| Summary: | Abstract Intrapleural tissue plasminogen activator (tPA) and deoxyribonuclease (DNase) therapy is a new treatment for pleural infection. Clinical experiences of tPA/DNase therapy, and its complications, are cumulating. We present a patient with multiloculated empyema but no initial evidence of a bronchopleural fistula. She was treated with antibiotics and chest tube drainage of the basal collection through which four doses of tPA/DNase were delivered with success. The lateral collection worsened necessitating separate tube drainage and tPA/DNase treatment. She reported chest “fullness” when instilled the second dose. The third instillation of tPA triggered immediate vigorous coughing and expectoration of salty‐tasting fluid, likely the tPA/saline solution. The symptoms spontaneously settled after 15 min, with no evidence of air leak. The loculated fluid was successfully evacuated. The patient made a full recovery after an antibiotic course with no long‐term consequences. Pulmonary migration of drugs via a bronchopleural communication, although rare, can occur with intrapleural tPA/DNase therapy.
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