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Blinded Invasive Diagnostic Procedures in Ventilator-Associated Pneumonia^*

^* From the Division of Pulmonary and Critical Care Medicine, Louisiana State University Medical Center, Shreveport, LA.

	Introduction

TOP Introduction Qualifications Conclusions

 
Because invasive diagnostic testing using fiberoptic bronchoscopy (FOB) is associated with inconvenience, expense, the need for operator expertise, and potential side effects, other methods have been developed for taking samples from the lower respiratory tract of patients suspected of having ventilator-associated pneumonia. As with other methods, issues of sensitivity and specificity arise because of the difficulty of accurately diagnosing pneumonia.

This section reviews 15 studies evaluating the accuracy of blinded sampling methods.^{20,30,31,37,45,84,93,119–126} The studies were performed in patients receiving mechanical ventilation in various types of ICUs. Included are small numbers of patients with community-acquired pneumonia who require ventilator support, as well as a few immunocompromised patients. These studies investigated 654 episodes of pneumonia, most of which were thought to be pneumonia on a clinical basis. Of these 654 episodes, 321 were identified as pneumonia using a variety of different methods.

The following three blinded procedures were evaluated: blinded bronchial sampling (BBS); mini-BAL; and blinded sampling with the protected-specimen brush (BPSB) technique, using several different protected brushes.

Five studies investigated BBS (Tables 16 , 17 ) using four different catheters.

Seven studies investigated the second procedure, mini-BAL. Three studies used the combicath, a single-sheathed, 50-cm, sterile, plugged, telescoping catheter,^20,37,84 one study used a different telescoping catheter,¹²¹ and the remaining three studies used unprotected catheters. The amount of lavage fluid instilled varied from 20 to 150 mL. Quantitative cultures were performed, and the bacterial concentration considered significant for the diagnosis of pneumonia ranged from 10³ to 10⁴ cfu/mL, a bacterial index of 5, or was not stated. Of the 317 episodes using mini-BAL, the diagnosis in 135 was pneumonia.

The last blinded-sampling method, BPSB, was investigated in five studies. This method incorporates a sterile brush that is protected from contamination. Two studies used the accucath, a sterile, single-use, 15F apparatus containing a nylon specimen brush 16 mm long at its tip, which is protected from contamination by an everting, air-filled balloon mechanism. The other three studies used a standard protected-specimen brush (PSB) technique. Quantitative cultures were performed, and a level of 10³ cfu/mL was considered significant for the diagnosis of pneumonia. BPSB was performed in 147 episodes, yielding a diagnosis of pneumonia in 70. Two studies simultaneously investigated two different types of blinded sampling procedures.^20,125

Most of the reported studies are case series, although four immediate postmortem studies are described. Enrollment was prospective but rarely consecutive. The length of time of mechanical ventilation varied considerably. In most studies, the test results and reference tests were assessed by investigators who were aware of the patient’s clinical evolution. The techniques and bacteriologic methods used generally were well described. A major limitation with interpreting the data is a general lack of standardization of collection methods and of quantitative levels for significance. Although not specifically addressed in three studies, in at least 250 episodes the patients were either receiving antibiotics or had received antibiotics in the recent past. There is no universal reference or "gold standard" test, even among the four studies with extensive postmortem investigations.^20,37,84,124 These four studies retrospectively diagnosed pneumonia by relying on traditional clinical, radiographic, and microbiological criteria or on the clinical pulmonary infection score.^{30,45,120,126}

The remaining seven studies investigated blinded sampling only in patients with clinical evidence of pneumonia. No control subjects were included, or the study was designed to measure concordance.^{31,93,121–123,127} All of these studies enrolled patients who were clinically identified as having pneumonia. Also, an FOB procedure was performed and lower respiratory tract samples were collected using a protected brush. BAL samples were obtained in only a few of these studies.

Since these seven investigations made up a significant proportion of the available studies, the results of the PSB sampling obtained by FOB was selected as the "gold standard." Thus, the methodology is fairly standard, and was followed in all studies. Additionally, recovery of at least one similar organism in sufficient bacterial concentration by both the PSB sampling method and BPSB was required for confirmation. In five studies, histology data were available in at least some patients, and in several of these, cultures of lung tissue also were obtained. Unless otherwise stated in the article, sensitivity and specificity were determined using only the findings from the lung histology studies. The major limitations of blinded procedures were that most were nondirected and rarely was positioning verified by radiographic methods. The sensi- tivity and specificity for each study varied and probably were dependent on prior antibiotic treatment, study population, and reference test employed.

	Qualifications

TOP Introduction Qualifications Conclusions

 
Studies
The 15 studies investigating blinded sampling were published after 1988 and covered 654 episodes of pneumonia. The vast majority of patients had ventilator-associated pneumonia (VAP), but a few had community-acquired pneumonia and required mechanical ventilation. Three different blinded methods were studied. Five studies investigated BBS sampling (Tables 16 , 17) .^21,120–123

Description of the Population
All patients were adults who were receiving mechanical ventilation. Mechanical ventilation was a requirement for enrollment in each study, but the minimum length of duration varied from 24 to 72 h. The average age of patients enrolled was the fourth decade of life in 1 study, the fifth or sixth decade in 10 studies, and the seventh decade in 3 studies. One study did not state the average age.

