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The Standardization of Bronchoscopic Techniques for Ventilator-Associated Pneumonia
The Standardization of Bronchoscoplc Techniques for Ventilator-Associated Pneumonia*
G. Umberto Meduri, M.D., F.C.C.P.; and]un C~. M.D.
D their reaean:h efforts at defining more efficient mouring the last decade, several centers have directed
dalities for the accurate diagnosis of ventilator-associated pneumonia (VAP). Accurate diagnosis is an essential prerequisite for clinical investigation. Initial studies, which correlated histologic findings and quantitative bacterial cultures of the lung with the findings of protected specimen brush cultures have stimulated clinical investigation of YAP. Two diagnostic techniques, protected specimen brushing (PSB) and bronchoalveolar lavage (BAL), have been extensively investigated and have shown promising results. Advancements in the field, however, have been limited by the lack of standardization, particularly for BAL. In this communication, we attempt to standardize methodology for presently available bronchoscopic techniques and interpretation of data obtained by bronchoscopy to facilitate comparisons among investigations and to promote multicenter collaboration. CoNDmoNs THAT ENHANCE THE RisK FOR BRONCHOSCOPY-RELATED COMPLICATIONS IN PATIENTS RECEIVING MECHANICAL VENTILATION
Background The most common complication encountered during or after diagnostic fiberoptic bronchoscopy (FOB) with PSB and BAL in patients receiving mechanical ventilation is a drop in Pa01 • 1•1 In one study, significant hypoxemia (Pa01 <60 mm Hg on 80 percent Flo.) was observed in 14 of 117 patients (12 percent) and was linked to severity of pulmonary dysfunction and decrease in alveolar ventilation. Hypoxemia was more frequent in patients with adult respiratory distress syndrome (ARDS) and in those who fought the ventilator during the procedure; the mean drop in Pa01 was 26 percent and persisted for up to 2 h.• Others have reported an increase in Flo1 requirements postbronchoscopy in 23 percent of patients receiving ventilation. 1 The size of the endotracheal tube in relation to the size of the bronchoscope was found to be an important factor in limiting lung inflation and decreasing ventilation in Pa01 in one study. 3 Protected specimen brushing may cause bleeding, particularly in patients with renal failure, coagulopathies, and (occasionally) pneumothorax.... Other reported complications have included arrhythmias, 7 transient worsening in pulmonary infiltrates,' and fever. Fever is seen more frequently with BAL and may be related to local release of cytokines. • There is no documentation indicating that diagnostic FOB may spread pneumonia to other lobes or has a negative effect on *From the Division of Pulmonary and Critical Care Medicine, The University of Tennessee, Memphis; and the Service de R6mimation M6dicale, Hospital Bichat, Paris, France.
Contributon: John B. Bau, M.D.; Robert P. Baughman, M.D.; ~Rodriquez De Castro, M.D.; M. C. Dombret, M.D.; CharluHugo Marquette; Maj Robert M. Middleton Ill, M.D.; Antonio lbrn1s, M.D.; Richard H. Winterbauer; M.D.
the infection.
Condition• that are woneMd by FOB (eg, hypolemia,
cardiac ischeinia) or that may predispose to complications (eg, bleeding) may pose a contraindication to bronchoscopy. In high-risk patients, the specimen can be obtained in a short period of time. Protected specimen brushing can generally be done in less than 1 min and BAL in less tru,n 4 min. In general, the risk for complications increases as procedure time increases. Strict guidelines that can be easily applied to each patient are difficult to establish. Since many factors are taken into account in evaluating the risks vs benefits of the procedure, a discrimination between absolute and relative contraindications cannot be made. Therefore, we will define conditions as being at high risk or at relatively high risk for complications.
Recommendations The following conditions place the patient at high risk for complications-(1) respiratory: Pa01 <70 mm Hg on Flo1 >70 percent, positive end-expiratory pressure (PEEP) 2:15 em H.O, active bronchospasm; (2) cardiac: recent acute myocardial infarction (:S48 h), unstable arrhythinia, mean arterial pressure <65 mm Hg on vasopressor therapy; (3) hematologic: platelet count <20,000 cu/mm. The following conditions place the patient at relatively high risk for complications-(1) respiratory: PEEP > 10 em H.O, significant auto-PEEP (2:15 em H.O); (2) hematologic: prothrombin time or partial thromboplastin time > 1.5 times control; (3) central nervous system: increased intracranial pressure. During and after bronchoscopy, a record should be kept of complications such as hemorrhage, arrhythmias, hypoxeInia, and pneumothorax and their degree of severity. A~
of Hlture Investigation
Additional studies of incidence and risk factors for complications of bronchoscopy in patients receiving ventilation are required. MANAGEMENT OF PATIENTS IN THE PERIBRONCHOSCOPY PERIOD
Background Diagnostic bronchoscopy should be performed with due caution and continuous monitoring of exhaled volumes and oxygen saturation. Hypoventilation can be minimized by decreasing peak inspiratory 8ow, increasing ventilatory rate, and adjusting peak pressure alarms. Monitoring of exhaled tidal volume allows for best titration of ventilator settings. Hypoxemia and patient-ventilator asynchrony is minimized by delivering a high Flo. (100 percent) and providing adequate sedation with or without short-lived paralysis. Few data are available on the effects of bronchoscopy on pulmonary physiology in patients receiving mechanical ventilation CHEST I 102 I 5 I NOVEMBER, 1982 I SUpplemlnl
Sl78
{MV). Cardiac monitoring provides continuous display of heart rate and recognition of rhythm abnormalities. Sinus bradycardia may result from auto-PEEP induced by instrumentation or air trapping and is minimized by premedication with atropine.
Recommendations Adaptor: An adaptor to minimize air leak is recommended. Endotracheal Thbe Size: The endotracheal tube should be large enough to allow for adequate ventilation during the procedure. For adult patients, the endotracheal tube size should be 2:1.5 mm larger than the external diameter of the flexible bronchoscope. lentilator Settings: Set Flo1 at 100 percent, respiratory rate at 15 to 20 breaths/min, and peak inspiratory flow at S60 Umin. The peak pressure alarm should be set to a level to allow adequate ventilation. Titrate the ventilator settings to maximize exhaled tidal volume. Premedication: Sedatives with or without a short-acting paralytic agent are recommended. A paralytic agent should be considered in patients at high risk for complications who are undergoing prolonged bronchoscopy. Monitoring: During bronchoscopy, the monitoring of the following cardiopulmonary parameters is recommended: ventilator-exhaled tidal volume and peak inspiratory pressure; oximetric-continuous oximetry; cardiac-continuous single-channel electrocardiography.
AmJS of .Rlture Investigation Various ventilatory maneuvers to maximize oxygenation, ventilation, and return of BAL fluid require investigation. The relationship of measured peak pressure to actual intrathoracic pressure during bronchoscopy also requires study. SAMPLING AREA
Background Selection of the sampling area may be important in obtaining meaningful results. The sampling area is selected based on the location of the new or progressive in6ltrate on chest radiograph or the segment visualized during bronchoscopy as having purulent secretions. Selection may be difficult in patients with diffuse in6ltrates. In the immunosuppressed host with diffuse inJiltrates (including ventilated patients), bilateral sampling has been advocated.9 One group has advocated bilateral sampling in patients with ARDS.'0 There is no convincing evidence that multiple specimens are more accurate than single specimens. Although autopsy studies indicate that VAP is frequently disseminated into each pulmonary lobe 11 and involves predominantly the posterior portion of the lower lobes, 11 two clinical studies of patients receiving ventilation with clinical pneumonia contradict these findings. 13•1• Baughman et al13 reported PSB cultures of the noninvolved lung to be sterile in three of four patients and positive in only one patient with pneumonia. Similarly, Belenchia et al" have described significant bacterial growth in only one of two contralateral sampled bronchi in patients with ARDS and fever. However, two recent studieslll·18 have found good correlation between cultures of blind nonbronchoscopic sampling of the lung 558S
periphery and samples obtained by bronchoscopy, even when obtained from different lobes or the contralateral lung. Purulent secretions are frequently present in the tracheobronchial tree of patients with acute respiratory failure . The site of origin of these secretions can be either the upper or lower respiratory tract (above or below the vocal cords). In the former, secretions originate from the nasopharynx, the sinuses, and the stomach and accumulate above the inflated endotracheal tube (ET) cuff before being introduced into the trachea. The portion of the upper trachea between the inflated ET cuff and the vocal cords behaves as a reservoir for collection of secretions that are sheltered from suction devices. Secretions in the lower airways can originate from either tracheobronchitis or a pneumonia. Therefore, the presence of purulent secretions in the large airways at bronchoscopy is neither sensitive nor specific for pneumonia. Fagon et al17 diagnosed VAP with PSB in only 22 of 75 patients receiving MV {29 percent) who had fever, leukocytosis, a new radiographic in6ltrate, and bronchoscopically visualized purulent tracheal secretions. Similar findings were described by Mauldin et al. 18
Controversies Does the finding of dissemination to both lungs in postmortem studies11•11 represent the terminal stage of pneumonia in terminally ill patients, or is it a true reflection of the anatomic distribution of pneumonia in all patients receiving MV? The literature does not provide clear guidelines for selecting a sampling area in patients with diffuse infiltrate without a discernible acute localized process.
Recommendations The sampling area is selected based on the location of the new or progressive in6ltrate on chest radiograph or the segment visualized during bronchoscopy as having purulent secretions. Collection of secretions in the lower trachea or mainstem bronchi, which may represent recently aspirated secretions, should be avoided. Sampling is directed to the abnormal subsegment in patients with endobronchial or purulent secretions.
