Melatonin: Is It Suitable for Use in Anesthesia?
Article Sidebar
Published:
Apr 19, 2019
Keywords:
melatonin, anesthesia
Main Article Content
Abstract
Melatonin is a hormone secreted from pineal gland.
It involves in the regulation of circadian rhythmicity and
seasonality in human and animals. It is widely used for the
treatment of insomnia and jet lag.
Melatonin has effects on anti-carcinogenesis and its
metastasis, antihypertension, anti-free radicals that protect
tissue and cells from oxidative stress, and inhibition of
white blood cell aggregation results in anti-inflammatory
activity.
Melatonin has 85% first-pass effect, 1-hour half-life
and renal clearance. Long administration of this hormone
yields adverse effects such as daytime yawning, dozing,
headache, dizziness, and short-term depression.
Surgery and anesthesia can interfere circadian rhythm.
These delay melatonin secretion at night. Exogenous
melatonin helps sleep onset latency back to normal as
soon as possible. In addition, it prevents delirium and
problems of postoperative cognitive dysfunction in early
24 hour without loss of orientation and affective function.
Though melatonin has anxiolytic and hypnotic
properties, its efficacy is not sufficient enough as an
alternative anesthetics, but an adjuvant for premedication,
general anesthesia, and pain relief. Melatonin differs from
midazolam in term of its early recovery time and less
postoperative agitation. It decreases the amount of
propofol, thopental and ketamine resulting in rapid
unconsciousness.
Remarkably, the American Food and Drug Administration
have not yet approved melatonin, except Ramelteon
(Rozerem®) for the treatment of insomnia.
Article Details
Section
Review articles
References
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pathophysiology of melatonin. Sleep Med Rev 2005; 9: 11-24.
6. Arendt J, Skene DJ. Melatonin as a chronobiotic. Sleep Med
Rev 2005; 9(1): 25-39.
7. Karasek M, Winczyk K. Melatonin in humans. J Physiol
Pharmacol 2006; 57(5): 19-39.
8. Zawilska JB, Skene Dj, Arendt J. Physiology and pharmacology
of melatonin in relation to biological rhythms. Pharmacol Rep
2009; 61(3): 383-410.
9. Pechanova O, Paulis L, Simko F. Peripheral and central
effects of melatonin on blood pressure regulation. Int J Mol
Sci 2014; 15: 17920-37.
10. Altun A, Ugur- Altun B. Melatonin: therapeutic and clinical
utilization. Int J Clin Pract 2007; 61(5): 835-45.
11. Ekmekcioglu C. Melatonin receptors in humans: biological
role and clinical relevance. Biomed Pharmacother 2006;
60(3): 97-108.
12. Dubbels R, Reiter RJ, Klenke E, et al. Melatonin in edible
plants identified by radioimmunoassay and by high
performance liquid chromatography-mass spectrometry.
J Pineal Res 1995; 18: 28-31.
13. Facciola G, Hidestrand M, von Bahr C, Tybring G.
Cytochrome P450 isoforms involved in melatonin metabolism
in human liver microsomes. Eur J Clin Pharmacol 2001; 56:
881-8.
14. Ma X, Idle JR, Krausz KW, Gonzalez FJ. Metabolism of
melatonin by human cytochromes p-450. Drug Metab Dispos
2005; 33(4): 489-94.
15. Steinhilber D, Brungs M, Werz O, et al. The nuclear receptor
for melatonin represses 5-lipoxygenase gene expression in
human B lymphocytes. J Biol Chem 1995; 270(13): 7037-40.Hazlerigg DG1, Thompson M, Hastings MH, Morgan PJ.
Regulation of mitogen-activated protein kinase in the pars
tuberalis of the ovine pituitary: interactions between melatonin,
insulin-like growth factor-1, and forskolin. Endocrinology
1996; 137(1): 210-18.
17. Sanchez-Barcelo EJ, Cos S, Mediavilla D, Martinez-Campa C,
Gonzalez A, Alonso-Gonzalez C. Melatonin-estrogen
interactions in breast cancer. J Pineal Res 2005; 38(4): 217-22.
18. Pandi-Perumal SR, Srinivasan V, Maestroni GJ, Cardinali DP,
Poeggeler B, Hardeland R. Melatonin: Nature’s most versatile
biological signal?. FEBS J 2006; 273(13): 2813-38.
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melatonin receptors in mammals. Endocrine 2005; 27(2):
101-10.
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MI. Molecular pharmacology, regulation and function of
mammalian melatonin receptors. Front Biosci 2003; 8: 1093-8.
