Most critically ill patients undergoing mechanical ventilation require the ­administration of at least two different sedative agents for a median of 3 (interquartile range 2–6) days to optimize patient comfort and safety, facilitate patient-ventilator synchrony and optimize oxygenation.1,2 With an increasing number of safety ­concerns associated with the administration of sedatives, the likelihood of patients experiencing an adverse drug event during their ICU admission is high.3 While many adverse effects are common pharmacologic manifestations of an agent (e.g., dexmedetomidine-associated bradycardia) and therefore frequently reversible, ­others are idiosyncratic (e.g., propofol-related infusion syndrome), unexpected, and may be associated with substantial morbidity and mortality.4,5


Renal Replacement Therapy Continuous Renal Replacement Therapy Adverse Drug Event Therapeutic Hypothermia Inactive Metabolite 
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  1. 1.
    Jacobi J, Fraser GL, Coursin DB, et al. Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult. Crit Care Med. 2002;30:119-141.PubMedCrossRefGoogle Scholar
  2. 2.
    Arroliga A, Frutos-Vivar F, Hall J, et al. Use of sedatives and neuromuscular blockers in a cohort of patients receiving mechanical ventilation. Chest. 2005;128:496-506.PubMedCrossRefGoogle Scholar
  3. 3.
    Devlin JW, Mallow-Corbett S, Riker RR. Adverse drug events associated with the use of analgesics, sedatives and antipsychotics in the intensive care unit. Crit Care Med. 2010;38(6 suppl):S231-S243.PubMedCrossRefGoogle Scholar
  4. 4.
    Gerlach AT, Murphy CV, Dasta JF. An updated focused review of dexmedetomidine in adults. Ann Pharmacother. 2009;43:2064-2074.PubMedCrossRefGoogle Scholar
  5. 5.
    Roberts RJ, Barletta JF, Fong JJ, et al. Incidence of propofol-related infusion syndrome in critically ill adults: a prospective, multicenter study. Crit Care. 2009;13(5):R169.PubMedCrossRefGoogle Scholar
  6. 6.
    Dyck JB, Maze M, Haack C, et al. The pharmacokinetics and hemodynamic effects of intravenous and intramuscular dexmedetomidine hydrochloride in adult human volunteers. Anesthesiology. 1993;78(5):813-820.PubMedCrossRefGoogle Scholar
  7. 7.
    Bokesch P, Riker R, Shehabi Y. Pharmacokinetics of dexmedetomidine for long-term infusion [abstract]. Anesth Anal. 2009;108:S298.Google Scholar
  8. 8.
    DeWolf AE, Fragen RJ, Avram MJ, et al. The pharmacokinetics of dexmedetomidine in volunteers with severe renal impairment. Anesth Analg. 2001;93:1205-1209.CrossRefGoogle Scholar
  9. 9.
    Pandharipande PP, Pun BT, Herr DL, et al. Effect of sedation with dexmedetomidine vs lorazepam on acute brain dysfunction in mechanically ventilated patients: the MENDS randomized controlled trial. JAMA. 2007;298(22):2644-2653.PubMedCrossRefGoogle Scholar
  10. 10.
    Riker RR, Shehabi Y, Bokesch PM, et al. Dexmedetomidine vs midazolam for sedation of critically ill patients: a randomized trial. JAMA. 2009;301:489-499.PubMedCrossRefGoogle Scholar
  11. 11.
    Maldonado JR, Wysong A, van der Starre PJA, et al. Dexmedetomidine and the reduction of postoperative delirium after cardiac surgery. Psychosomatics. 2009;50:206-217.PubMedCrossRefGoogle Scholar
  12. 12.
    Reade MC, O’Sullivan K, Bates S, et al. Dexmedetomidine vs. haloperidol in delirious, agitated, intubated patients: a randomized open-label trial. Crit Care. 2009;13:R75.PubMedCrossRefGoogle Scholar
  13. 13.
    Talke P, Tayefeh F, Sessler DI, Jeffrey R, Noursalehi M, Richardson C. Dexmedetomidine does not alter the sweating threshold, but comparably and linearly decreases the vasoconstriction and shivering thresholds. Anesthesiology. 1997;87:835-841.PubMedCrossRefGoogle Scholar
  14. 14.
    Gerlach At, Murphy CV. Dexmedetomidine-associated bradycardia progressing to pulseless electrical activity: case report and review of the literature. Pharmacotherapy. 2009;29:1492.PubMedCrossRefGoogle Scholar
  15. 15.
    Ebert TJ, Hall JE, Barney JA, et al. The effects of increasing plasma concentrations of dexmedetomidine in humans. Anesthesiology. 2000;93:382-394.PubMedCrossRefGoogle Scholar
  16. 16.
    Karol M, Maze M. Pharmacokinetics and interaction pharmacodynamics of dexmedetomidine in humans. Best Pract Res Clin Anaesthesiol. 2000;14(2):261-269.CrossRefGoogle Scholar
  17. 17.
    Gerlach AT, Dasta JF, Steinberg S, et al. A new dosing protocol reduces dexmedetomidine-associated hypotension in critically ill surgical patients. J Crit Care. 2009;24:568-574.PubMedCrossRefGoogle Scholar
  18. 18.
    Dasta JF, Kane-Gill SL, Durtschi AJ. Comapring dexmedetomidine prescribing patterns and safety in the naturalistic setting versus published data. Ann Pharmacother. 2004;38:1130-1135.PubMedCrossRefGoogle Scholar
  19. 19.
    Ruokonen E, Parviainen I, Jakob SM, et al. Dexmedetomidine versus propofol/midazolam for long-term sedation during mechanical ventilation. Intensive Care Med. 2009;35:282-290.PubMedCrossRefGoogle Scholar
  20. 20.
    Kress JP, Pohlman AS, O’Connor MF, et al. Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. N Engl J Med. 2000;342(20):1471-1477.PubMedCrossRefGoogle Scholar
  21. 21.
    Wagner BK, O’Hara DA. Pharmacokinetics and pharmacodynamics of sedatives and analgesics in the treatment of agitated critically ill patients. Clin Pharmacokinet. 1997;33(6):426-453.PubMedCrossRefGoogle Scholar
  22. 22.
    Yahwak JA, Riker RR, Fraser GL, et al. Determination of a lorazepam dose threshold for using the osmol gap to monitor for propylene glycol toxicity. Pharmacotherapy. 2008;28(8):984-991.PubMedCrossRefGoogle Scholar
  23. 23.
    Barr J, Zomorodi K, Bertaccini EJ, Shafer SL, Geller E. A double-blind, randomized comparison of IV lorazepam versus midazolam for sedation of ICU patients via a pharmacologic model. Anesthesiology. 2001;95(2):286-298.PubMedCrossRefGoogle Scholar
  24. 24.
    Tiwari AK, Souza RP, Müller DJ. Pharmacogenetics of anxiolytic drugs. J Neural Transm. 2009;116(6):667-677.PubMedCrossRefGoogle Scholar
  25. 25.
    Cammarano WB, Pittet JF, Weitz S, et al. Acute withdrawal syndrome related to the administration of analgesics and sedative medications in adult intensive care unit patients. Crit Care Med. 1998;26:676-684.PubMedCrossRefGoogle Scholar
  26. 26.
    Trissel L. Handbook on Injectable Drugs. 16th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2010.Google Scholar
  27. 27.
    Arroliga AC, Shehab N, McCarthy K, et al. Relationship of continuous infusion lorazepam to serum propylene glycol concentration in critically ill adults. Crit Care Med. 2004;32:1709-1714.PubMedCrossRefGoogle Scholar
  28. 28.
    Barnes BJ, Gerst C, Smith JR, et al. Osmol gap as a surrogate marker for serum propylene glycol concentrations in patients receiving lorazepam for sedation. Pharmacotherapy. 2006;26(1):23-33.PubMedCrossRefGoogle Scholar
  29. 29.
    Parker MG, Fraser GL, Watson DM, Riker RR. Removal of propylene glycol and correction of increased osmolar gap by hemodialysis in a patient on high dose lorazepam infusion therapy. Intensive Care Med. 2002;28(1):81-84.PubMedCrossRefGoogle Scholar
  30. 30.
    Pandharipande P, Shintani A, Peterson J, et al. Lorazepam is an independent risk factor for transitioning to delirium in intensive care unit patients. Anesthesiology. 2006;104(1):21-22.PubMedCrossRefGoogle Scholar
  31. 31.
    Devlin JW, Fong JJ, Fraser GL, Riker RR. Delirium assessment in the critically ill. Intensive Care Med. 2007;33(6):929-940.PubMedCrossRefGoogle Scholar
  32. 32.
    Kollef MH, Levy NT, Ahrens TS, Schaiff R, Prentice D, Sherman G. The use of continuous IV sedation is associated with prolongation of mechanical ventilation. Chest. 1998;114(2):541-548.PubMedCrossRefGoogle Scholar
  33. 33.
    Spina SP, Ensom MH. Clinical pharmacokinetic monitoring of midazolam in critically ill patients. Pharmacotherapy. 2007;27(3):389-398.PubMedCrossRefGoogle Scholar
  34. 34.
    Bauer TM, Ritz R, Haberthur C, et al. Prolonged sedation due to accumulation of conjugated metabolites of midazolam. Lancet. 1995;346(8968):145-147.PubMedCrossRefGoogle Scholar
  35. 35.
    Fukasawa T, Suzuki A, Otani K. Effects of genetic polymorphism of cytochrome P450 enzymes on the pharmacokinetics of benzodiazepines. J Clin Pharm Ther. 2007;32(4):333-341.PubMedCrossRefGoogle Scholar
  36. 36.
    Nishina K, Akamatsu H, Mikawa K, et al. The effects of clonidine and dexmedetomidine on human neutrophil functions. Anesth Analg. 1999;88(2):452-458.PubMedGoogle Scholar
  37. 37.
    Venn RM, Karol MD, Grounds RM. Pharmacokinetics of dexmedetomidine infusions for sedation of postoperative patients requiring intensive care. Br J Anaesth. 2002;88:669-675.PubMedCrossRefGoogle Scholar
  38. 38.
    Swart EL, van Schijndel RJ, van Loenen AC, et al. Continuous infusion of lorazepam versus midazolam in patients in the intensive care unit: sedation with lorazepam is easier to manage and is more cost-effective. Crit Care Med. 1999;27(8):1461-1465.PubMedCrossRefGoogle Scholar
  39. 39.
    Skrobik Y. Delirium prevention and treatment. Crit Care Clin. 2009;25(3):585-591.PubMedCrossRefGoogle Scholar
  40. 40.
    Bailie 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(5):486-491.PubMedCrossRefGoogle Scholar
  41. 41.
    Peeters MY, Bras LJ, DeJongh J, et al. Disease severity is a major determinant for the pharmacodynamics of propofol in critically ill patients. Clin Pharmacol Ther. 2008;83(3):443-451.PubMedCrossRefGoogle Scholar
  42. 42.
  43. 43.
    Carrasco G, Molina R, Costa J, et al. Propofol versus midazolam in short-, medium-, and long-term sedation of critically ill patients. Chest. 1993;103:557-564.PubMedCrossRefGoogle Scholar
  44. 44.
    Chamorro C, DeLatorre FJ, Montero A, et al. Comparative study of propofol versus midazolam in the sedation of critically ill patients: results of a prospective, randomized, multicenter trial. Crit Care Med. 1996;24:932-939.PubMedCrossRefGoogle Scholar
  45. 45.
    Williams C. Application of the IV medication harm index to assess the nature of harm averted by smart infusion safety systems. J Patient Saf. 2006;2:132-139.CrossRefGoogle Scholar
  46. 46.
    Mikawa K, Akamatsu H, Nishina K, et al. Propofol inhibits human neutrophil functions. Anesth Analg. 1998;87(3):695-700.PubMedGoogle Scholar
  47. 47.
    Sanders RD, Hussell T, Maze M. Sedation & immunomodulation. Crit Care Clin. 2009;25:551-570.PubMedCrossRefGoogle Scholar
  48. 48.
    Taniguchi T, Yamamoto K, Ohmoto N, et al. Effects of propofol on hemodynamic and inflammatory responses to endotoxemia in rats. Crit Care Med. 2000;28(4):1101-1106.PubMedCrossRefGoogle Scholar
  49. 49.
    Taniguchi T, Kanakura H, Yamamoto K. Effects of posttreatment with propofol on mortality and cytokine responses to endotoxin-induced shock in rats. Crit Care Med. 2002;30(4):904-907.PubMedCrossRefGoogle Scholar
  50. 50.
    Islander G, Vinge E. Severe neuroexcitatory symptoms after anaesthesia – with focus on propofol anaesthesia. Acta Anaesthesiol Scand. 2000;44(2):144-149.PubMedCrossRefGoogle Scholar
  51. 51.
    Marik PE, Varon J. The management of status epilepticus. Chest. 2004;126(2):582-591.PubMedCrossRefGoogle Scholar
  52. 52.
    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;25:1348-1352.PubMedCrossRefGoogle Scholar
  53. 53.
    Corbett SM, Montoya ID, Moore FA. Propofol-related infusion syndrome in intensive care patients. Pharmacotherapy. 2008;28:250-258.PubMedCrossRefGoogle Scholar
  54. 54.
    Kam PCA, Cardone D. Propofol infusion syndrome. Anaesthesia. 2007;62:690-701.PubMedCrossRefGoogle Scholar
  55. 55.
    Fudickar A, Bein B. Propofol infusion syndrome: update on clinical manifestation and pathophysiology. Minerva Anestesiol. 2009;75:339-344.PubMedGoogle Scholar
  56. 56.
    Vasile B, Rasulo F, Candiani A, et al. The pathophysiology of propofol infusion syndrome: a simple name for a complex syndrome. Intensive Care Med. 2003;29(9):1417-1425.PubMedCrossRefGoogle Scholar
  57. 57.
    Fong JJ, Sylvia L, Ruthazer R, et al. Predictors of mortality in patients with suspected propofol infusion syndrome. Crit Care Med. 2008;36:2281-2287.PubMedCrossRefGoogle Scholar
  58. 58.
    Devlin JW, Roberts RJ. Pharmacology of commonly used analgesics and sedatives in the ICU: benzodiazepines, propofol, and opioids. Crit Care Clin. 2009;25(3):431-449. vii. Review.PubMedCrossRefGoogle Scholar

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© Springer-Verlag London Limited 2011

Authors and Affiliations

  1. 1.Pharmacy PracticeNortheastern UniversityBostonUSA

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