Comparison of pleurodesis by erythromycin, talc, doxycycline, and diazepam in a rabbit model

Abstract

Background: Patients with malignant pleural effusion, recurrent spontaneous pneumothorax, and recurrent benign pleural effusions may have significant relief of their symptoms with chemical pleurodesis. Talc is the most frequently used chemical sclerosant; however, it has been known to induce Adult Respiratory Distress Syndrome (ARDS). Other agents such as doxycycline and erythromycin have documented efficacy as sclerosing agents in the pleura, but they are not in widespread clinical use and have significant documented adverse reactions. Diazepam may represent a potential sclerosing agent in the pleura, because of its local inflammatory profile in other tissues.

Materials and methods: Overall, 33 adult New Zealand White rabbits (Oryctolagus cuniculus) were randomized to 5 treatment groups. Each group received an intrapleural injection via 5 Fr silastic tubes of one of the following agents: 35-mg/kg erythromycin in 2 ml of saline, 70-mg/kg talc in 2 ml of saline, 10-mg/kg doxycycline in 2 ml of saline, 0.4-mg/kg diazepam in 2 ml of saline, or 2 ml of saline as a control. The animals were euthanized and necropsied 30 days after injection. The pleural surfaces were assessed for macroscopic and microscopic evidence of surrounding inflammation and fibrosis.

Results: Doxycycline resulted in severe pleural inflammation and fibrosis with pulmonary hemorrhage, whereas talc-treated animals had less effective fibrosis and granulomas. A trend toward higher mortality occurred in doxycycline-treated animals. Erythromycin demonstrated similar fibrosis (p=0.487) to doxycycline and had less inflammation (p<0.001). Diazepam treatment had little effect in the pleural cavity.

Conclusions: This study demonstrates that erythromycin may be the ideal sclerosing agent. It had the advantage of maximal fibrosis with minimal inflammation. Although doxycycline was the most potent pleural sclerosant, it caused severe local tissue damage. Talc treatment resulted in only mild fibrosis, and diazepam was ineffective.