Aretl3 of Future Investigation A scoring system for evaluating endobronchial abnormalities in patients undergoing bronchoscopy needs to be developed. The need for multiple sampling sites in patients with diffuse pulmonary in6ltrates (eg, ARDS) should be evaluated. Data are needed on the distribution of bacteria in the lungs of patients with and without VAP. The need for direct bronchoscopic sampling vs quantitative culture of the tracheal aspirate or other nonbronchoscopy techniques requires further evaluation. SAMPLING TECHNIQUES
Background Fiberoptic bronchoscopy provides direct access to the lower airways for sampling bronchial and parenchymal tissues. To reach the bronchial tree, however, the bronchoscope has to traverse the endotracheal tube, where contamination of the instrument is likely to occur with introduction into the suction channel of organisms contaminating (aspiSlandardlzallon of Techniques {Medurl, Chatltre)
-~
rated from above the ET cufl) or colonizing the endotracbeal tube and the central airways. 111.., Suction through the worldog channel of the FOB before obtaining PSB or BAL sampling increases the likelihood of contamination. Injection of lidocaine (topical anesthesia) carries contaminants that have accumu1ated in the broochosoope suction channel into the bronchial tree and compromises culture results. Lidocaine also bas bacteriostatic properties;11 however, the use of 1 to 2 ml of a 1 percent solution to anesthetize a lobe prior to BAL resulted in a concentration of lidocaine in the BAL efBuent below that reported to inhibit bacterial growth.-
Protected Specimen Bro8hlng The following methodology for PSB sampling was de-
scribed originally by Wimberley et al.u The tip of the bronchoscope is positioned next to the orifice of the sampling
area and \be fSB ~tbeter advanced aem out of the FOB to
avoid collection of pooled secretions on the catheter tip. The inner cannula is protruded to eject the distal carbon wax plug into a large airway, and the catheter is advanced into the desired subsegment. Ifpurulent secretions are visualized at a subsegmental level, the brush is rotated into them. After sampling, the brush is retracted into the inner cannula and the inner cannula into the outer cannula, and then the catheter is removed from the bronchoscope. A small quantity of brush secretions may be smeared into a sterile slide for a Gram stain. The distal portions of the outer and inner cannula are separately and sequentially wiped clean with 70 percent alcohol, cut with sterile scissors, and discarded. The brush is adyanced out and severed with a sterile wire clipper into a container with 1 ml of diluent to avoid drying and rapid loss of bacteria. The specimen is submitted for quantitative culture within 15 min. Higuchi et al• first described the use of PSB in animals receiving ventilation and introduced a modilication to the original protocol of WlDlberley et al.u With Higuchi's technique, the brush is wedged into a peripheral position after dislodging the occluding plug into the selected subsegment. This method was modified by Cbastre et al• in a series of patients dying of respiratory failure.
Bronchoaloeolar LAvoge
'
Bronchoalveolar lavage is obtained by infusion and aspiration of a sterile physiologic solution through a 8exible bronchoscope wedged into a bronchial subsegment. The amount ofBAL ftuid injected for the assessment of infectious lung disorden bas not been standardized. The BAL Cooperative Group Steering Committee bas recommended using 240 ml for the evaluation of patients with intentitial lung disease.11 In studies utilizing BAL for bacterial cultures, including studies with patients receiving MV, amounts of BAL ftuid have ranged from 100 to 240 mi. • At least 120 ml are necessary for retrieving secretions from the periphery of the lung subsegment. • The effect of dilution on culture results bas not been evaluated. Controversfes
Protected Spedmen 811J8hjng: Peripheral wedging of the brush may minimize the sampling area or cause sampling error. Peripheral wedging may also increase the risk for
pneumothorax. Obtaining smean for Gram stains may decrease the amount of secretions for cultures and oJI'er an additional risk for contamioatino. Bronchoaloeolar LAvoge: The amount of ftuid necessary to obtain adequate sampling and the amount of retrieved ftuid necessary for adequate microbiologic analysis are not agreed upon.
Recommendatimv General Recorntnendatio: Suction or injection of lidocaine through the worldog channel of the FOB should be avoided. Suction through the endotracheal tube before bronchoscopy should be performed. Protected specimen brushing is performed before BAL. Protected Spedmen 811J81dng: Purulent secretions shoold be sampled at a subsegmentallevel. If purulent secretions are not visualized, the brush should be advanced peripher-
ally Ufttilit iJ llOt viJualBd. hMq wWul Mt to we8p It
into a peripheral position. The brush is moved baclcward and forward and gently rotated several times. Bronchoaloeolar LAvoge: The tip of the &beroptic bronchoscope is wedged into a subsegment of the lung. and 20 ml sterile saline solution are injected, aspirated, and collected separately. This &rst aliquot shoold Dot be submitted for quantitative bacterial cultures or microscopic evaluation to identify intracellular organisms; however, it can be used for other microbiologic analysis. Additional aliquots of 20 to 60 ml are injected and aspirated baclc after each instillation. The total amount of ftuid injected should be 2:140 mi. AreuofFbhnl~
Investigation is required to assess the recovery of organisms at various volumes of BAL infusion and with each individual aliquot. Alternative location for placiDg the PSB should be investigated. ANALYSIS OF DATA
Definition of SotVjJctory Buplratory ~ Protected Specimen Bro81dng: The literature does not provide criteria to assess the adequacy of a PSB specimen. Hemorrhage is an occasional complication of brushing, but the effects of hemorrhage on culture results have not been reported.
BronchotJceolar LAvoge: In a study of nooventilated patients, Kahn and Jones» showed that the recovery of more than 1 percent squamous epithelial cells (SEC) in the cytocentrifuged BAL specimen was an accurate predictor of heavy contamination by oropharyngeal ftora. Columnar epithelial cells (CEC) are indicaton of tracheobronchial proximal sampling; however, their role has not been well characterized in patients receiving MV. Three studies of patients receiving Mv-.a have described the presence of CEC or SEC in tbe retrieYed BAL 8uid. Two studies reported the absence of epithelial cells, and one study reported the presence of > 1 percent SEC or CEC in 30 percent of samples. JJ Pneumonia is a highly cellular inflammatory reaction with neutrophilia predominance. Total cell count and absolute neutrophil count have not been used as a measure of specimen adequacy. Recomtrumdtztio: At least 5 ml of retrieved BAL are needed for adequate microscopic and microbiologic analysis. CHEST I 102 I 5 I NOVEMBER, 1882 I 8uppllmlnl
1M
The following infonnation should be recorded for BAL: (1) percentage of retrieved BAL, excluding the first aliquot; (2}
the presence and degree (minimal, moderate, large) of
hemorrhage by visual inspection; (3} location of the sampling in relation to radiographic infiltrate and presence of endobronchial pus. AtllaS of Future Investigation: Different criteria should be examined for assessing the adequacy of a PSB specimen, including visual inspection and cellular analysis of the specimen. Further research is also needed to evaluate the impact of percentage of ftuid retrieved and the presence of hemorrhage on culture results, to evaluate the percentage of epithelial cells as a marker of contamination, and to evaluate cellular content as an indicator of adequate sampling. Microscopic Analysis
Microscopic analyses of BAL have included the MayGriinwald Giemsa stain for evaluation of the alveolar cell population (cell count and differential), the percentage of cells (neutrophils) containing intracellular organisms, and the percentage of epithelial cells (indicator of oropharyngeal and bronchial sampling); stains have also been used for recognition of organisms (eg, Gram stain, potassium hydroxide, acid-fast}. A stain for elastin fibers has been used as an indicator of lung destruction. Cytologic studies have also been done. CeU Count and Differential: Several studies have shown a significant increase in total neutrophilic count in the BAL of patients with active YAP. The mean percentage of neutrophils varied from 77 to 82 percent. 18•31 •32 In patients with ARDS, neutrophilia of such a degree can also be associated with a noninfectious pulmonary inftammatory process. 10 &rcentage of CeUs Containing Intracellular Organisms: Microscopic analysis of the BAL may provide rapid identification of patients with pneumonia (presence of intracellular [ICO] and extracellular organisms} and allow early fonnulation of specific antimicrobial therapy (Gram stain) that can be modified later based on the results of quantitative culture and sensitivity. In a group of 61 ventilated patients investigated by Chastre et al,33 microscopic analysis ofBAL showed ICO in more than 7 percent of the recovered cells in 12 of 14 patients with pneumonia (86 percent sensitivity) and in only 2 of 47 without (96 percent specificity). In the remaining 45 patients without lung infection, 43 had less than 2 percent of total alveolar cells containing ICO. Pugin et al•• found ICO in 11 of 14 patients with bacterial pneumonia and in none of 25 samples in patients without lung infection. The ICO were expressed as a percentage of neutrophils (8.3± 11.5) instead of total cells. The correct mode of reporting ICO appears to be the one originally proposed by Cbastre et al, 33 since it takes into account the degree of inftammatory response. Meduri et al34 have reported patients without infection who had > 10 percent ICO as a percentage of neutrophils but
Gram Stain: Many investigators have reported a close correlation between the findings on the Gram stain of the
D/\L and the re&ulta of quantitative culturei. '
8 33 38 ' ' ,37
Elastin Fibers: One study bas reported the findings of elastin fibers in the BAL of 7 of 15 patients with YAP (47 percent) and in only 2 of 25 patients without infection (8 percent). 18 In infected patients, elastin fibers were associated with Gram-negative bacillary pneumonia and a radiographically localized pulmonary in6ltrate. Ahigh rate of positive results occurs in uninfected patients with ARDS. 18•38 Cytologic Analysis: Cytologic analysis ofBAL in intubated patients with clinical pneumonia bas established alternative diagnoses such as pulmonary hemorrhage, carcinoma of the lung, and opportunistic infections (Pneumocystis carinii and cytomegalovirus}. s ,J3,:u Recommend4tions: The Giemsa stain is discussed by the Consensus Conference Group on Laboratory Analysis in this supplement. Gram stain should be perfonned on the cytospun BAL and may be perfonned on the PSB. AtllaS of Futtl1"8 Investigation: Correlation between cytocentrifuged and direct Gram stain, Gram stain and culture results, and the percentage of intracellular and extracellular organisms on Giemsa stain and the results of quantitative culture should be investigated further. Diagnostic 11&reshold The concentration of organisms necessary to cause pneumonia varies in relation to the virulence of the bacteria and the competence of host defenses. Once bacterial infections of the lung manifest clinically, they contain at least 10' colony-forming-units (cfu)lg of tissue 11 . - and 10" or more bacteria per milliliter of exudate. 311•40 Quantitative cultures are used to assess the concentration of organisms present in respiratory secretions. A low colony count in patients not receiving antibiotic treatment indicates contamination, recent inoculation, or a partially successfUl attempt at eradication. A high colony count indicates that a significant concentration of bacteria is present in the sampled area. ltvtected Specifflen Brushing: In the late 1970s, Wunberley et al14 developed a double-catheter brush system with telescoping cannulas and a distal-occluding carbowax plug for collection of uncontaminated respiratory secretions. Independent investigators have concluded that the utility of PSB in diagnosing pneumonia rests upon its ability to recover organisms from lower respiratory tract secretions at a concentration :2::1()'1 cfu/ml. The volume of respiratory secretions retrieved by PSB is approximately 0.001 ml.14·" The methodology described above must be followed precisely to minimize contamination of the specimen. The brush is diluted in 1 ml of holding medium, which results in a 100to 1,000-fold dilution before plating. A growth of i2::10' cful ml in the culture plate indicates an initial concentration of 1()5 to 1()5 bacteria per milliliter in the retrieved secretions. •• The usefulness of PSB in evaluating patients receiving MY suspected of having pneumonia bas been extensively investigated in both human..,· 13•17. -·31 .:U.37.•1.., and animal11.111 studies. The findings of most studies are summarized in Table l. In experimental animals with ARDS who had histologically and bacteriologically proven pneumonia, Higuchi et al• showed that samples collected by PSB had a specificity of 100 percent and a sensitivity of70 percent for
Table 1-Findinga of Slullia &porting the RmJta of PSB Qua~ Culturea No. of Patients
Investigator Higuchi et alChastre et al• ATB* NoATB Baughman et al 13 Fagon etal• TorresetaF ATB NoATB
10
7/10
M)
6t6
8120
21 147
7/12
34134
1113 4176
4 14 17 9 8 103 349
True-Negative
False-Negative
M)
3110
12.120
5112 7/8 12113 72176
118
12118 214 1fi/14 11117
25
1btal
Vl
414 7/8
12
ATB NoATB De Castro et aJ4I
False-Positive
26
14
Pbametal'"
Percentage,
True-Positive
M
7n
(W
IW
fi/4
118 004
6118 214
37
4114
6117
519 &'8
~
Undeterminate
419 218
41149 1181142
141153
83
9
1137
3&'37
1391153 91
8149 241142 17
17 54 15
• ATB =antibiotics.
