The Use of Propofol for Continuous Deep Sedation at the End of Life: A Definitive Guide

References

• Thompson KA, Goodale DB. The recent development of propofol (DIPRIVAN). Intensive Care Med. 2000;26:S400–S404. doi:10.1007/PL00003783.
   PubMed Web of Science ®Google Scholar
• Khan MS, Zetterlund E-L, Gréen H, Oscarsson A, Zackrisson A-L, Svanborg E, Lindholm M-L, Persson H, Eintrei C. Pharmacogentics, plasma concentrations, clinical signs and EEG during propofol treatment. Basic Clin Pharmacol Toxicol. 2014;115:565–70.
   PubMed Web of Science ®Google Scholar
• Lichtenbelt B, Mertens M, Vuyk J. Strategies to optimize propofol-opioid anesthesia. Clin Pharmacokinet. 2004;43:577–93.
   PubMed Web of Science ®Google Scholar
• Choi GJ, Kang H, Baek CW, Jung YH, Lee JJ. Comparison of bolus versus continuous infusion of propofol for procedural sedation: a meta-anyalysis. Curr Med Res Opin. 2017;33:1935–43. doi:10.1080/03007995.2017.1370419.
   PubMed Web of Science ®Google Scholar
• Astra-Zeneca. Diprivan (package insert). [accessed 2018 Nov 10].
   Google Scholar
• Diprivan (propofol) injectible emulsion for IV administration. [accessed 2019 Mar 24]. http://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?id=4756.
   Google Scholar
• Longnecker D, Brown D, Newman N. Anaesthesiology. 2nd ed. New York (NY): McGraw Hill; 2012.
   Google Scholar
• Shafer S. Advances in propofol pharmacokinetics and pharmacodynamics. J Clin Anesth. 1993;5:14–21.
   Web of Science ®Google Scholar
• Miller R, Eriksson C, Fleisher L. Millers anesthia. 8th ed. Elsevier Health Services; 2014 [accessed 2015 May 30] http://books.google.com/books?isbn=0323280110.
   Google Scholar
• Katzung B, Trevor A. Basic & clinical pharmacology. 13th ed. New York (NY): McGraw Hill; 2015.
   Google Scholar
• Rex DK, Overley C, Kinser K, Coates M, Lee A, Goodwine BW, Strahl E, Lemler S, Sipe B, Rahmani E, et al. Safety of propofol administered by registered nurses with gastroenterologist supervision in 2000 endoscopic cases. Am J Gastroenterol. 2002;97:1159–63. doi:10.1111/j.1572-0241.2002.05683.x.
   PubMed Web of Science ®Google Scholar
• Bennett J, Shafer DM, Efaw D, Goupil M. Incremental bolus versus a continuous infusion of propofol for deep sedation/general anesthesia during dentoalveolar surgery. J Oral Maxillofac Surg. 1998;56:1049–53.
   PubMed Web of Science ®Google Scholar
• Albanese J, Martin C, Lacarelle B. Pharmocokinetics of long term propofol infusion used for sedation in ICU patients. Anaesthesiology. 1990;72:214–7. doi:10.1097/00000542-199008000-00004.
   Google Scholar
• Adult ICU pain and sedation guideline for mechanically ventilated patients. [accessed 2018 Apr 16] http://qio.ipro.org/wp-content/uploads/2016/02/ICU_Pain_and_Sedation_Guideline_508.pdf.
   Google Scholar
• Whitehouse T, Snelson C, Grounds M, Sedation committee of the Intensive Care Society United Kingdom. 2014. [accessed 2019 Apr 2] https://www.ics.ac.uk/AsiCommon/Controls/BSA/Downloader.aspx?iDocumentStorageKey=1c32a885-51fe-495b-a63f-1335323db5da&iFileTypeCode=PDF&iFileName=Sedation%20for%20Patients%20in%20ICU.
   Google Scholar
• Klemola UM, Mennander S, Saarnivaara L. Tracheal intubation without the use of muscle relaxants: remifentanil or alfentanil in combination with propofol. Acta Anaesthesiol Scand. 2000;44:465–9. doi:10.1034/j.1399-6576.2000.440419.x.
   PubMed Web of Science ®Google Scholar
• Erhan E, Ugur G, Alper I, Gunusen I, Ozyar B. Tracheal intubation without muscle relaxants: remifentanil or alfentanil in combination with propofol. Eur J Anaesth. 2003;20:37–43. doi:10.1097/00003643-200301000-00007.
   PubMed Web of Science ®Google Scholar
• Stecker MM, Kramer TH, Raps EC, O’Meeghan R, Dulaney E, Skaar DJ. Treatment of refractory status epilepticus with propofol: clinical and pharmacokinetic findings. Epilepsia. 1998;39:18–26.
   PubMed Web of Science ®Google Scholar
• Illievich UM, Petricek W, Schramm M. Electroencephalographic burst supression by propofol infusion in humans: hemodynamic consequences. Anesth Analg. 1993;77:155–60.
   PubMed Web of Science ®Google Scholar
• Lundstrom S, Zachrisson U, Furst C. Propofol as a sedative and antiemetic in palliative cancer care. J Pain Symptom Manage. 2005;30:570–7.
   PubMed Web of Science ®Google Scholar
• Sykes N, Thorns A. Sedative use in the last week of life and the implications for end-of-life decision making. Arch Intern Med. 2003;163:341–4.
   PubMed Web of Science ®Google Scholar
• Moyle J. The use of propofol in palliative medicine. J Pain Symptom Manage. 1995;10:643–6.
   PubMed Web of Science ®Google Scholar
• Mercadante S, De Conno F, Ripamonti C. Propofol in terminal care. J Pain Symptom Manage. 1995;10:639–42.
   PubMed Web of Science ®Google Scholar
• Bodnar J. A review of agents for palliative sedation/continuous deep sedation: pharmacology and practical applications. J Pain Palliat Care Pharmacother. 2017;31:16–37. doi:10.1080/15360288.2017.1279502.
   PubMed Web of Science ®Google Scholar
• Kettemann D, Funke A, Maier A, Rosseau S, Meyer R, Spittel S, Münch C, Meyer T. Clinical characteristics and course of dying in patients with amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener. 2017;18:53–9. doi:10.1080/21678421.2016.1214734.
   PubMed Web of Science ®Google Scholar
• Epker JL, Bakker J, Lingsma HF, Kompanje EJO. An observational study on a protocal for withdrawal of life-sustaining measures on two non-academic intesnive care units in the Netherlands: few signs of distress, no suffering? J Pain Symtom Manage. 2015;50:676–84. doi:10.1016/j.jpainsymman.2015.05.017.
   PubMed Web of Science ®Google Scholar
• Berger A, Shuster J, Von Roenn J. Palliative care and supportive oncology. Philadelphia (PA): Lippincott Williams and Wilkins; 2007.
   Google Scholar
• Johnson K. Clinical pharmacology for anesthesiology. New York (NY): McGraw Hill; 2015.
   Google Scholar
• Reeves JG, Glass PSA, Lubarsky DA. Non-barbiturate intravenous anesthetics. In: Miller R, editor. Anesthesia. Churchill Livingston; 2000. p. 249–56.
   Google Scholar
• Lichtenbelt B. PK-PD modelling of the interaction of propofol and midazolam: implementation and future perspectives. Leiden University Repository. [accessed 2018 Apr 20] https://openaccess.leidenuniv.nl/bitstream/handle/1887/20616/BJLichtenbelt.pdf?sequence=18.
