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British Journal of Anaesthesia Jan 2023Sedation techniques and drugs are increasingly used in children undergoing imaging procedures. In this systematic review and meta-analysis, we present an overview of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Sedation techniques and drugs are increasingly used in children undergoing imaging procedures. In this systematic review and meta-analysis, we present an overview of literature concerning sedation of children aged 0-8 yr for magnetic resonance imaging (MRI) procedures using needle-free pharmacological techniques.
METHODS
Embase, MEDLINE, Web of Science, and Cochrane databases were systematically searched for studies on the use of needle-free pharmacological sedation techniques for MRI procedures in children aged 0-8 yr. Studies using i.v. or i.m. medication or advanced airway devices were excluded. We performed a meta-analysis on sedation success rate. Secondary outcomes were onset time, duration, recovery, and adverse events.
RESULTS
Sixty-seven studies were included, with 22 380 participants. The pooled success rate for oral chloral hydrate was 94% (95% confidence interval [CI]: 0.91-0.96); for oral chloral hydrate and intranasal dexmedetomidine 95% (95% CI: 0.92-0.97); for rectal, oral, or intranasal midazolam 36% (95% CI: 0.14-0.65); for oral pentobarbital 99% (95% CI: 0.90-1.00); for rectal thiopental 92% (95% CI: 0.85-0.96); for oral melatonin 75% (95% CI: 0.54-0.89); for intranasal dexmedetomidine 62% (95% CI: 0.38-0.82); for intranasal dexmedetomidine and midazolam 94% (95% CI: 0.78-0.99); and for inhaled sevoflurane 98% (95% CI: 0.97-0.99).
CONCLUSIONS
We found a large variation in medication, dosage, and route of administration for needle-free sedation. Success rates for sedation techniques varied between 36% and 98%.
Topics: Child; Humans; Hypnotics and Sedatives; Midazolam; Dexmedetomidine; Administration, Oral; Chloral Hydrate; Administration, Intranasal; Conscious Sedation
PubMed: 36283870
DOI: 10.1016/j.bja.2022.09.007 -
EClinicalMedicine Jul 2023Melatonin has become a widely used sleeping aid for young individuals currently not included in existing guidelines. The aim was to develop a recommendation on the use...
Use of melatonin for children and adolescents with chronic insomnia attributable to disorders beyond indication: a systematic review, meta-analysis and clinical recommendation.
BACKGROUND
Melatonin has become a widely used sleeping aid for young individuals currently not included in existing guidelines. The aim was to develop a recommendation on the use of melatonin in children and adolescents aged 2-20 years, with chronic insomnia due to disorders beyond indication.
METHODS
We performed a systematic search for guidelines, systematic reviews, and randomised trials (RCTs) in Medline, Embase, Cochrane Library, PsycInfo, Cinahl, Guidelines International Network, Trip Database, Canadian Agency for Drugs and Technologies in Health, American Academy of Sleep Medicine, European Sleep Research Society and Scandinavian Health Authorities databases. A separate search for adverse events was also performed. The latest search for guidelines, systematic reviews, and adverse events was performed on March 17, 2023. The latest search for RCTs was performed on to February 6, 2023. The language was restricted to English, Danish, Norwegian, and Swedish. Eligible participants were children and adolescents (2-20 years of age) with chronic insomnia due to underlying disorders, in whom sleep hygiene practices have been inadequate and melatonin was tested. Studies exclusively on autism spectrum disorders or attention deficit hyperactive disorder were excluded. There were no restrictions on dosage, duration of treatment, time of consumption or release formula. Primary outcomes were quality of sleep, daytime functioning and serious adverse events, assessed at 2-4 weeks post-treatment. Secondary outcomes included total sleep time, sleep latency, awakenings, drowsiness, quality of life, non-serious adverse events, and all-cause dropouts (assessed at 2-4 weeks post-treatment), plus quality of sleep and daytime functioning (assessed at 3-6 months post-treatment). Pooled estimates were calculated using inverse variance random effects model. Statistical heterogeneity was calculated using I statistics. Risk of bias was assessed using Cochrane risk of bias tool. Publication bias was assessed using funnel plots. A multidisciplinary guideline panel constructed the recommendation using Grades of Recommendation, Assessment, Development and Evaluation (GRADE). The certainty of evidence was considered either high, moderate, low or very low depending on the extent of risk of bias, inconsistency, imprecision, indirectness, or publication bias. The evidence-to-decision framework was used to discuss the feasibility and acceptance of the constructed recommendation and its impact on resources and equity. The protocol is registered with the Danish Health Authority.
