Background
Methods
Results
Study characteristics
First author | Year | Country | n | Surgery / procedure | Age (years) | M:F | Anxious children | Anaesthesia | Melatonin dose | Melatonin formulation | Trade Name | Manufacturer | Preparation | Administration timing | Comparator(s) |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Almenrader | 2013 | Italy | 87 | Not specified | 1 - 5 | 77:10 | No | GA | 0.3 mg/kg | 6mg/ml | Melamil® | Milte Italia SpA, Italy | Not specified | 60 min prior to surgery | Clonidine 4μg/kg |
Ansari | 2018 | Iran | 23 | Dental surgery | 2 - 6 | 17:6 | Yes | Sedation | 0.5 mg/kg | Not specified | Not specified | Vitane Pharmaceuticals, USA | Dissolved in sweetened water | 30 minutes prior to IV sedation | Midazolam 0.5 mg/kg |
Faghihian | 2018 | Iran | 132 | Dental surgery | 3 - 6 | 55:77 | Yes | GA | 0.5 mg/kg | 15 ml | Melatonin tablets 3mg | Aristo pharmaceutical company, India | Dissolved in water | 40 min prior to induction | Midazolam 0.5 mg/kg; Placebo (15 ml dextrose and saline) |
Gitto | 2016 | Italy | 92 | Elective surgery | 5 - 14 | 62:30 | No | GA | 0.5 mg/kg
(max 20 mg) | Not specified | Melamil® oral drops | Milte Italia SpA, Italy | Dissolved in 5 ml water | 40 min prior to induction | Midazolam 0.5 mg/kg (max 20 mg) |
Impellizzeri | 2017 | Italy | 80 | Elective surgery | 8 - 14 | 64:16 | No | GA | 0.5 mg/kg
(max 20 mg) | Not specified | Melamil®
oral drops | Milte Italia SpA, Italy | Dissolved in 5 ml water | 40 min prior to induction | Midazolam 0.5 mg/kg (max 20 mg) |
Isik | 2008 | Turkey | 60 | Dental surgery | 3 - 8 | 31:29 | Yes | Sedation | 3mg; 0.5 mg/kg | Not specified | Melatonina® tablets (3mg) | Katowice, Poland | Dissolved in 3–10 ml water | 60 min prior to N2O/O2 sedation | Midazolam 15mg/3ml; Placebo (saline) |
Kain | 2009 | USA | 148 | Elective surgery | 2 - 8 | 82:66 | No | GA | 0.05; 0.2; 0.4 mg/kg | Not specified | Not specified | Sigma Chemical, USA | Prepared in an investigational pharmacy | 45 min prior to induction | Midazolam 0.5 mg/kg |
Khalifa | 2013 | Egypt | 120 | Adenotonsillectomy | 3 - 6 | 64:56 | No | GA | 0.1 mg/kg | Not specified | Not specified | Not specified | One tablet (5mg) dissolved in 10 ml glucose 5%. The calculated dose added with 15mg/kg oral paracetamol | 60 min prior to induction | Ketamine 0.5 mg/kg; Melatonin 0.05 mg/kg with Ketamine 0.25 mg/kg; Placebo (saline) |
Kurdi | 2016 | India | 100 | Elective surgery | 5 - 15 | 51:49 | No | LA and GA | 0.5; 0.75 mg/kg | 3mg/ml | Not specified | Life extension pharmaceuticals, Lauderdale, obtained online | Commercially available MT syrup (no preparation) | 60 min prior to induction | Midazolam 0.5 mg/kg; Placebo (multivitamin syrup) |
Ozcengiz | 2011 | Turkey | 100 | Esophageal dilatation procedures | 3 - 9 | 50:50 | No | GA | 0.1 mg/kg | Not specified | Not specified | Not specified | Given with 2–2.5 mg/kg oral paracetamol | 40–45 min prior to induction | Midazolam 0.5 mg/kg; Dexmedetomidine 2.5 μg/kg; Placebo (saline) |
Samarkandi | 2005 | USA | 105 | Inguinal hernia, undescended testis, hydrocoele and hypospadias | 2 - 5 | 73:32 | No | GA | 0.1; 0.25; 0.5 mg/kg | Not specified | Not specified | General Nutrition Corporation, USA | Mixed in 15mg/kg oral paracetamol | 45 min prior to induction | Midazolam (0.1; 0.25; 0.5 mg/kg); Placebo (acetaminophen) |
Comparators
Dose and formulation of melatonin
Outcome measures
Outcome theme | Outcome reported | Almenrader | Ansari | Faghihian | Gitto | Impellizzeri | Isik | Kain | Khalifa | Kurdi | Ozcengiz | Samarkandi |
---|---|---|---|---|---|---|---|---|---|---|---|---|
Anxiety | Pre-operative anxiety (n=433) | 0a | -a | +a | 0 | |||||||
Behaviour during separation from parents (n=100) | + | |||||||||||
Post-operative anxiety (n=80) | 0 | |||||||||||
Parental anxiety (n=228) | 0 | 0 | ||||||||||
Anaesthesia | Compliance to intravenous induction (n=460) | - | 0 | - | + | |||||||
Successful steal induction (n=87) | 0a | |||||||||||
Quality of mask induction (n=87) | 0 | |||||||||||
Required infusion of propofol (n=92) | +a | |||||||||||
Sedation | Sedation success (n=407) | - | - | 0 | - | -a | ||||||
Time to onset of sleep (n=87) | 0 | |||||||||||
Recovery | Recovery duration (n=324) | 0 | - | + | ||||||||
Recovery score (n=197) | 0 | 0 | ||||||||||
Emergence behaviour (n=368) | + | 0 | 0 | |||||||||
Hemodynamic variables (n=123) | 0 | 0 | ||||||||||
Maintenance of cognition & psychomotor skills (n=100) | +a | |||||||||||
Analgesia | Post-operative analgesia (n=237) | 0 | + | |||||||||
Long term follow-up | Behaviour (2-week post op) (n=105) | + |
Risk of bias assessment
Random sequence generation (selection bias) | Allocation concealment (selection bias) | Blinding of participants (performance bias) | Blinding of IMP administrators (performance bias) | Blinding of outcome assessment (detection bias) | Incomplete outcome data (attrition bias) | Selective reporting (reporting bias) | |
---|---|---|---|---|---|---|---|
Almenrader (2013) | + | + | – | – | + | + | + |
Ansari (2018) | + | / | + | – | + | + | + |
Faghihian (2018) | + | + | + | / | + | / | + |
Gitto (2016) | + | + | + | + | + | / | + |
Impellizzeri (2017) | + | + | + | + | + | + | + |
Isik (2008) | + | / | + | / | + | + | + |
Kain (2009) | + | + | + | + | + | + | + |
Khalifa (2013) | + | + | + | / | + | + | + |
Kurdi (2016) | + | + | + | – | + | + | + |
Ozcengiz (2011) | + | + | + | / | + | + | + |
Samarkandi (2005) | + | + | + | + | + | + | + |