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Marchesi, S., Ortiz-Nieto, F., Ahlgren, K. M., Roneus, A., Feinstein, R., Lipcsey, M., . . . Hedenstierna, G. (2018). Abdominal organ perfusion and inflammation in experimental sepsis;: a magnetic resonance imaging study.. American Journal of Physiology - Gastrointestinal and Liver Physiology
Open this publication in new window or tab >>Abdominal organ perfusion and inflammation in experimental sepsis;: a magnetic resonance imaging study.
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2018 (English)In: American Journal of Physiology - Gastrointestinal and Liver Physiology, ISSN 0193-1857, E-ISSN 1522-1547Article in journal (Refereed) Epub ahead of print
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.

Keywords
Abdominal organs, inflammation, magnetic resonance, perfusion, sepsis
National Category
Surgery Anesthesiology and Intensive Care
Identifiers
urn:nbn:se:uu:diva-364356 (URN)10.1152/ajpgi.00151.2018 (DOI)30335473 (PubMedID)
Available from: 2018-10-25 Created: 2018-10-25 Last updated: 2019-01-17Bibliographically approved
Skorup, P., Maudsdotter, L., Tano, E., Lipcsey, M., Castegren, M., Larsson, A. & Sjölin, J. (2018). Dynamics of Endotoxin, Inflammatory Variables, and Organ Dysfunction After Treatment With Antibiotics in an Escherichia coli Porcine Intensive Care Sepsis Model. Critical Care Medicine, 46(7), e634-e641
Open this publication in new window or tab >>Dynamics of Endotoxin, Inflammatory Variables, and Organ Dysfunction After Treatment With Antibiotics in an Escherichia coli Porcine Intensive Care Sepsis Model
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2018 (English)In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 46, no 7, p. e634-e641Article in journal (Refereed) Published
Abstract [en]

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

DESIGN: Prospective, placebo-controlled interventional experimental study.

SETTING: University research unit.

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

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

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

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

National Category
Infectious Medicine
Identifiers
urn:nbn:se:uu:diva-349226 (URN)10.1097/CCM.0000000000003139 (DOI)000435290400002 ()29595561 (PubMedID)
Available from: 2018-04-23 Created: 2018-04-23 Last updated: 2018-12-12Bibliographically approved
Horst, S., Kawati, R., Rasmusson, J., Pikwer, A., Castegren, M. & Lipcsey, M. (2018). Impact of resuscitation fluid bag size availability on volume of fluid administration in the intensive care unit. Acta Anaesthesiologica Scandinavica, 62(9), 1261-1266
Open this publication in new window or tab >>Impact of resuscitation fluid bag size availability on volume of fluid administration in the intensive care unit
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2018 (English)In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 62, no 9, p. 1261-1266Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Iatrogenic fluid overload is associated with increased mortality in the intensive care unit (ICU). Decisions on fluid therapy may, at times, be based on other factors than physiological endpoints. We hypothesized that because of psychological factors volume of available fluid bags would affect the amount of resuscitation fluid administered to ICU patients.

METHODS: We performed a prospective intervention cross-over study at 3 Swedish ICUs by replacing the standard resuscitation fluid bag of Ringer's Acetate 1000 mL with 500 mL bags (intervention group) for 5 separate months and then compared it with the standard bag size for 5 months (control group). Primary endpoint was the amount of Ringer's Acetate per patient during ICU stay. Secondary endpoints were differences between the groups in cumulative fluid balance and change in body weight, hemoglobin and creatinine levels, urine output, acute kidney failure (measured as the need for renal replacement therapy, RRT) and 90-day mortality.

RESULTS: Six hundred and thirty-five ICU patients were included (291 in the intervention group, 344 in the control group). There was no difference in the amount of resuscitation fluid per patient during the ICU stay (2200 mL [1000-4500 median IQR] vs 2245 mL [1000-5630 median IQR]), RRT rate (11 vs 9%), 90-day mortality (11 vs 10%) or total fluid balance between the groups. The daily amount of Ringer's acetate administered per day was lower in the intervention group (1040 (280-2000) vs 1520 (460-3000) mL; P = .03).

CONCLUSIONS: The amount of resuscitation fluid administered to ICU patients was not affected by the size of the available fluid bags. However, altering fluid bag size could have influenced fluid prescription behavior.

