60 units of bleomycin are dissolved in 50 to 100 mL Sodium Chloride for Injection, %, USP and administered through a thoracostomy tube following drainage of excess pleural fluid and confirmation of complete lung expansion. The literature suggests that successful pleurodesis is, in part, dependent upon complete drainage of the pleural fluid and reestablishment of negative intrapleural pressure prior to instillation of a sclerosing agent. Therefore, the amount of drainage from the chest tube should be as minimal as possible prior to instillation of bleomycin. Although there is no conclusive evidence to support this contention, it is generally accepted that chest tube drainage should be less than 100 mL in a 24-hour period prior to sclerosis. However, bleomycin instillation may be appropriate when drainage is between 100 to 300 mL under clinical conditions that necessitate sclerosis therapy. The thoracostomy tube is clamped after bleomycin instillation. The patient is moved from the supine to the left and right lateral positions several times during the next four hours. The clamp is then removed and suction reestablished. The amount of time the chest tube remains in place following sclerosis is dictated by the clinical situation.
The antineoplastic effect of bleomycin is unique among anticancer agents, and is thought to involve the production of single- and double-strand breaks in DNA (scission) by a complex of bleomycin, ferrous ions, and molecular oxygen [ 2,6,7 ]. Bleomycin binds to DNA by intercalation of the bithiazole moiety between base pairs of DNA and by electrostatic interactions of the terminal amines. The reduction of molecular oxygen by ferrous ions chelated by bleomycin leads to hydrogen subtraction from the C3 and C4 carbons of deoxyribose, resulting in cleavage of the C3-C4 bond and liberation of a base with a DNA strand break [ 6 ]. Bleomycin is inactivated in vivo by the enzyme bleomycin hydrolase, a cytosolic aminopeptidase that has lower activity in the skin and lungs.
Bleomycin induces the generation of reactive oxygen radicals by forming a complex with . Consistent with a direct pathologic role for this mechanism, iron chelators ameliorate the pulmonary toxicity of bleomycin in animal models [ 14 ]. Reactive oxygen species can produce direct toxicity through participation in redox reactions and subsequent fatty acid oxidation, which leads to membrane instability. Oxidants can cause inflammatory reactions within the lung. For example, the oxidation of arachidonic acid is the initial step in the metabolic cascade that produces active mediators including prostaglandins and leukotrienes. Cytokines such as interleukin-1, macrophage inflammatory protein-1, platelet-derived growth factor (PDGF), and transforming growth factor (TGF)- are released from alveolar macrophages in animal models of bleomycin toxicity, resulting in fibrosis [ 15 ]. Damage and activation of alveolar epithelial cells may result in the release of cytokines and growth factors that stimulate proliferation of myofibroblasts and secretion of a pathologic extracellular matrix, leading to fibrosis.