Codeine in Analgesic Doses Does not Depress Respiration in Patients with Severe Chronic Obstructive Lung Disease

Nineteen normocapnic patients with chronic obstructive lung disease participated in an open single dose safety study (part one) followed by a randomized double‐blind cross‐over study comparing two seven‐days treatment periods of 1 g of paracetamol t.i.d. with 60 mg of codeine plus 1 g of paracetamol t.i.d., respectively (part two). In part one, continuous monitoring after a single dose of 2 g of paracetamol and 120 mg of codeine revealed no deterioration in the respiration and gas tensions. In part two, respiratory parameters and arterial gas tensions were recorded one hour after the last morning dose. PaCO₂ increased insignificantly (0.05<P<0.10) by a median of 0.38 kPa during treatment with codeine and paracetamol compared to treatment with paracetamol alone. PaO₂ decreased by 0.12 kPa (P>0.10). There was no correlation between changes in PaCO₂ and changes in PaO₂. FVC, FEV₁ and dyspnoe at rest were unchanged. Gastrointestinal side effects were reported significantly (P < 0.02) more often during treatment with codeine plus paracetamol. There was no correlation between the plasma concentration of codeine or morphine and changes in respiratory parameters or adverse effects. The limitation for the short time clinical use of codeine as an analgesic to normocapnic patients with severe chronic obstructive lung disease in stable phase seem to be gastrointestinal side effects. 1990 Nordic Pharmacological Society