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J Pediatr Intensive Care 2016; 05(04): 172-181
DOI: 10.1055/s-0036-1583283
Review Article
Georg Thieme Verlag KG Stuttgart · New York

Melatonin in Critically Ill Children

Jennifer Ruth Foster
1   Department of Paediatrics, IWK Health Centre, Dalhousie University, Halifax, Nova Scotia, Canada
2   Department of Pediatrics, Western University, Ontario, Canada
3   Children's Health Research Institute, London, Ontario, Canada
4   Lawson Health Research Institute, London, Ontario, Canada
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Publikationsverlauf

06. Juni 2015

14. Oktober 2015

Publikationsdatum:
28. April 2016 (online)

    Lizenzen und Reprints

Abstract

Melatonin, while best known for its chronobiologic functions, has multiple effects that may be relevant in critical illness. It has been used for circadian rhythm maintenance, analgesia, and sedation, and has antihypertensive, anti-inflammatory, antioxidant, antiapoptotic, and antiexcitatory effects. This review examines melatonin physiology in health, the current state of knowledge regarding endogenous melatonin production in pediatric critical illness, and the potential uses of exogenous melatonin in this population, including relevant information from basic sciences and other fields of medicine. Pineal melatonin production and secretion appears to be altered in critical illness, though understanding in pediatric critical illness is in early stages, with only 102 children reported in the current literature. Exogenous melatonin may be used for circadian rhythm disturbances and, within the critically ill population, holds promise for diseases involving oxidant stress. There are no studies of exogenous melatonin administration to critically ill children beyond the neonatal period.

Keywords

melatonin - pineal gland - intensive care units - pediatric - critical care - circadian rhythm - antioxidants
 

  • References

  • 1 Hardeland R, Poeggeler B. Non-vertebrate melatonin. J Pineal Res 2003; 34 (4) 233-241
    CrossrefPubMedGoogle Scholar
  • 2 Hardeland R, Pandi-Perumal SR, Cardinali DP. Melatonin. Int J Biochem Cell Biol 2006; 38 (3) 313-316
    CrossrefPubMedGoogle Scholar
  • 3 Bojkowski CJ, Arendt J, Shih MC, Markey SP. Melatonin secretion in humans assessed by measuring its metabolite, 6-sulfatoxymelatonin. Clin Chem 1987; 33 (8) 1343-1348
    CrossrefPubMedGoogle Scholar
  • 4 Reppert SM, Godson C, Mahle CD, Weaver DR, Slaugenhaupt SA, Gusella JF. Molecular characterization of a second melatonin receptor expressed in human retina and brain: the Mel1b melatonin receptor. Proc Natl Acad Sci U S A 1995; 92 (19) 8734-8738
    CrossrefPubMedGoogle Scholar
  • 5 Reppert SM, Weaver DR, Ebisawa T. Cloning and characterization of a mammalian melatonin receptor that mediates reproductive and circadian responses. Neuron 1994; 13 (5) 1177-1185
    CrossrefPubMedGoogle Scholar
  • 6 Lewy AJ, Wehr TA, Goodwin FK, Newsome DA, Markey SP. Light suppresses melatonin secretion in humans. Science 1980; 210 (4475) 1267-1269
    CrossrefPubMedGoogle Scholar
  • 7 Hardeland R, Cardinali DP, Srinivasan V, Spence DW, Brown GM, Pandi-Perumal SR. Melatonin—a pleiotropic, orchestrating regulator molecule. Prog Neurobiol 2011; 93 (3) 350-384
    CrossrefPubMedGoogle Scholar
  • 8 Hardeland R. Chronobiology of melatonin beyond the feedback to the suprachiasmatic nucleus—consequences to melatonin dysfunction. Int J Mol Sci 2013; 14 (3) 5817-5841
    CrossrefPubMedGoogle Scholar
  • 9 Tricoire H, Locatelli A, Chemineau P, Malpaux B. Melatonin enters the cerebrospinal fluid through the pineal recess. Endocrinology 2002; 143 (1) 84-90
    CrossrefPubMedGoogle Scholar
  • 10 Reiter RJ. Pineal melatonin: cell biology of its synthesis and of its physiological interactions. Endocr Rev 1991; 12 (2) 151-180
    CrossrefPubMedGoogle Scholar
  • 11 Bagci S, Mueller A, Reinsberg J, Heep A, Bartmann P, Franz AR. Saliva as a valid alternative in monitoring melatonin concentrations in newborn infants. Early Hum Dev 2009; 85 (9) 595-598
    CrossrefPubMedGoogle Scholar
  • 12 Hardeland R. Antioxidative protection by melatonin: multiplicity of mechanisms from radical detoxification to radical avoidance. Endocrine 2005; 27 (2) 119-130
    CrossrefPubMedGoogle Scholar
  • 13 Bubenik GA. Gastrointestinal melatonin: localization, function, and clinical relevance. Dig Dis Sci 2002; 47 (10) 2336-2348
    CrossrefPubMedGoogle Scholar
  • 14 Bourne RS, Mills GH. Melatonin: possible implications for the postoperative and critically ill patient. Intensive Care Med 2006; 32 (3) 371-379
