The development of bronchoscopy and bronchoalveolar lavage (BAL) has led to an increase in their use in intensive care units (ICUs), where their applications for differential diagnosis of pulmonary diseases make them indispensable instruments for intensivists [1]. Despite their common use, a few studies have raised concerns about potential impacts on bronchoalveolar lavage fluid (BALF) dilution, which affects mainly the quantitative detection of soluble substances. Urea is a diffusible substance that can easily be detected in capillaries and alveolar spaces. The urea concentration in plasma and that in BALF are approximately equal and their ratio (urea plasma/urea BALF) has previously been applied as an index of BALF dilution. Furthermore, it has been shown that the ratio of high-quality lavage is low in clinical settings [2, 3].
We reviewed all ICU-admitted patients who received BAL from January 2016 to September 2018 in Ren Ji Hospital and analyzed their urea plasma/urea BALF values. Guidelines of the American Thoracic Society were followed during the BAL procedure [3]. (The procedure is described in Additional file 1.) Among 223 patients included, the median level of urea plasma/urea BALF was 4.2 (interquartile range of 3.2–8.6). The patients were categorized into groups A (urea plasma/urea BALF <4.2) and B (urea plasma/urea BALF ≥4.2). The patients in group A were more likely to receive bronchodilators (35.6% versus 15.9%, P <0.001) and a recruitment maneuver (15.5% versus 5.3%, P = 0.013) than those in group B. More invasive pulmonary aspergillosis (IPA) patients with BALF galactomannan of more than 0.5 could be detected in group A than in group B (84.6% versus 33.3%, respectively; P = 0.019) as well as more bacterial pneumonia patients with the quantitative cultures of BALF of more than 104 CFU/mL (90.6% versus 52.7%, respectively; P <0.001). Primary care physicians performed more BAL than residents did (58.3% versus 31.8%, respectively), especially in group A (Table 1).
Table 1.
Demographics and clinical characteristics of the patients
| Characteristics | All patients | Group A (urea plasma/urea BALF <4.2) |
Group B (urea plasma/urea BALF ≥4.2) |
P value |
|---|---|---|---|---|
| n = 223 | n = 110 | n = 113 | ||
| Age, years | 54 (43–67) | 51 (43–66) | 56 (43–67) | 0.945 |
| Gender, male | 103 (46.2) | 53 (48.2) | 50 (44.2) | 0.556 |
| BMI, kg/m2 | 21.9 (18.5–23.4) | 22.1 (18.4–23.4) | 21.8 (18.5–23.4) | 0.515 |
| PaO2/FiO2 | 210.4 (120.4–271.5) | 250.9 (206.7–320.5) | 137.4 (88.6–210.4) | <0.001 |
| Pulmonary disease | ||||
| AECOPD | 68 (30.5) | 33 (30.0) | 35 (30.9) | 0.875 |
| CAP | 61 (27.4) | 28 (25.5) | 35 (30.9) | 0.36 |
| HAP | 33 (14.8) | 17 (15.5) | 14 (12.4) | 0.508 |
| VAP | 16 (7.2) | 7 (6.4) | 9 (7.9) | 0.643 |
| IPA | 28 (12.6) | 13 (11.8) | 15 (13.3) | 0.743 |
| Others | 17 (7.5) | 12 (9.0) | 5 (4.6) | 0.068 |
| APACHE II score | 17 (13–23) | 16 (14–22) | 17 (13–23) | 0.799 |
| Intubation and mechanical ventilation | 47 (21.1) | 21 (19.1) | 26 (23.0) | 0.473 |
| Lesion location | ||||
| Upper lobe | 56 (25.1) | 26 (23.6) | 30 (26.5) | 0.616 |
| Middle and lower lobe | 93 (41.7) | 51 (46.4) | 42 (37.2) | 0.164 |
| Diffusive lesions | 74 (33.2) | 33 (30.3) | 41 (36.3) | 0.319 |
| Sedative and narcotic drugs | ||||
| Midazolam and fentanyl | 96 (43.0) | 51 (46.4) | 45 (39.8) | 0.324 |
| Propofol and fentanyl | 89 (39.9) | 42 (38.2) | 47 (41.6) | 0.603 |
| Dexmedetomidine | 38 (17.1) | 17 (15.4) | 21 (18.6) | 0.534 |
| Bronchodilators was given before BAL | 57 (25.6) | 39 (35.6) | 18 (15.9) | <0.001 |
| RM before BAL | 23 (10.3) | 17 (15.5) | 6 (5.3) | 0.013 |
| Operator | ||||
| Resident | 71 (31.8) | 5 (4.5) | 66 (58.4) | <0.001 |
| Primary care physician | 130 (58.3) | 93 (84.5) | 37 (32.7) | <0.001 |
| Others | 22 (9.9) | 12 (11.0) | 10 (8.9) | 0.616 |
| Diagnosed with bacterial pneumonia | 178 (79.8) | 85 (77.3) | 93 (82.3) | 0.348 |
| BALF GM >0.5 in IPA patients | 16 (57.1) | 11 (84.6) | 5 (33.3) | 0.019 |
| Quantitative cultures of BALF >104 CFU/mL in bacterial pneumonia patients | 126 (70.8) | 77 (90.6) | 49 (52.7) | <0.001 |
Data are expressed as median (Q1–Q3) or number (percentage). P values for comparison between urea plasma/urea BALF ≥4.2 and <4.2 groups.
