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Indian Journal of Pediatrics Mar 2024Neonatal hypoxic-ischemic encephalopathy is a major cause of perinatal death and neurodevelopmental impairment (NDI). Hypothermia (HT) is the standard of care; however,... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Neonatal hypoxic-ischemic encephalopathy is a major cause of perinatal death and neurodevelopmental impairment (NDI). Hypothermia (HT) is the standard of care; however, additional neuroprotective agents are required to improve prognosis. The authors searched for all drugs in combination with HT and compared their effects using a network meta-analysis.
METHODS
The authors searched PubMed, Embase, and Cochrane Library until September 24, 2022 for articles assessing mortality, NDI, seizures, and abnormal brain imaging findings in neonates with hypoxic-ischemic encephalopathy. Direct pairwise comparisons and a network meta-analysis was performed under random effects.
RESULTS
Thirteen randomized clinical trials enroled 902 newborns treated with six combination therapies: erythropoietin magnesium sulfate, melatonin (MT), topiramate, xenon, and darbepoetin alfa. The results of all comparisons were not statistically significant, except for NDI, HT vs. MT+HT: odds ratio = 6.67, 95% confidence interval = 1.14-38.83; however, the overall evidence quality was low for the small sample size.
CONCLUSIONS
Currently, no combination therapy can reduce mortality, seizures, or abnormal brain imaging findings in neonatal hypoxic-ischemic encephalopathy. According to low quality evidence, HT combined with MT may reduce NDI.
Topics: Infant, Newborn; Humans; Hypoxia-Ischemia, Brain; Hypothermia; Network Meta-Analysis; Hypothermia, Induced; Seizures
PubMed: 37199820
DOI: 10.1007/s12098-023-04563-3 -
Canadian Journal of Anaesthesia =... Sep 2019Postoperative sore throat negatively affects patient satisfaction and recovery. We conducted a systematic review and meta-analysis to examine the efficacy of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Postoperative sore throat negatively affects patient satisfaction and recovery. We conducted a systematic review and meta-analysis to examine the efficacy of preoperative topical administration of magnesium sulfate in preventing postoperative sore throat in adult patients.
METHODS
We searched Medline, EMBASE, China National Knowledge Infrastructure, and the Cochrane Central Register of Controlled Trials from inception to 6 October, 2018. We included randomized-controlled trials that assessed the efficacy and safety of topical application of magnesium preoperatively in adult patients who underwent endotracheal intubation for general anesthesia. We then pooled the data using a random-effects model and conducted a trial sequential analysis on the incidence of sore throat. Our primary outcome was the incidence of sore throat at 24 hr after surgery/extubation. Our secondary outcomes included the severity of sore throat at 24 hr after surgery/extubation and adverse events.
RESULTS
Eleven randomized-controlled trials involving 1,096 patients were included in this study. Topical application of magnesium was associated with reduced incidence of postoperative sore throat (risk ratio, 0.31; 95% confidence interval [CI], 0.21 to 0.45) as well as reduced severity of postoperative sore throat (standardized mean difference, - 2.66; 95% CI, - 3.89 to - 1.43). Three studies reported that significant adverse events were not associated with topical magnesium. The trial sequential analysis suggested that there is adequate evidence supporting the efficacy of topical magnesium in preventing postoperative sore throat.
CONCLUSION
Our study suggests that preoperative topical magnesium can effectively prevent postoperative sore throat.
TRIAL REGISTRATION
PROSPERO (CRD42018110019); registered 26 September, 2018.
Topics: Administration, Topical; Adult; Airway Extubation; Anesthesia, General; Humans; Intubation, Intratracheal; Magnesium Sulfate; Pharyngitis; Postoperative Complications; Randomized Controlled Trials as Topic
PubMed: 31119554
DOI: 10.1007/s12630-019-01396-7 -
Critical Care Explorations Jul 2020This systematic review and meta-analysis addresses the efficacy and safety of nonopioid adjunctive analgesics for patients in the ICU.
UNLABELLED
This systematic review and meta-analysis addresses the efficacy and safety of nonopioid adjunctive analgesics for patients in the ICU.
DATA SOURCES
We searched PubMed, Embase, the Cochrane Library, CINAHL Plus, and Web of Science.
