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Sökning: WFRF:(Oldner Anders Professor)

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1.
  • Marchesi, Silvia, MD, 1985- (författare)
  • The effect of mechanical ventilation on abdominal organs : Analysing the role of PEEP and perfusion.
  • 2019
  • Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Background: The effect of mechanical ventilation on abdominal organs is not well understood and investigated yet. Previous studies, using an animal sepsis-like model, found an association between mechanical ventilation (MV) and abdominal edema and inflammation.The presented thesis was aimed to investigate the role of perfusion in edema formation and inflammation, and to study the abdomen during mechanical ventilation in an ARDS model to reduce the confounding effect of inflammation related to sepsis.Methods: In the first paper presented, inflammation and edema in the abdomen were investigated in an endotoxin model. The study subjects were divided into two groups with different mean arterial pressures (MAP), another small group of healthy controls were studied as well. MRI analyses were used to measure perfusion in the different abdominal organs. In the second paper presented, differences in abdominal edema and inflammation were assessed in two groups of subjects, one group underwent MV and one group had spontaneously breathing.Results: In the first study, MRI analyses confirm that the group with higher MAP had better perfusion than the low MAP group. In the liver, perfusion was lower in LowMAP group compared to HighMAP group, but the HighMAP group had lower perfusion than the healthy controls. However, in the other studied organs HighMAP group and healthy controls had similar perfusion.Edema did not differ between the groups. Inflammation was globally higher in LowMAP group and correlated with hemodynamics. TNFα in liver tissue and portal vein serum correlated with intra-abdominal pressure (IAP).In the second study, the cytokine concentration was higher in serum in the MV group. MV did not increase abdominal edema or inflammation, compared to spontaneous breathing. Discussion and conclusion: Abdominal edema and inflammation are multifactorial phenomena, and many elements have to be included in the analysis. Perfusion plays an important role in determining inflammation and IAP. MV per se was not found to be related to increased edema and inflammation. In a previous study, the role of different levels of PEEP and different respiratory rate between mechanically ventilated and spontaneously breathing animals were not analyzed, but could have contributed to the results. The efforts made in this study to maintain similar respiratory rate and PEEP in both groups, could have contributed to the presented results.It is important to underline that, even if MV was not related to inflammation in abdomen, it was related to an increase in systemic inflammation, most probably because of an enhanced lung production of inflammatory mediators.Further studies, focusing on the role of respiratory rate and PEEP on abdomen, as well as the analysis of the inter-relations among inflammation, perfusion and edema, are needed to increase the pathophysiological understanding of these phenomena.
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2.
  • Sperber, Jesper (författare)
  • Protective Mechanical Ventilation in Inflammatory and Ventilator-Associated Pneumonia Models
  • 2016
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • 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.
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