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* From the Department of Pulmonary and Critical Care Research, Methodist Hospitals of Memphis, Memphis, TN.
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Introduction |
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 TOP Introduction Performance CharacteristicsResultsConclusions |
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A major methodological problem in assessing the sensitivity or specificity of these clinical criteria is obtaining the correct denominator. Instead of providing the total number of patients at risk, many studies give only the number who met at least one criterion or the number who gave a subjective clinical impression of being at risk for VAP. Therefore, sensitivities may be lower and specificities higher if data from these studies are applied to the entire population of ventilator-assisted patients.
Conversely, the sensitivity derived from the entire population is inappropriately high when applied only to a preselected population, such as all febrile patients or all patients with purulent tracheal secretions. The appropriate calculation depends on the question being addressed. If the clinical criteria are used to select a population at high risk of VAP, population-based statistics should be used. If, however, the goal is to discriminate between patients with VAP and those with a mimicking condition, the criteria characteristics in the suspected VAP group should be used. Both issues are clinically relevant, and operating characteristics in each population are calculated when possible. Use of the sensitivity and specificity calculated from these studies requires careful attention to the population being discussed.
Most studies assume that all patients who had no clinical findings did not have pneumonia. No study mentions that unsuspected pneumonia was documented in patients who did not meet study entry criteria. The fact that autopsy studies regularly show pneumonia in patients not treated with antibiotics suggests that a subjective clinical impression that pneumonia is not present may be inaccurate in some patients. Systematic overestimation of sensitivity may result. In one autopsy study, 9% of patients who were not given antibiotic therapy, and died, had VAP.84 Data on the original clinical suspicion were available for eight studies (Tables 7 8) .11,12,20,21,38–41
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Performance Characteristics |
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TOPIntroductionPerformance CharacteristicsResultsConclusions |
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The indications for study entry in the eight studies were as follows: autopsy, in four studies; suspected VAP, in three studies; and clinical findings and results of bronchoscopies performed at intervals driven by an ARDS protocol, in one study. The study of Sutherland et al12 correlated evidence of VAP in patients not overtly suspected of having VAP. In contrast, the primary end point of the study by Fagon et al11 was to examine the accuracy of the clinical diagnosis in patients suspected of having VAP. The only two studies using specific objective criteria (new or changing radiographic infiltrates and purulent tracheal secretions) rather than subjective criteria are the Fagon studies in 1988 and 1993.11,40
ARDS is somewhat overrepresented in the review studies. Three studies include only ARDS patients, and ARDS was present in at least 248 of the 567 patients (44%).
The incidence of VAP in the studies varies from 15 to 74%. The incidence in studies of patients clinically suspected of VAP was consistently in the 30 to 40% range and was consistently higher in autopsy studies. Since variable incidence rates affect subsequent sensitivity and specificity calculations, we partially compensated by calculating likelihood ratios.
Methodology
The only studies in which investigators were blinded to the
reference standard were three of the four autopsy
studies20,38,39 and the study of Sutherland et
al,12 in which data were collected prospectively and the
timing of bronchoscopy was not based on clinical
suspicion.
The quality of the assessments was only for the reference standard. Fagon et al11 had at least three independent subjective evaluations of the probability of VAP. To further validate the findings, several studies used clinical manipulation, including stopping antibiotics or determining alternate explanations if the findings from the reference culture were negative.
Reference Standard
Four studies compared clinical findings exclusively to histology
findings at autopsy. Confirmation of the accuracy of the test
results for bronchoscopic specimens was also available at
autopsy in another 33% of the remaining patients. A definite
diagnosis was available in 386 of the 597 patients (65%), or in 367 of
the 492 patients (75%) if the study of Sutherland et al12
is excluded. In addition to histology findings at autopsy,
definite diagnoses were based on the results of cultures of blood or
pleural fluid, and negative diagnoses were based on recovery without
antibiotic therapy.
Although the use of antibiotics is less important in this situation than in diagnosis based on culture results, 44 to 100% of patients were receiving antibiotics at the time of clinical evaluation. Partial antibiotic treatment may have altered some clinical findings, such as fever and leukocytosis.
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Results |
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TOPIntroductionPerformance CharacteristicsResultsConclusions |
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Combinations of the objective criteria of fever, leukocytosis, purulent secretions, and a radiographic infiltrate performed well in the population preselected for suspected VAP. When patients were not preselected, as in the studies of Andrews et al,39 Torres et al,41 and Sutherland et al,12 no individual sign or combination of signs increased the likelihood that the patient had VAP. While this finding may reflect the populations studied, which were composed predominantly of ARDS patients, the operating characteristics of these objective signs may be significantly worse if applied to an unselected group of patients.