Abbreviations: AECOPD acute exacerbation of chronic obstructive pulmonary disease, APACHE II Acute Physiology and Chronic Health Evaluation II, BAL bronchoalveolar lavage, BALF bronchoalveolar lavage fluid, BMI body mass index, CAP community-acquired pneumonia, CFU colony-forming units, FiO2 fractional concentration of inspired oxygen, GM galactomannan, HAP hospital acquired pneumonia, IPA invasive pulmonary aspergillosis, PaO2 partial pressure of arterial oxygen, RM recruitment maneuver, VAP ventilator-associated pneumonia.
Pulmonary function was associated with the urea plasma/urea BALF ratio. It was found that there was a correlation between urea plasma/urea BALF and partial pressure of arterial oxygen/fractional concentration of inspired oxygen (PaO2/FiO2) (R2 = 0.196, P <0.001). The less oxygen-deficient the patient was, the lower the urea plasma/urea BALF level was (Fig. 1a,b). Sixty-eight patients with chronic obstructive pulmonary disease (COPD) were enrolled in our study. The forced expiratory volume in the first second (FEV1) was suggested as a measure of bronchial obstruction. FEV1 of less than 50% of the predicted normal value indicated the presence of severe ventilatory impairment, which led to a lower volume of instilled saline flow into the alveoli. In our study, a correlation was also found between FEV1 and urea plasma/urea BALF (R2 = 0.299, P <0.001). A lower value of urea plasma/urea BALF was obtained in a group with FEV1 of at least 50% of the predicted value than in that with FEV1 of less than 50% of the predicted value (P <0.05, Fig. 1c, d).
Fig. 1.
a Correlation between PaO2/FiO2 and urea plasma/urea BALF. b Comparison of urea plasma/urea BALF in different PaO2/FiO2 groups. c Correlation between FEV1/FEV1 predicted and urea plasma/urea BALF in patients with COPD. d Comparison of urea plasma/urea BALF in different FEV1/FEV1 predicted groups in patients with COPD. *P <0.05 in each group. Abbreviations: BALF bronchoalveolar lavage fluid, COPD chronic obstructive pulmonary disease, FEV1 forced expiratory volume in the first second, FiO2 fractional concentration of inspired oxygen, PaO2 partial pressure of arterial oxygen.
Providing appropriate training in BAL skills to intensivists while ensuring patient safety is challenging [4]. Inter-operator variability in the recovery of lavage fluid during a BAL procedure may affect the concentration of soluble substances such as galactomannan and the results of quantitative cultures [5]. More attention should be paid to patients with hypoxia and impaired pulmonary function. Bronchodilators and a recruitment maneuver may improve BALF dilution during the procedure, and residents in ICUs need more practice.
Additional file
Guidelines of the American Thoracic Society were followed during the bronchoalveolar lavage (BAL) procedure. Selection of the segment for BAL was guided by chest x-ray changes. The right middle lobe or lingual lobe was selected when diffuse infiltrates were present. Five 20-mL aliquots of sterile saline were instilled and aspirated gently in each patient. The total volume of the retrieved liquid should be greater than or equal to 30% of the total volume of the instilled saline. (ZIP 492 kb)
Acknowledgments
None.
Funding
This work was supported by the National Key Research and Development Program of China (2017YFC0909002) and the Scientific Research Project of Shanghai Municipal Health Bureau (201840006).
Availability of data and materials
Not applicable.
Abbreviations
- BAL
Bronchoalveolar lavage
- BALF
Bronchoalveolar lavage fluid
- FEV1
Forced expiratory volume in the first second
- ICU
Intensive care unit
Authors’ contributions
YY and CL both conceived and designed the experiments. YY, CL, and YL performed the experiments. HS and ZZ analyzed the data. YY and YL contributed reagents, materials, and analysis tools. YY, LL, and YG helped to draft and edit the article. All authors approved the final manuscript.
Ethics approval and consent to participate
This study was approved by the ethics committee of Shanghai Jiao Tong University (2016-Clinical-Res-083), and written informed consent was obtained from either the patients or the next of kin.
Consent for publication
Not applicable.
Competing interests
The authors declare that they have no competing interests.
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Contributor Information
Yuetian Yu, Email: fishyyt@sina.com.
Chunyan Liu, Email: doctorlcy@sina.com.
Zhongheng Zhang, Email: zh_zhang1984@zju.edu.cn.
Hui Shen, Email: shenhui0712@163.com.
Yujie Li, Email: lyjemerg@sina.com.
Liangjing Lu, Email: lu_liangjing@163.com.
Yuan Gao, Email: gaoyuanzhuren@sina.com.
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Associated Data
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Supplementary Materials
Guidelines of the American Thoracic Society were followed during the bronchoalveolar lavage (BAL) procedure. Selection of the segment for BAL was guided by chest x-ray changes. The right middle lobe or lingual lobe was selected when diffuse infiltrates were present. Five 20-mL aliquots of sterile saline were instilled and aspirated gently in each patient. The total volume of the retrieved liquid should be greater than or equal to 30% of the total volume of the instilled saline. (ZIP 492 kb)
Data Availability Statement
Not applicable.