Targeting the Effect Site with a Computer Controlled Infusion Pump

  • Steven L. Shafer


Over the last decade computer controlled infusions have been used to rapidly achieve and maintain constant plasma drug concentrations for drugs having pharmacokinetics characterized by polyexponential disposition functions. For most drugs the plasma is not the site of drug effect. Thus, targeting the plasma drug concentration may not be a rational approach to optimal drug therapy. Drawing on previously described effect site models, an algorithm is developed for computer controlled infusion pumps to target the apparent concentration at the site of drug effect, rather than the concentration in the plasma. Simulations are based on the pharmacokinetics and plasma-effect site equilibration delay that have been reported for fentanyl, an intravenous opioid commonly used in anesthetic practice.


Drug Effect Bolus Injection Effect Site Plasma Drug Concentration Target Concentration 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    E. Krüger-Thiemer. Continuous intravenous infusion and multicompartment accumulation. Eur. J. Clin. Pharmacol 4:317–324 (1968).CrossRefGoogle Scholar
  2. 2.
    H. Schwilden. A general method for calculating the dosage scheme in linear pharmacokinetics. Eur. J. Clin. Pharmacol. 20:379–383 (1981).PubMedCrossRefGoogle Scholar
  3. 3.
    J. M. Alvis, J. G. Reves, A. V. Govier, P. G. Menkhaus, C. E. Henling, J. A. Spain, and E. Bradley. Computer-assisted continuous infusions of fentanyl during cardiac anesthesia: comparison with a manual method. Anesthesiology 63:41–49 (1985).PubMedCrossRefGoogle Scholar
  4. 4.
    J. M. Alvis, J. G. Reves, J. A. Spain, and L. C. Sheppard. Computer-assisted continuous infusion of the intravenous analgesic fentanyl during general anesthesia-an interactive system. IEEE T. Bio-med. Eng. 32:323–329 (1985).CrossRefGoogle Scholar
  5. 5.
    M. E. Ausems, D. R. Stanski, and C. C. Hug. An evaluation of the accuracy of pharmacokinetic data for the computer-assisted infusion of alfentanil. Brit. J. Anaesth. 57:1217–1225 (1985).PubMedCrossRefGoogle Scholar
  6. 6.
    S. L. Shafer, J. R. Varvel, N. Aziz, and J. C. Scott. The pharmacokinetics of fentanyl administered by computer-controlled infusion pump. Anesthesiology (in press).Google Scholar
  7. 7.
    D. B. Raemer, A. Buschman, J. R. Varvel, B. K. Philip, M. D. Johnson, D. A. Stein, and S. L. Shafer. The prospective use of population pharmacokinetics in a computer-driven infusion system for alfentanil. Anesthesiology 73:66–72 (1990).PubMedCrossRefGoogle Scholar
  8. 8.
    J. C. Scott, D. R. Stanski, S. Vozehs., R. D. Miller, and J. Ham. Simultaneous modeling of pharmacokinetics and pharmacodynamics: Application to d-tubocurarine. Clin. Pharmacol. Ther. 25:358–371 (1979).Google Scholar
  9. 9.
    L. B. Sheiner, D. R. Stanski, S. Vozeh S., R. D. Miller, and J. Ham. Simultaneous modeling of pharmacokinetics and pharmacodynamics: Application to d-tubocurarine. Clin. Pharmacol. Ther. 25:358–371 (1979).PubMedGoogle Scholar
  10. 10.
    C. J. Hull, H. B. Van Beem, K. McLeod, A. Sibbald, and M. J. Watson. A pharmacodynamic model for pancuronium. Brit. J. Anaesth. 50:1113–1123 (1978).PubMedCrossRefGoogle Scholar
  11. 11.
    J. C. Scott, K. V. Ponganis, and D. R. Stanski. EEG quantitation of narcotic effect: the comparative pharmacodynamics of fentanyl and alfentanil. Anesthesiology 62:234–241 (1985).PubMedCrossRefGoogle Scholar
  12. 12.
    S. L. Shafer, L. C. Siegel, J. E. Cooke, and J. C. Scott. Testing computer-controlled infusion pumps by simulation. Anesthesiology 68:261–266 (1988).PubMedCrossRefGoogle Scholar
  13. 13.
    P. O. Maitre and S. L. Shafer. A simple pocket calculator approach to predict anesthetic drug concentrations from pharmacokinetic data. Anesthesiology 73:332–336 (1990).PubMedCrossRefGoogle Scholar
  14. 14.
    P. S. A. Glass, J. R. Jacobs, L. R. Smith, B. Ginsberg, S. A. Bai, and J. G. Reves. Pharmacokinetic model-driven infusion of fentanyl. Anesthesiology (in press).Google Scholar
  15. 15.
    I. Schewiger, J. Bailey, and C. C. Hug Jr. Anesthetic interactions of computer-controlled and constant rate infusions of fentanyl and midazolam for cardiac surgery. Anesthesiology 71:A305 (1989).CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1991

Authors and Affiliations

  • Steven L. Shafer
    • 1
    • 2
  1. 1.Department of AnesthesiaStanford University School of MedicineUSA
  2. 2.Palo Alto Veterans Administration Medical CenterUSA

Personalised recommendations