing when clinically possible is a suggested choice.

    Delarbeten
    1. Abdominal lymph flow in an endotoxin sepsis model: Influence of spontaneous breathing and mechanical ventilation
    Öppna denna publikation i ny flik eller fönster >>Abdominal lymph flow in an endotoxin sepsis model: Influence of spontaneous breathing and mechanical ventilation
    2006 (Engelska)Ingår i: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 34, nr 11, s. 2792-2798Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    OBJECTIVE: Lymph flow from the abdomen was investigated in a sepsis model. We also compared the effect on thoracic duct lymph flow of mechanical ventilation with different levels of positive end-expiratory pressure (PEEP) and spontaneous breathing with continuous positive airway pressure (CPAP). DESIGN: Experimental study. SETTING: Research laboratory in a university hospital. SUBJECTS: Thirty-two pigs. INTERVENTIONS: Animals were anesthetized. In study 1 (n = 18), an ultrasonic flow probe was put around the intact thoracic duct just caudal to the diaphragm, and animals were randomized to receive mechanical ventilation with a PEEP of 5 cm H2O or 15 cm H2O or breathed spontaneously in CPAP with a PEEP of 5 cm H2O. In study 2 (n = 6), the thoracic duct was cannulated and the cannula externalized through the abdominal wall for lymph collection; animals were then ventilated as in study 1. In all animals, endotoxin was infused at 15 μg/kg/hr for 2.5 hrs and then continued at 5 μg/kg/hr. In study 3, healthy (n = 4) and endotoxin-exposed (n = 4) pigs had intra-abdominal pressure increased to 27 cm H2O for 2 hrs by pneumoperitoneum. Lymph flow was measured as in study 1. MEASUREMENTS AND MAIN RESULTS: Lymph flow (mean ± se) was 2.5 ± 0.4 mL/min at baseline and increased to 3.9 ± 0.8 mL/min after 90 mins and 6.3 ± 1.6 mL/min after 150 mins (p < .005) of endotoxin exposure. PEEP 15 cm H2O decreased lymph flow in pigs with intact thoracic duct (flow probe recording) and in pigs with cannulated lymph duct when drained against the central venous pressure. However, when drained against atmospheric pressure, PEEP increased flow. Spontaneous breathing increased flow both in intact and in cannulated animals. CONCLUSIONS: Endotoxin increases lymph flow from the abdomen. Mechanical ventilation with high PEEP impedes lymph drainage and could increase lymph production. Spontaneous breathing increases flow and improves drainage of abdominal edema.

    Nyckelord
    sepsis, lymph, abdomen, positive end-expiratory pressure, mechanical ventilation
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-19586 (URN)10.1097/01.CCM.0000242158.28619.09 (DOI)000241639900012 ()16971857 (PubMedID)
    Tillgänglig från: 2006-11-30 Skapad: 2006-11-30 Senast uppdaterad: 2017-12-08Bibliografiskt granskad
    2. Evaluating abdominal oedema during experimental sepsis using an isotope technique
    Öppna denna publikation i ny flik eller fönster >>Evaluating abdominal oedema during experimental sepsis using an isotope technique
    Visa övriga...
    2012 (Engelska)Ingår i: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 32, nr 3, s. 197-204Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Purpose: Abdominal oedema is common in sepsis. A technique for the study of such oedema may guide in the fluid regime of these patients.

    Procedures: We modified a double-isotope technique to evaluate abdominal organ oedema and fluid extravasation in 24 healthy or endotoxin-exposed (septic) piglets. Two different markers were used: red blood cells (RBC) labelled with Technetium99m (99mTc) and Transferrin labelled with Indium111 (111In). Images were acquired on a dual-head gamma camera. Microscopic evaluation of tissue biopsies was performed to compare data with the isotope technique.

    Results: No 99mTc activity was measured in the plasma fraction in blood sampled after labelling. Similarly, after molecular size gel chromatography, 111In activity was exclusively found in the high molecular fraction of the plasma. Extravasation of transferrin, indicating the degree of abdominal oedema, was 4 06 times higher in the LPS group compared to the healthy controls (P< 0 0001). Abdominal free fluid, studied in 3 animals, had as high 111In activity as in plasma, but no 99mTc activity. Intestinal lymphatic vessel size was higher in LPS (3 7 +/- 1 1 lm) compared to control animals (0 6 + 0 2 lm; P< 0 001) and oedema correlated to villus diameter (R 2 = 0 918) and lymphatic diameter (R 2 = 0 758). A correlation between a normalized index of oedema formation (NI) and intra-abdominal pressure (IAP) was also found: NI = 0 46* IAP) 3 3 (R2 = 0 56).

    Conclusions: The technique enables almost continuous recording of abdominal oedema formation and may be a valuable tool in experimental research, with the potential to be applied in the clinic.

    Nyckelord
    abdomen, double indicator, gamma camera, microscopy, oedema
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-173971 (URN)10.1111/j.1475-097X.2011.01077.x (DOI)000302545300006 ()
    Tillgänglig från: 2012-05-14 Skapad: 2012-05-09 Senast uppdaterad: 2017-12-07Bibliografiskt granskad
    3. Mechanical ventilation worsens abdominal edema and inflammation in porcine endotoxemia
    Öppna denna publikation i ny flik eller fönster >>Mechanical ventilation worsens abdominal edema and inflammation in porcine endotoxemia
    2013 (Engelska)Ingår i: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 17, nr 3, s. R126-Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    INTRODUCTION:

    We hypothesized that mechanical ventilation per se increases abdominal edema and inflammation in sepsis and tested this in experimental endotoxemia.

    METHODS:

    Thirty anesthetized piglets were allocated to one of five groups: healthy control pigs breathing spontaneously with continuous positive pressure of 5 cm H2O or mechanically ventilated with positive end-expiratory pressure (PEEP) of 5 cm H2O, and endotoxemic piglets during mechanical ventilation for 2.5 hours and then continued on mechanical ventilation with PEEP of either 5 or 15 cm H2O or switched to spontaneous breathing with continuous positive pressure of 5 cm H2O for another 2.5 hours. Abdominal edema formation was estimated by isotope technique and inflammatory markers were measured in liver, intestine, lung and plasma.

    RESULTS:

    In the healthy controls, 5 hours of spontaneous breathing did not increase abdominal fluid whereas mechanical ventilation did (Normalized Index increased from 1.0 to 1.6;1-3.3 (median and range, p<0.05)). In endotoxemic animals, Normalized Index increased almost six-fold after 5 hours of mechanical ventilation (5.9;4.9-6.9, p<0.05) with two-fold increase from 2.5 to 5 hours whether PEEP was 5 or 15, but only by 40% with spontaneous breathing (p<0.05 vs PEEP of 5 or 15 cm H2O). Tumor Necrosis Factor alpha (TNF-alpha) and interleukin (IL)-6 in intestine and liver were 2-3 times higher with mechanical ventilation than during spontaneous breathing (p<0.05) but similar in plasma and lung. Abdominal edema formation and TNF-alpha in intestine correlated inversely with abdominal perfusion pressure.

    CONCLUSIONS:

    Mechanical ventilation with PEEP increases abdominal edema and inflammation in intestine and liver in experimental endotoxemia by increasing systemic capillary leakage and impeding abdominal lymph drainage.

    Nationell ämneskategori
    Medicin och hälsovetenskap
    Forskningsämne
    Anestesiologi och intensivvård
    Identifikatorer
    urn:nbn:se:uu:diva-207180 (URN)10.1186/cc12801 (DOI)000329431100043 ()23799965 (PubMedID)
    Tillgänglig från: 2013-09-10 Skapad: 2013-09-10 Senast uppdaterad: 2017-12-06Bibliografiskt granskad
    4. Effect of increased intra-abdominal pressure (IAP) on lung function in a sepsis model
    Öppna denna publikation i ny flik eller fönster >>Effect of increased intra-abdominal pressure (IAP) on lung function in a sepsis model
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    We have previously shown that mechanical ventilation with positive pressure increases abdominal edema formation and causes an increase in intra-abdominal pressure (IAP) in a sepsis-like porcine model. In this study we investigated, in the same animal model effects of increase in IAP on the cardiovascular and respiratory system. Twelve pigs of Swedish country breed with a mean weight 28 kg were anesthetized and mechanically ventilated. Six animals received a continuous infusion of endotoxin and the other six served as controls. Catheters were inserted for vascular pressure recordings and cardiac output was measured by thermo-dilution. In both groups IAP was temporarily elevated to 20 mmHg by insufflation of CO2 into the abdominal cavity. Endotoxin infusion caused significant increases in pulmonary artery and central venous pressures and increase in shunt with fall in PaO2. Respiratory compliance was reduced. IAP elevation by CO2 insufflation increased these pressures as well as shunt further and caused additional decrease in compliance. Deflation of the abdomen returned vascular pressures to pre-insufflation but shunt remained increased and PaO2 was still reduced as was compliance. In control animals similar but smaller changes were seen on increase in IAP but with deflation not only vascular pressures but also shunt and PaO2 returned to normal. This suggests that in the sepsis-like condition, increased IAP causes persisting deterioration of lung function even when IAP has been normalized. We propose this to be caused by lung collapse that remains, at least for some time, after deflation.

    Nyckelord
    intra-abdominal pressure, IAP, pneumoperitoneum, shunt, MIGET, sepsis
    Nationell ämneskategori
    Anestesi och intensivvård Fysiologi
    Forskningsämne
    Anestesiologi och intensivvård; Klinisk fysiologi
    Identifikatorer
    urn:nbn:se:uu:diva-207402 (URN)
    Tillgänglig från: 2013-09-13 Skapad: 2013-09-13 Senast uppdaterad: 2018-05-31
  • 205.
    Lattuada, Marco
    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.
    Reinius, Henrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Hedenstierna, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi.
    Effect of increased intra-abdominal pressure (IAP) on lung function in a sepsis modelManuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    We have previously shown that mechanical ventilation with positive pressure increases abdominal edema formation and causes an increase in intra-abdominal pressure (IAP) in a sepsis-like porcine model. In this study we investigated, in the same animal model effects of increase in IAP on the cardiovascular and respiratory system. Twelve pigs of Swedish country breed with a mean weight 28 kg were anesthetized and mechanically ventilated. Six animals received a continuous infusion of endotoxin and the other six served as controls. Catheters were inserted for vascular pressure recordings and cardiac output was measured by thermo-dilution. In both groups IAP was temporarily elevated to 20 mmHg by insufflation of CO2 into the abdominal cavity. Endotoxin infusion caused significant increases in pulmonary artery and central venous pressures and increase in shunt with fall in PaO2. Respiratory compliance was reduced. IAP elevation by CO2 insufflation increased these pressures as well as shunt further and caused additional decrease in compliance. Deflation of the abdomen returned vascular pressures to pre-insufflation but shunt remained increased and PaO2 was still reduced as was compliance. In control animals similar but smaller changes were seen on increase in IAP but with deflation not only vascular pressures but also shunt and PaO2 returned to normal. This suggests that in the sepsis-like condition, increased IAP causes persisting deterioration of lung function even when IAP has been normalized. We propose this to be caused by lung collapse that remains, at least for some time, after deflation.

  • 206. Li, Qinghu
    et al.
    Dong, Jinlei
    Yang, Yongliang
    Wang, Guodong
    Wang, Yonghui
    Liu, Ping
    Robinson, Yohan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Zhou, Dongsheng
    Retroperitoneal packing or angioembolization for haemorrhage control of pelvic fractures-Quasi-randomized clinical trial of 56 haemodynamically unstable patients with Injury Severity Score ≥332016Ingår i: Injury, ISSN 0020-1383, E-ISSN 1879-0267, Vol. 47, nr 2, s. 395-401Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIMS: Both retroperitoneal pelvic packing and primary angioembolization are widely used to control haemorrhage related to pelvic fractures. It is still unknown which protocol is the safest. The primary aim of this study is to compare survival and complications of pelvic packing and angioembolization in massive haemorrhage related to pelvic fractures.

    METHODS: Patients with haemodynamically unstable pelvic fractures were quasi-randomized to either pelvic packing (PACK) or angiography (ANGIO) using the time of admission as separator. Physiological markers of haemorrhage, time to intervention, procedure/surgical time, transfusion requirements, complications and early mortality were recorded and analyzed.

    RESULTS: 29 patients were randomized to PACK and 27 patients to ANGIO. The Injury Severity Score (ISS) in the ANGIO group was lower than in the PACK group (43±7 vs 48±6) (p<0.01). The median time from admission to angiography for the ANGIO group was 102min (range 76-214), and longer than 77min (range 43-125) from admission to surgery for the PACK group (p<0.01). The procedure time for the ANGIO group was 84min (range 62-105); while the surgical time was 60min (range 41-92) for the PACK group (p<0.001). The ANGIO group received 6.4 units packed red blood cells (range 4-10) in the first 24h after angiography. The PACK group required 5.2 units (range 3-10) in the first 24h after leaving the operating theatre (p=0.124). 9 patients in the ANGIO group underwent pelvic packing for persistent bleeding. 6 patients in the PACK group required pelvic angiography after pelvic packing for ongoing hypotension following packing (p=0.353). 5 patients in the ANGIO group died (2 from exsanguination), while 4 in the PACK group died (none from exsanguination) (p=0.449). Complications occurred without differences in both groups.

    CONCLUSIONS: Compared with angioembolization, pelvic packing has shorter time to intervention and surgical time. Thus pelvic packing is the more rapid treatment of severe pelvic trauma than pelvic angioembolization. It is suitable for patients with haemodynamic instability at centers where the interventional radiology staff is not in-house at all times.

    REGISTRATION: ClinicalTrials.gov (NCT02535624) and ISRCTN registry (ISRCTN91713422).

  • 207. Li, Y.
    et al.
    Tesselaar, E.
    Borges, João Batista
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Bohm, S. H.
    Sjoberg, F.
    Janerot-Sjoberg, B.
    Hyperoxia affects the regional pulmonary ventilation/perfusion ratio: an electrical impedance tomography study2014Ingår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 58, nr 6, s. 716-725Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background The way in which hyperoxia affects pulmonary ventilation and perfusion is not fully understood. We investigated how an increase in oxygen partial pressure in healthy young volunteers affects pulmonary ventilation and perfusion measured by thoracic electrical impedance tomography (EIT). Methods Twelve semi-supine healthy male volunteers aged 21-36 years were studied while breathing room air and air-oxygen mixtures (FiO2) that resulted in predetermined transcutaneous oxygen partial pressures (tcPO2) of 20, 40 and 60kPa. The magnitude of ventilation (Zv) and perfusion (ZQ)-related changes in cyclic impedance variations, were determined using an EIT prototype equipped with 32 electrodes around the thorax. Regional changes in ventral and dorsal right lung ventilation (V) and perfusion (Q) were estimated, and V/Q ratios calculated. Results There were no significant changes in Zv with increasing tcPO2 levels. ZQ in the dorsal lung increased with increasing tcPO2 (P=0.01), whereas no such change was seen in the ventral lung. There was a simultaneous decrease in V/Q ratio in the dorsal region during hyperoxia (P=0.04). Two subjects did not reach a tcPO2 of 60kPa despite breathing 100% oxygen. Conclusion These results indicate that breathing increased concentrations of oxygen induces pulmonary vasodilatation in the dorsal lung even at small increases in FiO2. Ventilation remains unchanged. Local mismatch of ventilation and perfusion occurs in young healthy men, and the change in ventilation/perfusion ratio can be determined non-invasively by EIT.

  • 208.
    Lind, Anne-Li
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Biomarkers for Better Understanding of the Pathophysiology and Treatment of Chronic Pain: Investigations of Human Biofluids2017Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Chronic pain affects 20 % of the global population, causes suffering, is difficult to treat, and constitutes a large economic burden for society. So far, the characterization of molecular mechanisms of chronic pain-like behaviors in animal models has not translated into effective treatments.

    In this thesis, consisting of five studies, pain patient biofluids were analyzed with modern proteomic methods to identify biomarker candidates that can be used to improve our understanding of the pathophysiology chronic pain and lead to more effective treatments.