   Google Scholar
• Moon SH. Sedation regimens for gastrointestinal endoscopy. Clin Endosc. 2014;47:135–40. doi:10.5946/ce.2014.47.2.135.
   PubMedGoogle Scholar
• Morgan D, Campbell G, Crankshaw D. Pharmacokinetics of propofol when given by intravenous infusion. Br J Clin Pharmac. 1990;30:144–8.
   PubMed Web of Science ®Google Scholar
• Barr J, Egan TD, Sandoval NF, Zomorodi K, Cohane C, Gambus PL, Shafer SL. Propofol dosing regimens for ICU sedation based upon an integrated pharmacokinetic-pharmacodynamic model. Anesthesiology. 2001;95:324–33. doi:10.1097/00000542-200108000-00011.
   PubMed Web of Science ®Google Scholar
• Barrientos-Vega R, Mar Sánchez-Soria M, Morales-García C, Robas-Gómez A, Cuena-Boy R, Ayensa-Rincon A. Prolonged sedation of critically ill patients with midazolam or propofol: impact on weaning and costs. Crit Care Med. 1997;25:33–40. doi:10.1097/00003246-199701000-00009.
   PubMed Web of Science ®Google Scholar
• Weinbroum AA, Rudick V, Sorkine P, Freedman M, Geller E, Halpern P. Midazolam versus propofol for long-term sedation in the ICU: a randomized prospective comparison. Intensive Care Med. 1997;23:1258–63. doi:10.1007/s001340050495.
   PubMed Web of Science ®Google Scholar
• Higgins TL, Yared J-P, Estafanous FG, Coyle JP, Ko HK, Goodale DB. Propofol versus midazolam for intensive care unit sedation after coronary artery bypass grafting. Crit Care Med. 1994;22:1415–23. doi:10.1097/00003246-199409000-00011.
   PubMed Web of Science ®Google Scholar
• Beller JP, Pottecher T, Lugnier A, Mangin P, Otteni JC. Prolonged sedation with propofol in ICU patients: recovery and blood concentration changes during periodic interruptions in infusion. Br J Anaesth. 1988;61:583–8. doi:10.1093/bja/61.5.583.
   PubMed Web of Science ®Google Scholar
• Kumar P. Propofol. [accessed 2019 Mar 21] http://www.anesthesia.co.in/wp-content/uploads/2012/05/propofol.pdf.
   Google Scholar
• Garcia P, Kolesky S, Jenkins A. General anesthesia actions on GABAA receptors. Curr Neuropharm. 2010;8:2–9.
   PubMed Web of Science ®Google Scholar
• Sieghart W. Structure, pharmacology, and function of GABAA receptor subtypes. Adv Pharmacol. 2006;54:231–63.
   PubMedGoogle Scholar
• Franks NP, Lieb WR. Molecular and cellular mechanisms of general anesthesia. Nature. 1994;367:607–14. doi:10.1038/367607a0.
   PubMed Web of Science ®Google Scholar
• Saar TI, Uusi-Oukari M, Ahonen J. Enhancement of GABAergic activity: neuropharmacological effects of benzodiazepines and therapeutic use in anesthesia. Pharmacol Rev. 2011;63:243–67.
   PubMed Web of Science ®Google Scholar
• Rho JM, Donevan SD, Rogawski MA. Direct activation of GABAA receptors by bartiturates in cultured rat hippocampal neurons. J Physiol. 1996;497:509–22. doi:10.1113/jphysiol.1996.sp021784.
   PubMed Web of Science ®Google Scholar
• Rosen A, Bali M, Horenstein J, Akabas MH. Channel opening by anesthetics and GABAA induces similar changes in the GABAA receptor M2 segment. Biophys J. 2007;92:3130–9. doi:10.1529/biophysj.106.094490.
   PubMed Web of Science ®Google Scholar
• Bianchi MT, Botzolakis EJ, Lagrange AH, Macdonald RL. Benzodiazepine modulation of GABAA receptor opening frequency depends on activation context: a patch clamp and simulation study. Epilepsy Res. 2009;85:212–20. doi:10.1016/j.eplepsyres.2009.03.007.
   PubMed Web of Science ®Google Scholar
• Sanna E, Garau F, Harris RA. Novel properties of homomeric beta 1 gamma-aminobutyric acid type A receptors: actions of the anesthetics propofol and pentobarbital. Mol Pharmacol. 1995;47:213–7.
   PubMed Web of Science ®Google Scholar
• Orser BA, Wang LY, Pennefather PS, MacDonald JF. Propofol modulates activation and desensitization of GABAA receptors in cultered murine hippocampal neurons. J Neurosci. 1994;14:7747–60. doi:10.1523/JNEUROSCI.14-12-07747.1994.
   PubMed Web of Science ®Google Scholar
• Adodra S, Hales TG. Potentiation, activation, and blockade of GABAA receptors of clonal murine hypothalamic GT1-7 neurones by propofol. Br J Pharmacol. 1995;115:953–60.
   PubMed Web of Science ®Google Scholar
• Williams D, Akabas M. Structural evidence that propofol stabilizes different GABAA receptor states at potentiating and activing concentrations. J Neurosci. 2002;22:7417–24. doi:10.1523/JNEUROSCI.22-17-07417.2002.
   PubMed Web of Science ®Google Scholar
• Krasowski MD, Koltchine VV, Rick CE, Ye Q, Finn SE, Harrison NL. Propofol and other intravenous anesthetics have sites of action on the gamma-aminobutyric acid type A receptor distinct from that of isoflurane. Mol Pharmacol. 1998;53:530–8. doi:10.1124/mol.53.3.530.
   PubMed Web of Science ®Google Scholar
• McAdam L, Propofol and benzodiazepine modulation of GABAAR function. [accessed 2018 Mar 12] www.tspace.library.utoronto.ca.
   Google Scholar
• 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;274:353–60.
   PubMed Web of Science ®Google Scholar
• Lam DW, Reynolds JN. Modulatory and direct effects of propofol on recombinant GABAA receptors expressed in Xenopus oocytes: influence of alpha and gamma2 subunits. Brain Res. 1998;784:178–86.
   Web of Science ®Google Scholar
• McAdam LC, MacDonald JF, Orser BA. Isobolographic analysis of the interactions between midazolam and propofol at GABAA receptors in embryonic mouse neurons. Anesthesiology. 1998;6:1444–54.
   Google Scholar
• Kaci D. Propofol drug information professional drugs.com. 2019. [accessed 2019 March 16] www.drugs.com/mmx/propofol.html.
   Google Scholar
• Sprung J, Ogletree-Hughes ML, McConnell BK, Zakhary DR, Smolsky SM, Moravec CS. The effects of propofol on the contractility of failing and nonfailing human heart muscles. Anesth Analg. 2001;93:550–9.
   PubMed Web of Science ®Google Scholar
• Sutter Health. Society of Critical Care Medicine: Sacramento-Sierra Regional ICU delerium protocal. 2013. [accessed 2018 Apr 26] http://www.iculiberation.org/sitecollectiondocuments/implementation-sutter-health-order-set.pdf.
   Google Scholar
• Barr J, Egan TD, Sandoval NF, Zomorodi K, Cohane C, Gambus PL, Shafer SL. Propofol dosing regiments for ICU sedation based upon an integrated pharmacokinetic-pharmacodynamic model. Anesthesiology. 2001;95:324–33. doi:10.1097/00000542-200108000-00011.
