Original Research

Steroid-Induced Sleep Disturbance and Delirium: A Focused Review for Critically Ill Patients

Fed Pract. 2020 June;37(6):260-267

References

1. Simini B. Patients’ perceptions of intensive care. Lancet. 1999;354(9178):571-572. doi: 10.1016/S0140-6736(99)02728-2

2. Delaney LJ, Van Haren F, Lopez V. Sleeping on a problem: the impact of sleep disturbance on intensive care patients—a clinical review. Ann Intensive Care. 2015;15:3. doi: 10.1186/s13613-015-0043-2

3. Friese RS, Diaz-Arrastia R, McBride D, Frankel H, Gentilello LM. Quality and quantity of sleep in the surgical intensive care unit; are our patients sleeping? J Trauma. 2007;63(6):1210-1214. doi: 10.1097/TA.0b013e31815b83d7

4. Elliott R, McKinley S, Cistulli P, Fien M. Characterisation of sleep in intensive care using 24-hour polysomnography: an observational study. Crit Care 2013;17(2):R46.

5. Aurell J, Elmqvist D. Sleep in the surgical intensive care unit: continuous polygraphic recording of sleep in patients receiving postoperative care. BJM (Clin Res Ed). 1985;290(6474)1029-1032. doi: 10.1136/bmj.290.6474.1029

6. White DP, Douglas NJ, Pickett CK, Zwillich CW, Weil JV. Sleep deprivation and the control of ventilation. Am Rev Respir Dis. 1983;128(6):984-986. doi: 10.1164/arrd.1983.128.6.984

7. Series F, Roy N, Marc I. Effects of sleep deprivation and sleep fragmentation on upper airway collapsibility in normal subjects. Am J Respir Crit Care Med. 1994;150(2):481-485. doi: 10.1164/ajrccm.150.2.8049833

8. Tadjalli A, Peever J. Sleep loss reduces respiratory motor plasticity. Adv Exp Med Biol. 2010;669:289-292.

doi: 10.1007/978-1-4419-5692-7_59

9. Roche Campo F, Drouot X, Thille AW, et al. Poor sleep quality is associated with late noninvasive ventilation failure in patients with acute hypercapnic respiratory failure. Crit Care Med. 2010;38(2):447-485. doi: 10.1097/CCM.0b013e3181bc8243

10. Sauvet F, Leftheriotis G, Gomez-Merino D, et al. Effect of acute sleep deprivation on vascular function in healthy subjects. J Appl Physiol (1985). 2010;108(1):68-75. doi: 10.1152/japplphysiol.00851.2009

11. Frey DJ, Fleshner M, Wright KP Jr. The effects of 40 hours of total sleep deprivation on inflammatory markers in healthy young adults. Brain Behav Immun. 2007;21(8):1050-1057. doi: 10.1016/j.bbi.2007.04.003

12. Spiegel K, Sheridan JF, Van Cauter E. Effect of sleep deprivation on response to immunization. JAMA 2002;288(12):1471-1472. doi: 10.1001/jama.288.12.1471-a

13. Dinges DF, Douglas SD, Zuagg L, et al. Leukocytosis and natural killer cell function parallel neurobehavioral fatigue induced by 64 hours of sleep deprivation. J Clin Invest. 1994;93(5):1930-1939. doi: 10.1172/JCI117184

14. Weinhouse GL, Schwab RJ, Watson PL, et al. Bench-to-bedside review: delirium in ICU patients— importance of sleep deprivation. Crit Care. 2009;13(6):234. doi: 10.1186/cc8131

15. Ely EW, Shintani A, Truman B, et al. Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA. 2004;291(14):1753-1762. doi: 10.1001/jama.291.14.1753

16. Girard TD, Jackson JC, Pandharipande PP, et al. Delirium as a predictor of long-term cognitive impairment in survivors of critical illness. Crit Care Med. 2010;38(7):1513-1520. doi: 10.1097/CCM.0b013e3181e47be1

17. Devlin JW, Skrobik Y, Gelinas C, et al. Clinical practice guidelines for the prevention and management of pain, agitation/sedation, delirium, immobility, and sleep disruption in adult patients in the ICU. Crit Care Med. 2018;46(9):e825-e873

