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Potential pitfalls of propofol target controlled infusion delivery related to its pharmacokinetics and pharmacodynamics

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Abstract

Target controlled infusion (TCI) devices are increasingly used in clinical practice. These devices unquestionably aid optimization of drug dosage. However, it still remains to be determined if they sufficiently address differences in pharmacological make up of individual patients. The algorithms guiding TCI pumps are based on pharmacological data obtained from a relatively small number of healthy volunteers, which are then extrapolated, on the basis of sophisticated pharmacokinetic and pharmacodynamic modeling, to predict plasma concentrations of the drug and its effect on general population. One has to realize the limitation of this approach: these models may be less accurate when applied to patients in extreme clinical conditions: in intensive care units, with a considerable loss of blood, severe hypothermia or temporary changes in the composition of plasma, e.g., hypoalbuminemia. In the future, data obtained under these “extreme” clinical circumstances, may be used to modify the dosage algorithms of propofol TCI systems to match the clinical scenario.

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References

  1. Absalom A, Amutike D, Lal A, White M, Kenny GNC: Accuracy of the “Peadfusor” in children undergoing cardiac surgery or catherization. Br J Anaesth, 2005, 91, 507–513.

    Article  Google Scholar 

  2. Absalom A, Kenny G: ‘Paedfusor’ pharmacokinetic data set. Br J Anaesth, 2005, 95, 110–113.

    Article  CAS  PubMed  Google Scholar 

  3. Absalom AR, Mani V, Smet TD, Struys MMRF: Phar-macokinetic models for propofol - defining and illuminating the devil in the detail. Br J Anaesth, 2009, 103, 26–37.

    Article  CAS  PubMed  Google Scholar 

  4. Albanese J, Martin C, Lacarelle B, Saux P, Durand A, Gouin F: Pharmacokinetics of long-term propofol infusion used for sedation in ICU patients. Anesthesiology, 1990, 73, 214–217.

    Article  CAS  PubMed  Google Scholar 

  5. Allegaert K, de Hoon J, Verbesselt R, Naulaers G, Murat I: Maturational pharmacokinetics of single intravenous dose of propofol. Paediatr Anesth, 2007, 17, 1028–1034.

    Article  Google Scholar 

  6. Avidan MS, Zhang L, Burnshide BA, Finkel KJ, Searleman AC, Selvidge JA, Saager L et al.: Anesthesia awareness and the bispectral index. NEJM, 2008, 358, 1097–1108.

    Article  CAS  PubMed  Google Scholar 

  7. Banach M, Gurdziel E, Jêdrych M, Borowicz KK: Mela-tonin in experimental seizures and epilepsy. Pharmacol Rep, 2011, 63, 1–11.

    Article  CAS  PubMed  Google Scholar 

  8. Baerdemaeker L, Mortier E, Struys M: Pharmacokinetics in obese patients. Br J Anaesth - Contin Educ Anaesth Crit Care Pain, 2004, 4, 152–155.

    Article  Google Scholar 

  9. Bienert A, Kusza K, Wawrzyniak K, Grześkowiak E, Kokot ZJ, Matysiak J, Grabowski T et al.: Assessing cir-cadian rhythms in propofol PK and PD during prolonged infusion in ICU patients. J Pharmacokin Pharmacodyn, 2010, 37, 289–304.

    Article  CAS  Google Scholar 

  10. Bienert A, Płotek W, Zawidzka I, Ratajczak N, Szczêsny D, Wiczling P, Kokot ZJ et al.: Influence of time of day on propofol pharmacokinetics and pharmacodynamics in rabbits. Chronobiol Int, 2011, 28, 318–329.

    Article  CAS  PubMed  Google Scholar 

  11. Bienert A, Wiczling P, Żaba Cz, Żaba Z, Wolc A, Marciniak R, Grześkowiak E, Kusza K.: The influence of demographic factors, basic blood test parameters and opioid type on propofol pharmacokinetics and pharma-codynamics in ASA I - III patients. Arzneimittel-Forsch, 2011, 61, 545–552.

