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.
Article PDF
Similar content being viewed by others
References
Burns AM, Shelly MP, Park GR. The use of sedative agents in critically ill patients. Drugs 1992; 43: 507–15
Wheeler AP. Sedation, analgesia, and paralysis in the intensive care unit. Chest 1993; 104: 566–77
Nielson C. Pharmacologic considerations in critical care of the elderly. Clin Geriat Med 1994; 10: 71–89
Merriman HM. The techniques used to sedate ventilated patients. Intensive Care Med 1981; 7: 217–24
Wilson LM. Intensive care delirium: the effect of outside deprivation in a windowless unit. Arch Intern Med 1972; 130: 225–6
Lazarus HR, Hagen SJH. Prevention of psychosis following open heart surgery. Am J Psychiat 1968; 124: 1190–5
Shelly MP. The assessment of sedation. Br J Intens Care 1992; 2: 195–203
Sprung CL, Peduzzi PN, Shatney CH, et al. Impact of encephalopathy on mortality in the sepsis syndrome. Crit Care Med 1990; 18: 801–5
Ramsay MAE, Savage TM, Simpson BRJ, et al. Controlled sedation with alphaxalone-alphadolone. BMJ 1974; 2: 565–9
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: 244–51
Geddes SM, Gray WM, Asbury AT. Skin conductance responses in patients sedated with midazolam or propofol. Br J Anaesth 1994; 73: 345–9
Willats SM, Spencer EM. Sedation for ventilation in the critically ill. A role for isoflurane? Anaesthesia 1994; 49: 422–8
Woods JH, Katz JL, Winger G. Benzodiazepines: use, abuse, and consequences. Pharmacol Rev 1992; 44: 151–347
Ashton H. Benzodiazepine withdrawal: outcome in 50 patients. Br J Addict 1987; 82; 665–71
Mandelli M, Tognoni G, Garattini S, et al. Clinical pharmacokinetics of diazepam. Clin Pharmacodyn 1978; 3: 72–91
Bellantuono C, Reggi V, Tognoni G, et al. Benzodiazepines: clinical pharmacology and therapeutic use. Drugs 1980; 19: 195–219
Durbin CG. Sedation in the critically ill patient. New Horizons 1994; 2: 64–74
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: 311–20
Shelly MP, Mendel L, Park GR. Failure of critically ill patients to metabolise midazolam. Anaesthesia 1987; 42: 619–26
Shelly MP, Sultan MA, Bodenham A, et al. Midazolam infusions in critically ill patients. Eur J Anaesthesiol 1991; 8: 21–7
Malacrida R, Fritz ME, Sutter PM, et al. Pharmacokinetics of midazolam administered by continuous infusion to intensive care patients. Crit Care Med 1992; 20: 1123–6
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: 537–44
Dundee JW, Johnston HML, Gray RC. Lorazepam as a sedative-amnesic in the intensive care unit. Curr Med Res Opin 1976; 4: 290–5
Boucher BA, Kuhl DA, Fabian TC, et al. Effect of neurotrauma on hepatic drug clearance. Clin Pharmacol Ther 1991; 50: 487–97
Martyn J, Greenblatt DJ. Lorazepam conjugation is unimpaired in burn trauma. Clin Pharmacol Ther 1987; 43: 250–5
Kraus JW, Desmond PV, Marshall JP, et al. Effects of aging and liver disease on disposition of lorazepam. Clin Pharmacol Ther 1978; 24: 411–9
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: 1596–600
Brogden RN, Goa KL. Flumazenil: a reappraisal of its pharmacological properties and therapeutic efficacy as a benzodiazepine antagonist. Drugs 1991; 42: 1061–89
Ghouri AF, Ramirez Ruiz MA, White PF. Effect of flumazenil on recovery after midazolam and propofol sedation. Anesthesiology 1994; 81: 333–9
White PF, Shafer A, Boyle WA, et al. Benzodiazepine antagonism does not provoke a stress response. Anesthesiology 1989; 70: 636–9
Kerr B, Hill H, Coda B, et al. Concentration-related effects of morphine on cognition and motor control in human subjects. Neuropsychopharmacol 1991; 5: 157–66
Veselis RA, Reinsel RA, Feschenko VA, et al. Impaired memory and behavioral performance with fentanyl at low plasma concentrations. Anesth Analg 1994; 79: 952–60
Perry S, Inturrisi CE. Analgesia and morphine disposition in burn patients. J Burn Care Rehabil 1983; 4: 276–9