    CrossrefPubMedGoogle Scholar
  • 15 Brzezinski A. Melatonin in humans. N Engl J Med 1997; 336 (3) 186-195
    Google Scholar
  • 16 Claustrat B, Brun J, Chazot G. The basic physiology and pathophysiology of melatonin. Sleep Med Rev 2005; 9 (1) 11-24
    CrossrefPubMedGoogle Scholar
  • 17 Webley GE, Leidenberger F. The circadian pattern of melatonin and its positive relationship with progesterone in women. J Clin Endocrinol Metab 1986; 63 (2) 323-328
    CrossrefPubMedGoogle Scholar
  • 18 Commentz JC, Henke A, Dammann O, Hellwege HH, Willig RP. Decreasing melatonin and 6-hydroxymelatonin sulfate excretion with advancing gestational age in preterm and term newborn male infants. Eur J Endocrinol 1996; 135 (2) 184-187
    CrossrefPubMedGoogle Scholar
  • 19 Hartmann L, Roger M, Lemaitre BJ, Massias JF, Chaussain JL. Plasma and urinary melatonin in male infants during the first 12 months of life. Clin Chim Acta 1982; 121 (1) 37-42
    CrossrefPubMedGoogle Scholar
  • 20 Gitto E, Pellegrino S, Gitto P, Barberi I, Reiter RJ. Oxidative stress of the newborn in the pre- and postnatal period and the clinical utility of melatonin. J Pineal Res 2009; 46 (2) 128-139
    CrossrefPubMedGoogle Scholar
  • 21 Ardura J, Gutierrez R, Andres J, Agapito T. Emergence and evolution of the circadian rhythm of melatonin in children. Horm Res 2003; 59 (2) 66-72
    CrossrefPubMedGoogle Scholar
  • 22 Kennaway DJ, Stamp GE, Goble FC. Development of melatonin production in infants and the impact of prematurity. J Clin Endocrinol Metab 1992; 75 (2) 367-369
    Google Scholar
  • 23 Sivan Y, Laudon M, Tauman R, Zisapel N. Melatonin production in healthy infants: evidence for seasonal variations. Pediatr Res 2001; 49 (1) 63-68
    CrossrefPubMedGoogle Scholar
  • 24 Wetterberg L, Bratlid T, von Knorring L, Eberhard G, Yuwiler A. A multinational study of the relationships between nighttime urinary melatonin production, age, gender, body size, and latitude. Eur Arch Psychiatry Clin Neurosci 1999; 249 (5) 256-262
    CrossrefPubMedGoogle Scholar
  • 25 Griefahn B, Bröde P, Blaszkewicz M, Remer T. Melatonin production during childhood and adolescence: a longitudinal study on the excretion of urinary 6-hydroxymelatonin sulfate. J Pineal Res 2003; 34 (1) 26-31
    CrossrefPubMedGoogle Scholar
  • 26 Young IM, Francis PL, Leone AM, Stovell P, Silman RE. Constant pineal output and increasing body mass account for declining melatonin levels during human growth and sexual maturation. J Pineal Res 1988; 5 (1) 71-85
    CrossrefPubMedGoogle Scholar
  • 27 Bojkowski CJ, Arendt J. Factors influencing urinary 6-sulphatoxymelatonin, a major melatonin metabolite, in normal human subjects. Clin Endocrinol (Oxf) 1990; 33 (4) 435-444
    CrossrefPubMedGoogle Scholar
  • 28 Tetsuo M, Poth M, Markey SP. Melatonin metabolite excretion during childhood and puberty. J Clin Endocrinol Metab 1982; 55 (2) 311-313
    CrossrefPubMedGoogle Scholar
  • 29 Attanasio A, Borrelli P, Gupta D. Circadian rhythms in serum melatonin from infancy to adolescence. J Clin Endocrinol Metab 1985; 61 (2) 388-390
    CrossrefPubMedGoogle Scholar
  • 30 Waldhauser F, Weiszenbacher G, Tatzer E , et al. Alterations in nocturnal serum melatonin levels in humans with growth and aging. J Clin Endocrinol Metab 1988; 66 (3) 648-652
    CrossrefPubMedGoogle Scholar
  • 31 Waldhauser F, Weiszenbacher G, Frisch H, Zeitlhuber U, Waldhauser M, Wurtman RJ. Fall in nocturnal serum melatonin during prepuberty and pubescence. Lancet 1984; 1 (8373) 362-365
    PubMedGoogle Scholar
  • 32 Touitou Y, Auzéby A, Camus F, Djeridane Y. Daily profiles of salivary and urinary melatonin and steroids in healthy prepubertal boys. J Pediatr Endocrinol Metab 2009; 22 (11) 1009-1015
    PubMedGoogle Scholar
  • 33 Tauman R, Zisapel N, Laudon M, Nehama H, Sivan Y. Melatonin production in infants. Pediatr Neurol 2002; 26 (5) 379-382
    CrossrefPubMedGoogle Scholar
  • 34 Cardinali DP, Srinivasan V, Brzezinski A, Brown GM. Melatonin and its analogs in insomnia and depression. J Pineal Res 2012; 52 (4) 365-375
    CrossrefPubMedGoogle Scholar
  • 35 Gehlbach BK, Chapotot F, Leproult R , et al. Temporal disorganization of circadian rhythmicity and sleep-wake regulation in mechanically ventilated patients receiving continuous intravenous sedation. Sleep 2012; 35 (8) 1105-1114
    CrossrefPubMedGoogle Scholar
  • 36 Jan JE, Reiter RJ, Wong PK, Bax MC, Ribary U, Wasdell MB. Melatonin has membrane receptor-independent hypnotic action on neurons: an hypothesis. J Pineal Res 2011; 50 (3) 233-240