    Paper I is a proof of concept study, where a multiplex solid phase-proximity ligation assay (SP-PLA) was applied to cerebrospinal fluid (CSF) for the first time. CSF reference protein levels and four biomarker candidates for ALS were presented. The investigated proteins were not altered by spinal cord stimulation (SCS) treatment for neuropathic pain. In Paper II, patient CSF was explored by dimethyl and label-free mass spectrometric (MS) proteomic methods. Twelve proteins, known for their roles in neuroprotection, nociceptive signaling, immune regulation, and synaptic plasticity, were identified to be associated with SCS treatment of neuropathic pain. In Paper III, proximity extension assay (PEA) was used to analyze levels of 92 proteins in serum from patients one year after painful disc herniation. Patients with residual pain had significantly higher serum levels of 41 inflammatory proteins. In Paper IV, levels of 55 proteins were analyzed by a 100-plex antibody suspension bead array (ASBA) in CSF samples from two neuropathic pain patient cohorts, one cohort of fibromyalgia patients and two control cohorts. CSF protein profiles consisting of levels of apolipoprotein C1, ectonucleotide pyrophosphatase/phosphodiesterase family member 2, angiotensinogen, prostaglandin-H2 D-isomerase, neurexin-1, superoxide dismutases 1 and 3 were found to be associated with neuropathic pain and fibromyalgia. In Paper V, higher CSF levels of five chemokines and LAPTGF-beta-1were detected in two patient cohorts with neuropathic pain compared with healthy controls.

    In conclusion, we demonstrate that combining MS proteomic and multiplex antibody-based methods for analysis of patient biofluid samples is a viable approach for discovery of biomarker candidates for the pathophysiology and treatment of chronic pain. Several biomarker candidates possibly reflecting systemic inflammation, lipid metabolism, and neuroinflammation in different pain conditions were identified for further investigation.

    Delarbeten
    1. A Multiplex Protein Panel Applied to Cerebrospinal Fluid Reveals Three New Biomarker Candidates in ALS but None in Neuropathic Pain Patients
    Öppna denna publikation i ny flik eller fönster >>A Multiplex Protein Panel Applied to Cerebrospinal Fluid Reveals Three New Biomarker Candidates in ALS but None in Neuropathic Pain Patients
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    2016 (Engelska)Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, nr 2, artikel-id e0149821Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    The objective of this study was to develop and apply a novel multiplex panel of solid-phase proximity ligation assays (SP-PLA) requiring only 20 μL of samples, as a tool for discovering protein biomarkers for neurological disease and treatment thereof in cerebrospinal fluid (CSF). We applied the SP-PLA to samples from two sets of patients with poorly understood nervous system pathologies amyotrophic lateral sclerosis (ALS) and neuropathic pain, where patients were treated with spinal cord stimulation (SCS). Forty-seven inflammatory and neurotrophic proteins were measured in samples from 20 ALS patients and 15 neuropathic pain patients, and compared to normal concentrations in CSF from control individuals. Nineteen of the 47 proteins were detectable in more than 95% of the 72 controls. None of the 21 proteins detectable in CSF from neuropathic pain patients were significantly altered by SCS. The levels of the three proteins, follistatin, interleukin-1 alpha, and kallikrein-5 were all significantly reduced in the ALS group compared to age-matched controls. These results demonstrate the utility of purpose designed multiplex SP-PLA panels in CSF biomarker research for understanding neuropathological and neurotherapeutic mechanisms. The protein changes found in the CSF of ALS patients may be of diagnostic interest.

    Nationell ämneskategori
    Neurologi Teknik och teknologier
    Identifikatorer
    urn:nbn:se:uu:diva-281233 (URN)10.1371/journal.pone.0149821 (DOI)000371175700030 ()26914813 (PubMedID)
    Forskningsfinansiär
    VetenskapsrådetKnut och Alice Wallenbergs StiftelseEU, Europeiska forskningsrådet, 316929EU, Europeiska forskningsrådet, 294409
    Tillgänglig från: 2016-03-21 Skapad: 2016-03-21 Senast uppdaterad: 2017-11-30Bibliografiskt granskad
    2. Spinal Cord Stimulation Alters Protein Levels in the Cerebrospinal Fluid of Neuropathic Pain Patients: A Proteomic Mass Spectrometric Analysis
    Öppna denna publikation i ny flik eller fönster >>Spinal Cord Stimulation Alters Protein Levels in the Cerebrospinal Fluid of Neuropathic Pain Patients: A Proteomic Mass Spectrometric Analysis
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    2016 (Engelska)Ingår i: Neuromodulation (Malden, Mass.), ISSN 1094-7159, E-ISSN 1525-1403, Vol. 19, nr 6, s. 549-562Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    ObjectivesElectrical neuromodulation by spinal cord stimulation (SCS) is a well-established method for treatment of neuropathic pain. However, the mechanism behind the pain relieving effect in patients remains largely unknown. In this study, we target the human cerebrospinal fluid (CSF) proteome, a little investigated aspect of SCS mechanism of action. MethodsTwo different proteomic mass spectrometry protocols were used to analyze the CSF of 14 SCS responsive neuropathic pain patients. Each patient acted as his or her own control and protein content was compared when the stimulator was turned off for 48 hours, and after the stimulator had been used as normal for three weeks. ResultsEighty-six proteins were statistically significantly altered in the CSF of neuropathic pain patients using SCS, when comparing the stimulator off condition to the stimulator on condition. The top 12 of the altered proteins are involved in neuroprotection (clusterin, gelsolin, mimecan, angiotensinogen, secretogranin-1, amyloid beta A4 protein), synaptic plasticity/learning/memory (gelsolin, apolipoprotein C1, apolipoprotein E, contactin-1, neural cell adhesion molecule L1-like protein), nociceptive signaling (neurosecretory protein VGF), and immune regulation (dickkopf-related protein 3). ConclusionPreviously unknown effects of SCS on levels of proteins involved in neuroprotection, nociceptive signaling, immune regulation, and synaptic plasticity are demonstrated. These findings, in the CSF of neuropathic pain patients, expand the picture of SCS effects on the neurochemical environment of the human spinal cord. An improved understanding of SCS mechanism may lead to new tracks of investigation and improved treatment strategies for neuropathic pain.

    Nyckelord
    Cerebrospinal fluid, mechanism of action, neuropathic pain, spinal cord stimulation
    Nationell ämneskategori
    Neurologi Radiologi och bildbehandling
    Identifikatorer
    urn:nbn:se:uu:diva-304434 (URN)10.1111/ner.12473 (DOI)000382755300001 ()27513633 (PubMedID)
    Forskningsfinansiär
    VINNOVAVetenskapsrådet
    Tillgänglig från: 2016-10-05 Skapad: 2016-10-05 Senast uppdaterad: 2019-04-29Bibliografiskt granskad
    3. Inflammatory Serum Protein Profiling of Patients with Lumbar Radicular Pain One Year after Disc Herniation
    Öppna denna publikation i ny flik eller fönster >>Inflammatory Serum Protein Profiling of Patients with Lumbar Radicular Pain One Year after Disc Herniation
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    2016 (Engelska)Ingår i: INTERNATIONAL JOURNAL OF INFLAMMATION, ISSN 2090-8040, artikel-id UNSP 3874964Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Earlier studies suggest that lumbar radicular pain following disc herniation may be associated with a local or systemic inflammatory process. In the present study, we investigated the serum inflammatory protein profile of such patients. All 45 patients were recruited from Oslo University Hospital, Ulleval, Norway, during the period 2007-2009. The new multiplex proximity extension assay (PEA) technology was used to analyze the levels of 92 proteins. Interestingly, the present data showed that patients with radicular pain 12 months after disc herniation may be different from other patients with regard to many measurable serum cytokines. Given a false discovery rate (FDR) of 0.10 and 0.05, we identified 41 and 13 proteins, respectively, which were significantly upregulated in the patients with severe pain one year after disc herniation. On the top of the list ranked by estimated increase we found C-X-C motif chemokine 5 (CXCM5; 217% increase), epidermal growth factor (EGF; 142% increase), and monocyte chemotactic protein 4 (MCP-4; 70% increase). Moreover, a clear overall difference in the serum cytokine profile between the chronic and the recovered patients was demonstrated. Thus, the present results may be important for future protein serum profiling of lumbar radicular pain patients with regard to prognosis and choice of treatment. We conclude that serum proteins may be measurable molecular markers of persistent pain after disc herniation.

    Nationell ämneskategori
    Allmänmedicin
    Identifikatorer
    urn:nbn:se:uu:diva-317717 (URN)10.1155/2016/3874964 (DOI)000394106300001 ()27293953 (PubMedID)
    Forskningsfinansiär
    VINNOVAVetenskapsrådet, P29797-1
    Tillgänglig från: 2017-03-17 Skapad: 2017-03-17 Senast uppdaterad: 2018-01-13Bibliografiskt granskad
    4. Affinity Proteomics Applied to Patient CSF Identifies Protein Profiles Associated with Neuropathic Pain and Fibromyalgia
    Öppna denna publikation i ny flik eller fönster >>Affinity Proteomics Applied to Patient CSF Identifies Protein Profiles Associated with Neuropathic Pain and Fibromyalgia
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    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Objective: Today, there are no biological tests on which to base pain diagnoses, treatment choices or to understand the biological processes underlying and accompanying chronic pain for the individual pain patient. Relevant biological markers would greatly aid in diagnosis and treatment of patients with chronic pain. Our study aimed to find proteins in CSF associated with fibromyalgia and neuropathic pain, two common and poorly understood chronic pain conditions.

    Methods: We have performed CSF protein profiling of 55 proteins using a 100-plex antibody suspension bead array. We collected, analyzed and compared CSF samples from 25 patients with neuropathic pain (two independent sets, n=14 patients for discovery and n=11 for verification), 40 patients with fibromyalgia and 135 controls without neurological disease from two different populations.

    Results: We found significant differences in CSF protein levels between patients and controls (p<0.05). Among these proteins, Apolipoprotein C1 (APOC1) was found to be increased in CSF of neuropathic pain patients compared to controls and there was a non-significant trend for increased levels also in fibromyalgia patient CSF. Ectonucleotide pyrophosphatase (ENPP2, Autotaxin) was increased in the CSF of fibromyalgia patients compared to all other groups including neuropathic pain patients.  Multivariate analysis revealed partially overlapping and partially distinct CSF profiles in neuropathic pain patients compared with fibromyalgia and controls for several other proteins including angiotensinogen (AGT), prostaglandin-H2 D-isomerase (PTGDS), neurexin-1 (NRXN1), superoxide dismutase 1 (SOD1) and superoxide dismutase 3 (SOD3).

    Conclusions: Our results, suggest that the CSF protein profiles of neuropathic pain and fibromyalgia patients may be different from each other and from those of controls. CSF levels of APOC1, ENPP2, AGT, PTGDS, NRXN1, SOD1 and SOD3 should be further investigated for their potential to serve as biomarkers of different kinds of pain pathophysiology.

    Nyckelord
    cerebrospinal fluid, biomarker, human, chronic pain, neuropathic pain, fibromyalgia, spinal cord stimulation, mechanism of action, radiculopathy, protein, inflammation, neuroinflammation, mass spectrometry, antibody suspension bead array, protein profiling
    Nationell ämneskategori
    Neurovetenskaper Klinisk laboratoriemedicin Hälsovetenskaper Anestesi och intensivvård Biomedicinsk laboratorievetenskap/teknologi
    Forskningsämne
    Anestesiologi och intensivvård; Bioinformatik; Biokemi; Biologi med inriktning mot molekylärbiologi; Biomedicinsk laboratorievetenskap; Kemi med inriktning mot analytisk kemi; Klinisk kemi; Medicinsk vetenskap; Molekylär medicin
    Identifikatorer
    urn:nbn:se:uu:diva-326158 (URN)
    Projekt
    Berzelii Technology Centre of Neurodiagnostics
    Forskningsfinansiär
    AFA Försäkring, 140341VINNOVAVetenskapsrådet
    Tillgänglig från: 2017-07-03 Skapad: 2017-07-03 Senast uppdaterad: 2018-01-13
    5. High Levels of Cerebrospinal Fluid Chemokines Point to the Presence of Neuroinflammation in Peripheral Neuropathic Pain: A Cross-Sectional Study of Two Cohorts of Patients Compared to Healthy Controls
    Öppna denna publikation i ny flik eller fönster >>High Levels of Cerebrospinal Fluid Chemokines Point to the Presence of Neuroinflammation in Peripheral Neuropathic Pain: A Cross-Sectional Study of Two Cohorts of Patients Compared to Healthy Controls
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    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Animal models suggest that chemokines are important mediators in the pathophysiology of neuropathic pain. Indeed, these substances have been called “gliotransmitters”, a term that illustrates the close interplay between glial cells and neurons in the context of neuroinflammation and pain. However, evidence in humans is scarce. The aim of the study was to determine a comprehensive cerebrospinal fluid (CSF) inflammatory profile for neuropathic pain patients. Our hypothesis was that we would thereby find indications of a postulated on-going process of central neuroinflammation.  

    CSF samples were collected from two cohorts of patients with neuropathic pain (n=11 and n=16, respectively) and healthy controls (n=11). The samples were analyzed with a multiplex proximity extension assay in which 92 inflammation-related proteins were measured simultaneously (Proseek® Multiplex Inflammation I, Olink Bioscience, Uppsala, Sweden). Univariate testing with control of false discovery rate, as well as orthogonal partial least squares – discriminant analysis, were used for statistical analyses.

    CSF levels of chemokines CXCL6, CXCL10, CCL8, CCL11, CCL23, as well as protein LAPTGF-beta-1, were significantly higher in both neuropathic pain cohorts compared to healthy controls, pointing to neuroinflammation in patients. These 6 proteins were also major results in a recent similar study in fibromyalgia patients. The findings need to be confirmed in larger cohorts, and the question of causality remains to be settled. Since it has been suggested that prevalent co-morbidities to chronic pain (e.g., depression, anxiety, poor sleep, and tiredness) also are associated with inflammation, it will be important to determine whether inflammation is a common mediator.

    Nyckelord
    biomarker; cerebrospinal fluid; chemokines; cytokines; human; inflammation; neuroinflammation; neuropathic pain; protein profile; proximity extension assay (PEA), chronic pain
    Nationell ämneskategori
    Anestesi och intensivvård Klinisk laboratoriemedicin Biomedicinsk laboratorievetenskap/teknologi Neurovetenskaper Medicinsk laboratorie- och mätteknik
    Forskningsämne
    Anestesiologi och intensivvård; Biomedicinsk laboratorievetenskap; Kemi med inriktning mot analytisk kemi; Medicinsk vetenskap; Medicinsk biokemi; Molekylär medicin
    Identifikatorer
    urn:nbn:se:uu:diva-326161 (URN)
    Projekt
    Uppsala Berzelii Technology Centre for NeurodiagnosticsAFA Insurance (140341)Swedish Research Council (grant no. K2015-99x-21874-05-4)the Swedish Research Council (grant no. P29797-1).Swedish Governmental Agency for Innovation Systems (Vinnova)County Council of Östergötland (LIO-35923, SC-2013-00395-36)
    Forskningsfinansiär
    AFA Försäkring, 140341VINNOVA, P29797-1Vetenskapsrådet, P29797-1Vetenskapsrådet, K2015-99x-21874-05-4
    Tillgänglig från: 2017-07-03 Skapad: 2017-07-03 Senast uppdaterad: 2018-01-13
  • 209.
    Lind, Anne-Li
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Just, David
    SciLifeLab, School of Biotechnology, KTH – Royal Institute of Technology, Stockholm, Sweden.
    Mikus, Maria
    SciLifeLab, School of Biotechnology, KTH – Royal Institute of Technology, Stockholm, Sweden.
    Fredolini, Claudia
    SciLifeLab, School of Biotechnology, KTH – Royal Institute of Technology, Stockholm, Sweden.
    Ioannou, Marina
    SciLifeLab, School of Biotechnology, KTH – Royal Institute of Technology, Stockholm, Sweden.
    Gerdle, Björn
    Linköping University, Linköping, Sweden.
    Bäckryd, Emmanuel
    Linköping University, Linköping, Sweden.
    Tanum, Lars
    Akershus University Hospital, Lørenskog, Norway.
    Gordh, Torsten
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Nilsson, Peter
    SciLifeLab, School of Biotechnology, KTH – Royal Institute of Technology, Stockholm, Sweden.
    Månberg, Anna
    SciLifeLab, School of Biotechnology, KTH – Royal Institute of Technology, Stockholm, Sweden.
    Affinity Proteomics Applied to Patient CSF Identifies Protein Profiles Associated with Neuropathic Pain and FibromyalgiaManuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Objective: Today, there are no biological tests on which to base pain diagnoses, treatment choices or to understand the biological processes underlying and accompanying chronic pain for the individual pain patient. Relevant biological markers would greatly aid in diagnosis and treatment of patients with chronic pain. Our study aimed to find proteins in CSF associated with fibromyalgia and neuropathic pain, two common and poorly understood chronic pain conditions.

