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BACKGROUND: Current British Thoracic Society guidelines do not recommend routinely the combined use of a benzodiazepine and opiate during flexible bronchoscopy (FB). A randomised, placebo controlled, double blind study was undertaken to determine whether hydrocodone in combination with midazolan improves cough suppression during FB without increasing the risk of desaturation. METHODS: 120 patients were randomised to receive midazolam and 5 mg i.v. hydrocodone or midazolam and placebo with topical anaesthesia. Pulse oximetry was recorded continuously during FB. Bronchoscopists and nurses charted their perception of cough and the patients rated their discomfort during the procedure on a 10 cm visual analogue scale (VAS). RESULTS: There was no significant difference between the two groups with regard to the indication for FB, duration of procedure (21 (11) min v 22 (10) min, p = 0.570), doses of supplemental lignocaine (171 (60) mg v 173 (66) mg, p = 0.766) and midazolam (4.5 (2.3) mg v 4.9 (2.7) mg, p = 0.309), lowest oxygen saturation (94.8 (2.7) v 94.9 (2.7), p = 0.433), and desaturations < or =90%. Perception of cough by both the bronchoscopist and the nurse was significantly lower in the hydrocodone group (3 (0-10) and 3 (0-10)) than in the placebo group (6 (0-10) and 6 (0-10)), respectively (p = 0.001). According to the VAS scale, patients' tolerance was also significantly better with hydrocodone than with placebo (2 (0-8) v 3 (0-9), p = 0.043). CONCLUSION: The combination of midazolam and hydrocodone markedly reduces cough during FB without causing significant desaturation, especially when invasive diagnostic procedures are performed.