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CNS Drugs

, Volume 29, Issue 7, pp 543–563 | Cite as

Propofol: A Review of its Role in Pediatric Anesthesia and Sedation

  • Vidya Chidambaran
  • Andrew Costandi
  • Ajay D’Mello
Review Article

Abstract

Propofol is an intravenous agent used commonly for the induction and maintenance of anesthesia, procedural, and critical care sedation in children. The mechanisms of action on the central nervous system involve interactions at various neurotransmitter receptors, especially the gamma-aminobutyric acid A receptor. Approved for use in the USA by the Food and Drug Administration in 1989, its use for induction of anesthesia in children less than 3 years of age still remains off-label. Despite its wide use in pediatric anesthesia, there is conflicting literature about its safety and serious adverse effects in particular subsets of children. Particularly as children are not “little adults”, in this review, we emphasize the maturational aspects of propofol pharmacokinetics. Despite the myriad of propofol pharmacokinetic-pharmacodynamic studies and the ability to use allometrical scaling to smooth out differences due to size and age, there is no optimal model that can be used in target controlled infusion pumps for providing closed loop total intravenous anesthesia in children. As the commercial formulation of propofol is a nutrient-rich emulsion, the risk for bacterial contamination exists despite the Food and Drug Administration mandating addition of antimicrobial preservative, calling for manufacturers’ directions to discard open vials after 6 h. While propofol has advantages over inhalation anesthesia such as less postoperative nausea and emergence delirium in children, pain on injection remains a problem even with newer formulations. Propofol is known to depress mitochondrial function by its action as an uncoupling agent in oxidative phosphorylation. This has implications for children with mitochondrial diseases and the occurrence of propofol-related infusion syndrome, a rare but seriously life-threatening complication of propofol. At the time of this review, there is no direct evidence in humans for propofol-induced neurotoxicity to the infant brain; however, current concerns of neuroapoptosis in developing brains induced by propofol persist and continue to be a focus of research.

Keywords

Sevoflurane Dexmedetomidine Mitochondrial Disease Emergence Delirium Fospropofol 
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.

Notes

Compliance with ethical standards

Funding

Preparation of this manuscript was supported by the Department of Anesthesia, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA. No financial support except departmental salary support for the authors VC, AC, and AD. The writing of the review article was also facilitated by protected research time supported by Eunice Kennedy Shriver National Institute Of Child Health and Human Development of the National Institutes of Health under award number K23HD082782 (PI: VC)

Conflicts of interest

All authors (VC, AC, and AD) listed in this manuscript have no conflicts of interest relevant to this article to disclose.