21. Waldhauser F, Saletu B, Trinchard-Lugan I. Sleep laboratory
investigations on hypnotic properties of melatonin.
Psychopharmacology (Berl) 1990; 100(2): 222-6.
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of its physiological interactions. Endocr Rev 1991; 12: 151-80.
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rhythms in the fetus. Mol. Cell Endocrinol 2012; 349: 68-75.
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preserves fetal growth in rats by protecting against ischemia
reperfusion-induced oxidative/nitrosative mitochondrial
damage in the placenta. J Pineal Res 2008; 45: 271-6.
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melatonin. International Conference on Molecular and
Clinical Aspects of Melatonin; 2018 Aug 30-31; Chulabhorn
Graduate Institute. Bangkok: 2018
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Pediatrics. Int J Mol Sci 2015; 16(1): 1209-20.
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sleep on Melatonin-study group: Efficacy of melatonin with
behavioral sleep-wake scheduling for delayed sleep-wake
phase disorder: A double-blind, randomised clinical trial.
PLoS Med 2018;15(6): e1002587.
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melatonin supplementation on mental health, metabolic and
genetic profiles in patients under methadone maintenance
treatment. Addict Biol 2018; Jun 27: doi:10.1111/adb.12650.
29. Zhenlong Xin, Shuai Jiang, Peng Jiange. Melatonin as a
treatment for gastrointestinal cancer: a review. 2015; March
06: https://doi.org/10.1111/jpi.12227.
30. Papantoniou K, Kogevinas M, Martin Sanchez V. 0058
Colorectal cancer risk and shift work in a population-based
case-control study in Spain (MCC-Spain). Occup Environ
Med 2014; 71(Suppl.1): A5-A6.
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J. Night work and the risk of cancer among men. Am J
Epidemiol 2012; 176: 751-9.
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course of gastro-esophageal reflux disease?. World J
Gastrointest Pharmacol Ther 2011; 2: 50-1.
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Brzozowski TI. Mechanisms of esophageal protection gastro
protection and ulcer healing by melatonin Implications for
the therapeutic use of melatonin in gastroesophageal reflux
disease (GERD) and peptic ulcer disease. Curr Pharm Des
2014; 20: 4807-15.
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models of gastrointestinal inflammation and cancer. Life Sci
2014; 108(1): 1-6.
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therapeutic effect of melatonin in Gastro-Esophageal Reflux
Disease. BMC Gastroenterol 2010; 10: 7.
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Govitpong. Protective effects of melatonin n METH-induced
alteration of blood brain barrier (BBB) integrity. International
Conference on Molecular and Clinical Aspects of Melatonin.
2018 Aug 30-31; Chulabhorn Graduate Institute. Bangkok:
2018
37. Hill SM, Belancio VP, Dauchy RT, et al. Melatonin: an inhibitor
of breast cancer. Endocr Relat Cancer 2015; 22(3): R183-204.
38. Anisimov VN, Vinogradova IA, Panchenko AV, Popovich IG,
Zabezhinski MA. Light-at-night-induced circadian disruption,
cancer and aging. Curr Aging Sci 2012; 5: 170-7.
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cancer risk. Neuro Endocrinol Lett 2006; 27: 35-52.
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treatment. J Pineal Res 2007; 42(4): 319-22.
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expression in the cardiovascular system. Front Biosci (Schol
Ed) 2013; 5: 743-53.
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stress and cardio-metabolic risk in type 2 diabetic patients
with coronary heart disease: A randomized, double-blind,
placebo-controlled trial. Clin Nutr 2017; Dec 12: doi:
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treatment in peri- and postmenopausal women elevates
serum high-density lipoprotein cholesterol levels without
influencing total cholesterol levels. J Pineal Res 2008; 45(1):
101-5.
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melatonin supplementation on mental health, metabolic and
genetic profiles in patients under methadone maintenance
treatment. Addict Biol 2018; Jun 27: doi: 10.1111/adb.12650.
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EA. Neuroprotective effect of melatonin against hypoxia-induced
retinal ganglion cell death in neonatal rats.
J Pineal Res 2013; 54(2): 190-206.
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Service Anti-Cancer Agent: Inhibition of Initiation, Progression
and Metastasis. Int J Mol Sci 2017; 18(4): 843.
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universal nature unequal distribution and antioxidant
functions of melatonin and its derivatives. Mini Rev Med
Chem 2013; 13(3): 373-84.
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oocyte quality and melatonin protects oocytes from free
radical damage and improves fertilization rate. J Pineal Res
2008; 44(3): 280-7.
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in neonatal diseases. Oxid Med Cell Longev 2013: 980374.
