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* From the Servei de Pneumologia, Hospital Clínic, Barcelona, Spain.
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Introduction |
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 TOP Introduction QualificationsConclusions |
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We reviewed 23 studies evaluating the accuracy of BAL methods using fiberoptic bronchoscopy to diagnose VAP in a total of 957 patients. The number of reported VAP episodes was 431. Most reported studies are case series, although five immediate postmortem studies have been described since 1995.
Patient enrollment was prospective, but consecutive enrollment was used in only four studies. The duration of mechanical ventilation is described in most studies as lasting from 1 to 90 days. In most cases, except in the postmortem studies, investigators assessing the test results and reference tests were aware of the patients’ clinical histories. The techniques and bacteriologic methods used are well described, but in some studies the microbiological or BAL methods are referenced to prior publications.
BAL technique is not completely standardized. The amount of liquid instilled varies roughly from 130 to 150 mL. The first aliquot usually is discarded, and the rest are pooled for quantitative bacterial analysis. Serial dilutions and calibrated loop methods have been used for quantitative cultures. Four studies have used protected bronchoscopic methods with balloon occlusion, and one study employed the mini-BAL technique via fiberoptic bronchoscopy. Only two studies assessed the quality of BAL specimens, and they did so by the detection of squamous epithelial cells. No study assessed the presence of ciliated bronchial cells to indicate contamination by upper airway secretions. In most studies, BAL was compared with either bronchoscopic procedures (usually the protected-specimen brush [PSB] technique) or nonbronchoscopic methods (usually endotracheal aspiration and other blinded techniques). Most studies also used quantitative bacterial cultures to distinguish colonization from infection. For that purpose, the most frequent cutoff point was 104 cfu/mL. Information regarding prior antibiotic administration is lacking from some studies, but 457 patients are known to have received such treatment. The reference test "gold standard" is not standardized and varies among studies. Most studies combine clinical, microbiological, and histologic parameters. Immediate postmortem studies have used histology studies, lung cultures, or both. These studies are of particular value. The calculated sensitivity and specificity vary among studies, depending mainly on prior antibiotic treatment, type of study population, and the reference test employed. Some studies do not clearly state how sensitivity and specificity were calculated. Few studies reported receiver operating characteristic curves.
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Qualifications |
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TOPIntroductionQualificationsConclusions |
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How Were Patients Enrolled?
The study population was recruited prospectively in all 23
studies. In 4 studies, enrollment was consecutive; in the remaining 19,
patients were selected by the investigators. Some data in these studies
were collected retrospectively.
Description of the Population
The main descriptive parameter of the study populations was the
duration of mechanical ventilation, which varied from 24
h93,100 to 90 days.101 The average period was
10 days. One study102 did not mention the duration.
Another parameter was classification of the diagnosis as suspected,
unsuspected, or postmortem. In 16 studies, the pneumonia episode was
suspected on the patient’s inclusion into the study. In two of the
five postmortem studies, pneumonia was not suspected before the
patient’s death. In one study, the study population included suspected
and nonsuspected pneumonia cases (Table 12
).
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Were the Methods of Performing the Tests Described Adequately?
Overall, the test methods were well described. Usually, they were
of two types: bronchoscopic methods and microbiological methods. Five
studies did not adequately describe the
methodology;19,93,100–103 three of those referenced
microbiological methods to prior publications, and two referenced the
BAL method to prior publications (Table 12) .
Criteria Used to Assess the Quality of the Sample
The best way to assess the quality of a BAL sample is to examine
the cells of the fluid retrieved from preparations that had undergone
centrifugation. The presence of > 1% squamous epithelial cells is
evidence of oropharyngeal contamination. Ten studies did not mention
the use of any criteria to assess sample quality. The remaining studies
used cellular assessment, but only two looked for squamous epithelial
cells.18,19 To our knowledge, none of the studies looked
for ciliated bronchial cells as a marker of contamination.
Intracellular Organism Detection
Twelve studies looked for intracellular organisms (ICOs) as a
possible marker for VAP. Ten of these reported ICO thresholds ranging
from 2 to 25% to distinguish colonization from true infection. Of the
12 studies, eleven (92%) mentioned sensitivities and specificities.
Sensitivities ranged from 37%18 to 100%,24
and specificities ranged from 89%99 to
100%.18,24,30,97,101,103 These studies suggest that ICO
detection is a very specific marker for VAP.
Number of Patients and Episodes
A total of 957 patients receiving mechanical ventilation were
studied in the 23 series reported. The most patients in a single study
was 102,13,98 and the fewest was 9.19
As shown in parentheses in Table 13 , 431 episodes of VAP were studied. The criterion used for determining the number of episodes was the confirmation of VAP by clinical, microbiological, or histologic parameters. These parameters represent the reference standards. Many studies included control patients (ie, patients in whom pneumonia was not suspected). The selection of control patients was based on the absence of pulmonary infection or on the presence of a confirmed alternative diagnosis. Two studies prospectively included only control subjects.23,42 Some studies included patients who were suspected of having pneumonia but lacked definite criteria. These patients were not included in the 431 episodes we computed.