    Methods: We have performed CSF protein profiling of 55 proteins using a 100-plex antibody suspension bead array. We collected, analyzed and compared CSF samples from 25 patients with neuropathic pain (two independent sets, n=14 patients for discovery and n=11 for verification), 40 patients with fibromyalgia and 135 controls without neurological disease from two different populations.

    Results: We found significant differences in CSF protein levels between patients and controls (p<0.05). Among these proteins, Apolipoprotein C1 (APOC1) was found to be increased in CSF of neuropathic pain patients compared to controls and there was a non-significant trend for increased levels also in fibromyalgia patient CSF. Ectonucleotide pyrophosphatase (ENPP2, Autotaxin) was increased in the CSF of fibromyalgia patients compared to all other groups including neuropathic pain patients.  Multivariate analysis revealed partially overlapping and partially distinct CSF profiles in neuropathic pain patients compared with fibromyalgia and controls for several other proteins including angiotensinogen (AGT), prostaglandin-H2 D-isomerase (PTGDS), neurexin-1 (NRXN1), superoxide dismutase 1 (SOD1) and superoxide dismutase 3 (SOD3).

    Conclusions: Our results, suggest that the CSF protein profiles of neuropathic pain and fibromyalgia patients may be different from each other and from those of controls. CSF levels of APOC1, ENPP2, AGT, PTGDS, NRXN1, SOD1 and SOD3 should be further investigated for their potential to serve as biomarkers of different kinds of pain pathophysiology.

  • 210.
    Linder, Fredrik
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kärlkirurgi.
    Mani, Kevin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kärlkirurgi.
    Juhlin, Claes
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kärlkirurgi.
    Eklöf, Hampus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Routine whole body CT of high energy trauma patients leads to excessive radiation exposure2016Ingår i: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine, ISSN 1757-7241, E-ISSN 1757-7241, Vol. 24, nr 1Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Whole body computed tomography (WBCT) is an important adjunct in trauma care, which is often part of standard protocol in initial management of trauma patients. However, WBCT exposes patients to a significant dose of radiation. The use of WBCT was assessed in a modern trauma cohort in Sweden.

    METHODS: A two-center retrospective cohort study was performed. All consecutive trauma alert patients at a university hospital (July-December 2008), and a rural county hospital (January 2009- December 2010) were included. Patients were stratified into three groups (high, intermediate and low risk) based on documented suspected injuries at primary survey at the site of accident or at the emergency department. Injury severity score (ISS) was calculated. Case records were reviewed for clinical and radiological findings at the time of trauma, and during a ≥36 months of follow-up period to identify possible missed injuries.

    RESULTS: A total of 523 patients were included in the study (university hospital n = 273; rural county hospital n = 250), out of which 475 patients (91.0 %) underwent radiological examinations, 290 patients (55.4 %) underwent WBCT, which identified trauma related findings in 125 patients (43.1 % of those examined). The high-risk group (n = 62) had a mean age of 38.5 years (21.1 SD). Mean ISS was 16.48 (18.14 SD). In this group, WBCT resulted in a positive finding in 38 (74.5 %) patients. In the intermediate-risk group (n = 322; mean age 37.66, 20.24 SD) ISS was 4.42 (6.30 SD). A positive finding on WBCT was found in 87 of the intermediate group patients (44.8 %). The low-risk group (n = 139; mean age 32.5 years; 21.4 SD) had a mean ISS of 0.84 (1.57 SD) with no positive findings on WBCT and no missed injuries in medical records at ≥36 months.

    DISCUSSION: The risk of developing radiation induced cancer is significant for young people if exposed to relatively high dose radiation as is the case in WBCT. WBCT in high-energy trauma is important for planning of treatment in severely injured patients while it can be questioned in the seemingly not injured where it is used mainly to permit early discharge from the ED.

    CONCLUSIONS: Risk stratification criteria could in this retrospective study identify high energy trauma patients not in need of radiological imaging. WBCT in high-energy trauma does not affect patient care if the patient is mentally alert, not intoxicated nor shows signs of other than minor injuries when evaluated by a trauma-team. The risk of missing important traumatic findings in these patients is very low. Observation of the patient with reexamination instead of imaging may be considered in this group of often young patients where radiation dose is an issue.

  • 211. Lindgren, S
    et al.
    Pikwer, A
    Ricksten, S-E
    Åkeson, J
    Survey of central venous catheterisation practice in Sweden.2013Ingår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 57, nr 10, s. 1237-44Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Clinical guidelines on central venous catheterisation were introduced by the Swedish Society of Anaesthesiology and Intensive Care Medicine in 2011. The purpose of this study was to investigate current national practice and assess to what extent these guidelines influence clinical routines in Swedish operating wards and intensive care units.

    METHODS: An invitation to participate in an online survey regarding central venous catheterisation was sent to 65 departments of anaesthesiology and intensive care medicine in Sweden. The survey aimed at investigating routine standards (part 1) and 24-h clinical practice (part 2).

    RESULTS: Forty-seven (72%) and 49 (75%) of 65 departments took part in parts 1 and 2, respectively, and 73% adhered to the national guidelines. Many units monitored mechanical (42%) and infectious (69%) complications. Ultrasound was used by more than 50%. Checklists for insertion were used by 22%. Physicians inserted most catheters. No serious complications were reported during the 24-h study period. Ninety-seven non-tunnelled, 17 venous ports, 9 tunnelled and 8 peripheral central venous catheters were inserted. Ninety-three (71%) catheters were inserted in operating rooms, and 31 (24%) in intensive care units. Catheterisations were followed up by chest X-ray in most departments.

    CONCLUSION: Knowledge of the Swedish guidelines was adequate, and most participating departments had local catheterisation routines. We could identify some variation in practice, but overall adherence to the guidelines was good. Nevertheless, monitoring of procedures and complications of cannulation and maintenance could be in need of improvement.

  • 212.
    Lipcsey, Miklos
    et al.
    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.
    Chiong, Jonathan
    Subiakto, Ivan
    Kaufman, Melissa A.
    Schneider, Antoine G.
    Bellomo, Rinaldo
    Primary fluid bolus therapy for infection-associated hypotension in the emergency department2015Ingår i: CRITICAL CARE AND RESUSCITATION, ISSN 1441-2772, Vol. 17, nr 1, s. 6-11Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: The physiological changes associated with fluid bolus therapy (FBI) for patients with infection-associated hypotension in the emergency department (ED) are poorly understood. We describe the physiological outcomes of FBT in the first 6 hours (primary FBT) for patients presenting to the ED with infection-associated hypotension. Methods: We studied 101 consecutive ED patients with infection and a systolic blood pressure (SBP) <100 mmHg who underwent FBI in the first 6 hours. Results: We screened 1123 patients with infection and identified 101 eligible patients. The median primary FBI volume given was 1570 mL (interquartile range, 1000 2490 mL). The average mean arterial pressure (MAP) did not change from admission to 6 hours in the whole cohort, or in patients who were hypotensive on arrival at the ED. However, the average MAP increased from its lowest value during the first 6 hours (66 mmHg [SD, 10 mmHg]) to its value at 6 hours (73 mmHg [SD, 12 mmHg]; P < 0.001). The mean heart rate, body temperature, respiratory rate and plasma creatinine level decreased (P < 0.05). In patients who were severely hypotensive (SBP <90 mmHg) on arrival at the ED, the MAP increased from 54 mmHg (SD, 8 mmHg) to 70 mmHg (SD, 14 mmHg) (P < 0.001). At 6 hours, however, SBP was still <100 mmHg in 44 patients and <90 mmHg in 17 patients. When noradrenaline was used, in 10 patients, hypotension was corrected in all 10 and the MAP increased from 58 mmHg (SD, 9 mmHg) to 75 mmHg (SD, 13 mmHg). Conclusion: Among ED patients admitted to an Australian teaching hospital with infection, hypotension was uncommon. FBT for hypotension was limited in volumes given and failed to achieve a sustained SBP of > 100 mmHg in 40% of cases. In contrast, noradrenaline therapy corrected hypotension in all patients who received it.

  • 213.
    Lipcsey, Miklos
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Chua, Horng-Ruey
    Schneider, Antoine G
    Robbins, Raymond
    Bellomo, Rinaldo
    Clinically manifest thromboembolic complications of femoral vein catheterization for continuous renal replacement therapy2014Ingår i: Journal of critical care, ISSN 0883-9441, E-ISSN 1557-8615, Vol. 29, nr 1, s. 18-23Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE:

    The safety of femoral vein (FV) catheterization for continuous renal replacement therapy is uncertain. We sought to determine the incidence of clinically manifest venous thromboembolism (VTE) in such patients.

    METHODS:

    We retrospectively studied patients with femoral high flow catheters (≥13F) (December 2005 to February 2011). Discharge diagnostic codes were independently screened for VTE. The incidence of VTE was also independently similarly assessed in a control cohort of patients ventilated for more than 2 days (January 2011 to December 2011) in the same intensive care unit (ICU).

    RESULTS:

    We studied 380 patients. Their mean age was 61 years, and 59% were male. The mean Acute Physiology and Chronic Health Evaluation III score was 84; average duration of continuous renal replacement therapy was 74 hours, and 232 patients (61%) survived to hospital discharge with an average length of hospital stay of 22 days. Only 5 patients (1.3%) had clinically manifest VTE after FV catheterization. In the control cohort of 514 ICU patients, the incidence of VTE was 4.4% (P < .05 compared with FV group).

    CONCLUSION:

    The incidence of clinically manifest VTE after FV catheterization with high flow catheters is low and lower to that seen in general ICU patients.

  • 214.
    Lipcsey, Miklos
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Subiakto, Ivan
    Austin Hosp, Dept Intens Care, Melbourne, Vic, Australia..
    Chiong, Jonathan
    Austin Hosp, Dept Intens Care, Melbourne, Vic, Australia..
    Kaufman, Melissa A.
    Austin Hosp, Dept Intens Care, Melbourne, Vic, Australia..
    Schneider, Antoine G.
    Austin Hosp, Dept Intens Care, Melbourne, Vic, Australia..
    Bellomo, Rinaldo
    Austin Hosp, Dept Intens Care, Melbourne, Vic, Australia.;Monash Univ, Sch Publ Hlth & Prevent Med, Australian & New Zealand Intens Care Res Ctr, Melbourne, Vic, Australia..
    Epidemiology of secondary fluid bolus therapy for infection-associated hypotension2016Ingår i: CRITICAL CARE AND RESUSCITATION, ISSN 1441-2772, Vol. 18, nr 3, s. 165-173Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: Fluid bolus therapy (FBT) is a common therapy for hypotensive sepsis, but no studies have compared primary FBT (in the first 6 hours after presentation to the emergency department [ED]) with secondary FBT (6-24 hours after presentation to the ED). We aimed to describe the patterns of use, physiological sequelae and outcomes of patients with hypotensive sepsis who were treated with primary FBT or combined primary and secondary FBT (secondary FBT). Design, setting and patients: A retrospective observational study of patients with hypotensive sepsis presenting to the ED of a tertiary hospital from 1 January to 31 December 2010. Results: We studied 100 consecutive eligible patients (primary FBT, n = 52; secondary FBT, n = 48). Secondary FBT occurred in the ward (n = 31) or in the intensive care unit (n = 17). More patients receiving secondary FBT had sepsis with undefined focus or septic shock (P = 0.005, P = 0.0001, respectively), and fewer patients receiving secondary FBT had pneumonia (P = 0.0004). At 24 hours, the use of secondary FBT was similar for patients admitted to the ward and the ICU, and represented about 40% of all secondary fluids given. The volume of any bolus was greater during primary resuscitation, and the size of physiological changes associated with FBT diminished with time. The mortality rate at 28 days was 27%, and was similar for ward and ICU admissions. Conclusions: Secondary FBT is given to about half of patients presenting with hypotensive sepsis, takes place in wards more often than in the ICU and delivers a significant proportion of overall fluids, but is associated with limited changes in measured physiological variables.

  • 215.
    Lipcsey, Miklós
    et al.
    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.
    Aronsson, Anna
    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.
    Renlund, Henrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Gedeborg, Rolf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Multivariable models using administrative data and biomarkers to adjust for case mix in the ICU2019Ingår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 63, nr 6, s. 751-760Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Routinely collected laboratory biomarkers could improve control of confounding from disease severity in non-interventional studies of general intensive care unit (ICU) patients. Their ability to predict both short- and long-term mortality was evaluated.

    METHODS: The performance of age, sex, Charlson co-morbidity index, and baseline values of ten predefined blood biomarkers as predictors of 30-day and 1-year mortality was evaluated in 5505 general ICU stays.

    RESULTS: Regression models based on age, sex, Charlson index, and biomarkers were somewhat less accurate in predicting 30-day mortality (c-index 0.83, Brier score 0.27) compared to the SAPS II score (c-index = 0.88, Brier score = 0.09) and in predicting 1-year mortality (c-index = 0.82, Brier score = 0.31) compared to the SAPS II score (c-index = 0.85, Brier score = 0.13). Cystatin C improved predictive ability slightly compared to creatinine, but age and Charlson comorbidity index were more important predictors. Using multiple imputation to replace missing biomarker values notably improved predictive ability of the models.

    CONCLUSIONS: Automatically collected baseline variables are almost as predictive of both short- and long-term mortality in general ICU patients, as the SAPS II score. This can facilitate internal control of confounding in non-interventional studies of mortality using administrative data.

  • 216.
    Lipcsey, Miklós
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Castegren, Markus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Bellomo, R
    Hemodynamic management of septic shock2015Ingår i: Minerva Anestesiologica, ISSN 0375-9393, E-ISSN 1827-1596, Vol. 81, nr 11, s. 1262-1272Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We present a review of the hemodynamic management of septic shock. Although substantial amount of evidence is present in this area, most key decisions on the management of these patients remain dependent on physiological reasoning and on pathophysiological principles rather than randomized controlled trials. During primary (early) resuscitation, restoration of adequate arterial pressure and cardiac output using fluids and vasopressor and/or inotropic drugs is guided by basic hemodynamic monitoring and physical examination in the emergency department. When more advanced level of monitoring is present in these patients, i.e. during secondary resuscitation (later phase in the emergency department and in the ICU), hemodynamic management can be guided by more advanced measurements of the macro--circulation. Our understanding of the microcirculation in septic shock is limited and reliable therapeutic modalities to optimize it do not yet exist. No specific hemodynamic treatment strategy, be it medications including fluids, monitoring devices or treatment algorithms has yet been proved to improve outcome. Moreover, there is virtually no data on the optimal management of the resolution phase of septic shock. Despite these gaps in knowledge, the data from observational studies and trials suggests that mortality in septic shock has been generally decreasing during the last decade.

  • 217.
    Lipcsey, Miklós
    et al.
    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.
    Castegren, Markus
    Karolinska Univ Hosp, Dept Anaesthesia, Intens Care Serv, Solna, Sweden; Karolinska Univ Hosp, Dept Anaesthesia, Surg Serv, Solna, Sweden.
    Furebring, Mia
    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.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Should the Aminoglycoside β-Lactam Combination Be Abandoned in All Severely Ill Patients With Presumed Gram-Negative Infection?2018Ingår i: Clinical Infectious Diseases, ISSN 1058-4838, E-ISSN 1537-6591, Vol. 66, nr 3, s. 480-482Artikel i tidskrift (Övrigt vetenskapligt)
  • 218.
    Lipcsey, Miklós
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Mcnicol, L.
    Austin Hosp, Dept Anaesthesia, Melbourne, Vic 3084, Australia..
    Parker, F.
    Austin Hosp, Dept Anaesthesia, Melbourne, Vic 3084, Australia..
    Poustie, S.
    Austin Hosp, Dept Anaesthesia, Melbourne, Vic 3084, Australia..
    Liu, G.
    Austin Hosp, Dept Anaesthesia, Melbourne, Vic 3084, Australia..
    Uchino, S.
    Jikei Univ, Dept Intens Care, Tokyo, Japan..
    Kattula, A.
    Alfred Hlth, Clin Practice Improvement, Melbourne, Vic, Australia..
    Bellomo, R.
    Austin Hosp, Dept Intens Care, Melbourne, Vic 3084, Australia..
    Effect of perfusion pressure on the splanchnic circulation after CPB: a pilot study2015Ingår i: Minerva Anestesiologica, ISSN 0375-9393, E-ISSN 1827-1596, Vol. 81, nr 7, s. 752-764Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background. The impact of different blood pressure targets is unknown for post cardiac surgery patient in the intensive care unit. We, therefore, investigated the effects of a mean arterial pressure (MAP) target of 65 or 85 mmHg on splanchnic oxygenation, metabolic function, cytokine regulation and gastric tonometry after cardiopulmonary bypass. Methods. Sixteen patients were randomized to the HLH group (high-low-high) where MAP of 85-65-85 mmHg was targeted or the LHL group where MAP 65-85-65 mmHg was targeted with norepinephrine Results. MAP targets were achieved in all patients at all timepoints (64 +/- 3, 84 +/- 4; 65 +/- 5, LHL group; vs. 84 +/- 3; 66 +/- 2; 85 +/- 5 mmHg, HLH group). At corresponding timepoints, hepatic venous saturation was 41 +/- 15%; 58 +/- 24%; 56 +/- 21% in the LHL group vs. 50 +/- 19%; 43 +/- 20%; 41 +/- 18% in the HLH group (P<0.05). No changes were observed in cardiac output, global or trans-splanchnic lactate levels and cytokine levels or in gastric tonometry CO2. Conclusion. Achieving a MAP target of 85 mmHg by means of norepinephrine infusion after CPB appears safe for the splanchnic circulation.

