Nonbronchoscopic Lung Lavage for Diagnosis of Opportunistic Infection in AIDS

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clinical invesligaliOnS Nonbronchoscopic Lung Lavage for Diagnosis of Opportunistic Infection in AIDS· Jack M. Mann, M.D.;t Craig S. Altus, M.D.;t Carolyn A Webber, M.D.;+ Peter R. Smith, M.D., F.C.C.P.;§ Rudolph Muto, M.D., F.C.C.P.; and Albert E. Heurich, M.D.§

Thirty patients known to have or suspected of having acquired immunodeficiency syndrome (AIDS) were evaluated for opportunistic pulmonary infection using a double lumen lavage catheter (DLL). Lavage specimens obtained were cytocentrifuged and initially stained by the Papanicolaou technique as a means of rapid evaluation for Pneumocystis carini;. If no opportunistic organism was identified, the patient underwent further diagnostic investigations. In 18 patients receiving mechanical ventilatory support, the procedure was performed via the endotracheal tube. Twelve patients who were less severely ill underwent

the procedure via the transnasal route. In 43 percent (13/30), opportunistic infections were diagnosed by DLL. Twelve had P carinii, one of whom had cytomegalovirus and another of whom had Herpes simplex viruses, and one with Toxoplasma gondii. Thus, the sensitivity for all opportunistic infections was 86 percent (12/14). Ute volume of fluid recovered averaged 93 percent of that instilled. There was no significant difference between prelavage and postlavage PaD!. In this group of patients, double lumen lavage obviated the need for more invasive and expensive procedures.

Bronchoalveolar lavage (BAL) performed via the fiberoptic bronchoscope (FOB) has been shown to be effective in diagnosing Pneumocystis carinii and other opportunistic lung infections in patients with acquired immunodeficiency syndrome (AIDS) and in other immunocompromised hosts. 1-5 As the number of AIDS victims continues to increase, an alternative to FOB that is sensitive, safe, less time consuming, and less expensive in making the diagnosis of lung involvement would be of value." As an alternative to FOB, Caughey et aF found that a fluoroscopically guided catheter for lavage was of diagnostic value in patients whom he prophylactically intubated. In nonintubated patients, others have been successful in using induced sputum as an initial diagnostic approach. 8.9 Recently, we evaluated a double lumen suction catheter, designed to enhance removal of tracheobronchial secretions. Based on our preliminary

observations, we felt this technique could provide lavage specimens that were satisfactory for diagnostic purposes, especially in those patients with little or no secretions or too weak to effectively cough. Therefore, as an alternative to current techniques, this double lumen lavage catheter (DLL) was evaluated in a total of 30 patients, initially in intubated, and subsequently, in nonintubated patients, for use as a diagnostic bedside procedure.

*From the Pulmonary Disease Division, Department of Medicine and Department of Pathology (Cytopathology), State University of New York, Downstate Medical Center-Kings County Hospital Center, Brooklyn. tClinical Assistant Instructor of Medicine. +Clinical Assistant Professor of Pathology. §Assistant Professor of Medicine. Manuscript received January 15; revision accepted September 11. Reprint requests: Dr. Mann, 158 Lockwood Avenue, New Rochelle, New York 10801

MATERIALS AND METHODS

Thirty patients who were known to have or were suspected of having AIDS with pulmonary symptoms were studied. Patient characteristics are shown in Table 1. All had bilateral diffuse infiltrates on chest roentgenogram. Eighteen of them required

Table I-Patient Population Profile Nonintubated

Intubated Risk Factor

Men

Women

IV Drug abuser Homosexual Haitiant None known Total risks

9 1* 1 1 12

4

0

3

0

7

Men

8 1 2 0

11

All Patients

Women

Men

Women

1 0 0 0 1

17 2 3 1 23

5 0 3 0

8

*This one intubated homosexual patient also had IV drug abuse as a risk factor and was included above. tNo longer considered a risk group. CHEST / 91 / 3 / MARCH, 1987

319

FIGURE 1. Disposable double-lumen lavage catheter (DLL) used for pulmonary lavage.

