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Variability in analgesic responses to intramuscularly administered meperidine has been related to variable and unpredictable blood concentrations after injection. However, the contribution of variability in the relationship between blood concentration and effect has not been examined. The present study was designed to determine the relationship between blood meperidine concentrations and analgesic effects in nine patients during the first two postoperative days. Pain was estimated by subjective bioassay. The blood concentration-effect curves were steep, with a difference of as little as 0.05 microgram/ml between the mean concentrations associated with severe pain and those associated with effective analgesia. Each curve had two inflection points: the maximum concentration still associated with severe pain (MCP) (0.41 microgram/ml, SD = 0.17, n = 76) and the minimum effective analgesic concentration (MEAC) (0.46 microgram/ml, SD = 0.18, n = 19). Interpatient variability of MEAC was appreciable (coefficient of variation = 39 percent) and intrapatient variability was also detected. Variable pain control following intermittent intramuscular injections was shown to be due not only to variation in absorption, as reported previously, but also to variation in the blood meperidine concentration-analgesic response relationships. However, correlations were found between MCP and neuroticism and extroversion scores from a personality inventory and physical variables. Thus, equations that allow prediction of an individual's MCP were derived by multivariable regression. A blood meperidine concentration of 0.7 microgram/ml would be expected to provide freedom from severe pain in approximately 95 per cent of cases. An intravenous infusion regimen for achieving and maintaining this concentration is described.
Austin et al. (1980) studied this question.