VAP

Does this pt have VAP (JAMA 2007;297(14):1583)
Box. Centers for Disease Control and Prevention (CDC) National Healthcare Safety Network Definition for Ventilator-Associated Pneumonia

Clinical signs

At least 1 of the following:

• Fever (temperature >38°C [100.4°F] with no other recognized cause)
• Leukopenia (<4000 white blood cells/µL) or leukocytosis (12 000 white blood cells/µL)
• For adults 70 years or older, altered mental status with no other recognized cause

Plus at least 2 of the following:

• New onset of purulent sputum, or change in character of sputum, or increased respiratory secretions, or increased suctioning requirements
• New-onset or worsening cough, or dyspnea, or tachypnea
• Rales or bronchial breath sounds
• Worsening gas exchange (eg, O2 desaturations [eg, PaO2/FiO2   240], increased oxygen requirements, or increased ventilation demand

Microbiological criteria (optional)
At least 1 of the following:
       Positive growth in blood culture not related to another source of infection
       Positive growth in culture of pleural fluid
       Positive quantitative culture from bronchoalveolar lavage (104 colony-forming units/mL) or protected specimen brushing( 10³ colony-forming units/mL)
       Five percent or more of cells with intracellular bacteria on direct microscopic examination of Gram-stained bronchoalveolar lavage fluid
       Histopathological evidence of pneumonia
 

*In patients without underlying pulmonary or cardiac disease (eg, respiratory distress syndrome, bronchopulmonary dysplasia, pulmonary edema, or chronic obstructive pulmonary disease), 1 definitive chest radiograph is acceptable. first signs are slowly increasing fio2 requirement
 

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Assessment of a chest radiograph is a practical place to begin. The appearance of a new infiltrate suggests that VAP is possible (summary LR, 1.7; 95% CI, 1.1-2.5) and should prompt a second look at the patient's temperature, sputum purulence, and leukocyte count. When 2 or more of these signs are positive, then VAP becomes more likely (summary LR, 2.8; 95% CI, 0.97-7.9). Taking a 9.7% incidence as the prior probability for VAP among ventilated patients, ⁸ the above combination of findings will increase the likelihood of VAP to 23% (95% CI, 9.4%-46% after taking the limits of the LR confidence interval). Expert clinicians tend to also consider impairment of gas exchange as a necessary, albeit nonspecific and insufficient, criterion to diagnose VAP. ²⁴ This intuitive requirement was not formally assessed in the independent studies included in this review.

In contrast, the absence of new infiltrates substantively lowers the likelihood of VAP (summary LR, 0.35; 95% CI, 0.14-0.87). The absence of fever, sputum purulence, or an elevated white blood cell count does not add information to that gained from a radiograph without infiltrates. If the pretest probability of VAP is 9.7%, ⁸ then routine clinical evaluation including a stable chest radiograph without new infiltrates can lower the probability of VAP to 3.6% (95% CI, 1.5%-8.5%).

Analysis of pulmonary secretions can further refine the likelihood that VAP is present or absent. BAL fluid in which less than 50% of the cells are neutrophils argues against the presence of VAP, with an LR that ranges from 0.05 to 0.10. By contrast, the presence of microorganisms on a Gram stain of pulmonary secretions substantively increases the probability of VAP. The suggestiveness of a positive Gram stain result increases almost exponentially with progressively more invasive diagnostic techniques—the positive LR for a positive Gram stain result on a blind bronchial aspirate is only 2.1 (95% CI, 0.81-5.5), but this increases to 5.3 (95% CI, 1.3-22) with mini-BAL and up to 18 (95% CI, 1.1-302) on BAL fluid gathered via fiberoptic-guided bronchoscopy. Quantitative bacterial cultures of pulmonary secretions can also help diagnose VAP. Growth of more than 10⁵ colony-forming units/mL of bacteria from a blind bronchial aspirate is highly suggestive of VAP (summary LR, 9.6; 95% CI, 2.4-38). A threshold of only 10⁴ colony-forming units/mL on BAL fluid, by contrast, is not definitive. This is likely a reflection of greater potential for contaminant organisms to reach this lower growth threshold. Negative quantitative cultures of both bronchial aspirates and BAL fluid only moderately decrease the probability of VAP.

The finding that analysis of both blind bronchial aspirate and BAL can contribute useful information but that neither is definitive is consistent with a recent randomized clinical trial showing no difference in 28-day mortality regardless of which of these 2 diagnostic strategies was initially used. ⁵¹ Patients were selected to be included in that study if they manifested the classic clinical features of VAP analyzed in this review. All patients were given broad-spectrum antibiotics immediately after diagnostic sampling. Approximately 40% of the patients in both groups of the trial, however, were not cured by the end of the study, raising the possibility that their clinical syndrome was not caused by true, histological VAP but by some other etiology. This again bespeaks the imperfect accuracy of clinical signs for VAP. The trial teaches that obtaining blind bronchial aspirates might be a reasonable starting procedure for the majority of patients, but patients who do not improve with antibiotics guided by this strategy merit further diagnostic workup. This could include bronchoscopy to further evaluate whether VAP is present, as well as other specialized studies to assess for noninfectious causes of pulmonary disease.

The findings of this review support the consensus opinions published by the Infectious Diseases Society of America and the American Thoracic Society. ²⁴ Their guidelines acknowledge the lack of a definitive gold standard to diagnose VAP and the practical difficulty of making the diagnosis at the bedside. Both societies recommend a combination of clinical signs and quantitative microbiological data to diagnose and manage VAP, while emphasizing the importance of constant reevaluation of the diagnosis over time. Clinicians should suspect VAP when chest radiography reveals the presence of a new or progressive infiltrate and the patient has at least 2 of fever, abnormal white blood cell count, or purulent secretions. As soon as VAP is suspected, clinicians are urged to immediately obtain a lower respiratory tract specimen for microscopy and culture (quantitative or semiquantitative). Because of the uncertainty in diagnosis when a patient is initially examined, antibiotics are typically started unless the pretest probability for VAP is very low. After 48 to 72 hours of antibiotic therapy, clinical response should be assessed by reevaluating the patient's temperature, white blood cell count, oxygenation, and results of chest radiography, pulmonary secretion microscopy, and secretion culture. Absence of improvement should prompt a search for an alternative diagnosis or a reason for therapeutic failure.

The findings of this review are tempered by limitations of the source data. Many of the conclusions were based on a limited number of small studies that differed in both their methods and their findings. Moreover, even a histological gold standard is not without controversy. First, series limited to patients ultimately undergoing autopsy are inherently biased toward the sickest patients. Second, pulmonary biopsies risk missing the isolated patchy lesions that are characteristic of VAP. Third, interobserver agreement between pathologists has been reported to be only moderately good ( = 0.45). ¹⁰ Finally, the interpretation of pulmonary pathology is complicated by delay between the initial clinical development of pneumonia and the subsequent autopsy, during which interim healing and antibiotic exposure can complicate the histological picture.

The best available evidence suggests that clinical examination can be used to alert physicians to the possibility of VAP but that examination alone is insufficient to establish a definitive diagnosis. Examination of pulmonary secretions can help refine physicians' clinical suspicions. The presence of bacteria on Gram stain or bacterial growth above a quantitative threshold favors the diagnosis, while less than 50% neutrophils in a pulmonary specimen makes VAP less likely. The absence of a new infiltrate on chest radiograph also makes disease unlikely. Clinicians caring for ventilated patients with a clinical syndrome consistent with VAP should be ready to consider additional diagnoses and further investigations, particularly when an empirical trial of antibiotics does not lead to improvement within 48 to 72 hours.