PURPOSE: To evaluate the effectiveness of decreasing doses of two sclerosing agents, silver nitrate (SN) and Doxycycline (D), when administered daily over 1, 5 and 14 days.
METHODS: In-vivo experiment in rabbit pleurodesis model consisting of intrapleural administration of D, SN or placebo (normal saline - NS) daily for 1, 5 or 14 days. Pleurodesis was graded according to an 8 point scale, with a score of ≥5 considered significant for pleurodesis.
RESULTS: Table 1 describes the mean pleurodesis scores for each dose regimen tested. The lowest concentration of SN (2ml/kg) leading to pleurodesis scores ≥ 5 were 0.425%, 0.085% and 0.050% for the single day, 5 day and 14 day administration protocols respectively. Pleurodesis score was significantly higher in the 14 day versus single day administration group for SN at the 0.05% dose. In the D groups, single day administration of a 10 mg/kg dose achieved a score of 4.5, and only 2.5 at the 5 mg/kg dose. Repeating the 5-mg/kg dose for 5 and 14 days lead to a score of 5 and 7.5 respectively, the latter being statistically significant as compared to the single day 5 mg/kg dose (p=0 .014) as well as 14 day placebo dose (p= 0.005). At the lowest dose tested of 1 mg/kg, neither the 5 day nor 14 day regimen resulted in significant pleurodesis.
CONCLUSION: Repeated administration of low doses of sclerosing agents can lead to effective pleurodesis in this animal model. The dose reduction achieved is especially significant for silver nitrate where a near ten-fold reduction in dose could lead to effective pleurodesis when administered over 14 days.
CLINICAL IMPLICATIONS: Given that toxicity of sclerosing agents used for pleurodesis are dose dependent, administration of lower doses in a repeated fashion may result in effective pleurodesis while minimizing side effects.
DISCLOSURE: Alain Tremblay, None.