FINDINGS
We identified 13 RCTs, including 403 patients with a wide range of conditions. Melatonin reduced sleep latency by 14.88 min (95% CI 23.42-6.34, 9 studies, I = 60%) and increased total sleep time by 18.97 min (95% CI 0.37-37.57, 10 studies, I = 57%). The funnel plot for total sleep time showed no apparent indication of publication bias. No other clinical benefits were found. The number of patients experiencing adverse events was not statistically increased however, safety data was scarce. Certainty of evidence was low.
INTERPRETATION
Low certainty evidence supports a moderate effect of melatonin in treating sleep continuity parameters in children and adolescents with chronic insomnia due to primarily medical disorders beyond indication. The off-label use of melatonin for these patients should never be the first choice of treatment, but may be considered by medical specialists with knowledge of the underlying disorder and if non-pharmacological interventions are inadequate. If treatment with melatonin is initiated, adequate follow-up to evaluate treatment effect and adverse events is essential.
FUNDING
The Danish Health Authority. The Parker Institute, Bispebjerg and Frederiksberg Hospital, supported by the Oak Foundation.
PubMed: 37457114
DOI: 10.1016/j.eclinm.2023.102049 -
Journal of Neurosciences in Rural... Jan 2022
PubMed: 35110914
DOI: 10.1055/s-0041-1740579 -
Materials (Basel, Switzerland) May 2021To qualitatively and quantitatively review the use of melatonin as a topical/systemic formulation for the management of periodontitis. (Review)
Review
OBJECTIVES
To qualitatively and quantitatively review the use of melatonin as a topical/systemic formulation for the management of periodontitis.
MATERIALS AND METHODS
PubMed; Scopus; and Web of Science databases were searched using the MesH terms "melatonin" and "periodontitis". Title and abstracts were screened to eliminate irrelevant and duplicate articles. The full text data of the screened articles were assessed using the selection criteria.
RESULTS
Of 176 identified articles (PubMed-66; Scopus-56; Web of Science-52; Cross-reference-2), only 12 studies qualified to be included in the systematic review. Four studies assessed the independent effect of 1% topical melatonin formulation while 8 articles assessed the adjunctive use of systemic melatonin formulation (1-10 mg) following scaling and root planing (SRP). All studies showed an improvement in periodontal parameters such as pocket depth, clinical attachment loss, periodontal disease index, community periodontal index, gingival bleeding scores, and prognostic marker levels in saliva and serum. A meta-analysis of data from 2 studies revealed that 1-2 mg (systemic) melatonin supplementation reduced pocket depth; although the difference was not statistically significant and hence cannot be interpreted or used for conclusive evidence. Risk of Bias Assessment tool (RoBANS) and Cochrane Collaboration RoB tool elicited a high risk of bias in the included studies. GRADE (recommendation assessment, development, and evaluation) inferred a weak recommendation for the use of melatonin in periodontitis management.
CONCLUSIONS
Melatonin supplementation (topical and systemic) in periodontitis patients improved key periodontal parameters including pocket depth and clinical attachment loss.
CLINICAL RELEVANCE
Melatonin could be a potential host modulatory agent for periodontitis management; although the data from the present review should be interpreted carefully due to the associated high risk of bias.
PubMed: 34066498
DOI: 10.3390/ma14092417 -
Frontiers in Cardiovascular Medicine 2022The effectiveness of melatonin and its analogs in preventing postoperative delirium (POD) following cardiac surgery is controversial. The purpose of this systematic...
