The Safety and Diagnostic Accuracy of Minibronchoalveolar Lavage in Patients with Suspected Ventilator-Associated Pneumonia

Nosocomial pneumonia is the leading cause of death resulting from hospital-acquired infections among critically ill patients requiring mechanical ventilation (that is, ventilator-associated pneumonia) [1-5]. Several lines of investigation have suggested that previous administration of broad-spectrum antibiotics may predispose patients to develop ventilator-associated pneumonia caused by antibiotic-resistant pathogens [2, 3, 6-8]. Additionally, the reported mortality rates related to ventilator-associated pneumonia caused by antibiotic-resistant organisms are substantially greater than rates associated with antibiotic-sensitive pathogens [5-7]. These findings have fueled a growing debate about the need for more specific diagnostic techniques for ventilator-associated pneumonia that are aimed at directing antibiotic therapy and avoiding its needless administration in order to minimize the development of antibiotic-resistant infections [9-13]. Bronchoscopic sampling of lower airway secretions (for example, the protected specimen brush technique) is an accurate and reproducible method for the evaluation of suspected ventilator-associated pneumonia [3, 14-17]. As part of our ongoing quality improvement efforts [2, 8], we have developed a nonbronchoscopic techniqueminibronchoalveolar lavagefor establishing the diagnosis of ventilator-associated pneumonia and potentially guiding the administration of antimicrobial agents. Therefore, we did a prospective study to investigate the safety of minibronchoalveolar lavage and to compare the results of this method with those of the protected specimen brush technique (in which bronchoscopy is used). Methods Study Location and Patients Our study was done in the medical intensive care unit (19 beds) of Barnes Hospital, a 900-bed private teaching hospital, between October 1993 and September 1994. All patients receiving mechanical ventilation for more than 24 hours were prospectively evaluated. Patients suspected on clinical grounds of having ventilator-associated pneumonia were eligible for entry into the study. The study protocol was approved by the Human Studies Committee of the Washington University School of Medicine, and informed consent was obtained for all patients receiving bronchoscopic procedures. Data Collection The following data were prospectively collected by one of the investigators: patient age, sex, APACHE III (Acute Physiology and Chronic Health Evaluation III) score [18], Organ System Failure Index, hospital admission diagnosis, body temperature, leukocyte count, presence or absence of purulent tracheobronchial secretions, and antibiotic use at the time of the evaluation. All chest roentgenograms were prospectively reviewed by the principal investigator (MK), as were the roentgenographic reports (24 to 48 hours later) for independent confirmation of the presence or absence of pulmonary infiltrates. We also prospectively screened each patient for possible alternative causes for fever and radiographic densities as suggested by other investigators [19, 20]. Patients were also evaluated for the occurrence of complications caused by the sampling of airway secretions with either the minibronchoalveolar lavage or the protected specimen brush techniques. We also analyzed whether these procedures caused complications, including clinically significant arterial blood oxygen desaturation (< 90%), hypotension (mean arterial pressure < 60 mm Hg), tachycardia (heart rate > 120 beats/min), bradycardia (heart rate < 60 beats/min), arrhythmias, bronchial hemorrhage, pneumothorax, and death. Definitions The definition of ventilator-associated pneumonia was modified from criteria established by the American College of Chest Physicians [21]. Ventilator-associated pneumonia was considered to be present when a new or progressive pulmonary infiltrate developed in conjunction with one of the following: radiographic evidence of pulmonary abscess formation (that is, cavitation within preexisting pulmonary infiltrates), histologic evidence of pneumonia in lung tissue, presence of substantial growth on a quantitative culture obtained from the lower airways using techniques that minimize contamination with upper respiratory tract flora (for example, the minibronchoalveolar lavage or the protected specimen brush technique) [15, 22, 23], or a positive blood or pleural fluid culture. Blood and pleural fluid cultures could not be related to another source, and both had to be obtained within 48 hours before or after respiratory sampling. The microorganism(s) recovered from blood or pleural fluid cultures also had to be identical to the organisms recovered from cultures of lower airway secretions. Ventilator-associated pneumonia was considered to be absent when postmortem examination (done within 3 days of the suspicion of ventilator-associated pneumonia) showed no histologic evidence of lung infection; a definitive alternative