Efficacy and safety of intrapleural administration of sodium bicarbonate in patients with acute empyema and complicated parapneumonic effusion: protocol for a prospective, single-arm, interventional study.

BACKGROUND: The standard treatment for acute empyema/complicated parapneumonic effusion (CPPE) is antibiotic administration and continuous chest drainage. However, adequate drainage becomes impossible in multichambered pleural effusion and some patients may require surgery or may die. In Japan, intrapleural urokinase is frequently used to restore drainage effects; however, its supply was suspended in 2022 owing to difficulties in procuring the raw materials. In recent years, the effectiveness of intrapleural sodium bicarbonate administration for empyema/CPPE has been reported; however, complications such as hemothorax and pneumothorax occurred frequently because the research protocol involved repeated thoracentesis. Therefore, we designed an interventional study to investigate the efficacy and safety of intrapleural sodium bicarbonate administration combined with continuous chest drainage in patients with empyema/CPPE.

METHODS: This study will include patients with empyema/CPPE who have been administered antibiotics and still have pleural effusion after > 12 h of continuous chest drainage. Sodium bicarbonate (50 mL) will be administered into the pleural cavity through the double-lumen catheter of the chest tube once daily for a maximum of 3 days. The primary endpoint will be treatment success rate, defined as the rate of avoiding surgery or death within 30 days of sodium bicarbonate administration. The 95% confidence interval for the treatment success rate will be calculated using the Clopper-Pearson method.

DISCUSSION: Sodium bicarbonate can be chemically synthesized; therefore, there is little concern about supply shortages and it is inexpensive. Therefore, if it is effective against empyema/CPPE, it would prove beneficial for Japan and other countries. Once this study shows the efficacy and safety of intrapleural sodium bicarbonate administration for empyema/CPPE, we plan to conduct a prospective randomized controlled trial using a placebo.

TRIAL REGISTRATION: This study was approved by the Yokohama City University Clinical Research Review Committee (ethics approval number: CRB24-001) on May 8, 2024, and registered with the Japan Clinical Trials Registry (jRCTs031240093) on May 17, 2024. Written informed consent will be obtained from the participants or their proxies.