Conclusions EBUS-FNA under real-time ultrasound guidance can be undertaken at the same time as bronchoscopy and/or EUS-FNA under conscious sedation. EBUS-FNA has the potential for accurate sampling of lymph nodes and masses in the middle mediastinum and, when combined with EUS-FNA, offers the possibility of minimally invasive staging of the majority of the mediastinum. Larger studies of this new technique to define further its role in the staging of NSCLC are warranted. ACKNOWLEDGMENT: The authors thank Judith Wilson, Jennifer Matthews, and Helen Chisholm of the Endoscopy Unit at the Royal Infirmary of Edinburgh for their help in the evaluation of the prototype EBUS probe.
References 1 Dillemans B, Deneffe G, Verschakelen M, et al. Value of computed tomography and mediastinoscopy in preoperative evaluation of mediastinal nodes in non-small cell lung cancer. Eur J Cardiothorac Surg 1994; 9:37– 42 2 Luke WP, Pearson FG, Todd TR, et al. Prospective evaluation of mediastinoscopy for assessment of carcinoma of the lung. J Thorac Cardiovasc Surg 1986; 91:53–56 3 Silvestri GA, Hoffman BJ, Bhutani MS, et al. Endoscopic ultrasound with fine-needle aspiration in the diagnosis and staging of lung cancer. Ann Thorac Surg 1996; 61:1441–1446 4 Mountain CF, Dresler CM. Regional lymph node classification for lung cancer staging. Chest 1997; 111:1486 –1487 5 Wiersema MJ, Vazquez-Sequeiros E, Wiersema LM. Evaluation of mediastinal lymphadenopathy with endoscopic US-guided fine-needle aspiration biopsy. Radiology 2001; 219:252–257 6 Williams DB, Sahai AV, Aabakken L, et al. Endoscopic ultrasound guided fine needle aspiration biopsy: a large single centre experience. Gut 1999; 44:720 –726
Diagnostically Significant Variations in Pleural Fluid pH in Loculated Parapneumonic Effusions* Nick A. Maskell, BM, BS; Fergus V. Gleeson, BM, BS; Mike Darby, BM, BS; and Robert J. O. Davies, DM
Study objectives: Parapneumonic effusions are common, and measurement of pleural pH is one of the *From the Oxford Centre for Respiratory Medicine (Mr. Maskell and Dr. Davies) and Department of Radiology (Messrs. Gleeson and Darby), Churchill Hospital, John Radcliffe NHS Trust, Oxford, Oxfordshire, UK. Mr. Maskell is partly funded by a Medical Research Council (UK) grant. Manuscript received January 15, 2004; revision accepted July 21, 2004. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (e-mail:
[email protected]). Correspondence to: Nick A. Maskell, MRCP, Oxford Centre for Respiratory Medicine, Churchill Hospital, John Radcliffe NHS Trust, Oxford, Oxfordshire, UK; e-mail:
[email protected] 2022
most useful measurements in assessing the need for tube drainage. Use of pleural pH assumes that a single measurement conveys a representative picture of pH throughout the effusion. Often effusions are multiloculated, and varying concentrations of nondiffusible acids such as lactic acid, if present in different concentrations, could mean clinically significant variations in pH between locules. If these differences were large, a single pH measurement could misrepresent the “stage” that the parapneumonic effusion had reached. We therefore set out to test the hypothesis that pH varies significantly between locules in complicated parapneumonic effusions. Design: The study was performed in seven consecutive patients presenting to our institution with complicated parapneumonic effusions. Interventions: In each case, pleural pH was measured in several separate pleural fluid locules, using ultrasound-guided pleural fluid sampling. Results: Significant variations were found in pleural fluid visual appearance, pH, and lactate dehydrogenase between locules in four of seven patients. Three of seven patients had variations, resulting in pH levels both above and below 7.2, which is the threshold used in our institution to indicate the need for tube drainage. Conclusions: This is the first reported series of variation in pleural pH between different locules in complicated parapneumonic effusions. These variations are clinically important and cast light on the mechanisms responsible for the acidosis seen in infected effusions. Physicians should be aware of this when making drainage decisions in these patients using the clinical picture and a single pH result alone. (CHEST 2004; 126:2022–2024) Key words: empyema; parapneumonic effusions; pH; pleural effusion Abbreviation: LDH ⫽ lactate dehydrogenase
effusions are common and occur in apP arapneumonic proximately one third of patients hospitalized with bac-
terial pneumonia.1 The clinical usefulness of pleural pH in assessing if these effusions require drainage is well established.1– 4 The American College of Chest Physicians3 and British Thoracic Society4 guidelines suggest chest tube drainage for parapneumonic effusions that are culture negative but have a pleural pH ⬍ 7.2 may be appropriate.3,4 This guidance is based on a large meta-analysis5 showing pleural pH to have the most discriminative biochemical properties of poor outcome in pleural infection when compared to glucose or lactate dehydrogenase (LDH). Pleural effusion character is poorly assessed by chest radiography.6 Ultrasound examination often detects septations in pleural effusions that appear as apparently simple effusions on the chest radiograph.6 However, even ultrasound can miss loculations, which are only visualized at time of surgery. The pleural fluid becomes septated in the fibropurulent Selected Reports
phase of parapneumonic effusions, as the intrinsic fibrinolytic activity of the pleural space is suppressed.7 White cell and bacterial metabolism within these locules then lowers pH through the production of nondiffusible acids such as lactic acid (which is expected to remain in the locules) and diffusible carbon dioxide (which is expected to diffuse away). The clinical use of pH implicitly assumes that a single measurement conveys a general picture of pH throughout the effusion. The contributions of nondiffusible acids such as lactic acid, if present in different concentrations within a septated multiloculated effusion, could mean a disparity in the pH of different locules. If these differences were large, a single pH measurement could misclassify a patient, and potentially lead to inappropriate management. To assess whether this hypothesis is true, we measured pH in several separate pleural fluid locules, in patients with septated multiloculated effusions, using ultrasound-guided pleural fluid sampling.
