Triclofos 500mg/5ml oral solution

Abstract Introduction Triclofos and melatonin are commonly used oral sedatives in children for obtaining a sleep electroencephalogram (EEG) record. There has been no systematic review till now to compare the efficacy and safety of these two medications. Objectives The review intended to compare the efficacy of oral triclofos and melatonin in children <18 years of age for inducing adequate sedation for obtaining a sleep EEG record. We also attempted to compare the adverse effects, impact on EEG record, the yield of epileptiform abnormalities, and sleep onset latency in both groups. Methods A systematic search was conducted on “MEDLINE/PUBMED, Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, Web of Science, and Google Scholar” till November 30, 2020, with the following keywords/the Medical Subject Headings (MESH) terms while searching: “sleep EEG,” “electroencephalogram,” “triclofos,” “melatonin” OR “ramelteon” AND “epilepsy,” “seizure,” OR “convulsion.” ROB 2.0 and ROBINS-I tool was used to determine the risk of bias. To assess heterogeneity in studies, Higgins and Thompson's I 2 method was utilized. When I 2 was more than 50%, a random effects model was utilized and a fixed-effect model was used for other parameters. To assess the presence of publication bias, Egger's test was used. Results For describing the efficacy of triclofos in 1,284 and melatonin in 1,532 children, we selected 16 articles. The indirect comparison between the pooled estimate of all children receiving individual medications revealed comparable efficacy in obtaining successful sleep EEG record with a single dose (90 vs. 76%, p = 0.058) and repeat dose (p = 0.054), detection of epileptiform abnormalities (p = 0.06), and sleep onset latency (p = 0.06), but more proportion of children receiving triclofos had adverse effects (p = 0.001) and duration of sleep was also higher with triclofos (p = 0.001). Conclusion Efficacy of triclofos and melatonin are comparable in inducing sleep for recording EEG in children, although triclofos is more likely to cause adverse effects. However, the level of evidence is low for this conclusion and the weak strength of recommendation for the results of this review is likely to change in the future after completion of controlled trials exploring these two medications.

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Sleep state is vital for recording electroencephalogram (EEG), as it decreases the artifacts and can unwind certain epileptiform discharges (EDs). However, attaining the sleep state in children, especially in children with developmental challenges, is often tricky. To achieve this sleep state in uncooperative patients, both children and adults, oral sedatives are used for prompting sleep, in order to assist in performing EEG. Sedation can be defined as a state of drowsiness or sleep from which a patient can be roused.1 In a sedated state, patients’ vital respiratory reflexes remain intact, and they can respond to verbal commands. Scottish Intercollegiate Guidelines Network guideline is a national clinical guideline developed to highlight the special considerations for sedation in children.2 Various medications such as benzodiazepines, barbiturates, etc., have been tried in the past to achieve sedation. However, these drugs were noted to affect EEG recordings by either warping the background readings or stifling the EDs. Therefore, natural sleep was preferred for performing EEGs. To achieve this natural sleep state in uncooperative children, drugs such as chloral hydrate, chlorpromazine, and promethazine were previously favored. However, these drugs also lost their popularity over time due to their unacceptable adverse drug effects (ADE) profiles like prolonged sedation, respiratory depression, hypotension, and desaturation in certain cases. This lead to the advent of drugs with better safety profiles such asmelatonin, chloral hydrate, and triclofos.Melatonin is a hormone secreted by the pineal gland that acts primarily to regulate the circadian rhythm in humans. It is secreted at a serum concentration, varying extensively between 80 to 120 pg/mL during the night and 10 to 20 pg/mL during the day.3 Therefore, it can be considered as one of the best biomarkers of human biorhythms.4 Children with neurodevelopmental disorders present with sleep problems that are mostly related to behavioral factors and altered circadian rhythm due to abnormally low levels of melatonin.5 Over the years, various researches have given abundant evidence that exogenous melatonin administration is effective against sleep problems.5,6 Moreover, being an indigenous hormone, melatonin causes a minimal adverse reaction in humans when compared with benzodiazepines, barbiturates, and propofol. Wassmer et al conducted a study to evaluate the efficacy and safety of melatonin for inducing sleep and suggested that melatonin is an efficacious drug to induce sedation for various noninvasive procedures in adults, children, and even in those with developmental or behavioral challenges.7 Although the adverse effects of melatonin are minor, it causes fatigue, mood swings, and tainted psychomotor performances to a certain extent. Similarly, chloral hydrate derivatives are another group of drugs that are commonly used as oral sedatives. These drugs get metabolized to trichloroethanol. Since chloral hydrate has an unpleasant taste and causes gastric irritation, triclofos, a chloral hydrate derivative, is preferred as it is more palatable. The oral solution is well-absorbed, with the onset of action in 30 to 40minutes, and produces hypnosis for 6 to 8hours in doses of 25 to 75mg/kg.8 In this issue of the Journal of Neurosciences in Rural Practice, Panda et al have published a systematic review and meta-analysis to assess the efficacy and safety of melatonin and triclofos for inducing adequate sedation for sleep EEG in children.9 Their initial searches led to the retrieval of 203 articles that highlighted the use of either melatonin or triclofos for sedation of children to perform EEGs. However, after a thorough evaluation of the articles by the reviewers, only 16 articles met the inclusion criteria (11 studies describing the efficacy of melatonin and 5 studies describing

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Background: Effective and safe pediatric procedural sedation is still a concern especially in areas outside operation theatres. The aim of the study was to compare the efficacy and safety of oral triclofos and oral midazolam in children undergoing computed tomography. Methods: A prospective randomized double blind study was conducted in 100 children aged one to five years. Group-I (n=50) received oral triclofos 100 mg/kg and Group-II (n=50) oral midazolam 0.75 mg/kg. Both groups were given oral atropine 0.03 mg/kg and supplemented with intravenous midazolam upto 0.1 mg/kg in case of inadequate effect. Onset and duration of sedation, success for completion of procedure and time to recovery were noted. Student’s t test and Z test of proportions were used for statistical analysis. Results Majority of children 36(72%) in Group-I achieved Ramsay Sedation Score >4 as compared to 25(50%) in Group-II. Computed tomography scan could be successfully completed at comparable rate (52% vs 56%). Success rate improved to 96% vs 80% after supplementing intravenous midazolam in Group I & II respectively (p< 0.05). Onset (37.91minutes ± 7.96 vs 26 ± 10), duration of sedation ( 117.91minutes ± 72.41 vs 66.2minutes ± 33) were significantly shorter and recovery (98.19minutes ± 72.58 vs 47.4minutes ± 31.42) in Group I & II respectively was faster in children who received oral midazolam (p< 0.05). Conclusion We conclude that both drugs were equally effective and safe for computed tomography scan in children. However better recovery profile of midazolam makes it more suitable for day care procedures. Journal of Society of Anesthesiologists of Nepal 2015; 2(2): 41-45

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