708

:\OTES

References

1. Lester, W., Moulding, T., Fraser, R. I., McClatchy, J. K., and Fisher, D. A.: Quintuple drug regimens in the treatment of Battey-type infections, Trans 28th VA-Armed Forces Res Conf Pulm Dis, 1969, p. 83. 2. Yeager, H., and Raleigh, J. W.: Pulmonary disease due to Mycobacterium intrace/lulare, Am Rev Respir Dis, 1973,108,547. 3. Lederberg, J., and Lederberg, E. M.: Replica plating and indirect selection of bacterial mutants, J Bact, 1952, 63, 399. 4. ~chaefer, W. B.: Quoted by W. F. Russell and G. Middlebrook, in Chemotherapy of Tuberculosis, Charles C Thomas, Co., Springfield, Ill., 1961, p. 21. 5. Cannetti, G., Rist, N., and Grosset, l\'.: Mesurc de Ia sensibilite du bacille tuberculeux aux drogues antibacillaires par Ia methode des proportions, Rev Tuberc, 1963,27,217.

6. David, H. L.: Probability distribution of drugresistant mutants in unselected populations of Mycobacterium tuberculosis, Appl Microbiol, 1970,20, 810. 7. Gangadharam, P. R. J., Cohn, M. L., and Middlebrook, G.: Dynamic aspects of the sterilizing action of isoniazid on Mycobacterium tuberculosis, Am Rev Respir Dis, 1963, 88,558. 8. Stottmeier, K. D., Woodley, C. L., and Kubica, G. P.: New approach for the evaluation of antimycobacterial drug combinations in vitro (the laboratory model man), Appl Microbiol, 1969, 18,399. 9. Vischer, W. A.: Antimicrobial activity of the leprostatic drug 3- (P-Chloranilino)-10- (P-chlorphenyl-2, 10-dehydro-2- (isopropylimino)-phenazine (G 30320, B663), Arzneim Forsch, 1970, 20, 714. 10. Watson, B. M., and Smyth, J. T.: B663 and ethambutol in the treatment of Battey disease, Med J Aust, 1968,2,261.

DEATHS AND COMPLICATIONS ASSOCIATED WITH TRANSBRONCHIAL LUNG BIOPSY' Summary _ _ _ _ _ _ _ _ _ _ _ _ _ _ __

A questionnaire requesting information about complications resulting from transbronchial lung biopsy was sent to 178 directors of respirp.tory disease training programs in the United States and Canada. Ninety-six questionnaires (54 per cent) were returned, listing 5,450 transbronchial lung biopsy procedures. Thirteen deaths were directly or temporally related to the procedure. Nine patients died from hemorrhage. Eight of these patients had underlying diseases or were receiving drugs known to affect hemostasis. One also had pulmonary hypertension. One patient died from a tension pneumothorax that rapidly progressed more than two hours after the procedure. Analysis of the exact data, which were available for 2,628 procedures, indicated that pneumothorax, hemorrhage exceeding 50 ml, and death occurred in 5.5, 1.3, and 0.20 per cent of procedures, respectively.

Transbronchial lung biopsy has been recommended as a safe procedure for the diagnosis of pulmonary

(Received in original form October 26, 1976 and in revised form December 23,1976) 1

Requests for reprints should be addressed to Dr.

nodules and diffuse lung disease (1-8). The technique consists of passing biopsy forceps I to 2 mm in diameter through either a bronchoscope or a fluoroscopically placed catheter to the lesion, closing the forceps, and withdrawing bronchial and parenchymal tissue. Only two deaths related to the procedure have been reported (3, 9), and morbidity has varied from 0 to 15 per cent (l-8). Because transbronchial lung biopsy is a new procedure and reported series are small, we attempted to obtain more information about complications by surveying a large number of procedures from many centers. A questionnaire requesting information about complications related to transbronchial lung biopsy was sent to 178 directors of respiratory disease training programs in the United States and Canada (10). It asked physicians whether they performed transbronchial lung biopsies, what equipment they used, the total number of procedures performed, and the number of biopsies attempted per procedure. Physicians were also asked the number of patients who developed hemorrhage greater than 50 ml, pneumothorax requiring a chest tube, and pneumothorax not requiring a chest tube, and the number of patients who died. They were also asked whether their information was exact or approximate. Some physicians returned questionnaires that included results Suratt, Department of Internal Medicine, University of Virginia Medical Center, Charlottesville, Va. 22901.

