Bleomycin + Oxygen - Drug Interactions

Five patients treated with bleomycin,exposed to oxygen concentrations of 35 to 42 % during and immediately following anaesthesia, developed a severe respiratory distress syndrome and died. Bleomycin-induced pneumonitis and lung fibrosis were diagnosed at post-mortem. Another group of 12 matched patients who underwent same procedures but with lower oxygen concentrations (22 to 25%) had an uneventful postoperative course (See reference number 1).

Another comparative study(See reference number 2) similarly demonstrated that adult respiratory distress syndrome (ARDS) in patients receiving bleomycin was reduced by a technique allowing use of lower oxygen concentrations of 22 to 30%. Bleomycin-induced pulmonary toxicity,apparently related to oxygen concentrations, has also been described in other case reports (See reference number 3-7). Studies in animals have also confirmed that severity of bleomycin-induced pulmonary toxicity is increased by oxygen (See reference number 8-10). However, in two other series of patients treated with bleomycin and undergoing surgery there was no obvious increase in pulmonary complications despite use of usual concentrations of oxygen (See reference number 11,12).

Not understood. One suggestion is that bleomycin-injured lung tissue is less able to scavenge free oxygen radicals,which may be present, and damage occurs as a result (See reference number 3).

An established,well-documented, serious and potentially fatal interaction. It is advised that any patient receiving bleomycin and undergoing general anaesthesia should have their inspired oxygen concentrations limited to less than 30%, and fluid replacement should be carefully monitored to minimise crystalloid load. This is clearly very effective because one author has treated 700 patients following these guidelines without a single case of pulmonary failure (See reference number 13). It has also been suggested that reduced oxygen levels should be continued during recovery period and at any time during hospitalisation (See reference number 3). If an oxygen concentration equal to or greater than 30 % has to be used, short-term use of prophylactic corticosteroids should be considered. Intravenous corticosteroids should be given at once if bleomycin toxicity is suspected (See reference number 3).

Goldiner PL,Carlon GC, Cvitkovic E, Schweizer O, Howland WS. Factors influencing postoperative morbidity and mortality in patients treated with bleomycin. BMJ (1978) 1, 1664–7.

El-Baz N,Ivankovich AD, Faber LP, Logas WG. The incidence of bleomycin lung toxicityafter anesthesia for pulmonary resection: a comparison between HFV and IPPV. Anesthesiology (1984) 61, A107.

Gilson AJ,Sahn SA. Reactivation of bleomycin lung toxicity following oxygen administration. A second response to corticosteroids. Chest (1985) 88, 304–6.

Cersosimo RJ,Matthews SJ, Hong WK. Bleomycin pneumonitis potentiated by oxygen administration. Drug Intell Clin Pharm (1985) 19, 921–3.

Hulbert JC,Grossman JE, Cummings KB. Risk factors of anesthesia and surgery in bleomycin-treated patients. J Urol (Baltimore) (1983) 130, 163–4.

Donohue JP,Rowland RG. Complications of retroperitoneal lymph node dissection. J Urol (Baltimore) (1981) 125, 338–40.

Ingrassia TS,Ryu JH, Trastek VF, Rosenow EC. Oxygen-exacerbated bleomycin pulmonarytoxicity. Mayo Clin Proc (1991) 66, 173–8.

Toledo CH,Ross WE, Hood I, Block ER. Potentiation of bleomycin toxicity by oxygen. Cancer Treat Rep (1982) 66, 359–62.

Berend N. The effect of bleomycin and oxygen on rat lung. Pathology (1984) 16,136–9.

Rinaldo J,Goldstein RH, Snider GL. Modification of oxygen toxicity after lung injury by bleomycin in hamsters. Am Rev Respir Dis (1982) 126, 1030–3.

Douglas MJ,Coppin CML. Bleomycin and subsequent anesthesia: a retrospective study atVancouver General Hospital. Can Anaesth Soc J (1980) 27, 449–52.

Mandelbaum I,Williams SD, Einhorn LH. Aggressive surgical management of testicular carcinoma metastatic to lungs and mediastinum. Ann Thorac Surg (1980) 30, 224–9.

Goldiner PL. Editorial comment. J Urol (Baltimore) (1983) 130,164.