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Update 1990 pp 730-738 | Cite as

Pharmacokinetic and Pharmacodynamic Modeling of Sedation in the ICU: Future Perspectives

  • A. F. Ghouri
  • A. K. Mills
  • P. F. White
Conference paper
Part of the Update in Intensive Care and Emergency Medicine book series (UICM, volume 10)

Abstract

In the intensive care unit (ICU) environment sedation is often an integral component of critical care therapy. Patients who are being mechanically ventilated frequently require sedation because the endotracheal tube is extremely irritating and the ICU is an anxiety-provoking environment. In addition to alleviating anxiety, sedation may prevent sleep deprivation [1], a common problem for mechanically ventilated patients. Sleep deprivation may lead to disorientation and agitation (so-called “ICU psychosis”), as well as results in a decreased ventilatory response to hypoxia and hypercapnia [2], both of which may interfere with weaning from ventilatory support [3]. Furthermore, there is anecdotal evidence to suggest that restoration of a normal sleep-wake cycle can improve patient outcome in the ICU, and reduce the need for additional medications [4]. Thus, a sedation technique which would allow patients to rest comfortably (or sleep) may be of benefit in weaning patients from mechanical ventilation. Finally, effective sedation can decrease stress hormone levels in healthy patients and might produce similar effects in ICU patients. Since stress hormones can significantly increase both metabolic rate and protein catabolism, sedation may have the added benefit of decreasing ventilatory requirements.

Keywords

Sleep Deprivation Pharmacokinetic Model Pharmacodynamic Modeling Effect Compartment Emax Model 
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.