   PubMed Web of Science ®Google Scholar
• Bouillon TW, Bruhn J, Radulescu L, Andresen C, Shafer TJ, Cohane C, Shafer SL. Pharmacodynamic interaction between propofol and remifentanil regarding hypnosis, tolerance of laryngoscopy, bispectral index, and electroencephalographic approximate entropy. Anesthesiology. 2004;100:1353–72. doi:10.1097/00000542-200406000-00006.
   PubMed Web of Science ®Google Scholar
• Yufune S, Takamatsu I, Masui K, Kazama T. Effect of remifentanil on plasma propofol concentration and bispectral index during propofol anesthesia. Brit J Anaesth. 2011;106:208–14. doi:10.1093/bja/aeq334.
   PubMed Web of Science ®Google Scholar
• de Wit M, Epstein S. Administration of sedatives and level of sedation: comparative evaluation via the Sedation-Agitation Scale and the Bisspectral Index. Am J Crit Care. 2003;12:343–8.
   PubMed Web of Science ®Google Scholar
• Masica AL, Girard TD, Wilkinson GR, Thomason JWW, Truman Pun B, Nair UB, Light RW, Canonico AE, Dunn J, Pandharipande P, et al. Clinical sedation scores as indicators of sedative and analgesic drug exposure in intensive care unit patients. Am J Geriatr Pharmacother. 2007;5:218–30. doi:10.1016/j.amjopharm.2007.10.005.
   PubMedGoogle Scholar
• Glass PS, Bloom M, Kearse L, Rosow C, Sebel P, Manberg P. Bispectral analysis measures sedation and memory effects of propofol, midazolam, isoflurane, and alfentanil in healthy volunteers. Anesthesiology. 1997;86:836–47. doi:10.1097/00000542-199704000-00014.
   PubMed Web of Science ®Google Scholar
• Orser BA, McAdam LC, Roder S, MacDonald JF. General anaesthetics and their effects on GABAA receptor desensitization. Toxicol Lett. 1998;100-101:217–24. doi:10.1016/S0378-4274(98)00188-X.
   PubMed Web of Science ®Google Scholar
• Orser BA, Canning K, MacDonald JF. Mechanisms of general anesthesia. Curr Opin Anaesthesiol. 2002;15:427–33.
   PubMedGoogle Scholar
• Bai D, Pennefather PS, MacDonald JF, Orser BA. The general anesthetic propofol slows deactivation and desensitization of GABAA receptors. J Neurosci. 1999;19:10635–46. doi:10.1523/JNEUROSCI.19-24-10635.1999.
   PubMed Web of Science ®Google Scholar
• Oh DJ, Dichter MA. Desensitization of GABA-induced currents in cultured rat hippocampal neurons. Neuroscience. 1992;49:571–6. doi:10.1016/0306-4522(92)90227-s.
   PubMed Web of Science ®Google Scholar
• Overstreet L, Jones M, Westbrook G. Slow desensitization regulates the availabilty of synaptic GABAA receptors. J Neurosci. 2000;20:7914–21. doi:10.1523/JNEUROSCI.20-21-07914.2000.
   PubMed Web of Science ®Google Scholar
• Bianchi MT, MacDonald RL. Slow phases of GABAA receptor desensitization: structural determinants and possible relevance for synaptic function. J Physiol. 2002;544:3–18. doi:10.1113/jphysiol.2002.020255.
   PubMed Web of Science ®Google Scholar
• 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;73:214–7. doi:10.1097/00000542-199008000-00004.
   PubMed Web of Science ®Google Scholar
• Ballie GR, Cockshott ID, Douglas EJ, Bowles BJ. Pharmacokinetics of propofol during and after long term continuous infusion for maintenance of sedation in ICU patients. Br J Anaesth. 1992;68:486–91.
   PubMed Web of Science ®Google Scholar
• Frenkel C, Schüttler J, Ihmsen H, Heye H, Rommelsheim K. Pharmacokinetics and pharmacodynamics of propofol/alfentanil infusion for sedation in ICU patients. Intens Care Med. 1995;21:981–8.
   PubMed Web of Science ®Google Scholar
• Shafer A, Doze VA, Shafer SL, White PF. Pharmacokinetics and pharmacodynamics of propofol infusions during general anesthesia. Anesthesiology. 1988;69:348–56. doi:10.1097/00000542-198809000-00011.
   PubMed Web of Science ®Google Scholar
• Schuttler J, Stoeckel H, Schwilden H. Pharmacokinetic and pharmacodynamic modeling of propofol (Diprivan) in volunteers and surgical patients. Postgrad Med J. 1989;61:53–4.
   Google Scholar
• Peeters MYM, Bras LJ, DeJongh J, Wesselink RMJ, Aarts LPHJ, Danhof M, Knibbe CAJ. Disease severity is a major determinant for the pharmacodynamics of propofol in critically ill patients. Clin Pharmacol Ther. 2008;83:443–51. doi:10.1038/sj.clpt.6100309.
   PubMed Web of Science ®Google Scholar
• Eleveld DJ, Colin P, Absalom AR, Struys MMRF. Pharmacokinetic-pharmacodyamic model for propofol for broad application in anaesthesia and sedation. Br J Anesth. 2018;120:942–59. doi:10.1016/j.bja.2018.01.018.
   PubMed Web of Science ®Google Scholar
• Sahinovic M, Struys M, Absalom A. Clinical pharmacokinetics and pharmacodynamics of propofol. Clin Pharmacokinet. 2018;57:1539–58. doi:10.1007/s40262-018-0672-3.
   PubMed Web of Science ®Google Scholar
• Hiraoka H, Yamamoto K, Miyoshi S, Morita T, Nakamura K, Kadoi Y, Kunimoto F, Horiuchi R. Kidneys contribute to the extrahepatic clearance of propofol in humans, but not lungs and brain. Br J Clin Pharmacol. 2005;60:176–82. doi:10.1111/j.1365-2125.2005.02393.x.
   PubMed Web of Science ®Google Scholar
• 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;75:324–30. doi:10.1016/j.clpt.2003.12.004.
   PubMed Web of Science ®Google Scholar
• Knibbe CAJ, Zuideveld KP, DeJongh J, Kuks PFM, Aarts LPHJ, Danhof M. Population pharmacokinetic and pharmacodynamic modeling of propofol for long-term sedation in critically ill patients: a comparison between propofol 6% and propofol 1%%. Clin Pharmacol Ther. 2002;72:670–84. doi:10.1067/mcp.2002.129500.
   PubMed Web of Science ®Google Scholar
• Schuttler J, Ihmsen H. Population pharmacokinetics of propofol: a multicenter study. Anesthesiology. 2000;92:727–38. doi:10.1097/00000542-200003000-00017.
   PubMed Web of Science ®Google Scholar
• Gepts E, Camu F, Cockshott ID, Douglas EJ. Disposition of propofol administered as constant rate intravenous infusions in humans. Anesth Analg. 1987;66:1256–63.
   PubMed Web of Science ®Google Scholar
• Bailey JM, Mora CT, Shafer SL. Pharmacokinetics of propofol in adult patients undergoing coronary revascularization. The Multicenter Study Perioperative Ischemia Res Group. Anesthesiology. 1996;84:1288–97. doi:10.1097/00000542-199606000-00003.