quantitative cultures (~10' cfu/ml) and a 30 percent sensitivity for Gram stain. Chastre et al• performed bronchoscopy in 26 intubated patients with respiratory failure just after their deaths while MV was continued. After obtaining a PSB sample from the anterior segment of the left lower lung, this lung segment was removed by thoracostomy and subjected to histologic evaluation and quantitative bacterial culture. All six patients with pneumonia determined by histologic criteria had at least one microorganism that grew in concentrations greater than 10' cfu/g on lung cultures; four patients bad polymicrobial growth. Cultures of the PSB yielded 15 of the 19 bacteria present in the lung cultures and no additional organisms. All protected brush cultures had at least one microorganism in a concentration above 10' cfu/ml. 1\venty patients had no histologic evidence of pneumonia. Using the break-point oflO' cfu/ml to define a positive PSB culture, no false-negative results were observed. In the subgroup of 12 patients who were receiving antibiotics at the time of the study, however, 7 had at least 1 organism at a concentration > 10' cfu/ml (specificity, 60 percent). In the one who received no antibiotics, the false-positive rate was 23 percent (specificity, 87 percent). Baughman et al 13 subjected 21 intubated patients with a new infiltrate who had been off antibiotics for at least 48 h
c::::=J
Number
c=:J
True positive
-
to FOB with bilateral PSB. A growth ~10' cfu/ml was found in seven of eight patients with pneumonia and in none of the patients who had an alternative diagnosis established. Concurrent antibiotic use affects the diagnostic sensitivity ofPSB quantitative cultures. Figure 1 summarizes the results of three studies15·• ·37 that reported the results of cultures in patients receiving or not receiving antibiotics at the time of bronchoscopy. Torres et a}5 investigated the diagnostic utility PSB in 25 patients with clinical pneumonia who were receiving MV, all but 4 of whom had antimicrobial therapy stopped for more than 4 days. Of these 25 patients, 7 had a negative finding with an alternative diagnosis determined in all; 18 had pneumonia, confirmed by postmortem studies in 10 and by successful response to antibiotics in 8. Sensitivity was 50 percent (2 of 4) and 71 percent (10 of 14), respectively, in patients with and without antibiotics at the time of FOB, while the specificity was 100 percent for both. Pham et al 15 reported on the utility of PSB in 17 patients with definitive VAP. The test was falsely negative in 4 of 9 patients (44 percent) receiving antibiotics and in 2 of 8 (25 percent) not receiving antibiotics for at least 48 h. The amount of time that the patient does not receive antibiotics before bronchoscopy may also affect the concentration of organisms in the PSB sample. In one study,:w the odds in favor of a truepositive PSB culture increased an estimated 47 percent
26
False negative
15
On antibiotics
Off antibiotics
FIGURE 1. Effect of antibiotics on the results of PSB quantitative
cultures.
CHEST I 102 I 5 I NOVEMBER, 1992 I Supplement
IMS1S
(p<0.06) for each additional day without antibiotic treatment. Two groups of investigators have reported their experience using FOB with PSB in a large patient population and have used the results of cultures to direct treatment. Fagon et al• prospectively investigated 147 patients with clinical pneumonia receiving MV, 87 of whom had received antibiotic treatment for more than 3 days. Quantitative culture of the PSB had a growth C!:lO' cfu/ml (of at least one microorganism) in 45 patients (30 percent). The diagnosis of pneumonia was confirmed in 34 of these patients (28 by autopsy, 6 by
by contamination with upper airway bacteria, which have been found to a significant degree (> 10' cfulml) in one third of specimens. 31 •37 Two groups of investigators first described the role ofBAL in diagnosing bacterial lower respiratory tract infection in patients not receiving MV and found a growth in excess of lOS cfulml in the majority of patients with pneumonia.30•38 Four studies have compared the effectiveness of BAL and PSB in collecting lower airway secretions in animals" and patients'·31•37 receiving MV. In a baboon model of respiratory failure, Johanson et al11 compared the results of quantitative
defined in 7 and was excluded in 4 (false-positive rate, 11 percent). Of the 147 patients, 102 had either no growth (77 patients) or a PSB culture yield of <10' cfu/ml. None of them bad bacterial pneumonia, excluded in most at autopsy (34 patients) or by recovery without antibiotic therapy. The results are shown in 'Illble l. Positive predicted value of a positive culture was greater than 75 percent. De Castro et al• reported on the use of FOB with PSB in 103 patients, 53 already receiving antibiotics. In 49 patients, growth was C!:lO' cfu/ml. Pneumonia was confirmed in 41 and felt to be probable in 7. In 54 patients, growth was <10' cfulml; 33 had no pneumonia (autopsy confirmation in 2) and received no antibiotic (22) or change in therapy (11). Results were falsely negative in 8 patients, and the diagnosis was uncertain in 10. The PSB cultures had a positive predicted value of 83 percent and negative predicted value of66 percent. Bronchoolveolar Lavage: Bronchoalveolar lavage samples a large portion oflung parenchyma (approximately 1 million alveoli) since the alveolar surface distal to the tip of the wedged bronchoscope is estimated to be 100 times greater than that of the peripheral airways. .. The sensitivity of BAL in identifying patients with bacterial pneumonia rests upon the capacity of BAL to recover organisms at a significant concentration. The recovery of bacteria from the distal airways is affected by the amount of fluid injected, the concentration of organisms in the lung, and its dilution with BAL fluid. The dilution of lung secretions in the BAL fluid in patients without pneumonia is 10- to 100-fold (> 1 ml in 10 to 100 ml ofBAL efBuent). 1111•110 In patients with pneumonia, BALis estimated to recover at least 5 to 10 times the amount of organisms retrieved by PSB. 30·,. A colony count of 10' cful ml, therefore, represents lOS to lOS bacteria per milliliter in respiratory secretions. The specificity value of BAL cultures in excluding bacterial pneumonia has been limited in part
findings of open-lung biopsy. Six ventilated animals who did not receive antibiotics bad moderate to severe pneumonia on histologic exam and a polymicrobial growth on culture. The BAL recovered 74 percent of all species present in the lung tissue compared to 41 percent by PSB and 56 percent by needle aspirate. Bacterial growth in the BAL, expressed as bacterial index (sum of all the logarithmic concentrations of individual organisms), was linearly related to tissue values. TISsue cultures had a mean growth of 2.8 species at 10' cfu/g and 1.4 species at 10' cfu/g. In animals receiving antibiotics, absence of growth was frequently found despite histologic evidence of pneumonia. Guerra and Baughman• obtained BAL for quantitative bacterial culture at one dilution in 54 patients receiving MV who underwent bronchoscopy for clinical pneumonia (30) or a noninfectious process (24). Using a diagnostic threshold of 10' cfu/ml, a significant growth was seen in 16 of 18 patients (89 percent) with pneumonia and in none of those without. Of patients with bacterial pneumonia, 70 percent were receiving antimicrobials, and none of the significant organisms (> 10' cfu/ml) was sensitive to the administered antibiotic. Of patients in the control group, 75 percent were receiving antimicrobials, and this treatment was disoontinued after results of cultures were avai1able. Torres et al37 compared the diagnostic yield of PSB and BALin 25 patients with VAP recently treated with antibiotics (<12 h). Microbiologic processing of the BAL fluid was different from other previously described methods, 11 •30•31 .5'7 with quantitative cultures performed on a concentrated (tenfold) sample. A diagnostic threshold oflO' cfulml, similar to the one ofPSB, was used. Asignificant growth was found in 72 percent of patients with each technique and in 2 of 7 BAL samples in a control group (71 percent specificity). Five patients had only one of the two methods positive, and
response to treatment); pneumonia could not be accurately
cultures of BAL and PSB to the histologic and bacteriologic
Table l-&.ult. of BAL Culture m~ tDilh Bacterial PneumoniG cfulml•
No. of Investigator Chastreetal>'
Patients
BAL, ml
Significant Growth
5
100
10" cfulml
Isolates, n
<10'
~10'
~10"
~10"
15
4
5
2*
4*
52
22
12*
14*
4
7
9
23 9:1
17 20
415
'lbrres et aJ31
25
150
Gue~ and Baughman•
18
240
1btal
48
Percentage
10' cfulml 17125 10" cfulml 16118 37 77
18 (22)t 85 100
2 28
33
17 20
*Organisms that grew above the diagnostic threshold. tindividual bacterial growth was not reported.