    CrossrefPubMedGoogle Scholar
  • 37 Lipton J, Megerian JT, Kothare SV , et al. Melatonin deficiency and disrupted circadian rhythms in pediatric survivors of craniopharyngioma. Neurology 2009; 73 (4) 323-325
    CrossrefPubMedGoogle Scholar
  • 38 Kocher L, Brun J, Borson-Chazot F, Gonnaud PM, Claustrat B. Increased REM sleep associated with melatonin deficiency after pinealectomy: a case study. Chronobiol Int 2006; 23 (4) 889-901
    CrossrefPubMedGoogle Scholar
  • 39 Holmes SW, Sugden D. Proceedings: The effect of melatonin on pinealectomy-induced hypertension in the rat. Br J Pharmacol 1976; 56 (3) 360P-361P
    PubMedGoogle Scholar
  • 40 Carrillo-Vico A, Guerrero JM, Lardone PJ, Reiter RJ. A review of the multiple actions of melatonin on the immune system. Endocrine 2005; 27 (2) 189-200
    CrossrefPubMedGoogle Scholar
  • 41 Karaaslan C, Suzen S. Antioxidant properties of melatonin and its potential action in diseases. Curr Top Med Chem 2015; 15 (9) 894-903
    CrossrefPubMedGoogle Scholar
  • 42 Jimenez-Jorge S, Jimenez-Caliani AJ, Guerrero JM , et al. Melatonin synthesis and melatonin-membrane receptor (MT1) expression during rat thymus development: role of the pineal gland. J Pineal Res 2005; 39 (1) 77-83
    CrossrefPubMedGoogle Scholar
  • 43 Valero N, Bonilla E, Pons H , et al. Melatonin induces changes to serum cytokines in mice infected with the Venezuelan equine encephalomyelitis virus. Trans R Soc Trop Med Hyg 2002; 96 (3) 348-351
    CrossrefPubMedGoogle Scholar
  • 44 Morrey KM, McLachlan JA, Serkin CD, Bakouche O. Activation of human monocytes by the pineal hormone melatonin. J Immunol 1994; 153 (6) 2671-2680
    PubMedGoogle Scholar
  • 45 Srinivasan V, Mohamed M, Kato H. Melatonin in bacterial and viral infections with focus on sepsis: a review. Recent Pat Endocr Metab Immune Drug Discov 2012; 6 (1) 30-39
    CrossrefPubMedGoogle Scholar
  • 46 Reiter RJ, Paredes SD, Korkmaz A, Jou MJ, Tan DX. Melatonin combats molecular terrorism at the mitochondrial level. Interdiscip Toxicol 2008; 1 (2) 137-149
    CrossrefPubMedGoogle Scholar
  • 47 Reiter RJ, Paredes SD, Manchester LC, Tan DX. Reducing oxidative/nitrosative stress: a newly-discovered genre for melatonin. Crit Rev Biochem Mol Biol 2009; 44 (4) 175-200
    CrossrefPubMedGoogle Scholar
  • 48 Joo JY, Uz T, Manev H. Opposite effects of pinealectomy and melatonin administration on brain damage following cerebral focal ischemia in rat. Restor Neurol Neurosci 1998; 13 (3–4) 185-191
    PubMedGoogle Scholar
  • 49 Cavallo A, Dolan LM. 6-Hydroxymelatonin sulfate excretion in human puberty. J Pineal Res 1996; 21 (4) 225-230
    CrossrefPubMedGoogle Scholar
  • 50 Olofsson K, Alling C, Lundberg D, Malmros C. Abolished circadian rhythm of melatonin secretion in sedated and artificially ventilated intensive care patients. Acta Anaesthesiol Scand 2004; 48 (6) 679-684
    CrossrefPubMedGoogle Scholar
  • 51 Müller HL, Handwerker G, Wollny B, Faldum A, Sörensen N. Melatonin secretion and increased daytime sleepiness in childhood craniopharyngioma patients. J Clin Endocrinol Metab 2002; 87 (8) 3993-3996
    CrossrefPubMedGoogle Scholar
  • 52 Frisk U, Olsson J, Nylén P, Hahn RG. Low melatonin excretion during mechanical ventilation in the intensive care unit. Clin Sci (Lond) 2004; 107 (1) 47-53
    CrossrefPubMedGoogle Scholar
  • 53 Esposti D, Esposti G, Lissoni P, Parravicini L, Fraschini F. Action of morphine on melatonin release in the rat. J Pineal Res 1988; 5 (1) 35-39
    CrossrefPubMedGoogle Scholar
  • 54 Govitrapong P, Pariyanonth M, Ebadi M. The presence and actions of opioid receptors in bovine pineal gland. J Pineal Res 1992; 13 (3) 124-132
    CrossrefPubMedGoogle Scholar
  • 55 Hajak G, Rodenbeck A, Bandelow B, Friedrichs S, Huether G, Rüther E. Nocturnal plasma melatonin levels after flunitrazepam administration in healthy subjects. Eur Neuropsychopharmacol 1996; 6 (2) 149-153
    PubMedGoogle Scholar
  • 56 Gupta M, Kohli K, Gupta YK. Modulation of serum concentrations of melatonin by carbamazepine and valproate. Indian J Physiol Pharmacol 2006; 50 (1) 79-82
    PubMedGoogle Scholar
  • 57 Hallam KT, Olver JS, Norman TR. Effect of sodium valproate on nocturnal melatonin sensitivity to light in healthy volunteers. Neuropsychopharmacology 2005; 30 (7) 1400-1404
    CrossrefPubMedGoogle Scholar
  • 58 Paul T, Lemmer B. Disturbance of circadian rhythms in analgosedated intensive care unit patients with and without craniocerebral injury. Chronobiol Int 2007; 24 (1) 45-61
