VENTILATORY EFFECTS AND PLASMA CONCENTRATION OF MORPHINE IN MAN

Abstract

The relationship between the plasma concentration of morphine and morphine-induced changes in ventilation and the ventilatory response to carbon dioxide was studied in 17 healthy adults undergoing elective surgery under general anaesthesia. Each subject was given morphine sulphate 0.15 mg kg⁻¹ i.m.; ventilation ($V˙$E), end-tidal Pco₂(PE′_CO2), mixed venous PV_CO2(P$V&macr;$_CO2) and ventilatory response to carbon dioxide (Δ$V˙$E/ΔP_CO2) were measured before and within 90 min after injection. Mixed venous P_CO2 and Δ$V˙$E/ΔP_CO2 were measured by standard rebreathing methods; plasma morphine concentration was measured by radioimmunoassay. Maximum plasma morphine ranged from 30 to 120 ng ml⁻¹, between 4 and 60 min after injection. There was a significant increase in mixed venous PE′_CO2 (P<0.001), and PE′_CO2 (P<0.01) after morphine while $V˙$E decreased insignificantly. Morphine displaced the carbon dioxide response curve to the right (P<0.01) and Δ$V˙$E/ΔP_CO2 decreased from 12.3 to 10.0 litre min⁻¹ kPa⁻¹ (P<0.05). The magnitude of changes in $V˙$E and Δ$V˙$E/ΔP_CO2 were not related to the peak plasma concentration of morphine or to the mean concentration immediately before and after the carbon dioxide response measurement. Plasma concentrations of morphine, under the conditions of the present study, are not an objective indicator of pharmacological activity between one patient and another.