   PubMed Web of Science ®Google Scholar
• Takizawa D, Sato E, Hiraoka H, Tomioka A, Yamamoto K, Horiuchi R, Goto F. Changes in apparent systemtic clearance of propofol during transplantaion of living related donor liver. Br J Anaesth. 2005;95:643–7. doi:10.1093/bja/aei243.
   PubMed Web of Science ®Google Scholar
• Gemayel J, Geloen A, Mion F. Propofol-induced cytochrome P450 inhibition: an in vitro and in vivo study in rats. Life Sci. 2001;68:2957–65. doi:10.1016/s0024-3205(01)01091-8.
   PubMed Web of Science ®Google Scholar
• Yang L-Q, Yu W-F, Cao Y-F, Gong B, Chang Q, Yang G-S. Potential inhibition of cytochrome P450 3A4 by propofol in human primary hepatocytes. World J Gastroenterol. 2003;9:1959–62. doi:10.3748/wjg.v9.i9.1959.
   PubMed Web of Science ®Google Scholar
• Sweeney BP, Bromilow J. Liver enzyme induction and inhibition: implications for anaesthesia. Anesthesia. 2006;61:159–77. doi:10.1111/j.1365-2044.2005.04462.x.
   PubMed Web of Science ®Google Scholar
• Oda Y, Hamaoka N, Hiroi T, Imaoka S, Hase I, Tanaka K, Funae Y, Ishizaki T, Asada A. Involvement of human liver cytochrome P4502B6 in the metabolism of propofol. Br J Clin Pharmacol. 2001;51:281–5. doi:10.1046/j.1365-2125.2001.00344.x.
   PubMed Web of Science ®Google Scholar
• Vuyk J. Pharmacokinetic and pharmacodynamic interactions between opioids and propofol. J Clin Anesth. 1997;9:23S–6S.
   PubMed Web of Science ®Google Scholar
• Atchabahian A, Gupta K. The anesthesia guide. New York (NY): McGraw Hill; 2013.
   Google Scholar
• Mertens MJ, Vuyk J, Olofsen E, Bovill JG, Burm AG. Propofol alters the pharmacokinetics of alfentanil in healthy male volunteers. Anesthesiology. 2001;94:949–57. doi:10.1097/00000542-200106000-00006.
   PubMed Web of Science ®Google Scholar
• Vuyk J, Lim T, Engbers FHM, Burm AGL, Vletter AA, Bovill JG. The pharmacokinetic interaction of propofol and alfentanil during lower abdominal surgery in women. Anesthesiology. 1995;83:8–22. doi:10.1097/00000542-199507000-00003.
   PubMed Web of Science ®Google Scholar
• Mertens MJ, Olofsen E, Engbers FHM, Burm AGL, Bovill JG, Vuyk J. Propofol reduces perioperative remifentanil requirements in a synergistic manner. Response surface modeling of perioperative remifentanil-propofol interactions. Anesthesiology. 2003;99:347–59.
   PubMed Web of Science ®Google Scholar
• Ahonen J, Olkkola KT, Hynynen M, Seppälä T, Ikävalko H, Remmerie B, Salmenperä M. Comparison of alfentanil, fentanyl and sufentanil for total intravenous anesthesia with propofol in patients undergoing coronary bypass surgery. Brit J Anaesth. 2000;85:533–40. doi:10.1093/bja/85.4.533.
   PubMed Web of Science ®Google Scholar
• Smith D, McEwan A, Jhaveri R. The interaction of fentanyl on the Cp50 of propofol for loss of consciousness and skin incision. Anesthesiology. 1994;81:820–8.
   PubMed Web of Science ®Google Scholar
• Kazama T, Ikeda K, Morita K. Reduction by fentanyl of the CP50 values of propofol and hemodynamic responses to various noxious stimuli. Anesthesiology. 1997;87:213–7. doi:10.1097/00000542-199708000-00007.
   PubMed Web of Science ®Google Scholar
• 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;87:1549–62. doi:10.1097/00000542-199712000-00033.
   PubMed Web of Science ®Google Scholar
• Kodaka M, Okamoto Y, Handa F, Kawasaki J, Miyao H. Relation between fentanyl dose and predicted EC50 of propofol for laryngeal mask insertion. Br J Anaesth. 2004;92:238–241. doi:10.1093/bja/aeh033.
   PubMed Web of Science ®Google Scholar
• Borrat X, Valencia JF, Magrans R, Gimenez-Mila M, Mellado R, Sendino O, Perez M, Nunez M, Jospin M, Jensen EW, et al. Sedation-analgesia with propofol and remifentanil: concentrations required to avoid gag reflex in upper gastrointestinal endoscopy. Anesth Analg. 2015;121:90–6. doi:10.1213/ANE.0000000000000756.
   PubMed Web of Science ®Google Scholar
• Johnson KB, Syroid ND, Gupta DK, Manyam SC, Egan TD, Huntington J, White JL, Tyler D, Westenskow DR. Validation of remifentanil propofol response surfaces for sedation, surrogates of surgical stimuli, and laryngoscopy in patients undergoing surgery. Anesth Analg. 2008;106:471. doi:10.1213/ane0b013e3181606c62.
   PubMed Web of Science ®Google Scholar
• Li S, Yu F, Zhu H, Yang Y, Yang L, Lian J. The median effective concentration of propofol with different doses of fentanyl during colonoscopy in elderly patients. BMC Anesthesiol. 2015;16:24. doi:10.1186/s12871-016-0189-y.
   Web of Science ®Google Scholar
• Thaharavanich R, Sintavanuruk K, Laosuwan S, Pongruekdee S. Predicted EC50 of propofol using target controlled infusion with and without fentanyl for colonoscopy. J Med Assoc Thai. 2011;94:813–8.
   PubMedGoogle Scholar
• Mollhoff T, Herregods L, Moerman A, Blake D, MacAdams C, Demeyere R, Kirnö K, Dybvik T, Shaikh S; Remifentanil Study Group. Comparative efficacy and safety of remifentanil and fentanyl in 'fast track' coronary artery bypass graft surgery: a randomized, double-blind study. Br J Anaesth. 2001;87:718–26. doi:10.1093/bja/87.5.718.
   PubMed Web of Science ®Google Scholar
• Geisler FEA, de Lange S, Royston D, Demeyere R, Duthie DJR, Lehot J-J, Adt M, Dupeyron J-P, Mansfield M, Kirkham AJT, et al. Efficacy and safety of remifentanil in coronacry artery bipass graft surgery: a randomized, double-blind dose comparison study. J Cardiothorac Vasc Anesth. 2003;17:60–8. doi:10.1053/jcan.2003.11.
   PubMed Web of Science ®Google Scholar
• Xia Z, Huang Z, Ansley D. Large-dose propofol during cardiopulmonary bypass decreases biochemical markers of myocardial injury in coronary surgery patients: a comparison with isoflurane. Anesth Analg. 2006;103:527–32. doi:10.1213/01.ane.0000230612.29452.a6.
   PubMed Web of Science ®Google Scholar
• Bodnar J. Terminal withdrawal of mechanical ventilation: a hospice perspective for the intensivist. J Intensive Care Med. 2019;43:156–64. doi:10.1177/0885066618797918.
   Google Scholar
• Carrasco G, Cabre L, Sobrepere G, Costa J, Molina R, Cruspinera A, Lacasa C. Synergistic sedation with propofol and midazolam in intensive care patients after coronary artery bypass grafting. Crit Care Med. 1998;26:844–51. doi:10.1097/00003246-199805000-00015.