    CAS  Google Scholar 

  12. Björnsson MA, Norberg A, Kalman S, Karlsson MO, Simonsson US: A two-compartment effect site model describes the bispectral index after different rates of propofol infusion. J Pharmacokin Pharmacodyn, 2010, 37, 243–255.

    Article  CAS  Google Scholar 

  13. Bruhn J, Myles PS, Sneyd R, Struys MMRF: Depth of anesthesia monitoring: what’s available, what’s validated and what’s next? Br J Anaesth, 2006, 97, 85–94.

    Article  CAS  PubMed  Google Scholar 

  14. Challet E, Gourmelen S, Pevet P, Oberling P, Pain L: Reciprocal relationship between general (propofol) anesthesia and circadian time in rats. Neuropsychopharmacol-ogy, 2007, 32, 728–735.

    Article  CAS  Google Scholar 

  15. Cohen IT, Finkel JC, Hannallah RS, Hummer KA, Patel KM: Rapid emergence does not explain agitation following sevoflurane anesthesia in infants and children: a comparison with propofol. Paediatr Anaesth, 2003, 13, 63–67.

    Article  PubMed  Google Scholar 

  16. Constant I, Rigouzzo A: Which model for propofol TCI in children? Paediatr Anaesth, 2010, 20, 233–239.

    Article  PubMed  Google Scholar 

  17. Cortinez LI, Anderson BJ, Penna A, Olivares L, Munoz HR, Holford NH, Struys MM, Sepulveda P: Influence of obesity on propofol pharmacokinetics: derivation of a pharmacokinetics model. Br J Anaesth, 2010, 105, 448–456.

    Article  CAS  PubMed  Google Scholar 

  18. Dawidowicz AL, Kalitynski R, Kobielski M, Pieniadz J: Influence of propofol concentration in human plasma on free fraction of the drug; Chem Biol Interact, 2006, 159, 149–155.

    Article  CAS  PubMed  Google Scholar 

  19. Farag E, Chelune GJ, Schubert A, Mascha EJ: Is depth of anesthesia, as assessed by the bispectral index, related to postoperative cognitive dysfunction and recovery? Anesth Analg, 2006, 103, 633–640.

    Article  PubMed  Google Scholar 

  20. Frenkel C, Schuttler J, Ihmsen H, Heye H, Rommelsheim K: Pharmacokinetics and pharmacodynamics of propo-fol/alfentanil infusions for sedation in ICU patients. Intensive Care Med, 1995, 21, 981–988.

    Article  CAS  PubMed  Google Scholar 

  21. de la Fuente L, Lukas JC, Vazquez JA, Jauregizar N, Calvo R, Suarez E: “In vitro” binding of propofol to serum lipoproteins in thyroid dysfunction. Eur J Clin Pharmacol, 2002, 58, 615–619.

    Article  PubMed  CAS  Google Scholar 

  22. Gabrielsson J, Weiner D: Pharmacokinetics & Pharma-codynamics. Data Analysis: Concepts and Applications. 4th edn., Swedish Pharmaceutical Press, Stockholm, 2006.

    Google Scholar 

  23. Glass PSA. Intravenous Anesthesia: Concepts and practice. https://doi.org/cucrash.com/Handouts04/TIVAGlass.pdf, 20.05.2011.

    Google Scholar 

  24. Hiraoka H, Yamamoto K, Okano N, Morita T, Goto F, Horiuchi R: Changes in drug plasma concentrations of an extensively bound and highly extracted drug, propofol, in response to altered plasma binding. Clin Pharmacol Ther, 2004, 75, 324–330.

    Article  CAS  PubMed  Google Scholar 

  25. Hoymork SC, Raeder J, Grimsmo B, Steen PA: Bispectral index, predicted and measured drug levels of target-controlled infusions of remifentanil and propofol during laparoscopic cholecystectomy and emergence. Acta An-aesthesiol Scand, 2000, 44, 1138–1144.

    Article  CAS  Google Scholar 

  26. Hoymork SC, Raeder J, Grimsmo B, Steen PA: Bispectral index, serum drug concentrations and emergence associated with individually adjusted target-controlled infusions of remifentanil and propofol for laparoscopic surgery. Br J Anaesth, 2003, 91, 773–780.