References

  1. 1.
    Trapani G, Altomare C, Liso G, Sanna E, Biggio G. Propofol in anesthesia: mechanism of action, structure-activity relationships, and drug delivery. Curr Med Chem. 2000;7(2):249–71.PubMedCrossRefGoogle Scholar
  2. 2.
    Borgeat A, Popovic V, Meier D, Schwander D. Comparison of propofol and thiopental/halothane for short-duration ENT surgical procedures in children. Anesth Analg. 1990;71(5):511–5.PubMedCrossRefGoogle Scholar
  3. 3.
    Reed MD, Yamashita TS, Marx CM, Myers CM, Blumer JL. A pharmacokinetically based propofol dosing strategy for sedation of the critically ill, mechanically ventilated pediatric patient. Crit Care Med. 1996;24(9):1473–81.PubMedCrossRefGoogle Scholar
  4. 4.
    Reed MD, Blumer JL. Propofol bashing: the time to stop is now! Crit Care Med. 1996;24(1):175–6.PubMedCrossRefGoogle Scholar
  5. 5.
    Angelini G, Ketzler JT, Coursin DB. Use of propofol and other nonbenzodiazepine sedatives in the intensive care unit. Crit Care Clinics. 2001;17(4):863–80.CrossRefGoogle Scholar
  6. 6.
    Kulling D, Rothenbuhler R, Inauen W. Safety of nonanesthetist sedation with propofol for outpatient colonoscopy and esophagogastroduodenoscopy. Endoscopy. 2003;35(8):679–82. doi: 10.1055/s-2003-41518.PubMedCrossRefGoogle Scholar
  7. 7.
    Smith MC, Williamson J, Yaster M, Boyd GJ, Heitmiller ES. Off-label use of medications in children undergoing sedation and anesthesia. Anesth Analg. 2012;115(5):1148–54. doi: 10.1213/ANE.0b013e3182501b04.PubMedCrossRefGoogle Scholar
  8. 8.
    Langley MS, Heel RC. Propofol: a review of its pharmacodynamic and pharmacokinetic properties and use as an intravenous anaesthetic. Drugs. 1988;35(4):334–72.PubMedCrossRefGoogle Scholar
  9. 9.
    Fulton B, Sorkin EM. Propofol: an overview of its pharmacology and a review of its clinical efficacy in intensive care sedation. Drugs. 1995;50(4):636–57.PubMedCrossRefGoogle Scholar
  10. 10.
    Thompson KA, Goodale DB. The recent development of propofol (DIPRIVAN). Intensive Care Med. 2000;26(Suppl 4):S400–4.PubMedCrossRefGoogle Scholar
  11. 11.
    James R, Glen JB. Synthesis, biological evaluation, and preliminary structure-activity considerations of a series of alkylphenols as intravenous anesthetic agents. J Med Chem. 1980;23(12):1350–7.PubMedCrossRefGoogle Scholar
  12. 12.
    Briggs LP, Clarke RS, Watkins J. An adverse reaction to the administration of disoprofol (Diprivan). Anaesthesia. 1982;37(11):1099–101.PubMedCrossRefGoogle Scholar
  13. 13.
    Cummings GC, Dixon J, Kay NH, Windsor JP, Major E, Morgan M, et al. Dose requirements of ICI 35,868 (propofol, ‘Diprivan’) in a new formulation for induction of anaesthesia. Anaesthesia. 1984;39(12):1168–71.PubMedCrossRefGoogle Scholar
  14. 14.
    Baker MT, Gregerson MS, Martin SM, Buettner GR. Free radical and drug oxidation products in an intensive care unit sedative: propofol with sulfite. Crit Care Med. 2003;31(3):787–92. doi: 10.1097/01.CCM.0000053560.05156.73.PubMedCrossRefGoogle Scholar
  15. 15.
    Jensen V, Rappaport BA. The reality of drug shortages: the case of the injectable agent propofol. N Engl J Med. 2010;363(9):806–7. doi: 10.1056/NEJMp1005849.PubMedCrossRefGoogle Scholar
  16. 16.
    Calvo R, Telletxea S, Leal N, Aguilera L, Suarez E, De La Fuente L, et al. Influence of formulation on propofol pharmacokinetics and pharmacodynamics in anesthetized patients. Acta Anaesthesiol Scand. 2004;48(8):1038–48. doi: 10.1111/j.0001-5172.2004.00467.x.PubMedCrossRefGoogle Scholar
  17. 17.
    Larsen R, Beerhalter U, Erdkonig R, Larsen B. Injection pain from propofol-MCT–LCT in children. A comparison with propofol-LCT. Der Anaesth. 2001;50(9):676–8.CrossRefGoogle Scholar
  18. 18.
    Le Guen M, Grassin-Delyle S, Cornet C, Genty A, Chazot T, Dardelle D, et al. Comparison of the potency of different propofol formulations: a randomized, double-blind trial using closed-loop administration. Anesthesiology. 2014;120(2):355–64. doi: 10.1097/01.anes.0000435741.97234.04.PubMedCrossRefGoogle Scholar
  19. 19.
    Cho J, Cho JC, Lee P, Lee M, Oh E. Formulation and evaluation of an alternative triglyceride-free propofol microemulsion. Arch Pharm Res. 2010;33(9):1375–87. doi: 10.1007/s12272-010-0911-0.PubMedCrossRefGoogle Scholar
  20. 20.
    Sanna E, Mascia MP, Klein RL, Whiting PJ, Biggio G, Harris RA. Actions of the general anesthetic propofol on recombinant human GABAA receptors: influence of receptor subunits. J Pharmacol Exp Ther. 1995;274(1):353–60.PubMedGoogle Scholar
  21. 21.
    Collins GG. Effects of the anaesthetic 2,6-diisopropylphenol on synaptic transmission in the rat olfactory cortex slice. Br J Pharmacol. 1988;95(3):939–49.PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Sieghart W. Structure and pharmacology of gamma-aminobutyric acidA receptor subtypes. Pharmacol Rev. 1995;47(2):181–234.PubMedGoogle Scholar
  23. 23.
    Barnard EA, Skolnick P, Olsen RW, Mohler H, Sieghart W, Biggio G, et al. International Union of Pharmacology. XV. Subtypes of gamma-aminobutyric acidA receptors: classification on the basis of subunit structure and receptor function. Pharmacol Rev. 1998;50(2):291–313.PubMedGoogle Scholar
  24. 24.
    Imperato A, Dazzi L, Obinu MC, Gessa GL, Biggio G. Inhibition of hippocampal acetylcholine-release by benzodiazepines: antagonism by flumazenil. Eur J Pharmacol. 1993;238(1):135–7. doi: 10.1016/0014-2999(93)90518-M.PubMedCrossRefGoogle Scholar
  25. 25.
    Krasowski MD, Jenkins A, Flood P, Kung AY, Hopfinger AJ, Harrison NL. General anesthetic potencies of a series of propofol analogs correlate with potency for potentiation of gamma-aminobutyric acid (GABA) current at the GABA(A) receptor but not with lipid solubility. J Pharmacol Exp Ther. 2001;297(1):338–51.PubMedGoogle Scholar
  26. 26.
    Peduto VA, Concas A, Santoro G, Biggio G, Gessa GL. Biochemical and electrophysiologic evidence that propofol enhances GABAergic transmission in the rat-brain. Anesthesiology. 1991;75(6):1000–9. doi: 10.1097/00000542-199112000-00012.PubMedCrossRefGoogle Scholar
  27. 27.
    Sanna E, Murgia A, Casula A, Biggio G. Differential subunit dependence of the actions of the general anesthetics alphaxalone and etomidate at gamma-aminobutyric acid type A receptors expressed in Xenopus laevis oocytes. Mol Pharmacol. 1997;51(3):484–90.PubMedGoogle Scholar
  28. 28.
    Hales TG, Lambert JJ. The actions of propofol on inhibitory amino-acid receptors of bovine adrenomedullary chromaffin cells and rodent central neurons. Br J Pharmacol. 1991;104(3):619–28.PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    Machu TK, Harris RA. Alcohols and anesthetics enhance the function of 5-hydroxytryptamine(3) receptors expressed in Xenopus laevis oocytes. J Pharmacol Exp Ther. 1994;271(2):898–905.PubMedGoogle Scholar
  30. 30.
    Yamakura T, Sakimura K, Shimoji K, Mishina M. Effects of propofol on various Ampa-selective, kainate-selective and NMDA-selective glutamate-receptor channels expressed in Xenopus oocytes. Neurosci Lett. 1995;188(3):187–90. doi: 10.1016/0304-3940(95)11431-U.PubMedCrossRefGoogle Scholar
  31. 31.
    Simons PJ, Cockshott ID, Douglas EJ, Gordon EA, Hopkins K, Rowland M. Disposition in male-volunteers of a subanaesthetic intravenous dose of an oil in water emulsion of propofol-C-14. Xenobiotica. 1988;18(4):429–40.PubMedCrossRefGoogle Scholar