18. The Boston Collaborative Drug Surveillance Program. Acute adverse reactions to prednisone in relation to dosage. Clin Pharmacol Ther. 1972;13(5):694-698. doi: 10.1002/cpt1972135part1694

19. Rundell JR, Wise MG. Causes of organic mood disorder. J Neuropsychiatry Clin Neurosci. 1989;1(4):398-400. doi: 10.1176/jnp.1.4.398

20. Gaudreau JD, Gagnon P, Harel F, Roy MA, Tremblay A. Psychoactive medications and risk of delirium in hospitalized cancer patients. J Clin Oncol. 2005;23(27):6712-6718. doi: 10.1200/JCO.2005.05.140

21. Gaudreau JD, Gagnon P, Roy MA, Harel F, Tremblay A. Opioid medications and longitudinal risk of delirium in hospitalized cancer patients. Cancer. 2007;109(11):2365-2373.

doi: 10.1002/cncr.22665

22. Schreiber MP, Colantuoni E, Bienvenu OJ, et al. Corticosteroids and transition to delirium in patients with acute lung injury. Crit Care Med. 2014;42(6):1480-1486. doi: 10.1097/CCM.0000000000000247

23. Wolters AE, Veldhuijzen DS, Zaal IJ, et al. Systemic corticosteroids and transition to delirium in critically ill patients. Crit Care Med. 2015;43(12):e585-e588. doi: 10.1097/CCM.0000000000001302

24. Matschke J, Muller-Beissenhirtz H, Novotny J, et al. A randomized trial of daily prednisone versus pulsed dexamethasone in treatment-naïve adult patients with immune thrombocytopenia: EIS 2002 study. Acta Haematol. 2016;136(2):101-107. doi: 10.1159/000445420

25. Tilouche N, Hassen M, Ali HBS, Jaoued AHO, Gharbi R, Atrous SS. Delirium in the intensive care unit: incidence, risk factors, and impact on outcome. Indian J Crit Care Med. 2018;22:144-149. doi: 10.4103/ijccm.IJCCM_244_17

26. Young A, Marsh S. Steroid use in critical care. BJA Education. 2018;18(5):129-134. doi: 10.1016/j.bjae.2018.01.005

27. DiPiro J, Talbert R, Yee G, Matzke GR, Wells BG, Posey M. Pharmacotherapy: A Pathophysiologic Approach. 4th ed. New York: McGraw-Hill; 1999:1277-1278.

28. Schimmer BP, Parker KL. Adrenocorticotripic hormone; adrenocortical steroids and their synthetic analogs; inhibitors of the synthesis and actions of adrenocortical hormones. In: Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 9th ed. New York: McGraw-Hill; 1996:1459-1485.

29. Sarnes E, Crofford L, Watson M, Dennis G, Kan H, Bass D. Incidence of US costs of corticosteroid-associated adverse events: a systematic literature review. Clin Ther. 2011;33(10):1413-1432.

30. Idzikowsi C, Shapiro CM. ABC of sleep disorders, non-psychotropic drugs and sleep. BMJ. 1993;306(6885):1118-1120. doi: 10.1136/bmj.306.6885.1118

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31. Tasker JG, Herman JP. Mechanisms of rapid glucocorticoid feedback inhibition of the hypothalamic-pituitary-adrenal axis. Stress. 2011;14(4):398-406.

doi: 10.3109/10253890.2011.586446

32. Wolkowitz OM, Reus VI, Weingartner H, et al. Cognitive effects of corticosteroids. Am J Psychiatry 1990;147(10):1297-1303. doi: 10.1176/ajp.147.10.1297

33. McEwen BS, Davis PG, Parsons B, Pfaff DW. The brain as a target for steroid hormone action. Ann Rev Neurosci. 1979;2:65-112. doi: 10.1146/annurev.ne.02.030179.000433

34. Brown ES, Woolston DJ, Frol AM. Amygdala volume in patients receiving chronic corticosteroid therapy. Biol Psychiatry. 2008;63(7):705-709.

doi: 10.1016/j.biopsych.2007.09.014

35. Brown ES, Woolston D, Frol A, et al. Hippocampal volume, spectroscopy, cognition, and mood in patients receiving corticosteroid. Biol Psychiatry. 2004;55(5):538-545.

