REVIEW CURRENT OPINION Physiology of breathlessness associated with pleural effusions Rajesh Thomasa,b,c, Susan Jenkinsd,e,f, Peter R. Eastwood g,h Y.C. Gary Leea,b,c, and Bhajan Singhg,h Purpose of review Pleural effusions have a major impact on the cardiorespiratory system. This article reviews the pathophysiological effects of pleural effusions and pleural drainage, their relationship with breathlessness, 11/15/2020 on BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC1y0abggQZXdgGj2MwlZLeI= by http://journals.lww.com/co-pulmonarymedicine from Downloaded Downloaded and highlights key knowledge gaps. Recent findings from The basis for breathlessness in pleural effusions and relief following thoracentesis is not well understood. http://journals.lww.com/co-pulmonarymedicine Many existing studies on the pathophysiology of breathlessness in pleural effusions are limited by small sample sizes, heterogeneous design and a lack of direct measurements of respiratory muscle function. Gas exchange worsens with pleural effusions and improves after thoracentesis. Improvements in ventilatory capacity and lung volumes following pleural drainage are small, and correlate poorly with the volume of fluid drained and the severity of breathlessness. Rather than lung compression, expansion of the chest wall, including displacement of the diaphragm, appears to be the principle mechanism by which the effusion is accommodated. Deflation of the thoracic cage and restoration of diaphragmatic function after thoracentesis by may improve diaphragm effectiveness and efficiency, and this may be an important mechanism by which BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC1y0abggQZXdgGj2MwlZLeI= breathlessness improves. Effusions do not usually lead to major hemodynamic changes, but large effusions may cause cardiac tamponade and ventricular diastolic collapse. Patients with effusions can have impaired exercise capacity and poor sleep quality and efficiency. Summary Pleural effusions are associated with abnormalities in gas exchange, respiratory mechanics, respiratory muscle function and hemodynamics, but the association between these abnormalities and breathlessness remains unclear. Prospective studies should aim to identify the key mechanisms of effusion-related breathlessness and predictors of improvement following pleural drainage. Keywords breathlessness, pathophysiology, pleural effusion, thoracentesis INTRODUCTION aCentre for Asthma, Allergy and Respiratory Research, School of Medi- Over 1 million patients develop a pleural effusion cine and Pharmacology, University of Western Australia, bPleural Medi- annually in the United States alone [1]. Pleural cine Unit, Lung Institute of Western Australia, cDepartment of Respiratory effusions have more than 60 different causes, and Medicine, Sir Charles Gairdner Hospital, dPhysiotherapy Unit, Lung e vary in size and risk (and rates) of recurrence. Con- Institute of Western Australia, Department of Physiotherapy, Sir Charles Gairdner Hospital, fSchool of Physiotherapy and Exercise Science, gestive heart failure (CHF), malignancy, pulmonary Curtin University, gCentre for Sleep Science, School of Anatomy, Physi- infection and embolism account for over 90% of ology and Human Biology, University of Western Australia and hWest pleural effusions [2]. Australian Sleep Disorders Research Institute, Department of Pulmonary on Physiology and Sleep Medicine, Sir Charles Gairdner Hospital, Perth, 11/15/2020 Pleural effusions can impact profoundly on the cardiorespiratory system. Breathlessness, the com- Western Australia, Australia monest presentation, is often debilitating and signifi- Correspondence to Dr Rajesh Thomas, MBBS, FRACP, Department of cantly impairs quality of life. Relief of breathlessness Respiratory Medicine, B Block, QE II Medical Centre, Perth, WA 6009, Australia. Tel: +61 93463333; fax: +61 8 93462816; e-mail: rajesh. often necessitates therapeutic pleural interventions [email protected] with associated discomfort, risks of infection, bleed- Curr Opin Pulm Med 2015, 21:338–345 ing, pneumothorax and even death. Management of DOI:10.1097/MCP.0000000000000174 pleural effusions represents a significant healthcare This is an open-access article distributed under the terms of the Creative burden worldwide. Commons Attribution-NonCommercial-NoDerivatives 4.0 License, where To date, research on, and hence our understand- it is permissible to download and share the work provided it is properly ing of, the effects of pleural effusions on respiratory cited. The work cannot be changed in any way or used commercially. www.co-pulmonarymedicine.com Volume 21 Number 4 July 2015 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. Physiology of