  • 219.
    Lipcsey, Miklós
    et al.
    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.
    Tenhunen, Jyrki
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Frithiof, Robert
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Bendel, Stepani
    Kuopio Univ Hosp, Dept Intens Care, Kuopio, Finland..
    Flaatten, Hans
    UiB, Haukeland Univ Hosp, Dept Clin Med, Bergen, Norway..
    Kawati, Rafael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Kuitunen, Anne
    Tampere Univ Hosp, Crit Care Med Res Grp, POB 200033521, Tampere, Finland..
    Tonnessen, Tor Inge
    Oslo Univ Hosp, Div Emergencies & Crit Care, N-0450 Oslo, Norway.;Inst Clin Med, N-0450 Oslo, Norway..
    Rubertsson, Sten
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Abdominal Septic Shock - Endotoxin Adsorption Treatment (ASSET) - endotoxin removal in abdominal and urogenital septic shock with the Alteco (R) LPS Adsorber: study protocol for a double-blinded, randomized placebo-controlled trial2016Ingår i: Trials, ISSN 1745-6215, E-ISSN 1745-6215, Vol. 17, artikel-id 587Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Severe sepsis and septic shock are common in intensive care and carry high mortality rates. In patients with Gram-negative infections, early and extensive removal of endotoxin may limit the inflammatory response that characterizes septic shock. The Alteco (R) LPS Adsorber (hereafter referred to cited as the lipopolysaccharide (LPS) Adsorber) can be used for endotoxin removal and attenuate the deleterious inflammatory and clinical responses seen in septic shock. Methods/design: The Abdominal Septic Shock - Endotoxin Adsorption Treatment (ASSET) trial is a pilot study investigating the feasibility and safety of LPS Adsorber therapy. This pilot, multicenter, stratified, parallel, double-blinded, randomized, phase IIa, feasibility clinical investigation will be performed in five Scandinavian intensive care units. Thirty-two subjects with early septic shock and organ failure, following adequate resuscitation, will be randomized to receive either: extracorporeal veno-venous hemoperfusion therapy with the LPS Adsorber or veno-venous hemoperfusion therapy with a placebo adsorber (without active LPS-binding peptide). Patients will be stratified by infection focus such that 20 subjects with an abdominal focus (stratum A) and 12 subjects with a urogenital focus (stratum B) will be included in a parallel design. Thereafter, an interim analysis will be performed and an additional 12 patients may be included in the study. The study is designed as adaptive a priori: the patients from this study can be included in a later phase IIb study. The aim of the study is to investigate the feasibility of LPS Adsorber therapy commenced early in the time-course of septic shock. The primary endpoint will be a characterization of all reported unanticipated serious adverse device effects and anticipated serious adverse device effects. Secondary outcomes are decrease in endotoxin plasma concentration, impact on clinical outcome measures and impact on inflammatory response by LPS Adsorber therapy, as well as detailed description of the relevant mediators bound to the LPS Adsorber. Recruitment of patients will start in September 2015. Discussion: The ASSET trial will give insight into the feasibility and safety of this LPS Adsorber therapy and preliminary data on its potential clinical effects in septic shock. Moreover, this pilot trial will provide with necessary data for designing future studies.

  • 220.
    Liu, Xiaoli
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Experimental cardiopulmonary resuscitation : with special reference to cerebral eicosanoid production and free radical scavengers2002Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Reperfusion injury after restoration of spontaneous circulation (ROSC) is often considered one of the predominant factors in determining neurological outcome in cardiac arrest. Therefore one of the main targets of experimental and clinical studies has been to mitigate this reperfusion injury. Accumulated knowledge indicates that oxidative stress is perhaps the foremost cause of this reperfusion injury, and hence, free radical scavengers have been tried anticipating mitigation of the effects of ischaemia and reperfusion injury. In this series of experimental porcine studies of cardiac arrest and cardiopulmonary resuscitation (CPR), we aimed to find evidence for increased concentrations of indicators of oxidative stress and inflammation during reperfusion, to mitigate the reperfusion injury by free radiacal scavengers and alkaline buffers, and to improve 24 h neurological outcome by combining effective interventions. The results showed that the isoprostane 8-iso-PGF2alpha, an oxidative indicator, and the prostaglandin 15-keto-dihydro-PGF2alpha, an inflammatory indicator, are significantly increased in the jugular bulb plasma during reperfusion. We confirmed that S-PBN mitigated oxidative stress, as the concentration of 8-iso-PGF2alpha was lower and cerebral vascular autoregulation was better preserved during the early period of reperfusion after ROSC. Combining PBN with cerebral blood flow-promoting interventions, we found that 24 h after ROSC the neurological outcome determined by neurological deficit score (NDS) was significantly improved as compared with two control groups. The concentration of 8-iso-PGF2alpha and hypoxanthine in jugular bulb plasma were correlated to the 24 hy neurological outcome. Alkaline buffer administration during CPR could promote cerebral reperfusion and mitigate cerebral acidosis during the reperfusion period. In summary, reperfusion after ROSC induced oxidative and inflammatory reactions. The eicosanoids, 8-iso-PGF2alpha and 15-keto-dihydro-PGF2alpha determined in jugular bulb plasma can be used as biomarkers of cerebral oxidative and inflammatory reactions, and for evaluating the effectiveness of interventions. The free radical scavengers PBN and S-PBN could mitigate oxidative stress and promote distribution of cerebral cortical blood flow (CCBF). Combineing measures to promote cerebral blood flow and free radical scavenger PBN significantly improved neurological outcome 24 h after ROSC. Administration of alkaline buffers mitigates cerebral acidosis and promotes CCBF in the reperfusion phase after ROSC.

  • 221.
    Longo, Silvina
    et al.
    Hosp Privado Univ Cordoba, Dept Anesthesia, Cordoba, Argentina..
    Siri, Juan
    Acosta, Cecilia
    Hosp Privado Comunidad Mar Del Plata, Dept Anesthesia, Mar Del Plata, Buenos Aires, Argentina..
    Palencia, Alberto
    Hosp Privado Univ Cordoba, Dept Cardiovasc Surg, Cordoba, Argentina..
    Echegaray, Arturo
    Chiotti, Ivan
    Hosp Privado Univ Cordoba, Dept Intens Care, Cordoba, Argentina..
    Parisi, Andres
    Ricci, Lila
    Univ Nacl Mar del Plata, Fac Ciencias Exactas, Dept Math, Mar Del Plata, Buenos Aires, Argentina..
    Natal, Marcela
    Univ Nacl Mar del Plata, Fac Ciencias Exactas, Dept Math, Mar Del Plata, Buenos Aires, Argentina..
    Suarez-Sipmann, Fernando
    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. CIBERES, Madrid, Spain..
    Tusman, Gerardo
    Hosp Privado Comunidad Mar Del Plata, Dept Anesthesia, Mar Del Plata, Buenos Aires, Argentina..
    Lung recruitment improves right ventricular performance after cardiopulmonary bypass A randomised controlled trial2017Ingår i: European Journal of Anaesthesiology, ISSN 0265-0215, E-ISSN 1365-2346, Vol. 34, nr 2, s. 66-74Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND Atelectasis after cardiopulmonary bypass (CPB) can affect right ventricular (RV) performance by increasing its outflow impedance. OBJECTIVE The aim of this study was to determine whether a lung recruitment manoeuvre improves RV function by re-aerating the lung after CPB. DESIGN Randomised controlled study. SETTING Single-institution study, community hospital, Cordoba, Argentina. PATIENTS Forty anaesthetised patients with New York Heart Association class I or II, preoperative left ventricular ejection fraction at least 50% and Euroscore 6 or less scheduled for cardiac surgery with CPB. INTERVENTIONS Patients were assigned to receive either standard ventilation with 6 cmH(2)O of positive end-expiratory pressure (PEEP; group C, n = 20) or standard ventilation with a recruitment manoeuvre and 10 cmH(2)O of PEEP after surgery (group RM, n = 20). RV function, left ventricular cardiac index (CI) and lung aeration were assessed by transoesophageal echocardiography (TOE) before, at the end of surgery and 30 min after surgery. MAIN OUTCOME MEASURES RV function parameters and atelectasis assessed by TOE. RESULTS Haemodynamic data and atelectasis were similar between groups before surgery. At the end of surgery, CI had decreased from 2.9 +/- 1.1 to 2.6 +/- 0.9 l min(-1) m(-2) in group C (P = 0.24) and from 2.8 +/- 1.0 to 2.6 +/- 0.8 l min(-1) m +/- 2 in group RM (P = 0.32). TOE-derived RV function parameters confirmed a mild decrease in RV performance in 95% of patients, without significant differences between groups (multivariate Hotelling t-test P = 0.16). Atelectasis was present in 18 patients in group C and 19 patients in group RM (P = 0.88). After surgery, CI decreased further from 2.6 to 2.4 l min(-)1 m(-2) in group C (P = 0.17) but increased from 2.6 to 3.7 l min(-1) m(-2) in group RM (P<0.001). TOE-derived RV function parameters improved only in group RM (Hotelling t-test P<0.001). Atelectasis was present in 100% of patients in group C but only in 10% of those in group RM (P<0.001). CONCLUSION Atelectasis after CPB impairs RV function but this can be resolved by lung recruitment using 10 cm H2O of PEEP.

  • 222. Ludvigsson, Maria Landén
    et al.
    Peterson, Gunnel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    O'Leary, Shaun
    Dedering, Asa
    Peolsson, Anneli
    The Effect of Neck-specific Exercise with, or without a Behavioral Approach, on Pain, Disability and Self-efficacy in Chronic Whiplash-associated Disorders: A Randomized Clinical Trial2015Ingår i: The Clinical Journal of Pain, ISSN 0749-8047, E-ISSN 1536-5409, Vol. 31, nr 4, s. 249-303Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES:: The aim of this study was to compare the effect on self-rated pain, disability and self-efficacy of three interventions for the management of chronic Whiplash Associated Disorders (WAD): physiotherapist-led neck-specific exercise, physiotherapist-led neck-specific exercise with the addition of a behavioral approach, or prescription of physical activity.

    METHODS:: Two hundred and sixteen volunteers with chronic WAD participated in this randomized, assessor blinded, clinical trial of three exercise interventions. Self-rated pain/pain bothersomeness (Visual Analogue Scale), disability (Neck Disability Index) and self-efficacy (Self-Efficacy Scale) were evaluated at baseline and at three and six months.

    RESULTS:: The proportion of patients reaching substantial reduction in pain bothersomness (at least 50% reduction) was more evident (P<0.01) in the two neck-specific exercise groups (29-48%) compared to the prescription of physical activity group (5%) at three months. At six months 39-44% of the patients in the two neck-specific groups and 28% in the prescription of physical activity group reported substantial pain reduction. Reduction of disability was also larger in the two neck-specific exercise groups at both three and six months (P<0.02). Self-efficacy was only improved in the neck-specific exercise group without a behavioral approach (P=0.02). However there were no significant differences in any outcomes between the two physiotherapist-led neck-specific exercise groups.

    DISCUSSION:: Neck-specific exercise resulted in superior outcomes compared to prescription of physical activity in this study, but the observed benefits of adding a behavioral approach to the implementation of exercise in this study were inconclusive.

  • 223.
    Makdessi, M. J.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Barr, T. P.
    Xue, W.
    Strichartz, G. R.
    Bupivacaine inhibits endothelin-1-evoked increases in intracellular calcium in model sensory neurons2015Ingår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 59, nr 7, s. 936-945Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BackgroundEndothelin-1 (ET-1) induces pain-like behavior in animals and man by activating the G(q) protein-coupled receptor endothelin-A (ETA). Activation of ETA receptors on nociceptor membranes evokes intracellular calcium transients and alters membrane Na+ and K+ channel and TRPV1 currents, leading to neuronal hyper-excitability manifested by spontaneous and evoked pain behaviors in vivo. In addition to blocking sodium channels, local anesthetics inhibit the G(q) protein-coupled signaling of several inflammatory and pro-algesic mediators. In this study, we aimed to investigate the actions of local anesthetics on ETA-mediated increases in intracellular calcium in ND7/104 model sensory neurons. MethodsIncreases in intracellular calcium were measured by the fluorescent indicator fura-2 in a sensory neuron-derived cell line (ND7/104), which endogenously expresses ETA receptors. Effects of lidocaine and bupivacaine, along with their respective membrane-impermeant derivatives QX-314, LEA-123 and LEA-124, on peak calcium responses to ET-1 were measured. ResultsBupivacaine suppressed ET-1 responses in a concentration-dependent and non-competitive manner with an IC50 of 3.791.63mM. Bupivacaine (6mM) reduced the E-max for ET-1 from 50.07 +/- 1.91mM to 27.30 +/- 2.92mM. The actions of bupivacaine occurred quickly and were rapidly reversible. Membrane-impermeant analogs of bupivacaine (LEA-123 and LEA-124, 6mM) were without effect, as was lidocaine (10mM) and its quaternary derivative QX-314 (10mM). ConclusionBupivacaine inhibits ETA-mediated calcium transients at clinically relevant concentrations through an intracellular target. The anti-inflammatory and analgesic actions of bupivacaine may be at least partially due to its inhibitory action on G(q)-coupled receptors, including ETA.

  • 224.
    Marchesi, Silvia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    The effect of mechanical ventilation on abdominal organs: Analysing the role of PEEP and perfusion.2019Licentiatavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Background: The effect of mechanical ventilation on abdominal organs is not well understood and investigated yet. Previous studies, using an animal sepsis-like model, found an association between mechanical ventilation (MV) and abdominal edema and inflammation.The presented thesis was aimed to investigate the role of perfusion in edema formation and inflammation, and to study the abdomen during mechanical ventilation in an ARDS model to reduce the confounding effect of inflammation related to sepsis.Methods: In the first paper presented, inflammation and edema in the abdomen were investigated in an endotoxin model. The study subjects were divided into two groups with different mean arterial pressures (MAP), another small group of healthy controls were studied as well. MRI analyses were used to measure perfusion in the different abdominal organs. In the second paper presented, differences in abdominal edema and inflammation were assessed in two groups of subjects, one group underwent MV and one group had spontaneously breathing.Results: In the first study, MRI analyses confirm that the group with higher MAP had better perfusion than the low MAP group. In the liver, perfusion was lower in LowMAP group compared to HighMAP group, but the HighMAP group had lower perfusion than the healthy controls. However, in the other studied organs HighMAP group and healthy controls had similar perfusion.Edema did not differ between the groups. Inflammation was globally higher in LowMAP group and correlated with hemodynamics. TNFα in liver tissue and portal vein serum correlated with intra-abdominal pressure (IAP).In the second study, the cytokine concentration was higher in serum in the MV group. MV did not increase abdominal edema or inflammation, compared to spontaneous breathing. Discussion and conclusion: Abdominal edema and inflammation are multifactorial phenomena, and many elements have to be included in the analysis. Perfusion plays an important role in determining inflammation and IAP. MV per se was not found to be related to increased edema and inflammation. In a previous study, the role of different levels of PEEP and different respiratory rate between mechanically ventilated and spontaneously breathing animals were not analyzed, but could have contributed to the results. The efforts made in this study to maintain similar respiratory rate and PEEP in both groups, could have contributed to the presented results.It is important to underline that, even if MV was not related to inflammation in abdomen, it was related to an increase in systemic inflammation, most probably because of an enhanced lung production of inflammatory mediators.Further studies, focusing on the role of respiratory rate and PEEP on abdomen, as well as the analysis of the inter-relations among inflammation, perfusion and edema, are needed to increase the pathophysiological understanding of these phenomena.