36. Sapolsky RM, McEwen BS. Down-regulation of neural corticosterone receptors by corticosterone and dexamethasone. Brain Res. 1985;339(1):161-165.

doi: 10.1016/0006-8993(85)90638-9

37. Sorrells SF, Caso JR, Munhoz CD, Spolsky RM. The stressed CNS: when glucocorticoids aggravate inflammation. Neuron. 2009;64(1):33-39.

doi: 10.1016/j.neuron.2009.09.032

38. Wolkowitz OM, Burke H, Epel ES, Reus VI. Glucocorticoids: mood, memory, and mechanisms. Ann NY Acad Sci. 2009;1179:19-40. doi: 10.1111/j.1749-6632.2009.04980.x

39. Wolkowitz OM, Epel ES, Reus VI. Stress hormone-related psychopathology: pathophysiological and treatment implications. World J Biol Psychiatry. 2001;2(3):115-143. doi: 10.3109/15622970109026799

40. Paredes S, Barriga C, Reiter R, Rodrigues A. Assessment of the potential role of tryptophan as the precursor of serotonin and melatonin for the aged sleep-wake cycle and immune function: Streptopelia Risoria as a model. Int J Tryptophan Res. 2009;2:23-36. doi: 10.4137/ijtr.s1129

41. Soszyński P, Stowińska-Srzednicka J, Kasperlik-Zatuska A, Zgliczyński S. Decreased melatonin concentration in Cushing’s Syndrome. Horm Metab Res. 1989;21(12):673-674. doi: 10.1055/s-2007-1009317

42. Demish L, Demish K, Neckelsen T. Influence of dexamethasone on nocturnal melatonin production in healthy adult subjects. J Pineal Res. 1988;5(3):317-321. doi: 10.1111/j.1600-079x.1988.tb00657.x

43. Assaf N, Shalby AB, Khalil WK, Ahmed HH. Biochemical and genetic alterations of oxidant/antioxidant status of the brain in rats treated with dexamethasone: protective roles of melatonin and acetyl-L-carnitine. J Physiol Biochem. 2012;68(1):77-90. doi: 10.1007/s13105-011-0121-3

44. Clark MS, Russo AF. Tissue-specific glucocorticoid regulation of tryptophan hydroxylase mRNA levels. Brain Res Mol Brain Res. 1997;48(2):346-54. doi: 10.1016/s0169-328x(97)00106-x

45. Kram DE, Krasnow SM, Levasseur PR, Zhu X, Stork LC, Marks DL. Dexamethasone chemotherapy does not disrupt orexin signaling. PLoS One. 2016;11(12):e0168731. doi: 10.1371/journal.pone.0168731

46. Mellon S. Neurosteroids: biochemistry, modes of action, and clinical relevance. J Clin Endocrinol Metab. 1994;78(5):1003-1008. doi: 10.1210/jcem.78.5.8175951

47. Zorumski C, Paul SM, Izumi Y, Covey DF, Mennerick S . Neurosteroids, stress and depression: potential therapeutic opportunities. Neurosci Biobehav Rev. 2013;37(1):109-122. doi: 10.1016/j.neubiorev.2012.10.005

48. Monteleone P, Luisi M, Martiadis V, et al. Impaired reduction of enhanced levels of dehydroepiandrosterone by oral dexamethasone in anorexia nervosa. Psychoneuroendocrinology. 2006;31(4):537-542. doi: 10.1016/j.psyneuen.2005.08.015

49. Genazzani AR, Petraglia F, Bernardi F, et al. Circulating levels of allopregnanolone in humans: gender, age, and endocrine influences. J Clin Endocrinol Metab. 1998;83(6):2099-3103. doi: 10.1210/jcem.83.6.4905

50. Moser NJ, Phillips BA, Guthrie G, Barnett G. Effects of dexamethasone on sleep. Pharmacol Toxicol. 1996;79(2):100-102. doi: 10.1111/j.1600-0773.1996.tb00249.x

51. Curtis J, Westfall A, Allison J, et al. Population-based assessment of adverse events associated with long-term glucocorticoid use. Arthritis Rheum. 2006;55(3):420-426. doi: 10.1002/art.21984

52. Zhao J, Dai YH, Xi QS, Yu SY. A clinical study on insomnia in patients with cancer during chemotherapy containing high-dose glucocorticoids. Pharmazie. 2013;68(6):421-427