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Melatonin reduces hyperalgesia associated with
inflammation. J Pineal Res 2010; 49: 321-31.
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functions. Open Physiol J 2008; 1: 1-23.
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and anesthesia: a clinical perspective. J Pineal Res 2007;
42: 12-21.
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Melatonin Receptors: A Therapeutic Perspective. Annu Rev
Pharmacol Toxicol 2016; 56: 361-83.
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Yannielli DP. Daily variations in GABA receptor function in
Syrian hamster cerebral cortex. Neuroscience Letters 1995;
200(3): 211-3.
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of melatonin premedication on propofol and thiopental
induction dose-response curves: A prospective, randomized,
double-blind study. Anesth Analg 2006; 103: 1448-52.
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K. Melatonin premedication and the induction dose of
propofol. Eur J Anaesthesiol 2007; 24: 399-402
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effects of low doses of melatonin ingested in the evening.
Clin Pharmacol Ther 1995; 57(5): 552-8.
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AM. Melatonin for pre- and postoperative anxiety in adults.
Cochrane Database of Systematic Reviews 2015, Issue 4.
CD009861.
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development. Clinical pharmacology: Advances and
Applications 2014; 6: 127-37.
2. Lerner AB, Case JD, Takahashi Y, Lee TH, Mori W. Isolation
of melatonin the pineal gland factor that lightens melanocytes.
J Am Chem Soc 1958; 80(10), 2587.
3. Claustrata B, Bruna J, Chazotb G. The basic physiology and
pathophysiology of melatonin. Sleep Med Rev 2005; 1(9):
11-24.
4. Claustrat B, Leston J. Melatonin: Physiological effects in
humans. Neurochirurgie 2015; 61(2-3): 77-84.
5. Claustrat A, Brun J, Chazot G. The basic physiology and
pathophysiology of melatonin. Sleep Med Rev 2005; 9: 11-24.
6. Arendt J, Skene DJ. Melatonin as a chronobiotic. Sleep Med
Rev 2005; 9(1): 25-39.
7. Karasek M, Winczyk K. Melatonin in humans. J Physiol
Pharmacol 2006; 57(5): 19-39.
8. Zawilska JB, Skene Dj, Arendt J. Physiology and pharmacology
of melatonin in relation to biological rhythms. Pharmacol Rep
2009; 61(3): 383-410.
9. Pechanova O, Paulis L, Simko F. Peripheral and central
effects of melatonin on blood pressure regulation. Int J Mol
Sci 2014; 15: 17920-37.
10. Altun A, Ugur- Altun B. Melatonin: therapeutic and clinical
utilization. Int J Clin Pract 2007; 61(5): 835-45.
11. Ekmekcioglu C. Melatonin receptors in humans: biological
role and clinical relevance. Biomed Pharmacother 2006;
60(3): 97-108.
12. Dubbels R, Reiter RJ, Klenke E, et al. Melatonin in edible
plants identified by radioimmunoassay and by high
performance liquid chromatography-mass spectrometry.
J Pineal Res 1995; 18: 28-31.
13. Facciola G, Hidestrand M, von Bahr C, Tybring G.
Cytochrome P450 isoforms involved in melatonin metabolism
in human liver microsomes. Eur J Clin Pharmacol 2001; 56:
881-8.
14. Ma X, Idle JR, Krausz KW, Gonzalez FJ. Metabolism of
melatonin by human cytochromes p-450. Drug Metab Dispos
2005; 33(4): 489-94.
15. Steinhilber D, Brungs M, Werz O, et al. The nuclear receptor
for melatonin represses 5-lipoxygenase gene expression in
human B lymphocytes. J Biol Chem 1995; 270(13): 7037-40.Hazlerigg DG1, Thompson M, Hastings MH, Morgan PJ.
Regulation of mitogen-activated protein kinase in the pars
tuberalis of the ovine pituitary: interactions between melatonin,
insulin-like growth factor-1, and forskolin. Endocrinology
1996; 137(1): 210-18.
17. Sanchez-Barcelo EJ, Cos S, Mediavilla D, Martinez-Campa C,
Gonzalez A, Alonso-Gonzalez C. Melatonin-estrogen
interactions in breast cancer. J Pineal Res 2005; 38(4): 217-22.
18. Pandi-Perumal SR, Srinivasan V, Maestroni GJ, Cardinali DP,
Poeggeler B, Hardeland R. Melatonin: Nature’s most versatile
biological signal?. FEBS J 2006; 273(13): 2813-38.
19. Dubocovich ML, Markowska M. Functional MT1 and MT2
melatonin receptors in mammals. Endocrine 2005; 27(2):
101-10.
