5–7 years Partial crossover n = 20 3.99 Parallel n = 31 9 Parallel n = 30 Age range = 3–9 Parallel n = 90 (30 per group) Age range = 3–10 Parallel Transient desaturation

(n = 4) 0.75 mg/kg midazolam (n = 10) 1 mg/kg midazolam Nausea and drowsiness (n = 3) 0.5 mg/kg midazolam (n = 7) 0.75 mg/kg midazolam (n = 12) 1 mg/kg midazolam n = 21 7.3 Parallel n = 46 12.5 Crossover n = 35 7.4 Crossover n = 486 Mean ages ranged from 3.3 to 12.5 All of these studies had oral midazolam as an intervention and were prospective and subjects were assigned to groups randomly. More detailed assessment Nutlin 3a of the quality and risk of bias of these studies has been reported by Lourenço-Matharu et al.[3] In general, the quality of reporting

was low and a significant proportion were crossover studies (7, 44%) with the attendant problem of the carryover effect. No significant side effects were reported. Minor adverse Buparlisib manufacturer events were more common (n = 68, 14% of cases); classifications are further summarised in Table 3, with nausea and vomiting being the most common side effect reported (n = 30, 6%). After combining the results from Medline and Embase searches, hand searching and removing papers that did not meet the criteria, nine papers were included. Two further papers were found after searching the reference lists of included papers to bring the total to eleven[29-39]. Data from these papers are summarised in Table 2. Only the numbers of subjects having oral midazolam are described. Summary data are at the bottom of the table; only simple summary measures could be calculated due to the limited data available from some

studies. n = 15 Age range = 3–9 Retrospective study n = 101 Mean age between 2.9 and 5 (SD 1.6, 1.0) Retrospective study 250 treatment episodes (160 patients) 6.7 Prospective Sleep (n = 3) Dizziness (n = 1) n = 61 Age range  = 2–4.8 Non-randomised controlled trial comparing age range Hiccups, loss ofbalance and paradoxical agitation. Supplemental oxygen given. No numbers given 786 treatment episodes (579 patients) 5.4 Retrospective study Hallucinations (n = 2) Vomiting (n = 9) n = 109 Prospective study Agitation Oversedation Mild ‘inhalation problem No numbers given n = 24 3 years Prospective study 91 treatment episodes Demeclocycline (40 patients) Age range 1.3 and 9.3 Prospective study Paradoxical reactions (n = 3) Transient desaturation (n = 2) – group unclear, assumed oral n = 510 4.9 Prospective study Hiccups (n = 18) Diplopia (n = 18) Crying/agitation (n = 74) Enuresis (n = 5) n = 45 2–4.9 Prospective study n = 40 (20 per group) 2.5 (0.3) 0.7 mg/kg 1.7 (0.3) 1 mg/kg Retrospective study 0.7 mg/kg midazolam vs 1 mg/kg midazolam vs 0.7 mg/kg midazolam + 1.0 mg/kg meperidine vs 0.7 mg/kg midazolam + 1.5 mg/kg meperidine vs 1.0 mg/kg midazolam + 1.0 mg/kg meperidine vs 1.0 mg/kg midazolam + 1.5 mg/kg meperidine All oral n = 2032a Mean ages ranged from 1.7 to 6.