Indian Journal of Critical Care Medicine

Register      Login



Volume / Issue

Online First

Related articles

VOLUME 18 , ISSUE 4 ( April, 2014 ) > List of Articles


Propofol versus flunitrazepam for inducing and maintaining sleep in postoperative ICU patients

Cornelius Engelmann, Jan Wallenborn, Derk Olthoff, Udo X. Kaisers, Henrik Rüffert

Keywords : Bispectral index, intensive care unit, propofol, sleep

Citation Information : Engelmann C, Wallenborn J, Olthoff D, Kaisers UX, Rüffert H. Propofol versus flunitrazepam for inducing and maintaining sleep in postoperative ICU patients. Indian J Crit Care Med 2014; 18 (4):212-219.

DOI: 10.4103/0972-5229.130572

License: CC BY-ND 3.0

Published Online: 01-04-2014

Copyright Statement:  Copyright © 2014; Jaypee Brothers Medical Publishers (P) Ltd.


Context: Sleep deprivation is a common problem on intensive care units (ICUs) influencing not only cognition, but also cellular functions. An appropriate sleep-wake cycle should therefore be maintained to improve patients′ outcome. Multiple disruptive factors on ICUs necessitate the administration of sedating and sleep-promoting drugs for patients who are not analgo-sedated. Aims: The objective of the present study was to evaluate sleep quantity and sleep quality in ICU patients receiving either propofol or flunitrazepam. Settings and Design: Monocentric, randomized, double-blinded trial. Materials and Methods: A total of 66 ICU patients were enrolled in the study (flunitrazepam n = 32, propofol n = 34). Propofol was injected continuously (2 mg/kg/h), flunitrazepam as a bolus dose (0.015 mg/kg). Differences between groups were evaluated using a standardized sleep diary and the bispectral index (BIS). Statistical Analysis Used: Group comparisons were performed by Mann-Whitney U-Test. P < 0.05 was considered to be statistically significant. Results: Sleep quality and the frequency of awakenings were significantly better in the propofol group (Pg). In the same group lower BIS values were recorded (median BIS propofol 74.05, flunitrazepam 78.7 [P = 0.016]). BIS values had to be classified predominantly to slow-wave sleep under propofol and light sleep after administration of flunitrazepam. Sleep quality improved in the Pg with decreasing frequency of awakenings and in the flunitrazepam group with increasing sleep duration. Conclusions: Continuous low-dose injection of propofol for promoting and maintaining night sleep in ICU patients who are not analgo-sedated was superior to flunitrazepam regarding sleep quality and sleep structure.

