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Year : 2009  |  Volume : 53  |  Issue : 4  |  Page : 504-505 Table of Contents     

Melatonin for Anxiolysis in Children

Senior Prof. & Head, Department ofAnaesthesiology, R.N.T Medical College, Udaipur (Raj.), India

Date of Web Publication3-Mar-2010

Correspondence Address:
Pramila Bajaj
25, Polo Ground, Udaipur (Raj.)
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Source of Support: None, Conflict of Interest: None

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How to cite this article:
Bajaj P. Melatonin for Anxiolysis in Children. Indian J Anaesth 2009;53:504-5

How to cite this URL:
Bajaj P. Melatonin for Anxiolysis in Children. Indian J Anaesth [serial online] 2009 [cited 2021 Apr 21];53:504-5. Available from: https://www.ijaweb.org/text.asp?2009/53/4/504/60328

Up to 65% of children experience intense anxiety throughout the perioperative period, especially in the preoperative holding area and during induction of an­esthesia [1] . Intensity of perioperative anxiety is a predic­tor of both emergence delirium in the postanaesthesia care unit and new-onset maladaptive behavioral changes (e.g., nightmares, enuresis, separation anxiety) [2],[3],[4] . To reducepreoperative anxiety, midazolam is widely used forpremedication in children. Midazolam, which was first introduced as an oral premedication for children in the 1980s, rapidly achieved widespread acceptance as the preferred premedication before induction of an a esthesia. Currently, it is the preferred pre-medication more than 90% of the tune. [5],[6] Midazolam acquired widespread acceptance because of its rapid absorp­tion after oral ingestion; it can also be administered via multiple routes and confers areduced incidence ofnau­sea compared with other benzodiazepines. [7] However, midazolam has several drawbacks, including paradoxi­cal reactions, interactions with opioids, variable bio availability and elimination half-life, and delayed dis­charge from the post- anaesthesia care unit after brief procedures. [7] Moreover, the effects ofmidazolam have been shown to vary with the age and temperament of the child. [8] In light of these drawbacks, an alternative to midazo lam might have widespread appeal.

Consideration of these findings has generated a great deal of interest inthe potentialuses of melatonin in the perioperative setting. This nocturnal neurohorm one is secreted bythe pinealgland, retina, and gastrointesti­naltract. It has several diverse functions, including antioxi­dant, onco static, antiinflammatory, and anticonvulsant activities, as well as regulation of circadian thythms and the reproductive axis. [9],[10] Melatonin has numerous uses: treatment of sleep disorders and jet lag, [9],[10] reduction of oxidative stress in neonates in the perioperative period [11] , protection of the skin from ultraviolet damage, and treatment of psychosis inthe intensive care unit. [12] Most impor­tantly, its hypnotic effects [l3] may be exploited fonts use as a preoperative sedative.

Several studies reported that melatonin is as ef­fective as midazolam in reducing preoperative anxiety in adults, [14] akhough evidence does not support such a role in the elderly. [15] Two recent trials involving children reported that melatonin was as effective in reducing preoperative anxiety as midazolam. [16],[17] Moreover, mel­atonin was associated with a more rapid recovery, a reduced incidence of emergence delirium, and reduced incidence of sleep disturbances 2 weeks after surgery when compared with midazolam. However, both trials suffered from methodological deficiencies such as small sample sizes (with resultant low power) and failure to control for the time of day (important, given variability in endogenous melatonin levels throughoutthe day)

Currently there is no consensus on the appropri­ate dose ofmelatonin for sedation in children. Melato­nin dosing for children is reported to be between 0.3mg and 20 mg [18],[19] Doses as great as 20 mg have been administered to children without adverse side effects apart from sedation [20] . Nonetheless, what remains un­clear is the most appropriate dose to induce sedation. On the basis of these results the possibility can not be excluded, doses of melatonin in excess of 20 mg may be necessary to reduce anxiety.

