•  
  •  
 

Keywords

Pediatric critical care, Melatonin, Children, Sleep, Delirium

Abstract

Melatonin is an endogenous indoleamine synthesized by the pineal gland. Though melatonin is best known for its chronobiologic effects, regulating the circadian rhythm and sleep, it might play a wider role in critical illness. It has been proposed for use as an analgesic and sedative, an antihypertensive, an anti-inflammatory, and for the prevention of delirium. Melatonin use in children has increased dramatically over the years, but the evidence on its use in critically ill children remains limited. This review article aimed to describe the basic physiology and biology of melatonin, including its production and functions, dosing, and side effects, and provide current evidence on its potential roles in critically ill children.

References

1. Bastos Jr MAV, de Oliveira Bastos PR, E Paez LEF, et al. ``Seat of the soul''? The structure and function of the pineal glands in women with alleged spirit possession-results of two experimental studies. Brain Behav. 2020;10:e01693.
2. Lokhorst GJ. Descartes and the pineal gland. In: Zalta EN, ed. The Stanford Encyclopedia of Philosophy. Winter 2018 ed. Stanford, CA: Center for the Study of Language and Information, Stanford University. Accessed January 29, 2026. https://plato.stanford.edu/archives/win2018/entries/pineal-gland/
3. Foster JR. Melatonin in critically ill children. J Pediatr Intensive Care. 2016;5:172–181.
4. Procaccini DE, Kudchadkar SR. Melatonin administration patterns for pediatric inpatients in a tertiary children's hospital. Hosp. Pediatr. 2021;11:e308-e312.
5. Lelak K, Vohra V, Neuman MI, Toce MS, Sethuraman U. Pediatric melatonin ingestions – United States, 2012-2021. MMWR Morb Mortal Wkly Rep. 2022;71:725–729.
6. Jacobson JL, Tylka J, Glazer S, et al. Melatonin use in pediatric intensive care units: a single-center experience. Med Sci (Basel). 2023;11:55.
7. Kvetnoy IM. Extrapineal melatonin: location and role within diffuse neuroendocrine system. Histochem J. 1999;31:1–12.
8. Ortiz-Placin C, Salido GM, González A. Melatonin interplay in physiology and disease—the fountain of eternal youth revisited. Biomolecules. 2025;15:682.
9. Arendt J, Aulinas A. Physiology of the Pineal Gland and Melatonin. Updated October 30, 2022. In: Feingold KR, Adler RA, Ahmed SF, et al., eds. Endotext [Internet]. South Dartmouth, MA: MDText.com, Inc.; 2000-. Accessed January 29, 2026. https://www.ncbi.nlm.nih.gov/books/NBK550972/
10. Cipolla-Neto J, Amaral FGD. Melatonin as a hormone: new physiological and clinical insights. Endocr Rev. 2018;39:990–1028.
11. Gastel JA, Roseboom PH, Rinaldi PA, Weller JL, Klein DC. Melatonin production: proteasomal proteolysis in serotonin N-acetyltransferase regulation. Science (New York, NY). 1998;279:1358–1360.
12. Laakso ML, Hatonen T, Stenberg D, Alila A, Smith S. One-hour exposure to moderate illuminance (500 lux) shifts the human melatonin rhythm. J Pineal Res. 1993;15:21–26.
13. Gooley JJ, Chamberlain K, Smith KA, et al. Exposure to room light before bedtime suppresses melatonin onset and shortens melatonin duration in humans. J Clin Endocrinol Metab. 2011;96:E463–E472.
14. Paditz E. Postnatal development of the circadian rhythmicity of human pineal melatonin synthesis and secretion (Systematic review). Children. 2024;11:1197.
15. Kennaway DJ, Lushington K, Dawson D, Lack L, van den Heuvel C, Rogers N. Urinary 6-sulfatoxymelatonin excretion and aging: new results and critical review of the literature. J Pineal Res. 1999;27:210–220.
16. Alston M, Cain S, Rajaratnam S. Advances of Melatonin-Based Therapies in the treatment of Disturbed Sleep and Mood. Hanb Exp Pharmacol. 2019;253:305–319.
17. Lewy AJ, Ahmed S, Jackson JM, Sack RL. Melatonin shifts human circadian rhythms according to a phase-response curve. Chronobiol Int. 1992;9:380–392.
18. Sharkey KM, Eastman CI. Melatonin phase shifts human circadian rhythms in a placebo-controlled simulated night-work study. Am J Physiol Regul Integr Comp Physiol. 2002;282:R454–R463.
19. Comai S, Gobbi G. Melatonin, melatonin receptors and sleep: moving beyond traditional views. J Pineal Res. 2024;76:e13011.