  • 225.
    Marchesi, Silvia
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Ortiz-Nieto, Francisco
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Ahlgren, Kerstin M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Roneus, Agneta
    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.
    Feinstein, Ricardo
    Statens Veterinärmedicinska Anstalt, Uppsala, Sweden.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Larsson, Anders
    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.
    Ahlström, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Hedenstierna, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Abdominal organ perfusion and inflammation in experimental sepsis: a magnetic resonance imaging study2019Ingår i: American Journal of Physiology - Gastrointestinal and Liver Physiology, ISSN 0193-1857, E-ISSN 1522-1547, Vol. 316, nr 1, s. G187-G196Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Diffusion-weighted magnetic resonance imaging (DW-MRI) uses water as contrast and enables the study of perfusion in many organs simultaneously in situ. We used DW-MRI in a sepsis model, comparing abdominal organs perfusion with global hemodynamic measurements and inflammation. Sixteen anesthetized piglets were randomized into 3 groups: HighMAP (mean arterial pressure, MAP > 65 mmHg), LowMAP (MAP between 50 and 60 mmHg) and Healthy Controls (HC). Sepsis was obtained with endotoxin and the desired MAP maintained with noradrenaline. After 6 hours DW-MRI was performed. Acute inflammation was assessed with IL-6 and TNFα in abdominal organs, ascites, and blood and by histology of intestine (duodenum). Perfusion of abdominal organs was reduced in the LowMAP group compared to the HighMAP group and HC. Liver perfusion was still reduced by 25% in the HighMAP group compared with HC. Intestinal perfusion did not differ significantly between the study groups. Cytokines concentration were generally higher in the LowMAP group but did not correlate with global hemodynamics. However, cytokines correlated with regional perfusion and, for liver and intestine, also with intra-abdominal pressure. Histopathology of intestine worsened with decreasing perfusion. In conclusion, although a low MAP (≤60 mmHg) indicated impeded abdominal perfusion in experimental sepsis, it did not predict inflammation, nor did other global measures of circulation. Decreased abdominal perfusion predicted partially inflammation but intestine, occupying most of the abdomen, and liver, were also affected by intra-abdominal pressure.

  • 226.
    Martensson, J.
    et al.
    Austin Hosp, Dept Intens Care, Melbourne, Vic 3084, Australia.;Karolinska Inst, Sect Anesthesia & Intens Care Med, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Glassford, N. J.
    Austin Hosp, Dept Intens Care, Melbourne, Vic 3084, Australia.;Monash Univ, Sch Prevent Med & Publ Hlth, Australian & New Zealand Intens Care Res Ctr, Melbourne, Vic 3004, Australia..
    Jones, S.
    Austin Hosp, Dept Intens Care, Melbourne, Vic 3084, Australia..
    Eastwood, G. M.
    Austin Hosp, Dept Intens Care, Melbourne, Vic 3084, Australia.;Deakin Univ, Sch Nursing & Midwifery, Melbourne, Vic 3004, Australia..
    Young, H.
    Austin Hosp, Dept Intens Care, Melbourne, Vic 3084, Australia..
    Peck, L.
    Austin Hosp, Dept Intens Care, Melbourne, Vic 3084, Australia..
    Ostland, V.
    Intrins LifeSci LLC, La Jolla, CA USA..
    Westerman, M.
    Intrins LifeSci LLC, La Jolla, CA USA..
    Venge, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Bellomo, R.
    Austin Hosp, Dept Intens Care, Melbourne, Vic 3084, Australia.;Monash Univ, Sch Prevent Med & Publ Hlth, Australian & New Zealand Intens Care Res Ctr, Melbourne, Vic 3004, Australia..
    Urinary neutrophil gelatinase-associated lipocalin to hepcidin ratio as a biomarker of acute kidney injury in intensive care unit patients2015Ingår i: Minerva Anestesiologica, ISSN 0375-9393, E-ISSN 1827-1596, Vol. 81, nr 11, s. 1192-1200Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background. Labile iron is important in the pathogenesis of acute kidney injury (AKI). Neutrophil gelatinase-associated lipocalin (NGAL) and hepcidin control iron metabolism and are upregulated during renal stress. However, higher levels of urinary NGAL are associated with AKI severity whereas higher urinary hepcidin levels are associated with absence of AKI. We aimed to investigate the value of combining both biomarkers to estimate the severity and progression of AKI in intensive care unit (ICU) patients. Methods. Urinary NGAL and hepcidin were quantified within 48 hours of ICU admission in patients with the systemic inflammatory response syndrome and early kidney dysfunction (oliguria for >= 2 hours and/or a 25 mu mol/L creatinine rise from baseline). Diagnostic and prognostic characteristics were assessed by logistic regression and receiver operating characteristics (ROC) analysis. Results. Of 102 patients, 26 had mild AKI and 28 patients had severe AKI on admission. Sepsis (21%), cardiac surgery (17%) and liver failure (9%) were primary admission diagnoses. NGAL increased (P=0.03) whereas hepcidin decreased (P=0.01) with increasing AKI severity. The value of NGAL/hepcidin ratio to detect severe AKI was higher than when NGAL and hepcidin were used individually and persisted after adjusting for potential confounders (adjusted OR 2.40, 95% CI 1.20-4.78). The ROC areas for predicting worsening AKI were 0.50, 0.52 and 0.48 for NGAL, 1/hepcidin and the NGAL/hepcidin ratio. Conclusion. The NGAL/hepcidin ratio is more strongly associated with severe AKI than the single biomarkers alone. NGAL and hepcidin, alone or combined as a ratio, were unable to predict progressive AKI in this selected ICU cohort.

  • 227.
    May, Teresa L.
    et al.
    Maine Med Ctr, Dept Crit Care Serv, 22 Bramhall St, Portland, ME 04102 USA;Tufts Univ, Clin & Translat Sci Inst, Boston, MA 02111 USA.
    Lary, Christine W.
    Maine Med Ctr, Ctr Outcomes Res, Portland, ME 04102 USA.
    Riker, Richard R.
    Maine Med Ctr, Dept Crit Care Serv, 22 Bramhall St, Portland, ME 04102 USA.
    Friberg, Hans
    Lund Univ, Dept Anesthesia & Intens Care, Skane Univ Hosp, Lund, Sweden.
    Patel, Nainesh
    Lehigh Valley Hosp & Hlth Network, Div Cardiovasc Med, Allentown, PA USA.
    Soreide, Eldar
    Stavanger Univ Hosp, Crit Care & Anesthesiol Res Grp, Stavanger, Norway;Univ Bergen, Dept Clin Med, Bergen, Norway.
    McPherson, John A.
    Vanderbilt Univ, Med Ctr, Div Cardiovasc Med, Nashville, TN USA.
    Unden, Johan
    Lund Univ, Dept Clin Sci, S-22185 Lund, Sweden;Skane Univ Hosp, Dept Intens & Perioperat Care, Malmo, Sweden.
    Hand, Robert
    Eastern Maine Med Ctr, Dept Crit Care, Bangor, ME USA.
    Sunde, Kjetil
    Oslo Univ Hosp, Dept Anaesthesiol, Div Emergencies & Crit Care, Oslo, Norway;Univ Oslo, Inst Clin Med, Oslo, Norway.
    Stammet, Pascal
    Med Dept Natl Rescue Serv, 14 Rue Stumper, L-2557 Luxembourg, Luxembourg.
    Rubertsson, Sten
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Belohlvaek, Jan
    Charles Univ Prague, Dept Internal Med 2, Cardiovasc Med, Gen Teaching Hosp, Prague, Czech Republic;Charles Univ Prague, Med Sch 1, Prague, Czech Republic.
    Dupont, Allison
    Northeast Georgia Med Ctr, Dept Cardiol, Gainesville, FL USA.
    Hirsch, Karen G.
    Stanford Univ, Sch Med, Dept Neurol & Neurol Surg, Stanford Neurocrit Care Program, Stanford, CA 94305 USA.
    Valsson, Felix
    Landspitali Univ Hosp, Dept Anesthesia & Intens Care, Reykyavik, Iceland.
    Kern, Karl
    Univ Arizona, Div Cardiol, Sarver Heart Ctr, Tucson, AZ USA.
    Sadaka, Farid
    St Louis Univ, Mercy Hosp St Louis, St Louis, MO 63103 USA.
    Israelsson, Johan
    Kalmar Cty Hosp, Dept Internal Med, Div Cardiol, Kalmar, Sweden.
    Dankiewicz, Josef
    Vanderbilt Univ, Med Ctr, Div Cardiovasc Med, Nashville, TN USA;Skane Univ Hosp, Dept Intens & Perioperat Care, Lund, Sweden.
    Nielsen, Niklas
    Lund Univ, Dept Clin Sci Anesthesia & Intens Care, Helsingborg Hosp, Helsingborg, Sweden.
    Seder, David B.
    Maine Med Ctr, Dept Crit Care Serv, 22 Bramhall St, Portland, ME 04102 USA.
    Agarwal, Sachin
    Columbia Presbyterian Med Ctr, Dept Neurol, New York, NY 10032 USA.
    Variability in functional outcome and treatment practices by treatment center after out-of-hospital cardiac arrest: analysis of International Cardiac Arrest Registry2019Ingår i: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 45, nr 5, s. 637-646Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose

    Functional outcomes vary between centers after out-of-hospital cardiac arrest (OHCA) and are partially explained by pre-existing health status and arrest characteristics, while the effects of in-hospital treatments on functional outcome are less understood. We examined variation in functional outcomes by center after adjusting for patient- and arrest-specific characteristics and evaluated how in-hospital management differs between high- and low-performing centers.

    Methods

    Analysis of observational registry data within the International Cardiac Arrest Registry was used to perform a hierarchical model of center-specific risk standardized rates for good outcome, adjusted for demographics, pre-existing functional status, and arrest-related factors with treatment center as a random effect variable. We described the variability in treatments and diagnostic tests that may influence outcome at centers with adjusted rates significantly above and below registry average.

    Results

    A total of 3855 patients were admitted to an ICU following cardiac arrest with return of spontaneous circulation. The overall prevalence of good outcome was 11-63% among centers. After adjustment, center-specific risk standardized rates for good functional outcome ranged from 0.47 (0.37-0.58) to 0.20 (0.12-0.26). High-performing centers had faster time to goal temperature, were more likely to have goal temperature of 33 degrees C, more likely to perform unconscious cardiac catheterization and percutaneous coronary intervention, and had differing prognostication practices than low-performing centers.

    Conclusions

    Center-specific differences in outcomes after OHCA after adjusting for patient-specific factors exist. This variation could partially be explained by in-hospital management differences. Future research should address the contribution of these factors to the differences in outcomes after resuscitation.

  • 228. Meyhoff, Christian S.
    et al.
    Larsson, Anders
    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. Univ Hosp, Uppsala, Sweden.
    Perchiazzi, Gaetano
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Hedenstierna, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    In Reply2018Ingår i: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 128, nr 1, s. 222-224Artikel i tidskrift (Refereegranskat)
  • 229.
    Miclescu, Adriana
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Cerebral Protection in Experimental Cardiopulmonary Resuscitation: With Special Reference to the Effects of Methylene Blue2009Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Although survival rates are increasing, brain injury continues to be a leading cause of death after cardiac arrest (CA). Permanent brain damage after CA is determined by limited tolerance to ischemia from CA and cardiopulmonary resuscitation (CPR), as well as the unique cerebral response to reperfusion after return of spontaneous circulation (ROSC). A major pathway leading to neurotoxic cascade and neuronal injury after CA involves the increased presence of reactive oxygen and nitrogen species generated during ischemia and reperfusion. The magnitude of cerebral oxidative injury induced by free radicals increased with the duration of CA (Paper I). Nitric oxide (NO), a free radical responsible for the formation of reactive nitrogen species, is increased during global ischemia from CA and reperfusion (Paper IV). Hypothetically, the administration of a drug that counteracts the overproduction of NO and also acts as a scavenger of oxygen free radicals might be warranted in order to reduce the damage caused by nitrosative and oxidative stress. For these purposes we used methylene blue (MB), an old dye that has been used in medicine for almost half a century, and an experimental pig model of 20 min of ventricular fibrillation (VF) to reflect a clinical scenario of ischemia/reperfusion injury. Administration of MB added to a hypertonic-hyperoncotic solution (MBHSD) that was started during CPR and continued for 50 min after ROSC increased short-term survival by decreasing myocardial damage, as well as cerebral peroxidation and inflammatory injury (Paper II). Immunostaining of cerebral tissue collected at different time points after CA and ROSC (Paper IV) provided experimental evidence that cortical blood-brain barrier (BBB) disruption begins as early as  during the initial phase of untreated as well as treated CA. The results indicated that MB administration reduced the neurologic injury and BBB disruption considerably, but did not reverse the ongoing detrimental processes. The demonstrated positive effects of MB were related to a decrease of nitrite/nitrate tissue content, and thus to a decrease of excess NO due to the MB inhibitory effects on NOS isoforms. A mixture of MB in hypertonic sodium lactate (MBL) was investigated to facilitate administration of MB in “the field.” Based on findings that MBL cardio- and neuroprotective properties were similar to those of MBHSD, there is reason to believe that the use of MBL might be extended during ongoing CPR and after ROSC (Paper III). It would therefore make sense to try using MB as a pharmacological neuroprotectant during or after clinical CPR in order to expand the temporal therapeutic window before other measures for neuroprotection such as hypothermia are available.

    Delarbeten
    1. Evidence for Time-dependent Maximum Increase ofFree Radical Damage and Eicosanoid Formation in theBrain as Related to Duration of Cardiac Arrest andCardio-pulmonary Resuscitation
    Öppna denna publikation i ny flik eller fönster >>Evidence for Time-dependent Maximum Increase ofFree Radical Damage and Eicosanoid Formation in theBrain as Related to Duration of Cardiac Arrest andCardio-pulmonary Resuscitation
    Visa övriga...
    2003 (Engelska)Ingår i: Free radical research, ISSN 1071-5762, E-ISSN 1029-2470, Vol. 37, nr 3, s. 251-256Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Recovery of neurological function in patients following cardiac arrest and cardiopulmonary resuscitation (CPR) is a complex event. Free radical induced oxidative stress is supposed to be involved in this process. We studied levels of 8-iso-PGF2alpha (indicating oxidative injury) and 15-keto-dihydro-PGF2alpha (indicating inflammatory response) in venous plasma obtained from the jugular bulb in a porcine model of experimental cardiopulmonary resuscitation (CPR) where 2, 5, 8, 10 or 12 min of ventricular fibrillation (VF) was followed by 5 or 8 min of closed-chest CPR. A significant increase of 8-iso-PGF2alpha was observed immediately following restoration of spontaneous circulation in all experiments of various duration of VF and CPR. No such increase was seen in a control group. When compared between the groups there was a duration-dependent maximum increase of 8-iso-PGF2alpha which was greatest in animals subjected to the longest period (VF12 min + CPR8 min) of no or low blood flow. In contrast, the greatest increase of 15-keto-dihydro-PGF2alpha was observed in the 13 min group (VF8 min + CPR5 min). Thus, a time-dependent cerebral oxidative injury occurs in conjunction which cardiac arrest and CPR.

