The Takeaway

In pediatric surgical patients, the melatonin dosage does not affect children’s compliance with induction but impacts their postoperative behavior by reducing the likelihood of agitation.

Study Design

• Double-blinded randomized controlled trial
• 126 children
• Aged 4–14, of either sex, with an ASA I or II, scheduled for elective surgery
• 2 doses of oral melatonin (7 mg)
• Primary objective was to assess melatonin as premedication on orientation score, induction compliance, and emergency agitation of children undergoing surgeries.
• Exclusion Criteria: ASA III or more, lung, heart, neurological, CNS disorder, diabetes, psychiatric illness, thyroid storm, drug allergy, liver disease, sleep disorders, intake of antipsychotics, or history of recent surgery. Patients who have already experienced sedation; those who have taken benzodiazepines, opioids, or any other sedatives in the past month; patients undergoing emergency surgery; or who declined to participate

Physiology Refresh

Melatonin is a hormone primarily secreted by the pineal gland in the brain, and its release is tightly regulated by the light-dark cycle. It plays a central role in regulating circadian rhythms, particularly the sleep-wake cycle.

Synthesis and Release: Melatonin is synthesized from tryptophan, which is converted to serotonin and then to melatonin. Its production is stimulated by darkness and inhibited by light, especially blue light. The retina senses light and sends signals via the retinohypothalamic tract to the suprachiasmatic nucleus (SCN) of the hypothalamus, our “master clock.” From there, the signal travels through the sympathetic nervous system to the pineal gland, where melatonin is secreted.

Receptors and Mechanism: Melatonin acts primarily through MT1 and MT2 G-protein-coupled receptors, found in the SCN and other brain regions.

• MT1: Suppresses neuronal firing in the SCN, helping to promote sleep onset.
• MT2: Involved in phase-shifting circadian rhythms—helping reset the body clock in response to environmental changes, like jet lag.

When melatonin binds to these receptors, it decreases intracellular cAMP and inhibits calcium influx, leading to reduced neuronal excitability and promoting a state conducive to sleep.

Clinical Relevance in Anesthesia: Melatonin has mild sedative, anxiolytic, and analgesic properties, which is why it’s sometimes used as a premedication, especially in pediatric patients. Its mechanism is distinct from traditional sedatives—it doesn’t cause respiratory depression or impair cognition as profoundly, and its anxiolysis is mediated more through circadian and sleep regulation than direct GABAergic pathways.

Also, because circadian rhythms influence anesthetic drug metabolism and emergence, understanding melatonin’s role is relevant for optimizing perioperative care and timing of surgery.

Abstract

Background: Following sedation or general anesthesia, emergent agitation (EA) presents as a sequence of abrupt, complicated psychomotor problems marked by perceptual abnormalities, delusions, and disorientation. Studies have proved that melatonin significantly decreases the incidence of postoperative agitation in children after anesthesia. The primary objective of this study was to compare the effectiveness of two doses of oral melatonin as a premedication for orientation score, induction compliance, and emergency agitation of children undergoing surgeries.

Methods: In this double-blinded randomized controlled trial, 126 children, aged 4–14, of either sex, with an ASA I or II, scheduled for elective surgery were randomly assigned to get either melatonin 0.4 mg/kg (Group M4) or melatonin 0.2 mg/kg (Group M2), with 63 kids in each group. All children have had the same anesthetic strategy. As a primary outcome, orientation score, induction compliance to intravenous induction anesthesia, and decreased emergency agitation were assessed.

Results: Both groups were comparable in terms of demographic characteristics and baseline data. Orientation scores were similar between the groups. Preoperatively, all patients were oriented in both time and place. The two groups had no statistically significant difference according to induction compliance distribution (p = 0.065). There was a statistically significant difference in agitation behavior after 5, 10, and 15 min postoperatively in M 4, 2, and total participants (p < 0.001).

Conclusion: In pediatric surgical patients, the melatonin dosage does not affect children’s compliance with induction but impacts their postoperative behavior by reducing the likelihood of agitation. Administering oral melatonin before surgery could potentially aid in managing postoperative delirium in children.

Excerpts

Oral melatonin syrup effectively reduces pediatric morning preanesthetic anxiety, increases preoperative surgical scores, promotes early recovery, and reduces emergence agitation, regardless of the time of surgery or anesthetic used

It has been reported to raise sedation levels without compromising orientation and causing preoperative anxiolysis.

Children’s preoperative anxiety is linked to a variety of postoperative outcomes, including eating disorders, bedwetting, longer recovery-phase suffering, and postoperative regressive behavioral abnormalities

The causes of emerging agitation include pain, pr-operative worry, the type of surgical operations, the patient’s personality, too rapid waking, and the anesthetics used. The cause of emerging agitation cannot be attributed to one specific element

Numerous investigations revealed that the use of regional blocks, opioids, and nonsteroidal anti-inflammatory medications reduces the likelihood of emerging agitation. However, emerging agitation frequently happens even after good pain management or during nonpainful treatments.

Preoperative midazolam and melatonin were evaluated in two recent investigations in children. They reported that melatonin was superior to midazolam in reducing emerging delirium, the same as in the present trial. However, they also claimed that melatonin was just as powerful an antianxiety agent as midazolam taken orally.

Citation

Al Bareh,Haider Muhy, Al Kidsawi,Mohammed Jawad Kadhim, Al Ghrabiu,Zainab Zuhair Knaish, Kahloul,Mohamed, A Comparison of the Effect of Two Doses of Oral Melatonin as Premedication on Orientation Score, Induction Compliance, and Emergency Agitation of Children Undergoing Elective Surgeries: A Double-Blinded Randomized Trial, Anesthesiology Research and Practice, 2025, 8832216, 7 pages, 2025. https://doi.org/10.1155/anrp/8832216

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