This retrospective analysis yielded three main findings. First, patients with VAP may have high rates of ventilator dependence. Walkey et al. suggested that patients with VAP were more prone to ventilator dependence than with patients without VAP [24
]. Second, clinical variables such as underlying chronic cardiopulmonary disease, previous ADRS, high initial Fi02 and MAP support, high initial OI, high APACHE II and SOFA scores during the occurrence of VAP, COPD with acute exacerbation, a low initial respiratory rate, history of tracheostomy before the occurrence of VAP, and inappropriate initial use of antibiotics may have a negative influence on ventilator weaning rates. Patients with respiratory failure due to pneumonia including community acquired pneumonia, healthcare-associated pneumonia, and hospital acquired pneumonia supervening with ventilator associated pneumonia have a higher likelihood of developing ventilator dependence, despite the successful initial treatment of pneumonia. In addition, we determined that previously impaired cardiac function and high OI, APACHE II, and SOFA scores during the occurrence of VAP were independent factors in predicting ventilator dependence. Third, the appropriateness of initial empiric antibiotics was an important factor related to ventilator weaning among patients with VAP. Fourth, Pa02/Fi02 values stratified as four groups as >400, 300 ~ 400, 200 ~ 300, and <200 were highly correlated with ventilation duration.
Patients can become dependent on ventilator support for a variety of reasons. Often, hospitalized elderly patients who are nutritionally depleted develop pneumonia leading to respiratory failure [25
]. When patients have impaired underlying lung function and suffer from infections such as pneumonia, they fail to oxygenate the blood properly, leading to respiratory failure and the need for mechanical ventilation. When reversible conditions such as infection and malnutrition are properly and completely addressed, patients can be successfully weaned from their dependence on ventilators.
In this study, we found that underlying congestive heart failure and chronic respiratory disease may depress the ventilator-weaning rate in patients with VAP, and these underlying cardiopulmonary diseases may lead to impaired pulmonary function. If patients with cardiopulmonary diseases acquire VAP while being hospitalized, they are likely to suffer from ventilator dependence. Previous studies have suggested that cardiac surgery can lead to decreased pulmonary function (as measured by spirometry) and impaired pulmonary mechanics—even in the absence of diaphragmatic dysfunction—for several months following surgery [27
], and this may lead to the need for prolonged mechanical ventilation. COPD results from inflammation and/or alterations in repair mechanisms, the “spill-over” of inflammatory mediators into the circulation, may result in important systemic manifestations of the disease, such as wasting of skeletal muscle and cachexia [31
]. Furthermore, skeletal muscle can be wasted by sepsis syndrome [34
]. This acquired weakness results in prolonged mechanical ventilation and difficulty in weaning.
Using several scoring systems, intensive care physicians are able to accurately and reliably measure the severity of illness in the ICU. Most scoring systems focus on mortality as the main outcome measure. Disease severity as indicated by the APACHE II and SOFA scores also influences ventilator dependence in VAP patients in this study. Siempos and Vardakas suggested that disease severity and SOFA on the day of diagnosis with VAP could be independent predictors for mortality in meta-analysis [35
]. Gursel and Demirtas suggested that APACHE II scores at the time of diagnosis with VAP could be useful in predicting mortality in the pulmonary ICU population developing VAP [36
]. We also found that mortality and ventilator dependence were both related to poor APACHE II and SOFA scores. If patients receive an APACHE II score of >23.5 and a SOFA score of >8.5, this would imply profoundly compromised lung function and may increase the difficulty associated with ventilator weaning.
Oxygenation failure at any point during the course of acute hypoxemic respiratory failure has an impact both on the duration of mechanical ventilation and survival. This is best reflected by OI [37
]. Rapid deterioration of OI in intubated ventilated patients is associated with high mortality rates; a diminished improvement of OI appears to increase the risk of death in the course of acute respiratory failure. This emphasizes the importance of OI in monitoring oxygenation status in ventilated patients. Gajic et al. also suggested that age, OI, and cardiovascular failure three days after intubation are predictors of death or prolonged mechanical ventilation, and may inform decisions regarding specific interventions such as tracheostomy, particularly in terms of the design of clinical trials [38
]. In this study, we also determined that poor cardiopulmonary function and initial OI could be independent factors for predicting ventilator dependence, particularly among VAP patients with OI value over 12.01.
Mechanical ventilation leads to high morbidity, mortality, and financial cost. Because prolonged or delayed liberation from ventilators can cause harm, safe, expeditious weaning is highly desirable [39
]. Aggressive therapy to reduce the ventilatory workload should be pursued. In patients with nosocomial infections, appropriate initial antibiotic therapy is associated with increased survival rates, reduced hospital stays, and lower healthcare costs [42
]. Broad-spectrum antibiotics are an optimal initial choice for nosocomial pneumonia and severe sepsis [44
]. In this study, we also found that the appropriateness of initial empiric antibiotic therapy for patients with VAP may be helpful in weaning patients from mechanical ventilation. Timely administration of antibiotics is associated with decreased mortality as well as reduced impairment to the inflammatory response [42
]. If delaying the initiation of antibiotic therapy precludes prompt abatement of systemic inflammation, this would arouse intense inflammatory mediator responses. Pro-inflammatory mediators can be activated with consequent uncontrolled activation of the immune system causing lung damage, leading to acute lung injury or ARDS that would further damage underlying pulmonary function and eliminate any chance of ventilator weaning.
Mechanical ventilation may cause substantial morbidities such as VAP, further destroying pulmonary function. If patients under mechanical ventilation cannot be liberated in a timely manner, prolonged ventilation contributes to an increase in clinical morbidity running in a vicious cycle. This makes weaning an important clinical issue for patients and clinicians.
The important discovery of the present study is that initial appropriate empiric treatment with antibiotics shortens the duration with which ventilation must be maintained by addressing the underlying impairment to cardiopulmonary function. Disease of high severity also leads to ventilator dependence. A number of limitations should be mentioned when interpreting the results of this study. First, the retrospective design of the study may have passed over factors influencing the outcome. It is our hope that the design would generate hypotheses for future prospective controlled studies to confirm our final points. Second, bronchoalveolar lavage was not performed in every patient in this retrospective study. However, sputum cultures from endotracheal aspirate were used as a diagnostic method in patients suspected of carrying pulmonary infection. Third, ventilator settings could be one important factor that could contribute to ventilator dependence, and protective ventilation strategy may be helpful in ARDS patient. However, ventilation strategy was not described in this study. Indeed, we could not record ventilation setting in a retrospective manner because ventilator setting for VAP-ARDS patient is different individually by attending personnel. We also addressed this as a limitation.