The Relationship of Pleural Pressure to Symptom Development During Therapeutic Thoracentesis*

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1 Original Research INTERVENTIONAL PULMONOLOGY The Relationship of Pleural Pressure to Symptom Development During Therapeutic Thoracentesis* David Feller-Kopman, MD, FCCP; Allan Walkey, MD; David Berkowitz, MD; and Armin Ernst, MD, FCCP Study objective: To describe the relationship of patients symptoms during therapeutic thoracentesis to pleural pressure (Ppl). Design: Review of prospectively collected data during 169 therapeutic thoracentesis procedures. Setting: University Hospital in Boston, MA. Patients and methods: One hundred sixty-nine patients who had Ppl measured during therapeutic thoracentesis were included in this study. End-expiratory pressures were measured after the withdrawal of 5 ml of fluid and every 240 ml thereafter until the pressure was lower than 20 cm H 2 O, chest discomfort developed in the patient, or no more fluid could be removed. Patients symptoms, including chest pain, chest discomfort, and cough were recorded simultaneously. Results: There was no correlation between the amount of pleural fluid removed and the development of symptoms. The closing pressures and the total change in Ppl (see the Materials and Methods section for definitions), however, were significantly lower in the group of patients who experienced chest discomfort compared to patients who developed cough or were asymptomatic. There was also a trend toward a significantly lower pleural elastance in patients who developed cough compared to that in the other two groups. Additionally, only 22% of patients in whom chest discomfort developed, and 8.6% of patients in whom symptoms did not develop, had potentially dangerous Ppl values (ie, lower than 20 cm H 2 O). Conclusions: The development of chest discomfort is associated with a potentially unsafe drop in Ppl values and should be a sign to terminate thoracentesis. It is not necessary to terminate thoracentesis solely because of the development of cough. Without attention to pleural manometry, a significant percentage of patients may develop potentially dangerous Ppl. Although we recommend pleural manometry with all thoracenteses, when it is not used attention to symptoms remains a valuable surrogate. (CHEST 2006; 129: ) Key words: manometry; physiology; pleural; pleural effusion; pressure; symptoms; thoracentesis Abbreviations: Pel pleural space elastance; Ppl pleural pressure The monitoring of pleural pressure (Ppl) during thoracentesis not only provides a better understanding of the real-time physiology of the pleural *From the Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA. The authors have no financial disclosures to make. Manuscript received September 13, 2005; revision accepted November 7, Reproduction of this article is prohibited without written permission from the American College of Chest Physicians ( org/misc/reprints.shtml). Correspondence to: David Feller-Kopman, MD, FCCP, Interventional Pulmonology, Beth Israel Deaconess Medical Center, Deaconess 201, One Brookline Ave, Boston, MA 02215; dfellerk@bidmc.harvard.edu space, but also helps to prevent pressure-related complications such as reexpansion pulmonary edema, 1,2 to predict improvement in FVC, 3 and to predict the success of pleurodesis. 4 Despite this evidence, most thoracenteses are still performed at the bedside without attention to the Ppl. Thoracenteses are often terminated prior to the removal of maximal volumes of pleural fluid due to a concern for removing large volumes and inducing reexpansion edema, or for the development of symptoms such as cough or chest pain. The termination of thoracentesis prior to the removal of maximal volumes of fluid may result in incomplete symptom improvement, 3 multiple procedures, or inadequate 1556 Original Research

2 postprocedural imaging. Most studies of pleural manometry have stopped thoracentesis for Ppl values lower than 20 cm H 2 O or for symptoms such as cough or chest pain. 1 3 The value of 20 cm H 2 O was arbitrarily chosen by Light et al 1 based on prior animal studies 5,6 demonstrating minimal pulmonary edema with Ppl values of 20 mm Hg (approximately 27 cm H 2 O) but significant pulmonary edema with pressures of 40 mm Hg (approximately 54 cm H 2 O). Light et al 1 have noted that, at times, significant changes in Ppl were associated with chest tightness, although this relationship was not quantified. It is unknown whether the development of symptoms during thoracentesis correlate with Ppl values and represent a meaningful signal to stop the procedure. The purpose of this study was to determine whether symptoms that are recorded during thoracentesis relate to changes in Ppl. We hypothesize that the symptom of cough is not