  32. 32.
    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(4):324–30. doi: 10.1016/j.clpt.2003.12.004.PubMedCrossRefGoogle Scholar
  33. 33.
    Dawidowicz AL, Fornal E, Mardarowicz M, Fijalkowska A. The role of human lungs in the biotransformation of propofol. Anesthesiology. 2000;93(4):992–7. doi: 10.1097/00000542-200010000-00020.PubMedCrossRefGoogle Scholar
  34. 34.
    He YL, Ueyama H, Tashiro C, Mashimo T, Yoshiya I. Pulmonary disposition of propofol in surgical patients. Anesthesiology. 2000;93(4):986–91. doi: 10.1097/00000542-200010000-00019.PubMedCrossRefGoogle Scholar
  35. 35.
    Hiraoka H, Yamamoto K, Miyoshi S, Morita T, Nakamura K, Kadoi Y, et al. Kidneys contribute to the extrahepatic clearance of propofol in humans, but not lungs and brain. Br J Clin Pharmacol. 2005;60(2):176–82. doi: 10.1111/j.1365-2125.2005.02393.x.PubMedCentralPubMedCrossRefGoogle Scholar
  36. 36.
    Schuttler J, Ihmsen H. Population pharmacokinetics of propofol: a multicenter study. Anesthesiology. 2000;92(3):727–38.PubMedCrossRefGoogle Scholar
  37. 37.
    Rigby-Jones AE, Nolan JA, Priston MJ, Wright PM, Sneyd JR, Wolf AR. Pharmacokinetics of propofol infusions in critically ill neonates, infants, and children in an intensive care unit. Anesthesiology. 2002;97(6):1393–400.PubMedCrossRefGoogle Scholar
  38. 38.
    Al-Jahdari WS, Yamamoto K, Hiraoka H, Nakamura K, Goto F, Horiuchi R. Prediction of total propofol clearance based on enzyme activities in microsomes from human kidney and liver. Eur J Clin Pharmacol. 2006;62(7):527–33. doi: 10.1007/s00228-006-0130-2.PubMedCrossRefGoogle Scholar
  39. 39.
    Tateishi T, Nakura H, Asoh M, Watanabe M, Tanaka M, Kumai T, et al. A comparison of hepatic cytochrome P450 protein expression between infancy and postinfancy. Life Sci. 1997;61(26):2567–74.PubMedCrossRefGoogle Scholar
  40. 40.
    Allegaert K, Peeters MY, Verbesselt R, Tibboel D, Naulaers G, de Hoon JN, et al. Inter-individual variability in propofol pharmacokinetics in preterm and term neonates. Br J Anaesth. 2007;99(6):864–70. doi: 10.1093/bja/aem294.PubMedCrossRefGoogle Scholar
  41. 41.
    Johnson TN, Rostami-Hodjegan A, Tucker GT. Prediction of the clearance of eleven drugs and associated variability in neonates, infants and children. Clin Pharmacokinet. 2006;45(9):931–56. doi: 10.2165/00003088-200645090-00005.PubMedCrossRefGoogle Scholar
  42. 42.
    Constant I, Rigouzzo A. Which model for propofol TCI in children. Paediatr Anaesth. 2010;20(3):233–9. doi: 10.1111/j.1460-9592.2010.03269.x.PubMedCrossRefGoogle Scholar
  43. 43.
    Allegaert K, de Hoon J, Verbesselt R, Naulaers G, Murat I. Maturational pharmacokinetics of single intravenous bolus of propofol. Paediatr Anaesth. 2007;17(11):1028–34. doi: 10.1111/j.1460-9592.2007.02285.x.PubMedCrossRefGoogle Scholar
  44. 44.
    Anderson BJ. Pediatric models for adult target-controlled infusion pumps. Paediatr Anaesth. 2010;20(3):223–32. doi: 10.1111/j.1460-9592.2009.03072.x.PubMedCrossRefGoogle Scholar
  45. 45.
    Kataria BK, Ved SA, Nicodemus HF, Hoy GR, Lea D, Dubois MY, et al. The pharmacokinetics of propofol in children using three different data analysis approaches. Anesthesiology. 1994;80(1):104–22.PubMedCrossRefGoogle Scholar
  46. 46.
    Knibbe CA, Zuideveld KP, Aarts LP, Kuks PF, Danhof M. Allometric relationships between the pharmacokinetics of propofol in rats, children and adults. Br J Clin Pharmacol. 2005;59(6):705–11. doi: 10.1111/j.1365-2125.2005.02239.x.PubMedCentralPubMedCrossRefGoogle Scholar
  47. 47.
    Bartelink IH, Rademaker CM, Schobben AF, van den Anker JN. Guidelines on paediatric dosing on the basis of developmental physiology and pharmacokinetic considerations. Clin Pharmacokinet. 2006;45(11):1077–97. doi: 10.2165/00003088-200645110-00003.PubMedCrossRefGoogle Scholar
  48. 48.
    Jeleazcov C, Ihmsen H, Schmidt J, Ammon C, Schwilden H, Schuttler J, et al. Pharmacodynamic modelling of the bispectral index response to propofol-based anaesthesia during general surgery in children. Br J Anaesth. 2008;100(4):509–16. doi: 10.1093/bja/aem408.PubMedCrossRefGoogle Scholar
  49. 49.
    Rigouzzo A, Girault L, Louvet N, Servin F, De-Smet T, Piat V, et al. The relationship between bispectral index and propofol during target-controlled infusion anesthesia: a comparative study between children and young adults. Anesth Analga. 2008;106(4):1109–16. doi: 10.1213/ane.0b013e318164f388.CrossRefGoogle Scholar
  50. 50.
    Sadhasivam S, Ganesh A, Robison A, Kaye R, Watcha MF. Validation of the bispectral index monitor for measuring the depth of sedation in children. Anesth Analg. 2006;102(2):383–8. doi: 10.1213/01.ANE.0000184115.57837.30.PubMedCrossRefGoogle Scholar
  51. 51.
    Coppens M, Van Limmen JG, Schnider T, Wyler B, Bonte S, Dewaele F, et al. Study of the time course of the clinical effect of propofol compared with the time course of the predicted effect-site concentration: performance of three pharmacokinetic-dynamic models. Br J Anaesth. 2010;104(4):452–8. doi: 10.1093/bja/aeq028.PubMedCrossRefGoogle Scholar
  52. 52.
    Rigouzzo A, Servin F, Constant I. Pharmacokinetic-pharmacodynamic modeling of propofol in children. Anesthesiology. 2010;113(2):343–52. doi: 10.1097/ALN.0b013e3181e4f4ca.PubMedCrossRefGoogle Scholar
  53. 53.
    Bjornsson 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 Pharmacokinet Pharmacodyn. 2010;37(3):243–55. doi: 10.1007/s10928-010-9157-1.PubMedCrossRefGoogle Scholar
  54. 54.
    Wiczling P, Bienert A, Sobczynski P, Hartmann-Sobczynska R, Bieda K, Marcinkowska A, et al. Pharmacokinetics and pharmacodynamics of propofol in patients undergoing abdominal aortic surgery. Pharmacol Rep. 2012;64(1):113–22.PubMedCrossRefGoogle Scholar
  55. 55.
    McFarlan CS, Anderson BJ, Short TG. The use of propofol infusions in paediatric anaesthesia: a practical guide. Paediatr Anaesth. 1999;9(3):209–16.PubMedGoogle Scholar
  56. 56.
    Munoz HR, Cortinez LI, Ibacache ME, Leon PJ. Effect site concentrations of propofol producing hypnosis in children and adults: comparison using the bispectral index. Acta Anaesthesiol Scand. 2006;50(7):882–7. doi: 10.1111/j.1399-6576.2006.01062.x.PubMedCrossRefGoogle Scholar
  57. 57.
    Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of obesity and trends in body mass index among US children and adolescents, 1999–2010. JAMA. 2012;307(5):483–90. doi: 10.1001/jama.2012.40.PubMedCrossRefGoogle Scholar
  58. 58.
    Schilling PL, Davis MM, Albanese CT, Dutta S, Morton J. National trends in adolescent bariatric surgical procedures and implications for surgical centers of excellence. J Am Coll Surg. 2008;206(1):1–12. doi: 10.1016/j.jamcollsurg.2007.07.028.PubMedCrossRefGoogle Scholar
  59. 59.
    Chidambaran V, Sadhasivam S, Diepstraten J, Esslinger H, Cox S, Schnell BM, et al. Evaluation of propofol anesthesia in morbidly obese children and adolescents. BMC Anesthesiol. 2013;13(1):8. doi: 10.1186/1471-2253-13-8.PubMedCentralPubMedCrossRefGoogle Scholar
  60. 60.
    Igarashi T, Nagata O, Iwakiri H, Ikeda M, Uezono S, Ozaki M. Two cases of intraoperative awareness during intravenous anesthesia with propofol in morbidly obese patients. Masui. 2002;51(11):1243–7.PubMedGoogle Scholar