53. Naber D, Sand P, Heigl B. Psychopathological and neuropsychological effects of 8-days corticosteroid treatment. A prospective study. Psychoneuroendocrinology. 1996;21(1):25-31. doi: 10.1016/0306-4530(95)00031-3

54. Brown ES, Suppes T, Khan DA, Carmody TJ 3rd. Mood changes during prednisone bursts in outpatients with asthma. J Clin Psychopharmacol. 2002;22(1):55-61.

doi: 10.1097/00004714-200202000-00009

55. Warrington TP, Bostwick JM. Psychiatric adverse effects of corticosteroids. Mayo Clin Proc. 2006;81(10):1361-1367. doi: 10.4065/81.10.1361

56. Britt RC, Devine A, Swallen KC et al. Corticosteroid use in the intensive care unit: at what cost? Arch Surg. 2006;141(2):145-159. doi:10.1001/archsurg.141.2.145

57. Kiser TH, Allen RR, Valuck RJ, Moss M, Vanivier RW. Outcomes associated with corticosteroid dosage in critically ill patients in acute exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2014;189(9):1052-1064. doi: 10.1164/rccm.201401-0058OC

58. Bourne RS, Mills GH. Sleep disruption in critically ill patients—pharmacological considerations. Anaesthesia. 2004;59(4):374-384. doi: 10.1111/j. 1365-2044.2004.03664.x

59. Flaherty JH. Insomnia among hospitalized older persons. Clin Geriatr Med. 2008;24(1):51-67. doi: 10.1016/j.cger.2007.08.012

60. Sirios F. Steroid psychosis: a review. Gen Hosp Psychiatry. 2003;25(1):27-33. doi: 10.1016/s0163-8343(02)00241-4

Mitigating Effects

Although steroid therapy often cannot be altered in the critically ill population, research showed that steroid overuse is common in ICUs.^56,57 Minimizing dosage and duration are important ways clinicians can mitigate unwanted effects. CNS AEs seen with steroids often can be reversed once therapy is discontinued. Avoiding split-dose administration has been proposed given the natural diurnal production of cortisol.⁵⁸A review by Flaherty discusses the importance of avoiding pharmacologic agents in hospitalized older patients if possible due to known risks (falls, dependency, hip fractures, rebound insomnia, and risk of delirium) and provides a HELP ME SLEEP nomogram for nonpharmacologic interventions in hospitalized patients (Table 4).⁵⁹

Historically, lithium has been recommended for steroid-induced mania with chronic steroid use; however, given the large volume and electrolyte shifts seen in critically ill patients, this may not be a viable option. Antidepressants, especially tricyclics, should generally be avoided in steroid-induced psychosis as these may exacerbate symptoms. If symptoms are severe, either typical (haloperidol) or atypical (olanzapine, quetiapine, risperidone) antipsychotics have been used with success.⁶⁰ Given the known depletion of serum melatonin levels, melatonin supplements are an attractive and relatively safe option for steroid-induced insomnia; however, there are no robust studies specifically aimed at this intervention for this population.

Conclusions

With known, multimodal foci driving sleep impairment in ICU patients, PADIS guidelines recommend myriad interventions for improvement. Recommendations include noise and light reduction with earplugs and/or eyeshades to improve sleep quality. Nocturnal assist-control ventilation may improve sleep quality in ventilated patients. Finally, the development of institutional protocols for promoting sleep quality in ICU patients is recommended.¹⁷

References

1. Simini B. Patients’ perceptions of intensive care. Lancet. 1999;354(9178):571-572. doi: 10.1016/S0140-6736(99)02728-2

2. Delaney LJ, Van Haren F, Lopez V. Sleeping on a problem: the impact of sleep disturbance on intensive care patients—a clinical review. Ann Intensive Care. 2015;15:3. doi: 10.1186/s13613-015-0043-2

3. Friese RS, Diaz-Arrastia R, McBride D, Frankel H, Gentilello LM. Quality and quantity of sleep in the surgical intensive care unit; are our patients sleeping? J Trauma. 2007;63(6):1210-1214. doi: 10.1097/TA.0b013e31815b83d7

4. Elliott R, McKinley S, Cistulli P, Fien M. Characterisation of sleep in intensive care using 24-hour polysomnography: an observational study. Crit Care 2013;17(2):R46.