BACKGROUND
The effectiveness of melatonin and its analogs in preventing postoperative delirium (POD) following cardiac surgery is controversial. The purpose of this systematic review and meta-analysis was to confirm the benefits of melatonin and its analogs on delirium prevention in adults who underwent cardiac surgery.
METHODS
We systematically searched the PubMed, Cochrane Library, Web of Science, Embase, and EBSCOhost databases, the last search was performed in October 2021 and repeated before publication. The controlled studies were included if investigated the impact of melatonin and its analogs on POD in adults who underwent cardiac surgery. The primary outcome was the incidence of delirium. The Stata statistical software 17.0 was used to perform this study.
RESULTS
This meta-analysis included eight randomized controlled trials (RCTs) and two cohort studies with a total of 1,714 patients. The results showed that melatonin and ramelteon administration were associated with a significantly lower incidence of POD in adults who underwent cardiac surgery (odds ratio [OR], 0.46; 95% confidence interval [CI], 0.29-0.74; = 0.001). The subgroup analyses confirmed that melatonin 3 mg (OR, 0.37; 95% CI, 0.18-0.76; = 0.007) and 5 mg (OR, 0.34; 95% CI, 0.21-0.56; < 0.001) significantly reduced the incidence of POD.
CONCLUSION
Melatonin at dosages of 5 and 3 mg considerably decreased the risk of delirium in adults who underwent cardiac surgery, according to our results. Cautious interpretation of our results is important owing to the modest number of studies included in this meta-analysis and the heterogeneity among them.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO registration number: CRD42021246984.
PubMed: 35665270
DOI: 10.3389/fcvm.2022.888211 -
BMJ Open Mar 2023Postoperative delirium (POD) is common. It is associated with increased morbidity and mortality. Many cases may be preventable and melatonin offers promise as a... (Meta-Analysis)
Meta-Analysis
UNLABELLED
Postoperative delirium (POD) is common. It is associated with increased morbidity and mortality. Many cases may be preventable and melatonin offers promise as a preventative agent.
OBJECTIVE
This systematic review provides an up-to-date synthesis of the evidence on the effect of melatonin in preventing POD.
DESIGN
A systematic search of randomised controlled trials of melatonin in POD was run across multiple databases (EMBASE, MEDLINE, CINAHL, PsycINFO) and a clinical trials registry (ClinicalTrials.org) (1 January 1990 to 5 April 2022). Studies examining the effects of melatonin on POD incidence in adults are included. Risk of bias was assessed using the Cochrane risk of bias 2 tool.
OUTCOME MEASURES
The primary outcome is POD incidence. Secondary outcomes are POD duration and length of hospital stay. Data synthesis was undertaken using a random-effects meta-analysis and presented using forest plots. A summary of methodology and outcome measures in included studies is also presented.
RESULTS
Eleven studies, with 1244 patients from a range of surgical specialties were included. Seven studies used melatonin, in variable doses, and four used ramelteon. Eight different diagnostic tools were used to diagnose POD. Time points for assessment also varied. Six studies were assessed as low risk of bias and five as some concern. The combined OR of developing POD in the melatonin groups versus control was 0.41 (95% CI 0.21 to 0.80, p=0.01).
CONCLUSION
This review found that melatonin may reduce the incidence of POD in adults undergoing surgery. However, included studies displayed inconsistency in their methodology and outcome reporting. Further work to determine the optimum regime for melatonin administration, along with consensus of how best to evaluate results, would be beneficial.
PROSPERO REGISTRATION NUMBER
CRD42021285019.