    Article  CAS  PubMed  Google Scholar 

  27. Jannicke MO, Staender S, Whitaker DK, Smith AF: The Helsinki Declaration on Patient Safety in Anaesthe-siology. Eur J Anaesthesiol, 2010, 27, 592–597.

    Article  Google Scholar 

  28. Kataria BK, Ved SA, Nicodemus HF, Hoy GR, Lea D, Dubois MY, Maderna JW, Shafer SL: The pharmacoki-netics of propofol in children using three different data analysis approaches. Anesthesiology, 1994, 80, 104–22.

    Article  CAS  PubMed  Google Scholar 

  29. Knibbe CA, Zuideveld KP, DeJongh J, Kuks PF, Aarts LP, Danhof M: Population pharmacokinetic and pharma-codynamic modeling of propofol for longterm sedation in critically ill patients: a comparison between propofol 6% and propofol 1%. Clin Pharmacol Ther, 2002, 72, 670–684.

    Article  CAS  PubMed  Google Scholar 

  30. Johnson KB, Egan TD, Kern SE, White JL, Mc James SW, Syroid R, Whiddon D, Church T: The Influence of hemorrhagic shock on propofol a pharmacokinetic and pharmacodynamic analysis. Anesthesiology, 2003, 99, 409–420.

    Article  CAS  PubMed  Google Scholar 

  31. Kusza K, Zeev Goldik: How to adopt the European Diploma in Anaesthesiology as the National Board examination in anaesthesiology and intensive therapy - from euro ( ) to EDA I - three-year experience in Poland. Anaesthesiology Intensive Therapy, 2011, XLIII, 1, 6–8.

    Google Scholar 

  32. Laquay N, Prieur S, Greff B, Meyer P, Orliaguet G: Pro-pofol infusion syndrome. Ann Fr Anesth Reanim, 2010, 29, 377–86.

    Article  CAS  PubMed  Google Scholar 

  33. Mani V, Morton NS: Overview of total intravenous anesthesia in children. Paediatr Anaesth, 2010, 20, 211–222.

    Article  PubMed  Google Scholar 

  34. Marsh B, White M, Morton N, Kenny GN: Pharmacoki-netic model driven infusion of propofol in children. Br J Anaesth, 1991, 67, 41–48.

    Article  CAS  PubMed  Google Scholar 

  35. Mazoit JX, Samii K: Binding of propofol to blood components: implications for pharmacokinetics and pharma-codynamics. Br J Clin Pharmacol, 1999, 47, 35–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. McFarlan CS, Anderson BJ, Short TG: The use of propo-fol infusions in paediatric anesthesia: a practical guide. Paediatr Anaesth, 1999, 9, 209–216.

    CAS  PubMed  Google Scholar 

  37. McKeage K, Perry C M: Propofol. A review of its use in intensive care sedation of adults. CNS Drugs. 2003, 17, 235–272.

    Article  CAS  PubMed  Google Scholar 

  38. Mertens MJ, Olofsen E, Burm AG, Bovill JG, Vuyk J: Mixed effect modeling of the influence of alfentanil on propofol pharmacokinetics. Anesthesiology. 2004, 100, 795–805.

    Article  CAS  PubMed  Google Scholar 

  39. Minto CF, Schnider TW: Contributions of PK/PD modeling to intravenous anesthesia. Clin Pharmacol Ther, 2008, 84, 27–38.

    Article  CAS  PubMed  Google Scholar 

  40. Monk TG, Saini V, Weldon BC, Sigl JC: Anesthetic management and one-year mortality after non-cardiac surgery. Anesth Analg, 2005, 100, 4–10.

    Article  PubMed  Google Scholar 

  41. Murat I, Billard V, Vernois J, Zaouter M, Marsol P, Souron R, Farinotti R: Pharmacokinetics of propofol after a single dose in children aged 1–3 years with minor burns. Comparison of three data analysis approaches. Anesthesiology, 1996, 84, 526–532.