    CrossrefPubMedGoogle Scholar
  • 59 Mundigler G, Delle-Karth G, Koreny M , et al. Impaired circadian rhythm of melatonin secretion in sedated critically ill patients with severe sepsis. Crit Care Med 2002; 30 (3) 536-540
    CrossrefPubMedGoogle Scholar
  • 60 Miyazaki T, Kuwano H, Kato H , et al. Correlation between serum melatonin circadian rhythm and intensive care unit psychosis after thoracic esophagectomy. Surgery 2003; 133 (6) 662-668
    CrossrefPubMedGoogle Scholar
  • 61 Gottschlich MM, Jenkins ME, Mayes T , et al. The 1994 Clinical Research Award. A prospective clinical study of the polysomnographic stages of sleep after burn injury. J Burn Care Rehabil 1994; 15 (6) 486-492
    Google Scholar
  • 62 Riutta A, Ylitalo P, Kaukinen S. Diurnal variation of melatonin and cortisol is maintained in non-septic intensive care patients. Intensive Care Med 2009; 35 (10) 1720-1727
    CrossrefPubMedGoogle Scholar
  • 63 Bagci S, Yildizdas D, Horoz OO, Reinsberg J, Bartmann P, Mueller A. Use of nocturnal melatonin concentration and urinary 6-sulfatoxymelatonin excretion to evaluate melatonin status in children with severe sepsis. J Pediatr Endocrinol Metab 2011; 24 (11–12) 1025-1030
    PubMedGoogle Scholar
  • 64 Bagci S, Horoz ÖÖ, Yildizdas D, Reinsberg J, Bartmann P, Müller A. Melatonin status in pediatric intensive care patients with sepsis. Pediatr Crit Care Med 2012; 13 (2) e120-e123
    CrossrefPubMedGoogle Scholar
  • 65 Marseglia L, Aversa S, Barberi I , et al. High endogenous melatonin levels in critically ill children: a pilot study. J Pediatr 2013; 162 (2) 357-360
    CrossrefPubMedGoogle Scholar
  • 66 Gitto E, Aversa S, Reiter RJ, Barberi I, Pellegrino S. Update on the use of melatonin in pediatrics. J Pineal Res 2011; 50 (1) 21-28
    CrossrefPubMedGoogle Scholar
  • 67 Bruni O, Alonso-Alconada D, Besag F , et al. Paediatric use of melatonin [Author reply to D. J. Kennaway]. Eur J Paediatr Neurol 2015; 19 (4) 491-493
    CrossrefPubMedGoogle Scholar
  • 68 Fourtillan JB, Brisson AM, Gobin P, Ingrand I, Decourt JP, Girault J. Bioavailability of melatonin in humans after day-time administration of D(7) melatonin. Biopharm Drug Dispos 2000; 21 (1) 15-22
    CrossrefPubMedGoogle Scholar
  • 69 Mistraletti G, Sabbatini G, Taverna M , et al. Pharmacokinetics of orally administered melatonin in critically ill patients. J Pineal Res 2010; 48 (2) 142-147
    CrossrefPubMedGoogle Scholar
  • 70 Cavallo A, Ritschel WA. Pharmacokinetics of melatonin in human sexual maturation. J Clin Endocrinol Metab 1996; 81 (5) 1882-1886
    PubMedGoogle Scholar
  • 71 Bourne RS, Minelli C, Mills GH, Kandler R. Clinical review: sleep measurement in critical care patients: research and clinical implications. Crit Care 2007; 11 (4) 226
    Google Scholar
  • 72 Hardin KA. Sleep in the ICU: potential mechanisms and clinical implications. Chest 2009; 136 (1) 284-294
    CrossrefPubMedGoogle Scholar
  • 73 Nelson AB, Faraguna U, Tononi G, Cirelli C. Effects of anesthesia on the response to sleep deprivation. Sleep 2010; 33 (12) 1659-1667
    CrossrefPubMedGoogle Scholar
  • 74 Wyatt JK, Dijk DJ, Ritz-de Cecco A, Ronda JM, Czeisler CA. Sleep-facilitating effect of exogenous melatonin in healthy young men and women is circadian-phase dependent. Sleep 2006; 29 (5) 609-618
    CrossrefPubMedGoogle Scholar
  • 75 Braam W, Smits MG, Didden R, Korzilius H, Van Geijlswijk IM, Curfs LM. Exogenous melatonin for sleep problems in individuals with intellectual disability: a meta-analysis. Dev Med Child Neurol 2009; 51 (5) 340-349
    CrossrefPubMedGoogle Scholar
  • 76 Carr R, Wasdell MB, Hamilton D , et al. Long-term effectiveness outcome of melatonin therapy in children with treatment-resistant circadian rhythm sleep disorders. J Pineal Res 2007; 43 (4) 351-359
    CrossrefPubMedGoogle Scholar
  • 77 Gupta M, Aneja S, Kohli K. Add-on melatonin improves sleep behavior in children with epilepsy: randomized, double-blind, placebo-controlled trial. J Child Neurol 2005; 20 (2) 112-115
    CrossrefPubMedGoogle Scholar
  • 78 Kemp S, Biswas R, Neumann V, Coughlan A. The value of melatonin for sleep disorders occurring post-head injury: a pilot RCT. Brain Inj 2004; 18 (9) 911-919
    CrossrefPubMedGoogle Scholar
  • 79 Huang HW, Zheng BL, Jiang L , et al. Effect of oral melatonin and wearing earplugs and eye masks on nocturnal sleep in healthy subjects in a simulated intensive care unit environment: which might be a more promising strategy for ICU sleep deprivation?. Crit Care 2015; 19 (1) 124
    CrossrefPubMedGoogle Scholar