Bion JF, Logan BK, Newman PM, et al. Sedation in intensive care: morphine and renal function. Intensive Care Med 1986; 12: 359–65
Christie J, Markowsky SJ, Valdes C. Acute trauma alters morphine clearance. J Trauma 1995; 39: 749–52
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: 1053–60
Hughes MA, Glass PSA, Jacobs JR. Context-sensitive half-time in multicompartment pharmacokinetic models for intravenous anesthetic drugs. Anesthesiology 1992; 76: 334–41
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: 881–92
Dershwitz M, Hoke JF, Rosow CE, et al. Pharmacokinetics and pharmacodynamics of remifentanil in volunteer subjects with severe liver disease. Anesthesiology 1996; 84: 812–20
Evans TN, Park GR. Remifentanil in the critically ill. Anaesthesia 1997; 53: 797–811
Flacke JW, Flacke WE, William GD. Acute pulmonary edema following naloxone reversal of high-dose morphine anesthesia. Anesthesiology 1977; 47: 376–8
Newman LH, McDonald JC, Wallace PGM, et al. Propofol infusion for sedation in intensive care. Anaesthesia 1987; 42: 929–37
Aitkenhead AR, Willatts SM, Collins CH, et al. Comparison of propofol and midazolam for sedation in critically ill patients. Lancet 1989; 2: 704–9
Kress JP, O’Connor MF, Pohlman AS, et al. Sedation of critically ill patients during mechanical ventilation. Am J Respir Crit Med 1996; 153: 1012–8
Borgeat A, Wilder-Smith OHG, Suter PM. The nonhypnotic therapeutic applications of propofol. Anesthesiology 1994; 80: 642–56
Grounds RM, Laylor JM, Lumley J, et al. Propofol perfusion for sedation in intensive care unit: preliminary report. BMJ 1987; 294: 397–400
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: 1415–23
McMurray TJ, Collier PS, Carson IW, et al. Propofol sedation after open heart surgery: a clinical and pharmacokinetic study. Anaesthesia 1990; 45: 322–6
Seifert HA, Blouin RT, Conrad PF, et al. Sedative doses of propofol increase beta activity of the processed electroencephalogram. Anesth Analg 1993; 76: 976–8
Illievch UM, Petricek W, Schramm W, et al. Electroencephalographic burst suppression by propofol infusion in humans: hemodynamic consequences. Anesth Analg 1993; 77: 155–60
Bennett N, McNeil MM, Bland LA, et al. Postoperative infections traced to contamination of an intravenous anesthetic propofol. N Engl J Med 1995; 333: 147–54
Albanese J, Martin C, Lacarelle B, et al. Pharmacokinetics of long-term propofol infusion used for sedation in ICU patients. Anesthesiology 1990; 73: 214–7
Tietjen CS, Hurn PD, Ulatowski JA, et al. Treatment modalities for hypertensive patients with intracranial pathology: options and risks. Crit Care Med 1996; 24: 311–22
Borel C, Hanley D, Diringer MN, et al. Intensive management of severe head injury. Chest 1990; 98: 180–9
Reidenberg MM, Lowenthal DT, Briggs W, et al. Pentobarbital elimination in patients with poor renal function. Clin Pharmacol Ther 1976; 20: 67–71
Gold MS, Pottash ALC, Extein I, et al. Clinical utility of clonidine in opiate withdrawal. Natl Inst Drug Abuse Res Monogr Ser 1981; 34: 95–100
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: 557–64
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: 218–25
Searle N, Côté S, Taillefer J, et al. Propofol or midazolam for sedation and early extubation following cardiac surgery. Can J Anaesth 1997; 44: 629–35
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: 971–8
Kollef MH, Levy NT, Ahrens TS, et al. The use of continuous IV sedation is associated with prolongation of mechanical ventilation. Chest 1998; 114: 541–8
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Gravel, N.R., Searle, N.R., Sahab, P.G. et al. Sedation in Critically Ill Patients. Mol Diag Ther 11, 9–22 (1999). https://doi.org/10.2165/00023210-199911010-00002
Published:
Issue Date:
DOI: https://doi.org/10.2165/00023210-199911010-00002