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Effect of Ventilatory Support on Abdominal Fluid Balance in a Sepsis Model
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
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 [en]
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: urn:nbn:se:uu:diva-207218ISBN: 978-91-554-8787-4 (print)OAI: oai:DiVA.org:uu-207218DiVA: diva2:652481
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
List of papers
1. Abdominal lymph flow in an endotoxin sepsis model: Influence of spontaneous breathing and mechanical ventilation
Open this publication in new window or tab >>Abdominal lymph flow in an endotoxin sepsis model: Influence of spontaneous breathing and mechanical ventilation
2006 (English)In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 34, no 11, 2792-2798 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: Lymph flow from the abdomen was investigated in a sepsis model. We also compared the effect on thoracic duct lymph flow of mechanical ventilation with different levels of positive end-expiratory pressure (PEEP) and spontaneous breathing with continuous positive airway pressure (CPAP). DESIGN: Experimental study. SETTING: Research laboratory in a university hospital. SUBJECTS: Thirty-two pigs. INTERVENTIONS: Animals were anesthetized. In study 1 (n = 18), an ultrasonic flow probe was put around the intact thoracic duct just caudal to the diaphragm, and animals were randomized to receive mechanical ventilation with a PEEP of 5 cm H2O or 15 cm H2O or breathed spontaneously in CPAP with a PEEP of 5 cm H2O. In study 2 (n = 6), the thoracic duct was cannulated and the cannula externalized through the abdominal wall for lymph collection; animals were then ventilated as in study 1. In all animals, endotoxin was infused at 15 μg/kg/hr for 2.5 hrs and then continued at 5 μg/kg/hr. In study 3, healthy (n = 4) and endotoxin-exposed (n = 4) pigs had intra-abdominal pressure increased to 27 cm H2O for 2 hrs by pneumoperitoneum. Lymph flow was measured as in study 1. MEASUREMENTS AND MAIN RESULTS: Lymph flow (mean ± se) was 2.5 ± 0.4 mL/min at baseline and increased to 3.9 ± 0.8 mL/min after 90 mins and 6.3 ± 1.6 mL/min after 150 mins (p < .005) of endotoxin exposure. PEEP 15 cm H2O decreased lymph flow in pigs with intact thoracic duct (flow probe recording) and in pigs with cannulated lymph duct when drained against the central venous pressure. However, when drained against atmospheric pressure, PEEP increased flow. Spontaneous breathing increased flow both in intact and in cannulated animals. CONCLUSIONS: Endotoxin increases lymph flow from the abdomen. Mechanical ventilation with high PEEP impedes lymph drainage and could increase lymph production. Spontaneous breathing increases flow and improves drainage of abdominal edema.

Keyword
sepsis, lymph, abdomen, positive end-expiratory pressure, mechanical ventilation
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-19586 (URN)10.1097/01.CCM.0000242158.28619.09 (DOI)000241639900012 ()16971857 (PubMedID)
Available from: 2006-11-30 Created: 2006-11-30 Last updated: 2017-12-08Bibliographically approved
2. Evaluating abdominal oedema during experimental sepsis using an isotope technique
Open this publication in new window or tab >>Evaluating abdominal oedema during experimental sepsis using an isotope technique
Show others...
2012 (English)In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 32, no 3, 197-204 p.Article in journal (Refereed) Published
Abstract [en]

Purpose: Abdominal oedema is common in sepsis. A technique for the study of such oedema may guide in the fluid regime of these patients.

Procedures: We modified a double-isotope technique to evaluate abdominal organ oedema and fluid extravasation in 24 healthy or endotoxin-exposed (septic) piglets. Two different markers were used: red blood cells (RBC) labelled with Technetium99m (99mTc) and Transferrin labelled with Indium111 (111In). Images were acquired on a dual-head gamma camera. Microscopic evaluation of tissue biopsies was performed to compare data with the isotope technique.