STUDY SELECTION
Two independent reviewers screened citations. Eligible studies included randomized controlled trials comparing efficacy and safety of an adjuvant-plus-opioid regimen to opioids alone in adult ICU patients.
DATA EXTRACTION
We conducted duplicate screening of citations and data abstraction.
DATA SYNTHESIS
Of 10,949 initial citations, we identified 34 eligible trials. These trials examined acetaminophen, carbamazepine, clonidine, dexmedetomidine, gabapentin, ketamine, magnesium sulfate, nefopam, nonsteroidal anti-inflammatory drugs (including diclofenac, indomethacin, and ketoprofen), pregabalin, and tramadol as adjunctive analgesics. Use of any adjuvant in addition to an opioid as compared to an opioid alone led to reductions in patient-reported pain scores at 24 hours (standard mean difference, -0.88; 95% CI, -1.29 to -0.47; low certainty) and decreased opioid consumption (in oral morphine equivalents over 24 hr; mean difference, 25.89 mg less; 95% CI, 19.97-31.81 mg less; low certainty). In terms of individual medications, reductions in opioid use were demonstrated with acetaminophen (mean difference, 36.17 mg less; 95% CI, 7.86-64.47 mg less; low certainty), carbamazepine (mean difference, 54.69 mg less; 95% CI, 40.39-to 68.99 mg less; moderate certainty), dexmedetomidine (mean difference, 10.21 mg less; 95% CI, 1.06-19.37 mg less; low certainty), ketamine (mean difference, 36.81 mg less; 95% CI, 27.32-46.30 mg less; low certainty), nefopam (mean difference, 70.89 mg less; 95% CI, 64.46-77.32 mg less; low certainty), nonsteroidal anti-inflammatory drugs (mean difference, 11.07 mg less; 95% CI, 2.7-19.44 mg less; low certainty), and tramadol (mean difference, 22.14 mg less; 95% CI, 6.67-37.61 mg less; moderate certainty).
CONCLUSIONS
Clinicians should consider using adjunct agents to limit opioid exposure and improve pain scores in critically ill patients.
PubMed: 32696016
DOI: 10.1097/CCE.0000000000000157 -
Farmacia Hospitalaria : Organo Oficial... Apr 2021To describe and organize the current information available on binary, ternary and/or quaternary mixtures used in opioid-free anesthesia (OFA), as well as their...
OBJECTIVE
To describe and organize the current information available on binary, ternary and/or quaternary mixtures used in opioid-free anesthesia (OFA), as well as their physicochemical stability, in order to facilitate its correct administration, optimize its use, and prevent potential effectiveness and safety issues.
METHOD
A systematic review of the literature on OFA was conducted in PubMed/Medline, Trissel, Micromedex, Lexicomp, ww.ahfsdruginformation.com, ASHP's Extended Stability for Parenteral Drugs, and www.stabilis.org. Only articles published in English or Spanish until May 2020 and with access to full text were considered. MeSH terms used included: "drug incompatibility" AND "opioid-free anesthesia" AND "administration, intravenous" AND "dexmedetomidine" AND "lidocaine" AND "ketamine" AND "magnesium sulphate" OR "infusions, intravenous. A first search was carried out in PubMed/Medline that included OFA clinical cases. The results obtained were collected in a database. A second search was carried out on the incompatibilities of intravenous mixtures. Information was compiled on mutually-compatible/incompatible drugs, reference concentrations, stability time at room temperature (23 ± 2 °C) and under refrigeration (4 ± 2 ºC), type of administration recommended, and relevant results and conclusions. Two two-dimensional tables on the compatibility of each drug combination were created for administration as Y-site infusion or as a mixture in a single solution.
RESULTS
Seven hundred and eighty articles were identified, with the full text of 203 being accessed. A total of 4,762 cases treated with OFA protocols were chronologically collected from 32 different publications. Administration of two concomitant drugs was the most usual regimen (42.4%). The most frequently drugs were dexmedetomidine (25 studies), ketamine hydrochloride (25 studies) and lidocaine (14 studies). Compatibility/incompatibility data was collected for 11 drugs, associated to 7 pharmacological groups; compatibility with Y-site administration was found in 43 of 55 combinations (78.18%) and with integration into one single solution in 13 of 55 drug combinations (23.63%). None of the sources reviewed reported any adverse results related to potential pharmacological incompatibilities.