related to unsafe changes in Ppl values (ie, 20 cm H 2 O or lower) and likely represents a benign resolution of atelectasis during the removal of pleural fluid. Furthermore, we hypothesize, as Light et al 1 have observed, that chest tightness correlates with the development of lung entrapment or trapped lung and should be used as a signal to terminate thoracentesis. Materials and Methods Data were collected prospectively during thoracenteses performed by the Division of Interventional Pulmonology at Beth Israel Deaconess Medical Center from September 9, 2002, to December The 169 patients who underwent pleural manometry were included in this study. The study protocol was approved by our internal review board. Thoracentesis was performed using a kit (Pleura-Seal thoracentesis kit; Arrow-Clark; Reading, PA), and Ppl values were recorded as previously described. 7 Ppl measurements were made with both a simple water manometer, as well as an electronic transducer system (Biobench; National Instruments; Austin, TX). Doelken et al 7 have found a strong correlation between these two methods (r 0.97; p ). End-expiratory Ppl values were recorded after the withdrawal of 5 ml of fluid (opening pressure), and every 240 ml thereafter until there was no more fluid present, chest discomfort developed in the patient, or the Ppl was lower than 20 cm H 2 O (closing pressure). If drainage ceased, an attempt at obtaining a final closing Ppl was made. This requires the presence of a fluid column, and if there is actually no more pleural fluid and this final pressure could not be recorded, the last recorded pressure was used as the closing pressure. If lung entrapment or trapped lung were suspected, serial pressure measurements were made after the removal of 50 to 100 ml of fluid. We differentiated between two distinct descriptors of chest discomfort. One, described as sharp and occurring over the ipsilateral shoulder/ scapula, and the other, a more vague and typically anterior discomfort. As we postulated that the sharp pain could be due to diaphragmatic irritation from the catheter, and the more vague anterior discomfort from lung entrapment or trapped lung, if the patient developed the sharp pain, an attempt at repositioning the catheter was made and additional fluid was removed. If the pain continued, the procedure was terminated. For patients with the vague chest discomfort, a closing Ppl was recorded and the procedure was terminated. Pleural elastance (Pel) was calculated as the change in pressure (opening to closing) divided by the volume of fluid removed. All procedures were performed using ultrasound guidance (SonoSite 180 plus; SonoSite Inc; Bothell, WA). Statistical analysis was performed using a statistical software package (JMP, version 3.1.5; SAS Institute; Cary, NC). Differences between multiple groups were calculated using analysis of variance and subsequent Tukey-Kramer honestly significant differences for unequal groups (p 0.05). Results The baseline characteristics of the patients included in the study can be seen in Table 1. No significant differences were present for age, gender, or side of the effusion for patients in whom symptoms developed compared to those in whom they did not develop. The diagnoses made by thoracentesis are seen in Table 2, and, again, there were no differences between the patients in whom symptoms developed and those in whom they did not. Symptoms Symptoms developed in 29 of the 169 patients (17%) during thoracentesis (cough, 11 patients [6%]; chest tightness, 18 patients [11%]). The total volume of fluid removed and the opening Ppl values were not significantly different among the asymptomatic patients, the patients with cough, and the patients with chest discomfort (Table 3). Closing Ppl values, however, were significantly lower in the group of patients who experienced chest discomfort compared to the group of patients who did not have symptoms. There was no difference in closing pressures in the patients in whom cough developed compared to those who had chest tightness or in whom symptoms did not develop (Table 3). The total change in Ppl during thoracentesis was significantly different between the patients who developed chest discomfort and both the patients who Table 1 Baseline Characteristics of Patients* Characteristics Values Male gender 83/169 (49%) Mean age, yr Left side 82/158 (52%) Housestaff-operator 46% Mean volume removed L Range of fluid volume removed 50 ml to 6.5 L *No significance differences between symptom groups existed for the data. CHEST / 129 / 6/ JUNE,

