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Rapid Bolus Administration Does Not Increase the Extravasation Rate of Albumin: A Randomized Controlled Trial in the Endotoxemic Pig
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.ORCID iD: 0000-0003-3161-0402
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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.

Place, publisher, year, edition, pages
2017. Vol. 47, no 4, p. 514-519
Keyword [en]
Albumin, animal models, capillary leak syndrome, endotoxin, fluid resuscitation, sepsis
National Category
Infectious Medicine Hematology Surgery
Identifiers
URN: urn:nbn:se:uu:diva-305826DOI: 10.1097/SHK.0000000000000761ISI: 000396226300016PubMedID: 27749758OAI: oai:DiVA.org:uu-305826DiVA: diva2:1039301
Available from: 2016-10-23 Created: 2016-10-22 Last updated: 2017-08-13Bibliographically approved
In thesis
1. Oxygen delivery and mitochondrial dysfunction as assessed by microdialysis during interventions in experimental sepsis
Open this publication in new window or tab >>Oxygen delivery and mitochondrial dysfunction as assessed by microdialysis during interventions in experimental sepsis
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Early administration of broad-spectrum antibiotics is the first goal in sepsis treatment. Besides from bacteriostatic/bactericidal effects, some antibiotics may also modify the host´s response to infection. The novel antibiotic tigecycline may exert such properties; however, this property has not been evaluated in large-animal trials. We compared tigecycline with doxycycline and placebo in relation to anti-inflammatory, circulatory and organ dysfunction effects in a sterile pig model of sepsis. Doxycycline, but not tigecycline, reduced the inflammatory response as manifested by tumor necrosis factor alpha levels in plasma. Tigecycline, however, had a stabilizing effect on the circulation not exerted by doxycycline or placebo.

To achieve rapid restoration of the circulating blood volume - another major goal in sepsis treatment - fluid bolus administration of is some-times practiced. In addition to crystalloids, albumin-containing solutions are suggested. Yet, some animal-experimental data suggests that rapid bolus administration of albumin reduces albumin’s plasma-expanding effect. We compared a rapid intravenous bolus of radiolabeled albumin with a slow infusion in a sterile pig model of sepsis. Rapid bolus of administration did not reduce plasma levels of albumin following administration and did not increase the amount of albumin that left the circulation.

Inadequate oxygen delivery (DO2) by the circulation to the tissues may cause increased plasma lactate, which is the most striking effect of sepsis on the metabolism. However, experimental data and clinical trials refute this link, instead, suggesting other mechanisms, including impaired oxygen extraction, mitochondrial dysfunction and accelerated aerobic glycolysis. We investigated the impact of DO2, oxygen consumption (VO2), hemodynamic parameters and inflammatory response on plasma lactate and organ dysfunction in two experimental sepsis models. In the most severe cases of shock, with DO2, there was an increase in plasma lactate, but without a decrease in VO2, invalidating the assumption that the increase in lactate is due to anaerobic metabolism.

To identify critical steps in the sepsis-induced increase in lactate, we inhibited the major energy-producing step in the electron transport chain (ETC). The combination of sepsis and ETC inhibition led to a cellular energy crisis. This finding suggests that early sepsis induces a partial mitochondrial dysfunction.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2017. p. 83
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1352
Keyword
sepsis, animal models, microdialysis, endotoxin, Escherichia coli, tigecycline, doxycycline, albumins, capillary leak syndrome, lactic acid, oxygen delivery, multiple organ failure, mitochondria, tumor necrosis factor alpha, interleukin-6, cyanides, ouabain
National Category
Anesthesiology and Intensive Care
Research subject
Anaesthesiology and Intensive Care
Identifiers
urn:nbn:se:uu:diva-326788 (URN)978-91-513-0028-3 (ISBN)
Public defence
2017-09-29, Hedstrandsalen, Ing 70, Akademiska sjukhuset, Sjukhusvägen, Uppsala, 13:00 (English)
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Available from: 2017-09-08 Created: 2017-08-13 Last updated: 2017-10-17

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von Seth, MagnusLipcsey, MiklósLarsson, AndersHillered, LarsSjölin, Jan

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