  61. 61.
    Olutoye OA, Yu X, Govindan K, Tjia IM, East DL, Spearman R, et al. The effect of obesity on the ED(95) of propofol for loss of consciousness in children and adolescents. Anesth Analg. 2012;115(1):147–53. doi: 10.1213/ANE.0b013e318256858f.PubMedCrossRefGoogle Scholar
  62. 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(3):545–52.PubMedGoogle Scholar
  63. 63.
    Ingrande J, Brodsky JB, Lemmens HJ. Lean body weight scalar for the anesthetic induction dose of propofol in morbidly obese subjects. Anesth Analg. 2011;113(1):57–62. doi: 10.1213/ANE.0b013e3181f6d9c0.PubMedCrossRefGoogle Scholar
  64. 64.
    Lemmens HJ, Ingrande J. Pharmacology and obesity. Int Anesthesiol Clin. 2013;51(3):52–66. doi: 10.1097/AIA.0b013e31829a4d56.PubMedCrossRefGoogle Scholar
  65. 65.
    Cortinez LI, Anderson BJ, Penna A, Olivares L, Munoz HR, Holford NH, et al. Influence of obesity on propofol pharmacokinetics: derivation of a pharmacokinetic model. Br J Anaesth. 2010;105(4):448–56. doi: 10.1093/bja/aeq195.PubMedCrossRefGoogle Scholar
  66. 66.
    Diepstraten J, Chidambaran V, Sadhasivam S, Esslinger HR, Cox SL, Inge TH, et al. Propofol clearance in morbidly obese children and adolescents: influence of age and body size. Clin Pharmacokinet. 2012;51(8):543–51. doi: 10.2165/11632940-000000000-00000.PubMedCrossRefGoogle Scholar
  67. 67.
    van Kralingen S, Diepstraten J, Peeters MY, Deneer VH, van Ramshorst B, Wiezer RJ, et al. Population pharmacokinetics and pharmacodynamics of propofol in morbidly obese patients. Clin Pharmacokinet. 2011;50(11):739–50. doi: 10.2165/11592890-000000000-00000.PubMedCrossRefGoogle Scholar
  68. 68.
    Chidambaran V, Venkatasubramanian R, Sadhasivam S, Esslinger H, Cox S, Diepstraten J, et al. Population pharmacokinetic-pharmacodynamic modeling and dosing simulation of propofol maintenance anesthesia in severely obese adolescents. Paediatr Anaesth. 2015;. doi: 10.1111/pan.12684.PubMedGoogle Scholar
  69. 69.
    Diepstraten J, Chidambaran V, Sadhasivam S, Blusse van Oud-Alblas HJ, Inge T, van Ramshorst B, et al. An integrated population pharmacokinetic meta-analysis of propofol in morbidly obese and nonobese adults, adolescents, and children. CPT Pharmacometrics Syst Pharmacol. 2013;2:e73. doi: 10.1038/psp.2013.47.PubMedCentralPubMedCrossRefGoogle Scholar
  70. 70.
    Grossherr M, Hengstenberg A, Meier T, Dibbelt L, Igl BW, Ziegler A, et al. Propofol concentration in exhaled air and arterial plasma in mechanically ventilated patients undergoing cardiac surgery. Br J Anaesth. 2009;102(5):608–13. doi: 10.1093/bja/aep053.PubMedCrossRefGoogle Scholar
  71. 71.
    Perl T, Carstens E, Hirn A, Quintel M, Vautz W, Nolte J, et al. Determination of serum propofol concentrations by breath analysis using ion mobility spectrometry. Br J Anaesth. 2009;103(6):822–7. doi: 10.1093/bja/aep312.PubMedCrossRefGoogle Scholar
  72. 72.
    Anderson BJ, Hodkinson B. Are there still limitations for the use of target-controlled infusion in children? Curr Opin Anaesthesiol. 2010;23(3):356–62. doi: 10.1097/ACO.0b013e32833938db.PubMedCrossRefGoogle Scholar
  73. 73.
    Marsh B, White M, Morton N, Kenny GN. Pharmacokinetic model driven infusion of propofol in children. Br J Anaesth. 1991;67(1):41–8.PubMedCrossRefGoogle Scholar
  74. 74.
    Gepts E, Camu F, Cockshott ID, Douglas EJ. Disposition of propofol administered as constant rate intravenous infusions in humans. Anesth Analg. 1987;66(12):1256–63.PubMedCrossRefGoogle Scholar
  75. 75.
    Absalom A, Amutike D, Lal A, White M, Kenny GN. Accuracy of the ‘Paedfusor’ in children undergoing cardiac surgery or catheterization. Br J Anaesth. 2003;91(4):507–13.PubMedCrossRefGoogle Scholar
  76. 76.
    Coppens MJ, Eleveld DJ, Proost JH, Marks LA, Van Bocxlaer JF, Vereecke H, et al. An evaluation of using population pharmacokinetic models to estimate pharmacodynamic parameters for propofol and bispectral index in children. Anesthesiology. 2011;115(1):83–93. doi: 10.1097/ALN.0b013e31821a8d80.PubMedCrossRefGoogle Scholar
  77. 77.
    Schnider TW, Minto CF, Gambus PL, Andresen C, Goodale DB, Shafer SL, et al. The influence of method of administration and covariates on the pharmacokinetics of propofol in adult volunteers. Anesthesiology. 1998;88(5):1170–82.PubMedCrossRefGoogle Scholar
  78. 78.
    Iwakiri H, Nishihara N, Nagata O, Matsukawa T, Ozaki M, Sessler DI. Individual effect-site concentrations of propofol are similar at loss of consciousness and at awakening. Anesth Analg. 2005;100(1):107–10. doi: 10.1213/01.ANE.0000139358.15909.EA.PubMedCentralPubMedCrossRefGoogle Scholar
  79. 79.
    McCormack J, Mehta D, Peiris K, Dumont G, Fung P, Lim J, et al. The effect of a target controlled infusion of propofol on predictability of recovery from anesthesia in children. Paediatr Anaesth. 2010;20(1):56–62. doi: 10.1111/j.1460-9592.2009.03196.x.PubMedCrossRefGoogle Scholar
  80. 80.
    Vuyk J, Mertens MJ, Olofsen E, Burm AG, Bovill JG. Propofol anesthesia and rational opioid selection: determination of optimal EC50-EC95 propofol-opioid concentrations that assure adequate anesthesia and a rapid return of consciousness. Anesthesiology. 1997;87(6):1549–62.PubMedCrossRefGoogle Scholar
  81. 81.
    van Heusden K, Ansermino JM, Soltesz K, Khosravi S, West N, Dumont GA. Quantification of the variability in response to propofol administration in children. IEEE Trans Biomed Eng. 2013;60(9):2521–9. doi: 10.1109/TBME.2013.2259592.PubMedCrossRefGoogle Scholar
  82. 82.
    Reves JG, Glass P, Lubarsky DA. Intravenous anesthestics. Miller’s anesthesia. 7th ed. Philadelphia: Churchill Livingstone; 2010.Google Scholar
  83. 83.
    Robinson BJ, Ebert TJ, OBrien TJ, Colinco MD, Muzi M. Mechanisms whereby propofol mediates peripheral vasodilation in humans: sympathoinhibition or direct vascular relaxation? Anesthesiology. 1997;86(1):64–72. doi: 10.1097/00000542-199701000-00010.PubMedCrossRefGoogle Scholar
  84. 84.
    Vuyk J, Sitsen E, Reekers M. Intravenous anesthestics. Miller’s. 8th ed. Philadelphia: Elsevier; 2014.Google Scholar
  85. 85.
    Williams GD, Jones TK, Hanson KA, Morray JP. The hemodynamic effects of propofol in children with congenital heart disease. Anesth Analg. 1999;89(6):1411–6.PubMedGoogle Scholar
  86. 86.
    Cullen PM, Turtle M, Prys-Roberts C, Way WL, Dye J. Effect of propofol anesthesia on baroreflex activity in humans. Anesth Analg. 1987;66(11):1115–20.PubMedCrossRefGoogle Scholar
  87. 87.
    Liu Q, Kong AL, Chen R, Qian C, Liu SW, Sun BG, et al. Propofol and arrhythmias: two sides of the coin. Acta Pharmacol Sinica. 2011;32(6):817–23. doi: 10.1038/aps.2011.42.CrossRefGoogle Scholar
  88. 88.
    Szabo EZ, Luginbuehl I, Bissonnette B. Impact of anesthetic agents on cerebrovascular physiology in children. Paediatr Aaesth. 2009;19(2):108–18. doi: 10.1111/j.1460-9592.2008.02826.x.CrossRefGoogle Scholar
  89. 89.
    Karsli C, Luginbuehl I, Farrar M, Bissonnette B. Propofol decreases cerebral blood flow velocity in anesthetized children. Can J Anaesth. 2002;49(8):830–4. doi: 10.1007/BF03017417.PubMedCrossRefGoogle Scholar
  90. 90.
    Matta BF, Lam AM, Strebel S, Mayberg TS. Cerebral pressure autoregulation and carbon dioxide reactivity during propofol-induced EEG suppression. Br J Anaesth. 1995;74(2):159–63.PubMedCrossRefGoogle Scholar