CONCLUSIONS
Despite the availability of multiple OFA protocols, few studies analyze the compatibility between binary drug mixtures. No information exists as yet regarding compatibilities in the context of ternary and quaternary mixtures. Despite the availability of multiple OFA protocols, few studies analyze the compatibility between binary drug mixtures. No information exists as yet regarding compatibilities in the context of ternary and quaternary mixtures.
Topics: Analgesics, Opioid; Anesthesia; Drug Combinations; Drug Incompatibility; Humans; Pharmaceutical Preparations
PubMed: 33941057
DOI: 10.7399/fh.11614 -
BMJ Paediatrics Open May 2024To review the efficacy of nebulised magnesium sulfate (MgSO) in acute asthma in children. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To review the efficacy of nebulised magnesium sulfate (MgSO) in acute asthma in children.
METHODS
The authors searched Medline, Embase, Web of Science and Cochrane Library for randomised controlled trials (RCTs) published until 15 December 2023. RCTs were included if they compared the efficacy and safety of nebulised MgSO as a second-line agent in children presenting with acute asthma exacerbation. A random-effects meta-analysis was performed, and the Risk of Bias V.2 tool was used to assess the biases among them.
RESULTS
10 RCTs enrolling 2301 children with acute asthma were included. All trials were placebo controlled and administered nebulised MgSO/placebo and salbutamol (±ipratropium bromide). There was no significant difference in Composite Asthma Severity Score between the two groups (6 RCTs, 1953 participants; standardised mean difference: -0.09; 95% CI: -0.2 to +0.02, I=21%). Children in the MgSO group have significantly better peak expiratory flow rate (% predicted) than the control group (2 RCTs, 145 participants; mean difference: 19.3; 95% CI: 8.9 to 29.8; I=0%). There was no difference in the need for hospitalisation, intensive care unit admission or duration of hospital stay. Adverse events were minor, infrequent (7.3%) and similar among the two groups.
CONCLUSIONS
There is low-certainty evidence that nebulised MgSO as an add-on second-line therapy for acute asthma in children does not reduce asthma severity or a need for hospitalisation. However, it was associated with slightly better lung functions. The current evidence does not support the routine use of nebulised MgSO in paediatric acute asthma management.
PROSPERO REGISTRATION NUMBER
CRD42022373692.
Topics: Humans; Magnesium Sulfate; Asthma; Child; Nebulizers and Vaporizers; Acute Disease; Administration, Inhalation; Bronchodilator Agents; Randomized Controlled Trials as Topic; Anti-Asthmatic Agents
PubMed: 38782483
DOI: 10.1136/bmjpo-2024-002638 -
PLoS Medicine Aug 2022Preterm birth-related complications are the leading cause of death in newborns and children under 5. Health outcomes of preterm newborns can be improved with appropriate...
BACKGROUND
Preterm birth-related complications are the leading cause of death in newborns and children under 5. Health outcomes of preterm newborns can be improved with appropriate use of antenatal corticosteroids (ACSs) to promote fetal lung maturity, tocolytics to delay birth, magnesium sulphate for fetal neuroprotection, and antibiotics for preterm prelabour rupture of membranes. However, there are wide disparities in the rate and consistency in the use of these interventions across settings, which may underlie the differential health outcomes among preterm newborns. We aimed to assess factors (barriers and facilitators) affecting the appropriate use of ACS, tocolytics, magnesium sulphate, and antibiotics to improve preterm birth management.