  • 80 Saugstad OD. Oxidative stress in the newborn—a 30-year perspective. Biol Neonate 2005; 88 (3) 228-236
    CrossrefPubMedGoogle Scholar
  • 81 Shilo L, Dagan Y, Smorjik Y , et al. Effect of melatonin on sleep quality of COPD intensive care patients: a pilot study. Chronobiol Int 2000; 17 (1) 71-76
    CrossrefPubMedGoogle Scholar
  • 82 Ibrahim MG, Bellomo R, Hart GK , et al. A double-blind placebo-controlled randomised pilot study of nocturnal melatonin in tracheostomised patients. Crit Care Resusc 2006; 8 (3) 187-191
    PubMedGoogle Scholar
  • 83 Bourne RS, Mills GH, Minelli C. Melatonin therapy to improve nocturnal sleep in critically ill patients: encouraging results from a small randomised controlled trial. Crit Care 2008; 12 (2) R52
    CrossrefPubMedGoogle Scholar
  • 84 Mistraletti G, Umbrello M, Sabbatini G , et al. Melatonin reduces the need for sedation in ICU patients: a randomized controlled trial. Minerva Anestesiol 2015; 81 (12) 1298-1310
    PubMedGoogle Scholar
  • 85 Huang H, Jiang L, Shen L , et al. Impact of oral melatonin on critically ill adult patients with ICU sleep deprivation: study protocol for a randomized controlled trial. Trials 2014; 15: 327
    CrossrefPubMedGoogle Scholar
  • 86 Tan DX, Reiter RJ, Manchester LC , et al. Chemical and physical properties and potential mechanisms: melatonin as a broad spectrum antioxidant and free radical scavenger. Curr Top Med Chem 2002; 2 (2) 181-197
    CrossrefPubMedGoogle Scholar
  • 87 Tan DX, Manchester LC, Terron MP, Flores LJ, Reiter RJ. One molecule, many derivatives: a never-ending interaction of melatonin with reactive oxygen and nitrogen species?. J Pineal Res 2007; 42 (1) 28-42
    CrossrefPubMedGoogle Scholar
  • 88 Longoni B, Salgo MG, Pryor WA, Marchiafava PL. Effects of melatonin on lipid peroxidation induced by oxygen radicals. Life Sci 1998; 62 (10) 853-859
    CrossrefPubMedGoogle Scholar
  • 89 Rodriguez C, Mayo JC, Sainz RM , et al. Regulation of antioxidant enzymes: a significant role for melatonin. J Pineal Res 2004; 36 (1) 1-9
    CrossrefPubMedGoogle Scholar
  • 90 Fulia F, Gitto E, Cuzzocrea S , et al. Increased levels of malondialdehyde and nitrite/nitrate in the blood of asphyxiated newborns: reduction by melatonin. J Pineal Res 2001; 31 (4) 343-349
    CrossrefPubMedGoogle Scholar
  • 91 Gitto E, Romeo C, Reiter RJ , et al. Melatonin reduces oxidative stress in surgical neonates. J Pediatr Surg 2004; 39 (2) 184-189 , discussion 184–189
    CrossrefPubMedGoogle Scholar
  • 92 Gitto E, Reiter RJ, Cordaro SP , et al. Oxidative and inflammatory parameters in respiratory distress syndrome of preterm newborns: beneficial effects of melatonin. Am J Perinatol 2004; 21 (4) 209-216
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 93 Gitto E, Reiter RJ, Amodio A , et al. Early indicators of chronic lung disease in preterm infants with respiratory distress syndrome and their inhibition by melatonin. J Pineal Res 2004; 36 (4) 250-255
    CrossrefPubMedGoogle Scholar
  • 94 Gitto E, Reiter RJ, Sabatino G , et al. Correlation among cytokines, bronchopulmonary dysplasia and modality of ventilation in preterm newborns: improvement with melatonin treatment. J Pineal Res 2005; 39 (3) 287-293
    Google Scholar
  • 95 Wu JY, Tsou MY, Chen TH, Chen SJ, Tsao CM, Wu CC. Therapeutic effects of melatonin on peritonitis-induced septic shock with multiple organ dysfunction syndrome in rats. J Pineal Res 2008; 45 (1) 106-116
    CrossrefPubMedGoogle Scholar
  • 96 Erbaş O, Ergenoglu AM, Akdemir A, Yeniel AO, Taskiran D. Comparison of melatonin and oxytocin in the prevention of critical illness polyneuropathy in rats with experimentally induced sepsis. J Surg Res 2013; 183 (1) 313-320
    CrossrefPubMedGoogle Scholar
  • 97 Shang Y, Xu SP, Wu Y , et al. Melatonin reduces acute lung injury in endotoxemic rats. Chin Med J (Engl) 2009; 122 (12) 1388-1393
    PubMedGoogle Scholar
  • 98 Ozdemir D, Uysal N, Tugyan K , et al. The effect of melatonin on endotoxemia-induced intestinal apoptosis and oxidative stress in infant rats. Intensive Care Med 2007; 33 (3) 511-516
    CrossrefPubMedGoogle Scholar
  • 99 Escames G, López LC, Ortiz F , et al. Attenuation of cardiac mitochondrial dysfunction by melatonin in septic mice. FEBS J 2007; 274 (8) 2135-2147
    CrossrefPubMedGoogle Scholar
  • 100 Tekbas OF, Ogur R, Korkmaz A, Kilic A, Reiter RJ. Melatonin as an antibiotic: new insights into the actions of this ubiquitous molecule. J Pineal Res 2008; 44 (2) 222-226
    CrossrefPubMedGoogle Scholar