!128
sa.ndlrdlzdon of~ (Medurl, Chatltre)
four bad both negative (84 percent sensitivity for combined PSB and BAL). Agreement between BAL and PSB was 75 percent with respect to the type of organism recovered, but when concentration of organisms was also considered, it dropped to 56 percent. Combining the results ofquantitative cultures of these studies (fable 2), BAL bad a sensitivity of 77 percent and a specificity of 69 percent. t.31.37 Diagnostic thresholds of BAL have ranged from 10' cful
pneumonia. For BAL, the presence of >2 percent ICO or a positive Gram stain is suggestive of pneumonia. A negative microscopic analysis should not be considered definitive evidence for absence of pneumonia. Areas of ~ture Investigation: Comparative studies of histologic findings and lung tissue cultures (patients receiving MV) with microbiologic and microscopic analysis of secretions from the same lung segment obtained with BAL,
adopting a lower diagnostic break point improves sensitivity but lowers specificity of the test. Techniques that minimize contamination of the BAL may minimize this problem and improve specificity.....7 lilctors Affecting the Interpretation of Culture Results: While a cutoff point establishing the presence of pneumonia is well established in patients receiving MY without antibiotic treatment, the culture results of PSB and BAL done in patients on antimicrobial therapy can be difficult to interpret (Fig 1). When nosocomial bacterial pneumonia develops as a superinfection in a patient receiving systemic antibiotics, the etiologic organisms are likely to be resistant to the treatment regimen and their growth unaffected by them. A significant growth, however, has also been reported in patients receiving antibiotics without histologic evidence of pneumonia. • In patients recently started on antibiotics, a nonsignificant growth implies either absence of pneumonia or suppression of bacterial growth by the antibiotic used. One study indicates that bronchoscopic specimens (PSB and BAL) obtained within 12 h of starting antibiotics for presumptive pneumonia are still useful in identifying the causative pathogens and directing therapy, with a sensitivity of70 percent. 37 For this reason, an effort must be made to obtain bronchoscopic specimens before institution of antibiotic therapy. If treatment is initiated for a specific and documented infection (eg, peritonitis, meningitis), a full course of antibiotics has to be completed. The diagnostic accuracy of the microbiologic results is increased if antibiotics are discontinued 48 h before the procedure. In patients with pneumonia, FOB can yield negative results in the following situations: (1) bronchoscopy was done in an early infection with a bacterial burden below the concentration necessary to reach diagnostic significance; (2) bronchoscopy was done in an unaffected bronchial segment; (3) time without antibiotic therapy was insufficient; or (4) processing of the specimens was incorrect. Repeated bronchoscopy has been suggested for symptomatic patients with a concentration of bacteria in the PSB specimen between 1()l and 10' cfu/ml. 15 Controversy: The diagnostic value of PSB and BAL specimens is controversial in patients receiving antibiotics. Recommendoffons for Quantitative Cultures: For PSB, a value ~10' cfu/ml should be considered a significant level for bacterial YAP. For BAL, a value ~10C cfu/ml should be considered a significant level for bacterial YAP. Each morphotype present should be individually quantitated and reported. Y~ues within 1 log 10 of the cutoff should be interpreted cautiously. Recommendations for Mfcroscopic Anolysis: Microscopic analysis of the PSB and BAL may be useful indicators of pneumonia. For PSB, a positive Gram stain is suggestive of
for patients receiving antibiotics need to be developed.
ml to 10' cfu/ml. In addition to the factors presented above,
PSB, or other tecltnlquet are needed.
DiaiMtti~
mteria
REFERENCES 1 Guerra LF, Baughman RP. Use of broncboalveolar lavage to diagnose bacterial pneumonia in mecbanically venti1ated patients. Crit Care Med 1990; 18:169-73 2 Trouillet JL, Guiguet M, Gibert C, et al. Fiberoptic bronchoscopy in venti1ated patients: evaluation of cardiopulmooary risk under midazolam sedation. Chest 1990; 97:927-933 3 Lindholm CE, Oilman 8, Snyder Jv. et al. Cardiorespiratory effects of flexible Sberoptic bronchoscopy in critically ill patients. Chest 1978; 74:362-68 4 Fagon JY, Chastre J, Hance AJ, et al. Detection of nosocomial lung infection in venti1ated patients: use of a protected specimen brush and quantitative culture techniques in 147 patients. Am Rev Respir Dis 1988; 138:110..16 5 Torres A, De La Bellacasa JP, Rodriguez-lloisin R, et al. Diagnostic value of telescoping plugged catheters in mechanically venti1ated patients with bacterial pneumonia using the Metras catheter. Am Rev Respir Dis 1988; 138:117-20 6 Lambert RS , Vereen LE, George RB. Comparison of tracheal aspirates and protected brush catheter specimens for identifying pathogenic bacteria in mecbanically venti1ated patients. Am J Med Sci 1989; 297:377-82 7 Torres A, Aznar R, Gatell JM , et al. Incidence, risk, and prognosis factors of nosocomial pneumonia in venti1ated patients. Ann Rev Respir Dis 1990; 142:523-28 8 Standiford TJ, Kunkel SL, Strieter RM. Elevated serum levels of tumor necrosis factol'-alpha after bronchoscopy and bronchoalveolar lavage. Chest 1991; 99:1529-30 9 Meduri GU, Stover DE, Greeno R, et al. Bilateral broncboalveolar lavage in the diagnosis of opportunistic pulmonary infections. Chest 1991; 100:1272-76 10 Meduri GU, Belenchia JM, Estes RJ, et al. Fibroproliferative phase of ARDS: clinical findings and effects of corticosteroids. Chest 1991; 100:943-52 11 Johanson WG Jr, Seidenfeld JJ, Gomez P, et al. Bacteriologic diagnosis of nosocomial pneumonia following prolonged mechanical ventilation. Am Rev Respir Dis 1988; 137:259-64 12 Rouby JJ, Rossignon MD, Nicolas MH, et al. A prospective study of protected bronchoalveolar lavage in the diagnosis of nosocomial pneumonia. Anesthesiology 1989; 71:679-85 13 Baughman RP, Thorpe JE, Staneck J, et al. Use of the protected specimen brush in patients with endotracheal or tracheostomy tubes. Chest 1987; 91:233-35 14 Belenchia JM, Wunderink RG, Meduri GU, et al. Alternative causes of fever in ARDS patients suspected ofhaving pneumonia. Am Rev Respir Dis 1991; A683 15 Pham LH, Brun-Buisson C , Legrand P, et al. Diagnosis of nosocomial pneumonia in mecbanically venti1ated patients: comparison of a plugged telescoping catheter with the protected specimen brush. Am Rev Respir Dis 1991; 143:10155-61 16 Pugin J, Auckenthaler R, Mili N, et al. Diagnosis ofventi1atol'associated pneumonia by bacteriologic analysis ofbroncboscopic and nonbroncboscopic blind broncboalveolar lavage fluid . Am Rev Respir Dis 1991: 143:1121-29 17 Fagon JY, Chastre J, Domart Y, et al. Nosocomial pneumonia in CHEST I 102 I 5 I NOVEMBER, 1992 I SUppllmenl
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patients receiving continuous mechanical ventilation: prospective analysis of 52 episodes with use of a protected specimen brush and quantitative culture techniques. Am Rev Respir Dis 1989; 139:877-84 18 Mauldin GL, Meduri GU, Wunderink RG, et al. Causes of fever and pulmonary infiltrates in mechanically ventilated patients. Am Rev Respir Dis 1991; 143:A109 19 Bartlett JG, Alexander J, Mayhew J, et al. Should 6beroptic bronchoscopy aspirates be cultured? Am Rev Respir Dis 1976; 114:73-78 20 Fossieclc: BE Jr., Parker RH, Cohen MH, et al. Fiberoptic bronchoscopy and culture of bacteria from the lower respiratory tract. Chest 1977; 72:5-9 21 Wimberley N, Willey S, Sullivan N, Bartlett JG. Antibacterial properties of lidocaine. Chest 1979; 76:37-40 22 Rankin JA. Role of bronchoalveolar lavage in the diagnosis of pneumonia. Chest 1989; 95:187S-90S 23 Kirlcpatrick MB, Bass JB Jr. Quantitative bacterial cultures of bronchoalveolar lavage fluids and protected brush catheter specimens from normal subjects. Am Rev Respir Dis 1989; 139:546-48 24 Wimberley N, Faling LJ, Bartlett JG. A 6beroptic bronchoscopy technique to obtain uncontaminated lower airway secretions ror bacterial culture. Am Rev Respir Dis 1979; 119:337-43 25 Higuchi JH, Coalson JJ, Johanson WG Jr. Bacterial diagnosis of nosocomial pneumonia in primates: usefulness of the protected specimen brush. Am Rev Respir Dis 1982; 125:53-7 26 Chastre J, Viau F, Brun P, et al. Prospective evaluation of the protected specimen brush for the diagnosis of pulmonary infections in ventilated patients. Am Rev Respir Dis 1984; 130:924-29 27 The BAL Cooperative Group Steering Committee. Bronchoalveolar lavage constituents in healthy individuals, idiopathic pulmonary 6brosis, and selected comparison groups. Am Rev Respir Dis 1990; 141:169-202 28 Meduri GU , Baselski V. The role of bronchoalveolar lavage in diagnosing nonopportunistic bacterial pneumonia. Chest 1991; 100:179-90 