Materials and Methods We prospectively measured pleural fluid characteristics from seven consecutive patients with complicated parapneumonic effusions presenting to our respiratory unit (Oxford Centre for Respiratory Medicine, Oxford) over an 8-month period (December 2001 to August 2002). Patients are referred to the Oxford unit directly from general practitioners (60%), from other local hospital consultants (30%), and occasionally from respiratory consultants in other neighboring health authorities (⬍ 10%). Patients were included if they presented with a parapneumonic effusion and if ultrasound examination showed it to be a multiseptated loculated effusion. Pleural fluid was obtained from up to three different locules by using ultrasound-guided needle placement. The skin was cleaned and then infiltrated with 10 mL of 2% lignocaine, and a 19-gauge spinal needle inserted into the effusion. After a 5- to 10-mL sample was aspirated, the needle was then advanced into an adjoining locule, and 5 mL of fluid from this locule was aspirated and discarded. A fresh 10-mL syringe was then used to sample fluid for measurement. After this was performed, the procedure was then repeated for the third sample. The specimens were collected within minutes of each other. Pleural fluid pH was immediately evaluated using a blood gas analyzer (IL-1620; Instrumentation Laboratory; Warrington, UK). This machine is extremely accurate, with good reproducibility, and quantitative intertest reproducibility of the pH analyzer for pleural fluid had been previously shown to be ⬍ 5% when measuring acidic fluid in our institute. The pleural fluid pH was analyzed in all cases other than thick purulent pus, when it was not performed to avoid damage to the blood gas machine. The LDH was measured using an Airoset machine (Abbott Laboratories; Abbott Park, IL), and the normal laboratory normal range was 110 to 250 U/L.
Results The seven patients studied had a median age of 67 years (range, 32 to 83 years). Four patients were men, and three patients were women, and they all presented with community-acquired complicated parapneumonic effusions. Five patients had received antibiotics prior to hospital admission. None had a medical history of pleural disease or cancer. Blood culture specimens were obtained in all cases, and all results were negative. Pleural fluid cytology was negative for malignancy in all cases. The pleural fluid characteristics are given in Table 1. In www.chestjournal.org
Table 1—Characteristics of the Pleural Fluid From Seven Consecutive Patients With Complicated Parapneumonic Effusions* Patient No./Sample
Appearance
pH
Glucose, mmol/L
Protein, g/L
LDH U/L
Cloudy Clear Thick frank pus
6.3 7.24 NR
⬍1 ⬍1 NR
58 49 NR
4,661 982 NR
a b c
Clear Cloudy Cloudy/bloody
7.27 7.16 6.84
1.1 ⬍1 ⬍1
54 56 61
10,531 14,715 16,082
a b
Cloudy Cloudy
6.67 6.79
⬍1 ⬍1
47 38
624 710
a b c
Cloudy Clear Cloudy/pus
7.16 7.25 6.85
NR NR NR
39 38 36
3,141 1,836 16,757
a b
Serous Cloudy
6.64 6.61
⬍1 ⬍1
46 16
2,499 4,136
a b c
Cloudy Cloudy Clear
6.84 6.93 7.03
⬍1 ⬍1 2.2
42 43 42
1,806 1,920 691
a b c
Cloudy/pus Blood stained Bloody pus
7.26 7.34 7.3
⬍1 ⬍1 ⬍1
73 28 76
18,506 246 16,106
1† a b c 2†
3
4†
5
6
7
*NR ⫽ not reported. †Indicates cases in which single pleural sampling might have given misleading information.
three of these seven consecutive patients, substantial variations in pH between different locules were found (patients 1, 2, and 4). These variations resulted in pH levels both above and below 7.2. The hydrogen ion concentration variations inferred by these differences are substantial since pH is a logarithmic scale. In patient 1, this difference is nearly tenfold. In addition, two patients had marked visual differences in their pleural fluid samples ranging from pus to clear fluid.
