Melatonin Premedication in Children Undergoing Surgery

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

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.

Study Overview

• Status: Completed
• Conditions: Anaesthesia; Premedication
• Intervention / Treatment: Drug: melatonin in children premedication; Drug: midazolam in children premedication

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 92
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 10 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: melatonin; 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
Active Comparator: midazolam; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Azienda Ospedaliera Universitaria Policlinico "G. Martino"
• Collaborators: Eloisa Gitto; Lucia Marseglia; Gabriella D'Angelo; Sara Manti; Simona Montalto; Pietro Impellizzeri
• Investigators: Study Chair: Carmelo Romeo, Prof, Azienda Ospedaliera Universitaria Policlinico "G. Martino"

Publications and helpful links

General Publications

• Acil M, Basgul E, Celiker V, Karagoz AH, Demir B, Aypar U. Perioperative effects of melatonin and midazolam premedication on sedation, orientation, anxiety scores and psychomotor performance. Eur J Anaesthesiol. 2004 Jul;21(7):553-7. doi: 10.1017/s0265021504007094.
• Naguib M, Gottumukkala V, Goldstein PA. Melatonin and anesthesia: a clinical perspective. J Pineal Res. 2007 Jan;42(1):12-21. doi: 10.1111/j.1600-079X.2006.00384.x.
• Naguib M, Samarkandi AH, Moniem MA, Mansour Eel-D, Alshaer AA, Al-Ayyaf HA, Fadin A, Alharby SW. The effects of melatonin premedication on propofol and thiopental induction dose-response curves: a prospective, randomized, double-blind study. Anesth Analg. 2006 Dec;103(6):1448-52. doi: 10.1213/01.ane.0000244534.24216.3a.
• Kurdi MS, Patel T. The role of melatonin in anaesthesia and critical care. Indian J Anaesth. 2013 Mar;57(2):137-44. doi: 10.4103/0019-5049.111837.

Study record dates

Study Major Dates

• Study Start: September 1, 2012
• Primary Completion (Actual): October 1, 2013
• Study Completion (Actual): October 1, 2013

Study Registration Dates

• First Submitted: October 7, 2014
• First Submitted That Met QC Criteria: October 15, 2014
• First Posted (Estimate): October 16, 2014

Study Record Updates

• Last Update Posted (Estimate): October 16, 2014
• Last Update Submitted That Met QC Criteria: October 15, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Keywords: melatonin; midazolam; children
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Protective Agents; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Antioxidants; Midazolam; Melatonin
• Other Study ID Numbers: 797/2012