5. Aurell J, Elmqvist D. Sleep in the surgical intensive care unit: continuous polygraphic recording of sleep in patients receiving postoperative care. BJM (Clin Res Ed). 1985;290(6474)1029-1032. doi: 10.1136/bmj.290.6474.1029

6. White DP, Douglas NJ, Pickett CK, Zwillich CW, Weil JV. Sleep deprivation and the control of ventilation. Am Rev Respir Dis. 1983;128(6):984-986. doi: 10.1164/arrd.1983.128.6.984

7. Series F, Roy N, Marc I. Effects of sleep deprivation and sleep fragmentation on upper airway collapsibility in normal subjects. Am J Respir Crit Care Med. 1994;150(2):481-485. doi: 10.1164/ajrccm.150.2.8049833

8. Tadjalli A, Peever J. Sleep loss reduces respiratory motor plasticity. Adv Exp Med Biol. 2010;669:289-292.

doi: 10.1007/978-1-4419-5692-7_59

9. Roche Campo F, Drouot X, Thille AW, et al. Poor sleep quality is associated with late noninvasive ventilation failure in patients with acute hypercapnic respiratory failure. Crit Care Med. 2010;38(2):447-485. doi: 10.1097/CCM.0b013e3181bc8243

10. Sauvet F, Leftheriotis G, Gomez-Merino D, et al. Effect of acute sleep deprivation on vascular function in healthy subjects. J Appl Physiol (1985). 2010;108(1):68-75. doi: 10.1152/japplphysiol.00851.2009

11. Frey DJ, Fleshner M, Wright KP Jr. The effects of 40 hours of total sleep deprivation on inflammatory markers in healthy young adults. Brain Behav Immun. 2007;21(8):1050-1057. doi: 10.1016/j.bbi.2007.04.003

12. Spiegel K, Sheridan JF, Van Cauter E. Effect of sleep deprivation on response to immunization. JAMA 2002;288(12):1471-1472. doi: 10.1001/jama.288.12.1471-a

13. Dinges DF, Douglas SD, Zuagg L, et al. Leukocytosis and natural killer cell function parallel neurobehavioral fatigue induced by 64 hours of sleep deprivation. J Clin Invest. 1994;93(5):1930-1939. doi: 10.1172/JCI117184

14. Weinhouse GL, Schwab RJ, Watson PL, et al. Bench-to-bedside review: delirium in ICU patients— importance of sleep deprivation. Crit Care. 2009;13(6):234. doi: 10.1186/cc8131

15. Ely EW, Shintani A, Truman B, et al. Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA. 2004;291(14):1753-1762. doi: 10.1001/jama.291.14.1753

16. Girard TD, Jackson JC, Pandharipande PP, et al. Delirium as a predictor of long-term cognitive impairment in survivors of critical illness. Crit Care Med. 2010;38(7):1513-1520. doi: 10.1097/CCM.0b013e3181e47be1

17. Devlin JW, Skrobik Y, Gelinas C, et al. Clinical practice guidelines for the prevention and management of pain, agitation/sedation, delirium, immobility, and sleep disruption in adult patients in the ICU. Crit Care Med. 2018;46(9):e825-e873

18. The Boston Collaborative Drug Surveillance Program. Acute adverse reactions to prednisone in relation to dosage. Clin Pharmacol Ther. 1972;13(5):694-698. doi: 10.1002/cpt1972135part1694

19. Rundell JR, Wise MG. Causes of organic mood disorder. J Neuropsychiatry Clin Neurosci. 1989;1(4):398-400. doi: 10.1176/jnp.1.4.398

20. Gaudreau JD, Gagnon P, Harel F, Roy MA, Tremblay A. Psychoactive medications and risk of delirium in hospitalized cancer patients. J Clin Oncol. 2005;23(27):6712-6718. doi: 10.1200/JCO.2005.05.140

21. Gaudreau JD, Gagnon P, Roy MA, Harel F, Tremblay A. Opioid medications and longitudinal risk of delirium in hospitalized cancer patients. Cancer. 2007;109(11):2365-2373.

doi: 10.1002/cncr.22665

22. Schreiber MP, Colantuoni E, Bienvenu OJ, et al. Corticosteroids and transition to delirium in patients with acute lung injury. Crit Care Med. 2014;42(6):1480-1486. doi: 10.1097/CCM.0000000000000247

