Relationship between plasma morphine concentrations and pharmacologic effects in postoperative patients using patient-controlled analgesia.

In postoperative patients using patient-controlled analgesia (PCA) to administer i.v. doses of morphine sulfate, respiratory rates and subjective rankings of pain, sedation, and liking for the drug were correlated with plasma morphine concentrations. In 12 patients selected before surgery, the initial morphine sulfate dose of 0.6 mg/sq m was increased or decreased as needed. Every two hours, cumulative morphine sulfate dose, respiratory rate, and sedation were recorded by the nurse, along with the patient's evaluation of pain and liking for the drug. Plasma was collected in the morning and evening during PCA therapy for morphine analysis. Data were analyzed by analysis of covariance. Dosing rates and rankings of pain, sedation, and liking decreased as a function of time postoperatively, but respiratory rates did not. Sedation and respiratory rates were independent of morphine concentration. Liking of the drug increased directly with plasma morphine concentration but decreased with time. A high level of pain was directly related to morphine use. For all significant relationships, there was high interpatient variability, with the exception of changes in pain rankings induced by morphine. Patients defined a minimum effective plasma morphine concentration of 20-40 ng/mL. The maximum plasma morphine concentration achieved by self-administration was 82 ng/mL. These postoperative patients used patient-controlled analgesia to deliver morphine sulfate i.v. for pain relief, not for euphoria, and did not exhibit sedation or respiratory depression. Morphine was consistently effective at plasma concentrations of 40 ng/mL or greater.