METHODS AND FINDINGS
We conducted a mixed-methods systematic review including primary qualitative, quantitative, and mixed-methods studies. We searched MEDLINE, EMBASE, CINAHL, Global Health, and grey literature from inception to 16 May 2022. Eligible studies explored perspectives of women, partners, or community members who experienced preterm birth or were at risk of preterm birth and/or received any of the 4 interventions, health workers providing maternity and newborn care, and other stakeholders involved in maternal care (e.g., facility managers, policymakers). We used an iterative narrative synthesis approach to analysis, assessed methodological limitations using the Mixed Methods Appraisal Tool, and assessed confidence in each qualitative review finding using the GRADE-CERQual approach. Behaviour change models (Theoretical Domains Framework; Capability, Opportunity, and Motivation (COM-B)) were used to map barriers and facilitators affecting appropriate use of these interventions. We included 46 studies from 32 countries, describing factors affecting use of ACS (32/46 studies), tocolytics (13/46 studies), magnesium sulphate (9/46 studies), and antibiotics (5/46 studies). We identified a range of barriers influencing appropriate use of the 4 interventions globally, which include the following: inaccurate gestational age assessment, inconsistent guidelines, varied knowledge, perceived risks and benefits, perceived uncertainties and constraints in administration, confusion around prescribing and administering authority, and inadequate stock, human resources, and labour and newborn care. Women reported hesitancy in accepting interventions, as they typically learned about them during emergencies. Most included studies were from high-income countries (37/46 studies), which may affect the transferability of these findings to low- or middle-income settings.
CONCLUSIONS
In this study, we identified critical factors affecting implementation of 4 interventions to improve preterm birth management globally. Policymakers and implementers can consider these barriers and facilitators when formulating policies and planning implementation or scale-up of these interventions. Study findings can inform clinical preterm birth guidelines and implementation to ensure that barriers are addressed, and enablers are reinforced to ensure these interventions are widely available and appropriately used globally.
Topics: Anti-Bacterial Agents; Female; Humans; Infant, Newborn; Magnesium Sulfate; Parturition; Pregnancy; Premature Birth; Tocolytic Agents
PubMed: 35998205
DOI: 10.1371/journal.pmed.1004074 -
Journal of Clinical Anesthesia Sep 2024Investigating the effect of magnesium sulfate (MS) on emergence agitation (EA) in adult surgical patients following general anesthesia (GA). (Meta-Analysis)
Meta-Analysis
The effect of magnesium sulfate on emergence agitation in surgical adult patients undergoing general anesthesia: A systematic review and meta-analysis of randomized controlled trials.
STUDY OBJECTIVE
Investigating the effect of magnesium sulfate (MS) on emergence agitation (EA) in adult surgical patients following general anesthesia (GA).
DESIGN
Systematic literature review and meta-analysis (PROSPERO number: CRD42023461988).
SETTING
Review of published literature.
PATIENTS
Adults undergoing GA.
INTERVENTIONS
Intravenous administration of MS.
MEASUREMENTS
We searched PubMed/MEDLINE, EMBASE, the Cochrane Library, Scopus, and Web of Science for publications until September 14, 2023. The primary outcome was the incidence of EA, while the secondary outcomes included the impact of MS on postoperative agitation score (PAS), emergence variables and adverse events. Relative risk (RR) with 95% confidence interval (CI) measured dichotomous outcome, while standardized mean difference (SMD) or mean difference (MD) with 95% CI measured continuous outcomes.
MAIN RESULTS
Meta-analysis of five randomized controlled trials (RCTs) indicated that MS was associated with a lower incidence of EA at various time points (0 min: RR = 0.62, 95% CI [0.41, 0.95]; p = 0.183, I = 43.6%; 5 min: RR = 0.29, 95% CI [0.16, 0.52]; p = 0.211, I = 36%; 10 min: RR = 0.14, 95% CI [0.06, 0.32]; p = 0.449, I = 0%; 15 min: RR = 0.11, 95% CI [0.02, 0.55]; p = 0.265, I = 19.5%; 30 min: RR = 0.05, 95% CI [0.00, 0.91]; the postoperative period: RR = 0.21, 95% CI [0.09, 0.49]; p = 0.724, I = 0%;). Additionally, MS was associated with a reduced PAS at various time points except for 0 min. However, no significant differences were observed in extubation time, the length of stay in the post-anesthesia care unit, postoperative nausea and vomiting or total complications.
CONCLUSIONS
Limited available evidence suggests that MS was associated with a lower incidence of EA. Nevertheless, further high-quality studies are warranted to strengthen and validate the effect of MS in preventing EA in adult surgical patients.