    CAS  PubMed  Google Scholar 

  42. De Paepe P, Belpaire FM, Rosseel MT, Van Hoey G, Boon PA, Buylaert WA: Influence of hypovolemia on the pharmacokinetics and the electroencephalographic effect of propofol in the rat. Anesthesiology, 2000, 93, 1482–1490.

    Article  PubMed  Google Scholar 

  43. Paul T, Lemmer B: Disturbance of circadian rhythms in analgosedated intensive care unit patients with and without craniocerebral injury. Chronobiol Int, 2007, 24, 45–61.

    Article  CAS  PubMed  Google Scholar 

  44. Peeters MY, Aarts LP, Boom FA, Bras LJ, Tibboel D, Danhof M, Knibbe CA: Pilot study on the influence of liver blood flow and cardiac output on the clearance of in critically ill patients. Eur J Clin Pharmacol, 2008, 64, 329–334.

    Article  CAS  PubMed  Google Scholar 

  45. Peeters MYM, Bras LJ, De Jongh J: Disease severity is a major determinant for the pharmacodynamics of propofol in critically ill patients. Clin Pharmacol Ther, 2008, 83, 443–451.

    Article  CAS  PubMed  Google Scholar 

  46. Perneger TV: The Swiss cheese model of safety incidents: are there holes in the metaphor? BMC Health Serv Res, 2005, 9, 5–71.

    Google Scholar 

  47. Practice Advisory for Intraoperative Awareness and Brain Function Monitoring. A Report by the American Society of Anesthesiologists Task Force on Intraopera-tive Awareness. Anesthesiology, 2006, 104, 847–864.

    Article  Google Scholar 

  48. Restrepo JG, Garcia-Martin E, Martinez C, Agundez JA: Polymorphic drug metabolism in anaesthesia. Curr Drug Metab, 2009, 10, 236–246.

    Article  CAS  PubMed  Google Scholar 

  49. Rigouzzo A, Servin F, Constant I: Pharmacokinetic-pharmacodynamic modeling of propofol in children. Anesthesiology, 2010, 113, 343–352.

    Article  CAS  PubMed  Google Scholar 

  50. Roberts FL, Dixon J, Lewis GT, Tackley RM, Prys-Roberts C: Induction and maintenance of propofol anesthesia. A manual infusion scheme. Anesthesia, 1988, 43, Suppl, 14–17.

    Article  Google Scholar 

  51. Sadean MR, Glass Peter SA: Pharmacokinetics in the elderly. Best Pract Res Clin Anaesthesiol, 2003, 17, 191–205.

    Article  CAS  PubMed  Google Scholar 

  52. Saint-Maurice C, Cockshott ID, Douglas EJ, Richard MO, Harmey IL: Pharmacokinetics of propofol in young children after a single dose. Br J Anaesth, 1989, 63, 667–670.

    Article  CAS  PubMed  Google Scholar 

  53. Schnider TW, Minto CF, Gambus PL, Andresen C, Goodale B, Shafer SL, Youngs EJ: The influence of method of administration and covariates on the pharma-cokinetics of propofol in adult volunteers. Anesthesiol-ogy, 1998, 88, 1170–1182.

    Article  CAS  Google Scholar 

  54. Schnider TW, Minto CF, Shafer SL, Gambus PL, Andre-sen C, Goodale DB, Youngs EJ: The influence of age on propofol pharmacodynamics. Anesthesiology, 1999, 90, 1502–1516.

    Article  CAS  PubMed  Google Scholar 

  55. Schüttler J, Ihmsen H: Population pharmacokinetics of propofol. A multicenter study. Anesthesiology, 2000, 92, 727–738.

    PubMed  Google Scholar 

  56. Servin F, Farinotti R, Haberer JP, Desmonts JM: Propofol infusion for maintenance of anesthesia in morbidly obese patients receiving nitrous oxide. A clinical and pharma-cokinetic study. Anesthesiology, 1993, 78, 657–665.

    Article  CAS  PubMed  Google Scholar 

  57. Shafer A, Doze BS, Shafer SL, White P: Pharmacokinet-ics and pharmacodynamics of propofol infusions during general anesthesia. Anesthesiology, 1988, 69, 348–356.