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Antibiotics
Sixteen studies included patients with and without prior
antibiotic treatment, four studies included only patients not receiving
antibiotic therapy,19,24,42,101 and one study included
only patients receiving antibiotic treatment.41 In three
studies, the presence or absence of antibiotic therapy is
unknown.30,103,104
More patients (544) received antibiotics than did not (375). Most studies stated the presence of antibiotics as a dichotomous variable.
Reference Standard
Several reference standards have been used to differentiate
between the presence and absence of pneumonia. Seventeen studies used
histology studies as the reference standard. The histologic criterion
was the presence of neutrophilic infiltration in the alveoli. Five of
the 17 studies used immediate postmortem
histology.18–20,97,99 Eleven studies combined histologic
and clinical or microbiological data. Only one study used postmortem
lung cultures as the reference test.99 Seven additional
studies used clinical data with or without microbiological reference
tests (Table 13)
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Clinical reference standards varied among studies and included the following: the presence of radiographic cavitation; classical signs of pulmonary infection (chest radiographic infiltrates, fever, leukocytosis, and purulent secretions); and good response to antibiotics. All reference standards included ruling out alternative diagnoses that could explain the presence of fever and pulmonary infiltrates. In one study,30 the authors developed a clinical pulmonary infection score that included the following six points: body temperature, leukocyte count, characteristics of tracheal secretions, oxygenation, chest radiographic findings, and a semiquantitative score for cultures of tracheal aspiration. The threshold to distinguish infection from noninfection was six points. Other studies used microbiological standards as reference tests. Most studies included the results of blood and pleural fluid cultures, the isolation of definite pathogens, and the isolation of pathogens above threshold levels from respiratory sample cultures.
Sensitivity
Sensitivity values are reported in all but two
studies,23,42 which included control patients
(ie, patients without pneumonia). The BAL method to detect
VAP had a variable sensitivity (22% in the study by Torres et
al97 to 100% in the study by Meduri et
al100). The calculated mean (± SD) sensitivity in the 23
studies was 73 ± 18%. The variability depends on prior antibiotic
treatment, type of study population, and the reference test used. In
six studies, the calculated sensitivity differed from that reported by
the authors.15,20,93,100–102 In three studies,
sensitivity could not be calculated.18,21,97 In some
studies, sensitivity was calculated for patients with and without prior
antibiotic treatment. Obviously, such treatment decreased sensitivity.
The method of calculating sensitivity was not standardized among studies, although formulas were applied uniformly. Sensitivity can be calculated by taking into account the number of patients or the number of microorganisms, and only one study23 made this distinction in computing the diagnostic yield parameters, although it did not do so specifically for sensitivity. The remaining articles do not describe how sensitivity was calculated in relation to this issue. Importantly, the calculation of sensitivity depends on the cutoff points of quantitative cultures. Most manuscripts used 104 cfu/mL, one study used 103 cfu/mL,15 and another study used 105 cfu/mL.42 One study30 calculated sensitivity by using the bacterial index instead of a definite threshold of quantitative cultures. The bacterial index is the sum of the logarithms base 10 (log10) of the different isolated microorganisms. The cutoff point used was 5. Another study104 used a similar index (simplified bacterial index) with a cutoff point of 4. Several articles13,18,20,21 calculated sensitivity using different cutoff points.
Specificity
The situation regarding the specificity of BAL is similar to that
of sensitivity. Three studies14,33,93 included only
patients with VAP, so they did not report specificity values. The mean
(± SD) calculated for specificity in the 23 studies considered was
82 ± 19%. The two studies that investigated only specificity for
BAL reported values of 65% and 82%, respectively.23,42
In eight studies, specificity was reported by the authors but could not
be calculated.18,21,30,93,97,98,101,104 In the remaining
studies, the calculated and reported specificities were the same.
Variability in specificity and in sensitivity is explained by differences in prior antibiotic treatment, the type of study population, and the manner in which pneumonia was confirmed (the reference test). The way specificity was calculated was not standardized among the studies, although formulas apparently were applied uniformly. Specificity can be calculated on the basis of the number of patients or the number of microorganisms, and we found only one article that specifically addressed this concern.23 Several articles13,18,20,21,23 calculate sensitivity using different cutoff points. Receiver operating characteristic curves were reported in only four studies.13,18,21,104
Risks
BAL is not without risk. The risks are of the following two types:
those inherent to the use of the fiberoptic bronchoscope (which this
report does not address); and those inherent to the instillation of
fluid during bronchoscopy. The most important and most common
consequences involve blood-gas exchange and include important decreases
in oxygenation and slight increases in CO2
values. In addition, hemodynamic parameters can be altered after the
BAL procedure. Alterations in blood-gas exchange depend on the type of
lavage used (conventional BAL or protected BAL) and the amount of
liquid instilled, which ranges from 50 mL in mini-BAL to 150 mL in
conventional BAL.