mechanical ventilation because of severe hypoxemic respiratory failure. The remaining 12 patients could be maintained on supplemental oxygen alone. Patients were selected for the study on the basis of timely availability or lack thereof, of a bronchoscope to perform BAL for diagnostic purposes (sterilization and aeration of the bronchoscope made it unavailable for periods of up to 24 hours). A disposable double lumen lavage catheter was used to perform the lavage (Fig 1). In those patients mechanically ventilated, no preoperative medications were given. The catheter was passed into the endotracheal tube and the tracheobronchial tree via a standard ventilator adapter. An attempt was made to wedge the catheter in its maximally advanced position for several seconds and then reposition it by partial withdrawal, rotation, and readvancement. The double curved catheter tip facilitated directioning of the catheter in the lung. One hundred to 250 ml of continuously flowing normal saline solution was introduced and simultaneously withdrawn via continuous suction. Recovered fluid was sent for cytologic studies, staining, and culture for microorganisms, as previously reported. 1 The entire procedure took between two and five minutes, depending on the volume administered. The study was approved by the human research committee and written consent was obtained. For the intubated patients, during the procedure, Flo, was increased to 90 percent as a precaution and returned to original settings immediately afterward. TIdal volumes were adjusted to maintain baseline values. Oxygen saturation was continuously monitored by oximetry. Arterial blood gas values were obtained immediately before and 30 minutes after the procedure. In the nonintubated group, anesthesia of the upper airways was obtained using nebulized 2 percent lidocaine solution. Viscous lidocaine was applied intranasally. Patients were initially placed in a sitting position with the chin resting on the chest and the tongue extended as much

as possible. The catheter was then inserted via the nasopharyngeal route. The patient was asked to repeat the letter ICE" until its quality changed indicating that the catheter had passed the vocal cords. Once the trachea was entered, the patient was placed in the supine position. Supplemental nasal oxygen was increased to 8 Uminute and returned to pre study settings after finishing the procedure. From this point, the procedure followed that used for the intubated patients. If a diagnosis was not made by DLL, other diagnostic investigations were undertaken, ie, 6beroptic bronchoscopy with BAL and transbronchial biopsy (TBB)or open lung biopsy. In other instances, final diagnosis was concluded based upon clinical course or postmortem examination if the patient died before further studies could be performed. RESULTS

The diagnosis obtained by double-lumen lavage (DLL) and the final diagnosis determined either by autopsy, transbronchial biopsy, BAL, open lung biopsy, or clinical course are compared in Table 2. Seven of the 18 intubated patients were found to have opportunistic infections. Six had P carinii pneumonia (PCP), one of whom also had Herpes simplex virus (HSV), and another who had Toxoplasma gondii alone. In four patients, nonopportunistic bacterial pathogens recovered on culture were found to be the cause of pneumonia. In the remaining seven patients (three post mortem, one FOB, one open lung biopsy, and two improved without therapy for opportunistic lung infec-

Table 2-Diagnosed Opportunistic Infections Intubated

PCp· CMV TOXO HSV Totall

Nonintubated

DLL Dx

Missed by DLL

Total

DLL Dx

Missed by DLL

Total

DLL Dx

Missed by DLL

Total

6 0 1 1 8

0 0 0 0 0

6 0 1 1 8

4 1 0 0 5

2 0 0 0 2

6 1 0 0 7

10 1 1 1 13

2 0 0 0 2

12 1 1 1 15

·PCP is Pneumocystis carinii pneumonia; CM~ 320

Total

cytomegalovirus; TOXQ, Toxoplasma gondii; and HS~

Herpes simplex virus. OpportunisticInfectionsin AIDS (Mann et 81)

tions and refused further evaluation), and no definitive pathogens were recovered. Seven opportunistic infections were diagnosed in six of the 12 non intubated patients. Pneumocystis carinii was recovered from four DLL specimens, a fifth by BAL, and the sixth was a presumptive diagnosis based on the response of pentamidine isethionate (this patient refused further diagnostic procedures). Double lumen lavage from the patient false negative for P carinii cultured cytomegalovirus. Four patients had no opportunists found either by DLL or FOB. A fifth who underwent open lung biopsy was not found to have P carinii. The final patient was found to have subacute bacterial endocarditis and heart failure and responded to appropriate therapy. In all, 43 percent (13/30) of patients were found to have opportunistic infections, one with T gondii and 12 with PC~ finding concomitant CMV in one and HSV in another. Thus, the sensitivity of double lumen lavage for all opportunistic infections was 87 percent (13/15). The volume of fluid recovered in the intubated group averaged 102 percent (93 to 125 percent) of that instilled. There was greater variation in the nonintubated group, with a mean return volume of 89 percent (65 to 133 percent). All samples were found to contain alveolar macrophages and bronchial epithelial cells. Mean pre Pa02 (8 ± 30 mm Hg) and postprocedure Pa02 (85 ± 29 mm Hg) available from ten intubated patients was not significantly different. In six nonintubated patients who permitted serial arterial blood gas measurements, pre Pa02 (72 ± 19 mm Hg) and postprocedure Pa02 (66 ± 19) showed a significant difference (p<0.025, Student's t-test). Oxygen saturation remained stable throughout in both groups, and all patients tolerated the procedure well. DISCUSSION