  91. 91.
    Noterman J, Berre J, Vandesteene A, Brotchi J. Monitoring of intracranial pressure during the postoperative period of aneurysms. Neurochirurgie. 1988;34(3):161–3.PubMedGoogle Scholar
  92. 92.
    Bacon RC, Razis PA. The effect of propofol sedation in pregnancy on neonatal condition. Anaesthesia. 1994;49(12):1058–60.PubMedCrossRefGoogle Scholar
  93. 93.
    Lanigan C, Sury M, Bingham R, Howard R, Mackersie A. Neurological sequelae in children after prolonged propofol infusion. Anaesthesia. 1992;47(9):810–1.PubMedCrossRefGoogle Scholar
  94. 94.
    Trotter C, Serpell MG. Neurological sequelae in children after prolonged propofol infusion. Anaesthesia. 1992;47(4):340–2.PubMedCrossRefGoogle Scholar
  95. 95.
    Bendiksen A, Larsen LM. Convulsions, ataxia and hallucinations following propofol. Acta Anaesthesiol Scand. 1998;42(6):739–41.PubMedCrossRefGoogle Scholar
  96. 96.
    Macrae D, James IG. Propofol sedation of children. Anaesthesia. 1992;47(9):811.PubMedCrossRefGoogle Scholar
  97. 97.
    Fredriksson A, Ponten E, Gordh T, Eriksson P. Neonatal exposure to a combination of N-methyl-D-aspartate and gamma-aminobutyric acid type A receptor anesthetic agents potentiates apoptotic neurodegeneration and persistent behavioral deficits. Anesthesiology. 2007;107(3):427–36. doi: 10.1097/01.anes.0000278892.62305.9c.PubMedCrossRefGoogle Scholar
  98. 98.
    Loepke AW, McGowan FX Jr, Soriano SG. CON: the toxic effects of anesthetics in the developing brain: the clinical perspective. Anesth Analg. 2008;106(6):1664–9. doi: 10.1213/ane.0b013e3181733ef8.PubMedCrossRefGoogle Scholar
  99. 99.
    Loepke AW, Soriano SG. An assessment of the effects of general anesthetics on developing brain structure and neurocognitive function. Anesth Analg. 2008;106(6):1681–707. doi: 10.1213/ane.0b013e318167ad77.PubMedCrossRefGoogle Scholar
  100. 100.
    Ergun R, Akdemir G, Sen S, Tasci A, Ergungor F. Neuroprotective effects of propofol following global cerebral ischemia in rats. Neurosurg Rev. 2002;25(1–2):95–8.PubMedCrossRefGoogle Scholar
  101. 101.
    Bayona NA, Gelb AW, Jiang Z, Wilson JX, Urquhart BL, Cechetto DF. Propofol neuroprotection in cerebral ischemia and its effects on low-molecular-weight antioxidants and skilled motor tasks. Anesthesiology. 2004;100(5):1151–9.PubMedCrossRefGoogle Scholar
  102. 102.
    Engelhard K, Werner C, Eberspacher E, Pape M, Stegemann U, Kellermann K, et al. Influence of propofol on neuronal damage and apoptotic factors after incomplete cerebral ischemia and reperfusion in rats: a long-term observation. Anesthesiology. 2004;101(4):912–7.PubMedCrossRefGoogle Scholar
  103. 103.
    San-juan D, Chiappa KH, Cole AJ. Propofol and the electroencephalogram. Clin Neurophysiol. 2010;121(7):998–1006. doi: 10.1016/j.clinph.2009.12.016.PubMedCrossRefGoogle Scholar
  104. 104.
    Devlin VJ, Schwartz DM. Intraoperative neurophysiologic monitoring during spinal surgery. J Am Acad Orthopaed Surg. 2007;15(9):549–60.Google Scholar
  105. 105.
    Sloan TB, Heyer EJ. Anesthesia for intraoperative neurophysiologic monitoring of the spinal cord. J Clin Neurophysiol. 2002;19(5):430–43.PubMedCrossRefGoogle Scholar
  106. 106.
    Fung NY, Hu Y, Irwin MG, Chow BE, Yuen MY. Comparison between sevoflurane/remifentanil and propofol/remifentanil anaesthesia in providing conditions for somatosensory evoked potential monitoring during scoliosis corrective surgery. Anaesth Intensive Care. 2008;36(6):779–85.PubMedGoogle Scholar
  107. 107.
    Wang AC, Than KD, Etame AB, La Marca F, Park P. Impact of anesthesia on transcranial electric motor evoked potential monitoring during spine surgery: a review of the literature. Neurosurg Focus. 2009;27(4):E7. doi: 10.3171/2009.8.FOCUS09145.PubMedCrossRefGoogle Scholar
  108. 108.
    Dahan A, Nieuwenhuijs DJ, Olofsen E. Influence of propofol on the control of breathing. Adv Exp Med Biol. 2003;523:81–92.PubMedCrossRefGoogle Scholar
  109. 109.
    Goodman NW, Black AM, Carter JA. Some ventilatory effects of propofol as sole anaesthetic agent. Br J Anaesth. 1987;59(12):1497–503.PubMedCrossRefGoogle Scholar
  110. 110.
    Jonsson MM, Lindahl SG, Eriksson LI. Effect of propofol on carotid body chemosensitivity and cholinergic chemotransduction. Anesthesiology. 2005;102(1):110–6.PubMedCrossRefGoogle Scholar
  111. 111.
    Eastwood PR, Platt PR, Shepherd K, Maddison K, Hillman DR. Collapsibility of the upper airway at different concentrations of propofol anesthesia. Anesthesiology. 2005;103(3):470–7.PubMedCrossRefGoogle Scholar
  112. 112.
    Nakayama M, Murray PA. Ketamine preserves and propofol potentiates hypoxic pulmonary vasoconstriction compared with the conscious state in chronically instrumented dogs. Anesthesiology. 1999;91(3):760–71.PubMedCrossRefGoogle Scholar
  113. 113.
    Nishiyama T, Hanaoka K. Propofol-induced bronchoconstriction: two case reports. Anesth Analg. 2001;93(3):645–6.PubMedCrossRefGoogle Scholar
  114. 114.
    Rigby-Jones AE, Sneyd JR. Propofol and children: what we know and what we do not know. Paediatr Anaesth. 2011;21(3):247–54. doi: 10.1111/j.1460-9592.2010.03454.x.PubMedCrossRefGoogle Scholar
  115. 115.
    Steur RJ, Perez RS, De Lange JJ. Dosage scheme for propofol in children under 3 years of age. Paediatr Anaesth. 2004;14(6):462–7. doi: 10.1111/j.1460-9592.2004.01238.x.PubMedCrossRefGoogle Scholar
  116. 116.
    Wheeler DS, Vaux KK, Ponaman ML, Poss BW. The safe and effective use of propofol sedation in children undergoing diagnostic and therapeutic procedures: experience in a pediatric ICU and a review of the literature. Pediatr Emerg Care. 2003;19(6):385–92.PubMedCrossRefGoogle Scholar
  117. 117.
    Malherbe S, Whyte S, Singh P, Amari E, King A, Ansermino JM. Total intravenous anesthesia and spontaneous respiration for airway endoscopy in children—a prospective evaluation. Paediatr Anaesth. 2010;20(5):434–8. doi: 10.1111/j.1460-9592.2010.03290.x.PubMedCrossRefGoogle Scholar
  118. 118.
    Koroglu A, Teksan H, Sagir O, Yucel A, Toprak HI, Ersoy OM. A comparison of the sedative, hemodynamic, and respiratory effects of dexmedetomidine and propofol in children undergoing magnetic resonance imaging. Anesthes Analg. 2006;103(1):63–7. doi: 10.1213/01.ANE.0000219592.82598.AA.CrossRefGoogle Scholar
  119. 119.
    Wu J, Mahmoud M, Schmitt M, Hossain M, Kurth D. Comparison of propofol and dexmedetomedine techniques in children undergoing magnetic resonance imaging. Paediatr Anaesth. 2014;24(8):813–8. doi: 10.1111/pan.12408.PubMedCrossRefGoogle Scholar
  120. 120.
    Mahmoud M, Jung D, Salisbury S, McAuliffe J, Gunter J, Patio M, et al. Effect of increasing depth of dexmedetomidine and propofol anesthesia on upper airway morphology in children and adolescents with obstructive sleep apnea. J Clin Anesth. 2013;25(7):529–41. doi: 10.1016/j.jclinane.2013.04.011.PubMedCrossRefGoogle Scholar
  121. 121.
    Cravero JP, Beach ML, Blike GT, Gallagher SM, Hertzog JH, Pediatric Sedation Research Consortium. The incidence and nature of adverse events during pediatric sedation/anesthesia with propofol for procedures outside the operating room: a report from the Pediatric Sedation Research Consortium. Anesthes Analg. 2009;108(3):795–804. doi: 10.1213/ane.0b013e31818fc334.CrossRefGoogle Scholar