AMERICAN REVIEW OF RESPIRATORY DISEASE, VOLUME 115, 1977

709

NOTES

of both bronchial and transbronchial lung biopsies. Therefore, second letters were mailed to respondents who did not indicate that their data were confined solely to transbronchial lung biopsy. Additional in. formation about deaths was solicited through letters and/ or telephone calls. Statistical analysis was performed only on data that physicians indicated were exact. Multiple regression equations of the numbers of complications against various technical factors and measures of experience of the bronchoscopists were calculated. The analysis of variance for regression was used to measure the goodness of fit of the regression line. The contribution of each variable was tested by calculating t values for each regression coefficient. The technical factors that were analyzed included the total number of transbronchial lung biopsies performed, the number of biopsies per procedure, and the size of the biopsy forceps. Biopsy forceps were divided into two groups. Small forceps were less than 2 mm in diameter and 2.2 mm in jaw length and were inserted through a bronchofiberscope. Large forceps were 2 mm in diamter and 4 mm in jaw length and were inserted through an open bronchoscope. Ninety-six of the 178 questionnaires mailed (54 per cent) were returned. They contained information about 5,450 transbronchial lung biopsy procedures. Forty-five physicians reported exact data (2,628 transbronchial lung biopsy procedures); 26 reported approximate data (2,822 transbronchial lung biopsy procedures); 9 replies were incomplete because physicians did not respond to the second letter; and 16 respondents did not perform transbronchial lung biopsy. The frequency of death was 0.20 per cent (table I), as calculated from exact data. Specific information about the 13 patients who died is reported in table 2. Hemorrhage accounted for 9 deaths. Eight of these 9 patients (Patients I through 4 and 7 through 10) had abnormal coagulation studies. In 3, however, the abnormality was a minor decrease in the platelet count to 85,000 and 100,000 per mm3. These 8 patients also either had diseases or were receiving drugs known to affect hemostasis. One of the 8 patients (Patient 3) had Hodgkin's disease and a platelet count of 85,000 per mm3; autopsy revealed an organizing saddle embolus in his pulmonary artery. His physician believed that the patient's severe hemorrhage was facilitated by pulmonary hypertension and a low platelet count. Only one patient who died from hemorrhage (Patient 5) had normal coagulation studies. His physician indicated that even in retrospect there was nothing to suggest that this patient would bleed. One patient (Patient 13) died from a tension pneumothorax. He developed a small pneumothorax immediately after transbronchial lung biopsy; a chest roentgenogram 2 hours later showed no progression. Six to 8 hours after the procedure, he rapidly developed respiratory distress, and his chest roentgenogram demonstrated a tension pneumothorax. He

TABLE 1 NUMBER OF CASES OF PNEUMOTHORAX, HEMORRHAGE, AND DEATH AFTER TRANSBRONCHIAL LUNG BIOPSY Exact Data

No. of procedures Pneumothorax Hemorrhage> 50 ml Death Total complications

Total Data

(no.)

(%)

(no.)

(%)

2,628 145 33 5

5.5 1.3 0.20

5,450 210 68 13

3.8 1.2 0.24

183

7.0

291

5.3

died before a chest tube could be inserted. Three patients (Patients 6, II, and 12) died of unknown causes after the procedure. Information about complications of pneumothorax, hemorrhage greater than 50 ml, and deaths calculated from exact data are tabulated in table 2. Hemorrhage greater than 50 ml occurred in 1.3 pe1· cent of patients; 13 per cent of these patients died. Pneumothorax occurred in 5.5 per cent of patients; 45 per cent of them required closed tube drainage. No significant correlation was found between complications, whether analyzed separately or together, and the number of procedures performed, the number of biopsies per procedure, or the size of the biopsy forcepts (P always> 0.15).

• • • Hemorrhage was the most frequent cause of death in our study. Abnormal coagulation studies or diseases and drugs known to affect hemostasis were involved in most deaths due to hemorrhage. Flick and associates (9) reported a patient who died from transbronchial lung biopsy who also had recognizable abnormalities in hemostasis. Their patient had lymphocytic leukemia, lymphocytic lymphoma, and a platelet count of 85,000 per mm3. The lack of correlation between hemorrhage and technical factors also suggests that severe hemorrhage ls related primarily to host factors. Pneumothorax caused one death and was the most frequently reported complication. The delayed progression to a tension pneumothorax in the patient who died from this condition emphasizes the importance of close observation of patients with pneumothorax treated without a thoracostomy tube. The frequencies of death and pneumothorax in this study were similar to that found by Zavala (II), who reviewed 9 series, including a total of 438 patients. Both studies report a frequency of death of 0.20 per cent. The frequency of pneumothorax was 5.5 per cent in our study, compared to 3.7 per cent in the combined series. The frequency of hemorrhage reported in the present study (1.3 per cent) was lower than that reported in the combined series (9 per cent), probably because only hemorrhages greater than 50 ml were described in our report.

