VAP is a common complication associated with invasive ventilator support and contributes to a significant mortality and morbidity in these patients.[14
] Because of poor specificity of the clinical diagnosis of VAP, reliance is often placed on radiologic and microbiologic diagnosis. Microbiologic diagnosis comprises culture of blood, pleural fluid and respiratory secretions including proximal (tracheal aspirate) and distal airways (BAL and brush). It is important to keep in mind that the sensitivity of blood culture for diagnosis of VAP is less than 25%, and even when positive, the organism may originate from an extrapulmonary site of infection in as many as 64% of cases, even when VAP is present.[16
ETA is the most commonly used method of airway sampling in ICUs all over the world. Gram stain, non-quantitative and semi-quantitative culture of tracheal secretions has the advantage of reproducibility and of requiring little technical expertise and no specialized equipment or technique. However, these studies add little to the sensitivity and specificity of the clinical diagnosis of VAP, as the upper respiratory tract is frequently colonized with potential pathogens, even in the absence of pneumonia.[12
] Thus, if an organism is cultured or noted on gram stain, one does not know if it is the cause of pneumonia or simply colonization. Our study too questioned the value of microbiologic diagnosis of VAP based on ETA culture results by demonstrating its poor microbiologic agreement with distal airway sampling techniques. It highlights that ETA does not represent a true distal airway sample. Therefore, treating VAP based on ETA microbiology may not be the optimum management of these patients.
Studies from various countries have shown that bronchoscopic procedures are important part of evaluation of patients with VAP. However, these are associated with false-positive and false-negative results.[18
] Canadian Critical Care Trial group, in a large multicentric study, demonstrated that there was no difference in clinical outcome among patients treated for VAP based on bronchoscopic or non-bronchoscopic procedures.[21
] Further, in developing countries like India, this facility is not routinely available for patients admitted to ICU. Therefore, it is important to evaluate the role of non-bronchoscopic techniques in our setting. Our study has shown that NBAL has good sensitivity, specificity, PPV and NPV. Inherent advantages of non-bronchoscopic techniques include less invasiveness, lesser compromise of oxygenation, ventilation and respiratory mechanics during the procedure, less likelihood of increasing intracranial pressure and arrhythmia, lack of contamination through the bronchoscopic channel, and lower cost.
Although NBAL is a blind procedure, its concordance with bronchoscopic brush proves the fact that protected sample adequately represents the lower airway secretions (either side) and efficiently diagnoses VAP. The utility of NBAL for diagnosis of VAP has been demonstrated by other researchers also, both in clinical as well as autopsy studies.[5
] Rouby et al
. showed that the sensitivity and specificity of NBAL were 70 and 69%, respectively, using post-mortem histologic and bacteriologic analysis of lung as the gold standard for the diagnosis of VAP.[22
] Pugin et al
. used CPIS as the diagnostic criteria for VAP and found that sensitivity, specificity, and PPV of non-bronchoscopic BAL were 73, 96, and 92%, respectively.[5
] Many other researchers also have shown that NBAL has high sensitivity (70–70%) and specificity (69–69%) depending on the criteria used to diagnose VAP.[5
] Our study results are comparable to these and we hope that this technique would find utility in clinical practice.
We observed a good agreement for the type of microorganisms among bronchoscopic BAL, brush and non-bronchoscopic BAL. The predominant pathogens cultured were identical in 84% of samples. Kollef et al
. in their study showed that NBAL done by a respiratory physiotherapist has shown good microbiologic agreement (83.3%) with bronchoscopic protected brush.[24
] These results signify that blind sampling techniques like NBAL are good modalities for microbiologic diagnosis of VAP. As shown in another recent trial,[26
] our study also highlights that ETA does not represent a true distal airway sample. The concordance of NBAL with bronchoscopic brush proves the fact that protected sample adequately represents lower airway secretions (either side) and accurately diagnoses VAP.[5
] Therefore, ETA should be replaced by NBAL for microbiologic diagnosis of VAP.