   PubMed Web of Science ®Google Scholar
• McAdam LC, Propofol and benzodiazepine modulation of GABAAR function. 1997. [accessed 2018 Dec 6]. www.tspace.library.utoronto.ca/bitstream/1807/115/7/1/MQ29.
   Google Scholar
• Teh J, Short TG, Wong J, Tan P. Pharmacokinetic interactions between midazolam and propofol: an infusion study. Br J Anaesth. 1994;72:62–5. doi:10.1093/bja/72.1.62.
   PubMed Web of Science ®Google Scholar
• Vuyk J, Lichtenbelt BJ, Olofsen E, van Kleef JW, Dahan A. Mixed-effects modeling of the influence of midazolam on propofol pharmacokinetics. Anesth Analg. 2009;108:1522–30. doi:10.1213/ane.0b013e31819e4058.
   PubMed Web of Science ®Google Scholar
• Michalk S, Moncorge C, Fichelle A, Huot O, Servin F, Farinotti R, Desmonts JM. Midazolam infusion for basal sedation in intensive care: absence of accumulation. Intensive Care Med. 1988;15:37–41. doi:10.1007/bf00255634.
   PubMed Web of Science ®Google Scholar
• Schmidt J, Hering W, Albrecht S. Total intravenous anesthesia with propofol and remifentanil. Results of a mulicenter study of 6,161 patients. Anaesthesist. 2005;54:17–28.
   PubMed Web of Science ®Google Scholar
• Miner J, Burton J. Clinical practice advisory: emergency department procedural sedation with propofol. Ann Emer Med. 2007;50:182–7.
   PubMed Web of Science ®Google Scholar
• Burton JH, Miner JR, Shipley ER, Strout TD, Becker C, Thode HC. Propofol for emergency department procedural sedation and analgesia: a tale of three centers. Acad Emerg Med. 2006;13:24–30.
   PubMed Web of Science ®Google Scholar
• Coll-Vincent B, Sala X, Fernandez C, Bragulat E, Espinosa G, Miró O, Millá J, Sánchez M. Sedation for cardioversion in the emergency department: analysis of effectiveness in four protocols. Ann Emerg Med. 2003;42:767–72. doi:10.1016/S0196-0644(03)00510-9.
   PubMedGoogle Scholar
• Miner JR, Biros MH, Krieg S, Johnson C, Heegaard W, Plummer D. Randomized clinical trial of propofol versus methohexital for procedural sedation during fracture and dislocation reduction in the emergency department. Acad Emerg Med. 2003;10:931–7. doi:10.1197/S1069-6563(03)00310-5.
   PubMed Web of Science ®Google Scholar
• Miner JR, Biros MH, Heegaard W, Plummer D. Bispectral electroencephalographic analysis of patients undergoing procedural sedation in emergency department. Acad Emergency Med. 2003;10:638–43. doi:10.1111/j.1553-2712.2003.tb00048.x.
   PubMed Web of Science ®Google Scholar
• Miner JR, Martel ML, Meyer M, Reardon R, Biros MH. Procedural sedation of critically ill patients in the emergency department. Acad Emerg Med. 2005;12:124–8. doi:10.1197/j.aem.2004.08.054.
   PubMedGoogle Scholar
• Miner JR, Bachman A, Kosman L, Teng B, Heegaard W, Biros MH. Assessment of the onset and persistence of amnesia during procedural sedation with propofol. Acad Emerg Med. 2005;12:491–5. doi:10.1197/j.aem.2005.01.011.
   PubMed Web of Science ®Google Scholar
• Sacchetti A, Senula G, Strickland J, Dubin R. Procedural sedation in the community emergency department: initial results of the ProSCED registry. Acad Emerg Med. 2007;14:41–6.
   PubMed Web of Science ®Google Scholar
• Frazee BW, Park RS, Lowery D, Baire M. Propofol for deep procedural sedation in the ED. Am J Emerg Med. 2005;23:190–5.
   PubMed Web of Science ®Google Scholar
• Frank LR, Strote J, Hauff SR, Bigelow SK, Fay K. Propofol by infusion protocol for ED procedural sedation. Am J Emerg Med. 2006;24:599–602.
   PubMed Web of Science ®Google Scholar
• Ramsay MAE, Newman KB, Jacobson RM, Richardson CT, Rogers L, Brown BJ, Hein HAT, Vol EBD, Daoud YA. Sedation levels during propofol administration for outpatient colonoscopies. Proc (Bayl Univ Med Cent). 2014;27:12–15.
   PubMedGoogle Scholar
• Rex DK, Heuss LT, Walker JA, Qi R. Trained registered nurses/endoscopy teams can administer propofol safely for endoscopy. Gastroenterology. 2005;129:1384–91.
   PubMed Web of Science ®Google Scholar
• Walker JA, Schleinitz PF, Jacobson KN, Haulk AA, Adesman PW. Propofol: multiple advantages for endoscopy and colonoscopy in 1,424 consecutive patients. Gastrointest Endosc. 2000;51:AB59.
   Web of Science ®Google Scholar
• Walker JA, McIntyre RD, Schleinitz PF, Jacobson KN, Haulk AA, Adesman P, Tolleson S, Parent R, Donnelly R, Rex DK, et al. Nurse-administered propofol sedation without anesthesia specialists in 9152 endoscopic cases in an ambulatory surgery center. Am J Gastroenterol. 2003;98:1744–50. doi:10.1111/j.1572-0241.2003.07605.x.
   PubMed Web of Science ®Google Scholar
• Butterworth J, Mackey D, Wisnick D. Morgan and Mikhail’s clinical anesthesiology. 5th ed. New York (NY): McGraw Hill; 2015.
   Google Scholar
• WebMD. RxList Diprivan. 2018. [accessed 2019 Feb 24]. http://www.rxlist.com/diprivan-drug/clinical-pharmacology.htm.
   Google Scholar
• Osborne GA, Rudkin GE, Curtis NJ, Vickers D, Craker AJ. Intraoperative patient controlled sedation. Comparison of patient-controlled propofol with anaesthetist-administered midazolam and fentanyl. Anaesthesia. 1991;46:553–6.
   PubMed Web of Science ®Google Scholar
• Claeys MA, Gepts E, Camu F. Haemodynamic changes during anaesthesia induced and maintained with propofol. Br J Anaesth. 1988;60:3–9. doi:10.1093/bja/60.1.3.
   PubMed Web of Science ®Google Scholar
• Goodman NW, Black AM, Carter JA. Some ventilatory effects of propofol as sole anaesthetic agent. Br J Anaesth. 1987;9:271–6.
   Google Scholar
• Taylor MB, Grounds RM, Mulrooney PD, Morgan M. Ventilatory effects of propofol during induction of anaesthesia. Comparison with thiopentone. Anaesthesia. 1986;41:816–20. doi:10.1111/j.1365-2044.1986.tb13123.x.
   PubMed Web of Science ®Google Scholar
• Sebel PS, Lowdon JD. Propofol: a new intraveous anesthetic. Anesthesiology. 1989;71:260–77. doi:10.1097/00000542-198908000-00015.
   PubMed Web of Science ®Google Scholar
• Larijani GE, Gratz I, Afshar M, Jacobi AG. Clinical pharmacology of propofol: an intravenous anesthetic agent. DICP. 1989;23:743–9.
