| Summary: | 博士 === 國立陽明大學 === 生理學研究所 === 102 === Critically ill patients who undergo respiratory failure and receive mechanical ventilation have a necessity of intensive care unit (ICU) admission. The principle of managing mechanically ventilated ICU patients is based on the pathophysiology of respiratory failure and underlying disease. Therefore, to investigate disease pathogenesis can provide the critical information for intensivists to refine the management of these mechanically ventilated patients in the ICU setting. Chronic obstructive pulmonary disease (COPD) is one of the important diseases leading to respiratory failure in ICUs. The pathogenesis and disease development of COPD is associated with chronic lung inflammation. The first aim of the study is to investigate the contribution of the inflammatory mediator, high-mobility group box 1 (HMGB1), in the lung inflammation and disease development of COPD. The results show: 1) plasma HMGB1 levels negatively correlate with post-bronchodilator forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) ratio in smokers; and 2) In smokers with COPD compared with smokers without COPD, plasma HMGB1 levels are significantly elevated, and numbers and portion of HMGB1 expressing cells in epithelium and submucosal areas are also significantly increased. These results suggest that high expression of HMGB1 in the blood and lungs is related to the lung function impairment and appears to be associated with the development of COPD in smokers.
Nosocomial infection is one of the important issues for hospitalized patients. Among nosocomial infections in the ICU setting, ICU-acquired bacteremia (IAB) has been reported to be associated with high medical expenditure and ICU mortality. However, clinical features and patient outcomes for mechanically ventilated ICU patients who develop IAB have not yet been investigated. The second aim of the study is to describe the clinical features of IAB and to investigate the impact of IAB on patient outcomes in mechanically ventilated ICU patients. The results show: 1) ventilator support for COPD and congestive heart failure, and patients admitted from nursing home as the independent risk factors for developing IAB; 2) patients with IAB significantly associated with longer length of ICU stay, prolonged ventilator use, lower rate of successful weaning, higher rate of ventilator dependence, and higher rate of ICU mortality as compared to those without IAB; 3) IAB as the independent risk factor for ICU mortality; 4) IAB due to Pseudomonas aeruginosa being likely polymicrobial, lung source and prior antibiotic use; 5) IAB due to Escherichia coli developing earlier and originating from urinary tract source; 6) IAB due to methicillin-resistant Staphylococcus aureus related to a placement of central venous catheter and multiple sets of positive hemoculture; and 7) Elizabethkingia meningoseptica significantly associated with delayed/inappropriate antibiotic treatment. Conclusively, IAB is significantly associated with poor patient outcomes in mechanically ventilated ICU patients. The clinical features related to IAB and clinical characteristics of IAB based on specific bacterial species may be utilized to refine the management of IAB and improve the quality of critical care.
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