Recent articles have examined the effects of BAL on gas exchange. Steinberg and coworkers105 did not find significant changes in oxygenation, mean arterial pressure, heart rate, peak inspiratory pressure, or static thoracic compliance after BAL in 110 patients with ARDS. Papazian and colleagues20 found a significant decrease in PaO2 after BAL and a moderate drop in PaCO2. Guerra and Baughman102 observed a median decrease in PaO2 of 8 mm Hg (range, 63 to 29 mm Hg), which could be treated by increasing the fraction of inspired oxygen. However, the authors concluded that BAL using fiberoptic bronchoscopy is well tolerated in critically ill patients who are receiving mechanical ventilation.
Our group examined the effects on oxygenation of protected BAL and mini-BAL in patients with VAP and in control subjects. We found important reductions in the PaO2/fraction of inspired oxygen ratio 5 and 24 h after the procedure (a 20% drop from baseline to postbronchoscopy values). The decrease was independent of the type of BAL used. PaCO2 values showed a minor, transient increase (average, 7 mm Hg).106
Montravers et al25 observed similar effects on arterial oxygenation 3 and 5 h after BAL. These authors did not find important alterations in hemodynamic parameters (arterial pressure, heart rate, and cardiac index) after BAL. From these studies, it seems that the major side effect of BAL is the postprocedural reduction in arterial oxygenation in VAP patients. The patient may recover from the oxygenation impairment after several hours or may not recover completely. The variables involved in this response need detailed study. They include type of lavage, amount of liquid instilled, prior alteration in blood-gas exchange, and severity of the VAP.
One study described sepsis-like effects after BAL in VAP patients.107 This response is characterized by fever and by a decrease in mean arterial pressure and arterial oxygenation, and it seems related to the level of endotoxins in the BAL fluid. The reaction may be a bacterial migration-like effect from the alveoli to the systemic circulation during BAL. Further investigation is warranted.
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Conclusions |
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TOPIntroductionQualificationsConclusions |
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Footnotes |
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This article has been cited by other articles:
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  S. M. Koenig and J. D. Truwit Ventilator-Associated Pneumonia: Diagnosis, Treatment, and Prevention Clin. Microbiol. Rev., October 1, 2006; 19(4): 637 - 657. [Abstract] [Full Text] [PDF]
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 I. Porzecanski and D. L. Bowton Diagnosis and treatment of ventilator-associated pneumonia. Chest, August 1, 2006; 130(2): 597 - 604. [Abstract] [Full Text] [PDF]
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 M. Woodhead, F. Blasi, S. Ewig, G. Huchon, M. Leven, A. Ortqvist, T. Schaberg, A. Torres, G. van der Heijden, and T. J. M. Verheij Guidelines for the management of adult lower respiratory tract infections Eur. Respir. J., December 1, 2005; 26(6): 1138 - 1180. [Abstract] [Full Text] [PDF]
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 Guidelines for the Management of Adults with Hospital-acquired, Ventilator-associated, and Healthcare-associated Pneumonia Am. J. Respir. Crit. Care Med., February 15, 2005; 171(4): 388 - 416. [Full Text] [PDF]
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 G. Hugues, L. Olivier, G. Benoit, B. Allaouchiche, E. Boselli, S. Gibot, B. Levy, and M.-C. Bene Soluble TREM-1 and the Diagnosis of Pneumonia N. Engl. J. Med., April 29, 2004; 350(18): 1904 - 1905. [Full Text] [PDF]
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D. E. Ost, C. S. Hall, G. Joseph, C. Ginocchio, S. Condon, E. Kao, M. LaRusso, R. Itzla, and A. M. Fein Decision Analysis of Antibiotic and Diagnostic Strategies in Ventilator-associated Pneumonia Am. J. Respir. Crit. Care Med., November 1, 2003; 168(9): 1060 - 1067. [Abstract] [Full Text] [PDF]
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S. Michaud, S. Suzuki, and S. Harbarth Effect of Design-related Bias in Studies of Diagnostic Tests for Ventilator-associated Pneumonia Am. J. Respir. Crit. Care Med., November 15, 2002; 166(10): 1320 - 1325. [Full Text] [PDF]
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J. Chastre and J.-Y. Fagon Ventilator-associated Pneumonia Am. J. Respir. Crit. Care Med., April 1, 2002; 165(7): 867 - 903. [Abstract] [Full Text] [PDF]
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