cause was established; or no substantial growth occurred on a reliable lower airway culture in association with the resolution of one of the following: fever, infiltrate, or leukocytosis. This last criterion was required to occur without the addition of new antimicrobial therapy or without a change in preexisting antimicrobial therapy. All other cases were defined as indeterminate. Scores from the APACHE III test were calculated in a standard manner [18], and the Organ System Failure Index was modified from that used by Rubin and coworkers [24]. Minor bronchial hemorrhage was defined by the presence of new red blood streaking of airway secretions aspirated from the endotracheal tube. Major bronchial hemorrhage was defined as the aspiration of more than 30 mL of red blood from the endotracheal tube. Collecting Lower Airway Secretions By local protocol, the fraction of inspired oxygen was increased to 1.0 before both minibronchoalveolar lavage and bronchoscopy were done. Patients first had bronchoscopy in which the protected specimen brush technique was used and then had minibronchoalveolar lavage. Both procedures were done within 4 hours of one another. The lung being sampled was selected by the principal investigator on the basis of the distribution of the pulmonary infiltrates. Pulse oximetry, heart rate, and arterial blood pressure were continuously monitored during and after these procedures. All respiratory therapists doing minibronchoalveolar lavage were shown how to do this technique and were supervised by the principal investigator before doing the procedure independently. Protected specimen brush samples were obtained using bronchoscopy in a standard manner [15]. Intravenous sedation with either diazepam or midazolam was administered along with 10 mL of 1% lidocaine solution instilled down the endotracheal tube before passage of the bronchoscope. The bronchoscope was then advanced through the endotracheal tube to a position proximal to the segmental orifice to be sampled. A sheathed protected catheter (Microbiology Specimen Brush: Microvasive, Boston Scientific Corporation, Watertown, Massachusetts) was advanced 3 cm out of the bronchoscope, and the inner cannula was protruded to eject the distal carbon wax plug into the large airway. The inner catheter was then advanced into the desired segmental orifice, and the brush was subsequently protruded to obtain airway secretions. Minibronchoalveolar lavage was done using a prepackaged, commercially available telescoping catheter (BAL Cath, Ballard Medical Products, Draper, Utah). The telescoping catheter was passed through the endotracheal tube using an accompanying prepackaged access port adapter, with the curved tip of the catheter directed toward the desired lung [25]. The catheter was advanced until resistance was met, after which the inner catheter was similarly advanced until resistance was again encountered, signifying that it was in a wedged position. Twenty-five milliliters of sterile, physiologic saline solution was then injected through the catheter and then reaspirated using the same syringe. The aspirated lavage sample and the cut end of the protected specimen brush were placed in sterile tubes containing 1 mL of sterile physiologic saline solution for transfer to the microbiology laboratory. Microbiological Analysis The tubes containing the respiratory specimens were first vortexed for 15 seconds. A 0.01-mL calibrated loop was placed into the respective specimens and then onto the center of three media plates (blood agar, chocolate agar, and MacConkey agar). The media plates were then streaked using the pin-wheel streak method and incubated in CO2 at 35 C [23]. Bacterial culture growth was quantitated according to the number of colonies observed per plate: Fewer than 10 colonies per plate represented less than 103 colony-forming units (CFU)/mL; 10 to 100 colonies per plate represented 103 to 104 CFU/mL; 100 to 1000 colonies per plate represented 104 to 105 CFU/mL; and more than 1000 colonies per plate represented greater than 105 CFU/mL. All identified microorganisms were reported with their antibiotic sensitivities. We used a previously established and validated quantitative threshold ( 103 CFU/mL) for both sampling methods to support the diagnosis of ventilator-associated pneumonia [15, 22, 23]. Statistical Analysis The safety of minibronchoalveolar lavage was assessed by comparing the patient's baseline heart rate, blood pressure, and pulse oximetry readings (obtained before doing the procedure during a period of inactivity) with the values most changed from baseline (obtained during the procedure and for 5 minutes after its completion). A paired statistical analysis was done using the Student t-test for this portion of the analysis. The individual complication rates for the two procedures were compared using the chi-square statistic. All changes in heart rate, blood pressure, and pulse oximetry are reported as average within-person changes along with their variance. All other results are expressed as