710

NOTES

TABLE 2 THIRTEEN DEATHS ASSOCIATED WITH APPROXIMATELY 5,450 TRANSBRONCHIAL LUNG BIOPSY PROCEDURES Patient

Age Sex (years)

2

M

2

F

28

Underlying Disease

Coagulation Status

Cause of Death

Pathologic Findings

Renal transplant, immunosuppressive therapy

Prothrombin time and Hemorthage partial thromboplastin time, normal; platelets, 1 00,000/mm3

Hemorrhage occluding trachea and bronchi, Pneu-

Acute leukemia, lung infiltrate

White blood cell count, 37,000 cells/mm3; platelets, 1 00,000/

Hemorrhage causing hypoxemia and shock; died 3 days

Biopsy: bronchial wall, no alveoli

Hemorrhage

Organizing saddle embolus

mocystis carinii

mm3; prothrombin time, normal; carbenicillin therapy 3

43

4B Hodgkin's disease radiation fibrosis, pulmonary hypertension

Platelets, 85,000/mm3; "other coagulation

Cirrhotic

Prothrombin time, 17/10

Hemorrhage

Normal prothrombin time, partialthromboplastin time, and platelet count

Hemorrhage

4

M

5

M

72

Pulmonary mass, R/0 cancer

6

M

55

Diabetic ketoacidosis

7-10

tests normal"

Biopsy: small vessel. Necropsy: no tumor

Hypotension, hypoxia "Clotting defects secondary to disease or drugs." No further information available

Hemorrhage

11

M

50

Lymphosarcoma cell leukemia, suppressive therapy

Died suddenly 1 hour after procedure

Biopsy: leukemic infiltrates

12

M

15

Acute myelogenous leukemia, immunosuppressive therapy

Hypotension

Leukemic infiltrates

13

M

70

Lymphoma, immunosup-

Tension pneumothorax

pressive therapy

The results of our study suggest that transbronchial lung biopsy is a relatively safe procedure in patients with normal hemostasis and without pulmonary hypertension.

Acknowledgment The writers wish to thank Dan Spyker, M.D., and William O'Brien, M.D. for their assistance with the statistical analysis. They also wish to thank Ms.

Carolyn Lucas for her help in preparing the manuscript. STEVEN PAUL

M.

M.

HERF

SURATT

NARINDER S. ARORA

Department of Internal Medicine University of Virginia Medical Center Charlottesville, Virginia 22901

711

NOTES

References I. Anderson, H. A., Fontana, R. S., and Harrison, E. G., Jr.: Transbronchoscopic biopsy in diffuse pulmonary diseases, Dis Chest, 1965, 48, 187. 2. Fennessy, J. J.: Bronchial brushings and transbronchial forceps biopsy in the diagnosis of pulmonary lesions, Dis Chest, 1968,53,377. 3. Anderson, H. A., and Fontana, R. S.: Transbronchial lung biopsy for diffuse pulmonary disease: Technique and results in 450 cases, Chest, 1972, 62, 125. 4. Levin, D. C., Wicks, A. B., and Ellis, J. H., Jr.: Transbronchial lung biopsy via fiberoptic bronchoscope, Am Rev Respir Dis, 1974, 110, 4. 5. Scheinhorn, D. J., Joyner, L. P., and Whitcomb, M. E.: Transbronchial forceps lung biopsy through fiberoptic bronchoscope in Pneumocystis carinii pneumonia, Chest, 1974,66,294. 6. Ellis, J. H.: Transbronchial lung biopsy via

7.

8.

9.

10.

II.

fiberoptic bronchoscope: Experience with 107 consecutive cases and comparison with brush biopsy, Chest, 1975, 68, 524. Zavala, D.: Diagnostic fiberoptic bronchoscopy techniques and results in 600 patients, Chest, 1975, 68, 12. Koener, S. K., Sakowitz, A. S., Appelman, R. I., Becker, N. H., and Schoenbaum, S. W.: Transbronchial lung biopsy for the diagnosis of sarcoidosis, N Eng! J Med, 1975,293,268. Flick, M. R., Wasson, K., Dunn, L. J., and Block, A. J.: Fatal pulmonary hemorrhage after transbronchial lung biopsy through the fiberoptic bronchoscope, Am Rev Respir Dis, 1975, 111, 853. American Lung Association: Training programs in respiratory disease, Am Rev Respir Dis, 1975,112,281. Zavala, D.: Pulmonary hemorrhage in fiberoptic trans bronchial biopsy, Chest, 1976, 70,584.

Deaths and complications associated with transbronchial lung biopsy.

708 :\OTES References 1. Lester, W., Moulding, T., Fraser, R. I., McClatchy, J. K., and Fisher, D. A.: Quintuple drug regimens in the treatment of...
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