Pleural Disease Management: Manometry-guided Thoracentesis, Optimal Drainage Regimen of Indwelling Pleural Catheters, and Talc Poudrage versus Slurry for Malignant Pleural Effusion

Recommended Reading from the Virginia Commonwealth University Pulmonary/Critical Care and Interventional Pulmonary Fellows

Samira Shojaee, M.D., M.P.H., Interventional Pulmonary Program Fellowship Director

Lentz RJ, et al. Routine Monitoring with Pleural Manometry during Therapeutic Large-Volume Thoracentesis to Prevent Pleural-Pressure-related Complications: A Multicentre, Single-Blind Randomised Controlled Trial. Lancet Respir Med (1)

Reviewed by Andrea Mytinger

Pleural effusion remains a common (2) medical problem encountered in clinical practice, making thoracentesis a routine procedure performed by pulmonologists worldwide. Although thoracentesis is relatively safe, complications related to negative pleural pressure such as chest discomfort, pneumothorax ex vacuo, and reexpansion pulmonary edema (3) have led to the use of pleural manometry (Plm) for intrapleural pressure monitoring during the procedure. However, literature supporting its use for complication prevention is lacking.

Lentz and colleagues (1) performed a prospective, randomized, single-blinded study of patients with pleural effusions estimated to be at least 0.5 L in volume to investigate the impact of Plm on chest discomfort during thoracentesis. Patients with known expandable lung and those with non–free-flowing effusions were excluded. Patients were randomized 1:1 to receive thoracentesis guided by symptoms alone or symptoms plus Plm. Drainage was paused for 5–10 seconds at prespecified intervals in both groups where pleural pressure was measured in the experimental arm and degree of chest discomfort was assessed in both groups using a 100-mm visual analog scale (VAS). The primary outcome was patient-reported chest discomfort from the start to 5 minutes after the end of drainage.

One hundred twenty-four patients were included in the final analysis (62 patients per group), and malignant disease was the most common comorbidity (63%). Primary outcome scores in the control group (23.0 mm) compared with the manometry group (25.4 mm) had a mean difference of 2.4 mm, showing no significant difference between groups (95% confidence interval [95% CI], −5.7 to 10.5; P = 0.56). There was no significant difference in procedure duration, effusion volume drained, and frequency of complete lung reexpansion after the procedure. Pneumothorax ex vacuo was significantly higher in the control group compared with the manometry group (10% vs. 0%; P = 0.01); however, none of the patients with pneumothorax were symptomatic or required intervention.

The authors concluded that routine use of manometry during thoracentesis does not reduce chest discomfort or prevent any serious procedural complications. Other studies have shown that intraprocedural manometry does not protect against reexpansion pulmonary edema, pneumothorax ex vacuo, or chest discomfort (4–7). The strength of the current study is in its randomized design. Limiting bias and providing more accurate effect estimates, the trial reports negative results while investigating a patient-centric primary endpoint immediately applicable at the bedside. There are, however, limitations in this study. Because of the volume of fluid drained (mean ∼1,100 ml, SD ∼500 ml) in this study, the results of this trial cannot be generalized to effusions >1,500 ml, which are commonly encountered and may benefit from intraprocedural manometry. This study shows that routine use of Plm during thoracentesis is not necessary; however, its potential benefit for larger-volume effusions and its utility in predicting pleurodesis success need assessment in future studies.

Muruganandan S, et al. Aggressive versus Symptom-guided Drainage of Malignant Pleural Effusion via Indwelling Pleural Catheters (AMPLE-2): An Open-Label Randomised Trial. Lancet Respir Med (8)

Reviewed by Trevor Taylor

Malignant pleural effusion (MPE) is often associated with a high symptom burden leading to a decreased quality of life (QOL) (9, 10). Management guidelines recommend the use of indwelling pleural catheters (IPCs) as an effective strategy for symptom management in recurrent MPE (11); additionally, IPCs can lead to spontaneous pleurodesis in select populations (12). Daily IPC drainage has been shown to result in higher pleurodesis rates compared with every-other-day drainage in a randomized trial in patients with MPEs (13). Despite the ubiquity of IPCs, there remains uncertainty as to the optimal frequency of drainage.

Muruganandan and colleagues compared aggressive IPC drainage, defined as daily drainage for the first 60 days, with symptom-guided drainage in patients with MPEs in a multicenter randomized trial. Baseline assessments of breathlessness, pain, and QOL were measured on a 100-mm VAS before IPC insertion. Patients were randomized in a 1:1 fashion minimized for cancer type, performance status, pleural space physiology, and prior pleurodesis and were instructed to record their daily breathlessness and pain scores for the first 60 days.