    Article  CAS  PubMed  Google Scholar 

  58. Snyder GL, Greenberg S: Effect of anaesthetic technique and other perioperative factors on cancer reccurence. Br J Anaesth, 2010, 105, 106–115.

    Article  CAS  PubMed  Google Scholar 

  59. Swinhoe CF, Peacock JE, Glen JB, Reilly CS: Evaluation of the predictive performance of a Dipriphusor TCI system. Anesthesia, 1998, 53, Suppl, 61–67.

    Article  CAS  Google Scholar 

  60. Takata K, Kurita T, Morishima Y, Morita K, Uraoka M, Sato S: Do the kidneys contribute to propofol elimination? Br J Anaesth, 2008, 101, 648–652.

    Article  CAS  PubMed  Google Scholar 

  61. Uezono S, Goto T, Terui K, Ichinose F, Ishquro Y, Nakata Y, Morita S: Emergence agitation after sevo-flurane versus propofol in pediatric patients. Anesth Analg, 2000, 91, 563–566.

    Article  CAS  PubMed  Google Scholar 

  62. Upton RN, Ludbrook GL, Grant C, Martinez AM: Cardiac output is a determinant of the initial concentrations of propofol after short-infusion administration. Anesth Analg, 1999, 89, 541–544.

    Article  Google Scholar 

  63. Vuyk J: Pharmacodynamics in the ederly. Best Pract Res Clin Anaesthesiol, 2003, 17, 207–218.

    Article  CAS  PubMed  Google Scholar 

  64. White PF. Textbook of intravenous anesthesia. Williams & Wilkins, Baltimore, 1997.

    Google Scholar 

  65. Wiczling P, Bienert A, Sobczyński P, Hartmann-Sobczyńska R, Bieda K, Marcinkowska A, Malatyńska M, Grześkowiak E: Pharmacokinetics and pharmacody-namics of propofol in patients undergoing abdominal aortic surgery. Pharmacol Rep, 2012, 64, 113–122.

    Article  CAS  PubMed  Google Scholar 

  66. Yamashita S, Kaneda K, THan TH: Population pharma-cokinetics of a propofol bolus administrated in patients with major burns. Burns, 2010, 36, 1215–1221.

    Article  PubMed  Google Scholar 

  67. Zaccheo MM, Bucher DH: Propofol infusion syndrome a rare complication with potentially fatal results. Crit Care Nurse, 2008, 28, 18–25.

    Article  PubMed  Google Scholar 

  68. Zi-jing H, Yong-hua H, Zhi-yi F: Median effective effect-site concentration of intravenous anesthetics for loss of consciousness in neoadjuvant chemotherapy patients. Chin Med J, 2011, 124, 504–508.

    Google Scholar 

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Authors and Affiliations

  1. Department of Clinical Pharmacy and Biopharmacy, Karol Marcinkowski University of Medical Sciences, Marii Magdaleny 14, PL 61-861, Poznań, Poland

    Agnieszka Bienert & Edmund Grzśkowiak

  2. Department of Biopharmaceutics and Pharmacodynamics, Medical Univeristy of Gdańsk, Hallera 107, PL 80-401, Gdańsk, Poland

    Paweł Wiczling

  3. Departments of General Anesthesiology and Outcome Research, Cleveland Clinic, 9500, Euclid Avenue, Cleveland, Ohio, 44195, USA

    Jacek B. Cywiński

  4. Department of Anesthesiology and Intensive Therapy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Marii Skłodowskiej-Curie 9, PL 85-094, Bydgoszcz, Poland

    Krzysztof Kusza

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  1. Agnieszka Bienert
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  2. Paweł Wiczling
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Correspondence to Agnieszka Bienert.

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Bienert, A., Wiczling, P., Grzśkowiak, E. et al. Potential pitfalls of propofol target controlled infusion delivery related to its pharmacokinetics and pharmacodynamics. Pharmacol. Rep 64, 782–795 (2012). https://doi.org/10.1016/S1734-1140(12)70874-5

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