Conclusions We believe this is the first reported series of variation in pleural pH between different locules in complicated parapneumonic effusions. These variations are large, clinically important, and cast light on the mechanisms predominantly responsible for the acidosis seen in infected effusions. In three of our patients, if only the first pleural fluid sample had been obtained showing the recorded pleural pH of ⬎ 7.2, it would have implied that they probably did not require chest tube drainage, despite the very acidic nature of the third sample. We accept that many institutions would decide to place chest tubes in all parapneumonic effusions that are heavily loculated regardless of the pH value. However, many physicians rely on the clinical CHEST / 126 / 6 / DECEMBER, 2004
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setting, a plain chest radiograph, and a diagnostic pleural tap. In this setting, we feel that the chest radiograph could fail to show the presence of loculated fluid and the physician be misled by a single high pH reading. The disparity in the pH and LDH from different locules emphasizes that much of the pleural acidosis of infections is attributable to soluble acids, such as lactic acid. Our findings are consistent with the case report from Light and colleagues,8 who found wide variation in pH values in two different locules in one patient. However, unlike these researchers,8 we did not formally measure carbon dioxide in our samples, as we unable to confirm the intertest reproducibility of the pH analyzer in measuring carbon dioxide in pleural fluid samples. Interestingly, we found low glucose levels in some of the samples that had pH levels above and below the 7.2 threshold. This is surprising, as it is generally thought that pleural fluid pH falls before the pleural fluid glucose. However, the meta-analysis by Heffner et al5 showed pH to be the most accurate measurement of need for formal chest tube drainage. It should also be emphasized pH measurement must be taken using the accuracy of a blood gas machine and not with indicator strips or pH meters. The major factors reducing pleural pH are leukocytes and bacteria.8 –11 These both utilize glucose to produce carbon dioxide and lactic acid that accumulates in the pleural space, reducing its pH. Since carbon dioxide is freely diffusible and will distribute throughout the pleural space, and then diffuse away, this cannot explain the pH disparity between locules, implying the differences in lactic acid and other soluble acid concentrations are the likely explanations for these observational changes. From our small study, we can conclude that pleural pH may vary to a significant extent between different locules in multiseptated loculated infected pleural effusions. It also suggests that it is the different concentrations in lactic acid and the other soluble acid concentrations that results in these variations. Physicians should be aware of this
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when making chest tube drainage decisions in patients with parapneumonic effusions. If a surprisingly high pleural pH is found in a patient with a high clinical probability of pleural infection, further tests should be considered. These might include an ultrasound for the presence of loculation and consideration of a repeat pleural sample from a different area.
References 1 Light RW, Girard WM, Jenkinson SG, et al. Parapneumonic effusions. Am J Med 1980; 69:507–512 2 Potts DE, Taryle DA, Sahn SA. The glucose-pH relationship in parapneumonic effusions. Arch Intern Med 1978; 138: 1378 –1380 3 Colice GL, Curtis A, Deslauriers J, et al. Medical and surgical treatment of parapneumonic effusions: an evidence-based guideline. Chest 2000; 118:4 –71 4 British guideline on the management of pleural diseases. Thorax 2003; 58(suppl):1–52 5 Heffner JE, Brown LK, Barbieri C, et al. Pleural fluid chemical analysis in parapneumonic effusions: a meta-analysis. Am J Respir Crit Care Med 1995; 151:1700 –1708 6 Idell S, Girard W, Koenig KB, et al. Abnormalities of pathways of fibrin turnover in the human pleural space. Am Rev Respir Dis 1991; 144:187–194 7 McLoud TC, Flower CD. Imaging the pleura: sonography, CT, and MR imaging. AJR Am J Roentgenol 1991; 156:1145– 1153 8 Light RW, Moller DJ, George RB. Low pleural fluid pH in parapneumonic effusion [letter]. Chest 1975; 68:273–274 9 Sahn SA, Reller LB, Taryle DA, et al. The contribution of leukocytes and bacteria to the low pH of empyema fluid. Am Rev Respir Dis 1983; 128:811– 815 10 Light RW, MacGregor MI, Ball WCJ, et al. Diagnostic significance of pleural fluid pH and Pco2. Chest 1973; 64:591–596 11 Sahn S. Pleural pH in the normal state and in diseases affecting the pleural space: the pleura in health and disease. New York, NY: Marcel Dekker, 1985; 253–266
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