   PubMedGoogle Scholar
• Robinson BJ, Ebert TJ, O’brien TJ, Colinco MD, Muzi M. Mechanisms whereby propofol mediates peripheral vasodilation in humans. Anesthesiology. 1997;86:64–72. doi:10.1097/00000542-199701000-00010.
   PubMed Web of Science ®Google Scholar
• Langley M, Heel R. Propofol. A review of its pharmacodynamic and pharmacokinetic properties and use as an intravenous anesthetic. Drugs. 1988;35:334–72.
   PubMed Web of Science ®Google Scholar
• Kazama T, Ikeda K, Morita K, Ikeda T, Kikura M, Sato S. Relation between initial blood distribution volume and propofol induction dose requirement. Anesthesiology. 2001;94:205–10. doi:10.1097/00000542-200102000-00007.
   PubMed Web of Science ®Google Scholar
• Oh C-S, Lee Y, Kang W-S, Kim S-H. Impact of effect-site concentration of propofol on cardiac systolic function assessed by tissue Doppler image. J Int Med Res. 2016;44:453–61.
   PubMed Web of Science ®Google Scholar
• Hsu W-H, Wang SS, Shih H-Y, Wu M-C, Chen Y-Y, Kuo F-C, Yang H-Y, Chiu S-L, Chu K-S, Cheng K-I, et al. Low effect-site concentration of propofol target-controlled infusion reduces the risk of hypotension during endoscopy in a Taiwanese population. J Dig Dis. 2013;14:147–52. doi:10.1111/1751-2980.12020.
   PubMed Web of Science ®Google Scholar
• Nieuwenhuijs D, Sarton E, Teppema LJ, Kruyt E, Olievier I, van Kleef J, Dahan A. Respiratory sites of action of propofol: absence of depression of peripheral chemoreflex loop by low-dose propofol. Anesthesiology. 2001;95:889–95. doi:10.1097/00000542-200110000-00017.
   PubMed Web of Science ®Google Scholar
• Bouillon T, Bruhn J, Radu-Radulescu L, Andresen C, Cohane C, Shafer SL. Mixed-effects modeling of the intrinsic ventilatory depressant potency of propofol in the non-steady state. Anesthesiology. 2003;99:779–87. doi:10.1097/00000542-200310000-00007.
   PubMed Web of Science ®Google Scholar
• Lee MH, Yang K-H, Lee CS, Lee HS, Moon SY, Hwang S-I, Song J-H. The effect-site concentration of propofol producing respiratory depression during spinal anesthesia. Korean J Anesthesiol. 2011;61:122–6. doi:10.4097/kjae.2011.61.2.122.
   PubMedGoogle Scholar
• Lee YS. Effects of propofol target-controlled infusion on haemodynamic and respiratory changes with regard to safety. J Int Med Res. 2004;32:19–24. doi:10.1177/147323000403200103.
   PubMed Web of Science ®Google Scholar
• Ghimire A, Bhattarai TR, Rahman TR, Singh SN, Koirala S, Tripathi M. Propofol sedation during spinal anaesthesia—a dose finding study. Kathmandu Univ Med J (KUMJ). 2011;35:170–3. doi:10.3126/kumj.v9i3.6299.
   Google Scholar
• Blouin RT, Seifert HA, Babenco HD, Conard PF, Gross JB. Propofol depresses the hypoxic ventilatory response during conscious sedation and isohypercapnia. Anesthesiology. 1993;79:1177–82. doi:10.1097/00000542-199312000-00007.
   PubMed Web of Science ®Google Scholar
• Church JA, Stanton PD, Kenny GNC, Anderson JR. Propofol for sedation during endoscopy: assessment of a computer controlled infusion system. Gastrointest Endos. 1991;37:175–9. doi:10.1016/S0016-5107(91)70680-9.
   PubMed Web of Science ®Google Scholar
• Ebert T. Sympathetic and hemodynamic effects of moderate and deep sedation with propofol in humans. Anesthesiology. 2005;103:20–4. doi:10.1097/00000542-200507000-00007.
   PubMed Web of Science ®Google Scholar
• Wolf A, Weir P, Segar P, Stone J, Shield J. Impaired fatty acid oxidation in propofol infusion syndrome. Lancet. 2001;357:606–7. doi:10.1016/S0140-6736(00)04064-2.
   PubMed Web of Science ®Google Scholar
• Kam PCA, Cardone D. Propofol infusion syndrome. Anaesthesia. 2007;62:690–701. doi:10.1111/j.1365-2044.2007.05055.x.
   PubMed Web of Science ®Google Scholar
• Bray RJ. Propofol infusion syndrome in children. Paediatr Anaesth. 1998;8:491–9.
   PubMed Web of Science ®Google Scholar
• Li X, Zhao Z, Liu X, Ma G, Zhu MJ. Encephalopathy associated with propofol infusion syndrome: a case report. Medicine (Baltimore). 2018;91:e9521. doi:10.1097/MD.0000000000009521.
   Google Scholar
• Imam T. Propofol related infusion syndrome: role of propofol in medical complications of sedated critical care patients. Perm J. 2013;17:85–7. doi:10.7812/TPP/12-114.
   PubMedGoogle Scholar
• Motsch J, Roggenbach J. Propofol infusion syndrome. Anaesthesist. 2004; 53:1009–22. doi:10.1007/s00101-004-0756-3.
   PubMed Web of Science ®Google Scholar
• American Academy of Hospice and Palliative Medicine. Statement on palliative sedation. 2014. [accessed 2018 Sept 16]. www.aahprn.org/po#ition.
   Google Scholar
• Roberts RJ, Barletta JF, Fong JJ, Schumaker G, Kuper PJ, Papadopoulos S, Yogaratnam D, Kendall E, Xamplas R, Gerlach AT, et al. Incidence of propofol related infusion syndrome in critically ill adults: a prospective, multi-center study. Crit Care. 2009;13:R169. doi:10.1186/cc8145.
   PubMed Web of Science ®Google Scholar
• Cremer OL, Moons KG, Bouman EA, Kruijswijk JE, de Smet AMGA, Kalkman CJ. Long term propofol infusion and cardiac failure in adult head-injured patients. Lancet. 2001;357:117–8. doi:10.1016/S0140-6736(00)03547-9.
   PubMed Web of Science ®Google Scholar
• 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;29:1417–25.
   PubMed Web of Science ®Google Scholar
• Krajcova A, Waldauf P, Andel M, Duška F. Propofol infuison syndrome: a structured review of experimental studies and 153 published case reports. Crit Care. 2015;19:398. doi:10.1186/s13054-015-1112-5.
   PubMed Web of Science ®Google Scholar
• Peacock JE, Lewis RP, Reilly CS, Nimmo WS. Effect of different rates of infusion of propofol for induction of anaesthesia in elderly patients. Br J Anaesth. 1990;65:346–52. doi:10.1093/bja/65.3.346.
   PubMed Web of Science ®Google Scholar
• Rolly G, Versichelen L, Huyghe L, Mungroop H. Effect of speed of injection on induction of anaesthesia using propofol. Br J Anaesth. 1985;57:743–6. doi:10.1093/bja/57.8.743.
   PubMed Web of Science ®Google Scholar
• Picard P, Tramer MR. Prevention of pain on injection with propofol: a quantitative systematic review. Anesth Analg. 2000;90:963–9.
