f specificity of the clinical syndrome, the identification of patients with pulmonary toxicity due to Bleomycin has been extremely difficult. The earliest symptom associated with Bleomycin pulmonary toxicity is dyspnea. The earliest sign is fine rales.
Radiographically, Bleomycin-induced pneumonitis produces nonspecific patchy opacities, usually of the lower lung fields. The most common changes in pulmonary function tests are a decrease in total lung volume and a decrease in vital capacity. However, these changes are not predictive of the development of pulmonary fibrosis.
The microscopic tissue changes due to Bleomycin toxicity include bronchiolar squamous metaplasia, reactive macrophages, atypical alveolar epithelial cells, fibrinous edema, and interstitial fibrosis. The acute stage may involve capillary changes and subsequent fibrinous exudation into alveoli producing a change similar to hyaline membrane formation and progressing to a diffuse interstitial fibrosis resembling the Hamman-Rich syndrome. These microscopic findings are nonspecific; e.g., similar changes are seen in radiation pneumonitis and pneumocystic pneumonitis.
To monitor the onset of pulmonary toxicity, roentgenograms of the chest should be taken every 1 to 2 weeks (see WARNINGS). If pulmonary changes are noted, treatment should be discontinued until it can be determined if they are drug related. Recent studies have suggested that sequential measurement of the pulmonary diffusion capacity for carbon monoxide (DLCO) during treatment with Bleomycin may be an indicator of subclinical pulmonary toxicity. It is recommended that the DLCO be monitored monthly if it is to be employed to detect pulmonary toxicities, and thus the drug should be discontinued when the DLCO falls below 30% to 35% of the pretreatment value.
Because of Bleomycin's sensitization of lung tissue, patients who have received Bleomycin are at greater risk of developing pulmonary toxicity when oxygen is administered in surgery. While long exposure to very high oxygen concentrations is a known cause of lung damage, after Bleomycin administration, lung damage can occur at lower concentrations that are usually considered safe. Suggested preventive measures are:
Maintain FlO2 at concentrations approximating that of room air (25%) during surgery and the postoperative period.
Monitor carefully fluid replacement, focusing more on colloid administration rather than crystalloid.
Sudden onset of an acute chest pain syndrome suggestive of pleuropericarditis has been reported during Bleomycin infusions. Although each patient must be individually eva luated, further courses of Bleomycin do not appear to be contraindicated.
Pulmonary adverse events which may be related to the intrapleural administration of Bleomycin have been reported.
Idiosyncratic Reactions
In approximately 1% of the lymphoma patients treated with Bleomycin, an idiosyncratic reaction, similar to anaphylaxis clinically, has been reported. The reaction may be immediate or delayed for several hours, and usually occurs after the first or second dose (see WARNINGS). It consists of hypotension, mental confusion, fever, chills, and wheezing. Treatment is symptomatic including volume expansion, pressor agents, antihistamines, and corticosteroids.
Integument and Mucous Membranes
These adverse reactions have been reported in approximately 50% of treated patients. They consist of erythema, rash, striae, v |