Requiring all three clinical findings and radiographic abnormalities increased the specificity but lowered the sensitivity to an unacceptable 48%.11,12,21 Requiring two rather than one clinical finding with abnormal radiographic findings did not improve accuracy.
Objective criteria did not help to distinguish between patients with and without VAP if clinical suspicion was present. Diagnostic accuracy was not improved by the presence or absence of any sign, the degree of abnormality of any sign (data not shown), or the combinations of signs.
Reproducibility
Fever and leukocytosis are quantitative observations and would be
expected to be highly reproducible. The presence and degree of
purulence and the volume of tracheal secretions are subjective
observations, and no study has documented their consistency. Recent
data suggest that the presence of aspirated material near the
endotracheal tubes in critically ill patients might increase the amount
of secretions, without necessarily indicating pneumonia.88
The presence of aspirated material is subject to variables: patient
positioning, gastric emptying, endotracheal tube cuff pressures, and
other factors.
Interobserver reliability was suggested only in the study of Fagon et al.40 They found no significant differences in the accuracy of the clinical suspicion of VAP between either individual physicians or physicians grouped by level of training. The likelihood ratios for clinical impression ranged from 2.5 to 5.0 between the worst and the best individual clinicians. Unanimous decisions occurred in only 58%, but increased the likelihood ratio to 10.
Risk
The risks of inaccurate clinical diagnosis are antibiotic
treatment of patients without VAP and lack of treatment of those with
VAP. A false diagnosis of pneumonia increases the possibility of
missing an alternative cause of the clinical manifestations. Meduri et
al83 demonstrated that multiple potential alternative
sites of infection can be found in patients with negative findings from
quantitative bronchoscopy cultures. Timsit et al89 and
Papazian et al81 have found that the mortality rate of
patients with negative findings on bronchoscopy is equal to that of
patients who are suspected of having VAP who have positive results of
cultures. Perhaps other potentially lethal infections are not
accurately diagnosed, and, even if antibiotics are prescribed, the
spectrum of coverage may be inappropriate for the actual infection.
In addition, antibiotic therapy for noninfectious problems may increase
the risk of subsequent infection with drug-resistant organisms. VAP
associated with these more lethal organisms may be an important cause
of death. Using decision analysis and data from the literature,
Sterling et al90 found that overall survival was greater
if antibiotics were withheld in patients with VAP who were
diagnosed by clinical criteria. One-way sensitivity analysis suggested
that withholding antibiotic therapy is favored when the positive
predictive value of clinical criteria is 
28%, the mortality rate
of antibiotic-treated patients with VAP is 
40%, the mortality rate
of untreated patients with VAP is 86%, or the risk of developing
VAP is 22%. Two-way sensitivity analysis demonstrated that the
model was most sensitive to the positive predictive value of the
clinical diagnosis and the mortality rate of antibiotic-treated
patients with VAP. While this decision analysis is only as accurate as
the data used for the calculations, the results illustrate that
empirical antibiotic therapy for clinical pneumonia is not without
risk.
A third aspect of the overdiagnosis of VAP using clinical criteria is that much of the epidemiologic data for empirical treatment are based on studies using clinical criteria. Requiring all three clinical criteria (fever, leukocytosis, and purulent tracheal secretions) in addition to abnormal radiograph findings may increase the probability that the patient has VAP but does so at the risk of missing 50% of cases. Whether using loose or restrictive clinical criteria for the diagnosis of VAP, the risk factors, prevention strategies, and treatment outcomes found may be incorrect.
The alternative dilemma is that if antibiotic treatment is withheld in patients with true pneumonia, morbidity and mortality may be adversely affected. Little accurate data exist to determine the risk of withholding antibiotics, even temporarily, but the mortality rate in patients given inappropriate antibiotic therapy is approximately 50%.44 These data are skewed for more lethal organisms, such as Pseudomonas spp, for which inadequate antibiotic therapy is more likely than for Haemophilus spp or Streptococcus spp.90
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Conclusions |
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TOPIntroductionPerformance CharacteristicsResultsConclusions |
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The only way to increase the specificity of clinical criteria is to require all four criteria, but this results in an unacceptably low sensitivity (< 50%).
These findings suggest that the presence of abnormal clinical manifestations, combined with abnormal radiographic findings, can be used for the initial screening for VAP. However, the lack of specificity with this method suggests that additional procedures are needed, such as cultures of lower respiratory tract secretions (grade B recommendation).
In the final analysis, clinical suspicion is as sensitive and specific as any fixed objective set of criteria, with the possible exception of composite CPIS score. Unfortunately, in most cases the complete score can be calculated only in retrospect, after VAP is suspected clinically.
The operating characteristics of the clinical diagnosis of VAP suggest that the high sensitivity is appropriate for initial clinical suspicion and screening, but that the lack of specificity suggests the need for additional testing or information.
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Footnotes |
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