   PubMed Web of Science ®Google Scholar
• Kim DH, Chae YJ, Chang HS, Kim JA, Joe HB. Intravenous licocaine pretreatment with venous occlusion for reducing microemulsion propofol induced pain: comparison of three doses of lidocaine. J Int Med Res. 2014;42:368–75. doi:10.1177/0300060513507391.
   PubMed Web of Science ®Google Scholar
• Massad IM, Abu-Ali HM, Al-Ghanem SA, Badran IZ, Ammari BA, Daradkeh SS. Duration of venous occlusion with lidocaine for preventing propofol induced pain. Saudi Med J. 2008;29:971–4.
   PubMed Web of Science ®Google Scholar
• Massad IM, Abu-Ali HM, Abu-Halaweh SA, Badran IZ. Venous occlusion with lidocaine for preventing propofol induced pain. A prospective double-blind randomized study. Saudi Med J. 2006;27:997–1000.
   PubMed Web of Science ®Google Scholar
• Stokes DN, Robson N, Hutton P. Effect of diluting propofol on the incidence of pain on injection and venous sequelae. Br J Anaesth. 1989;62:202–3. doi:10.1093/bja/62.2.202.
   PubMed Web of Science ®Google Scholar
• Hepner DL, Castells MC. Anaphylaxis during the perioperative period. Anesth Analg. 2003;97:1381–95. doi:10.1213/01.ane.0000082993.84883.7d.
   PubMed Web of Science ®Google Scholar
• Axon AD, Hunter JM, Editorial III: anaphylaxis and anaesthesia-all clear now? Br J Anaesth. 2004;93:501–4. doi:10.1093/bja/aeh203.
   PubMed Web of Science ®Google Scholar
• Asserhøj LL, Mosbech H, Krøigaard M, Garvey LH. No evidence for contraindications to the use of propofol in adults allergic to egg, soy or peanut†. Br J Anaesth. 2016;116:77–82. doi:10.1093/bja/aev360.
   PubMed Web of Science ®Google Scholar
• Harper N. Propofol and food allergy. Br J Anaesth. 2016;116:11–13. doi:10.1093/bja/aev401.
   PubMed Web of Science ®Google Scholar
• De Cosmo G, Congedo E, Clemente A, Aceto P. Sedation in PACU: the role of propofol. Curr Drug Targets. 2005;6:741–4. doi:10.2174/138945005774574425.
   PubMed Web of Science ®Google Scholar
• Stollings JL, Diedrich DA, Oyen LJ, Brown DR. Rapid-sequence intubation: a review of the process and considerations when choosing medications. Ann Pharmacother. 2014;48:62–78. doi:10.1177/1060028013510488.
   PubMed Web of Science ®Google Scholar
• MacPherson RD. Pharmaceutics for the anaesthetist. Anaesthesia. 2001; 56:965–79. doi:10.1046/j.1365-2044.2001.02216.x.
   PubMed Web of Science ®Google Scholar
• WebMD Currently Approved Package Insert for Versed. 2018. [accessed 2018 Nov 17]. www.fda.gov/…/cpoooo1_exhibit_02.pdf.
   Google Scholar
• Shapiro BA, Warren J, Egol AB, Greenbaum DM, Jacobi J, Nasraway SA, Schein RM, Spevetz A, Stone JR. Practice parameters for intravenous analgesia and sedation for adult patients in the intensive care unit: an executive summary. Crit Care Med. 1995;23:1596–600.
   PubMed Web of Science ®Google Scholar
• Fulwood D, Sargent S. An overview of sedation for adult patients in hospital. Nurs Stand. 2010;24:48–50.
   Google Scholar
• Hosgood JR, Kimbrel JM, Protus BM, Grauer PA. Evaluation of subcutaneous phenobarbital administration in hospice patients. Am J Hosp Palliat Care. 2016;33:209–13. doi:10.1177/1049909114555157.
   PubMed Web of Science ®Google Scholar
• Koytchev R, Alken RG, Kirkov V, Neshev G, Vagaday M, Kunter U. Absolute bioavailability of chlorpromazine, promazine, and promethazine. Arzneimittelforschung. 1994;44:121–5.
   PubMed Web of Science ®Google Scholar
• Claessens P, Menten J, Schotsmans P, Broeckaert B. Palliative sedation: a review of the research literature. J Pain Symptom Manage. 2008;36:310–33. doi:10.1016/j.jpainsymman.2007.10.004.
   PubMed Web of Science ®Google Scholar
• Cherny NI, ESMO Guidelines Working Group. ESMO clinical practice guidelines for the management of refractory symptoms at the end of life and the use of palliative sedation. Ann Oncol. 2014;25:iii143–52.
   PubMed Web of Science ®Google Scholar
• Cherny NI, Radbruch L, The Board of the European Association for Palliative Care. European Association for Palliative Care (EAPC) recommended framework for the use of sedation in palliative care. Palliat Med. 2009;23:581–93. doi:10.1177/0269216309107024.
   PubMed Web of Science ®Google Scholar
• Schildmann EK, Schildmann J, Kiesewetter I. Medication and monitoring in palliative sedation therapy: a systematic review and quality assessment of published guidelines. J Pain Symptom Manage. 2015;49:734–46. doi:10.1016/j.jpainsymman.2014.08.013.
   PubMed Web of Science ®Google Scholar
• Berger J. Preemptive use of palliative sedation and amyotrophic lateral sclerosis. J Pain Symptom Manage. 2012;43:802–5.
   PubMed Web of Science ®Google Scholar
• Truog RD, Cist AF, Brackett SE, Burns JP, Curley MA, Danis M, DeVita MA, Rosenbaum SH, Rothenberg DM, Sprung CL, et al. Recommendations for end-of-life care in the intensive care unit: the Ethics Committee of the Society of Critical Care Medicine. Crit Care Med. 2001;29:2332–48. doi:10.1097/00003246-200112000-00017.
   PubMed Web of Science ®Google Scholar
• Billings A. Humane terminal extubation reconsidered: the role for preemptive analgesia and sedation. Crit Care Med. 2012;40:625–30. doi:10.1097/CCM.0b013e318228235d.
   PubMed Web of Science ®Google Scholar
• Billings A. Terminal extubation in an alert person. J Palliat Med. 2011;14:800–1.
   PubMed Web of Science ®Google Scholar
• Epker J, Bakker J, Kompanje E. The use of opioids and sedatives and time until death after withdrawing mechanical ventilation and vasoactive drugs in a Dutch intensive care unit. Anesth Analg. 2011;112:628–34. doi:10.1213/ANE.0b013e31820ad4d9.
   PubMed Web of Science ®Google Scholar
• Harlos M. Ventilator withdrawal of patients with “ZeroCapability” for respiratory function. AMA J Ethics. 2003;5:8–11. [accessed 2019 Feb 3]. www.journalofethics.ama-assn.org/2003/01/ccas-0301.html.
   Google Scholar
• Harlos M. Symptom management in palliative ICU patients. 2014. [accessed 2019 Mar 2]. www.palliative.info/teaching_material/CriticalCareSymposiumMay22_2015.pdf.
   Google Scholar
• Truog R, Brock D, White D. Should patients receive general anesthesia prior to extubation at the end of life? Crit Care Med. 2012;40:631–3. doi:10.1097/CCM.0b013e3182413b8a.
   PubMed Web of Science ®Google Scholar
• Coelho CBT, Yankaskas JR. New concepts in palliative care in the intensive care unit. Rev Bras Ter Intensiva. 2017;29:222–30. doi:10.5935/0103-507X.20170031.