The primary endpoint was the mean daily breathlessness VAS score in the first 60 days and did not differ between the daily versus symptom-guided drainage groups (13.1 vs. 17.3 mm; P = 0.18), respectively. Among the secondary outcomes, the pleurodesis rate was significantly higher in the daily (37.2%) versus the symptom-guided group (11.4%). Patients in the daily-drainage group had better QOL (a secondary outcome) compared with the symptom-guided group. No significant difference was noted in adverse events and survival.

This study shows that daily versus symptom-guided drainage of IPC results in no significant difference in 60-day breathlessness score with similar adverse event profile including infections, despite daily handling of the catheter. Given that both strategies lead to comparable symptomatic relief, drainage frequency can be focused on patient preferences, with aggressive drainage in patients in whom IPC removal is the primary goal and as long as daily drainage does not result in pain. Inclusion of patients with trapped lung (with similar 6-mo pleurodesis rate compared with expandable lung in post hoc analysis), a population often excluded from studies, selection of a patient-centric primary outcome and the study’s randomized design using minimization are among its important strengths. Lower pleurodesis rates in this study compared with reported pleurodesis rates (up to 57%) in observational studies highlight the importance of randomized controlled trials in the development of more accurate effect estimates. There are, however, limitations of an open-labeled design and short interval primary endpoint assessment, given that >30% of the study participants had mesothelioma, a group that enjoys a longer survival than other categories of MPE. Other factors such as cost and burden to patients and family over a longer time period are not evaluated in this trial in which a substantial number of patients were alive at 6 months, and those factors may be the subject of future studies.

Bhatnagar R, et al. Effect of Thoracoscopic Talc Poudrage versus Talc Slurry via Chest Tube on Pleurodesis Failure Rate among Patients with Malignant Pleural Effusions: A Randomized Clinical Trial. JAMA (14)

Reviewed by Evgeni Gershman

More than 50% of MPEs reaccumulate after initial drainage, and chemical pleurodesis is a key management option for patients with recurrent MPEs and expandable pleural space physiology (11, 15–17). Talc is by far the most commonly used and the most effective pleurodesis agent (18, 19). Talc may be delivered through an intercostal chest tube mixed with a sterile fluid (talc slurry) or sprayed directly on the pleural surface as a dry powder during a thoracoscopic procedure (talc poudrage). The optimal method for talc pleurodesis has been controversial (17, 20). Dresler and colleagues showed no significant difference in pleurodesis rate at 1 month between slurry and poudrage; however, this trial was limited by short-interval follow-up and did not minimize for important variables such as cancer type (21). Recent MPE management clinical practice guidelines noted that there was no significant difference in talc pleurodesis success in slurry versus poudrage and provided conditional recommendations with a low level of confidence to use either method depending on need for pleural biopsy, patient-related factors, providers’ skill, and equipment availability (11). The investigators’ low confidence in the recommendation was due to heterogeneity in patient population, selection bias, and inconsistencies in studied endpoints.

The study by Bhatnagar and colleagues (14) was a randomized, open-label, parallel-group superiority trial comparing talc poudrage versus slurry. The study was conducted in 17 hospitals in the United Kingdom using 1:1 randomization with minimization algorithm (minimized for cancer type and World Health Organization performance status) and powered to detect a 15% difference between groups. Patients were eligible if they were >18 years of age, had a confirmed diagnosis of MPE, and could undergo thoracoscopy with local anesthesia. Patients were followed up to 180 days after randomization.

The primary outcome was pleurodesis failure at 90 days and was not significantly different among the poudrage (36/161, 22%) versus slurry (38/159, 24%) groups (adjusted odds ratio, 0.91 [95% CI, 0.54 to 1.55]; P = 0.74; difference, −1.8% [95% CI, −10.7 to 7.2]). No statistically significant differences were noted in any of the secondary outcomes including pleurodesis failure in 180 days, patient-reported pain or dyspnea score at different time intervals throughout the study, QOL, hospital length of stay, adverse events, or all-cause mortality.

Although the study is limited by its open-labeled design and underpowered to detect differences <15%, it addresses numerous shortcomings of prior literature such as selection bias and heterogeneity and includes a relatively large sample size of 330 to address its primary and a priori presented secondary outcomes. This study shows that talc slurry is as effective as talc poudrage; hence, talc poudrage should not be chosen over slurry based on its efficacy. Other factors such as the need for thoracoscopy and pleural biopsy, providing an opportunity for talc poudrage, should dictate the method of choice for talc pleurodesis.