Learning objectives
- Describe the effects and underlying mechanisms of bleomycin therapy
- Diagnose bleomycin pulmonary toxicity
- Manage patients who have received bleomycin therapy
Background
- Bleomycin is an antitumor antibiotic often used to treat germ cell tumors and Hodgkin’s disease
- Side-effect: Potential for subacute pulmonary damage that can progress to life-threatening pulmonary fibrosis
- Pulmonary toxicity occurs in 6–10% of patients
- Exposure to high-inspired concentration oxygen therapy, even for short periods, can cause rapidly progressive pulmonary toxicity in patients previously treated with bleomycin
- Lung injury typically develops within 6 months after the start of bleomycin treatment
- The potential for high-inspired fractions of oxygen to provoke pulmonary toxicity remains a life-long risk in these patients
- Symptoms of bleomycin-induced pulmonary toxicity include dry cough, breathlessness, pleuritic chest pain, and fever
Pathophysiology
- Bleomycin oxidatively damages DNA by binding to metal ions such as iron, resulting in reactive oxygen species formation
- Is inactivated by bleomycin hydrolase
- Low concentrations of bleomycin hydrolase in skin and lung tissues contribute to the sensitivity to bleomycin of these tissues
- Contributing factors to bleomycin pulmonary toxicity:
- Inflammatory cell infiltration into pulmonary endothelial cells
- Fibrotic changes with elevated collagen content
- Increased expression of fibrogenic mediators (TGF-beta, connective tissue growth factor, PDGF-C) in endothelial cells
- Decrease in thapsigargin-induced prostaglandin I2 and nitric oxide (vasodilators) in endothelial pneumocytes
Risk factors for pulmonary toxicity
- Advanced age
- Renal insufficiency
- Increased cumulative drug dose
- Severity of underlying malignancy
- FiO2 use
- Concomitant radiation therapy
- Other chemotherapeutic agents
- Smoking
Diagnosis
| Physical examination | Dyspnea |
| Pulmonary crackles | |
| Hypoxemia | |
| Radiology | Linear interstitial shadowing, which can look similar to Kerly B lines seen in pulmonary edema |
| Confluent airspace shadowing, which may be diagnosed as infection if the diagnosis of bleomycin lung injury is not considered |
|
| Pneumothorax and pneumomediastinum are recognized complications in severe bleomycin lung injury |
Management of patients who have received bleomycin
- Acoid oxygen therapy when possible
- Avoid clinical procedures (and leisure activities) involving a high FiO2
- If a patient is hypoxic, O2 therapy should be minimized to maintain O2 saturation of 88–92%
- High oxygen concentrations should be used with extreme caution for immediate life-saving indications only (to maintain O2 saturation of 88–92%)
- Minimize IV fluids to avoid volume overload
Suggested reading
- Groenewold MD, Olthof CG, Bosch DJ. Anaesthesia after neoadjuvant chemotherapy, immunotherapy or radiotherapy. BJA Educ. 2022;22(1):12-19.
- Brandt JP, Gerriets V. Bleomycin. [Updated 2022 Aug 29]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK555895/
- Della Latta V, Cecchettini A, Del Ry S, Morales MA. Bleomycin in the setting of lung fibrosis induction: From biological mechanisms to counteractions. Pharmacological Research. 2015;97:122-30.
- Allan N, Siller C, Breen A. Anaesthetic implications of chemotherapy. Continuing Education in Anaesthesia Critical Care & Pain. 2012;12(2):52-6.
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