    Nyckelord
    Ischemia reperfusion, Prostaglandins, Isoprostanes
    Nationell ämneskategori
    Anestesi och intensivvård
    Identifikatorer
    urn:nbn:se:uu:diva-106804 (URN)10.1080/1071576021000043058 (DOI)12688420 (PubMedID)
    Tillgänglig från: 2009-07-06 Skapad: 2009-07-04 Senast uppdaterad: 2017-12-13Bibliografiskt granskad
    2. Cardio-cerebral and metabolic effects of methylene blue in hypertonic sodium lactate during experimental cardiopulmonary resuscitation
    Öppna denna publikation i ny flik eller fönster >>Cardio-cerebral and metabolic effects of methylene blue in hypertonic sodium lactate during experimental cardiopulmonary resuscitation
    2007 (Engelska)Ingår i: Resuscitation, ISSN 0300-9572, E-ISSN 1873-1570, Vol. 75, nr 1, s. 88-97Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    BACKGROUND: Methylene blue (MB) administered with a hypertonic-hyperoncotic solution reduces the myocardial and cerebral damage due to ischaemia and reperfusion injury after experimental cardiac arrest and also increases short-term survival. As MB precipitates in hypertonic sodium chloride, an alternative mixture of methylene blue in hypertonic sodium lactate (MBL) was developed and investigated during and after cardiopulmonary resuscitation (CPR). METHODS: Using an experimental pig model of cardiac arrest (12 min cardiac arrest and 8 min CPR) the cardio-cerebral and metabolic effects of MBL (n=10), MB in normal saline (MBS; n=10) or in hypertonic saline dextran (MBHSD; n=10) were compared. Haemodynamic variables and cerebral cortical blood flow (CCBF) were recorded. Biochemical markers of cerebral oxidative injury (8-iso-PGF2alpha), inflammation (15-keto-dihydro-PGF2alpha), and neuronal damage (protein S-100beta) were measured in blood from the sagittal sinus, whereas markers of myocardial injury, electrolytes, and lactate were measured in arterial plasma. RESULTS: There were no differences between groups in survival, or in biochemical markers of cerebral injury. In contrast, the MBS group exhibited not only increased CKMB (P<0.001) and troponin I in comparison with MBHSD (P=0.019) and MBL (P=0.037), but also greater pulmonary capillary wedge pressure 120 min after return of spontaneous circulation (ROSC). Lactate administration had an alkalinizing effect started 120 min after ROSC. CONCLUSIONS: Methylene blue in hypertonic sodium lactate may be used against reperfusion injury during experimental cardiac arrest, having similar effects as MB with hypertonic saline-dextran, but in addition better myocardial protection than MB with normal saline. The neuroprotective effects did not differ.

    Nyckelord
    Cardiopulmonary resuscitation, Dextran, Hypertonic solutions, Methylene blue, Oxidative injury, Sodium lactate
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-16049 (URN)10.1016/j.resuscitation.2007.03.014 (DOI)000250265300013 ()17482336 (PubMedID)
    Tillgänglig från: 2008-05-31 Skapad: 2008-05-31 Senast uppdaterad: 2017-12-08Bibliografiskt granskad
    3. Methylene blue added to a hypertonic-hyperoncotic solution increases short-term survival in experimental cardiac arrest
    Öppna denna publikation i ny flik eller fönster >>Methylene blue added to a hypertonic-hyperoncotic solution increases short-term survival in experimental cardiac arrest
    2006 (Engelska)Ingår i: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 34, nr 11, s. 2806-2813Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    OBJECTIVE: Methylene blue (MB), a free-radical scavenger inhibiting the production and actions of nitric oxide, may counteract excessive vasodilatation induced by nitric oxide during cardiac arrest. Effects of MB in cardiac arrest and cardiopulmonary resuscitation were investigated. DESIGN: Randomized, prospective, laboratory animal study. SETTING: University animal research laboratory. SUBJECTS: A total of 63 piglets of both sexes. INTERVENTIONS: A pig model of extended cardiac arrest (12 mins of untreated cardiac arrest and 8 mins of cardiopulmonary resuscitation) was employed to assess the addition or no addition of MB to a hypertonic saline-dextran solution. These two groups (MB and hypertonic saline-dextran group [MB group] and hypertonic saline-dextran-only group) of 21 animals were each compared with a group receiving isotonic saline (n = 21). MEASUREMENTS AND MAIN RESULTS: Although the groups were similar in baseline values, 4-hr survival in the MB group was increased (p = .02) in comparison with the isotonic saline group. Hemodynamic variables were somewhat improved at 15 mins after restoration of spontaneous circulation in the MB group compared with the other two groups. The jugular bulb levels of 8-isoprostane-prostaglandin F2alpha and 15-keto-dihydro-prostaglandin F2alpha (indicators of peroxidation and inflammation) were significantly decreased in the MB group compared with the isotonic saline group. Significant differences were recorded between the three groups in levels of protein S-100beta (indicator of neurologic injury), with lower levels in the MB group compared with the isotonic saline and hypertonic saline-dextran-only groups. Troponin I and myocardial muscle creatine kinase isoenzyme arterial concentrations (indicators of myocardial damage) were also significantly lower in the MB group. CONCLUSIONS: MB co-administered with a hypertonic-hyperoncotic solution increased 4-hr survival vs. saline in an experimental porcine model of cardiac arrest and reduced oxidative, inflammatory, myocardial, and neurologic injury.

    Nyckelord
    experimental cardiac arrest, methylene blue, saline hypertonic, circulation, survival, organ injury
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-106803 (URN)10.1097/01.CCM.0000242517.23324.27 (DOI)000241639900014 ()16957637 (PubMedID)
    Tillgänglig från: 2009-07-06 Skapad: 2009-07-04 Senast uppdaterad: 2017-12-13Bibliografiskt granskad
    4. Methylene blue administration during cardio-pulmonary resuscitation and early reperfusion protects against cortical blood-brain barrier disruption
    Öppna denna publikation i ny flik eller fönster >>Methylene blue administration during cardio-pulmonary resuscitation and early reperfusion protects against cortical blood-brain barrier disruption
    (Engelska)Manuskript (preprint) (Övrig (populärvetenskap, debatt, mm))
    Abstract [en]

    Objective: The present study was designed to study the effects of cardiac arrest and cardiopulmonary resuscitation (CPR) on blood-brain barrier (BBB) permeability and subsequent neurological injury. It also tests the cerebral effects of MB on the maintenance of BBB integrity, the production of nitric oxide (NO) and regulation of nitric oxide synthases (NOS) in cerebral cortex.

    Intervention: The control group (CA, n=16) underwent 12 min cardiac arrest without subsequent CPR, after which the brain of the animals was removed immediately or after 15 and 30 min. The other two groups with 12 min cardiac arrest and subsequent 8 min CPR received either an infusion of saline (CA-MB group, n=10) or an infusion of saline with MB (CA+MB, n= 12) started one minute after the start of CPR and continued 50 min after return of spontaneous circulation (ROSC).  In both the latter (CA-MB and CA+MB) groups the brains were removed for histological analysis at the following time points: 30, 60, 180 min after ROSC.

    Main Results: In all the groups an increase of necrotic neurons and albumin immunoreactivity was demonstrated with increasing duration of ischemia and reperfusion time. The immunohistochemistry analysis indicated less blood brain barrier disruption in the animals receiving MB (CA+MB group) evidenced by decreased albumin leakage (P<0.01), water content (P=0.02), potassium (P=0.04), but also decreased neuronal injury (P<0.001) in this group in comparison with the group that was not treated with MB (CA-MB). Similarly, MB treatment reduced nitrite/nitrate ratio (P=0.02), iNOS expression (P<0.01), nNOS expression (P<0.01).

    Conclusion: Cerebral edema, increase BBB permeability and neurologic injury are observed early in ischemia induced by cardiac arrest. MB markedly reduced BBB disruption and subsequent neurologic injury. These cerebral cortical effects after the exposure to MB appear to be associated with a decrease of NO measured by nitrate/nitrite and different effects on NOS.

    Nyckelord
    Methylene blue, blood brain barrier, cardiopulmonary resuscitation, cardiac arrest, nitric oxide, nitric oxide synthases
    Nationell ämneskategori
    Anestesi och intensivvård Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-106805 (URN)
    Tillgänglig från: 2009-07-06 Skapad: 2009-07-04 Senast uppdaterad: 2015-06-09Bibliografiskt granskad
  • 230.
    Miclescu, Adriana
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Cerebral protection in experimental cardiopulmonary resuscitation (with special references to the effects of methylene blue)2010Övrigt (Övrigt vetenskapligt)
  • 231.
    Miclescu, Adriana
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    The switch from buprenorphine to tapentadol: is it worth?2016Ingår i: Romanian Journal of Anaesthesia and Intensive Therapy, ISSN 2392-7518, Vol. 23, nr 2, s. 133-139Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Opioid analgesia continues to be the primary pharmacologic intervention for managing acute pain and malignant pain in both hospitalized and ambulatory patients. The increasing use of opioids in chronic nonmalignant pain is more problematic. Opioid treatment is complicated with the risks raised by adverse effects, especially cognitive disturbance, respiratory depression but also the risk of tolerance, opioid abuse and drug–disease interactions. Despite the growing number of available opioids within the last years, adequate trials of opioid rotation are lacking and most of the information is anecdotal. This article reviews the clinical evidence surrounding the switch from transdermal buprenorphine to tapentadol in malignant and non-malignant pain. Tapentadol acts on both the µ-opioid receptors (MOR) and on the neuronal reuptake of noradrenaline with a limited usefulness in acute pain management while buprenorphine is a mixed agonistantagonist, and both present some advantages over other opioids. Both drugs show particular pharmacodynamic and pharmacokinetic properties which reduce the risks of development of tolerance, opioid abuse, diversion and determine fewer hormone changes than the “classical opioids” making these opioids more attractive than other opioids in long term opioid treatment. However, in the absence of powered clinical trials, the evidence to support the method used for transdermal buprenorphine rotation to tapentadol is weak.

  • 232.
    Miclescu, Adriana
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Butler, Stephen
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och preventivmedicin.
    Karlsten, Rolf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    The changing face of the acute pain2016Konferensbidrag (Övrigt vetenskapligt)
    Abstract [en]

    Aims: To distinguishthe risk factors associated with uncontrolled and problematic pain by prospectively assessing the current acute pain service (APS) activity in an academic hospital and theeffects of this activity on both surgical and medical pain intensity.

    Method: This prospective cohort study was conducted at Uppsala University Hospital (a Swedish tertiary and quaternary care hospital) during one year. All the patients referred to APS team were enrolled. A standardized data collection template of demographic data, medical history, pain diagnosis, associated diseases, duration of treatment, number of visits by the APS team and type of treatment was employed. The primary outcomes were pain scores before and after treatment. The patients were visited by APS at regular intervals and divided after the number of visits by APS team in several groups: group 1 (one visit and upto 2 follow ups); group 2 (3 to 4 follow-ups); group 3(5 to 10times follow-ups); group 4 (10 to 20 follow-ups); group 5 more than 20 follow–ups. The groups and the difference between groups were analyzed.

    Results: Patients (n=730) (mean age 56±4, female 58%, men 42%) were distributed by service to medical (41%) and surgical (58%). Of these, 48% of patients reported a pain score of moderate to severe pain and 27% reported severe pain on the first assessment. On the last examination before discharge, they reported 25–30% less pain (P=0.002). The median NRS (numerical rating scores) decreased significantly from 9.6 (95% confidence interval, 3.4–5.3) to 6.3 (1.0–2.0) for the severe pain (p<0.0001), from 3.8 (3.1–3.8) to 2.4 (2.2–2.4) for the mild pain. Respiratory depression related to pain treatment was reported in 1.6% patients. The APS treated cognitive deficits related to pain treatment, in 30% of the patients, recognized and treated opioid overdose in 14%. The patients who required more than 5 visits by the APS(280 patients representing 38% of all the patients) demonstrated an increased prevalence of psychiatric diseases (from 10% in group 1 to 42% in group 5), opioid dependency (13% in group 1 to 100% in group 5) and chronic painresulted from both nociceptive (gradually increasing from 38% in group 1 to 85% in group 5) and neuropathic pain (from 13 % in group 1 increasing to 35% in group 5). The diagnoses encountered in the patients with frequent visits by the APS team were cancer related pain (17%), endometriosis (9%), reoperation(12%), burn injury(5%).

    Conclusions: Beside the benefits of APS in reducing of pain intensity, and in treating analgesia side effects, this study demonstrates the uncertain role of APS in the treatment of acute pain. The focus of APS has been shifted from the traditional treatment of acute surgical pain to the clinical challenges of treating hospitalized patients who suffered adverse effects from pain treatment and have a high of comorbidities aspsychiatric diseases, opioid dependency and non-surgical chronic pain.

  • 233.
    Miclescu, Adriana
    et al.
    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.
    Nitric oxide and pain: ‘Something old, something new’2009Ingår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 53, nr 9, s. 1107-1120Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Challenges have emerged following the revival of nitric oxide (NO) from “something old”, a simple gas derived from nitrogen and oxygen with a role in the early stages of evolution, into “something new”, an endogenously formed biological mediator regulating a wide variety of physiological functions.  Although pain is a common sensation, it encompasses multiple neurobiologic components of which NO is only one. In pain research, the study of NO is complicated by convoluted problems related mostly to the effects of NO, which are pro- or antinociceptive depending on the circumstances. This dual function reflects the multi-faceted roles of the NO molecule described in physiology. This review covers current information about NO and its implications in pain mechanisms. In addition, it follows the pain pathways, demonstrating the role of NO in peripheral nociceptive transmission as well in central sensitization. This knowledge may provide the scientific basis for developing new drugs that are indicated for different types of pain, drugs that may be related to the chemical links of NO. A comprehensive approach to understanding the effects of NO will help clinicians identify novel agents that combine the pharmacological profile of native drugs with a controllable manner of NO release. Inhibitors of NO synthesis may have analgesic effects and would be of interest for treating inflammatory and neuropathic pain. Unfortunately, only a few of these compounds have reached the stage of clinical pain trials.

  • 234.
    Miclescu, Adriana
    et al.
    Multidisciplinary Pain Center, Uppsala University Hospital, Sweden.
    Schmelz, Martin
    Gordh, Torsten
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Differential analgesic effects of local lidocaine on spontaneous and evoked pain in neuropathic pain: A double blind, randomized controlled study2015Ingår i: Scandinavian Journal of Pain, ISSN 1877-8860, E-ISSN 1877-8879, Vol. 8, s. 37-44Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background

    Both peripheral nerve injury and neuroma pain are the result of changes in sodium channel expression. Lidocaine selectively inhibits the spontaneous ectopic activity by binding to sodium channels. Subanesthetics concentrations of lidocaine are able to produce a differential block of the ectopic discharges, but not propagation of impulses, suppressing differentially the associated neuropathic pain symptoms. The aim of this study was to investigate the differences between the analgesic effects of lidocaine 0.5% and a control group of lidocaine 0.1% on several neuroma related pain modalities.

    Methods

    Sixteen patients with neuropathic pain due to painful neuromas caused by nerve injury participated in this randomized, double-blind experiment. The patterns of sensory changes were compared before and after injection of 1 ml lidocaine 0.5% and 0.1% close to the neuroma, the sessions being 1–2 weeks apart. Spontaneous and evoked pains were assessed using a visual analogue scale (VAS), quantitative and qualitative sensory testing. The primary end-point measure was defined as the change in pain score measured from baseline until 60 min after injection. Assessments of spontaneous pain and evoked pain were done post injection at 15 s, 30 s, 1 min, and at 5-min intervals for the first 30-min post injection and then every 10-min to 1 hr post injection. The assessments of pain were performed between the limbs in the following order: spontaneous pain, then assessment of dynamic mechanical allodynia and then hyperalgesia.

    Results

    Lidocaine dose-dependently reduced spontaneous and evoked pain scores by more than 80% with maximum effects between 1 and 5 min for evoked pain and between 3 and 15 min for spontaneous pain. While evoked pain normalized rapidly reaching about 50% of the control level 20 min after the injection, spontaneous pain levels continue to be lower in comparison with baseline values for more than 60 min. When comparing the time course of analgesia between spontaneous and evoked pain, lidocaine-induced a greater reduction of evoked pain, but with shorter duration than spontaneous pain. The differences between evoked pain and spontaneous pain were statistically significant in both groups (lidocaine 0.5% group; p = 0.02 and lidocaine 0.1% group; p = 0.01). Reproducibility was high for all assessed variables. Surprisingly, both lidocaine concentrations produced a sensory loss within the area with hyperalgesia and allodynia: hypoesthesia occurred earlier and lasted longer with lidocaine 0.5% (between 30 s and 5 min) in comparison with lidocaine 0.1% (p = 0.018).

    Conclusion

    Differential analgesic effects of subanesthetic concentrations of local lidocaine on evoked and spontaneous pain in human neuroma suggest that different mechanisms underlie these two key clinical symptoms. Spontaneous pain and evoked pain need an ongoing peripheral drive and any possible CNS amplification change is temporally closely related to this peripheral input.

    Implications

    Painful neuroma represents a clinical model of peripheral neuropathic pain that could lead to a significant step forward in the understanding of pain pathophysiology providing the opportunity to study spontaneous and evoked pain and the underlying mechanisms of neuropathic pain. The proposed model of neuropathic pain allows testing new substances by administration of analgesics directly where the pain is generated.

  • 235.
    Miclescu, Adriana
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Sharma, Hari Shanker
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Martijn, Cécile
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Wiklund, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Methylene blue administration during cardio-pulmonary resuscitation and early reperfusion protects against cortical blood-brain barrier disruptionManuskript (preprint) (Övrig (populärvetenskap, debatt, mm))
    Abstract [en]

    Objective: The present study was designed to study the effects of cardiac arrest and cardiopulmonary resuscitation (CPR) on blood-brain barrier (BBB) permeability and subsequent neurological injury. It also tests the cerebral effects of MB on the maintenance of BBB integrity, the production of nitric oxide (NO) and regulation of nitric oxide synthases (NOS) in cerebral cortex.