Topics: Humans; Adult; Melatonin; Emergence Delirium; Incidence; Length of Stay
PubMed: 36990485
DOI: 10.1136/bmjopen-2022-069950 -
Indian Journal of Critical Care... Sep 2023Delirium, being a common disorder among critically ill patients, has a reported incidence ranging 45-83% in the intensive care unit (ICU) population. The prophylactic... (Review)
Review
INTRODUCTION
Delirium, being a common disorder among critically ill patients, has a reported incidence ranging 45-83% in the intensive care unit (ICU) population. The prophylactic use of melatonin and melatonergics has been shown to have a positive effect in reducing the incidence of delirium in many clinical trials. Our study was thus proposed to find out the role of melatonin on the incidence and severity of ICU delirium, ICU and hospital length of stay (LOS), requirement, duration of mechanical ventilation, and ICU mortality.
METHODOLOGY
A systematic search of various databases was performed to find out the trials which compare melatonin with a placebo or standard therapy for delirium prevention with the results conveyed as mean differences (MDs) or risk ratios. The statistical software, Review Manager (RevMan, version 5.4), was used for data synthesis.
RESULTS
Twelve studies were included in the meta-analysis. Prophylactic administration of melatonin or ramelteon was not associated with a statistically significant reduction in the incidence of delirium (odds ratio [OR] 0.63; confidence interval [CI]: 0.60, 1.32; = 0.22), the severity of delirium (MD: 0.22; 95% CI: From -1.36 to 1.81; = 0.78), ICU LOS (MD: 0.05; 95% CI: From -0.65 to 0.75; = 0.89), hospital LOS (MD: -1.46; 95% CI: From -4.50 to -1.59; = 0.35), need for mechanical ventilation (OR: 0.74, 95% CI: 0.38-1.44; = 0.37), and ICU mortality (MD: 0.78; 95% CI: 0.56; 1.11; = 0.62). However, a significant reduction in the duration of mechanical ventilation (MD: -0.85; 95% CI: From -1.64 to -0.06; = 0.03) was found.
CONCLUSION
Our meta-analysis suggests that melatonin when given prophylactically has no significant role in reducing the incidence and severity of delirium, ICU and hospital LOS, need for mechanical ventilation, duration of mechanical ventilation, and ICU mortality. Further studies are warranted.
HOW TO CITE THIS ARTICLE
Mukundarajan R, Soni KD, Trikha A. Prophylactic Melatonin for Delirium in Intensive Care Unit: An Updated Systematic Review and Meta-analysis of Randomized Controlled Trials. Indian J Crit Care Med 2023;27(9):675-685.
PubMed: 37719343
DOI: 10.5005/jp-journals-10071-24529 -
Brain, Behavior, and Immunity Mar 2021Chronic inflammation contributes to multiple diseases including cardiovascular diseases, autoimmune disorders, metabolic disorders, and psychiatric conditions.... (Meta-Analysis)
Meta-Analysis
Chronic inflammation contributes to multiple diseases including cardiovascular diseases, autoimmune disorders, metabolic disorders, and psychiatric conditions. Melatonin, a hormone responsible for circadian rhythm, plays a complex role within the immune system, including having an anti-inflammatory effect. While there are numerous animal studies demonstrating this effect, few human clinical trials have been conducted. This systematic review of clinical trials examined whether exogenous melatonin reduces levels of inflammatory markers in humans. We searched PubMed, Embase, Cochrane Library, Scopus, and PsycINFO, and the references of the identified articles for randomized and non-randomized placebo-controlled trials. Data were extracted from the articles and meta-analyses were conducted using a random effects model to calculate standardized mean differences (SMDs, i.e., Cohen's d). From an initial search result of 4548 references, 31 studies met the inclusion criteria and were included involving 1517 participants. Melatonin had significant anti-inflammatory effects on interleukin (IL)-1 (SMD -1.64; 95% confidence interval [CI] -2.86, -0.43; p = 0.008), IL-6 (-3.84; -5.23, -2.46; p < 0.001), IL-8 (-21.06; -27.27, -14.85; p < 0.001), and tumor necrosis factor (TNF) (-1.54; -2.49, -0.58; p = 0.002), but not on C-reactive protein (CRP) (-0.18; -0.91, 0.55; p = 0.62). Trimming outlier studies with large effect sizes eliminated publication bias, and summary effect sizes were significant for IL-1 (SMD -1.11; 95% CI -1.90, -0.32; p = 0.006), IL-6 (-1.91; -2.98, -0.83; p = 0.001), and IL-8 (-13.46; -18.88, -8.04; p < 0.001), but not for TNF (-0.45; -1.13, 0.23; p = 0.19). Exogenous melatonin reduced levels of inflammatory markers and may be useful for prevention and adjuvant treatment of inflammatory disorders. Melatonin is safe with few side effects, which makes it an excellent agent for prevention of inflammatory disorders. Because chronic inflammation increases with aging and inflammation plays a role in the etiology of numerous diseases that affect older populations, melatonin has the potential to be widely used particularly in older adults.