  122. 122.
    Kamat PP, McCracken CE, Gillespie SE, Fortenberry JD, Stockwell JA, Cravero JP, et al. Pediatric critical care physician-administered procedural sedation using propofol: a report from the Pediatric Sedation Research Consortium Database. Pediatr Crit Care Med. 2015;16(1):11–20. doi: 10.1097/PCC.0000000000000273.PubMedCrossRefGoogle Scholar
  123. 123.
    Mallory MD, Baxter AL, Yanosky DJ, Cravero JP, Pediatric Sedation Research Consortium. Emergency physician-administered propofol sedation: a report on 25,433 sedations from the pediatric sedation research consortium. Ann Emerg Med. 2011;57(5):462–8 e1. doi: 10.1016/j.annemergmed.2011.03.008.
  124. 124.
    Devlin JW, Lau AK, Tanios MA. Propofol-associated hypertriglyceridemia and pancreatitis in the intensive care unit: an analysis of frequency and risk factors. Pharmacotherapy. 2005;25(10):1348–52. doi: 10.1592/phco.2005.25.10.1348.PubMedCrossRefGoogle Scholar
  125. 125.
    Bray RJ. Propofol infusion syndrome in children. Paediatr Anaesth. 1998;8(6):491–9.PubMedCrossRefGoogle Scholar
  126. 126.
    Hermanns H, Lipfert P, Ladda S, Stevens MF. Propofol infusion syndrome during anaesthesia for scoliosis surgery in an adolescent with neonatal progeroid syndrome. Acta Anaesthesiol Scand. 2006;50(3):392–4. doi: 10.1111/j.1399-6576.2006.00917.x.PubMedCrossRefGoogle Scholar
  127. 127.
    Lerman J. Surgical and patient factors involved in postoperative nausea and vomiting. Br J Anaesth. 1992;69(7 Suppl 1):24S–32S.PubMedCrossRefGoogle Scholar
  128. 128.
    Gan TJ, Glass PS, Howell ST, Canada AT, Grant AP, Ginsberg B. Determination of plasma concentrations of propofol associated with 50% reduction in postoperative nausea. Anesthesiology. 1997;87(4):779–84.PubMedCrossRefGoogle Scholar
  129. 129.
    Erdem AF, Yoruk O, Alici HA, Cesur M, Atalay C, Altas E, et al. Subhypnotic propofol infusion plus dexamethasone is more effective than dexamethasone alone for the prevention of vomiting in children after tonsillectomy. Paediatr Anaesth. 2008;18(9):878–83. doi: 10.1111/j.1460-9592.2008.02675.x.PubMedCrossRefGoogle Scholar
  130. 130.
    Erdem AF, Yoruk O, Silbir F, Alici HA, Cesur M, Dogan N, et al. Tropisetron plus subhypnotic propofol infusion is more effective than tropisetron alone for the prevention of vomiting in children after tonsillectomy. Anaesth Intensive Care. 2009;37(1):54–9.PubMedGoogle Scholar
  131. 131.
    Unlugenc H, Guler T, Gunes Y, Isik G. Comparative study of the antiemetic efficacy of ondansetron, propofol and midazolam in the early postoperative period. Eur J Anaesthesiol. 2004;21(1):60–5.PubMedCrossRefGoogle Scholar
  132. 132.
    Apfel CC, Korttila K, Abdalla M, Kerger H, Turan A, Vedder I, et al. A factorial trial of six interventions for the prevention of postoperative nausea and vomiting. N Engl J Med. 2004;350(24):2441–51. doi: 10.1056/NEJMoa032196.PubMedCentralPubMedCrossRefGoogle Scholar
  133. 133.
    Tramer M, Moore A, McQuay H. Meta-analytic comparison of prophylactic antiemetic efficacy for postoperative nausea and vomiting: propofol anaesthesia vs omitting nitrous oxide vs total i.v. anaesthesia with propofol. Br J Anaesth. 1997;78(3):256–9.PubMedCrossRefGoogle Scholar
  134. 134.
    Tramer M, Moore A, McQuay H. Propofol anaesthesia and postoperative nausea and vomiting: quantitative systematic review of randomized controlled studies. Br J Anaesth. 1997;78(3):247–55.PubMedCrossRefGoogle Scholar
  135. 135.
    Gan TJ, Diemunsch P, Habib AS, Kovac A, Kranke P, Meyer TA, et al. Consensus guidelines for the management of postoperative nausea and vomiting. Anesth Analg. 2014;118(1):85–113. doi: 10.1213/ANE.0000000000000002.PubMedCrossRefGoogle Scholar
  136. 136.
    Olympio MA. Postanesthetic delirium: historical perspectives. J Clin Anesth. 1991;3(1):60–3.PubMedCrossRefGoogle Scholar
  137. 137.
    Kain ZN, Caldwell-Andrews AA, Maranets I, McClain B, Gaal D, Mayes LC et al. Preoperative anxiety and emergence delirium and postoperative maladaptive behaviors. Anesth Analg. 2004;99(6):1648–54. doi: 10.1213/01.ANE.0000136471.36680.97.
  138. 138.
    Chandler JR, Myers D, Mehta D, Whyte E, Groberman MK, Montgomery CJ, et al. Emergence delirium in children: a randomized trial to compare total intravenous anesthesia with propofol and remifentanil to inhalational sevoflurane anesthesia. Paediatr Anaesth. 2013;23(4):309–15. doi: 10.1111/pan.12090.PubMedCrossRefGoogle Scholar
  139. 139.
    Abu-Shahwan I. Effect of propofol on emergence behavior in children after sevoflurane general anesthesia. Paediatr Anaesth. 2008;18(1):55–9. doi: 10.1111/j.1460-9592.2007.02376.x.PubMedGoogle Scholar
  140. 140.
    Cameron E, Johnston G, Crofts S, Morton NS. The minimum effective dose of lignocaine to prevent injection pain due to propofol in children. Anaesthesia. 1992;47(7):604–6.PubMedCrossRefGoogle Scholar
  141. 141.
    Picard P, Tramer MR. Prevention of pain on injection with propofol: a quantitative systematic review. Anesth Analg. 2000;90(4):963–9.PubMedCrossRefGoogle Scholar
  142. 142.
    Jalota L, Kalira V, George E, Shi YY, Hornuss C, Radke O, et al. Prevention of pain on injection of propofol: systematic review and meta-analysis. BMJ. 2011;342:d1110. doi: 10.1136/bmj.d1110.PubMedCrossRefGoogle Scholar
  143. 143.
    Briggs LP, Clarke RS, Dundee JW, Moore J, Bahar M, Wright PJ. Use of di-isopropyl phenol as main agent for short procedures. Br J Anaesth. 1981;53(11):1197–202.PubMedCrossRefGoogle Scholar
  144. 144.
    Hannallah RS, Baker SB, Casey W, McGill WA, Broadman LM, Norden JM. Propofol: effective dose and induction characteristics in unpremedicated children. Anesthesiology. 1991;74(2):217–9.PubMedCrossRefGoogle Scholar
  145. 145.
    Scott RP, Saunders DA, Norman J. Propofol: clinical strategies for preventing the pain of injection. Anaesthesia. 1988;43(6):492–4.PubMedCrossRefGoogle Scholar
  146. 146.
    Stark RD, Binks SM, Dutka VN, O’Connor KM, Arnstein MJ, Glen JB. A review of the safety and tolerance of propofol (‘Diprivan’). Postgrad Med J. 1985;61(Suppl 3):152–6.PubMedGoogle Scholar
  147. 147.
    Klement W, Arndt JO. Pain on injection of propofol: effects of concentration and diluent. Br J Anaesth. 1991;67(3):281–4.PubMedCrossRefGoogle Scholar
  148. 148.
    Doenicke AW, Roizen MF, Rau J, Kellermann W, Babl J. Reducing pain during propofol injection: the role of the solvent. Anesth Analg. 1996;82(3):472–4.PubMedGoogle Scholar
  149. 149.
    Nakane M, Iwama H. A potential mechanism of propofol-induced pain on injection based on studies using nafamostat mesilate. Br J Anaesth. 1999;83(3):397–404.PubMedCrossRefGoogle Scholar
  150. 150.
    Stokes DN, Robson N, Hutton P. Effect of diluting propofol on the incidence of pain on injection and venous sequelae. Br J Anaesth. 1989;62(2):202–3.PubMedCrossRefGoogle Scholar
  151. 151.
    McCrirrick A, Hunter S. Pain on injection of propofol: the effect of injectate temperature. Anaesthesia. 1990;45(6):443–4.PubMedCrossRefGoogle Scholar
  152. 152.
    Barker P, Langton JA, Murphy P, Rowbotham DJ. Effect of prior administration of cold saline on pain during propofol injection: a comparison with cold propofol and propofol with lignocaine. Anaesthesia. 1991;46(12):1069–70.PubMedCrossRefGoogle Scholar