    Intervention: The control group (CA, n=16) underwent 12 min cardiac arrest without subsequent CPR, after which the brain of the animals was removed immediately or after 15 and 30 min. The other two groups with 12 min cardiac arrest and subsequent 8 min CPR received either an infusion of saline (CA-MB group, n=10) or an infusion of saline with MB (CA+MB, n= 12) started one minute after the start of CPR and continued 50 min after return of spontaneous circulation (ROSC).  In both the latter (CA-MB and CA+MB) groups the brains were removed for histological analysis at the following time points: 30, 60, 180 min after ROSC.

    Main Results: In all the groups an increase of necrotic neurons and albumin immunoreactivity was demonstrated with increasing duration of ischemia and reperfusion time. The immunohistochemistry analysis indicated less blood brain barrier disruption in the animals receiving MB (CA+MB group) evidenced by decreased albumin leakage (P<0.01), water content (P=0.02), potassium (P=0.04), but also decreased neuronal injury (P<0.001) in this group in comparison with the group that was not treated with MB (CA-MB). Similarly, MB treatment reduced nitrite/nitrate ratio (P=0.02), iNOS expression (P<0.01), nNOS expression (P<0.01).

    Conclusion: Cerebral edema, increase BBB permeability and neurologic injury are observed early in ischemia induced by cardiac arrest. MB markedly reduced BBB disruption and subsequent neurologic injury. These cerebral cortical effects after the exposure to MB appear to be associated with a decrease of NO measured by nitrate/nitrite and different effects on NOS.

  • 236.
    Miclescu, Adriana
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Sharma, Hari Shanker
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Martijn, Cécile
    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.
    Methylene blue protects the cortical blood-brain barrier against ischemia/reperfusion-induced disruptions2010Ingår i: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 38, nr 11, s. 2199-2206Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: To investigate the effects of cardiac arrest and the reperfusion syndrome on blood-brain barrier permeability and evaluate whether methylene blue counteracts blood-brain barrier disruption in a pig model of controlled cardiopulmonary resuscitation. Design: Randomized, prospective, laboratory animal study. Setting: University-affiliated research laboratory. Subjects: Forty-five piglets. Interventions: Forty-five anesthetized piglets were subjected to cardiac arrest alone or 12-min cardiac arrest followed by 8 mins cardiopulmonary resuscitation. The first group (n = 16) was used to evaluate blood-brain barrier disruptions after untreated cerebral ischemia after 0, 15, or 30 mins after untreated cardiac arrest. The other two groups received either an infusion of saline (n = 10) or infusion of saline with methylene blue (n = 12) 1 min after the start of cardiopulmonary resuscitation and continued 50 mins after return of spontaneous circulation. In these groups, brains were removed for immunohistological analyses at 30, 60, and 180 mins after return of spontaneous circulation. Measurements and Main Results: An increase of injured neurons and albumin immunoreactivity was demonstrated with in-creasing duration of ischemia/reperfusion. Less blood-brain barrier disruption was observed in subjects receiving methylene blue as demonstrated by decreased albumin leakage (p<.01), water content (p<.05), and neuronal injury (p<.01). Methylene blue treatment reduced cerebral tissue nitrite/nitrate content (p<.05) and the number of inducible and neuronal nitric oxide synthase-activated cortical cells during administration (p<.01). Meanwhile, the number of cortical endothelial nitric oxide synthase-activated cells increased over time (p<.001). Conclusion: Cerebral tissue water content, blood-brain barrier permeability and neurologic injury were increased early in reperfusion after cardiac arrest. Methylene blue exerted neuroprotective effects against the brain damage associated with the ischemia/reperfusion injury and ameliorated the blood-brain barrier disruption by decreasing nitric oxide metabolites. (Crit Care Med 2010; 38: 2199-2206)

  • 237.
    Miclescu, Adriana
    et al.
    Multidisciplinary Pain Clinic, Uppsala University Hospital, Sweden.
    Svanh, Martin
    Multidisciplinary Pain Clinic, Uppsala University Hospital, Sweden.
    Gordh, Torsten
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Evaluation of the protein biomarkers and the analgesic response to systemic methylene blue in patients with refractory neuropathic pain: a double blind, controlled study2015Ingår i: Journal of Pain Research, ISSN 1178-7090, E-ISSN 1178-7090, Vol. 8, s. 387-397Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aim:

    This study was carried out in patients with neuropathic pain in order to assess the analgesic effects and changes in protein biomarkers after the administration of methylene blue (MB), a diaminophenothiazine with antioxidant and anti-inflammatory properties, and with inhibitory effects on nitric oxide.

    Materials and methods:

    Ten patients with chronic refractory neuropathic pain were randomized to receive either MB (10 mg/mL Methylthioninium chloride) 2 mg/kg (MB group) or MB 0.02 mg/kg (control group) infused over 60 minutes. Sensory function and pain (Numerical Rating Scale) were evaluated at baseline and at 60 minutes after the start of the infusion. The patients kept a pain diary during the next 24 hours and for the following 4 days. Plasma and urinary concentrations of 8-isoprostane-prostaglandin F2α (8-iso-PGF2α) and plasma protein biomarkers prior to and after the infusions were measured with radioimmunoassay and with proximity extension assay.

    Results:

    A decrease of the Numerical Rating Scale at 60 minutes in comparison with baseline was observed in the MB (P=0.047) group. The decrease was significant between the MB and the control group on the day of and day after MB infusion (P=0.04 and P=0.008, respectively). There was no difference in systemic protein expressions between groups except for prolactin (PRL) (P=0.02). Three patients demonstrated diminished dynamic mechanical allodynia.

    Conclusion:

    MB decreased the pain levels in patients with chronic therapy-resistant neuropathic pain on the first 2 days after administration. Known as an endocrine modulator on the anterior pituitary gland, MB infusion produced a decrease of PRL. The detailed role of PRL effects in chronic neuropathic pain remains undetermined.

  • 238.
    Miclescu, Adriana
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Walan, Johanna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten.
    Essemark, Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten.
    Karlsten, Rolf
    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.
    Persistent neuropathic pain after nerve suture surgery2016Ingår i: 16Th World Congress of  Pain IASP26-29 Th September Yokohama, Japan, 2016Konferensbidrag (Övrigt vetenskapligt)
    Abstract [en]

    Aim of Investigation: Iatrogenic nerve injury has been proposed as the main factor responsable for long term-postsurgical pain. The prevalence of chronic neuropathic pain after a known somatosensory lesion in the upper extremity nerves followed by suture surgery was determined.

    Methods:The Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) Pain Scale questionnaires were sent out in January 2016 to 1078 patients who underwent nerve repairs operations after traumatic or surgical nerve injuries of the upper limbs between 2006 to 2014 at the Hand Surgery Clinic.

    Results: Three hundred eighty-two patients returned the questionnaire (response rate 35%). Post trauma or post-surgical pain was present in 186 patients (48 %) from those 382 patients who responded to the questionnaire. A total of 87 patients (47 %) of these 186 patients developed chronic pain after the operation. The most common symptom experienced by the patients was the enhanced sensitivity to cold in 69 % of the patients that led to pain and discomfort at temperatures that normally were perceived as being innocuously cool. Other symptoms were diminished sensitivity to stimulation in 55% of the patients and allodynia to light pressure, cold presented in 50% of the patients. The majority of the patients with pain resulting from traumatic or surgical nerve injury (77% of the patients) had no medication for pain, despite the presence of pain more than 50 VAS.

    Conclusions: Persistent neuropathic pain occured in 48% of the patients following nerve suture surgery. Cold intolerance has a high prevalence both in the group of patients with pain and in the group without pain.

  • 239.
    Miclescu, Adriana
    et al.
    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.
    Methylene blue, an old drug with new indications?2010Ingår i: Jurnalul Roman de Anestezie Terapie Intaensiva, ISSN 1582-652X, Vol. 17, nr 1, s. 35-41Artikel, forskningsöversikt (Övrigt vetenskapligt)
    Abstract [en]

    Just when we thought we finally understood methylene blue (MB) after it has been used clinically for more than a century, the old properties are revived and therefore possible new indications appears. Nitric oxide (NO) stimulates soluble guanylate cyclase, which converts guanosine triphosphate into cyclic guanosine monophosphate. Increases in cGMP concentration, in turn, through a cascade of protein kinases, induce smooth muscle relaxation and vasodilation. Methylene blue (MB) has direct inhibitory effects on nitric oxide synthases (NOS), both constitutive and inducible and blocks accumulation of cyclic guanosine monophosphate (cGMP) by inhibiting the enzyme guanylate cyclase. Also, MB blocks the iron-containing enzymes such as xanthine oxidase and has antioxidants effects. New indications are therefore described in relation with MB as in the vasoplegic syndrome following cardiopulmonary bypass in humans and in the settings of cardiac arrest in animals.

  • 240.
    Milton, A.
    et al.
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden;Karolinska Univ Hosp, Dept Perioperat Med & Intens Care, Stockholm, Sweden.
    Schandl, A.
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
    Soliman, I. W.
    Univ Utrecht, Univ Med Ctr Utrecht, Dept Intens Care Med, Utrecht, Netherlands.
    Meijers, K.
    Soder Sjukhuset, Dept Anaesthesiol & Intens Care, Stockholm, Sweden.
    van den Boogaard, M.
    Radboud Univ Nijmegen, Med Ctr, Dept Intens Care Med, Nijmegen, Netherlands.
    Larsson, Ing-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Brorsson, C.
    Umea Univ, Dept Surg & Perioperat Sci, Umea, Sweden.
    Ostberg, U.
    Ostersund Hosp, Dept Anaesthesiol & Intens Care, Ostersund, Sweden.
    Oxenboll-Collet, M.
    Rigshosp Copenhagen, Dept Intens Care, Copenhagen, Denmark.
    Savilampi, J.
    Orebro Univ Hosp, Dept Anaesthesiol & Intens Care, Orebro, Sweden.
    Paskins, S.
    Odense Univ Hosp, Dept Intens Care, Odense, Denmark.
    Bottai, M.
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden.
    Sackey, P. V.
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.
    Development of an ICU discharge instrument predicting psychological morbidity: a multinational study2018Ingår i: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 44, nr 12, s. 2038-2047Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PurposeTo develop an instrument for use at ICU discharge for prediction of psychological problems in ICU survivors.MethodsMultinational, prospective cohort study in ten general ICUs in secondary and tertiary care hospitals in Sweden, Denmark and the Netherlands. Adult patients with an ICU stay12h were eligible for inclusion. Patients in need of neurointensive care, with documented cognitive impairment, unable to communicate in the local language, without a home address or with more than one limitation of therapy were excluded. Primary outcome was psychological morbidity 3months after ICU discharge, defined as Hospital Anxiety and Depression Scale (HADS) subscale score11 or Post-traumatic Stress Symptoms Checklist-14 (PTSS-14) part B score>45.ResultsA total of 572 patients were included and 78% of patients alive at follow-up responded to questionnaires. Twenty percent were classified as having psychological problems post-ICU. Of 18 potential risk factors, four were included in the final prediction model after multivariable logistic regression analysis: symptoms of depression [odds ratio (OR) 1.29, 95% confidence interval (CI) 1.10-1.50], traumatic memories (OR 1.44, 95% CI 1.13-1.82), lack of social support (OR 3.28, 95% CI 1.47-7.32) and age (age-dependent OR, peak risk at age 49-65years). The area under the receiver operating characteristics curve (AUC) for the instrument was 0.76 (95% CI 0.70-0.81).ConclusionsWe developed an instrument to predict individual patients' risk for psychological problems 3months post-ICU, http://www.imm.ki.se/biostatistics/calculators/psychmorb/. The instrument can be used for triage of patients for psychological ICU follow-up.Trial registrationThe study was registered at clinicaltrials.gov, NCT02679157.

  • 241. Moa, Gunnar
    et al.
    Nilsson, Kjell
    Zetterström, Henrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Jonsson, Lars O
    A new device för administration of nasal CPAP in the newborn1988Ingår i: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 16, s. 1238-1242Artikel i tidskrift (Refereegranskat)
  • 242. Moa, Gunnar
    et al.
    Zetterström, Henrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Sublingual buprenorphin as postoperative analgesic - a double blind comparison with pethidine1990Ingår i: Acta Anaesthesiologica Scandinavica, Vol. 34, s. 69-71Artikel i tidskrift (Refereegranskat)
  • 243.
    Mogensen, Stefan
    et al.
    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.
    Nilsson, Pelle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Engquist, Henrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Knutson, Folke
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Nowinski, Daniel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Plastikkirurgi.
    Frykholm, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    An evaluation of the mixed pediatric unit for blood loss replacement in pediatric craniofacial surgery2017Ingår i: Pediatric Anaesthesia, ISSN 1155-5645, E-ISSN 1460-9592, Vol. 27, nr 7, s. 711-717Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Surgical correction for craniosynostosis is often associated with significant perioperative hemorrhage. We implemented a transfusion strategy with a strict protocol including transfusion triggers, frequent assessment of coagulation tests, and the use of a novel transfusion unit, the mixed pediatric unit. Aim: The aim of the study was to evaluate if the applied transfusion strategy could reduce total blood loss and number of blood donors. Methods: Children <1 year old admitted for craniosynostosis surgery were included for the study. On the day before surgery, an adult red blood cell unit was mixed with plasma and split into two mixed pediatric units-one intended for intraoperative use and the other saved for the postoperative period. A series of blood samples were obtained for standard coagulation parameters as well as thromboelastography to evaluate potential coagulopathy. Estimated blood loss, the number of additional standard packed red cell units opened in the first 24 h after surgery, the volume of fluid administered, and the total transfusion volumes were compared to a historical control group with similar age and characteristics. Results: Nineteen infants were included in the study group, and were compared to 21 historical controls. There was a significant reduction of intraoperative transfusion volume. Twelve patients were transfused postoperatively, but in 8 of these additional exposure to packed red cell donor blood was avoided by using the saved mixed pediatric unit. In the historical controls, a total of 10 packed red cell units were used in nine patients postoperatively. No additional transfusions of plasma, platelets, fibrinogen, or tranexamic acid were needed in either group, and the coagulation parameters including thromboelastography remained within their respective normal ranges in the study group. Conclusion: For craniofacial surgery in infants, moderate perioperative blood loss and avoidance of coagulopathy is possible when a multifactorial approach is implemented. In this setting, intraoperative, but not total perioperative blood loss was reduced with the studied protocol. The study indicates that there may be a role for mixed pediatric units to reduce exposure to multiple donors although the reduction in total donor exposure was not significant.

  • 244.
    Molnar, Maria
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Lindblom, Rickard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Thoraxkirurgi.
    Israelsson, Charlotte
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Fridman, Belinda
    Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Wiklund, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Lennmyr, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Differential regulation of cerebral metabolic genes after hyperglycemic and normoglycemic cardiac arrestManuskript (preprint) (Övrigt vetenskapligt)
  • 245.
    Monge Garcia, Manuel Ignacio
    et al.
    Hosp SAS Jerez, Serv Cuidados Intens, C Circunvalac S-N, Jerez de la Frontera 11407, Spain.
    Santos, Arnoldo
    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. CIBER Enfermedades Resp CIBERES, Avd Monforte de Lemos 3-5,Pabellon 11,Planta 0, Madrid 28029, Spain.
    Diez Del Corral, Beatriz
    Hosp SAS Jerez, Serv Cuidados Intens, C Circunvalac S-N, Jerez de la Frontera 11407, Spain.
    Guijo Gonzalez, Pedro
    Hosp SAS Jerez, Serv Cuidados Intens, C Circunvalac S-N, Jerez de la Frontera 11407, Spain.
    Gracia Romero, Manuel
    Hosp SAS Jerez, Serv Cuidados Intens, C Circunvalac S-N, Jerez de la Frontera 11407, Spain.
    Gil Cano, Anselmo
    Hosp SAS Jerez, Serv Cuidados Intens, C Circunvalac S-N, Jerez de la Frontera 11407, Spain.
    Cecconi, Maurizio
    St Georges Univ London, London SW17 0QT, England;St Georges Healthcare NHS Trust, Dept Intens Core Med, London SW17 0QT, England.
    Noradrenaline modifies arterial reflection phenomena and left ventricular efficiency in septic shock patients: A prospective observational study2018Ingår i: Journal of critical care, ISSN 0883-9441, E-ISSN 1557-8615, Vol. 47, s. 280-286Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: To determine whether noradrenaline alters the arterial pressure reflection phenomena in septic shock patients and the effects on left ventricular (LV) efficiency.