29 Kelly CA, IC:otre CJ, Ward C, et al. Anatomical distribution of bronchoalveolar lavage ftuid as assessed by digital subtraction radiography. Thorax 1987; 42:624-28 30 Kahn Fw, Jones JM. Diagnosing bacterial respiratory infection by bronchoalveolar lavage. J Infect Dis 1987; 155:862-69 31 Chastre J, Fagon JY, Soler P, et al. Diagnosis of nosocomial bacterial pneumonia in intubated patients undergoing ventilation: comparison of the usefulness ofbronchoalveolar lavage and the protected specimen brush. Am J Med 1988; 85:499-506 32 Gaussorgues P, Piperno D, Bachmann P, et al. Comparison of nonbronchosoopic bronchoalveolar lavage to open lung biopsy ror bacteriologic diagnosis of pulmonary infections in mechanically ventilated patients. Intensive Care Med 1989; 15:94-8 33 Chastre J, Fagon JY, Soler P, et al. Quantification of BAL cells containing intracellular bacteria rapidly identifies ventilated patients with nosocomial pneumonia. Chest 1989; 95:190S-92S 34 Meduri GU, Beals D, Maijub G, et al. Protected bronchoalveolar lavage: a new bronchosoopic technique to retrieve uncontaminated distal airway secretions. Am Rev Respir Dis 1991; 143:855-64 35 Dotson RG, Pingleton SIC:. Bronchoalveolar lavage and protected specimen brush cultures in ventilator associated pneumonia. Chest 1991; 100:365 36 Thorpe JE, Baughman RP, Frame Pr, et al. Bronchoalveolar lavage ror diagnosing acute bacterial pneumonia. J Infect Dis 1987; 155:85.S-61 37 Thrres A, De La Bellacasa JP, Xaubet A, et al. Diagnostic value of quantitative cultures ofbronchoalveolar lavage and telescoping plugged catheters in mechanically ventilated patients with
bacterial pneumonia. Am Rev Respir Dis 1989; 140:306-10 38 Shepherd IC:, Lynch IC:, Wilson R, et al. Diagnosis of pneumonia in patients with adult respiratory distress syndrome. Chest 1988; 98(suppl):4S 39 Bartlett JG, Finegold SM . Bacteriology of expectorated sputum with quantitative culture and wash technique compared to transtracheal aspirates. Am Rev Respir Dis 1978; 117:1019-27 40 Bartlett JG. Invasive diagnostic techniques in pulmonary infections. In: Pennington JE, ed. Respiratory infections: diagnosis and management. 2nd ed. New York: Raven Press, 1989; 52-68 41 Marquette CH, Ramon P, Courool R, et al. Bronchoscopic protected catheter brush ror the diagnosis of pulmonary infections. Chest 1988; 93:746-55 42 De Castro FR, Violan JS, Capuz BL, et al. Reliability of the bronchoscopic protected catheter brush in the diagnosis of pneumonia in mechanically ventilated patients. Crit Care Med 1991; 19:171-75 43 Martos JA, Ferrer M, Torres A, et al. Specificity of quantitative cultures of protected specimen brush and bronchoalveolar lavage in mechanically ventilated patients [abstract]. Am Rev Respir Dis 1990; 14l:A276 44 Villers D, Derriennic M, Raffi F, et al. Reliability of the bronchoscopic protected catheter brush in intubated and ventilated patients. Chest 1985; 88:527-30 45 El-Ebiary M, Torres A, Gonzalez J, et al. Diagnosis of ventilatorassociated (VA) pneumonia: diagnostic value of quantitative cultures of endotracheal aspirates (EA) [abstract]. Am Rev Respir Dis 1991; 143:Al08 46 Middleton RM, Kirkpatrick MB. Comparison of fOur methods to assess airway bacteriology in the intubated mechanicallyventilated patient [abstract]. Am Rev Respir Dis 1991; 143:Al07 47 Baigelman W, Bellin S, Cupples LA, et al. Bacteriologic assessment of the lower respiratory tract in intubated patients. Crit Care Med 1986; 14:864-67 48 Papazian L, Martin C, Albanese J, et al. Comparison of two methods of bacteriologic sampling of the lower respiratory tract: a study in ventilated patients with nosocomial bronchopneumonia. Crit Care Med 1989; 17:461-64 49 Zucker A, Pollack M, Katz R. Blind use of the double-lumen plugged catheter for dlagnosis of respiratory tract infections in critically ill children. Crit Care Med 1984; 12:867-70 50 Joshi JH , Wang IC:P, DeJongh CA, et al. A comparative evaluation of two fiberoptic bronchoscopy catheters: the plugged telescoping catheter versus the single sheathed nonplugged catheter. Am Rev Respir Dis 1982; 126:860-63 51 Hayes DA, McCarthy LC, Friedman M . Evaluation of two broncho6bersoopic methods of culturing the lower respiratory tract. Am Rev Respir Dis 1980; 122:319-23 52 Glanville AR, Marlin GE , Hartnett BJS, et al. The use of 6beroptic bronchoscopy with sterile catheter in the diagnosis of pneumonia. Aust NZ J Med 1985; 15:309-19 53 Torzillo PJ, McWilliam DB, Young IH, et al. Use of protected telescoping brush system in the management of bacterial pulmonary infection in intubated patients. Br J Dis Chest 1985; 79:125-31 54 Reynolds HY. Bronchoalveolar lavage. Am Rev Respir Dis 1987; 135:250-63 55 Baughman RP, Bosken CH, Loudon RG, et al. Quantitation of bronchoalveolar lavage with methylene blue. Am Rev Respir Dis 1983; 128:266-70 56 Rennard S, Basset G, Lecossier D, et al. Estimations of the absolute volume of epithelial lining fluid recovered by bronchoalveolar lavage using urea as an endogenous marker of dilution. J Appl Physioll986; 60:532-38 57 Castella J, Puzo C, Ausina V. et al. Diagnosis of pneumonia with a method of protected bronchoalveolar lavage [abstract]. Eur Respir Jour 1991; 4:407S
G. Umberto Meduri, M.D., F.C.C.P.; and]un C~. M.D.
D their reaean:h efforts at defining more efficient mouring the last decade, several centers have directed
dalities for the accurate diagnosis of ventilator-associated pneumonia (VAP). Accurate diagnosis is an essential prerequisite for clinical investigation. Initial studies, which correlated histologic findings and quantitative bacterial cultures of the lung with the findings of protected specimen brush cultures have stimulated clinical investigation of YAP. Two diagnostic techniques, protected specimen brushing (PSB) and bronchoalveolar lavage (BAL), have been extensively investigated and have shown promising results. Advancements in the field, however, have been limited by the lack of standardization, particularly for BAL. In this communication, we attempt to standardize methodology for presently available bronchoscopic techniques and interpretation of data obtained by bronchoscopy to facilitate comparisons among investigations and to promote multicenter collaboration. CoNDmoNs THAT ENHANCE THE RisK FOR BRONCHOSCOPY-RELATED COMPLICATIONS IN PATIENTS RECEIVING MECHANICAL VENTILATION
Background The most common complication encountered during or after diagnostic fiberoptic bronchoscopy (FOB) with PSB and BAL in patients receiving mechanical ventilation is a drop in Pa01 • 1•1 In one study, significant hypoxemia (Pa01 <60 mm Hg on 80 percent Flo.) was observed in 14 of 117 patients (12 percent) and was linked to severity of pulmonary dysfunction and decrease in alveolar ventilation. Hypoxemia was more frequent in patients with adult respiratory distress syndrome (ARDS) and in those who fought the ventilator during the procedure; the mean drop in Pa01 was 26 percent and persisted for up to 2 h.• Others have reported an increase in Flo1 requirements postbronchoscopy in 23 percent of patients receiving ventilation. 1 The size of the endotracheal tube in relation to the size of the bronchoscope was found to be an important factor in limiting lung inflation and decreasing ventilation in Pa01 in one study. 3 Protected specimen brushing may cause bleeding, particularly in patients with renal failure, coagulopathies, and (occasionally) pneumothorax.... Other reported complications have included arrhythmias, 7 transient worsening in pulmonary infiltrates,' and fever. Fever is seen more frequently with BAL and may be related to local release of cytokines. • There is no documentation indicating that diagnostic FOB may spread pneumonia to other lobes or has a negative effect on *From the Division of Pulmonary and Critical Care Medicine, The University of Tennessee, Memphis; and the Service de R6mimation M6dicale, Hospital Bichat, Paris, France.
Contributon: John B. Bau, M.D.; Robert P. Baughman, M.D.; ~Rodriquez De Castro, M.D.; M. C. Dombret, M.D.; CharluHugo Marquette; Maj Robert M. Middleton Ill, M.D.; Antonio lbrn1s, M.D.; Richard H. Winterbauer; M.D.
the infection.
Condition• that are woneMd by FOB (eg, hypolemia,
cardiac ischeinia) or that may predispose to complications (eg, bleeding) may pose a contraindication to bronchoscopy. In high-risk patients, the specimen can be obtained in a short period of time. Protected specimen brushing can generally be done in less than 1 min and BAL in less tru,n 4 min. In general, the risk for complications increases as procedure time increases. Strict guidelines that can be easily applied to each patient are difficult to establish. Since many factors are taken into account in evaluating the risks vs benefits of the procedure, a discrimination between absolute and relative contraindications cannot be made. Therefore, we will define conditions as being at high risk or at relatively high risk for complications.