breathlessness with pleural effusions Thomas et al. PATHOPHYSIOLOGICAL EFFECTS OF A KEY POINTS PLEURAL EFFUSION Pleural effusions can affect the cardiorespiratory system, Most studies on the pathophysiologic effects of exercise capacity and sleep. effusions have included small numbers of patients who are heterogeneous in their underlying pleural Gas exchange worsens with pleural effusions and improves following thoracentesis. and systemic diseases, and many have been con- ducted in different settings (e.g. ventilated vs. spon- Improvements in ventilatory capacity and lung volumes taneous breathing patients). Therefore, care must be following pleural drainage are small, and correlate executed in interpreting their findings. poorly with the volume of fluid drained and the severity of breathlessness. Chest wall expansion and displacement of the Gas exchange diaphragm are the principle mechanisms by which the Pleural effusions can worsen gas exchange. Instilla- effusion is accommodated; deflation of the thoracic tion of physiological saline into both pleural spaces cage and restoration of diaphragmatic function after of mechanically ventilated pigs has been shown to thoracentesis may be important mechanisms by which breathlessness improves. induce early and dose-related hypoxemia [6]. Intra- pulmonary shunt was shown to underlie the hypo- Effusions do not usually cause major hemodynamic xemia when Agusti et al. [7] examined patients changes, but large effusions may cause cardiac (n ¼ 9) with recent-onset pleural effusions using tamponade and ventricular diastolic collapse. the multiple inert gas elimination technique. Thoracentesis appears to improve gas exchange. A meta-analysis of 19 studies (1124 patients) [8&]on physiology and breathlessness has been limited. The thoracentesis in mechanically ventilated patients conventional belief that pleural effusions cause showed an average improvement in PaO2:FiO2 of breathlessness through compression of the lung is 18%. Improvements in gas exchange are more con- overly simplistic. The severity of breathlessness sistently found at 24 h [5,9], rather than immedi- often correlates poorly with the size of the effusion & ately [7,10–12] after thoracentesis. Hypoxemia has [3 ,4,5] Conversely, symptom reduction from fluid been shown to worsen up to 2 h after thoracentesis drainage varies significantly between patients, and [13]. These observations have been attributed to re- no reliable predictors exist to identify those who will expansion pulmonary edema or delayed pulmonary benefit. Most previous studies have involved small re-expansion. cohorts and examined specific etiological factors in Several factors may influence the improvement isolation; few have compared physiological changes in gas exchange with thoracentesis. In mechanically with symptom benefits in patients. ventilated patients, improvements in PaO2:FiO2 This article reviews published literature on the have been associated with the volume drained pathophysiological effects of pleural effusions [14] and the increase in end-expiratory lung volume (and their therapeutic evacuation). Key knowledge & [15 ]; those with lower PaO2:FiO2 ratios appeared to gaps are highlighted which may guide future have greater benefit. Patients with acute respiratory research. distress syndrome appeared to have less improve- ment in gas exchange [15&,16]. In mechanically LITERATURE SEARCH ventilated patients with CHF effusions, the improvement in PaO2:FiO2 after thoracentesis cor- Medline, Excerpta Medica dataBASE (EMBASE) and related inversely with pleural elastance [17]. the Cochrane Database of Systematic Reviews were Improvements in oxygenation are greater in interrogated using the following search terms, such as patients with diaphragm paradox [18]. No evidence ‘pleural effusion’ and ‘oxygenation’ (gas exchange, links abnormal gas exchange caused by pleural effu- hypoxemia and oxygen desaturation), ‘pulmonary sions (and their improvements postthoracentesis) to function test’ (lung function test, respiratory function the symptom of breathlessness. test and spirometry), ‘pleural pressure’ (Ppl, pleural elastance), ‘exercise’ [6-min walk test (6MWT), car- diopulmonary exercise test], ‘sleep’, ‘cardiac’ (hemo- Pulmonary function and respiratory dynamic effects, hypotension) and ‘dyspnea’ mechanics (breathlessness). References and their citation lists Studies of pleural effusion and pulmonary function were scrutinized. Studies pertaining to the effects of are often heterogeneous in their designs and phys- pleural effusion on pulmonary physiology and iological indices measured. Nonetheless, most stud- breathlessness were included. ies agree that increases in lung volumes are small 1070-5287 Copyright