Theoretically, there may be concern of diluting the alveolar fluid for the bronchoscopic samples when invasive samples (BAL and brush) are obtained after the non-bronchoscopic samples (NBAL). However, most of the studies have followed this protocol and did not find significant effect of this dilution on microbiology of the sample.[13
] This effect will be further nullified by setting different thresholds for CFU/ml for each microbiologic sample, such as 103
for brush and 104
An important consideration in our study is the financialimplications associated with providing these diagnostic procedures. Bronchoscopic procedures are expensive, require expertise and are not freely available, whereas NBAL is a simple procedure which can be performed by resident doctors and paramedics (nurses) posted at the ICU after a small demonstration. This will result in significant reduction in the cost of management of VAP as shown in a report by Kollef et al
., where about $1000 was saved per substitution of bronchoscopic brush with NBAL.[24
] Similar benefits should be expected in our setting as the catheters and mucus extractor used in our study cost only
50 per patient. However, total savings depend both on these direct savings andon the balance of false-positive and false-negative resultsproduced by these tests with their ensuing costs and patientcharges.
An important limitation of our study is the validity of the exact operating characteristics (sensitivity, specificity, PPV, and NPV) for various sampling techniques, which may be questioned in the absence of the gold standard for the diagnosis of VAP. Autopsy examination of lung tissue (bacteriologic and histologic) has beenused as a gold standard to determinethe precise diagnostic yield of similar bronchoscopic and non-bronchoscopicprocedures.[22
] However, this has a limitation that it is not useful in clinical decision making. The diagnostic utilityof this approach may be further compromised due to histologic sampling errors, the effects of previous antibiotic administration on tissuecultures, and problems related to the timing of postmortem lungexamination.[22
] It has been suggested that the diagnostic criteria used for VAP should have high sensitivity. This approach is based on the premisethat the risk for not treating an individual patient with pneumoniaprobably outweighs the risk for unnecessary antibiotic administration.[31
] For this study, we used CPIS as the standard, which has high sensitivity for the diagnosis of VAP.[5
] However, there are other studies where usefulness of CPIS for the diagnosis of VAP was questioned.[32
] Therefore, one should keep this limitation in mind during interpretation of the results of our study.
Another important limitation of our study is a relatively small cohort. Larger studies from other parts of the world have shown comparable results.[5
] Indian data comparing these diagnostic modalities using independent criteria (histologic and blood orpleural fluid cultures) to establish the diagnosis of VAP are lacking; therefore, it is difficult to determine the exactoperating characteristics (sensitivity, specificity, PPV and NPV) of these non-bronchoscopic techniques. Because of this lack of established diagnostic criterion standard, we could not perform a complete economic analysis; therefore, the effect of cost associated with thetreatment of false-positive culture results cannot be commented upon.
Finally, one would expect that ETA will grow more organisms and will show false-positive results more frequently. However, our study has shown that ETA has a lower yield than NBAL, BAL and bronchoscopic brush. Although empirical broad-spectrum antibiotics might have altered the microbiologic result, however, this would have a similar effect on other microbiologic samples. This has been observed previously in antibiotic naïve as well in patients who were on empirical antibiotics.[21
Till date, the optimal strategy for the diagnosis of VAP remains to be defined. The American Thoracic Society guidelines do provide expert opinion supporting quantitative or semi-quantitative cultures of respiratory specimens, although the panel favors invasive quantitative techniques. Our study has shown that NBAL is an acceptable alternative to bronchoscopyfor the evaluation of suspected VAP.Therefore, our observations, if verified in other ICUs, might simplify the approach for the diagnosis of VAP. This conclusion is based on the fact that NBAL is relatively inexpensive, requires lesser expertise, and may bea useful method for the serial evaluation of suspected nosocomialpneumonia in patients on mechanical ventilation.