Mohsen, T.A., Zeid, A.A., Meshref, M., Tawfeek, N., Redmond, K., Ananiadou, O.G., & Haj-Yahia, S. (2011). Local iodine pleurodesis versus thoracoscopic talc insufflation in recurrent malignant pleural effusion: A prospective randomized control trial. European Journal of Cardio-Thoracic Surgery: Official Journal of the European Association for Cardio-Thoracic Surgery, 40(2), 282-286.

The objective of the study was to compare the efficacy and safety of 10% povidone-iodine and thoracoscopic talc insufflation for pleurodesis of recurrent malignant pleural effusions due to metastatic breast cancer.

Forty-two participants were randomized into two groups. Patients assigned to Group A received video-assisted thoracoscopic (VATS) drainage, mechanical adhesiolysis, and 4 g of talc poudrage, while the 20 patients assigned to Group B received VATS drainage, mechanical adhesiolysis, bedside pleurodesis with 20 mL of 10% povidone-iodine diluted in 30 mL of normal saline. Therapeutic thoracentesis was performed in all participants, and pleural fluid volume was recorded and sent for biochemical (pH, LDH, glucose), bacteriologic, and cytologic evaluation. All patients were scheduled for a follow-up every three months at which symptoms and chest x-rays were evaluated, and efficacy of pleurodesis was gauged on three levels: complete (absence of pleural fluid reaccumulation), partial (residual pleural fluid or reaccumulation that remained asymptomatic and not requiring thoracentesis), or failed (necessitating pleural procedures). Success was defined as a normal chest x-ray or radiologic reaccumulation of pleural fluid without recurrence of dyspnea or need for thoracentesis. Repeated ultrasound-guided thoracentesis was provided for patients with failed pleurodesis and reaccumulation of effusion at weekly intervals, and a PleurX^® catheter was offered for home management of effusions when required.

• The study reported on a sample of 42 patients.
• In Group A, the mean age was 48 years (SD = 9 years), and the range was 29–64 years.
• In Group B, the mean age was 50.2 years (SD = 7 years), and the range was 32–62 years.
• Data were not available to determine the percentage of males and females.
• Participants had malignant pleural effusion secondary to metastatic breast cancer.
• All patients either had either metastasis as their first presentation or had relapsed after chemotherapy during their follow-up.
• Patients were excluded from the study if they had a performance status greater than three, known allergies to iodine, a trapped lung, no change in the Medical Research Council (MRC) dyspnea scale after thoracentesis, pleural fluid pH less than 7.2 or glucose less than 60 mg/dL, and an extrathoracic metastasis.
• Both groups received the same protocol for adjuvant chemotherapy (i.e., 5FU, Adriamycin^®, and chlophosphamide (FAC), or docetaxel).
• No difference in preoperative demographic and clinical details between the two groups were noted.
   

This single-site study was conducted in an outpatient setting in the Department of Chest Medicine and Cardiothoracic Surgery in Cairo University Hospitals.
 

• Patients were in the transition phase after initial treatment.
• The study has clinical applicability for end-of-life and palliative care and late effects and survivorship.
   

The study was a prospective, randomized controlled trial.

• Medical Research Council (MRC) dyspnea scale to assess breathlessness
• Performance status scale (ECOG) to assess functional ability
• Diagnostic thoracentesis
   

Dyspnea and cough symptoms were improved in all patients after drainage and pleurodesis, and no mortality related to the procedure or perioperative mortality were observed. Survival rates between the two groups and totally at follow-up were 32 patients (76%) at eight months, 22 patients (52%) at two years, and 10 patients (23%) at four years. All had good outcomes with no bleeding complications and were discharged when both radiologic and clinical evidence confirmed complete resolution of pleural effusion. Group B experienced a significantly lesser post-procedural hospital stay (mean 5.7 days [SD = 2 days]) than Group A (mean 4.5 days [SD = 1.1 days]) (p = 0.009). During early follow-up in Group A, successful/complete response was achieved in 19 patients (87%), failure in 2 patients (9%), and partial response with radiologic reaccumulation at two months post-procedure but remaining asymptomatic during the 14 months’ follow-up. Early follow-up in Group B resulted in 17 (85%) complete response, no partial response, and three failures (15%) with recurrence of dyspnea at 33, 41, and 49 days respectively. No loculations were observed in Group B, thus a small-bore chest tube was placed and iodine was used again. In Group A, observed loculations were repeatedly aspirated with an ultrasound guide, and when repeated reaccumulation was experienced, an ultrasound-guided PleurX^® catheter was offered. No recurrence was detected at more than six months during follow-up, and no statistical difference between long-term success (four years) rates in Groups A (91%) and B (85%) were observed. Complications of pleuritic pain were observed in four participants of Group A (18%) but none in Group B, and fever was observed in four participants (18%) in Group A, and one participant (5%) in Group B.

Authors concluded that povidone-iodine pleurodesis is a safe and effective alternative to talc pleurodesis in the prevention of recurrent malignant pleural effusion at 30 days post-procedure. Additionally, while chest pain and fever are the most common adverse effects of pleurodesis, those in the iodine-povidone population (Group B) experienced less analgesic requirements and reports of fever, albeit at no statistical significance. Authors also emphasized that the dose of 10% povidone-iodine was administered in dilute form, thereby significantly increasing povidone safety with decreased toxicity when compared to other studies.

• The study had a small sample size, with less than 100 participants.
• The study results are only significant to a population of patients with malignant pleural effusion secondary to metastatic breast cancer; more research is warranted for efficacy among other population types.
• The clinical practice of providing mechanical adhesiolysis through the VATS procedure may have contributed to successful pleurodesis in both groups; true translation of this evidence would require performing a VATS procedure prior to the instillation of povidine-iodine, which is an uncommon practice. (Patients usually have a VATS procedure with talc insufflations or a chest catheter bedside procedure but not a surgical procedure followed by a bedside procedure.)
• Statistical analysis was limited by a lack of computed confidence intervals to safely exclude clinically relevant differences, as well as a lack of survival analysis.
   

Given its good success rate and fewer complications, povidone-iodine appears to be a successful, safe, and cost-effective alternative to talc pleurodesis for palliative management of malignant pleural effusion stemming from metastatic breast cancer.