Melatonin Premedication in Children Undergoing Surgery

Study Overview
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Brief Summary
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Melatonin has been proposed as alternative to midazolam as a premedication in procedures preceding anaesthesia induction. The objective of this prospective, randomized, double-blind study is to investigate the possible effect of melatonin premedication on the required infusion of propofol in comparison to midazolam, evaluating the efficacy of oral melatonin on sedation in children undergoing surgery. Preoperative anxiety and postoperative analgesia are also assessed in both groups.

Detailed Description
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Children between the age of 5 and 14 years scheduled for elective surgery will be prospectively enrolled between September 2012 and October 2013. A physician will perform the clinical examination for each child, and anamnestic data will be collected in the medical records. Exclusion criteria will be: patients who had taken benzodiazepines, opioid drugs, or other sedative in the previous month; those who had sedation previously, or those with a temperament disorder, patients undergoing emergency surgery. Patients will be randomly assigned to 2 groups based on whether they will receive 0.2 mg/kg (max 5 mg) oral melatonin premedication (group A) or 0.5 mg/kg (max 20 mg) oral midazolam premedication (group B) before induction anaesthesia with propofol. For elective surgery, premedication will be performed between 07:30 and 09:30 h. Approximately 40 min before the induction of general anaesthesia, patients will be transported in a quiet room in the operating suite where they will receive orally melatonin or midazolam. The melatonin will be prepared by a dedicated resident in a fixed volume of 5 ml adding water in a syringe without needle. To simulate the sweet taste of the formulation of melatonin used, midazolam will be expanded to the fixed volume with 5% dextrose. The content of the syringe, in both cases marked with a coded label, will be blindly administrated to patients by the attendant nurse, not involved in the study. The child's level of sedation will be assessed and recorded by a resident before the premedication and 40 min after the administration of melatonin or midazolam, using the University of Michigan Sedation Scale (UMSS). In the operating room, an initial bolus dose of 1 mg/kg of intravenous propofol will be administered to both groups, followed by similar bolus doses of propofol until the patient will be anesthetized. Children will be considered anesthetized when asleep and not arousable. Anaesthesia will be maintained with inhalated sevoflurane. The total dose of propofol administrated will be recorded by the anaesthetist blinded to premedication group assignment. To provide objective information on the physical condition of patients after anaesthesia, Aldrete scale will be calculated after 10 min from conclusion of anaesthesia. Preoperative anxiety and postoperative analgesia will be also assessed in both groups.

Official Title
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Assessment of the Effects of Melatonin on Preoperative Anxiety and Postoperative Analgesia in Children Undergoing Surgery: a Prospective, Randomized Clinical Trial

Conditions
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Premedication, Anaesthesia

Intervention / Treatment
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* Drug: melatonin in children premedication
* Drug: midazolam in children premedication


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Children between the age of 5 and 14 years scheduled for elective surgery Exclusion Criteria: Patients who had taken benzodiazepines, opioid drugs, or other sedative in the previous month Those who had sedation previously, or those with a temperament disorder, patients undergoing emergency surgery

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 14 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: melatonin<br>0.5 mg/kg (max 20 mg) oral melatonin premedication will be administered approximately 40 min before the induction of general anaesthesia with propofol. The melatonin will be prepared in a fixed volume of 5 ml adding water in a syringe without needle. | Drug: melatonin in children premedication<br> <br> |
| Active Comparator: midazolam<br>0.5 mg/kg (max 20 mg) oral midazolam premedication will be administered approximately 40 min before the induction of general anaesthesia with propofol. The melatonin will be prepared in a fixed volume of 5 ml adding 5% dextrose in a syringe without needle. | Drug: midazolam in children premedication<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| efficacy of melatonin as premedicant in children undergoing elective surgery | the required infusion of propofol required during induction of general anaesthesia in both groups will be evaluated | day 1: 40-45 min after melatonin or midazolam premedication | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| effect of melatonin premedication in postoperative analgesia in children undergoing elective surgery | The child's level of sedation will be assessed and recorded using the University of Michigan Sedation Scale (UMSS). | day 1: 40 min after melatonin or midazolam premedication | 
| effect of melatonin premedication in postoperative analgesia in children undergoing elective surgery | post procedural pain will be assessed and recorded in both groups | day 1: 3, 6, and 12 hours post surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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melatonin, midazolam, children