A computer-based system for controlling plasma opioid concentration according to patient need for analgesia

Microprocessor-controlled infusion pumps, which allow a patient to self-administer bolus doses of an analgesic to relieve pain, are becoming commonplace. While these patient-controlled analgesia (PCA) systems overcome the large interpatient variations in pharmacokinetics, they do not provide steady relief from pain since they rely on delivering a drug in small, incremental doses. To overcome this problem, the authors developed an algorithm and computer-pump system that allows patients to control their own plasma concentration of analgesic. This approach uses individually predetermined pharmacokinetic parameters to provide steady plasma opioid concentrations that can be increased or decreased by the patient in line with the need for more pain relief or fewer side effects. The control software uses a novel, recursive algorithm to compute the pump rates necessary to maintain constant plasma drug (e.g. morphine) concentrations at desired values and to reach a new steady concentration in response to patient requests. This report describes the mathematical approach to the problem of control of plasma opioid concentration, the application of this new drug delivery system to management of persistent pain in cancer patients undergoing bone marrow transplantation, and the magnitude of pharmacokinetic variability with morphine in this patient population. Results are presented from individual patients using this adjustable drug delivery system continuously for up to 2 weeks to control pain from oral mucositis.