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Lipcsey, Miklós
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Publications (10 of 59) Show all publications
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, 514-519 p.Article 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.

Keyword
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, 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.

Keyword
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, 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.

Keyword
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, 230-232 p.Article 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, 597-600 p.Article 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, 811-818 p.Article 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.

Keyword
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, 752-764 p.Article 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.

Keyword
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
von Seth, M., Sjölin, J., Larsson, A., Eriksson, M., Hillered, L. & Lipcsey, M. (2015). Effects of Tigecycline and Doxycycline on Inflammation and Hemodynamics in Porcine Endotoxemia: a Prospective, Randomized and Placebo Controlled Trial. Shock, 43(6), 604-611.
Open this publication in new window or tab >>Effects of Tigecycline and Doxycycline on Inflammation and Hemodynamics in Porcine Endotoxemia: a Prospective, Randomized and Placebo Controlled Trial
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2015 (English)In: Shock, ISSN 1073-2322, E-ISSN 1540-0514, Vol. 43, no 6, 604-611 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Antibiotics might, apart from an antimicrobial effect, also exert anti-inflammatory effects. The novel antibiotic tigecycline, potentially useful in septic shock from Gram-negative multi-resistant bacteria, is structurally related to antibiotics with known anti-inflammatory properties. However, its anti-inflammatory effects have previously not been explored in vivo. Using a sterile integrative porcine sepsis model, we investigated the anti-inflammatory and circulatory effects of tigecycline in comparison to doxycycline and placebo.

METHODS: Eighteen pigs were randomized to receive tigecycline 100 mg, doxycycline 200 mg or placebo and subjected to 6 h endotoxin infusion at 0.5 μg x kg x h. Markers of inflammation, nitric oxide (NO) production, vascular permeability, hemodynamics, organ dysfunction, tissue metabolism and acid-base parameters were monitored.

RESULTS: Peak plasma tumor necrosis alpha (TNF-α) was lower in the doxycycline group (P=0.031) but not in the tigecycline group (P=0.86) compared to placebo with geometric mean plasma concentrations of 16, 79 and 63 ng x ml, respectively. Mean arterial pressure was higher 4-6 h in the tigecycline group with values at 6 h of 107± 9 mmHg compared to the placebo and doxycycline groups (85 ± 27 mmHg and 90 ± 32 mmHg, respectively) (P=0.025). The white blood cell and the neutrophil granulocyte counts were less reduced in the doxycycline group, but not in the tigecycline group at 4-6 h (P=0.009 and p=0.019, respectively). Other markers of inflammation, organ dysfunction, tissue metabolism and acid-base parameters were unaffected by tigecycline.

CONCLUSIONS: Consistent with known anti-inflammatory properties, doxycycline yielded decreased TNF-α levels. Tigecycline did not affect cytokine levels but counteracted hypotension and hypoperfusion.

National Category
Anesthesiology and Intensive Care
Identifiers
urn:nbn:se:uu:diva-244766 (URN)10.1097/SHK.0000000000000351 (DOI)000354734300013 ()25664982 (PubMedID)
Available from: 2015-02-20 Created: 2015-02-20 Last updated: 2017-12-04Bibliographically approved
Sperber, J., Lipcsey, M., Larsson, A., Larsson, A., Sjölin, J. & Castegren, M. (2015). Evaluating the effects of protective ventilation on organ-specific cytokine production in porcine experimental postoperative sepsis. BMC Pulmonary Medicine, 15, Article ID 60.
Open this publication in new window or tab >>Evaluating the effects of protective ventilation on organ-specific cytokine production in porcine experimental postoperative sepsis
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2015 (English)In: BMC Pulmonary Medicine, ISSN 1471-2466, E-ISSN 1471-2466, Vol. 15, 60Article in journal (Refereed) Published
Abstract [en]

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

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

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

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

National Category
Anesthesiology and Intensive Care
Identifiers
urn:nbn:se:uu:diva-253174 (URN)10.1186/s12890-015-0052-9 (DOI)000354840700001 ()25958003 (PubMedID)
Available from: 2015-05-23 Created: 2015-05-23 Last updated: 2017-12-04Bibliographically approved
Lipcsey, M., Castegren, M. & Bellomo, R. (2015). Hemodynamic management of septic shock. Minerva Anestesiologica, 81(11), 1262-1272.
Open this publication in new window or tab >>Hemodynamic management of septic shock
2015 (English)In: Minerva Anestesiologica, ISSN 0375-9393, E-ISSN 1827-1596, Vol. 81, no 11, 1262-1272 p.Article in journal (Refereed) Published
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.

National Category
Medical and Health Sciences Anesthesiology and Intensive Care
Identifiers
urn:nbn:se:uu:diva-265779 (URN)000367565200014 ()25369134 (PubMedID)
Available from: 2015-11-03 Created: 2015-11-03 Last updated: 2017-12-01Bibliographically approved
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