The majority of AIDS victims at Kings County Hospital Center are intravenous substance abusers (Table 1). This population tends to seek medical attention at a time when they are seriously debilitated, often requiring ventilatory assistance prior to ascertaining the underlying etiology of their respiratory failure. Some patients are often unable to followinstructions or cooperate with simple diagnostic studies. Numerous reports in the literature have documented the sensitivity of TBB and BAL in the diagnosis of opportunistic pulmonary infection in patients with AIDS.4.5 They report P carinii to be the most common treatable pathogen present. The complications, as well as the expense, specialized equipment, facilities, and manpower needed to perform TBB and BAL have been discussed. S.8 The bronchoscopic capacities of large urban centers such as this one, where most of the AIDS suspects and

victims are treated, is being taxed. Prolonged sterilization needed for the committed bronchoscopes greatly diminishes the instruments availability and life expectancy. Because of this, alternatives to bronchoscopy have been sought. Several recent studies have shown that PCP can be diagnosed from induced sputum as an initial diagnostic screen.v" Others have not been as successful. 10 The diagnostic utility of various forms of modified conventional suction catheters in intubated patients has been discussed in abstract form by Zackson and Cole, II Karpel and co-workers" and by us." The percentage of lavage return from the latter study was greater than 95 percent as compared to less than 50 percent in the former two, thus decreasing the risk of hypoxia secondary to retained fluid. Similarly, instillation of lavage via a fluoroscopically guided suction catheter seems sensitive, but again risks hypoxemia from unrecovered lavage fluid. 7 We feel that the DLL catheter is far more effective in recovering instilled fluid because of the vortex effect (unpublished data). This may result in a negative pressure within the airways (Bernoulli principle) causing the evacuation of contents from peripheral sites, as evidenced by the presence of alveolar macrophages and bronchial epithelial cells in all samples. At the same time, the continuously flowing fluid prevents local collapse of the airway in the vicinity of the catheter. This effect may be responsible for more effective clearance of secretions as seen in those patients whose return volume is greater than that instilled. Lower yields in two of the nonintubated patients were probably secondary to technique and gravitational effects. Maintenance of adequate oxygenation in our patients is due to the excellent return of lavage fluid. Mean preprocedure and postprocedure Pa02 values for the combined groups of intubated and non intubated patients were not significantly different. The statistical difference in the subset of nonintubated patients can be attributed to the lower return rate. The enhanced removal of secretions in some patients resulted in improved oxygenation; however, a significant correlation between improved Pa0 2 and percentage of DLL return could not be demonstrated. Many of our patients were critically ill and presented with progressive respiratory failure. Therefore, it was impossible to separate the effect of progressive respiratory failure from that of DLL on the Pa02 or the chest roentgenogram in some of our patients. Since the DLL return averaged 97 percent, there would appear to be little chance for derangement of the gas-exchanging units from retention of lavage fluid. A total of 15 opportunistic infections were identified in 13 patients. Double lumen lavage identified ten P carinii infections, one HS~ one T gondii, and one CHEST / 91 / 3 / MARCH. 1987

321

DLL is safe, effective, and can be done at the bedside with minimal training. Positive diagnosis can be ascertained in as little as one hour. It is also an inexpensive technique (about the same as a conventional suction cath eter) in this era of cost containment. In our hands, DLL has often obviated th e need for more invasive and expen sive procedures. ACKNOWLEDGMENTS: The invaluahle assistance of our bron choscopy nurses and the cytopathology technicians is gratefully appreciated. REFERENCES

2

3

4 FIGURE 2. Papanicolaou stained double lumen catheter lavage sediment showing alveolar cast of Pneurnocystis, ciliated bronchial cells . and alveolar macrophages (original magnification x 500).

