Relationship of ventilatory depression to steady-state blood pethidine concentrations

An i.v. infusion regimen was developed to permit rapid attainment of steady-state blood pethidine concentrations (Cpss). In 10 adult volunteers (12 studies) the relationship of pethidine Cpss to the ventilatory effects of the drug were examined. Mean pethidine Cpss ranged from 170 to 320 ng ml-1, with a median Cpss of 480 ng ml-1. Increased end-tidal (PE'CO2) and mixed venous (PVCO2) and decreased slope (delta VI/delta PCO2) and position (ISO-VI) of the carbon dioxide response were all significant (P less than 0.001) for Cpss (1) less than or equal to 480 and (2) greater than 480 ng ml-1. The averaged changes in PE'CO2, PVCO2, delta VI/delta PCO2, and ISO-VI expressed as a per cent of respective control variables, were shown to be linear functions of Cpss. It is concluded that, under conditions of Cpss, significant ventilatory depression occurs at blood pethidine concentrations less than those required for analgesia. The possible significance of these findings in volunteers is discussed in terms of this application to the clinical setting of postoperative pain and its management after general anaesthesia.