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Exposure to Mechanical Ventilation and Endotoxin for 24 Hours Before Infection Influences Pseudomonas Aeruginosa Growth During Experimental Porcine Ventilator-Associated Pneumonia
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
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.
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(English)Manuscript (preprint) (Other academic)
National Category
Anesthesiology and Intensive Care
Identifiers
URN: urn:nbn:se:uu:diva-282601OAI: oai:DiVA.org:uu-282601DiVA: diva2:917229
Available from: 2016-04-05 Created: 2016-04-05 Last updated: 2016-05-12
In thesis
1. Protective Mechanical Ventilation in Inflammatory and Ventilator-Associated Pneumonia Models
Open this publication in new window or tab >>Protective Mechanical Ventilation in Inflammatory and Ventilator-Associated Pneumonia Models
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Severe infections, trauma or major surgery can each cause a state of systemic inflammation. These causes for systemic inflammation often coexist and complicate each other. Mechanical ventilation is commonly used during major surgical procedures and when respiratory functions are failing in the intensive care setting. Although necessary, the use of mechanical ventilation can cause injury to the lungs and other organs especially under states of systemic inflammation. Moreover, a course of mechanical ventilator therapy can be complicated by ventilator-associated pneumonia, a factor greatly influencing mortality. The efforts to avoid additional ventilator-induced injury to patients are embodied in the expression ‘protective ventilation’.

With the use of pig models we have examined the impact of protective ventilation on systemic inflammation, on organ-specific inflammation and on bacterial growth during pneumonia. Additionally, with a 30-hour ventilator-associated pneumonia model we examined the influence of mechanical ventilation and systemic inflammation on bacterial growth. Systemic inflammation was initiated with surgery and enhanced with endotoxin. The bacterium used was Pseudomonas aeruginosa.

We found that protective ventilation during systemic inflammation attenuated the systemic inflammatory cytokine responses and reduced secondary organ damage. Moreover, the attenuated inflammatory responses were seen on the organ specific level, most clearly as reduced counts of inflammatory cytokines from the liver. Protective ventilation entailed lower bacterial counts in lung tissue after 6 hours of pneumonia. Mechanical ventilation for 24 h, before a bacterial challenge into the lungs, increased bacterial counts in lung tissue after 6 h. The addition of systemic inflammation by endotoxin during 24 h increased the bacterial counts even more. For comparison, these experiments used control groups with clinically common ventilator settings.

Summarily, these results support the use of protective ventilation as a means to reduce systemic inflammation and organ injury, and to optimize bacterial clearance in states of systemic inflammation and pneumonia.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2016. 84 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1208
Keyword
Mechanical ventilation, Systemic inflammation, Pneumonia, Ventilator-associated pneumonia, Endotoxin
National Category
Anesthesiology and Intensive Care
Research subject
Anaesthesiology and Intensive Care
Identifiers
urn:nbn:se:uu:diva-282602 (URN)978-91-554-9546-6 (ISBN)
Public defence
2016-05-28, Scenkonst Sörmland, John Engellaus Gata 3, 633 42, Eskilstuna, 09:15 (Swedish)
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Supervisors
Available from: 2016-05-02 Created: 2016-04-05 Last updated: 2016-05-12

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Sperber, JesperLipcsey, MiklósLarsson, AndersSjölin, JanCastegren, Markus

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Infectious DiseasesCentrum för klinisk forskning i Sörmland (CKFD)Anaesthesiology and Intensive CareBiochemial structure and function
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