20. Dubocovich ML, Rivera-Bermudez MA, Gerdin MJ, Masana
MI. Molecular pharmacology, regulation and function of
mammalian melatonin receptors. Front Biosci 2003; 8: 1093-8.
21. Waldhauser F, Saletu B, Trinchard-Lugan I. Sleep laboratory
investigations on hypnotic properties of melatonin.
Psychopharmacology (Berl) 1990; 100(2): 222-6.
22. Reiter RJ. Pineal melatonin: cell biology of its synthesis and
of its physiological interactions. Endocr Rev 1991; 12: 151-80.
23. Seron-Ferre M, Mendez N, Abarzua-Catalan L, et al. Circadian
rhythms in the fetus. Mol. Cell Endocrinol 2012; 349: 68-75.
24. Nagai R, Watanabe K, Wakatsuki A, et al. Melatonin
preserves fetal growth in rats by protecting against ischemia
reperfusion-induced oxidative/nitrosative mitochondrial
damage in the placenta. J Pineal Res 2008; 45: 271-6.
25. Aroonsri Priprem. Delivery system for regional and/or topical
melatonin. International Conference on Molecular and
Clinical Aspects of Melatonin; 2018 Aug 30-31; Chulabhorn
Graduate Institute. Bangkok: 2018
26. Marseglia L, D’Angelo G, Manti S, et al. Analgesic, Anxiolytic
and Anaesthetic Effects of Melatonin: New Potential Uses in
Pediatrics. Int J Mol Sci 2015; 16(1): 1209-20.
27. Sletten TL, Magee M, Murray JM, Rajaratnam SMW. Delayed
sleep on Melatonin-study group: Efficacy of melatonin with
behavioral sleep-wake scheduling for delayed sleep-wake
phase disorder: A double-blind, randomised clinical trial.
PLoS Med 2018;15(6): e1002587.
28. Ghaderi A, Banafshe HR, Mirhosseini N, et al. The effects of
melatonin supplementation on mental health, metabolic and
genetic profiles in patients under methadone maintenance
treatment. Addict Biol 2018; Jun 27: doi:10.1111/adb.12650.
29. Zhenlong Xin, Shuai Jiang, Peng Jiange. Melatonin as a
treatment for gastrointestinal cancer: a review. 2015; March
06: https://doi.org/10.1111/jpi.12227.
30. Papantoniou K, Kogevinas M, Martin Sanchez V. 0058
Colorectal cancer risk and shift work in a population-based
case-control study in Spain (MCC-Spain). Occup Environ
Med 2014; 71(Suppl.1): A5-A6.
31. Parent ME, El-Zein M, Rousseau MC, Pintos J, Siemiatycki
J. Night work and the risk of cancer among men. Am J
Epidemiol 2012; 176: 751-9.
32. Madalinski MH. Does a melatonin supplement alter the
course of gastro-esophageal reflux disease?. World J
Gastrointest Pharmacol Ther 2011; 2: 50-1.
33. Brzozowska I, Strzalka M, Drozdowicz D, Konturek SJ,
Brzozowski TI. Mechanisms of esophageal protection gastro
protection and ulcer healing by melatonin Implications for
the therapeutic use of melatonin in gastroesophageal reflux
disease (GERD) and peptic ulcer disease. Curr Pharm Des
2014; 20: 4807-15.
34. Lu L, Chan RL, Luo XM, Wu WK, Shin VY, Cho CH. Animal
models of gastrointestinal inflammation and cancer. Life Sci
2014; 108(1): 1-6.
35. Kandil TS, Mousa AA, El-Gendy AA Abbas AM. The potential
therapeutic effect of melatonin in Gastro-Esophageal Reflux
Disease. BMC Gastroenterol 2010; 10: 7.
36. Jatuporn Namyen, Kannika Permpoonputtana, Piyarat
Govitpong. Protective effects of melatonin n METH-induced
alteration of blood brain barrier (BBB) integrity. International
Conference on Molecular and Clinical Aspects of Melatonin.
2018 Aug 30-31; Chulabhorn Graduate Institute. Bangkok:
2018
37. Hill SM, Belancio VP, Dauchy RT, et al. Melatonin: an inhibitor
of breast cancer. Endocr Relat Cancer 2015; 22(3): R183-204.
38. Anisimov VN, Vinogradova IA, Panchenko AV, Popovich IG,
Zabezhinski MA. Light-at-night-induced circadian disruption,
cancer and aging. Curr Aging Sci 2012; 5: 170-7.