CMV infection, giving double lumen lavage a sensitivity of 85.7 percent. BAL identified two additional PCP. The morphology of P carinii in the DLL specimens is similar to that seen in conventional BAL. The use of Papanicolaou staining (Fig 2) allows the easy and rapid «60 minutes) cytopathologic diagnosis . GramWeigert and methenamine silver stained smears were examined for confirmation . We did not examine Giemsa stained smears as did Bigby et al. 8 The continuous fluid vehicle during DLL prevents drying, and this maintains excellent specimen morphology. The double curved catheter tip situated 180 degrees from the suction port helps facilitate placement of the catheter into the area of roentgenographically proven lung involvement. If localized disease is present, the catheter can be fluoroscopically guided to the involved area. Auscultation of the chest with a stethoscope can confirm the catheter position in slender patients. All of this can be efficaciously accomplished by one individual at the bedside with a totally disposable and inexpensive system. In intubated patients, the double lumen catheter can be used as a first line diagnostic procedure. In nonintubated patients, it offers an alternative to bronchoscopy when induced sputum is nondiagnostic or where the patient will not cooperate for sputum induction. 322

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14

Orenstein M. Webber C. Heurich A. Cytologic diagnosis of Pneumocystis carinii infection in bronchial alveolar lavage in acquired immunodeficiency syndrome. Acta Cytologica 1985; 29:727-31 Orenstein M. Webber CA, Cash M. Heurich AE . Value of bronchoalveolar lavage in the diagnosis of pulmonary infection in acquired immune deficiency syndrome. Thorax 1986; 41 :345-49 Broaddus C, Dake MD . Stulbarg MS. Blumenfeld. Hadley WK . Golden JA, et al. Bronchoalveolar lavage and tr ansbronchial b iopsy for the diagnosis of pulmonary infections in the acquired immunodeficiency syndrome. Ann Intern Med 1985; 102:747-52 Stover DE . White DA. Romano PA. Gellene RA. Robeson WA. Spectrum of pulmonary diseases associated with the acquired immunodeficiency syndrome. Am J Med 1985; 78:429-37 Coleman DL. Dodek PM , Luce JM , Golden JA. Gold W~I . Murray JF. Diagnostic utility of fiberoptic bronchoscopy in patients with Pneumocystis carinii pneumonia and the acquired immunodefici ency syndrome . Am Rev Respir Dis 1983 ; 132(suppl):180 Rankin JA. Bronchoalveolar lavage for research purposes in the immunocompromised host. Chest 1985; 88:319-20 Caughey G. Wong H, Gamsu G, Golden J. Nonbronchoscopic bronchoalveolar lavage for the diagnosis of Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. Ch est 1985; 88:659-62 Bigby TO. Margolskee D. Curtis JL. Micha el PF. Sheppard D. Hadley WK . et al. The usefulness of induced sputum in th e diagnosi s of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome. Am Rev Respir Dis 1986; 133:515-18 Pitchenik AE. Gangei P,Torres A. Evans OA, Rubin E . Baier H. Sputum examination for the diagn osis of Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. Am Rev Respir Dis 1986; 133:226-29 Brown SM. Sithole L. Aranda C. Induced sputum in the diagnosis ofPneumocystis carinii pneumonia. Am Rev Respir Dis 1986; 132(suppl) :180 Zackson HJ. Cole RP. A simple technique for diagnosing Pneu mocystis carinii pneumonia in intubated pat ients. Am Rev Respir Dis 1986; 132(suppl):181 Karpel JP, Prezant D, Appel D. Bezahler G. Endotracheal lavage for the diagnosis of Pneumocystis carinii pneumonia in intubated patients with acquired immune deficiency syndrome. Am Rev Resp ir Dis 1986; 132(suppl) :181 Mann JM. Altus CS. Heurich AE. Webber CA. Smith PRoMuto R. Nonbronchoscopic lung lavage for diagnosis of opportunistic infections in acquired immunodeficiency synd rome . Am Rev Respir Dis 1986; 132(suppl) :181 Mann JM . Altus CS. Heurich AE. Webber CA, Smith PRo Muto R. Nonbronchoscopic lung lavage in non intubated patients for the diagnosis of opportunistic infection in acquired imm unod eficiency syndrome. Chest 1986; 89(suppl):511

Opportunislic Infections in AIDS (Mann at al)