  • 101 Rahman MA, Azuma Y, Fukunaga H , et al. Serotonin and melatonin, neurohormones for homeostasis, as novel inhibitors of infections by the intracellular parasite chlamydia. J Antimicrob Chemother 2005; 56 (5) 861-868
    CrossrefPubMedGoogle Scholar
  • 102 Wiid I, Hoal-van Helden E, Hon D, Lombard C, van Helden P. Potentiation of isoniazid activity against Mycobacterium tuberculosis by melatonin. Antimicrob Agents Chemother 1999; 43 (4) 975-977
    CrossrefPubMedGoogle Scholar
  • 103 Ben-Nathan D, Maestroni GJ, Lustig S, Conti A. Protective effects of melatonin in mice infected with encephalitis viruses. Arch Virol 1995; 140 (2) 223-230
    CrossrefPubMedGoogle Scholar
  • 104 Tan DX, Korkmaz A, Reiter RJ, Manchester LC. Ebola virus disease: potential use of melatonin as a treatment. J Pineal Res 2014; 57 (4) 381-384
    CrossrefPubMedGoogle Scholar
  • 105 Gitto E, Karbownik M, Reiter RJ , et al. Effects of melatonin treatment in septic newborns. Pediatr Res 2001; 50 (6) 756-760
    CrossrefPubMedGoogle Scholar
  • 106 Galley HF, Lowes DA, Allen L, Cameron G, Aucott LS, Webster NR. Melatonin as a potential therapy for sepsis: a phase I dose escalation study and an ex vivo whole blood model under conditions of sepsis. J Pineal Res 2014; 56 (4) 427-438
    CrossrefPubMedGoogle Scholar
  • 107 Ochoa JJ, Vílchez MJ, Palacios MA, García JJ, Reiter RJ, Muñoz-Hoyos A. Melatonin protects against lipid peroxidation and membrane rigidity in erythrocytes from patients undergoing cardiopulmonary bypass surgery. J Pineal Res 2003; 35 (2) 104-108
    CrossrefPubMedGoogle Scholar
  • 108 Dobsak P, Siegelova J, Eicher JC , et al. Melatonin protects against ischemia-reperfusion injury and inhibits apoptosis in isolated working rat heart. Pathophysiology 2003; 9 (3) 179-187
    CrossrefPubMedGoogle Scholar
  • 109 Wang Z, Zhang J, Liu H , et al. Melatonin, a potent regulator of hemeoxygenase-1, reduces cardiopulmonary bypass-induced renal damage in rats. J Pineal Res 2009; 46 (3) 248-254
    CrossrefPubMedGoogle Scholar
  • 110 Huang H, Yin R, Zhu J , et al. Exogenous melatonin ameliorates hepatic injury in a rat cardiopulmonary bypass model. Eur J Pharmacol 2008; 580 (3) 416-424
    CrossrefPubMedGoogle Scholar
  • 111 Sokullu O, Sanioğlu S, Kurç E , et al. Does the circadian rhythm of melatonin affect ischemia-reperfusion injury after coronary artery bypass grafting?. Heart Surg Forum 2009; 12 (2) E95-E99
    CrossrefPubMedGoogle Scholar
  • 112 Maldonado MD, Murillo-Cabezas F, Calvo JR , et al. Melatonin as pharmacologic support in burn patients: a proposed solution to thermal injury-related lymphocytopenia and oxidative damage. Crit Care Med 2007; 35 (4) 1177-1185
    CrossrefPubMedGoogle Scholar
  • 113 Wiggins-Dohlvik K, Han MS, Stagg HW , et al. Melatonin inhibits thermal injury-induced hyperpermeability in microvascular endothelial cells. J Trauma Acute Care Surg 2014; 77 (6) 899-905 , discussion 905
    CrossrefPubMedGoogle Scholar
  • 114 Bekyarova G, Apostolova M, Kotzev I. Melatonin protection against burn-induced hepatic injury by down-regulation of nuclear factor kappa B activation. Int J Immunopathol Pharmacol 2012; 25 (3) 591-596
    CrossrefPubMedGoogle Scholar
  • 115 Bekyarova G, Tancheva S, Hristova M. The effects of melatonin on burn-induced inflammatory responses and coagulation disorders in rats. Methods Find Exp Clin Pharmacol 2010; 32 (5) 299-303
    CrossrefPubMedGoogle Scholar
  • 116 Görgülü A, Palaoğlu S, Ismailoğlu O , et al. Effect of melatonin on cerebral edema in rats. Neurosurgery 2001; 49 (6) 1434-1441 , discussion 1441–1442
    CrossrefPubMedGoogle Scholar
  • 117 Sarrafzadeh AS, Thomale UW, Kroppenstedt SN, Unterberg AW. Neuroprotective effect of melatonin on cortical impact injury in the rat. Acta Neurochir (Wien) 2000; 142 (11) 1293-1299
    CrossrefPubMedGoogle Scholar
  • 118 Beni SM, Kohen R, Reiter RJ, Tan DX, Shohami E. Melatonin-induced neuroprotection after closed head injury is associated with increased brain antioxidants and attenuated late-phase activation of NF-kappaB and AP-1. FASEB J 2004; 18 (1) 149-151
    CrossrefPubMedGoogle Scholar
  • 119 Uchida K, Aoki T, Ishizuka B. Postoperative delirium and plasma melatonin. Med Hypotheses 1999; 53 (2) 103-106
    CrossrefPubMedGoogle Scholar
  • 120 Shigeta H, Yasui A, Nimura Y , et al. Postoperative delirium and melatonin levels in elderly patients. Am J Surg 2001; 182 (5) 449-454
    CrossrefPubMedGoogle Scholar
  • 121 Yoshitaka S, Egi M, Morimatsu H, Kanazawa T, Toda Y, Morita K. Perioperative plasma melatonin concentration in postoperative critically ill patients: its association with delirium. J Crit Care 2013; 28 (3) 236-242