3 Table 2 Diagnostic Information From Pleural Fluid* Pleural Effusions No. Exudates Total 89 (58%) Nondiagnostic 28 Parapneumonic 9 Postthoracotomy 3 Empyema 2 Hemothorax 2 Tuberculosis 1 Rheumatic 1 Subdiaphragmatic abscess 1 Malignant 42 NSCLC 15 Breast 7 Lymphoma 5 Renal cell carcinoma 4 Ovarian 2 Small cell 2 Parathyroid 2 Plasma cell 1 Primary peritoneal 1 Parotid 1 Melanoma 1 Esophageal 1 Transudates Total 64 (42%) Nondiagnostic 25 CHF 22 Hepatic hydrothorax 9 Postthoracotomy 1 Malignant 7 Lymphoma 3 Ovarian 1 Mesothelioma 1 Gastric 1 NSCLC 1 *CHF congestive heart failure; NSCLC non-small cell carcinoma. No significant differences existed for the type of effusion and symptoms. were asymptomatic and those in whom cough developed (p 0.05) [Table 3]. This is depicted graphically in Figure 1. The Pel was calculated for all subjects with available pressure and volume data (n 163) as the change in Ppl/total volume of fluid removed. The Pel ranged from 0 to 252 cm H 2 O/L (mean [ SD], cm H 2 O/L; median, 10 cm H 2 O/L). There were no significant differences in Pel between patients in whom symptoms developed and those in whom they did not, although there was a trend toward lower Pel in the patients in whom cough developed (Table 3). Interestingly, only 4 of the 18 patients (22%) in whom chest discomfort developed had Ppl lower than 20 cm H 2 O. None of the patients in whom cough developed had Ppl lower than 20 cm H 2 O, yet 12 of the 140 patients (8.6%) without symptoms had Ppl values lower than 20 cm H 2 O. There was no significant difference in the number of patients who had Ppl values lower than 20 cm H 2 O and in whom chest discomfort developed compared to those who did not have discomfort. Complications Pneumothorax occurred in 5 of 169 patients (3%). There were no significant differences in symptoms for patients in whom pneumothorax developed compared to those in whom it did not (p 0.06). Lung entrapment or trapped lung was suggested by the Pel curves in two of these patients, both of whom described chest discomfort. Only one of the patients in whom pneumothorax developed required further intervention with chest tube drainage aimed at treating the pneumothorax. This patient was receiving mechanical ventilation and did not have trapped lung/lung entrapment physiology. One of the patients with lung entrapment/trapped lung was successfully palliated (PleurX catheter; Denver Biomedical; Denver, CO), and the other changed the goals of their care to comfort without additional pleural procedures. Fifty of the thoracenteses were performed by medical housestaff, and 119 were performed by the interventional pulmonology fellow or interventional pulmonology attending physician. All of the procedures performed by housestaff were supervised by the interventional pulmonology fellow or the attending physician. There were no differences in complications stratified by level of training. Discussion Attention to Ppl values during thoracentesis allows for the safe removal of large volumes of pleural fluid and can help to predict the success of pleurodesis in patients with malignant pleural disease by identifying those with lung-entrapment physiology. Unfortunately, pleural manometry is rarely preformed. This likely stems from the lack of attention given to Ppl values during training in residency and fellowship, as well as a misconception that special techniques are required. In this study, we found that patient symptoms during thoracentesis, specifically the development of a vague chest discomfort can be used as a surrogate for the identification of potentially unsafe negative Ppl values. This is clinically important, as both cough and the descriptor of a sharp pain in the shoulder should not prompt termination of the procedure. During thoracentesis, one should ideally remove as much fluid as is safely possible. This allows for maximizing symptomatic improvement, the information gained 1558 Original Research

4 Table 3 Symptoms and Pleural Pressures* Symptoms Patients, No. Total Volume, L Pel, cm H 2 O/L Ppl, cm H 2 O Opening Closing Change None (58 to 43) (38 to 45) (0 to 39) Cough (10 to 4) (0.8 to 10.5) (2.8 to 20) Discomfort (16 to 4.5) (1.4 to 46) (5 to 43) p Value NS NS NS *Values are given as the mean SD (range). NS not significant. For discomfort vs none; other comparisons were not significant. For discomfort vs no discomfort and discomfort vs cough; other comparisons were not significant. from postthoracentesis imaging, as well as likely reducing the number of procedures the patient will require. Additionally, if entertaining the possibility of future pleurodesis, it is crucial to document full lung reexpansion (ie, apposition of the pleurae) after removal of all of the pleural fluid. If the lung is entrapped, patients can still achieve palliation of their dyspnea with a long-term indwelling pleural catheter (PleurX catheter; Denver Biomedical). There were no differences between groups for the volume of fluid removed or complications. It is possible that the incidence of pneumothorax would have been higher in the patients with lung entrapment physiology if fluid removal continued despite the development of chest discomfort or Ppl values lower than 20 cm H 2 O. This is supported in the study by Petersen and colleagues, who found that the use of a vacuum bottle was associated with a higher incidence of pneumothorax. 