Effect of repeated administration of low-dose silver nitrate for pleurodesis in a rabbit model

Background and objective: Both the efficacy and toxicity of sclerosing agents are likely to be dose‐dependent. Clinical pleurodesis strategies typically involve single bolus dose administration of drugs. This study was designed to test whether repeated administration of low doses of silver nitrate (SN) could lead to effective pleurodesis. Methods: Intrapleural administration, to rabbits, of decreasing doses of SN or normal saline was undertaken daily over 1, 5 or 14 days. Assessment of the degree of pleurodesis was by visual inspection (score 1–8) and histological examination and scoring of inflammation and fibrosis (score 0–4). The untreated contralateral side was used as a control. A visual pleurodesis score of ≥5 was considered to be positive. Results: The lowest concentrations of SN leading to a visual pleurodesis score ≥5 were 0.425%, 0.085% and 0.05% for 1, 5 and 14 day administration protocols respectively (P < 0.05 vs control side). Visual pleurodesis scores decreased as the dose of SN decreased within each administration regimen groups (P < 0.05 for single and 14 day groups, P = 0.058 in 5 day group). A significant correlation was noted between visual pleurodesis scores and histology fibrosis scores. Conclusions: Effective pleurodesis can be achieved in an animal model with repeated daily administration of SN at doses significantly lower than the lowest effective single day dose. This finding could lead to better tolerated pleurodesis regimens.