Most enrollment criteria required a clinical suspicion of pneumonia or a high risk that pneumonia would develop. However, one study enrolled control patients who were without clinical evidence of pneumonia.³⁷ The remaining studies attempted to exclude pneumonia histologically or clinically, or simply compared blinded procedures with FOB-directed diagnostic methods.

Were the Test Results and the Reference Standard Assessed by Investigators Unaware of the Results of the Other Investigators?
The reference tests used in most studies were not standardized. Based on a review of the 15 studies, it appears that only in the 4 postmortem studies were the test results and reference standards interpreted blindly by investigators who unaware of the findings of other investigators. In the remaining 11 studies, it is unclear whether the investigators were aware of other test results.

Were Methods of Performing the Test Described Adequately?
Most studies adequately described the methods used so that an investigator could reproduce the results. The procedure, the collection device, and the method of processing the material varied among the studies, presumably because of the investigator’s preference.

What Criteria Were Used to Assess the Quality of the Sample?
Because of the different sampling methods used, many studies did not assess the quality of the sample other than by using quantitative cultures. One of the BBS studies attempted to assess the quality of the sample, and the criteria included direct examination for the presence of elastin fibrils, bacteria, intracellular organisms, and squamous cells. Three of the studies investigating mini-BAL assessed quality by looking for epithelial squamous cells or bronchial cells.^37,84,124 The BPSB studies used only quantitative culturing (Tables 18 , 19) .

Study Design
The most common design was to study a case series in which the investigators selected patients with suspected VAP. One study evaluated control subjects prospectively, and others determined control subjects later based on histology or clinical follow-up.

Antibiotics
Most studies did not exclude patients who had recently received or were receiving antibiotics. In only one study was the recent use of antibiotics an exclusionary criterion. Among the 251 episodes in the five BBS studies, recent or ongoing antibiotic use was noted in 118. Three of the seven mini-BAL studies (Table 20) did not discuss antibiotic use, but, in the four that did, recent or ongoing antimicrobial therapy was noted in 115 of 176 episodes. Finally, in the five studies investigating BPSB (Table 21) , antibiotic therapy was recent or ongoing in 55 or 147 episodes. The effect of antibiotics was specifically addressed in one study,¹²⁵ and the authors noted that BPSB sensitivity was reduced from 94 to 70%.

Specificity
Specificity varied from 74 to 100% for BBS, from 66 to 96% for mini-BAL, and from 71 to 100% for BPSB. Again, these variations were probably affected by other factors, including different sampling methods and devices, variations in patient populations, and the need to compare blinded study results to those with FOB-directed PSB.

Concordance
As mentioned above, six studies looked only at concordance or agreement between the results using an FOB-directed PSB technique and a blinded technique. Agreement between results using blinded diagnostic methods and the FOB-directed PSB method varied from 73 to 100%. With BBS, agreement was 93% and 87%, respectively.^121,122 One study looked at mini-BAL and found that agreement with the results using the FOB-directed PSB method was 83%.¹²⁷ In the three studies comparing BPSB with FOB-directed PSB, results were 73%, 85%, and 84%, with agreement reaching 90 to 100% when sampling occurred in patients with either right-sided or bilateral pneumonia.^31,123,125

Risks
Three studies dealt exclusively with postmortem results, where side effects are not evaluated. Of the remaining 12 studies, 4 stated that there were no significant complications, and 2 did not discuss complications. Bleeding or hemoptysis, described as minimal, was noted in one or two patients following a blinded procedure in each of the four remaining studies. One patient developed a pneumothorax following BBS.

Two studies described complications in detail.^123,127 Kollef et al¹²⁷ compared the FOB-directed PSB method to mini-BAL and noted that the PSB method was associated with a higher incidence of severe hypoxemia (four patients vs one patient, respectively) and tachycardia (five patients vs one patient, respectively), and with a lower incidence of minor hemorrhage (four vs five patients). Leal-Noval et al¹²³ compared the use of an FOB-directed, telescoping, protected catheter to the BPSB method. During FOB, the following data were noted: intracranial pressure increased in seven patients; arterial oxygen saturation decreased in six patients; hemoptysis occurred in five patients; hemo- dynamic alterations occurred in five patients; and pneumothorax was occurred in one patient.

	Conclusions

TOP Introduction Qualifications Conclusions

 

Three blinded, nonbronchoscopic techniques have been investigated.

There was a lack of standardization in the type of catheter used, position of the catheter, and, in the case of BAL, the volume of fluid instilled.

The limited number of studies performed to date suggests that the sensitivity of blinded techniques is similar to that of FOB techniques, ranging from 74 to 97% for BBS, from 63 to 100% for mini-BAL, and from 58 to 86% for BPSB. The specificity of these blinded techniques also is similar to that with FOB techniques, ranging from 74 to 100% for BBS, from 66 to 96% for mini-BAL, and from 71 to 100% for BPSB.

Side effects for blinded techniques appear to be minimal and, at worst, are similar to those for FOB-directed diagnostic techniques.

	Footnotes

 
Abbreviations: BBS = blinded bronchial sampling; BPSB = blinded protected-specimen brush; FOB = fiberoptic bronchoscopy; PSB = protected-specimen brush; VAP = ventilator-associated pneumonia

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