23. Wolters AE, Veldhuijzen DS, Zaal IJ, et al. Systemic corticosteroids and transition to delirium in critically ill patients. Crit Care Med. 2015;43(12):e585-e588. doi: 10.1097/CCM.0000000000001302

24. Matschke J, Muller-Beissenhirtz H, Novotny J, et al. A randomized trial of daily prednisone versus pulsed dexamethasone in treatment-naïve adult patients with immune thrombocytopenia: EIS 2002 study. Acta Haematol. 2016;136(2):101-107. doi: 10.1159/000445420

25. Tilouche N, Hassen M, Ali HBS, Jaoued AHO, Gharbi R, Atrous SS. Delirium in the intensive care unit: incidence, risk factors, and impact on outcome. Indian J Crit Care Med. 2018;22:144-149. doi: 10.4103/ijccm.IJCCM_244_17

26. Young A, Marsh S. Steroid use in critical care. BJA Education. 2018;18(5):129-134. doi: 10.1016/j.bjae.2018.01.005

27. DiPiro J, Talbert R, Yee G, Matzke GR, Wells BG, Posey M. Pharmacotherapy: A Pathophysiologic Approach. 4th ed. New York: McGraw-Hill; 1999:1277-1278.

28. Schimmer BP, Parker KL. Adrenocorticotripic hormone; adrenocortical steroids and their synthetic analogs; inhibitors of the synthesis and actions of adrenocortical hormones. In: Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 9th ed. New York: McGraw-Hill; 1996:1459-1485.

29. Sarnes E, Crofford L, Watson M, Dennis G, Kan H, Bass D. Incidence of US costs of corticosteroid-associated adverse events: a systematic literature review. Clin Ther. 2011;33(10):1413-1432.

30. Idzikowsi C, Shapiro CM. ABC of sleep disorders, non-psychotropic drugs and sleep. BMJ. 1993;306(6885):1118-1120. doi: 10.1136/bmj.306.6885.1118

31. Tasker JG, Herman JP. Mechanisms of rapid glucocorticoid feedback inhibition of the hypothalamic-pituitary-adrenal axis. Stress. 2011;14(4):398-406.

doi: 10.3109/10253890.2011.586446

32. Wolkowitz OM, Reus VI, Weingartner H, et al. Cognitive effects of corticosteroids. Am J Psychiatry 1990;147(10):1297-1303. doi: 10.1176/ajp.147.10.1297

33. McEwen BS, Davis PG, Parsons B, Pfaff DW. The brain as a target for steroid hormone action. Ann Rev Neurosci. 1979;2:65-112. doi: 10.1146/annurev.ne.02.030179.000433

34. Brown ES, Woolston DJ, Frol AM. Amygdala volume in patients receiving chronic corticosteroid therapy. Biol Psychiatry. 2008;63(7):705-709.

doi: 10.1016/j.biopsych.2007.09.014

35. Brown ES, Woolston D, Frol A, et al. Hippocampal volume, spectroscopy, cognition, and mood in patients receiving corticosteroid. Biol Psychiatry. 2004;55(5):538-545.

36. Sapolsky RM, McEwen BS. Down-regulation of neural corticosterone receptors by corticosterone and dexamethasone. Brain Res. 1985;339(1):161-165.

doi: 10.1016/0006-8993(85)90638-9

37. Sorrells SF, Caso JR, Munhoz CD, Spolsky RM. The stressed CNS: when glucocorticoids aggravate inflammation. Neuron. 2009;64(1):33-39.

doi: 10.1016/j.neuron.2009.09.032

38. Wolkowitz OM, Burke H, Epel ES, Reus VI. Glucocorticoids: mood, memory, and mechanisms. Ann NY Acad Sci. 2009;1179:19-40. doi: 10.1111/j.1749-6632.2009.04980.x

39. Wolkowitz OM, Epel ES, Reus VI. Stress hormone-related psychopathology: pathophysiological and treatment implications. World J Biol Psychiatry. 2001;2(3):115-143. doi: 10.3109/15622970109026799

40. Paredes S, Barriga C, Reiter R, Rodrigues A. Assessment of the potential role of tryptophan as the precursor of serotonin and melatonin for the aged sleep-wake cycle and immune function: Streptopelia Risoria as a model. Int J Tryptophan Res. 2009;2:23-36. doi: 10.4137/ijtr.s1129