Keywords
adverse effects, critical care, crystalloid solutions, fluid therapy, psychological factors
National Category
Anesthesiology and Intensive Care
Identifiers
urn:nbn:se:uu:diva-362676 (URN)10.1111/aas.13161 (DOI)000443673500011 ()29851027 (PubMedID)
Available from: 2018-10-08 Created: 2018-10-08 Last updated: 2018-11-06Bibliographically approved
Lipcsey, M., Castegren, M., Furebring, M. & Sjölin, J. (2018). Should the Aminoglycoside β-Lactam Combination Be Abandoned in All Severely Ill Patients With Presumed Gram-Negative Infection? [Letter to the editor]. Clinical Infectious Diseases, 66(3), 480-482
Open this publication in new window or tab >>Should the Aminoglycoside β-Lactam Combination Be Abandoned in All Severely Ill Patients With Presumed Gram-Negative Infection?
2018 (English)In: Clinical Infectious Diseases, ISSN 1058-4838, E-ISSN 1537-6591, Vol. 66, no 3, p. 480-482Article in journal, Letter (Other academic) Published
National Category
Infectious Medicine Anesthesiology and Intensive Care
Identifiers
urn:nbn:se:uu:diva-350197 (URN)10.1093/cid/cix780 (DOI)000423321200034 ()29020234 (PubMedID)
Note

WoS title: Should the Aminoglycoside beta-Lactam Combination Be Abandoned in All Severely III Patients With Presumed Gram-Negative Infection?

Available from: 2018-05-08 Created: 2018-05-08 Last updated: 2018-05-08Bibliographically approved
Laake, J. H., Tonnessen, T. I., Chew, M. S., Lipcsey, M., Hjelmqvist, H., Wilkman, E., . . . Moller, M. H. (2018). The SSAI fully supports the suspension of hydroxyethyl-starch solutions commissioned by the European Medicines Agency [Letter to the editor]. Acta Anaesthesiologica Scandinavica, 62(6), 874-875
Open this publication in new window or tab >>The SSAI fully supports the suspension of hydroxyethyl-starch solutions commissioned by the European Medicines Agency
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2018 (English)In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 62, no 6, p. 874-875Article in journal, Letter (Other academic) Published
National Category
Anesthesiology and Intensive Care
Identifiers
urn:nbn:se:uu:diva-365118 (URN)10.1111/aas.13120 (DOI)000434205100018 ()29658984 (PubMedID)
Available from: 2018-11-12 Created: 2018-11-12 Last updated: 2018-11-12Bibliographically approved
Strandberg, G., Walther, S., Öhman, C. A. & Lipcsey, M. (2017). Long-term mortality after severe sepsis and septic shock in Swedish intensive care units 2005-2015. Acta Anaesthesiologica Scandinavica, 61(8), 1039-1039
Open this publication in new window or tab >>Long-term mortality after severe sepsis and septic shock in Swedish intensive care units 2005-2015
2017 (English)In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 61, no 8, p. 1039-1039Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
WILEY, 2017
National Category
Anesthesiology and Intensive Care
Identifiers
urn:nbn:se:uu:diva-342131 (URN)000407231100130 ()
Available from: 2018-02-22 Created: 2018-02-22 Last updated: 2018-02-22
von Seth, M., Lipcsey, M., Engström, P., Larsson, A., Hillered, L., Maripuu, E., . . . Sjölin, J. (2017). Rapid Bolus Administration Does Not Increase the Extravasation Rate of Albumin: A Randomized Controlled Trial in the Endotoxemic Pig. Shock, 47(4), 514-519
Open this publication in new window or tab >>Rapid Bolus Administration Does Not Increase the Extravasation Rate of Albumin: A Randomized Controlled Trial in the Endotoxemic Pig
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2017 (English)In: Shock, ISSN 1073-2322, E-ISSN 1540-0514, Vol. 47, no 4, p. 514-519Article in journal (Refereed) Published
Abstract [en]