    Material and methods: Thirty-seven septic shock patients with a planned change in noradrenaline dose. Timing and magnitude (Reflection Magnitude and Augmentation Index) of arterial reflections were evaluated. Total, steady, and oscillatory LV power (also expressed as fraction of the total power), subendocardial viability ratio (SEVR), energy efficiency and transmission ratios were used as a marker of LV efficiency.

    Results: An incremental change in noradrenaline increased Reflection Magnitude [0.28(0.09) to 0.31(0.1], Augmentation Index [-6.4(23.6) to 4.8(20.7)%], and LV total power [0.79(IQR:0.47-1) to 0.98(IQR:0.57-127) W], all p < 0.001; whereas decreased arrival time of reflected waves [from 95(87 to 121) to 83(79 to 101)ms; p < 0.001]. Variables of LV performance showed a decreased efficiency: oscillatory fraction and energy efficiency ratio increased [20.9(5.7) to 22.8(4.9)%, and 82(1.7) to 10.1(2) mW.min.litre(-1); p < 0.001, respectively]; and energy transmission ratio and SEVR decreased [73.8(9.9) to 72(9.8)% and 146(IQR:113-188) to 143 (IQR:109-172)%, p = 0.003 and p = 0.041, respectively].

    Conclusions: Noradrenaline increased reflection phenomena, increasing LV workload and worsening LV performance in septic shock patients. These conditions could explain the detrimental effects during long-term use of noradrenaline.

  • 246.
    Morais, Caio C. A.
    et al.
    Univ Sao Paulo, Fac Med, Hosp Clin, Div Pneumol,Inst Coracao Incor, Sao Paulo, Brazil.
    Koyama, Yukiko
    Osaka Univ Hosp, Intens Care Unit, Suita, Osaka, Japan.
    Yoshida, Takeshi
    Osaka Univ Hosp, Intens Care Unit, Suita, Osaka, Japan;Univ Toronto, Hosp Sick Children, Dept Crit Care Med & Anesthesia, Translat Med, 686 Bay St, Toronto, ON M5G 0A4, Canada.
    Plens, Glauco M.
    Univ Sao Paulo, Fac Med, Hosp Clin, Div Pneumol,Inst Coracao Incor, Sao Paulo, Brazil.
    Gomes, Susimeire
    Univ Sao Paulo, Fac Med, Hosp Clin, Div Pneumol,Inst Coracao Incor, Sao Paulo, Brazil.
    Lima, Cristhiano A. S.
    Univ Sao Paulo, Fac Med, Hosp Clin, Div Pneumol,Inst Coracao Incor, Sao Paulo, Brazil.
    Ramos, Ozires P. S.
    Univ Sao Paulo, Fac Med, Hosp Clin, Div Pneumol,Inst Coracao Incor, Sao Paulo, Brazil.
    Pereira, Sergio M.
    Univ Sao Paulo, Fac Med, Hosp Clin, Div Pneumol,Inst Coracao Incor, Sao Paulo, Brazil.
    Kawaguchi, Naomasa
    Osaka Univ, Sch Allied Hlth Sci, Dept Pathol, Grad Sch Med, Suita, Osaka, Japan.
    Yamamoto, Hirofumi
    Osaka Univ, Sch Allied Hlth Sci, Dept Pathol, Grad Sch Med, Suita, Osaka, Japan.
    Uchiyama, Akinori
    Osaka Univ Hosp, Intens Care Unit, Suita, Osaka, Japan.
    Batista Borges, João
    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.
    Melo, Marcos F. Vidal
    Harvard Univ, Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA.
    Tucci, Mauro R.
    Univ Sao Paulo, Fac Med, Hosp Clin, Div Pneumol,Inst Coracao Incor, Sao Paulo, Brazil.
    Amato, Marcelo B. P.
    Univ Sao Paulo, Fac Med, Hosp Clin, Div Pneumol,Inst Coracao Incor, Sao Paulo, Brazil.
    Kavanagh, Brian P.
    Univ Toronto, Hosp Sick Children, Dept Crit Care Med & Anesthesia, Translat Med, 686 Bay St, Toronto, ON M5G 0A4, Canada.
    Costa, Eduardo L. V.
    Univ Sao Paulo, Fac Med, Hosp Clin, Div Pneumol,Inst Coracao Incor, Sao Paulo, Brazil.
    Fujino, Yuji
    Osaka Univ Hosp, Intens Care Unit, Suita, Osaka, Japan.
    High Positive End-Expiratory Pressure Renders Spontaneous Effort Noninjurious2018Ingår i: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 197, nr 10, s. 1285-1296Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Rationale: In acute respiratory distress syndrome (ARDS), atelectatic solid-like lung tissue impairs transmission of negative swings in pleural pressure (Ppl) that result from diaphragmatic contraction. The localization of more negative Ppl proportionally increases dependent lung stretch by drawing gas either from other lung regions (e.g., nondependent lung [pendelluft]) or from the ventilator. Lowering the level of spontaneous effort and/or converting solid-like to fluid-like lung might render spontaneous effort noninjurious.

    Objectives: To determine whether spontaneous effort increases dependent lung injury, and whether such injury would be reduced by recruiting atelectatic solid-like lung with positive end-expiratory pressure (PEEP).

    Methods: Established models of severe ARDS (rabbit, pig) were used. Regional histology (rabbit), inflammation (positron emission tomography; pig), regional inspiratory Ppl (intrabronchial balloon manometry), and stretch (electrical impedance tomography; pig) were measured. Respiratory drive was evaluated in 11 patients with ARDS.

    Measurements and Main Results: Although injury during muscle paralysis was predominantly in nondependent and middle lung regions at low (vs. high) PEEP, strong inspiratory effort increased injury (indicated by positron emission tomography and histology) in dependent lung. Stronger effort (vs. muscle paralysis) caused local overstretch and greater tidal recruitment in dependent lung, where more negative Ppl was localized and greater stretch was generated. In contrast, high PEEP minimized lung injury by more uniformly distributing negative Ppl, and lowering the magnitude of spontaneous effort (i.e., deflection in esophageal pressure observed in rabbits, pigs, and patients).

    Conclusions: Strong effort increased dependent lung injury, where higher local lung stress and stretch was generated; effort-dependent lung injury was minimized by high PEEP in severe ARDS, which may offset need for paralysis.

  • 247.
    Mueller, Christian
    et al.
    Univ Basel Hosp, Dept Cardiol, Basel, Switzerland.;Univ Basel Hosp, Cardiovasc Res Inst Basel, Basel, Switzerland..
    Giannitsis, Evangelos
    Univ Heidelberg Hosp, Heidelberg, Germany..
    Christ, Michael
    Paracelsus Med Univ, Gen Hosp, Dept Emergency & Crit Care Med, Nurnberg, Germany..
    Ordonez-Llanos, Jorge
    Inst Invest Biomed St Pau, Dept Clin Biochem, Barcelona, Spain..
    deFilippi, Christopher
    Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA..
    McCord, James
    Henry Ford Heart & Vasc Inst, Henry Ford Hlth Syst, Detroit, MI USA..
    Body, Richard
    Cent Manchester Univ Hosp NHS Fdn Trust, Manchester, Lancs, England..
    Panteghini, Mauro
    Univ Milan, Sch Med, Dept Biomed & Clin Sci Luigi Sacco, Milan, Italy..
    Jernberg, Tomas
    Karolinska Inst, Dept Med, Huddinge, Sweden..
    Plebani, Mario
    Univ Hosp Padova, Dept Lab Med, Padua, Italy..
    Verschuren, Franck
    Clin Univ St Luc, Dept Acute Med, Brussels, Belgium.;Catholic Univ Louvain, Brussels, Belgium..
    French, John
    Liverpool Hosp, Liverpool, NSW, Australia.;Univ New S Wales, Liverpool, NSW, Australia..
    Christenson, Robert
    Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA..
    Weiser, Silvia
    Roche Diagnost Germany, Penzberg, Germany..
    Bendig, Garnet
    Roche Diagnost Germany, Penzberg, Germany..
    Dilba, Peter
    Roche Diagnost Germany, Penzberg, Germany..
    Lindahl, Bertil
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Multicenter Evaluation of a 0-Hour/1-Hour Algorithm in the Diagnosis of Myocardial Infarction With High-Sensitivity Cardiac Troponin T2016Ingår i: Annals of Emergency Medicine, ISSN 0196-0644, E-ISSN 1097-6760, Vol. 68, nr 1, s. 76-87Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Study objective: We aim to prospectively validate the diagnostic accuracy of the recently developed 0-h/1-h algorithm, using high-sensitivity cardiac troponin T (hs-cTnT) for the early rule-out and rule-in of acute myocardial infarction. Methods: We enrolled patients presenting with suspected acute myocardial infarction and recent (<6 hours) onset of symptoms to the emergency department in a global multicenter diagnostic study. Hs-cTnT (Roche Diagnostics) and sensitive cardiac troponin I (Siemens Healthcare) were measured at presentation and after 1 hour, 2 hours, and 4 to 14 hours in a central laboratory. Patient triage according to the predefined hs-cTnT 0-hour/1-hour algorithm (hs-cTnT beloow 12 ng/L and Delta 1 hour below 3 ng/L to rule out; hs-cTnT at least 52 ng/L r Delta 1 hour at least 5 ng/L to rule in; remaining patients to the "observational zone") was compared against a centrally adjudicated final diagnosis by 2 independent cardiologists (reference standard). The final diagnosis was based on all available information, including coronary angiography and echocardiography results, follow-up data, and serial measurements of sensitive cardiac troponin I, whereas adjudicators remained blinded to hs-cTnT. Results: Among 1,282 patients enrolled, acute myocardial infarction was the final diagnosis for 213 (16.6%) patients. Applying the hs-cTnT 0-hour/1-hour algorithm, 813 (63.4%) patients were classified as rule out, 184 (14.4%) were classified as rule in, and 285 (22.2%) were triaged to the observational zone. This resulted in a negative predictive value and sensitivity for acute myocardial infarction of 99.1% (95% confidence interval [CI] 98.2% to 99.7%) and 96.7% (95% CI 93.4% to 98.7%) in the rule-out zone (7 patients with false-negative results), a positive predictive value and specificity for acute myocardial infarction of 77.2% (95% CI 70.4% to 83.0%) and 96.1% (95% CI 94.7% to 97.2%) in the rule-in zone, and a prevalence of acute myocardial infarction of 22.5% in the observational zone. Conclusion: The hs-cTnT 0-hour/1-hour algorithm performs well for early rule-out and rule-in of acute myocardial infarction.

  • 248.
    Mueller, Christian
    et al.
    Univ Basel Hosp, Dept Cardiol, CH-4031 Basel, Switzerland.;Univ Basel Hosp, Cardiovasc Res Inst Basel, CH-4031 Basel, Switzerland..
    Giannitsis, Evangelos
    Univ Heidelberg Hosp, Heidelberg, Germany..
    Lindahl, Bertil
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Multicenter Evaluation of a 0-Hour/1-Hour Algorithm in the Diagnosis of Myocardial Infarction With High-Sensitivity Cardiac Troponin T Reply2016Ingår i: Annals of Emergency Medicine, ISSN 0196-0644, E-ISSN 1097-6760, Vol. 67, nr 6, s. 794-795Artikel i tidskrift (Refereegranskat)
  • 249.
    Muresanu, Dafin F.
    et al.
    RoNeuro Inst Neurol Res & Diagnost, Cluj Napoca, Romania.;Univ Med & Pharm Iuliu Haticganu, Dept Clin Neurosci, Cluj Napoca, Romania..
    Sharma, Aruna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Lafuente, Jose V.
    Univ Basque Country, Dept Neurosci, LaNCE, Bilbao, Spain.;Univ Autonoma Chile, Fac Hlth Sci, Santiago, Chile..
    Patnaik, Ranjana
    Banaras Hindu Univ, Sch Biomed Engn, Indian Inst Technol, Dept Biomat, Varanasi 221005, Uttar Pradesh, India..
    Tian, Z. Ryan
    Univ Arkansas, Dept Chem & Biochem, Fayetteville, AR 72701 USA..
    Nyberg, Fred
    Uppsala Univ, Biomed Ctr, Dept Pharmaceut Biosci Biol Res Drug Dependence, Uppsala, Sweden..
    Sharma, Hari S.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Univ Basque Country, Dept Neurosci, LaNCE, Bilbao, Spain..
    Nanowired Delivery of Growth Hormone Attenuates Pathophysiology of Spinal Cord Injury and Enhances Insulin-Like Growth Factor-1 Concentration in the Plasma and the Spinal Cord2015Ingår i: Molecular Neurobiology, ISSN 0893-7648, E-ISSN 1559-1182, Vol. 52, nr 2, s. 837-845Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Previous studies from our laboratory showed that topical application of growth hormone (GH) induced neuroprotection 5 h after spinal cord injury (SCI) in a rat model. Since nanodelivery of drugs exerts superior neuroprotective effects, a possibility exists that nanodelivery of GH will induce long-term neuroprotection after a focal SCI. SCI induces GH deficiency that is coupled with insulin-like growth factor-1 (IGF-1) reduction in the plasma. Thus, an exogenous supplement of GH in SCI may enhance the IGF-1 levels in the cord and induce neuroprotection. In the present investigation, we delivered TiO2-nanowired growth hormone (NWGH) after a longitudinal incision of the right dorsal horn at the T10-11 segments in anesthetized rats and compared the results with normal GH therapy on IGF-1 and GH contents in the plasma and in the cord in relation to blood-spinal cord barrier (BSCB) disruption, edema formation, and neuronal injuries. Our results showed a progressive decline in IGF-1 and GH contents in the plasma and the T9 and T12 segments of the cord 12 and 24 h after SCI. Marked increase in the BSCB breakdown, as revealed by extravasation of Evans blue and radioiodine, was seen at these time points after SCI in association with edema and neuronal injuries. Administration of NWGH markedly enhanced the IGF-1 levels and GH contents in plasma and cord after SCI, whereas normal GH was unable to enhance IGF-1 or GH levels 12 or 24 h after SCI. Interestingly, NWGH was also able to reduce BSCB disruption, edema formation, and neuronal injuries after trauma. On the other hand, normal GH was ineffective on these parameters at all time points examined. Taken together, our results are the first to demonstrate that NWGH is quite effective in enhancing IGF-1 and GH levels in the cord and plasma that may be crucial in reducing pathophysiology of SCI.

  • 250. Muresanu, Dafin F.
    et al.
    Sharma, Aruna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Sharma, Hari Shanker
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Diabetes aggravates heat stress-induced blood-brain barrier breakdown, reduction in cerebral blood flow, edema formation, and brain pathology: Possible neuroprotection with growth hormone2010Ingår i: Annals of the New York Academy of Sciences, ISSN 0077-8923, E-ISSN 1749-6632, Vol. 1199, s. 15-26Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The possibility that diabetes influences the outcome of heat stress-induced brain pathology was examined in our experimental rat model. Because growth hormone (GH) deficiency is an important factor in diabetes, the possible neuroprotective role of GH supplements was also examined in diabetic rats following heat stress. Rats receiving streptozotocine once daily for three days (50 mg/kg, i.p.) and allowed to survive four weeks resulted in diabetes (blood glucose level 18 and 20 mMol/L) compared to controls (blood glucose 4-6 mMol/L). Control or diabetic rats when subjected to four hours' heat stress at 38 degrees C in a biological oxygen demand incubator (BOD) showed profound disruption of the blood-brain barrier (BBB), reduction in cerebral blood flow (CBF), brain edema formation, and cell injury. These effects were most pronounced in diabetic rats. Pretreatment with GH (50 mu g/kg/min for 10 min before heat stress) significantly attenuated brain pathology in normal animals subjected to hyperthermia. On the other hand, almost a double dose of the growth hormone (80 to 120 mu g/g/min for 10 min) is needed in diabetic rats to induce considerable neuroprotection following heat stress. These observations are the first to suggest that diabetic rats are more vulnerable to heat stress-induced brain pathology and further show that the efficacy of neuroprotective drugs is also severely reduced in diabetic rats. Taken together, our results demonstrate that the dosage of neuroprotective drugs requires adjustment to enhance neuroprotection depending on the patient's endocrine or metabolic status, for example, diabetes mellitus, a finding not reported earlier.

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