uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Mechanical ventilation worsens abdominal edema and inflammation in porcine endotoxemia
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
Department of Medical Physics, University Hospital, Uppsala, Sweden.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
2013 (English)In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 17, no 3, R126- p.Article in journal (Refereed) Published
Abstract [en]

INTRODUCTION:

We hypothesized that mechanical ventilation per se increases abdominal edema and inflammation in sepsis and tested this in experimental endotoxemia.

METHODS:

Thirty anesthetized piglets were allocated to one of five groups: healthy control pigs breathing spontaneously with continuous positive pressure of 5 cm H2O or mechanically ventilated with positive end-expiratory pressure (PEEP) of 5 cm H2O, and endotoxemic piglets during mechanical ventilation for 2.5 hours and then continued on mechanical ventilation with PEEP of either 5 or 15 cm H2O or switched to spontaneous breathing with continuous positive pressure of 5 cm H2O for another 2.5 hours. Abdominal edema formation was estimated by isotope technique and inflammatory markers were measured in liver, intestine, lung and plasma.

RESULTS:

In the healthy controls, 5 hours of spontaneous breathing did not increase abdominal fluid whereas mechanical ventilation did (Normalized Index increased from 1.0 to 1.6;1-3.3 (median and range, p<0.05)). In endotoxemic animals, Normalized Index increased almost six-fold after 5 hours of mechanical ventilation (5.9;4.9-6.9, p<0.05) with two-fold increase from 2.5 to 5 hours whether PEEP was 5 or 15, but only by 40% with spontaneous breathing (p<0.05 vs PEEP of 5 or 15 cm H2O). Tumor Necrosis Factor alpha (TNF-alpha) and interleukin (IL)-6 in intestine and liver were 2-3 times higher with mechanical ventilation than during spontaneous breathing (p<0.05) but similar in plasma and lung. Abdominal edema formation and TNF-alpha in intestine correlated inversely with abdominal perfusion pressure.

CONCLUSIONS:

Mechanical ventilation with PEEP increases abdominal edema and inflammation in intestine and liver in experimental endotoxemia by increasing systemic capillary leakage and impeding abdominal lymph drainage.

Place, publisher, year, edition, pages
2013. Vol. 17, no 3, R126- p.
National Category
Medical and Health Sciences
Research subject
Anaesthesiology and Intensive Care
Identifiers
URN: urn:nbn:se:uu:diva-207180DOI: 10.1186/cc12801ISI: 000329431100043PubMedID: 23799965OAI: oai:DiVA.org:uu-207180DiVA: diva2:647032
Available from: 2013-09-10 Created: 2013-09-10 Last updated: 2017-12-06Bibliographically approved
In thesis
1. Effect of Ventilatory Support on Abdominal Fluid Balance in a Sepsis Model
Open this publication in new window or tab >>Effect of Ventilatory Support on Abdominal Fluid Balance in a Sepsis Model
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

In patients affected by acute respiratory failure or acute respiratory distress syndrome (ARDS) the leading cause of death is failure of different vital organs other than the lungs, so called multiple organ dysfunction syndrome (MODS). The abdominal organs have a crucial role in the pathogenesis of this syndrome.

There is a lack of knowledge regarding the mechanisms by which mechanical ventilation can affect the abdominal compartment. One hypothesis is that mechanical ventilation can interfere with abdominal fluid balance causing edema and inflammation.

We addressed the question whether different levels of ventilatory support (mechanical ventilation with different levels of positive end-expiratory pressure, PEEP, and spontaneous breathing with or without PEEP) can influence abdominal edema and inflammation in both healthy and endotoxin-exposed animals.

The effect on lymphatic drainage from the abdomen exerted by different degrees of ventilatory support was evaluated (paper I). We demonstrated that endotoxin increases abdominal lymph production, that PEEP and mechanical ventilation increase lymph production but also impede lymphatic drainage; spontaneous breathing improves lymphatic drainage from the abdomen.

By adapting a non-invasive nuclear medicine imaging technique and validating it (paper II), we have been able to evaluate extravascular fluid accumulation (edema formation) in the abdomen over time (paper III) demonstrating that edema increases during endotoxemia, mimicking a sepsis-like condition, and that spontaneous breathing, compared to mechanical ventilation, reduces extravascular fluid. Pro-inflammatory cytokines TNF-α and IL-6 in intestinal biopsies are reduced during spontaneous breathing compared to mechanical ventilation.

Abdominal edema results in increased intra-abdominal pressure (IAP): in paper IV we analyzed the effect of increased intra-abdominal pressure on the respiratory system. Pulmonary shunt fraction increased with high IAP both in healthy and LPS animals, resulting in decreased level of oxygenation. These changes are only partially reversible by reducing IAP.

In conclusion, mechanical ventilation is a life-saving tool but the possible side effect at the extra-pulmonary level should be considered, and the introduction of some degree of spontaneous breathing when clinically possible is a suggested choice.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2013. 35 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 941
Keyword
mechanical ventilation, lymph flow, spontaneous breathing, positive end-expiratory pressure, PEEP, abdominal edema, inflammation, intra-abdominal pressure, IAP
National Category
Anesthesiology and Intensive Care Physiology
Research subject
Anaesthesiology and Intensive Care; Clinical Physiology
Identifiers
urn:nbn:se:uu:diva-207218 (URN)978-91-554-8787-4 (ISBN)
Public defence
2013-12-09, Enghoffsalen, Entrance 50, University Hospital, Uppsala, 13:15 (English)
Opponent
Supervisors
Funder
Swedish Heart Lung FoundationSwedish Research Council, 5315
Available from: 2013-11-15 Created: 2013-09-10 Last updated: 2014-01-23

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Authority records BETA

Bergquist, MariaHedenstierna, Göran

Search in DiVA

By author/editor
Bergquist, MariaHedenstierna, Göran
By organisation
Clinical Physiology
In the same journal
Critical Care
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 377 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf