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CNS Drugs

, Volume 11, Issue 1, pp 9–22 | Cite as

Sedation in Critically Ill Patients

Practical Recommendations
  • Normand R. Gravel
  • Norman R. Searle
  • Philippe G. Sahab
  • Michel Carrier
Disease Management

Abstract

Provision of anxiolysis and analgesia in critically ill patients is mandatory to improve patient comfort without undue autonomic or haemodynamic adverse effects. The assessment of the level of sedation in the intensive care unit (ICU) by means of scoring systems is important because both undersedation and over-sedation can be counterproductive. Scoring systems, such as the Ramsay Sedation Score or the Modified Observer’s Assessment of Alertness/Sedation Scale, offer an accurate means of communicating clinical information and monitoring clinical progress.

Understanding how the pharmacokinetic and pharmacodynamic profiles of sedative and analgesic agents are altered in critically ill patients is essential for administering effective care. Midazolam and lorazepam are commonly used to provide anxiolysis and amnesia. Although there are variations in morphine metabolism and/or excretion in certain disease states, it remains the opioid of choice for critically ill patients. Because of its unique pharmacokinetic properties, remifentanil may eventually prove to be an interesting alternative. Propofol possesses many characteristics of the ideal sedative agent: rapid onset of effect, easy titration, unaltered pharmacokinetics in hepatic and renal dysfunction, and rapid recovery after prolonged infusion.

Conditions most likely encountered in the ICU are reviewed and practical recommendations are provided. Sedation in patients with multiple organ failure raises several interesting problems regarding distribution volumes, plasma protein binding, metabolic rate, tissue perfusion, drug excretion and requirement for prolonged sedation. Weaning from prolonged sedation can be difficult and may reveal drug dependency. The use of propofol can ease the transition from long term benzodiazepine use.

Patients with respiratory failure are a special group in whom propofol seems to have a favourable profile. Unless absolutely necessary, neuromuscular blocking agents should be avoided. If these agents must be used, it is incumbent to provide appropriate sedation and monitor the neuromuscular junction with a peripheral nerve stimulator. Opioid drugs should be used sparingly.

Compared with other medical conditions, sedation post-cardiac surgery has received a lot of attention. Propofol or midazolam in association with morphine are effective and well tolerated. Both can be use for short term sedation without jeopardising early tracheal extubation.

Keywords

Intensive Care Unit Morphine Fentanyl Adis International Limited Midazolam 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Burns AM, Shelly MP, Park GR. The use of sedative agents in critically ill patients. Drugs 1992; 43: 507–15PubMedCrossRefGoogle Scholar
  2. 2.
    Wheeler AP. Sedation, analgesia, and paralysis in the intensive care unit. Chest 1993; 104: 566–77PubMedCrossRefGoogle Scholar
  3. 3.
    Nielson C. Pharmacologic considerations in critical care of the elderly. Clin Geriat Med 1994; 10: 71–89Google Scholar
  4. 4.
    Merriman HM. The techniques used to sedate ventilated patients. Intensive Care Med 1981; 7: 217–24PubMedCrossRefGoogle Scholar
  5. 5.
    Wilson LM. Intensive care delirium: the effect of outside deprivation in a windowless unit. Arch Intern Med 1972; 130: 225–6PubMedCrossRefGoogle Scholar
  6. 6.
    Lazarus HR, Hagen SJH. Prevention of psychosis following open heart surgery. Am J Psychiat 1968; 124: 1190–5PubMedGoogle Scholar
  7. 7.
    Shelly MP. The assessment of sedation. Br J Intens Care 1992; 2: 195–203Google Scholar
  8. 8.
    Sprung CL, Peduzzi PN, Shatney CH, et al. Impact of encephalopathy on mortality in the sepsis syndrome. Crit Care Med 1990; 18: 801–5PubMedCrossRefGoogle Scholar
  9. 9.
    Ramsay MAE, Savage TM, Simpson BRJ, et al. Controlled sedation with alphaxalone-alphadolone. BMJ 1974; 2: 565–9CrossRefGoogle Scholar
  10. 10.
    Chernik DA, Gillings D, Laine H, et al. Validity and reliability of the Observer’s Assessment of Alertness/Sedation Scale: study with intravenous midazolam. J Clin Psychopharmacol 1990; 10: 244–51PubMedCrossRefGoogle Scholar
  11. 11.
    Geddes SM, Gray WM, Asbury AT. Skin conductance responses in patients sedated with midazolam or propofol. Br J Anaesth 1994; 73: 345–9PubMedCrossRefGoogle Scholar
  12. 12.
    Willats SM, Spencer EM. Sedation for ventilation in the critically ill. A role for isoflurane? Anaesthesia 1994; 49: 422–8CrossRefGoogle Scholar
  13. 13.
    Woods JH, Katz JL, Winger G. Benzodiazepines: use, abuse, and consequences. Pharmacol Rev 1992; 44: 151–347Google Scholar
  14. 14.
    Ashton H. Benzodiazepine withdrawal: outcome in 50 patients. Br J Addict 1987; 82; 665–71PubMedCrossRefGoogle Scholar
  15. 15.
    Mandelli M, Tognoni G, Garattini S, et al. Clinical pharmacokinetics of diazepam. Clin Pharmacodyn 1978; 3: 72–91CrossRefGoogle Scholar
  16. 16.
    Bellantuono C, Reggi V, Tognoni G, et al. Benzodiazepines: clinical pharmacology and therapeutic use. Drugs 1980; 19: 195–219PubMedCrossRefGoogle Scholar
  17. 17.
    Durbin CG. Sedation in the critically ill patient. New Horizons 1994; 2: 64–74PubMedGoogle Scholar
  18. 18.
    Calvo R, Suarez E, Rodriguez-Sasiain JM, et al. The influence of renal failure on the kinetics of intravenous midazolam: an in vivo and in vitro study. Res Commun Chem Pathol Pharmacol 1992; 78: 311–20PubMedGoogle Scholar
  19. 19.
    Shelly MP, Mendel L, Park GR. Failure of critically ill patients to metabolise midazolam. Anaesthesia 1987; 42: 619–26PubMedCrossRefGoogle Scholar
  20. 20.
    Shelly MP, Sultan MA, Bodenham A, et al. Midazolam infusions in critically ill patients. Eur J Anaesthesiol 1991; 8: 21–7PubMedGoogle Scholar
  21. 21.
    Malacrida R, Fritz ME, Sutter PM, et al. Pharmacokinetics of midazolam administered by continuous infusion to intensive care patients. Crit Care Med 1992; 20: 1123–6PubMedCrossRefGoogle Scholar
  22. 22.
    Vree TB, Shimoda M, Driessen JJ, et al. Decreased plasma albumin concentration results in increased volume of distribution and decreased elimination of midazolam in intensive care patients. Clin Pharmacol Ther 1989; 46: 537–44PubMedCrossRefGoogle Scholar
  23. 23.
    Dundee JW, Johnston HML, Gray RC. Lorazepam as a sedative-amnesic in the intensive care unit. Curr Med Res Opin 1976; 4: 290–5PubMedCrossRefGoogle Scholar
  24. 24.
    Boucher BA, Kuhl DA, Fabian TC, et al. Effect of neurotrauma on hepatic drug clearance. Clin Pharmacol Ther 1991; 50: 487–97PubMedCrossRefGoogle Scholar
  25. 25.
    Martyn J, Greenblatt DJ. Lorazepam conjugation is unimpaired in burn trauma. Clin Pharmacol Ther 1987; 43: 250–5CrossRefGoogle Scholar
  26. 26.
    Kraus JW, Desmond PV, Marshall JP, et al. Effects of aging and liver disease on disposition of lorazepam. Clin Pharmacol Ther 1978; 24: 411–9PubMedGoogle Scholar
  27. 27.
    Shapiro BA, Warren I, Egol AB, et al. Practice parameters for intravenous analgesia and sedation for adult patients in the intensive care unit: an executive summary. Crit Care Med 1995; 23: 1596–600PubMedCrossRefGoogle Scholar
  28. 28.
    Brogden RN, Goa KL. Flumazenil: a reappraisal of its pharmacological properties and therapeutic efficacy as a benzodiazepine antagonist. Drugs 1991; 42: 1061–89PubMedCrossRefGoogle Scholar
  29. 29.
    Ghouri AF, Ramirez Ruiz MA, White PF. Effect of flumazenil on recovery after midazolam and propofol sedation. Anesthesiology 1994; 81: 333–9PubMedCrossRefGoogle Scholar
  30. 30.
    White PF, Shafer A, Boyle WA, et al. Benzodiazepine antagonism does not provoke a stress response. Anesthesiology 1989; 70: 636–9PubMedCrossRefGoogle Scholar
  31. 31.
    Kerr B, Hill H, Coda B, et al. Concentration-related effects of morphine on cognition and motor control in human subjects. Neuropsychopharmacol 1991; 5: 157–66Google Scholar
  32. 32.
    Veselis RA, Reinsel RA, Feschenko VA, et al. Impaired memory and behavioral performance with fentanyl at low plasma concentrations. Anesth Analg 1994; 79: 952–60PubMedCrossRefGoogle Scholar
  33. 33.
    Perry S, Inturrisi CE. Analgesia and morphine disposition in burn patients. J Burn Care Rehabil 1983; 4: 276–9CrossRefGoogle Scholar
  34. 34.
    Bion JF, Logan BK, Newman PM, et al. Sedation in intensive care: morphine and renal function. Intensive Care Med 1986; 12: 359–65PubMedCrossRefGoogle Scholar
  35. 35.
    Christie J, Markowsky SJ, Valdes C. Acute trauma alters morphine clearance. J Trauma 1995; 39: 749–52PubMedCrossRefGoogle Scholar
  36. 36.
    Mostert JW, Evers JL, Hobika GH, et al. Cardiorespiratory effects of anaesthesia with morphine or fentanyl in chronic renal failure and cerebral toxicity after morphine. Br J Anaesth 1971; 43: 1053–60PubMedCrossRefGoogle Scholar
  37. 37.
    Hughes MA, Glass PSA, Jacobs JR. Context-sensitive half-time in multicompartment pharmacokinetic models for intravenous anesthetic drugs. Anesthesiology 1992; 76: 334–41PubMedCrossRefGoogle Scholar
  38. 38.
    Westmoreland CL, Hoke JF, Sebel PS, et al. The pharmacokinetics of remifentanil (GI87084B) and its major metabolite (GI90291) in patients undergoing elective inpatient surgery. Anesthesiology 1993; 79: 881–92CrossRefGoogle Scholar
  39. 39.
    Dershwitz M, Hoke JF, Rosow CE, et al. Pharmacokinetics and pharmacodynamics of remifentanil in volunteer subjects with severe liver disease. Anesthesiology 1996; 84: 812–20PubMedCrossRefGoogle Scholar
  40. 40.
    Evans TN, Park GR. Remifentanil in the critically ill. Anaesthesia 1997; 53: 797–811Google Scholar
  41. 41.
    Flacke JW, Flacke WE, William GD. Acute pulmonary edema following naloxone reversal of high-dose morphine anesthesia. Anesthesiology 1977; 47: 376–8PubMedCrossRefGoogle Scholar
  42. 42.
    Newman LH, McDonald JC, Wallace PGM, et al. Propofol infusion for sedation in intensive care. Anaesthesia 1987; 42: 929–37PubMedCrossRefGoogle Scholar
  43. 43.
    Aitkenhead AR, Willatts SM, Collins CH, et al. Comparison of propofol and midazolam for sedation in critically ill patients. Lancet 1989; 2: 704–9PubMedCrossRefGoogle Scholar
  44. 44.
    Kress JP, O’Connor MF, Pohlman AS, et al. Sedation of critically ill patients during mechanical ventilation. Am J Respir Crit Med 1996; 153: 1012–8Google Scholar
  45. 45.
    Borgeat A, Wilder-Smith OHG, Suter PM. The nonhypnotic therapeutic applications of propofol. Anesthesiology 1994; 80: 642–56PubMedCrossRefGoogle Scholar
  46. 46.
    Grounds RM, Laylor JM, Lumley J, et al. Propofol perfusion for sedation in intensive care unit: preliminary report. BMJ 1987; 294: 397–400PubMedCrossRefGoogle Scholar
  47. 47.
    Higgins TI, Yared J-P, Estafanous FG, et al. Propofol versus midazolam for intensive care unit sedation after coronary artery bypass grafting. Crit Care Med 1994; 9: 1415–23CrossRefGoogle Scholar
  48. 48.
    McMurray TJ, Collier PS, Carson IW, et al. Propofol sedation after open heart surgery: a clinical and pharmacokinetic study. Anaesthesia 1990; 45: 322–6PubMedCrossRefGoogle Scholar
  49. 49.
    Seifert HA, Blouin RT, Conrad PF, et al. Sedative doses of propofol increase beta activity of the processed electroencephalogram. Anesth Analg 1993; 76: 976–8PubMedCrossRefGoogle Scholar
  50. 50.
    Illievch UM, Petricek W, Schramm W, et al. Electroencephalographic burst suppression by propofol infusion in humans: hemodynamic consequences. Anesth Analg 1993; 77: 155–60Google Scholar
  51. 51.
    Bennett N, McNeil MM, Bland LA, et al. Postoperative infections traced to contamination of an intravenous anesthetic propofol. N Engl J Med 1995; 333: 147–54PubMedCrossRefGoogle Scholar
  52. 52.
    Albanese J, Martin C, Lacarelle B, et al. Pharmacokinetics of long-term propofol infusion used for sedation in ICU patients. Anesthesiology 1990; 73: 214–7PubMedCrossRefGoogle Scholar
  53. 53.
    Tietjen CS, Hurn PD, Ulatowski JA, et al. Treatment modalities for hypertensive patients with intracranial pathology: options and risks. Crit Care Med 1996; 24: 311–22PubMedCrossRefGoogle Scholar
  54. 54.
    Borel C, Hanley D, Diringer MN, et al. Intensive management of severe head injury. Chest 1990; 98: 180–9PubMedCrossRefGoogle Scholar
  55. 55.
    Reidenberg MM, Lowenthal DT, Briggs W, et al. Pentobarbital elimination in patients with poor renal function. Clin Pharmacol Ther 1976; 20: 67–71PubMedGoogle Scholar
  56. 56.
    Gold MS, Pottash ALC, Extein I, et al. Clinical utility of clonidine in opiate withdrawal. Natl Inst Drug Abuse Res Monogr Ser 1981; 34: 95–100Google Scholar
  57. 57.
    Carrasco G, Molina R, Costa J, et al. Propofol vs midazolam in short-, medium-, and long-term sedation of critically ill patients. Chest 1993; 103: 557–64PubMedCrossRefGoogle Scholar
  58. 58.
    Chappie DJ, Miller AA, Ward JB, et al. Cardiovascular and neurological effects of laudanosine: studies in mice and rats, and in conscious and anaesthetized dogs. Br J Anaesth 1987; 59: 218–25CrossRefGoogle Scholar
  59. 59.
    Searle N, Côté S, Taillefer J, et al. Propofol or midazolam for sedation and early extubation following cardiac surgery. Can J Anaesth 1997; 44: 629–35PubMedCrossRefGoogle Scholar
  60. 60.
    Hall RI, MacLaren C, Smith MS, et al. Light versus heavy sedation after cardiac surgery: myocardial ischemia and the stress response. Anesth Analg 1997; 85: 971–8PubMedGoogle Scholar
  61. 61.
    Kollef MH, Levy NT, Ahrens TS, et al. The use of continuous IV sedation is associated with prolongation of mechanical ventilation. Chest 1998; 114: 541–8PubMedCrossRefGoogle Scholar

Copyright information

© Adis International Limited 1999

Authors and Affiliations

  • Normand R. Gravel
    • 1
  • Norman R. Searle
    • 1
  • Philippe G. Sahab
    • 1
  • Michel Carrier
    • 1
  1. 1.Department of AnaesthesiaMontreal Heart InstituteMontrealCanada

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