Results: No 99mTc activity was measured in the plasma fraction in blood sampled after labelling. Similarly, after molecular size gel chromatography, 111In activity was exclusively found in the high molecular fraction of the plasma. Extravasation of transferrin, indicating the degree of abdominal oedema, was 4 06 times higher in the LPS group compared to the healthy controls (P< 0 0001). Abdominal free fluid, studied in 3 animals, had as high 111In activity as in plasma, but no 99mTc activity. Intestinal lymphatic vessel size was higher in LPS (3 7 +/- 1 1 lm) compared to control animals (0 6 + 0 2 lm; P< 0 001) and oedema correlated to villus diameter (R 2 = 0 918) and lymphatic diameter (R 2 = 0 758). A correlation between a normalized index of oedema formation (NI) and intra-abdominal pressure (IAP) was also found: NI = 0 46* IAP) 3 3 (R2 = 0 56).

Conclusions: The technique enables almost continuous recording of abdominal oedema formation and may be a valuable tool in experimental research, with the potential to be applied in the clinic.

Keyword
abdomen, double indicator, gamma camera, microscopy, oedema
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-173971 (URN)10.1111/j.1475-097X.2011.01077.x (DOI)000302545300006 ()
Available from: 2012-05-14 Created: 2012-05-09 Last updated: 2017-12-07Bibliographically approved
3. Mechanical ventilation worsens abdominal edema and inflammation in porcine endotoxemia
Open this publication in new window or tab >>Mechanical ventilation worsens abdominal edema and inflammation in porcine endotoxemia
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.

National Category
Medical and Health Sciences
Research subject
Anaesthesiology and Intensive Care
Identifiers
urn:nbn:se:uu:diva-207180 (URN)10.1186/cc12801 (DOI)000329431100043 ()23799965 (PubMedID)
Available from: 2013-09-10 Created: 2013-09-10 Last updated: 2017-12-06Bibliographically approved
4. Effect of increased intra-abdominal pressure (IAP) on lung function in a sepsis model
Open this publication in new window or tab >>Effect of increased intra-abdominal pressure (IAP) on lung function in a sepsis model
(English)Manuscript (preprint) (Other academic)
Abstract [en]

We have previously shown that mechanical ventilation with positive pressure increases abdominal edema formation and causes an increase in intra-abdominal pressure (IAP) in a sepsis-like porcine model. In this study we investigated, in the same animal model effects of increase in IAP on the cardiovascular and respiratory system. Twelve pigs of Swedish country breed with a mean weight 28 kg were anesthetized and mechanically ventilated. Six animals received a continuous infusion of endotoxin and the other six served as controls. Catheters were inserted for vascular pressure recordings and cardiac output was measured by thermo-dilution. In both groups IAP was temporarily elevated to 20 mmHg by insufflation of CO2 into the abdominal cavity. Endotoxin infusion caused significant increases in pulmonary artery and central venous pressures and increase in shunt with fall in PaO2. Respiratory compliance was reduced. IAP elevation by CO2 insufflation increased these pressures as well as shunt further and caused additional decrease in compliance. Deflation of the abdomen returned vascular pressures to pre-insufflation but shunt remained increased and PaO2 was still reduced as was compliance. In control animals similar but smaller changes were seen on increase in IAP but with deflation not only vascular pressures but also shunt and PaO2 returned to normal. This suggests that in the sepsis-like condition, increased IAP causes persisting deterioration of lung function even when IAP has been normalized. We propose this to be caused by lung collapse that remains, at least for some time, after deflation.

Keyword
intra-abdominal pressure, IAP, pneumoperitoneum, shunt, MIGET, sepsis
National Category
Anesthesiology and Intensive Care Physiology
Research subject
Anaesthesiology and Intensive Care; Clinical Physiology
Identifiers
urn:nbn:se:uu:diva-207402 (URN)
Available from: 2013-09-13 Created: 2013-09-13 Last updated: 2014-01-23

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