Some experimental data suggest that rapid bolus administration of albumin causes less plasma-expanding effects than slow, continuous infusion. To determine whether rapid bolus administration, in comparison with slow infusion, results in greater extravasation of albumin in experimental septic shock we performed a randomized controlled trial with 32 endotoxemic pigs. The animals were monitored and ventilated with standard intensive care equipment and given 10 mL x kg 5% albumin labeled with Technetium-99m, either as a rapid 15-minute bolus (Bolus group, n = 16) or as a 2-hour (h) infusion (Infusion group, n = 16). Radioactivity was monitored in plasma, extracellular microdialysate and urine for 6 h. Physiological parameters were monitored hourly. Radioactivity in the liver, spleen, kidney and lung was analyzed post-mortem.The plasma area under the curve (AUC) activity0-6h was 4.4 ± 0.9 x 10 in the Bolus group and 4.4 ± 1.1 x 10 counts x min x mL x h in the Infusion group. Blood hemoglobin levels increased in both groups, suggesting severe capillary leakage. Yet, there were no group differences in albumin radioactivity in plasma, muscle tissue, urine or in the post-mortem analysis of the organs. Following albumin administration, circulatory and respiratory parameters were similar in the two groups.In conclusion, the present results suggest that albumin might be given as a bolus without leading to increased extravasation of albumin, in contrast to previous animal experiments in rodents.

Keywords
Albumin, animal models, capillary leak syndrome, endotoxin, fluid resuscitation, sepsis
National Category
Infectious Medicine Hematology Surgery
Identifiers
urn:nbn:se:uu:diva-305826 (URN)10.1097/SHK.0000000000000761 (DOI)000396226300016 ()27749758 (PubMedID)
Available from: 2016-10-23 Created: 2016-10-22 Last updated: 2017-08-13Bibliographically approved
Lipcsey, M., Tenhunen, J., Sjölin, J., Frithiof, R., Bendel, S., Flaatten, H., . . . Rubertsson, S. (2016). 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 trial. Trials, 17, Article ID 587.
Open this publication in new window or tab >>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 trial
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2016 (English)In: Trials, ISSN 1745-6215, E-ISSN 1745-6215, Vol. 17, article id 587Article in journal (Refereed) Published
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.

Keywords
Septic shock, Endotoxins, Hemoperfusion, Gram-negative bacteria
National Category
Anesthesiology and Intensive Care
Identifiers
urn:nbn:se:uu:diva-313532 (URN)10.1186/s13063-016-1723-4 (DOI)000390388800006 ()
Funder
Swedish Research Council, 523-2014-2569
Available from: 2017-02-01 Created: 2017-01-20 Last updated: 2017-11-29Bibliographically approved
Strandberg, G., Lipcsey, M., Eriksson, M. B., Lubenow, N. & Larsson, A. (2016). Analysis of Thromboelastography, PT, APTT and Fibrinogen in Intraosseous and Venous Samples: An Experimental Study. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine, 24, Article ID 131.
Open this publication in new window or tab >>Analysis of Thromboelastography, PT, APTT and Fibrinogen in Intraosseous and Venous Samples: An Experimental Study
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2016 (English)In: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine, ISSN 1757-7241, E-ISSN 1757-7241, Vol. 24, article id 131Article in journal (Refereed) Published
Abstract [en]

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

Keywords
Blood coagulation; Haemorrhage; Infusions; Intraosseous; Thrombelastography
National Category
Anesthesiology and Intensive Care
Identifiers
urn:nbn:se:uu:diva-306587 (URN)10.1186/s13049-016-0318-0 (DOI)000386860300001 ()
Available from: 2016-10-29 Created: 2016-10-29 Last updated: 2017-11-29Bibliographically approved
Eriksson, M. & Larsson, A. (2016). Emergency intraosseous access: novel diagnostic and therapeutic possibilities and limitations. ICU Management & Practice, 16(4), 230-232
Open this publication in new window or tab >>Emergency intraosseous access: novel diagnostic and therapeutic possibilities and limitations
2016 (English)In: ICU Management & Practice, Vol. 16, no 4, p. 230-232Article in journal (Refereed) Published
Abstract [en]

The intraosseous needle is an essential tool in emergency settings when initial vascular access is difficult to achieve. This paper focuses on possible biochemical analyses on blood from emergency intraosseous needles, suggesting principles of use as well as pointing out advantages and shortcomings.

National Category
Anesthesiology and Intensive Care
Identifiers
urn:nbn:se:uu:diva-309519 (URN)
Available from: 2016-12-05 Created: 2016-12-05 Last updated: 2016-12-09Bibliographically approved
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ORCID iD: ORCID iD iconorcid.org/0000-0002-1976-4129

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