    CrossrefPubMedGoogle Scholar
  • 122 Al-Aama T, Brymer C, Gutmanis I, Woolmore-Goodwin SM, Esbaugh J, Dasgupta M. Melatonin decreases delirium in elderly patients: a randomized, placebo-controlled trial. Int J Geriatr Psychiatry 2011; 26 (7) 687-694
    CrossrefPubMedGoogle Scholar
  • 123 Sultan SS. Assessment of role of perioperative melatonin in prevention and treatment of postoperative delirium after hip arthroplasty under spinal anesthesia in the elderly. Saudi J Anaesth 2010; 4 (3) 169-173
    CrossrefPubMedGoogle Scholar
  • 124 Kain ZN, MacLaren JE, Herrmann L , et al. Preoperative melatonin and its effects on induction and emergence in children undergoing anesthesia and surgery. Anesthesiology 2009; 111 (1) 44-49
    CrossrefPubMedGoogle Scholar
  • 125 Daoud A, Duff JP, Joffe AR, Alberta Sepsis N ; Alberta Sepsis Network. Diagnostic accuracy of delirium diagnosis in pediatric intensive care: a systematic review. Crit Care 2014; 18 (5) 489
    CrossrefPubMedGoogle Scholar
  • 126 Papp M, Litwa E, Gruca P, Mocaër E. Anxiolytic-like activity of agomelatine and melatonin in three animal models of anxiety. Behav Pharmacol 2006; 17 (1) 9-18
    PubMedGoogle Scholar
  • 127 Yousaf F, Seet E, Venkatraghavan L, Abrishami A, Chung F. Efficacy and safety of melatonin as an anxiolytic and analgesic in the perioperative period: a qualitative systematic review of randomized trials. Anesthesiology 2010; 113 (4) 968-976
    CrossrefPubMedGoogle Scholar
  • 128 Ismail SA, Mowafi HA. Melatonin provides anxiolysis, enhances analgesia, decreases intraocular pressure, and promotes better operating conditions during cataract surgery under topical anesthesia. Anesth Analg 2009; 108 (4) 1146-1151
    CrossrefPubMedGoogle Scholar
  • 129 Schmidt CM, Knief A, Deuster D, Matulat P. am Zehnhoff-Dinnesen AG. Melatonin is a useful alternative to sedation in children undergoing brainstem audiometry with an age dependent success rate—a field report of 250 investigations. Neuropediatrics 2007; 38 (1) 2-4
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 130 Ashrafi MR, Mohammadi M, Tafarroji J, Shabanian R, Salamati P, Zamani GR. Melatonin versus chloral hydrate for recording sleep EEG. Eur J Paediatr Neurol 2010; 14 (3) 235-238
    CrossrefPubMedGoogle Scholar
  • 131 Almenrader N, Haiberger R, Passariello M. Steal induction in preschool children: is melatonin as good as clonidine? A prospective, randomized study. Paediatr Anaesth 2013; 23 (4) 328-333
    CrossrefPubMedGoogle Scholar
  • 132 Samarkandi A, Naguib M, Riad W , et al. Melatonin vs. midazolam premedication in children: a double-blind, placebo-controlled study. Eur J Anaesthesiol 2005; 22 (3) 189-196
    CrossrefPubMedGoogle Scholar
  • 133 Sury MR, Fairweather K. The effect of melatonin on sedation of children undergoing magnetic resonance imaging. Br J Anaesth 2006; 97 (2) 220-225
    CrossrefPubMedGoogle Scholar
  • 134 Isik B, Baygin O, Bodur H. Premedication with melatonin vs midazolam in anxious children. Paediatr Anaesth 2008; 18 (7) 635-641
    CrossrefPubMedGoogle Scholar
  • 135 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 (6) 1448-1452
    CrossrefPubMedGoogle Scholar
  • 136 Turkistani A, Abdullah KM, Al-Shaer AA, Mazen KF, Alkatheri K. Melatonin premedication and the induction dose of propofol. Eur J Anaesthesiol 2007; 24 (5) 399-402
    CrossrefPubMedGoogle Scholar
  • 137 Borazan H, Tuncer S, Yalcin N, Erol A, Otelcioglu S. Effects of preoperative oral melatonin medication on postoperative analgesia, sleep quality, and sedation in patients undergoing elective prostatectomy: a randomized clinical trial. J Anesth 2010; 24 (2) 155-160
    CrossrefPubMedGoogle Scholar
  • 138 Mistraletti G, Mantovani ES, Cadringher P , et al; SedaEN investigators. Enteral vs. intravenous ICU sedation management: study protocol for a randomized controlled trial. Trials 2013; 14: 92
    CrossrefPubMedGoogle Scholar
  • 139 Wilhelmsen M, Amirian I, Reiter RJ, Rosenberg J, Gögenur I. Analgesic effects of melatonin: a review of current evidence from experimental and clinical studies. J Pineal Res 2011; 51 (3) 270-277
    CrossrefPubMedGoogle Scholar
  • 140 Caumo W, Levandovski R, Hidalgo MP. Preoperative anxiolytic effect of melatonin and clonidine on postoperative pain and morphine consumption in patients undergoing abdominal hysterectomy: a double-blind, randomized, placebo-controlled study. J Pain 2009; 10 (1) 100-108
    CrossrefPubMedGoogle Scholar
