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Lung protective ventilation induces immunotolerance and nitric oxide metabolites in porcine experimental postoperative sepsis
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, 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, 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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2013 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 12, e83182- p.Article in journal (Refereed) Published
Abstract [en]

Low tidal volume ventilation is beneficial in patients with severe pulmonary dysfunction and would, in theory, reduce postoperative complications if implemented during routine surgery. The study aimed to investigate whether low tidal volume ventilation and high positive end-expiratory pressure (PEEP) in a large animal model of postoperative sepsis would attenuate the systemic inflammatory response and organ dysfunction. Thirty healthy pigs were randomized to three groups: Group Prot-7h, i.e. protective ventilation for 7 h, was ventilated with a tidal volume of 6 mL x kg-1 for 7 h; group Prot-5h, i.e. protective ventilation for 5 h, was ventilated with a tidal volume of 10 mL x kg-1 for 2 h, after which the group was ventilated with a tidal volume of 6 mL x kg-1; and a control group that was ventilated with a tidal volume of 10 mL x kg-1 for 7 h. In groups Prot-7h and Prot-5h PEEP was 5 cmH2O for 2 h and 10 cmH2O for 5 h. In the control group PEEP was 5 cmH2O for the entire experiment. After surgery for 2 h, postoperative sepsis was simulated with an endotoxin infusion for 5 h. Low tidal volume ventilation combined with higher PEEP led to lower levels of interleukin 6 and 10 in plasma, higher PaO2/FiO2, better preserved functional residual capacity and lower plasma troponin I as compared with animals ventilated with a medium high tidal volume and lower PEEP. The beneficial effects of protective ventilation were seen despite greater reductions in cardiac index and oxygen delivery index. In the immediate postoperative phase low VT ventilation with higher PEEP was associated with reduced ex vivo plasma capacity to produce TNF-α upon endotoxin stimulation and higher nitrite levels in urine. These findings might represent mechanistic explanations for the attenuation of systemic inflammation and inflammatory-induced organ dysfunction.

Place, publisher, year, edition, pages
2013. Vol. 8, no 12, e83182- p.
National Category
Basic Medicine
Identifiers
URN: urn:nbn:se:uu:diva-213610DOI: 10.1371/journal.pone.0083182ISI: 000328731800101PubMedID: 24349457OAI: oai:DiVA.org:uu-213610DiVA: diva2:682769
Available from: 2013-12-30 Created: 2013-12-30 Last updated: 2017-12-06Bibliographically approved
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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Available from: 2016-05-02 Created: 2016-04-05 Last updated: 2016-05-12

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