  153. 153.
    Fletcher GC, Gillespie JA, Davidson JA. The effect of temperature upon pain during injection of propofol. Anaesthesia. 1996;51(5):498–9.PubMedCrossRefGoogle Scholar
  154. 154.
    Valtonen M, Iisalo E, Kanto J, Tikkanen J. Comparison between propofol and thiopentone for induction of anaesthesia in children. Anaesthesia. 1988;43(8):696–9.PubMedCrossRefGoogle Scholar
  155. 155.
    McCulloch MJ, Lees NW. Assessment and modification of pain on induction with propofol (Diprivan). Anaesthesia. 1985;40(11):1117–20.PubMedCrossRefGoogle Scholar
  156. 156.
    Nicol ME, Moriarty J, Edwards J, Robbie DS, A’Hern RP. Modification of pain on injection of propofol: a comparison between lignocaine and procaine. Anaesthesia. 1991;46(1):67–9.PubMedCrossRefGoogle Scholar
  157. 157.
    Tan CH, Onsiong MK. Pain on injection of propofol. Anaesthesia. 1998;53(5):468–76.PubMedCrossRefGoogle Scholar
  158. 158.
    Nyman Y, von Hofsten K, Georgiadi A, Eksborg S, Lonnqvist PA. Propofol injection pain in children: a prospective randomized double-blind trial of a new propofol formulation versus propofol with added lidocaine. Br J Anaesth. 2005;95(2):222–5. doi: 10.1093/bja/aei156.PubMedCrossRefGoogle Scholar
  159. 159.
    Rochette A, Hocquet AF, Dadure C, Boufroukh D, Raux O, Lubrano JF, et al. Avoiding propofol injection pain in children: a prospective, randomized, double-blinded, placebo-controlled study. Br J Anaesth. 2008;101(3):390–4. doi: 10.1093/bja/aen169.PubMedCrossRefGoogle Scholar
  160. 160.
    Varghese E, Krishna HM, Nittala A. Does the newer preparation of propofol, an emulsion of medium/long chain triglycerides cause less injection pain in children when premixed with lignocaine? Paediatr Anaesth. 2010;20(4):338–42. doi: 10.1111/j.1460-9592.2010.03272.x.PubMedCrossRefGoogle Scholar
  161. 161.
    Shenoi AN, Fortenberry JD, Kamat P. Accidental intra-arterial injection of propofol. Pediatr Emergency Care. 2014;30(2):136. doi: 10.1097/PEC.0000000000000071.CrossRefGoogle Scholar
  162. 162.
    Ang BL. Prolonged cutaneous sequelae after intra-arterial injection of propofol. Singapore Med J. 1998;39(3):124–6.PubMedGoogle Scholar
  163. 163.
    Hepner DL, Castells MC. Anaphylaxis during the perioperative period. Anesth Analg. 2003;97(5):1381–95.PubMedCrossRefGoogle Scholar
  164. 164.
    Savage JH, Kaeding AJ, Matsui EC, Wood RA. The natural history of soy allergy. J Allergy Clin Immunol. 2010;125(3):683–6. doi: 10.1016/j.jaci.2009.12.994.PubMedCrossRefGoogle Scholar
  165. 165.
    Gangineni K, Scase AE, Fearn J. Propofol and peanut allergy. Anaesthesia. 2007;62(11):1191. doi: 10.1111/j.1365-2044.2007.05337.x.PubMedCrossRefGoogle Scholar
  166. 166.
    Bradley AE, Tober KE, Brown RE. Use of propofol in patients with food allergies. Anaesthesia. 2008;63(4):439. doi: 10.1111/j.1365-2044.2008.05505.x.PubMedCrossRefGoogle Scholar
  167. 167.
    Ring J. Allergy in practice. Berlin: Springer; 2005.Google Scholar
  168. 168.
    Lizaso BMTL, Sainz SA, Puebla AMJ. Cutaneous response to Diprivan (propofol) and Intralipid in patients with leguminous and egg allergy. Rev Esp Alergol Immunol Clin. 1998;13:153–7.Google Scholar
  169. 169.
    Murphy A, Campbell DE, Baines D, Mehr S. Allergic reactions to propofol in egg-allergic children. Anesth Analg. 2011;113(1):140–4. doi: 10.1213/ANE.0b013e31821b450f.PubMedCrossRefGoogle Scholar
  170. 170.
    de Leon-Casasola OA, Weiss A, Lema MJ. Anaphylaxis due to propofol. Anesthesiology. 1992;77(2):384–6.PubMedCrossRefGoogle Scholar
  171. 171.
    Rigoulet M, Devin A, Averet N, Vandais B, Guerin B. Mechanisms of inhibition and uncoupling of respiration in isolated rat liver mitochondria by the general anesthetic 2,6-diisopropylphenol. Eur J Biochem. 1996;241(1):280–5.PubMedCrossRefGoogle Scholar
  172. 172.
    Wallace JJ, Perndt H, Skinner M. Anaesthesia and mitochondrial disease. Paediatr Anaesth. 1998;8(3):249–54.PubMedCrossRefGoogle Scholar
  173. 173.
    Branca D, Roberti MS, Vincenti E, Scutari G. Uncoupling effect of the general anesthetic 2,6-diisopropylphenol in isolated rat liver mitochondria. ArchBiochem Biophysics. 1991;290(2):517–21.CrossRefGoogle Scholar
  174. 174.
    Bains R, Moe MC, Vinje ML, Berg-Johnsen J. Sevoflurane and propofol depolarize mitochondria in rat and human cerebrocortical synaptosomes by different mechanisms. Acta Anaesthesiol Scand. 2009;53(10):1354–60. doi: 10.1111/j.1399-6576.2009.02047.x.PubMedCrossRefGoogle Scholar
  175. 175.
    Mehta N, DeMunter C, Habibi P, Nadel S, Britto J. Short-term propofol infusions in children. Lancet. 1999;354(9181):866–7. doi: 10.1016/S0140-6736(05)75936-5.PubMedCrossRefGoogle Scholar
  176. 176.
    Vanlander AV, Okun JG, de Jaeger A, Smet J, De Latter E, De Paepe B, et al. Possible pathogenic mechanism of propofol infusion syndrome involves coenzyme q. Anesthesiology. 2015;122(2):343–52. doi: 10.1097/ALN.0000000000000484.PubMedCrossRefGoogle Scholar
  177. 177.
    Muravchick S, Levy RJ. Clinical implications of mitochondrial dysfunction. Anesthesiology. 2006;105(4):819–37.PubMedCrossRefGoogle Scholar
  178. 178.
    Driessen J, Willems S, Dercksen S, Giele J, van der Staak F, Smeitink J. Anesthesia-related morbidity and mortality after surgery for muscle biopsy in children with mitochondrial defects. Paediatr Anaesth. 2007;17(1):16–21. doi: 10.1111/j.1460-9592.2006.02043.x.PubMedCrossRefGoogle Scholar
  179. 179.
    Niezgoda J, Morgan PG. Anesthetic considerations in patients with mitochondrial defects. Paediatr Anaesth. 2013;23(9):785–93. doi: 10.1111/pan.12158.PubMedCentralPubMedCrossRefGoogle Scholar
  180. 180.
    Farag E, Deboer G, Cohen BH, Niezgoda J. Metabolic acidosis due to propofol infusion. Anesthesiology. 2005;102(3):697–8.Google Scholar
  181. 181.
    Parke TJ, Stevens JE, Rice AS, Greenaway CL, Bray RJ, Smith PJ, et al. Metabolic acidosis and fatal myocardial failure after propofol infusion in children: five case reports. BMJ. 1992;305(6854):613–6.PubMedCentralPubMedCrossRefGoogle Scholar
  182. 182.
    Vernooy K, Delhaas T, Cremer OL, Di Diego JM, Oliva A, Timmermans C, et al. Electrocardiographic changes predicting sudden death in propofol-related infusion syndrome. Heart Rhythm. 2006;3(2):131–7. doi: 10.1016/j.hrthm.2005.11.005.PubMedCentralPubMedCrossRefGoogle Scholar
  183. 183.
    Felmet K, Nguyen T, Clark RS, Orr D, Carcillo J. The FDA warning against prolonged sedation with propofol in children remains warranted. Pediatrics. 2003;112(4):1002–3 (author reply-3).Google Scholar
  184. 184.
    Cornfield DN, Tegtmeyer K, Nelson MD, Milla CE, Sweeney M. Continuous propofol infusion in 142 critically ill children. Pediatrics. 2002;110(6):1177–81.PubMedCrossRefGoogle Scholar
  185. 185.
    Fong JJ, Sylvia L, Ruthazer R, Schumaker G, Kcomt M, Devlin JW. Predictors of mortality in patients with suspected propofol infusion syndrome. Critical Care Med. 2008;36(8):2281–7. doi: 10.1097/CCM.0b013e318180c1eb.CrossRefGoogle Scholar
  186. 186.
    Diaz JH, Prabhakar A, Urman RD, Kaye AD. Propofol infusion syndrome: a retrospective analysis at a level 1 trauma center. Critical Care Res Pract. 2014;2014:346968. doi: 10.1155/2014/346968.Google Scholar