  • 141 Shavali S, Ho B, Govitrapong P , et al. Melatonin exerts its analgesic actions not by binding to opioid receptor subtypes but by increasing the release of beta-endorphin an endogenous opioid. Brain Res Bull 2005; 64 (6) 471-479
    CrossrefPubMedGoogle Scholar
  • 142 Pang CS, Tsang SF, Yang JC. Effects of melatonin, morphine and diazepam on formalin-induced nociception in mice. Life Sci 2001; 68 (8) 943-951
    CrossrefPubMedGoogle Scholar
  • 143 Zahn PK, Lansmann T, Berger E, Speckmann EJ, Musshoff U. Gene expression and functional characterization of melatonin receptors in the spinal cord of the rat: implications for pain modulation. J Pineal Res 2003; 35 (1) 24-31
    CrossrefPubMedGoogle Scholar
  • 144 Aydin ON, Ugur B, Kir E, Ozkan SB. Effect of single-dose fentanyl on the cardiorespiratory system in elderly patients undergoing cataract surgery. J Clin Anesth 2004; 16 (2) 98-103
    CrossrefPubMedGoogle Scholar
  • 145 Mantovani M, Kaster MP, Pertile R, Calixto JB, Rodrigues AL, Santos AR. Mechanisms involved in the antinociception caused by melatonin in mice. J Pineal Res 2006; 41 (4) 382-389
    CrossrefPubMedGoogle Scholar
  • 146 Yu CX, Zhu CB, Xu SF, Cao XD, Wu GC. Selective MT(2) melatonin receptor antagonist blocks melatonin-induced antinociception in rats. Neurosci Lett 2000; 282 (3) 161-164
    CrossrefPubMedGoogle Scholar
  • 147 Gitto E, Aversa S, Salpietro CD , et al. Pain in neonatal intensive care: role of melatonin as an analgesic antioxidant. J Pineal Res 2012; 52 (3) 291-295
    CrossrefPubMedGoogle Scholar
  • 148 Jonas M, Garfinkel D, Zisapel N, Laudon M, Grossman E. Impaired nocturnal melatonin secretion in non-dipper hypertensive patients. Blood Press 2003; 12 (1) 19-24
    PubMedGoogle Scholar
  • 149 Cavallo A, Daniels SR, Dolan LM, Bean JA, Khoury JC. Blood pressure-lowering effect of melatonin in type 1 diabetes. J Pineal Res 2004; 36 (4) 262-266
    CrossrefPubMedGoogle Scholar
  • 150 Scheer FA, Van Montfrans GA, van Someren EJ, Mairuhu G, Buijs RM. Daily nighttime melatonin reduces blood pressure in male patients with essential hypertension. Hypertension 2004; 43 (2) 192-197
    CrossrefPubMedGoogle Scholar
  • 151 Muñoz-Hoyos A, Sánchez-Forte M, Molina-Carballo A , et al. Melatonin's role as an anticonvulsant and neuronal protector: experimental and clinical evidence. J Child Neurol 1998; 13 (10) 501-509
    CrossrefPubMedGoogle Scholar
  • 152 Brigo F, Del Felice A. Melatonin as add-on treatment for epilepsy. Cochrane Database Syst Rev 2012; 6: CD006967
    PubMedGoogle Scholar
  • 153 Jain S, Besag FM. Does melatonin affect epileptic seizures?. Drug Saf 2013; 36 (4) 207-215
    CrossrefPubMedGoogle Scholar
  • 154 Goldberg-Stern H, Oren H, Peled N, Garty BZ. Effect of melatonin on seizure frequency in intractable epilepsy: a pilot study. J Child Neurol 2012; 27 (12) 1524-1528
    CrossrefPubMedGoogle Scholar
  • 155 Cummings C ; Canadian Paediatric Society, Community Paediatrics Committee. Melatonin for the management of sleep disorders in children and adolescents. Paediatr Child Health (Oxford) 2012; 17 (6) 331-336
    PubMedGoogle Scholar
  • 156 Kennaway DJ. Potential safety issues in the use of the hormone melatonin in paediatrics. J Paediatr Child Health 2015; 51 (6) 584-589
    CrossrefPubMedGoogle Scholar
  • 157 Nickkholgh A, Schneider H, Sobirey M , et al. The use of high-dose melatonin in liver resection is safe: first clinical experience. J Pineal Res 2011; 50 (4) 381-388
    CrossrefPubMedGoogle Scholar
  • 158 Seabra ML, Bignotto M, Pinto Jr LR, Tufik S. Randomized, double-blind clinical trial, controlled with placebo, of the toxicology of chronic melatonin treatment. J Pineal Res 2000; 29 (4) 193-200
    CrossrefPubMedGoogle Scholar
  • 159 Weishaupt JH, Bartels C, Pölking E , et al. Reduced oxidative damage in ALS by high-dose enteral melatonin treatment. J Pineal Res 2006; 41 (4) 313-323
    CrossrefPubMedGoogle Scholar
  • 160 Hoebert M, van der Heijden KB, van Geijlswijk IM, Smits MG. Long-term follow-up of melatonin treatment in children with ADHD and chronic sleep onset insomnia. J Pineal Res 2009; 47 (1) 1-7
    CrossrefPubMedGoogle Scholar
  • 161 Aversa S, Marseglia L, Arco A, D'Angelo G, Cusumano E, Barberi I. Efficacy and safety of melatonin in neonates. Arch Dis Child 2012; 97 (Suppl2): A464
    PubMedGoogle Scholar
  • 162 Buscemi N, Vandermeer B, Hooton N , et al. Efficacy and safety of exogenous melatonin for secondary sleep disorders and sleep disorders accompanying sleep restriction: meta-analysis. BMJ 2006; 332 (7538) 385-393
    CrossrefPubMedGoogle Scholar