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References

  1. 1.
    Aurell J, Elmqvist D (1985) Sleep in the surgical intensive care unit: continuous polygraphic recording of sleep in nine patients receiving postoperative care. Br Med J 290:1029–1032CrossRefGoogle Scholar
  2. 2.
    Ochiai R, Motoyama EK, Winter PM, Walczak SA (1986) Sleep deprivation attenuates ventilatory response to hypoxia. Anesthesiology 65:A491CrossRefGoogle Scholar
  3. 3.
    Ochiai R, Motoyama EK, Winter PM, Walczak SA (1987) Sleep deprivation attenuates hypercapnic ventilator response in man. Anesthesiology 67:A331CrossRefGoogle Scholar
  4. 4.
    Shapiro MD, Westphal LM, White PF, Sladen RN, Rosenthal MH (1986) Midazolam infusion for sedation in the intensive care unit: effect on adrenal function. Anesthesiology 64:394–398PubMedCrossRefGoogle Scholar
  5. 5.
    Merriman HM (1981) The techniques used to sedate ventilated patients. Intensive Care Med 7:217–224PubMedCrossRefGoogle Scholar
  6. 6.
    Dobb GJ, Murphy DF (1985) Sedation and analgesia during intensive care. Clinics in Anesthesia 3:1055–1085Google Scholar
  7. 7.
    Korttila K, Aromaa U (1980) Venous complications after intravenous injection of diazepam, flunitrazepam, thiopentanon, and etomidate. Acta Anaesthesiol Scand 24:227–230PubMedCrossRefGoogle Scholar
  8. 8.
    Greenblatt DJ, Allen MD, Marmatz HS, Shader RI (1980) Diazepam disposition determinants. Clin Pharmacol Ther 27:301–312PubMedCrossRefGoogle Scholar
  9. 9.
    Greenblatt DJ (1987) Simulataneous gas chromatographic analysis for diazepam and its major metabolite, desmethyldiazepam, with use of double internal standardization. Clin Chem 24:1838–1841Google Scholar
  10. 10.
    Edbrooke DL, Newby DM, Mather SJ, Sixon AM, Hebron BS (1982) Safer sedation for ventilated patients - a new application for etomidate. Anaesthesia 37:765–771PubMedCrossRefGoogle Scholar
  11. 11.
    Bird TM, Edbrooke DL, Newby DM, Hebron BS (1984) Intravenous sedation for the intubated and spontaneously breathing patient in the intensive care unit. Acta Anaesthesiol Scan 28:640–643CrossRefGoogle Scholar
  12. 12.
    Ledingham IM, Watt I (1983) Influence of sedation of mortality in critically ill, multiple trauma patients. Lancet 1:1270PubMedCrossRefGoogle Scholar
  13. 13.
    Wagner RL, White PF, Kan PB, Rosenthal MH, Feldman D (1984) Inhibition of adrenal steroidogenesis by the anesthetic etomidate. N Engl J Med 310:1415–1421PubMedCrossRefGoogle Scholar
  14. 14.
    Greenblatt DJ, Locniskar A, Ochus HR, Lauven PM (1981) Automated gas chromatography for studies of midazolam pharmacokinetics. Anesthesiology 55:176–179PubMedCrossRefGoogle Scholar
  15. 15.
    White PF, Vasconez LO et al. (1988) Comparison of midazolam and diazepam for sedation during plastic surgery. J Plastic Recon Surg vol 81, 5:703–709CrossRefGoogle Scholar
  16. 16.
    Smith MT, Eadie MJ, Brophy TO (1981) The pharmacokinetics of midazolam in man. Eur J Clin Pharmacol 10:271–278CrossRefGoogle Scholar
  17. 17.
    Allonen H, Ziegler G, Klotz U (1981) Midazolam kinetics. Clin Pharmacol Ther 30:653–661PubMedCrossRefGoogle Scholar
  18. 18.
    Heizmann P, Eckert M, Ziegler WH (1983) Pharmacokinetics and bioavailability of midazolam in man. Br J Clin Pharmacol 16:43s-49sPubMedGoogle Scholar
  19. 19.
    Greenblatt DJ, Arendt RM, Abernathy OR, Giles GH, Sellers EM, Shader RI (1983) In vitro quantitation of benzodiazepine lipophilicity: relation to in vivo distribution. Br J Anaesth 55:985–989PubMedCrossRefGoogle Scholar
  20. 20.
    Westphal LM, Cheng E, White PF, Sladen RN, Rosenthal MH (1987) Use of midazolam infusion for sedation following cardiac surgery. Anesthesiology 66:223–226CrossRefGoogle Scholar
  21. 21.
    White PF (1983) Use of continuous infusion versus intermittent bolus administration of fentanyl or ketamine during outpatient anesthesia. Anesthesiology 59:294–300PubMedCrossRefGoogle Scholar
  22. 22.
    White PF (1989) Clinical uses of intravenous anesthesic and analgesic infusions. Anaesth Analg 68:161–171CrossRefGoogle Scholar
  23. 23.
    Holford NH, Sheiner LB (1981) Understanding the dose-effect relationship: clinical application of pharmacokinetic-pharmacodynamic models. Clin Pharm 6:429–453CrossRefGoogle Scholar
  24. 24.
    Holford NH, Sheiner LBL (1982) Kinetics of the pharmacological response. Pharm Ther 23:2–24Google Scholar
  25. 25.
    Koopmans R, Dingemanse J, Danhof M, Horsten GPM, van Boxtel CJ (1988) Pharmacokinetic and pharmacodynamic modeling of midazolam effects on the human central nervous system. Clin Pharmacol Ther 44:14–22PubMedCrossRefGoogle Scholar
  26. 26.
    Kroboth PD, Smith RB, Erb RJ (1983) Tolerance to alprazolam after intravenous bolus and continuous infusion: psychomotor and EEG effects. Clin Pharmacol Ther 43:270–277CrossRefGoogle Scholar
  27. 27.
    Hudson RJ, Stanski DR, Saidman LJ, Meathe E (1983) A model for studying depth of anesthesia and acute tolerance to thiopental. Anesthesiology 59:301–308PubMedCrossRefGoogle Scholar
  28. 28.
    Schwilden H (1981) A general method for calculating the dosage scheme in linear pharmacokinetics. Eur J Clin Pharmacol 20:379–386PubMedCrossRefGoogle Scholar
  29. 29.
    Schwilden H, Schuttler J, Stoeckel H (1983) Pharmacokinetics as applied to total intravenous anesthesia. Anaesthesia 38:51–56PubMedCrossRefGoogle Scholar
  30. 30.
    Alvis JM, Reves JG, Govier AV, et al (1985) Computer-assisted continous infusions of fentanyl during cardiac anesthesia - comparison with a manual method. Anesthesiology 63:41–49PubMedCrossRefGoogle Scholar
  31. 31.
    Glass P, Jacobs J, Alvis M, Bai S, Reves JG (1987) Computer-assisted continous infusion of alfentanil during noncardiac anesthesia - a comparison with a manual method. Anesthesiology 65: A546Google Scholar
  32. 32.
    Mills AK, Ghouri AF, Monk TG, White PF (1990) Lack of correlation between electroen-cephalographic and hemodynamic changes during general anesthesia. Anesth Analg (in press)Google Scholar
  33. 33.
    White PF, Boyle WA (1989) Relationship between hemodynamic and electroencephalographic changes during general anesthesia. Anesth Analg 68:177–181PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1990

Authors and Affiliations

  • A. F. Ghouri
  • A. K. Mills
  • P. F. White

There are no affiliations available

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