Topics: Aged; Animals; Anti-Inflammatory Agents; C-Reactive Protein; Dietary Supplements; Humans; Inflammation; Melatonin
PubMed: 33581247
DOI: 10.1016/j.bbi.2021.01.034 -
Frontiers in Pharmacology 2024Cerebral ischemia-reperfusion (I/R) injury is the predominant causes for the poor prognosis of ischemic stroke patients after reperfusion therapy. Currently, potent... (Review)
Review
Cerebral ischemia-reperfusion (I/R) injury is the predominant causes for the poor prognosis of ischemic stroke patients after reperfusion therapy. Currently, potent therapeutic interventions for cerebral I/R injury are still very limited. Melatonin, an endogenous hormone, was found to be valid in preventing I/R injury in a variety of organs. However, a systematic review covering all neuroprotective effects of melatonin in cerebral I/R injury has not been reported yet. Thus, we perform a comprehensive overview of the influence of melatonin on cerebral I/R injury by collecting all available literature exploring the latent effect of melatonin on cerebral I/R injury as well as ischemic stroke. In this systematic review, we outline the extensive scientific studies and summarize the beneficial functions of melatonin, including reducing infarct volume, decreasing brain edema, improving neurological functions and attenuating blood-brain barrier breakdown, as well as its key protective mechanisms on almost every aspect of cerebral I/R injury, including inhibiting oxidative stress, neuroinflammation, apoptosis, excessive autophagy, glutamate excitotoxicity and mitochondrial dysfunction. Subsequently, we also review the predictive and therapeutic implications of melatonin on ischemic stroke reported in clinical studies. We hope that our systematic review can provide the most comprehensive introduction of current advancements on melatonin in cerebral I/R injury and new insights into personalized diagnosis and treatment of ischemic stroke.
PubMed: 38375039
DOI: 10.3389/fphar.2024.1356112 -
Neuroscience and Biobehavioral Reviews Aug 2022We conducted the first systematic review and series of meta-analyses to assess the efficacy and tolerability of melatonin in children/adolescents or adults with sleep or... (Meta-Analysis)
Meta-Analysis Review
We conducted the first systematic review and series of meta-analyses to assess the efficacy and tolerability of melatonin in children/adolescents or adults with sleep or mental health disorders, using the same set of criteria across disorders and ages. Based on a pre-registered protocol (PROPSPERO: CRD42021289827), we searched a broad range of electronic databases up to 02.02.2021 for randomized control trials (RCTs) of melatonin. We assessed study quality using the Risk of Bias tool, v2. We included a total of 34 RCTs (21 in children/adolescents: N = 984; 13 in adults: N = 1014). We found evidence that melatonin significantly improved sleep onset latency and total sleep time, but not sleep awaking, in children and adolescents with a variety of neurodevelopmental disorders, and sleep onset latency (measured by diary) as well as total sleep time (measured with polysomnography) in adults with delayed sleep phase disorder. No evidence of significant differences between melatonin and placebo was found in terms of tolerability. We discuss clinical and research implications of our findings.
Topics: Adolescent; Child; Humans; Melatonin; Neurodevelopmental Disorders; Sleep; Sleep Wake Disorders
PubMed: 35691474
DOI: 10.1016/j.neubiorev.2022.104723