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SCIENTIFIC LETTER

Cough during therapeutic thoracentesis: Friend or foe? MONIKA ZIELINSKA-KRAWCZYK,1 MARCIN MICHNIKOWSKI,2 ELZBIETA M. GRABCZAK,1 KRZYSZTOF J. PALKO,2 PIOTR KORCZYNSKI,1 TOMASZ GOLCZEWSKI2 AND RAFAL KRENKE1 1 Department of Internal Medicine, Pneumonology and Allergology, Medical University of Warsaw and 2Department for Mathematical Modelling of Physiological Processes, Nalecz Institute of Biocybernetics and Biomedical Engineering, Polish Academy of Sciences, Warsaw, Poland

We report intriguing preliminary observations on the effect of cough on pleural pressure changes during therapeutic thoracentesis. We found that coughrelated elevation of pleural pressure persisted even when the cough had stopped. Thus, we hypothesize that cough during therapeutic thoracentesis may have a beneficial effect preventing the excessive drop in pleural pressure. The true role of cough-related elevation of pleural pressure is unknown, but it seems to be an interesting subject for further research. Key words: cough, pleural effusion, pleural manometry, pleural pressure, thoracentesis. Abbreviations: Epl, pleural elastance; Ppl, pleural pressure.

Dyspnoea, cough and reduced exercise tolerance are common manifestations of moderate to large volume pleural effusion. The symptoms are closely related to both volume and pressure effects of pleural fluid accumulation.1 Alterations in the chest wall position, including compression and flattening of the diaphragm as well as lung compression atelectasis are regarded as major factors responsible for the sensation of breathing discomfort.2 Thoracentesis not only plays a pivotal role in the diagnostic work-up of patients with pleural effusion, but is also an important therapeutic procedure.3 Fluid withdrawal usually allows lung re-expansion and restoration of normal or near normal anatomical relations. In consequence, a decrease or even complete symptom resolution might be expected. According to the Medicare data, approximately 130,000 thoracenteses are performed annually in the United States.4 The volume of pleural fluid that can be withdrawn during a single procedure is limited by potential side-effects. The most serious complication that is thought to be closely related to a decrease in pleural pressure (Ppl) is re-expansion pulmonary Correspondence: Rafal Krenke, Department of Internal Medicine, Pneumonology and Allergology, Medical University of Warsaw, Banacha 1A; 02-097 Warsaw, Poland. Email: [email protected] Clinical trial registration: ClinicalTrial.gov (NCT02192138) at 14 July 2014. Received 8 August 2014; invited to revise 25 August 2014; revised 2 September 2014; accepted 5 September 2014 (Associate Editor: David Feller-Kopman). © 2014 Asian Pacific Society of Respirology

oedema.5,6 To reduce the risk of re-expansion pulmonary oedema during therapeutic thoracentesis, measurement of Ppl seems to be a reasonable option.7,8 Since the measurement of Ppl is not widely available, a recommendation to terminate the procedure after the withdrawal of 1000–1500 mL of pleural fluid has been proposed.2,9 This recommendation is, however, not strict and in case of easily expandable lung (pleural elastance (Epl) usually below 14.5 cmH2O/L), larger volumes can be withdrawn without a significant decrease of Ppl.10 In practice, symptoms reported by the patients, with chest discomfort/pain and progressive dyspnoea, often impose the decision to terminate pleural fluid withdrawal. On the other hand, it should be emphasized that the symptoms are not sensitive enough and re-expansion pulmonary oedema can develop even without any preceding signs. Feller-Kopman et al. found that nearly 9% of patients with potentially dangerous decline in Ppl (below −20 cmH2O) were asymptomatic.11 In the context of the relationship between the volume of withdrawn pleural fluid, Ppl changes and the risk of re-expansion pulmonary oedema— strategies that can increase lung compliance and improve lung re-expansion during therapeutic thoracentesis seem to be an interesting issue.2,10,11 Previously, we reported the development of an electronic pleural manometer that has several advantages over water manometer including overdamped water manometer.12,13 A new research project that is aimed at the assessment of the pathophysiological effects of Ppl changes during therapeutic thoracentesis has been recently undertaken in our institution. The study was approved by the Institutional Review Board and registered at ClinicalTrial.gov (NCT02192138). The use of the manometer to follow Ppl alterations clearly showed that in some patients, cough during therapeutic thoracentesis can increase Ppl. This may preclude an uncontrolled pressure drop that carries the risk of procedure-related complications. Below, we present data registered in three patients that demonstrate the effect of cough on Ppl changes during therapeutic thoracentesis. Patients with moderate or large volume pleural effusions who required therapeutic thoracentesis Respirology (2015) 20, 166–168 doi: 10.1111/resp.12426