PDF Share
  1. Freedman NS, Gazendam J, Levan L, Pack AI, Schwab RJ. Abnormal sleep/wake cycles and the effect of environmental noise on sleep disruption in the intensive care unit. Am J Respir Crit Care Med 2001;163:451-7.
  2. Gabor JY, Cooper AB, Hanly PJ. Sleep disruption in the intensive care unit. Curr Opin Crit Care 2001;7:21-7.
  3. Oztürk L, Pelin Z, Karadeniz D, Kaynak H, Cakar L, Gözükirmizi E. Effects of 48 hours sleep deprivation on human immune profile. Sleep Res Online 1999;2:107-11.
  4. Bonnet MH. Sleep deprivation. In: Kryger MH, Roth T, Dement WC, editors. Principles and Practice of Sleep Medicine. 2 nd ed. Philadelphia: W.B. Saunders and Co.; 1994. p. 50-67.
  5. Talwar A, Liman B, Greenberg H, Feinsilver SH, Vijayan VK. Sleep in the intensive care unit. Indian J Chest Dis Allied Sci 2008;50:151-62.
  6. Parrino L, Terzano MG. Polysomnographic effects of hypnotic drugs. A review. Psychopharmacology (Berl) 1996;126:1-16.
  7. Alkire MT, Pomfrett CJ, Haier RJ, Gianzero MV, Chan CM, Jacobsen BP, et al. Functional brain imaging during anesthesia in humans: Effects of halothane on global and regional cerebral glucose metabolism. Anesthesiology 1999;90:701-9.
  8. Nelson LE, Lu J, Guo T, Saper CB, Franks NP, Maze M. The alpha2-adrenoceptor agonist dexmedetomidine converges on an endogenous sleep-promoting pathway to exert its sedative effects. Anesthesiology 2003;98:428-36.
  9. Tanase D, Baghdoyan HA, Lydic R. Dialysis delivery of an adenosine A1 receptor agonist to the pontine reticular formation decreases acetylcholine release and increases anesthesia recovery time. Anesthesiology 2003;98:912-20.
  10. Fiset P, Paus T, Daloze T, Plourde G, Meuret P, Bonhomme V, et al. Brain mechanisms of propofol-induced loss of consciousness in humans: A positron emission tomographic study. J Neurosci 1999;19:5506-13.
  11. Tung A, Bluhm B, Mendelson WB. The hypnotic effect of propofol in the medial preoptic area of the rat. Life Sci 2001;69:855-62.
  12. Tung A, Bergmann BM, Herrera S, Cao D, Mendelson WB. Recovery from sleep deprivation occurs during propofol anesthesia. Anesthesiology 2004;100:1419-26.
  13. Rabelo FA, Braga A, Küpper DS, De Oliveira JA, Lopes FM, de Lima Mattos PL, et al. Propofol-induced sleep: Polysomnographic evaluation of patients with obstructive sleep apnea and controls. Otolaryngol Head Neck Surg 2010;142:218-24.
  14. Leslie K, Sleigh J, Paech MJ, Voss L, Lim CW, Sleigh C. Dreaming and electroencephalographic changes during anesthesia maintained with propofol or desflurane. Anesthesiology 2009;111:547-55.
  15. Shyr MH, Yang CH, Kuo TB, Pan WH, Tan PP, Chan SH. Power spectral analysis of the electroencephalographic and hemodynamic correlates of propofol anesthesia in the rat: Intravenous bolus administration. Neurosci Lett 1993;153:161-4.
  16. McLeod G, Wallis C, Dick J, Cox C, Patterson A, Colvin J. Use of 2% propofol to produce diurnal sedation in critically ill patients. Intensive Care Med 1997;23:428-34.
  17. Mayers AG, van Hooff JC, Baldwin DS. Quantifying subjective assessment of sleep and life-quality in antidepressant-treated depressed patients. Hum Psychopharmacol 2003;18:21-7.
  18. Sleigh JW, Andrzejowski J, Steyn-Ross A, Steyn-Ross M. The bispectral index: A measure of depth of sleep? Anesth Analg 1999;88:659-61.
  19. Knab B, Engel RR. Perception of waking and sleeping: Possible implications for the evaluation of insomnia. Sleep 1988;11:265-72.
  20. Boyko Y, Ording H, Jennum P. Sleep disturbances in critically ill patients in ICU: How much do we know? Acta Anaesthesiol Scand 2012;56:950-8.
  21. Uchida S, Okudaira N, Nishihara K, Iguchi Y. Flunitrazepam effects on human sleep EEG spectra: Differences in NREM, REM and individual responses. Life Sci 1996;58:PL199-205.
  22. Treggiari-Venzi M, Borgeat A, Fuchs-Buder T, Gachoud JP, Suter PM. Overnight sedation with midazolam or propofol in the ICU: Effects on sleep quality, anxiety and depression. Intensive Care Med 1996;22:1186-90.
  23. Benini F, Trapanotto M, Sartori S, Capretta A, Gobber D, Boniver C, et al. Analysis of the bispectral index during natural sleep in children. Anesth Analg 2005;101:641-4.
  24. Kanno O, Watanabe H, Kazamatsuri H. Effects of zopiclone, flunitrazepam, triazolam and levomepromazine on the transient change in sleep-wake schedule: Polygraphic study, and the evaluation of sleep and daytime condition. Prog Neuropsychopharmacol Biol Psychiatry 1993;17:229-39.
  25. Haenggi M, Ypparila-Wolters H, Buerki S, Schlauri R, Korhonen I, Takala J, et al. Auditory event-related potentials, bispectral index, and entropy for the discrimination of different levels of sedation in intensive care unit patients. Anesth Analg 2009;109:807-16.
  26. Iselin-Chaves IA, Flaishon R, Sebel PS, Howell S, Gan TJ, Sigl J, et al. The effect of the interaction of propofol and alfentanil on recall, loss of consciousness, and the Bispectral Index. Anesth Analg 1998;87:949-55.
  27. Suzuki M, Edmonds HL Jr, Tsueda K, Malkani AL, Roberts CS. Effect of ketamine on bispectral index and levels of sedation. J Clin Monit Comput 1998;14:373.
  28. Mi WD, Sakai T, Singh H, Kudo T, Kudo M, Matsuki A. Hypnotic endpoints vs. the bispectral index, 95% spectral edge frequency and median frequency during propofol infusion with or without fentanyl. Eur J Anaesthesiol 1999;16:47-52.
  29. Ibrahim AE, Taraday JK, Kharasch ED. Bispectral index monitoring during sedation with sevoflurane, midazolam, and propofol. Anesthesiology 2001;95:1151-9.
  30. Shilo L, Dagan Y, Smorjik Y, Weinberg U, Dolev S, Komptel B, et al. Patients in the intensive care unit suffer from severe lack of sleep associated with loss of normal melatonin secretion pattern. Am J Med Sci 1999;317:278-81.
  31. Cooper AB, Thornley KS, Young GB, Slutsky AS, Stewart TE, Hanly PJ. Sleep in critically ill patients requiring mechanical ventilation. Chest 2000;117:809-18.
  32. Hardin KA, Seyal M, Stewart T, Bonekat HW. Sleep in critically ill chemically paralyzed patients requiring mechanical ventilation. Chest 2006;129:1468-77.
PDF Share
PDF Share

© Jaypee Brothers Medical Publishers (P) LTD.