Recommendations The following conditions place the patient at high risk for complications-(1) respiratory: Pa01 <70 mm Hg on Flo1 >70 percent, positive end-expiratory pressure (PEEP) 2:15 em H.O, active bronchospasm; (2) cardiac: recent acute myocardial infarction (:S48 h), unstable arrhythinia, mean arterial pressure <65 mm Hg on vasopressor therapy; (3) hematologic: platelet count <20,000 cu/mm. The following conditions place the patient at relatively high risk for complications-(1) respiratory: PEEP > 10 em H.O, significant auto-PEEP (2:15 em H.O); (2) hematologic: prothrombin time or partial thromboplastin time > 1.5 times control; (3) central nervous system: increased intracranial pressure. During and after bronchoscopy, a record should be kept of complications such as hemorrhage, arrhythmias, hypoxeInia, and pneumothorax and their degree of severity. A~
of Hlture Investigation
Additional studies of incidence and risk factors for complications of bronchoscopy in patients receiving ventilation are required. MANAGEMENT OF PATIENTS IN THE PERIBRONCHOSCOPY PERIOD
Background Diagnostic bronchoscopy should be performed with due caution and continuous monitoring of exhaled volumes and oxygen saturation. Hypoventilation can be minimized by decreasing peak inspiratory 8ow, increasing ventilatory rate, and adjusting peak pressure alarms. Monitoring of exhaled tidal volume allows for best titration of ventilator settings. Hypoxemia and patient-ventilator asynchrony is minimized by delivering a high Flo. (100 percent) and providing adequate sedation with or without short-lived paralysis. Few data are available on the effects of bronchoscopy on pulmonary physiology in patients receiving mechanical ventilation CHEST I 102 I 5 I NOVEMBER, 1982 I SUpplemlnl
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{MV). Cardiac monitoring provides continuous display of heart rate and recognition of rhythm abnormalities. Sinus bradycardia may result from auto-PEEP induced by instrumentation or air trapping and is minimized by premedication with atropine.
Recommendations Adaptor: An adaptor to minimize air leak is recommended. Endotracheal Thbe Size: The endotracheal tube should be large enough to allow for adequate ventilation during the procedure. For adult patients, the endotracheal tube size should be 2:1.5 mm larger than the external diameter of the flexible bronchoscope. lentilator Settings: Set Flo1 at 100 percent, respiratory rate at 15 to 20 breaths/min, and peak inspiratory flow at S60 Umin. The peak pressure alarm should be set to a level to allow adequate ventilation. Titrate the ventilator settings to maximize exhaled tidal volume. Premedication: Sedatives with or without a short-acting paralytic agent are recommended. A paralytic agent should be considered in patients at high risk for complications who are undergoing prolonged bronchoscopy. Monitoring: During bronchoscopy, the monitoring of the following cardiopulmonary parameters is recommended: ventilator-exhaled tidal volume and peak inspiratory pressure; oximetric-continuous oximetry; cardiac-continuous single-channel electrocardiography.
AmJS of .Rlture Investigation Various ventilatory maneuvers to maximize oxygenation, ventilation, and return of BAL fluid require investigation. The relationship of measured peak pressure to actual intrathoracic pressure during bronchoscopy also requires study. SAMPLING AREA
Background Selection of the sampling area may be important in obtaining meaningful results. The sampling area is selected based on the location of the new or progressive in6ltrate on chest radiograph or the segment visualized during bronchoscopy as having purulent secretions. Selection may be difficult in patients with diffuse in6ltrates. In the immunosuppressed host with diffuse inJiltrates (including ventilated patients), bilateral sampling has been advocated.9 One group has advocated bilateral sampling in patients with ARDS.'0 There is no convincing evidence that multiple specimens are more accurate than single specimens. Although autopsy studies indicate that VAP is frequently disseminated into each pulmonary lobe 11 and involves predominantly the posterior portion of the lower lobes, 11 two clinical studies of patients receiving ventilation with clinical pneumonia contradict these findings. 13•1• Baughman et al13 reported PSB cultures of the noninvolved lung to be sterile in three of four patients and positive in only one patient with pneumonia. Similarly, Belenchia et al" have described significant bacterial growth in only one of two contralateral sampled bronchi in patients with ARDS and fever. However, two recent studieslll·18 have found good correlation between cultures of blind nonbronchoscopic sampling of the lung 558S
periphery and samples obtained by bronchoscopy, even when obtained from different lobes or the contralateral lung. Purulent secretions are frequently present in the tracheobronchial tree of patients with acute respiratory failure . The site of origin of these secretions can be either the upper or lower respiratory tract (above or below the vocal cords). In the former, secretions originate from the nasopharynx, the sinuses, and the stomach and accumulate above the inflated endotracheal tube (ET) cuff before being introduced into the trachea. The portion of the upper trachea between the inflated ET cuff and the vocal cords behaves as a reservoir for collection of secretions that are sheltered from suction devices. Secretions in the lower airways can originate from either tracheobronchitis or a pneumonia. Therefore, the presence of purulent secretions in the large airways at bronchoscopy is neither sensitive nor specific for pneumonia. Fagon et al17 diagnosed VAP with PSB in only 22 of 75 patients receiving MV {29 percent) who had fever, leukocytosis, a new radiographic in6ltrate, and bronchoscopically visualized purulent tracheal secretions. Similar findings were described by Mauldin et al. 18
Controversies Does the finding of dissemination to both lungs in postmortem studies11•11 represent the terminal stage of pneumonia in terminally ill patients, or is it a true reflection of the anatomic distribution of pneumonia in all patients receiving MV? The literature does not provide clear guidelines for selecting a sampling area in patients with diffuse infiltrate without a discernible acute localized process.
Recommendations The sampling area is selected based on the location of the new or progressive in6ltrate on chest radiograph or the segment visualized during bronchoscopy as having purulent secretions. Collection of secretions in the lower trachea or mainstem bronchi, which may represent recently aspirated secretions, should be avoided. Sampling is directed to the abnormal subsegment in patients with endobronchial or purulent secretions.
Aretl3 of Future Investigation A scoring system for evaluating endobronchial abnormalities in patients undergoing bronchoscopy needs to be developed. The need for multiple sampling sites in patients with diffuse pulmonary in6ltrates (eg, ARDS) should be evaluated. Data are needed on the distribution of bacteria in the lungs of patients with and without VAP. The need for direct bronchoscopic sampling vs quantitative culture of the tracheal aspirate or other nonbronchoscopy techniques requires further evaluation. SAMPLING TECHNIQUES
Background Fiberoptic bronchoscopy provides direct access to the lower airways for sampling bronchial and parenchymal tissues. To reach the bronchial tree, however, the bronchoscope has to traverse the endotracheal tube, where contamination of the instrument is likely to occur with introduction into the suction channel of organisms contaminating (aspiSlandardlzallon of Techniques {Medurl, Chatltre)
-~
rated from above the ET cufl) or colonizing the endotracbeal tube and the central airways. 111.., Suction through the worldog channel of the FOB before obtaining PSB or BAL sampling increases the likelihood of contamination. Injection of lidocaine (topical anesthesia) carries contaminants that have accumu1ated in the broochosoope suction channel into the bronchial tree and compromises culture results. Lidocaine also bas bacteriostatic properties;11 however, the use of 1 to 2 ml of a 1 percent solution to anesthetize a lobe prior to BAL resulted in a concentration of lidocaine in the BAL efBuent below that reported to inhibit bacterial growth.-
Protected Specimen Bro8hlng The following methodology for PSB sampling was de-
scribed originally by Wimberley et al.u The tip of the bronchoscope is positioned next to the orifice of the sampling
area and \be fSB ~tbeter advanced aem out of the FOB to
avoid collection of pooled secretions on the catheter tip. The inner cannula is protruded to eject the distal carbon wax plug into a large airway, and the catheter is advanced into the desired subsegment. Ifpurulent secretions are visualized at a subsegmental level, the brush is rotated into them. After sampling, the brush is retracted into the inner cannula and the inner cannula into the outer cannula, and then the catheter is removed from the bronchoscope. A small quantity of brush secretions may be smeared into a sterile slide for a Gram stain. The distal portions of the outer and inner cannula are separately and sequentially wiped clean with 70 percent alcohol, cut with sterile scissors, and discarded. The brush is adyanced out and severed with a sterile wire clipper into a container with 1 ml of diluent to avoid drying and rapid loss of bacteria. The specimen is submitted for quantitative culture within 15 min. Higuchi et al• first described the use of PSB in animals receiving ventilation and introduced a modilication to the original protocol of WlDlberley et al.u With Higuchi's technique, the brush is wedged into a peripheral position after dislodging the occluding plug into the selected subsegment. This method was modified by Cbastre et al• in a series of patients dying of respiratory failure.
Bronchoaloeolar LAvoge
'
Bronchoalveolar lavage is obtained by infusion and aspiration of a sterile physiologic solution through a 8exible bronchoscope wedged into a bronchial subsegment. The amount ofBAL ftuid injected for the assessment of infectious lung disorden bas not been standardized. The BAL Cooperative Group Steering Committee bas recommended using 240 ml for the evaluation of patients with intentitial lung disease.11 In studies utilizing BAL for bacterial cultures, including studies with patients receiving MV, amounts of BAL ftuid have ranged from 100 to 240 mi. • At least 120 ml are necessary for retrieving secretions from the periphery of the lung subsegment. • The effect of dilution on culture results bas not been evaluated. Controversfes
Protected Spedmen 811J8hjng: Peripheral wedging of the brush may minimize the sampling area or cause sampling error. Peripheral wedging may also increase the risk for
pneumothorax. Obtaining smean for Gram stains may decrease the amount of secretions for cultures and oJI'er an additional risk for contamioatino. Bronchoaloeolar LAvoge: The amount of ftuid necessary to obtain adequate sampling and the amount of retrieved ftuid necessary for adequate microbiologic analysis are not agreed upon.
Recommendatimv General Recorntnendatio: Suction or injection of lidocaine through the worldog channel of the FOB should be avoided. Suction through the endotracheal tube before bronchoscopy should be performed. Protected specimen brushing is performed before BAL. Protected Spedmen 811J81dng: Purulent secretions shoold be sampled at a subsegmentallevel. If purulent secretions are not visualized, the brush should be advanced peripher-
ally Ufttilit iJ llOt viJualBd. hMq wWul Mt to we8p It
into a peripheral position. The brush is moved baclcward and forward and gently rotated several times. Bronchoaloeolar LAvoge: The tip of the &beroptic bronchoscope is wedged into a subsegment of the lung. and 20 ml sterile saline solution are injected, aspirated, and collected separately. This &rst aliquot shoold Dot be submitted for quantitative bacterial cultures or microscopic evaluation to identify intracellular organisms; however, it can be used for other microbiologic analysis. Additional aliquots of 20 to 60 ml are injected and aspirated baclc after each instillation. The total amount of ftuid injected should be 2:140 mi. AreuofFbhnl~
Investigation is required to assess the recovery of organisms at various volumes of BAL infusion and with each individual aliquot. Alternative location for placiDg the PSB should be investigated. ANALYSIS OF DATA
Definition of SotVjJctory Buplratory ~ Protected Specimen Bro81dng: The literature does not provide criteria to assess the adequacy of a PSB specimen. Hemorrhage is an occasional complication of brushing, but the effects of hemorrhage on culture results have not been reported.