41. Soszyński P, Stowińska-Srzednicka J, Kasperlik-Zatuska A, Zgliczyński S. Decreased melatonin concentration in Cushing’s Syndrome. Horm Metab Res. 1989;21(12):673-674. doi: 10.1055/s-2007-1009317

42. Demish L, Demish K, Neckelsen T. Influence of dexamethasone on nocturnal melatonin production in healthy adult subjects. J Pineal Res. 1988;5(3):317-321. doi: 10.1111/j.1600-079x.1988.tb00657.x

43. Assaf N, Shalby AB, Khalil WK, Ahmed HH. Biochemical and genetic alterations of oxidant/antioxidant status of the brain in rats treated with dexamethasone: protective roles of melatonin and acetyl-L-carnitine. J Physiol Biochem. 2012;68(1):77-90. doi: 10.1007/s13105-011-0121-3

44. Clark MS, Russo AF. Tissue-specific glucocorticoid regulation of tryptophan hydroxylase mRNA levels. Brain Res Mol Brain Res. 1997;48(2):346-54. doi: 10.1016/s0169-328x(97)00106-x

45. Kram DE, Krasnow SM, Levasseur PR, Zhu X, Stork LC, Marks DL. Dexamethasone chemotherapy does not disrupt orexin signaling. PLoS One. 2016;11(12):e0168731. doi: 10.1371/journal.pone.0168731

46. Mellon S. Neurosteroids: biochemistry, modes of action, and clinical relevance. J Clin Endocrinol Metab. 1994;78(5):1003-1008. doi: 10.1210/jcem.78.5.8175951

47. Zorumski C, Paul SM, Izumi Y, Covey DF, Mennerick S . Neurosteroids, stress and depression: potential therapeutic opportunities. Neurosci Biobehav Rev. 2013;37(1):109-122. doi: 10.1016/j.neubiorev.2012.10.005

48. Monteleone P, Luisi M, Martiadis V, et al. Impaired reduction of enhanced levels of dehydroepiandrosterone by oral dexamethasone in anorexia nervosa. Psychoneuroendocrinology. 2006;31(4):537-542. doi: 10.1016/j.psyneuen.2005.08.015

49. Genazzani AR, Petraglia F, Bernardi F, et al. Circulating levels of allopregnanolone in humans: gender, age, and endocrine influences. J Clin Endocrinol Metab. 1998;83(6):2099-3103. doi: 10.1210/jcem.83.6.4905

50. Moser NJ, Phillips BA, Guthrie G, Barnett G. Effects of dexamethasone on sleep. Pharmacol Toxicol. 1996;79(2):100-102. doi: 10.1111/j.1600-0773.1996.tb00249.x

51. Curtis J, Westfall A, Allison J, et al. Population-based assessment of adverse events associated with long-term glucocorticoid use. Arthritis Rheum. 2006;55(3):420-426. doi: 10.1002/art.21984

52. Zhao J, Dai YH, Xi QS, Yu SY. A clinical study on insomnia in patients with cancer during chemotherapy containing high-dose glucocorticoids. Pharmazie. 2013;68(6):421-427

53. Naber D, Sand P, Heigl B. Psychopathological and neuropsychological effects of 8-days corticosteroid treatment. A prospective study. Psychoneuroendocrinology. 1996;21(1):25-31. doi: 10.1016/0306-4530(95)00031-3

54. Brown ES, Suppes T, Khan DA, Carmody TJ 3rd. Mood changes during prednisone bursts in outpatients with asthma. J Clin Psychopharmacol. 2002;22(1):55-61.

doi: 10.1097/00004714-200202000-00009

55. Warrington TP, Bostwick JM. Psychiatric adverse effects of corticosteroids. Mayo Clin Proc. 2006;81(10):1361-1367. doi: 10.4065/81.10.1361

56. Britt RC, Devine A, Swallen KC et al. Corticosteroid use in the intensive care unit: at what cost? Arch Surg. 2006;141(2):145-159. doi:10.1001/archsurg.141.2.145

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Steroid-Induced Sleep Disturbance and Delirium: A Focused Review for Critically Ill Patients

References

Mitigating Effects

Conclusions

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