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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: 2018-08-31Bibliographically 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
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
Eriksson, M., Strandberg, G., Lipcsey, M. & Larsson, A. (2016). Evaluation of intraosseous sampling for measurements of alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, creatinine kinase, gamma-glutamyl transferase and lactate dehydrogenase.. Scandinavian Journal of Clinical and Laboratory Investigation, 76(8), 597-600
Open this publication in new window or tab >>Evaluation of intraosseous sampling for measurements of alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, creatinine kinase, gamma-glutamyl transferase and lactate dehydrogenase.
2016 (English)In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 76, no 8, p. 597-600Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Intraosseous (IO) access can be established faster than a venous or arterial access when there is an urgent need for rapid initiation of treatment. The access can also be used to draw marrow samples. The aim of the present study was to evaluate the potential use of IO samples for enzyme determinations using a porcine model.

MATERIALS AND METHODS: Bilateral tibial intraosseous cannulae and an arterial catheter were used for blood sampling from five healthy anesthetized pigs. Samples were collected at baseline and thereafter hourly for 6 h and analyzed for alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, creatinine kinase, gamma-glutamyl transferase and lactate dehydrogenase.

RESULTS: Creatinine kinase, lactate dehydrogenase and alkaline phosphatase levels decreased over time. The differences between IO and arterial sampling were limited for all studied markers.

CONCLUSION: The correlation between marrow and blood analysis for liver function tests and CK is sufficiently accurate in an emergency situation.

National Category
Anesthesiology and Intensive Care
Identifiers
urn:nbn:se:uu:diva-305836 (URN)10.1080/00365513.2016.1230774 (DOI)000388748300001 ()27687698 (PubMedID)
Available from: 2016-10-22 Created: 2016-10-22 Last updated: 2017-11-29Bibliographically approved
Simm, M., Söderberg, E., Larsson, A., Castegren, M., Nilsen, T., Eriksson, M. & Lipcsey, M. (2016). Performance of plasma calprotectin as a biomarker of early sepsis: a pilot study. Biomarkers in Medicine, 10(8), 811-818
Open this publication in new window or tab >>Performance of plasma calprotectin as a biomarker of early sepsis: a pilot study
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2016 (English)In: Biomarkers in Medicine, ISSN 1752-0363, E-ISSN 1752-0371, Vol. 10, no 8, p. 811-818Article in journal (Refereed) Published
Abstract [en]

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

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

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

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

Keywords
calprotectin; sepsis; systemic inflammatory response syndrome
National Category
Anesthesiology and Intensive Care
Identifiers
urn:nbn:se:uu:diva-299540 (URN)10.2217/bmm-2016-0032 (DOI)000383776800003 ()27414210 (PubMedID)
Available from: 2016-07-22 Created: 2016-07-22 Last updated: 2017-11-28Bibliographically approved
Lipcsey, M., Mcnicol, L., Parker, F., Poustie, S., Liu, G., Uchino, S., . . . Bellomo, R. (2015). Effect of perfusion pressure on the splanchnic circulation after CPB: a pilot study. Minerva Anestesiologica, 81(7), 752-764
Open this publication in new window or tab >>Effect of perfusion pressure on the splanchnic circulation after CPB: a pilot study
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2015 (English)In: Minerva Anestesiologica, ISSN 0375-9393, E-ISSN 1827-1596, Vol. 81, no 7, p. 752-764Article in journal (Refereed) Published
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.

Keywords
Intensive Care Unit, Cardiac surgical procedures, Blood pressure, Splanchnic circulation, Cytokines
National Category
Anesthesiology and Intensive Care
Identifiers
urn:nbn:se:uu:diva-265602 (URN)000362381600009 ()25357214 (PubMedID)
Available from: 2015-11-02 Created: 2015-11-02 Last updated: 2017-12-01Bibliographically approved
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Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-1976-4129

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