BronchotJceolar LAvoge: In a study of nooventilated patients, Kahn and Jones» showed that the recovery of more than 1 percent squamous epithelial cells (SEC) in the cytocentrifuged BAL specimen was an accurate predictor of heavy contamination by oropharyngeal ftora. Columnar epithelial cells (CEC) are indicaton of tracheobronchial proximal sampling; however, their role has not been well characterized in patients receiving MV. Three studies of patients receiving Mv-.a have described the presence of CEC or SEC in tbe retrieYed BAL 8uid. Two studies reported the absence of epithelial cells, and one study reported the presence of > 1 percent SEC or CEC in 30 percent of samples. JJ Pneumonia is a highly cellular inflammatory reaction with neutrophilia predominance. Total cell count and absolute neutrophil count have not been used as a measure of specimen adequacy. Recomtrumdtztio: At least 5 ml of retrieved BAL are needed for adequate microscopic and microbiologic analysis. CHEST I 102 I 5 I NOVEMBER, 1882 I 8uppllmlnl
1M
The following infonnation should be recorded for BAL: (1) percentage of retrieved BAL, excluding the first aliquot; (2}
the presence and degree (minimal, moderate, large) of
hemorrhage by visual inspection; (3} location of the sampling in relation to radiographic infiltrate and presence of endobronchial pus. AtllaS of Future Investigation: Different criteria should be examined for assessing the adequacy of a PSB specimen, including visual inspection and cellular analysis of the specimen. Further research is also needed to evaluate the impact of percentage of ftuid retrieved and the presence of hemorrhage on culture results, to evaluate the percentage of epithelial cells as a marker of contamination, and to evaluate cellular content as an indicator of adequate sampling. Microscopic Analysis
Microscopic analyses of BAL have included the MayGriinwald Giemsa stain for evaluation of the alveolar cell population (cell count and differential), the percentage of cells (neutrophils) containing intracellular organisms, and the percentage of epithelial cells (indicator of oropharyngeal and bronchial sampling); stains have also been used for recognition of organisms (eg, Gram stain, potassium hydroxide, acid-fast}. A stain for elastin fibers has been used as an indicator of lung destruction. Cytologic studies have also been done. CeU Count and Differential: Several studies have shown a significant increase in total neutrophilic count in the BAL of patients with active YAP. The mean percentage of neutrophils varied from 77 to 82 percent. 18•31 •32 In patients with ARDS, neutrophilia of such a degree can also be associated with a noninfectious pulmonary inftammatory process. 10 &rcentage of CeUs Containing Intracellular Organisms: Microscopic analysis of the BAL may provide rapid identification of patients with pneumonia (presence of intracellular [ICO] and extracellular organisms} and allow early fonnulation of specific antimicrobial therapy (Gram stain) that can be modified later based on the results of quantitative culture and sensitivity. In a group of 61 ventilated patients investigated by Chastre et al,33 microscopic analysis ofBAL showed ICO in more than 7 percent of the recovered cells in 12 of 14 patients with pneumonia (86 percent sensitivity) and in only 2 of 47 without (96 percent specificity). In the remaining 45 patients without lung infection, 43 had less than 2 percent of total alveolar cells containing ICO. Pugin et al•• found ICO in 11 of 14 patients with bacterial pneumonia and in none of 25 samples in patients without lung infection. The ICO were expressed as a percentage of neutrophils (8.3± 11.5) instead of total cells. The correct mode of reporting ICO appears to be the one originally proposed by Cbastre et al, 33 since it takes into account the degree of inftammatory response. Meduri et al34 have reported patients without infection who had > 10 percent ICO as a percentage of neutrophils but
Gram Stain: Many investigators have reported a close correlation between the findings on the Gram stain of the
D/\L and the re&ulta of quantitative culturei. '
8 33 38 ' ' ,37
Elastin Fibers: One study bas reported the findings of elastin fibers in the BAL of 7 of 15 patients with YAP (47 percent) and in only 2 of 25 patients without infection (8 percent). 18 In infected patients, elastin fibers were associated with Gram-negative bacillary pneumonia and a radiographically localized pulmonary in6ltrate. Ahigh rate of positive results occurs in uninfected patients with ARDS. 18•38 Cytologic Analysis: Cytologic analysis ofBAL in intubated patients with clinical pneumonia bas established alternative diagnoses such as pulmonary hemorrhage, carcinoma of the lung, and opportunistic infections (Pneumocystis carinii and cytomegalovirus}. s ,J3,:u Recommend4tions: The Giemsa stain is discussed by the Consensus Conference Group on Laboratory Analysis in this supplement. Gram stain should be perfonned on the cytospun BAL and may be perfonned on the PSB. AtllaS of Futtl1"8 Investigation: Correlation between cytocentrifuged and direct Gram stain, Gram stain and culture results, and the percentage of intracellular and extracellular organisms on Giemsa stain and the results of quantitative culture should be investigated further. Diagnostic 11&reshold The concentration of organisms necessary to cause pneumonia varies in relation to the virulence of the bacteria and the competence of host defenses. Once bacterial infections of the lung manifest clinically, they contain at least 10' colony-forming-units (cfu)lg of tissue 11 . - and 10" or more bacteria per milliliter of exudate. 311•40 Quantitative cultures are used to assess the concentration of organisms present in respiratory secretions. A low colony count in patients not receiving antibiotic treatment indicates contamination, recent inoculation, or a partially successfUl attempt at eradication. A high colony count indicates that a significant concentration of bacteria is present in the sampled area. ltvtected Specifflen Brushing: In the late 1970s, Wunberley et al14 developed a double-catheter brush system with telescoping cannulas and a distal-occluding carbowax plug for collection of uncontaminated respiratory secretions. Independent investigators have concluded that the utility of PSB in diagnosing pneumonia rests upon its ability to recover organisms from lower respiratory tract secretions at a concentration :2::1()'1 cfu/ml. The volume of respiratory secretions retrieved by PSB is approximately 0.001 ml.14·" The methodology described above must be followed precisely to minimize contamination of the specimen. The brush is diluted in 1 ml of holding medium, which results in a 100to 1,000-fold dilution before plating. A growth of i2::10' cful ml in the culture plate indicates an initial concentration of 1()5 to 1()5 bacteria per milliliter in the retrieved secretions. •• The usefulness of PSB in evaluating patients receiving MY suspected of having pneumonia bas been extensively investigated in both human..,· 13•17. -·31 .:U.37.•1.., and animal11.111 studies. The findings of most studies are summarized in Table l. In experimental animals with ARDS who had histologically and bacteriologically proven pneumonia, Higuchi et al• showed that samples collected by PSB had a specificity of 100 percent and a sensitivity of70 percent for
Table 1-Findinga of Slullia &porting the RmJta of PSB Qua~ Culturea No. of Patients
Investigator Higuchi et alChastre et al• ATB* NoATB Baughman et al 13 Fagon etal• TorresetaF ATB NoATB
10
7/10
M)
6t6
8120
21 147
7/12
34134
1113 4176
4 14 17 9 8 103 349
True-Negative
False-Negative
M)
3110
12.120
5112 7/8 12113 72176
118
12118 214 1fi/14 11117
25
1btal
Vl
414 7/8
12
ATB NoATB De Castro et aJ4I
False-Positive
26
14
Pbametal'"
Percentage,
True-Positive
M
7n
(W
IW
fi/4
118 004
6118 214
37
4114
6117
519 &'8
~
Undeterminate
419 218
41149 1181142
141153
83
9
1137
3&'37
1391153 91
8149 241142 17
17 54 15
• ATB =antibiotics.
quantitative cultures (~10' cfu/ml) and a 30 percent sensitivity for Gram stain. Chastre et al• performed bronchoscopy in 26 intubated patients with respiratory failure just after their deaths while MV was continued. After obtaining a PSB sample from the anterior segment of the left lower lung, this lung segment was removed by thoracostomy and subjected to histologic evaluation and quantitative bacterial culture. All six patients with pneumonia determined by histologic criteria had at least one microorganism that grew in concentrations greater than 10' cfu/g on lung cultures; four patients bad polymicrobial growth. Cultures of the PSB yielded 15 of the 19 bacteria present in the lung cultures and no additional organisms. All protected brush cultures had at least one microorganism in a concentration above 10' cfu/ml. 1\venty patients had no histologic evidence of pneumonia. Using the break-point oflO' cfu/ml to define a positive PSB culture, no false-negative results were observed. In the subgroup of 12 patients who were receiving antibiotics at the time of the study, however, 7 had at least 1 organism at a concentration > 10' cfu/ml (specificity, 60 percent). In the one who received no antibiotics, the false-positive rate was 23 percent (specificity, 87 percent). Baughman et al 13 subjected 21 intubated patients with a new infiltrate who had been off antibiotics for at least 48 h
c::::=J
Number
c=:J
True positive
-
to FOB with bilateral PSB. A growth ~10' cfu/ml was found in seven of eight patients with pneumonia and in none of the patients who had an alternative diagnosis established. Concurrent antibiotic use affects the diagnostic sensitivity ofPSB quantitative cultures. Figure 1 summarizes the results of three studies15·• ·37 that reported the results of cultures in patients receiving or not receiving antibiotics at the time of bronchoscopy. Torres et a}5 investigated the diagnostic utility PSB in 25 patients with clinical pneumonia who were receiving MV, all but 4 of whom had antimicrobial therapy stopped for more than 4 days. Of these 25 patients, 7 had a negative finding with an alternative diagnosis determined in all; 18 had pneumonia, confirmed by postmortem studies in 10 and by successful response to antibiotics in 8. Sensitivity was 50 percent (2 of 4) and 71 percent (10 of 14), respectively, in patients with and without antibiotics at the time of FOB, while the specificity was 100 percent for both. Pham et al 15 reported on the utility of PSB in 17 patients with definitive VAP. The test was falsely negative in 4 of 9 patients (44 percent) receiving antibiotics and in 2 of 8 (25 percent) not receiving antibiotics for at least 48 h. The amount of time that the patient does not receive antibiotics before bronchoscopy may also affect the concentration of organisms in the PSB sample. In one study,:w the odds in favor of a truepositive PSB culture increased an estimated 47 percent
26
False negative
15
On antibiotics
Off antibiotics
FIGURE 1. Effect of antibiotics on the results of PSB quantitative
cultures.