8 In this group of patients, it is probable that the vacuum bottle continued to remove fluid despite the creation of significantly negative Ppl values. Pel was measured as the total change in pressure divided by the total change in volume. Pel of 19 cm H 2 O after the removal of the initial 500 ml of pleural fluid has been associated with an increased risk for lung entrapment and unsuccessful pleurodesis. 4 In our study, there was a trend toward lower Pel in patients who had cough, compared with those with chest discomfort. This may indicate the resolution of atelectasis/lung reexpansion that should be expected with thoracentesis. Studies with larger sam- Figure 1. Change in Ppl and symptoms during thoracentesis. CHEST / 129 / 6/ JUNE,

5 ple sizes are needed to elucidate the relationship between symptoms and Pel. Interestingly, only 22% of patients who developed chest discomfort had Ppl values lower than 20 cm H 2 O. This percentage would likely have been higher if the thoracentesis continued without regard to pleural manometry findings. Additionally, potentially dangerous Ppl values develop in almost 9% of patients who were asymptomatic. It is unclear why symptoms did not develop or were not described in these patients. This strongly favors the use of manometry, as the lack of attention to Ppl values in these patients could have been associated with adverse outcomes. This study lends support to the practice of stopping a thoracentesis procedure in any patient who has vague chest discomfort, as this correlates with the development of potentially unsafe negative Ppl values. Given that there were minimal changes in Ppl in patients in whom cough developed, this symptom should not, in and of itself, be an indication to terminate a thoracentesis procedure. Conclusion We encourage practitioners to measure Ppl values during all thoracenteses. This practice leads to an improved understanding of pleural physiology and has been shown to predict lung reexpansion, which is an important determinant of successful pleurodesis. Additionally, the lack of attention to pleural manometry could miss a subset of patients in whom potentially unsafe pressures develop yet who do not describe chest discomfort. If pressures are not being measured, the development of vague chest discomfort should prompt the termination of the thoracentesis procedure as this correlates with the development of negative Ppl values. Cough, however, should not necessarily prompt termination of the thoracentesis procedure. Prior to their undergoing a procedure, we routinely tell our patients that cough is expected and is in fact generally a good sign, indicating lung reexpansion. This serves to allay any fears that may arise from the development of this symptom during the procedure. In our experience, this symptom typically lasts for only approximately 20 min and resolves spontaneously. Future studies are needed to investigate the relationship between symptoms and Pel, and to confirm the ideal phase in the respiratory cycle in which to measure Ppl (ie, mean vs end-inspiratory vs end-expiratory phase). ACKNOWLEDGMENT: The authors acknowledge the contributions of Drs. Momen Wahidi, William Lunn, and Rabih Bechara in their supervision and performance of the thoracenteses References 1 Light RW, Jenkinson SG, Minh VD, et al. Observations on pleural fluid pressures as fluid is withdrawn during thoracentesis. Am Rev Respir Dis 1980; 121: Villena V, Lopez-Encuentra A, Pozo F, et al. Measurement of pleural pressure during therapeutic thoracentesis. Am J Respir Crit Care Med 2000; 162: Light RW, Stansbury DW, Brown SE. The relationship between pleural pressures and changes in pulmonary function after therapeutic thoracentesis. Am Rev Respir Dis 1986; 133: Lan RS, Lo SK, Chuang ML, et al. Elastance of the pleural space: a predictor for the outcome of pleurodesis in patients with malignant pleural effusion. Ann Intern Med 1997; 126: Pavlin J, Cheney FW Jr. Unilateral pulmonary edema in rabbits after reexpansion of collapsed lung. J Appl Physiol 1979; 46: Miller WC, Toon R, Palat H, et al. Experimental pulmonary edema following re-expansion of pneumothorax. Am Rev Respir Dis 1973; 108: Doelken P, Huggins JT, Pastis NJ, et al. Pleural manometry: technique and clinical implications. Chest 2004; 126: Petersen WG, Zimmerman R. Limited utility of chest radiograph after thoracentesis. Chest 2000; 117: Original Research

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