   PubMedGoogle Scholar
• Franken LG, de Winter BCM, Masman AD, van Dijk M, Baar FPM, Tibboel D, Koch BCP, van Gelder T, Mathot RAA. Population pharmacodynamic modelling of midazolam induced sedation in terminally ill adults. Br J Clin Pharmacol. 2018;84:320–30. doi:10.1111/bcp.13442.
   PubMed Web of Science ®Google Scholar
• Riessen R, Pech R, Tränkle P, Blumenstock G, Haap M. Comparison of the RAMSAY score and the Richmond Agitation Sedation Score for the measurement of sedation depth. Crit Care. 2012;16:P326. doi:10.1186/cc10933.
   Google Scholar
• Barr J, Fraser GL, Puntillo K, Ely EW, Gélinas C, Dasta JF, Davidson JE, Devlin JW, Kress JP, Joffe AM, et al. Clinical practice guidelines for the management of pain, agitation, and delerium in adult patients in the intensive care unit. Crit Care Med. 2013;41:263–306. doi:10.1097/CCM.0b013e3182783b72.
   PubMed Web of Science ®Google Scholar
• UMC Health System ICU Pain/Agitation/Delirium Reference. 2016. [accessed 2018 Apr 26]. https://www.umchealthsystem.com/docs/default-source/medical-orders/Ref—ICU-Pain-Aggitation-Delirium.pdf.
   Google Scholar
• Sardin B, Marsaud JP, Quesnel PA, et al. When midazolam fails. Minireview and Limoges guidelines. Med Palliat. 2018;17(1). doi:10.1016/jmedpal.2017.12.004.
   Google Scholar
• Miyake W, Oda Y, Ikeda Y, Hagihira S, Iwaki H, Asada A. Electroencephalographic response following midazolam-induced general anesthesia: relationship to plasma and effect-site midazolam concentrations. J Anesth. 2010;24:386–93. doi:10.1007/s00540-010-0907-4.
   PubMed Web of Science ®Google Scholar
• Ingrande J, Lemmens HJM. Dose adjustment of anesthetics in the morbidly obese. Br J Anaesth. 2010;105:116–23.
   PubMed Web of Science ®Google Scholar
• Dong D, Peng X, Liu J, Qian H, Li J, Wu B. Morbid obesity alters both pharmacokinetics and pharmacodynamics of propofol: dosing recommendation for anesthesia induction. Drug Metab Dispos. 2016;44:1579–83. doi:10.1124/dmd.116.071605.
   PubMed Web of Science ®Google Scholar
• Ingrande J, Brodsky J, Lemmens H. Lean body weight scalar for the anesthetic induction dose of propofol in morbidly obese subjects. Anesth Analg. 2011;113:57–62. doi:10.1213/ANE.0b013e3181f6d9c0.
   PubMed Web of Science ®Google Scholar
• Cortinez LI. What is the ke0 and what does it tell me about propofol? Anaesthesia. 2014;69:399–419.
   PubMed Web of Science ®Google Scholar
• Thomson AJ, Morrison G, Thomson E, Beattie C, Nimmo AF, Glen JB. Induction of general anaesthesia by effect-site target-controlled infusion of propofol: influence of pharmacokinetic model and ke0 value. Anaesthesia. 2014;69:429–35. doi:10.1111/anae.12597.
   PubMed Web of Science ®Google Scholar
• Struys MMRF, Coppens MJ, De Neve N, Mortier EP, Doufas AG, Van Bocxlaer JFP, Shafer SL. Influence of administration rate on propofol plasma-effect site equilibrium. Anesthesiology. 2007;107:386–96. doi:10.1097/01.anes.0000278902.15505.f8.
   PubMed Web of Science ®Google Scholar
• Absalom AR, Mani V, De Smet T, Struys MMRF. Pharmacokinetic models for propofol-defining and illuminating the devil in the detail. Br J Anaesth. 2009;103:26–37. doi:10.1093/bja/aep143.
   PubMed Web of Science ®Google Scholar
• Practice Advisory Council. Fraser health refractory symptoms and palliative sedation therapy guidelines. [accessed 2019 Mar 8]. www.fraserhealth.ca/media/refractorysymptomsandpalliativesedationtherapyguidelines.
   Google Scholar
• Propofol. Palliative Drugs.com. 15. [accessed 2019 Mar 10]. www.palliativedrugs.com.
   Google Scholar
• United States Food and Drug Administration. Propofol Offical FDA information, side effects, and usages. 2017. [accessed 2015 Feb 24]. www.drugs.com/propofol.html.
   Google Scholar
• Weingart S, Bhagwans S. Mount Sinai Hospital ED protocal for administration of propofol to tracheally intubated adult patients. 2010. [accessed 2019 Decr 21]. sinaiemcc.blogspot.com/2006/07/ed-protocol-for….
   Google Scholar
• The University of Connecticut Health Center John Dempsey Hospital – Department of Nursing Emergency Department Unit Practice Manual Protocol for propofol, administration for conscious sedation in the ED. 2002. [accessed 2019 Feb 24]. www.learningacc.com/doc/2805270/d9004e732ef09238008.
   Google Scholar
• United States Food and Drug Administration. Diprivan injectable emulsion for IV administration. 2014. [accessed 2018 Mar 1]. www.dailymed.nlm.nih/gov/dailymed/fda/fdaDrugXsl.cfmd?id=4756.
   Google Scholar
• Stokes DN, Hutton P. Rate-dependent induction phenomena with propofol: implications for the relative potency of intravenous anesthetics. Anesth Analg. 1991;72:578–83. doi:10.1213/00000539-199105000-00002.
   PubMed Web of Science ®Google Scholar
• Urfali S, Akkurt BCO. Efficiency of propofol co-adminstered with remifentanil and fentanyl over larygeneal mask airway insertion. Farmacia. 2017;65:472–8.
   Google Scholar
• Dewhirst E, Lancaster C, Tobias J. Hemodynamic changes following the adminstration of propofol to facilitate endotracheal intubation during sevoflurane anesthesia. Int J Clin Exp Med. 2013;6:26–9.
   PubMed Web of Science ®Google Scholar
• Shah NK, Harris M, Govindugari K, Rangaswamy HB, Jeon H. Effect of propofol titration v/s bolus during induction of anesthesia on hemodynamics and bispectral index. Middle East J Anaesthesiol. 2011;21:275–81.
   PubMedGoogle Scholar
• South Thames Retrieval Service. PICU drug boluses—South Thames retrieval service. 2014. [accessed 2019 Feb 24]. www.strs.nhs.uk/resources/pdf/guidelines/drugbolus/pdf.
   Google Scholar
• Providence Health Care. Drug name compatability incompatible with—vhphamrsci.com. 2017. [accessed 2019 Mar 8]. www.vhpharmsci.com/Resources/PTDM/AdditionalY-Site.
   Google Scholar
• Cayo L. IV drug compatability chart–Weebly. SFGH Pharmacies. 2009. [accessed 2019 Mar 8]. www.pharmaceutical-specialist.weebly.com/uploads/7/1/7/3.
   Google Scholar
• Michaels M, Stauffer G, Haas D. Propofol compatibility with other intravenous drug products-two new methods of evaluating IV emulsion compatability. Ann Pharmacother. 1996;30:228–32. doi:10.1177/106002809603000303.
   PubMed Web of Science ®Google Scholar