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EDITORIAL
Year : 2016  |  Volume : 60  |  Issue : 10  |  Page : 701-702  

Melatonin - marvel in the making?


Department of Anaesthesia, Dharwad Institute of Mental Health and Neurosciences, Dharwad, Karnataka, India

Date of Web Publication7-Oct-2016

Correspondence Address:
Goneppanavar Umesh
Department of Anaesthesia, Dharwad Institute of Mental Health and Neurosciences, Dharwad, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-5049.191662

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How to cite this article:
Umesh G. Melatonin - marvel in the making?. Indian J Anaesth 2016;60:701-2

How to cite this URL:
Umesh G. Melatonin - marvel in the making?. Indian J Anaesth [serial online] 2016 [cited 2017 Aug 19];60:701-2. Available from: http://www.ijaweb.org/text.asp?2016/60/10/701/191662

Ever since Aaron Bunsen Lerner isolated melatonin (N-acetyl-5-methoxytryptamine) from pineal glands of cattle in 1958, the hormone has been found to have several uses in humans. Endogenous melatonin is well recognised for its role in regulation of the circadian rhythm. [1] Exogenous melatonin has been studied for various indications in anaesthesia such as hypnosis, anxiolysis, sedation and analgesia. It has also been used effectively for the prevention of emergence agitation and delirium in postoperative as well as intensive care unit patients. Melatonin's antioxidative, immunomodulatory and cardioprotective properties have found utility in a variety of surgical procedures such as organ transplantation, liver resection and cardiovascular surgery. [2],[3],[4],[5]

Systematic reviews and meta-analyses have shown that oral melatonin (0.05-0.2 mg/kg or 3-15 mg bolus) decreases the preoperative anxiety in adults scheduled for a wide range of surgeries. It is also devoid of amnesic effects unlike benzodiazepines. Conflicting evidence exists in literature regarding melatonin's ability to provide postoperative anxiolysis, pain intensity reduction and probable opioid sparing effects. [6],[7] Limited evidence suggests that melatonin may reduce the induction dose requirements of intravenous induction agents [8],[9] but not of sevoflurane. [10] Melatonin is a poor facilitator of paediatric steal induction compared to clonidine. [11] Melatonin administration improves the baroreflex response and decreases the sympathetic output without affecting cardiac contractility. [12] A study in this issue of Indian Journal of Anaesthesia (IJA) explores the possibility of melatonin for suppressing pressor response to direct laryngoscopy and intubation. [13]

Children form a special group where preoperative anxiety can be very severe and can have serious sequelae. Their anxiety can be due to fear of the unknown, parental separation, hospital atmosphere, past experience of needles, bitter medications, etc. Several studies show the beneficial effects of oral melatonin in alleviating preoperative anxiety in children. Although conflicting evidence exists regarding melatonin's superiority over oral midazolam in this regard, melatonin may be favoured over midazolam as it has least hangover effects and other adverse effects attributable to midazolam. [14],[15],[16],[17],[18] In a study of 100 children aged 5-15 years posted for elective surgery, published in this issue of IJA, oral melatonin 0.75 mg/kg provided better preoperative anxiolysis without affecting cognitive or psychomotor behaviour. [19]

Exogenously administered melatonin has very few side effects with virtually no serious or life-threatening complications attributable even at a dose of 1 g/day or 50 mg/kg administered as a bolus. [20],[21] Although benzodiazepines are commonly used for sedation and anxiolysis in anaesthesia and intensive care, melatonin appears to have a distinct edge due to its ability to provide the same without any hangover or other side effects associated with benzodiazepines. Blood melatonin levels are known to be subnormal in a large variety of disease conditions. [4] All these factors along with its ease of availability (classified as a dietary supplement) are encouraging clinicians to delve into further depths of related research. However, one should note that the long-term consequences of high-dose melatonin are yet to be ascertained - it has been shown to contribute to altered sperm motility in healthy men and its use as a contraceptive has been contemplated. [22],[23],[24]

The high therapeutic index of melatonin, lack of life-threatening adverse effects, ease of access coupled with its beneficial effects on various organ systems and in a variety of pathological conditions hint at a marvel in the making. The evidence is convincing regarding its anxiolytic and sedative properties, but robust evidence is lacking in other areas. Future studies regarding appropriate dose and timing of administration of melatonin for other indications might unravel the true potential of melatonin.