39. Anisimov VN. Light pollution, reproductive function and
cancer risk. Neuro Endocrinol Lett 2006; 27: 35-52.
40. Simko F, Paulis L. Melatonin as a potential antihypertensive
treatment. J Pineal Res 2007; 42(4): 319-22.
41. Zeman M, Herichova I. Melatonin and clock genes
expression in the cardiovascular system. Front Biosci (Schol
Ed) 2013; 5: 743-53.
42. Farba R, Vahidreza O, Fereshteh B, Russel J, Reiter, Zatollah
A. Melatonin administration lowers biomarkers of oxidative
stress and cardio-metabolic risk in type 2 diabetic patients
with coronary heart disease: A randomized, double-blind,
placebo-controlled trial. Clin Nutr 2017; Dec 12: doi:
10.1016/j.clnu.2017.12.004.Tamura H, Nakamura Y, Narimatsu A, et al. Melatonin
treatment in peri- and postmenopausal women elevates
serum high-density lipoprotein cholesterol levels without
influencing total cholesterol levels. J Pineal Res 2008; 45(1):
101-5.
44. Ghaderi A, Banafshe HR, Mirhosseini N, et al. The effects of
melatonin supplementation on mental health, metabolic and
genetic profiles in patients under methadone maintenance
treatment. Addict Biol 2018; Jun 27: doi: 10.1111/adb.12650.
45. Kaur C, Sivakumar V, Robinson R, Foulds WS, Luu CD, Ling
EA. Neuroprotective effect of melatonin against hypoxia-induced
retinal ganglion cell death in neonatal rats.
J Pineal Res 2013; 54(2): 190-206.
46. Reiter RJ, Rosales-Corral SA, Tan DX, et al. Melatonin, a Full
Service Anti-Cancer Agent: Inhibition of Initiation, Progression
and Metastasis. Int J Mol Sci 2017; 18(4): 843.
47. Reiter RJ, Tan DX, Rosales-Corral S, Manchester LC. The
universal nature unequal distribution and antioxidant
functions of melatonin and its derivatives. Mini Rev Med
Chem 2013; 13(3): 373-84.
48. Tamura H, Takasaki A, Miwa I, et al. Oxidative stress impairs
oocyte quality and melatonin protects oocytes from free
radical damage and improves fertilization rate. J Pineal Res
2008; 44(3): 280-7.
49. Gitto E, Marseglia L, Manti S, et al. Protective role of melatonin
in neonatal diseases. Oxid Med Cell Longev 2013: 980374.
50. Esposito E, Paterniti I, Mazzon E, Bramanti P, Cuzzocrea S.
Melatonin reduces hyperalgesia associated with
inflammation. J Pineal Res 2010; 49: 321-31.
51. Hardeland R, Poeggeler B. Melatonin beyond its classical
functions. Open Physiol J 2008; 1: 1-23.
52. Naguib M, Gottumukkala V, Peter A. Goldstein. Melatonin
and anesthesia: a clinical perspective. J Pineal Res 2007;
42: 12-21.
53. Liu J, Clough SJ, Hutchinson AJ, et al. MT1 and MT2
Melatonin Receptors: A Therapeutic Perspective. Annu Rev
Pharmacol Toxicol 2016; 56: 361-83.
54. Beatriz I, Kanterewicz RE, Rosenstein DA, Golombek PC,
Yannielli DP. Daily variations in GABA receptor function in
Syrian hamster cerebral cortex. Neuroscience Letters 1995;
200(3): 211-3.
55. Naguib M, Samarkandi AH, Moniem MA, et al. The effects
of melatonin premedication on propofol and thiopental
induction dose-response curves: A prospective, randomized,
double-blind study. Anesth Analg 2006; 103: 1448-52.
56. Turkistani A, Abdullah KM, Al-Shaer AA, Mazen KF, Alkatheri
K. Melatonin premedication and the induction dose of
propofol. Eur J Anaesthesiol 2007; 24: 399-402
57. Zhdanova IV1, Wurtman RJ, Lynch HJ, et al. Sleep-inducing
effects of low doses of melatonin ingested in the evening.
Clin Pharmacol Ther 1995; 57(5): 552-8.
58. Hansen MV, Halladin NL, Rosenberg J, Gogenur I, Moller
AM. Melatonin for pre- and postoperative anxiety in adults.
Cochrane Database of Systematic Reviews 2015, Issue 4.
CD009861.
59. Kain ZN, MacLaren JE, Leslie H, et al. Preoperative melatonin
and its effects on induction and emergence in children
undergoing anesthesia and surgery. Anesthesiology 2009;
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