20. Waldhauser F, Boepple PA, Schemper M, et al. Serum melatonin in central precocious puberty is lower than in aged-matched pubertal children. J Clin Endocrinol Metab. 1991;73:793–796.
21. Andersen CC, Kjaer EKR, Vase CB, et al. Melatonin secretion across puberty: a systematic review and meta-analysis. Psychoneuroendocrinol. 2025;173:107281.
22. Chen W, Zhang X, Huang W. Pain control by melatonin: physiological and pharmacological effects. Exp Ther Med. 2016;12:1963–1968.
23. Shenoy P, Etcheverry A, Ia J, Witmans M, Tablizo MA. Melatonin use in pediatrics: a clinical review on indications, multisystem effects, and toxicity. Children (Basel). 2024;11:323.
24. Wei S, Smits MG, Tang X, et al. Efficacy and safety of melatonin for sleep onset insomnia in children and adolescents: a meta-analysis of randomized controlled trials. Sleep Med. 2019;68:1–8.
25. Skrzelowski M, Brookhaus A, Shea LA, Berlau DJ. Melatonin use in pediatrics: evaluating the discrepancy in evidence based on country and regulations regarding production. J Pediatr Pharmacol Ther. 2022;26:4–20.
26. Van Geijlswijk IM, van der Herijden KB, Egberts ACG, Korzilius HPLM, Smits MG. Dose finding of melatonin for chronic idiopathic childhood sleep onset insomnia: an RCT. Psychopharmacology (Berl). 2010;212:379–391.
27. Auger RR, Burgess HJ, Emens JS, Deriy LV, Thomas SM, Sharkey KM. Clinical practice guideline for the treatment of intrinsic circadian rhythm sleep-wake disorders: advanced sleep-wake phase disorder (ASWPD), delayed sleep-wake phase disorder (DSWPD), non-24 hour sleep-wake rhythm disorder (N24SWD), and irregular sleep-wake rhythm disorder (ISWRD). An updated for 2015: An American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med. 2015;11:1199–1236.
28. Kracht CL, Bollamperti G, Breeden R. Melatonin use in young children: a systematic review. JAMA Netw Open. 2026;9:e2551958.
29. García-San Prudencio M, Manrique G, Cieza R, et al. Relationship of melatonin levels in blood and urine with sleep quality in children admitted to pediatric intensive care unit. Children. 2025;12:1074.
30. Hosseini SN, Walton JC, SheikhAnsari I, Kreidler N, Nelson RJ. An architectural solution to a biological problem: a systematic review of lighting designs in healthcare environments. Appl Sci. 2024;14:2945.
31. Bradford C, Miller JL, Harkin M, Chaaban H, Neely SB, Johnson PN. Melatonin use in infants admitted to the intensive care units. J Pediatr Pharmacol Ther. 2023;28(7):635–642.
32. Esposito E, Paterniti I, Mazzon E, Bramanti P, Cuzzocrea S. Melatonin reduces hyperalgesia associated with inflammation. J Pineal Res. 2010;49:321–331.
33. 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;16:1209–1220.
34. Laudone TW, Beck SD, Lahr HJ. Evaluation of melatonin practices for delirium in pediatric critically ill patients. J Pediatr Pharmacol Ther. 2021;26:361–365.
35. Marseglia L, Manti S, D'Angelo G, et al. Potential use of melatonin in procedural anxiety and pain in children undergoing blood withdrawal. J Biol Regul Homeost Agents. 2015;29:509–514.
36. Procaccini D, Lobner K, Azamfirei R, Kudchadkar SR. Melatonin for anaesthetic indications in paediatric patients: a systematic review. Anaesthesia. 2021;76:837–849.
37. Mellor K, Papaioannou D, Thomason A, et al. Melatonin for pre-medication in children: a systematic review. BMC Pediatrics. 2022;22:107.
38. Lakbar I, Poole D, Delamarre L, et al. Melatonin and delirium in the intensive care units: a systematic review and meta-analysis of randomized controlled trials. Intensive Care Med. 2025;51:2079–2092.
39. Reiter PD, Schwab-Daugherty E, Daugherty J, Hohenstein E, Cripe P. Melatonin use and association with delirium burden among children admitted to an intensive care unit within a large pediatric healthcare organization. J Pharm Pract. 2026;39:40–46.
40. Smith HAB, Besunder JB, Betters KA, et al. 2022 Society of Critical Care Medicine clinical practice guidelines on prevention and management of pain, agitation, neuromuscular blockade, and delirium in critically ill pediatric patients with consideration of the ICU environment and early mobility. Pediatr Crit Care Med. 2022;23:e74–e110.

Download

Share

COinS