   References Top

1.Kain ZN, Mayes LC, O' Connor TZ, Cicchetti D V Preop­erative anxiety in children: Predictors and outcomes. Arch PediatrAdol Med 1996;150:123 8-45.  Back to cited text no. 1      
2.2. Kain ZN, Caldwefl-Andrews A, Martinets I, Wang S, Gaal G, McClainB, Mayes L: Preoperative anxiety, emer­gence delirium and postoperative maladaptive behav­iors: Are they related? A new conceptual framework. Anesth Analg 2004; 99:1648-54.  Back to cited text no. 2      
3.3. Aouad MT Nasr VG, Aouad MT, Nasr VG Emergence agitation in children: An update. Cun Opin Anaesthesiol 2005;18:6149.  Back to cited text no. 3      
4.4. Kain Wang SM, Mayes LC, Caramico LA, Hofstadter MB. Distress during the induction of anesthesia and postoperative behavioral outcomes. AnesthAnalg 1999; 88:1042-7.  Back to cited text no. 4      
5.5. KainZN, Caldwell-AndrewsAA, Krivutza DM, LoDo lee ME, Wang SM, Gaal D. Trends in the practice of paren­tal presence during induction of anesthesia and the use of preoperative sedative premeditation in the United States, 1995-2002: Results of a follow up study Anesth Analg 2003; 98:1252-9.  Back to cited text no. 5      
6.6. Kain ZN, Mayes LC, Bell C, Weisman S, Hofstadter MB, Rimar S: Premeditation in the United States: A status report AnesthAnalg 1997;84:427-32.  Back to cited text no. 6      
7.7. McCann M, Kain Z. Management of preoperative anxi­ety in children: An update. Anesth Analg 2001; 93:98­105.  Back to cited text no. 7      
8.8. Kain ZN, MacLaren J, McClain BC, et al. Effects of age and emotionality on the effectiveness of midazolam administered preoperatively to children. Anesthesiol­ogy2007;107:545-52.  Back to cited text no. 8      
9.9. Pandi-Perumal SR, Srinivassn V Maestrom GJ, Cardinali DP, Poeggeler B, Hardeland R: Melatonin: Nature'smost versa­tilebiological signal? FEES Joumal2006;273:2813-38.  Back to cited text no. 9      
10.10. BrzezinskiA: Melatonininhumans. NEngl JMed 1997; 336:186-95.  Back to cited text no. 10      
11.11. Gitto E, Romeo C, Reiter RJ, et al. Melatonin reduces oxidative stress in surgical neonates. J Pediatr Surg 2004; 39:184-9.  Back to cited text no. 11      
12.12. Miyazaki T, Kuwano H, Kato H, et al.Correlation between serum melatonin circadian rhythm and intensive care unit psychosis after thoracic esophagectomy. Sur­gery2003;133:662-8.  Back to cited text no. 12      
13.13. Guardiola-LemaitreB,LenegreA,PorsoltRD.Combined effects of diazepam and melatonin in two tests for anxiolytic activity in the mouse. Pharmacol Biochem Behav 1992;41:405-8.  Back to cited text no. 13      
14.14. Acil M, BasgulE, Celiker V, KaragozAH,Demir B, Aypar U. Perioperative effects of m elatonin and midazolam pre­medication on sedation, orientation, anxiety scores and psychomotor performance. Eur J Anaesthesiol 2004; 21:553-7.  Back to cited text no. 14      
15.15. Capuzzo M, ZanardiB, Schiffino E, etal. Melatonin does not reduce anxiety more than placebo in the elderly un­dergoing surgery. AnesthAnalg 2006: 103:121-3.  Back to cited text no. 15      
16.16. Samarkandi A, Naguib M, Riad W et al. Melatonin ver­sus midazolam premeditation in children: Adoubleblind, placebo-controlled study. Eur J Anaesthesiol 2005: 22:189-96.  Back to cited text no. 16      
17.17. Johnson K, Page A, Williams H, Wassemer E, Whitehouse W. The use of melatonin as an alternative to sedation in uncooperative children undergoing an MRIexamination C1inRadiol2002;57:502-6.  Back to cited text no. 17      
18.18. Cauffield JS, ForbesHJ. Dietary supplements used in the treatment of depression, anxiety, and sleep disor­ders. Lippiincotts Prim Care Pract 1999;3:290-304.  Back to cited text no. 18      
19.19. Jan SE, Hamilton D, SewardN, Fast DK, Freeman RD, Laudon M. Clinical trials of controlled-release m alatonin in children with sleep-wake cycle disorders. J Pineal Res 200029:34-9.  Back to cited text no. 19      
20.20. Gitto E, Karbownikn, Reiter RJ, Tan DX, Cuzzocrea S, Chiurazzi P, Cordara5, Corona G, TrimarchiCc BarberiI. Effects of melatotonin treatment in septic newborns. Pediatr Res 2001;50:756-60.  Back to cited text no. 20      


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