CHEST I 102 I 5 I NOVEMBER, 1992 I Supplement
IMS1S
(p<0.06) for each additional day without antibiotic treatment. Two groups of investigators have reported their experience using FOB with PSB in a large patient population and have used the results of cultures to direct treatment. Fagon et al• prospectively investigated 147 patients with clinical pneumonia receiving MV, 87 of whom had received antibiotic treatment for more than 3 days. Quantitative culture of the PSB had a growth C!:lO' cfu/ml (of at least one microorganism) in 45 patients (30 percent). The diagnosis of pneumonia was confirmed in 34 of these patients (28 by autopsy, 6 by
by contamination with upper airway bacteria, which have been found to a significant degree (> 10' cfulml) in one third of specimens. 31 •37 Two groups of investigators first described the role ofBAL in diagnosing bacterial lower respiratory tract infection in patients not receiving MV and found a growth in excess of lOS cfulml in the majority of patients with pneumonia.30•38 Four studies have compared the effectiveness of BAL and PSB in collecting lower airway secretions in animals" and patients'·31•37 receiving MV. In a baboon model of respiratory failure, Johanson et al11 compared the results of quantitative
defined in 7 and was excluded in 4 (false-positive rate, 11 percent). Of the 147 patients, 102 had either no growth (77 patients) or a PSB culture yield of <10' cfu/ml. None of them bad bacterial pneumonia, excluded in most at autopsy (34 patients) or by recovery without antibiotic therapy. The results are shown in 'Illble l. Positive predicted value of a positive culture was greater than 75 percent. De Castro et al• reported on the use of FOB with PSB in 103 patients, 53 already receiving antibiotics. In 49 patients, growth was C!:lO' cfu/ml. Pneumonia was confirmed in 41 and felt to be probable in 7. In 54 patients, growth was <10' cfulml; 33 had no pneumonia (autopsy confirmation in 2) and received no antibiotic (22) or change in therapy (11). Results were falsely negative in 8 patients, and the diagnosis was uncertain in 10. The PSB cultures had a positive predicted value of 83 percent and negative predicted value of66 percent. Bronchoolveolar Lavage: Bronchoalveolar lavage samples a large portion oflung parenchyma (approximately 1 million alveoli) since the alveolar surface distal to the tip of the wedged bronchoscope is estimated to be 100 times greater than that of the peripheral airways. .. The sensitivity of BAL in identifying patients with bacterial pneumonia rests upon the capacity of BAL to recover organisms at a significant concentration. The recovery of bacteria from the distal airways is affected by the amount of fluid injected, the concentration of organisms in the lung, and its dilution with BAL fluid. The dilution of lung secretions in the BAL fluid in patients without pneumonia is 10- to 100-fold (> 1 ml in 10 to 100 ml ofBAL efBuent). 1111•110 In patients with pneumonia, BALis estimated to recover at least 5 to 10 times the amount of organisms retrieved by PSB. 30·,. A colony count of 10' cful ml, therefore, represents lOS to lOS bacteria per milliliter in respiratory secretions. The specificity value of BAL cultures in excluding bacterial pneumonia has been limited in part
findings of open-lung biopsy. Six ventilated animals who did not receive antibiotics bad moderate to severe pneumonia on histologic exam and a polymicrobial growth on culture. The BAL recovered 74 percent of all species present in the lung tissue compared to 41 percent by PSB and 56 percent by needle aspirate. Bacterial growth in the BAL, expressed as bacterial index (sum of all the logarithmic concentrations of individual organisms), was linearly related to tissue values. TISsue cultures had a mean growth of 2.8 species at 10' cfu/g and 1.4 species at 10' cfu/g. In animals receiving antibiotics, absence of growth was frequently found despite histologic evidence of pneumonia. Guerra and Baughman• obtained BAL for quantitative bacterial culture at one dilution in 54 patients receiving MV who underwent bronchoscopy for clinical pneumonia (30) or a noninfectious process (24). Using a diagnostic threshold of 10' cfu/ml, a significant growth was seen in 16 of 18 patients (89 percent) with pneumonia and in none of those without. Of patients with bacterial pneumonia, 70 percent were receiving antimicrobials, and none of the significant organisms (> 10' cfu/ml) was sensitive to the administered antibiotic. Of patients in the control group, 75 percent were receiving antimicrobials, and this treatment was disoontinued after results of cultures were avai1able. Torres et al37 compared the diagnostic yield of PSB and BALin 25 patients with VAP recently treated with antibiotics (<12 h). Microbiologic processing of the BAL fluid was different from other previously described methods, 11 •30•31 .5'7 with quantitative cultures performed on a concentrated (tenfold) sample. A diagnostic threshold oflO' cfulml, similar to the one ofPSB, was used. Asignificant growth was found in 72 percent of patients with each technique and in 2 of 7 BAL samples in a control group (71 percent specificity). Five patients had only one of the two methods positive, and
response to treatment); pneumonia could not be accurately
cultures of BAL and PSB to the histologic and bacteriologic
Table l-&.ult. of BAL Culture m~ tDilh Bacterial PneumoniG cfulml•
No. of Investigator Chastreetal>'
Patients
BAL, ml
Significant Growth
5
100
10" cfulml
Isolates, n
<10'
~10'
~10"
~10"
15
4
5
2*
4*
52
22
12*
14*
4
7
9
23 9:1
17 20
415
'lbrres et aJ31
25
150
Gue~ and Baughman•
18
240
1btal
48
Percentage
10' cfulml 17125 10" cfulml 16118 37 77
18 (22)t 85 100
2 28
33
17 20
*Organisms that grew above the diagnostic threshold. tindividual bacterial growth was not reported.
!128
sa.ndlrdlzdon of~ (Medurl, Chatltre)
four bad both negative (84 percent sensitivity for combined PSB and BAL). Agreement between BAL and PSB was 75 percent with respect to the type of organism recovered, but when concentration of organisms was also considered, it dropped to 56 percent. Combining the results ofquantitative cultures of these studies (fable 2), BAL bad a sensitivity of 77 percent and a specificity of 69 percent. t.31.37 Diagnostic thresholds of BAL have ranged from 10' cful
pneumonia. For BAL, the presence of >2 percent ICO or a positive Gram stain is suggestive of pneumonia. A negative microscopic analysis should not be considered definitive evidence for absence of pneumonia. Areas of ~ture Investigation: Comparative studies of histologic findings and lung tissue cultures (patients receiving MV) with microbiologic and microscopic analysis of secretions from the same lung segment obtained with BAL,
adopting a lower diagnostic break point improves sensitivity but lowers specificity of the test. Techniques that minimize contamination of the BAL may minimize this problem and improve specificity.....7 lilctors Affecting the Interpretation of Culture Results: While a cutoff point establishing the presence of pneumonia is well established in patients receiving MY without antibiotic treatment, the culture results of PSB and BAL done in patients on antimicrobial therapy can be difficult to interpret (Fig 1). When nosocomial bacterial pneumonia develops as a superinfection in a patient receiving systemic antibiotics, the etiologic organisms are likely to be resistant to the treatment regimen and their growth unaffected by them. A significant growth, however, has also been reported in patients receiving antibiotics without histologic evidence of pneumonia. • In patients recently started on antibiotics, a nonsignificant growth implies either absence of pneumonia or suppression of bacterial growth by the antibiotic used. One study indicates that bronchoscopic specimens (PSB and BAL) obtained within 12 h of starting antibiotics for presumptive pneumonia are still useful in identifying the causative pathogens and directing therapy, with a sensitivity of70 percent. 37 For this reason, an effort must be made to obtain bronchoscopic specimens before institution of antibiotic therapy. If treatment is initiated for a specific and documented infection (eg, peritonitis, meningitis), a full course of antibiotics has to be completed. The diagnostic accuracy of the microbiologic results is increased if antibiotics are discontinued 48 h before the procedure. In patients with pneumonia, FOB can yield negative results in the following situations: (1) bronchoscopy was done in an early infection with a bacterial burden below the concentration necessary to reach diagnostic significance; (2) bronchoscopy was done in an unaffected bronchial segment; (3) time without antibiotic therapy was insufficient; or (4) processing of the specimens was incorrect. Repeated bronchoscopy has been suggested for symptomatic patients with a concentration of bacteria in the PSB specimen between 1()l and 10' cfu/ml. 15 Controversy: The diagnostic value of PSB and BAL specimens is controversial in patients receiving antibiotics. Recommendoffons for Quantitative Cultures: For PSB, a value ~10' cfu/ml should be considered a significant level for bacterial YAP. For BAL, a value ~10C cfu/ml should be considered a significant level for bacterial YAP. Each morphotype present should be individually quantitated and reported. Y~ues within 1 log 10 of the cutoff should be interpreted cautiously. Recommendations for Mfcroscopic Anolysis: Microscopic analysis of the PSB and BAL may be useful indicators of pneumonia. For PSB, a positive Gram stain is suggestive of
for patients receiving antibiotics need to be developed.
ml to 10' cfu/ml. In addition to the factors presented above,
PSB, or other tecltnlquet are needed.
DiaiMtti~
mteria
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