Clinical Utility of Routine Pleural Manometry During Large Volume Thoracentesis: A Multicenter Randomized Trial

Background: In patients with non-expandable lung, pleural fluid removal can result in excessively negative pleural pressure, associated with chest discomfort, pneumothorax, and reexpansion pulmonary edema. Monitoring pleural pressure during thoracentesis may reduce discomfort and protect against complications. Methods: In this prospective randomized single-blind trial, subjects with large pleural effusions at two academic medical centers were randomly assigned (1:1 ratio) to symptom-guided (control) versus symptom-plus-manometry-guided (manometry) thoracentesis. All had free-flowing effusions meeting pre-specified criteria suggesting volume of at least 500 milliliters. Subjects, who were blinded to assignment, rated chest discomfort on visual analog scales before, during, and after drainage. Pleural pressure was measured at regular intervals in the manometry group. Drainage was discontinued before complete evacuation for persistent chest discomfort, incessant cough, complication, rapidly falling pleural pressure, or end-expiratory pleural pressure lower than -20 cm H2O (latter two only in the manometry group). We performed a modified intention-to-treat analysis. The primary outcome was overall procedural chest discomfort through 5 minutes post-procedure. Findings: Between March 4, 2016 and September 8, 2017, 191 patients were screened. One hundred twenty-eight eligible subjects were randomized with four excluded from the final analysis of 62 subjects per group due to manometer malfunction (n=2), inability to access effusion due to pleural tumor burden (n=1), and inability to remain seated (n=1). There was no difference in the primary outcome of overall procedural chest discomfort between groups (mean difference 2.4, 95% CI -5.7-10.5; p = 0.78). Six asymptomatic pneumothoraces ex-vacuo occurred in the control group; no serious complications occurred in either group. Interpretation: Measurement of pleural pressure during large-volume thoracentesis does not alter procedure-related chest discomfort. This is the first study to directly assess the impact of pleural manometry on important patient-centered clinical outcomes during thoracentesis, and does not support its routine use. This trial was registered at clinicaltrials.gov, NCT02677883 Funding: Centurion Medical Products Declaration of Interest: No authors report any financial or non-financial conflicts of interest pertinent to this work outside the declared funding source for this trial (see below re: role of funding source). Ethics Approval Statement: This randomized single-blind trial recruited inpatient and outpatient subjects at two academic medical centers (Vanderbilt University Medical Center, Nashville, TN, USA and Johns Hopkins Hospital, Baltimore, MD, USA). Institutional Review Boards of both institutions approved this trial (VUMC IRB number 151492; JHU IRB number 00119664).