Cough during therapeutic thoracentesis

were enrolled. Thoracentesis and pleural manometry were performed as described elsewhere.12 Briefly, baseline Ppl was registered and then the measurements were subsequently repeated after withdrawal of each 200 mL of pleural fluid up to a total volume of 1000 mL. When the volume of withdrawn fluid exceeded 1000 mL, the measurements were performed after removal of each 100 mL. Vital signs and symptoms were registered together with Ppl changes. Cough during the procedure was noted in four of the first six patients who were recruited to the abovementioned project. Cough-related elevation of Ppl was demonstrated in three of these patients. Baseline Ppl in patient #1 was 2.3 cmH2O and gradually decreased to −8.8 cmH2O after withdrawal of 1200 mL of fluid (Fig. 1a). After a short episode of cough, the pressure increased to −5.7 cmH2O and finally decreased to −16.4 cmH2O after withdrawal of further 400 mL. Ultimately, 1600 mL of pleural fluid was evacuated, and the estimated Epl was

167 11.7 cmH2O/L (Epl was calculated as the quotient of change in Ppl and total volume of withdrawn pleural fluid). In patient #2, Ppl decreased from baseline 2.4 cmH2O to −11.0 cmH2O after the withdrawal of 1400 mL of pleural fluid (Fig. 1b). Spontaneous cough at this time point resulted in pressure elevation to −7.9 cmH2O. After the removal of 2700 mL in total, Ppl reached −19.5 cmH2O. Epl was calculated as 8.1 cmH2O/L. The initial Ppl in patient #3 was 5.9 cmH2O and decreased to −11.8 cmH2O after withdrawal of 1800 mL of pleural fluid (Fig. 1c). Again, spontaneous cough resulted in Ppl elevation to −9.6 cmH2O. Further removal of 300 mL was associated with a decrease of Ppl to −14.4 cmH2O. Thus, the total volume of withdrawn pleural fluid and Epl was 2100 mL and 9.7 cmH2O/L, respectively. To our best knowledge, this is the first report highlighting the potential beneficial effect of cough during

Figure 1 Cough-related changes in pleural pressure during therapeutic thoracentesis in three patients (a-c). Horizontal axes show pleural pressure, whereas vertical axes show withdrawn pleural fluid volume. Each graph includes multiple vertical lines and one polygonal curve. Multiple vertical lines represent instantaneous pleural pressure measured at different withdrawn fluid volumes. The duration of each measurement was approximately 60 s; hence, it covered at least 15 respiratory cycles. Polygonal curves show trends in mean pleural pressure changes during the procedure. White arrows represent time points where cough episodes were noted. See text for specific numerical data on pleural pressure changes that followed cough episodes. © 2014 Asian Pacific Society of Respirology

Respirology (2015) 20, 166–168

168 therapeutic thoracentesis. Although pleural manometry has been increasingly used to study pleural pathophysiology, previous papers mainly focused on technical issues and different aspects of unexpandable lung, including lung entrapment and trapped lung.10,11,13–15 It should be emphasized that the detailed analysis of the effect of cough on Ppl as a function of time could not have been made with water manometer and overdamped water manometer used in some earlier studies.13 Of note, until now, cough during therapeutic thoracentesis has been considered as an adverse effect associated with lung re-expansion and possibly with re-expansion pulmonary oedema.5 The essence of our observations is that the cough-related elevation of Ppl was not only found during the cough episode, but also persisted after the cough had stopped. We may speculate that the major mechanism of post-cough elevation of Ppl could be a local increase in transpulmonary pressure, which results in opening of atelectatic lung regions.7 Regional differences between airway and Ppl alterations during cough might be a prerequisite for this phenomenon. Higher increase in airway as compared with Ppl in some lung regions might promote small airway and alveolar distension. Opening of collapsed bronchioles and alveoli could increase lung volume and cause the shift towards less negative Ppl. It cannot be excluded that a deep inspiration in the first phase of cough may also contribute to the above-described effects. In the three presented patients, a similar effect was noted at different levels of Ppl ranging from −11.8 cmH2O to −8.8 cmH2O. It is not known whether the same effect could be observed at higher or lower levels of Ppl. There are other relevant questions emerging from our study. These include the following: Does a spontaneous and voluntary cough produce the same effect? Can the cough-related increase in Ppl be observed in all patients undergoing therapeutic thoracentesis? And finally, can the volume of pleural fluid, which can be safely withdrawn during therapeutic thoracentesis, be increased by cough during the procedure? These questions cannot be answered yet. Further studies are necessary to elucidate these issues. In conclusion, we found that cough during therapeutic thoracentesis may have an advantageous consequence, namely the prevention of excessive drop in Ppl. This observation needs to be confirmed in larger studies. The true role of cough-related elevation of Ppl and its mechanisms is unknown, but it seems to be an interesting subject for further research.

Respirology (2015) 20, 166–168

M Zielinska-Krawczyk et al.

Acknowledgement The study was partially supported by a research grant from the National Research Centre, Poland (Grant No. 2012/05/B/NZ5/ 01343).

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© 2014 Asian Pacific Society of Respirology

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Cough during therapeutic thoracentesis: friend or foe?

We report intriguing preliminary observations on the effect of cough on pleural pressure changes during therapeutic thoracentesis. We found that cough...
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