 
   References Top

1.
Mowafi HA, Ismail SA. The uses of melatonin in anesthesia and surgery. Saudi J Med Med Sci 2014;2:134-41.  Back to cited text no. 1
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2.
Dawoodi Z, Shah N, De Sousa A. Melatonin agonists: A brief clinical review. Delhi Psychiatry J 2012;15:268-73.  Back to cited text no. 2
    
3.
Anderson LP, Werner MU, Rosenberg J, Gogenur I. Melatonin in surgery and critical care medicine. J Anesth Clin Res 2014;5:5.  Back to cited text no. 3
    
4.
Bellapart J, Boots R. Potential use of melatonin in sleep and delirium in the critically ill. Br J Anaesth 2012;108:572-80.  Back to cited text no. 4
    
5.
Kurdi MS, Patel T. The role of melatonin in anaesthesia and critical care. Indian J Anaesth 2013;57:137-44.  Back to cited text no. 5
[PUBMED]  Medknow Journal  
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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;113:968-76.  Back to cited text no. 6
    
7.
Andersen LP, Werner MU, Rosenberg J, Gögenur I. A systematic review of peri-operative melatonin. Anaesthesia 2014;69:1163-71.  Back to cited text no. 7
    
8.
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.  Back to cited text no. 8
    
9.
Naguib M, Samarkandi AH, Moniem MA, Mansour Eel-D, Alshaer AA, Al-Ayyaf HA, 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.  Back to cited text no. 9
    
10.
Evagelidis P, Paraskeva A, Petropoulos G, Staikou C, Fassoulaki A. Melatonin premedication does not enhance induction of anaesthesia with sevoflurane as assessed by bispectral index monitoring. Singapore Med J 2009;50:78-81.  Back to cited text no. 10
    
11.
Almenrader N, Haiberger R, Passariello M. Steal induction in preschool children: is melatonin as good as clonidine? A prospective, randomized study. Paediatr Anaesth 2013;23:328-33.  Back to cited text no. 11
    
12.
Paulis L, Simko F. Blood pressure modulation and cardiovascular protection by melatonin: potential mechanisms behind. Physiol Res 2007;56:671-84.  Back to cited text no. 12
    
13.
Gupta P, Jethava D, Choudhary R, Jethava DD. Role of melatonin in attenuation of haemodynamic responses to laryngoscopy and intubation. Indian J Anaesth 2016;60:712-8.  Back to cited text no. 13
  Medknow Journal  
14.
Johnson K, Page A, Williams H, Wassemer E, Whitehouse W. The use of melatonin as an alternative to sedation in uncooperative children undergoing an MRI examination. Clin Radiol 2002;57:502-6.  Back to cited text no. 14
    
15.
Wassmer E, Fogarty M, Page A, Johnson K, Quin E, Seri S, et al. Melatonin as a sedation substitute for diagnostic procedures: MRI and EEG. Dev Med Child Neurol 2001;43:136.  Back to cited text no. 15
    
16.
Samarkandi A, Naguib M, Riad W, Thalaj A, Alotibi W, Aldammas F, et al. Melatonin vs. midazolam premedication in children: a double-blind, placebo-controlled study. Eur J Anaesthesiol 2005;22:189-96.  Back to cited text no. 16
    
17.
Kain ZN, MacLaren JE, Herrmann L, Mayes L, Rosenbaum A, Hata J, et al. Preoperative melatonin and its effects on induction and emergence in children undergoing anesthesia and surgery. Anesthesiology 2009;111:44-9.  Back to cited text no. 17
    
18.
Isik B1, Baygin O, Bodur H. Premedication with melatonin vs. midazolam in anxious children. Paediatr Anaesth 2008;18:635-41.  Back to cited text no. 18
    
19.
Kurdi MS, Muthukalai SP. A comparison of the effect of two doses of oral melatonin with oral midazolam and placebo on pre-operative anxiety, cognition and psychomotor function in children: A randomised double-blind study. Indian J Anaesth 2016;60:745-51.  Back to cited text no. 19
    
20.
Nickkholgh A, Schneider H, Sobirey M, Venetz WP, Hinz U, Pelzl le H, et al. The use of high-dose melatonin in liver resection is safe: first clinical experience. J Pineal Res 2011;50:381-8.  Back to cited text no. 20
    
21.
Nordlund JJ, Lerner AB. The effects of oral melatonin on skin color and on the release of pituitary hormones. J Clin Endocrinol Metab 1977;45:768-74.  Back to cited text no. 21
    
22.
Puig-Domingo M, Webb SM, Serrano J, Peinado MA, Corcoy R, Ruscalleda J, et al. Brief report: melatonin-related hypogonadotropic hypogonadism. N Engl J Med 1992;327:1356-9.  Back to cited text no. 22
    
23.
Luboshitzky R, Shen-Orr Z, Nave R, Lavi S, Lavie P. Melatonin administration alters semen quality in healthy men. J Androl 2002;23:572-8.  Back to cited text no. 23
    
24.
Silman RE. Melatonin: a contraceptive for the nineties. Eur J Obstet Gynecol Reprod Biol 1993;49:3-9.  Back to cited text no. 24
    




 

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