  187. 187.
    Vasile B, Rasulo F, Candiani A, Latronico N. The pathophysiology of propofol infusion syndrome: a simple name for a complex syndrome. Intensive Care Med. 2003;29(9):1417–25. doi: 10.1007/s00134-003-1905-x.PubMedCrossRefGoogle Scholar
  188. 188.
    Holzki J, Aring C, Gillor A. Death after re-exposure to propofol in a 3-year-old child: a case report. Paediatr Anaesth. 2004;14(3):265–70.PubMedCrossRefGoogle Scholar
  189. 189.
    Fudickar A, Bein B, Tonner PH. Propofol infusion syndrome in anaesthesia and intensive care medicine. Curr Opin Anaesthesiol. 2006;19(4):404–10. doi: 10.1097/01.aco.0000236140.08228.f1.PubMedCrossRefGoogle Scholar
  190. 190.
    Culp KE, Augoustides JG, Ochroch AE, Milas BL. Clinical management of cardiogenic shock associated with prolonged propofol infusion. Anesth Analg. 2004;99(1):221–6.PubMedCrossRefGoogle Scholar
  191. 191.
    Crawford MW, Dodgson BG, Holtby HH, Roy WL. Propofol syndrome in children. CMAJ = journal de l’Association medicale canadienne. 2003;168(6):669.Google Scholar
  192. 192.
    Koriyama H, Duff JP, Guerra GG, Chan AW, Sedation W, Analgesia T. Is propofol a friend or a foe of the pediatric intensivist? Description of propofol use in a PICU*. Pediatr Crit Care Med. 2014;15(2):e66–71. doi: 10.1097/PCC.0000000000000021.PubMedCrossRefGoogle Scholar
  193. 193.
    Fodale V, La Monaca E. Propofol infusion syndrome: an overview of a perplexing disease. Drug Saf. 2008;31(4):293–303.PubMedCrossRefGoogle Scholar
  194. 194.
    Wolf A, Weir P, Segar P, Stone J, Shield J. Impaired fatty acid oxidation in propofol infusion syndrome. Lancet. 2001;357(9256):606–7. doi: 10.1016/S0140-6736(00)04064-2.PubMedCrossRefGoogle Scholar
  195. 195.
    Orser BA, Bertlik M, Wang LY, MacDonald JF. Inhibition by propofol (2,6 di-isopropylphenol) of the N-methyl-d-aspartate subtype of glutamate receptor in cultured hippocampal neurones. Br J Pharmacol. 1995;116(2):1761–8.PubMedCentralPubMedCrossRefGoogle Scholar
  196. 196.
    Kingston S, Mao L, Yang L, Arora A, Fibuch EE, Wang JQ. Propofol inhibits phosphorylation of N-methyl-d-aspartate receptor NR1 subunits in neurons. Anesthesiology. 2006;104(4):763–9.PubMedCrossRefGoogle Scholar
  197. 197.
    Anker-Moller E, Spangsberg N, Arendt-Nielsen L, Schultz P, Kristensen MS, Bjerring P. Subhypnotic doses of thiopentone and propofol cause analgesia to experimentally induced acute pain. Br J Anaesth. 1991;66(2):185–8.PubMedCrossRefGoogle Scholar
  198. 198.
    Merrill AW, Barter LS, Rudolph U, Eger EI, 2nd, Antognini JF, Carstens MI, et al. Propofol’s effects on nociceptive behavior and spinal c-fos expression after intraplantar formalin injection in mice with a mutation in the gamma-aminobutyric acid-type(A) receptor beta3 subunit. Anesth Analg. 2006;103(2):478–83. doi:  10.1213/01.ane.0000223847.50233.1b.
  199. 199.
    Frolich MA, Price DD, Robinson ME, Shuster JJ, Theriaque DW, Heft MW. The effect of propofol on thermal pain perception. Anesth Analg. 2005;100(2):481–6. doi: 10.1213/01.ANE.0000142125.61206.7A.PubMedCrossRefGoogle Scholar
  200. 200.
    Cheng SS, Yeh J, Flood P. Anesthesia matters: patients anesthetized with propofol have less postoperative pain than those anesthetized with isoflurane. Anesth Analg. 2008;106(1):264–9. doi: 10.1213/01.ane.0000287653.77372.d9.
  201. 201.
    Tan T, Bhinder R, Carey M, Briggs L. Day-surgery patients anesthetized with propofol have less postoperative pain than those anesthetized with sevoflurane. Anesth Analg. 2010;111(1):83–5. doi: 10.1213/ANE.0b013e3181c0ee9e.PubMedGoogle Scholar
  202. 202.
    Fassoulaki A, Melemeni A, Paraskeva A, Siafaka I, Sarantopoulos C. Postoperative pain and analgesic requirements after anesthesia with sevoflurane, desflurane or propofol. Anesth Analg. 2008;107(5):1715–9. doi: 10.1213/ane.0b013e318182d84e.PubMedCrossRefGoogle Scholar
  203. 203.
    Boccara G, Mann C, Pouzeratte Y, Bellavoir A, Rouvier A, Colson P. Improved postoperative analgesia with isoflurane than with propofol anaesthesia. Can J Anaesth. 1998;45(9):839–42. doi: 10.1007/BF03012216.PubMedCrossRefGoogle Scholar
  204. 204.
    Singler B, Troster A, Manering N, Schuttler J, Koppert W. Modulation of remifentanil-induced postinfusion hyperalgesia by propofol. Anesth Analg. 2007;104(6):1397–403. doi: 10.1213/01.ane.0000261305.22324.f3.
  205. 205.
    Bandschapp O, Filitz J, Ihmsen H, Berset A, Urwyler A, Koppert W, et al. Analgesic and antihyperalgesic properties of propofol in a human pain model. Anesthesiology. 2010;113(2):421–8. doi: 10.1097/ALN.0b013e3181e33ac8.PubMedCrossRefGoogle Scholar
  206. 206.
    Hasani A, Gecaj-Gashi A, Llullaku S, Jashari H. Postoperative analgesia in children after propofol versus sevoflurane anesthesia. Pain Med. 2013;14(3):442–6. doi: 10.1111/pme.12031.PubMedCrossRefGoogle Scholar
  207. 207.
    Wang QY, Cao JL, Zeng YM, Dai TJ. GABAA receptor partially mediated propofol-induced hyperalgesia at superspinal level and analgesia at spinal cord level in rats. Acta Pharmacol Sinica. 2004;25(12):1619–25.Google Scholar
  208. 208.
    Bercker S, Bert B, Bittigau P, Felderhoff-Muser U, Buhrer C, Ikonomidou C, et al. Neurodegeneration in newborn rats following propofol and sevoflurane anesthesia. Neurotoxicity Res. 2009;16(2):140–7. doi: 10.1007/s12640-009-9063-8.CrossRefGoogle Scholar
  209. 209.
    Ikonomidou C, Bosch F, Miksa M, Bittigau P, Vockler J, Dikranian K, et al. Blockade of NMDA receptors and apoptotic neurodegeneration in the developing brain. Science. 1999;283(5398):70–4.PubMedCrossRefGoogle Scholar
  210. 210.
    Cattano D, Young C, Straiko MM, Olney JW. Subanesthetic doses of propofol induce neuroapoptosis in the infant mouse brain. Anesth Analg. 2008;106(6):1712–4. doi: 10.1213/ane.0b013e318172ba0a.PubMedCrossRefGoogle Scholar
  211. 211.
    Creeley C, Dikranian K, Dissen G, Martin L, Olney J, Brambrink A. Propofol-induced apoptosis of neurones and oligodendrocytes in fetal and neonatal rhesus macaque brain. Br J Anaesth. 2013;110(Suppl 1):i29–38. doi: 10.1093/bja/aet173.PubMedCentralPubMedCrossRefGoogle Scholar
  212. 212.
    Pearn ML, Hu Y, Niesman IR, Patel HH, Drummond JC, Roth DM, et al. Propofol neurotoxicity is mediated by p75 neurotrophin receptor activation. Anesthesiology. 2012;116(2):352–61. doi: 10.1097/ALN.0b013e318242a48c.PubMedCentralPubMedCrossRefGoogle Scholar
  213. 213.
    Cortinez LI, De la Fuente N, Eleveld DJ, Oliveros A, Crovari F, Sepulveda P, et al. Performance of propofol target-controlled infusion models in the obese: pharmacokinetic and pharmacodynamic analysis. Anesth Analg. 2014;119(2):302–10. doi: 10.1213/ANE.0000000000000317.PubMedCrossRefGoogle Scholar
  214. 214.
    Eleveld DJ, Proost JH, Cortinez LI, Absalom AR, Struys MM. A general purpose pharmacokinetic model for propofol. Anesth Analg. 2014;118(6):1221–37. doi: 10.1213/ANE.0000000000000165.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Vidya Chidambaran
    • 1
    • 2
  • Andrew Costandi
    • 1
    • 2
  • Ajay D’Mello
    • 1
  1. 1.Department of AnesthesiaCincinnati Children’s Hospital Medical CenterCincinnatiUSA
  2. 2.Department of Anesthesia and Pediatrics, College of MedicineUniversity of CincinnatiCincinnatiUSA

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