Topics: Humans; Anesthesia, General; Magnesium Sulfate; Randomized Controlled Trials as Topic; Emergence Delirium; Anesthesia Recovery Period; Adult; Incidence
PubMed: 38749290
DOI: 10.1016/j.jclinane.2024.111499 -
BJOG : An International Journal of... Sep 2020Ordinary meta-analyses indicate that magnesium sulphate (MgSO ) treatment in women at imminent risk for preterm delivery decreases the offspring's risk of cerebral palsy... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Ordinary meta-analyses indicate that magnesium sulphate (MgSO ) treatment in women at imminent risk for preterm delivery decreases the offspring's risk of cerebral palsy (CP). However, repetitive testing of cumulative data calls for statistical caution, e.g. by trial sequential analysis (TSA), for which there are previously insufficient samples to draw a firm conclusion. Recently, a randomised controlled trial (RCT) provided additional data that potentially increased the sample size such that a new TSA might detect a statistically significant effect.
OBJECTIVES
To assess the possible fetal neuroprotective effect of MgSO for women at imminent risk for preterm delivery in an updated systematic review with meta-analysis and TSA.
SEARCH STRATEGY
We searched MEDLINE, Embase, Cochrane and ClinicalTrials.gov on 8 October 2019. The search strategy clustered terms describing the MgSO intervention and preterm delivery.
SELECTION CRITERIA
RCTs.
DATA COLLECTION AND ANALYSIS
Two reviewers extracted the data. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using fixed-effects models. A TSA was applied to the primary outcome, CP. The quality of the evidence was assessed using GRADE. The protocol was registered in PROSPERO (registration: CRD42019151441).
MAIN RESULTS
We identified six eligible trials (5917 women). MgSO intervention in women at imminent risk for preterm birth decreased the offspring's CP risk (meta-analysis RR 0.68, 95% CI 0.54-0.85; TSA RR 0.69, 95% CI 0.48-0.97).
CONCLUSIONS
This systematic review with meta-analysis and TSA shows conclusively that MgSO , when given to women at imminent risk for preterm delivery, decreases the offspring's CP risk.
TWEETABLE ABSTRACT
Antenatal magnesium sulphate decreases the risk of cerebral palsy in children born preterm.
Topics: Cerebral Palsy; Female; Humans; Infant, Newborn; Infant, Premature; Magnesium Sulfate; Neuroprotective Agents; Pregnancy; Premature Birth; Prenatal Care; Randomized Controlled Trials as Topic; Risk Assessment
PubMed: 32237069
DOI: 10.1111/1471-0528.16238 -
Lung India : Official Organ of Indian... 2023The purpose of this meta-analysis was to evaluate the efficacy of nebulised magnesium in the treatment of acute exacerbation of COPD. PubMed and Embase databases were...
Nebulised magnesium sulphate as an adjuvant to the treatment of acute exacerbation of COPD: A systematic review and meta-analysis of randomised controlled trials with trial sequential analysis.
The purpose of this meta-analysis was to evaluate the efficacy of nebulised magnesium in the treatment of acute exacerbation of COPD. PubMed and Embase databases were searched for randomised controlled trials comparing any dose of nebulised magnesium sulphate with placebo for treatment of acute exacerbation of COPD, published from database inception till 30 June 2022. Bibliographic mining of relevant results was performed to identify any additional studies. Data extraction and analyses were done independently by review authors and any disagreements were resolved through consensus. Meta-analysis was done using a fixed-effect model at clinically significant congruent time points reported across maximum studies to ensure comparability of treatment effect. Four studies met the inclusion criteria, randomly assigning 433 patients to the comparisons of interest in this review. Pooled analysis showed that nebulised magnesium sulphate improved pulmonary expiratory flow function at 60 minutes after initiation of intervention compared to placebo [median difference (MD) 9.17%, 95% confidence interval (CI) 2.94 to 15.41]. Analysis of expiratory function in terms of standardised mean differences (SMD) revealed a small yet significant positive effect size (SMD 0.24, 95% CI 0.04 to 0.43). Among the secondary outcomes, nebulised magnesium sulphate reduced the need for ICU admission (risk ratio 0.52, 95% CI 0.28 to 0.95), amounting to 61 fewer ICU admissions per 1000 patients. No difference was noted in the need for hospital admission, need for ventilatory support, or mortality. No adverse events were reported. Nebulised magnesium sulphate improves pulmonary expiratory flow function and reduces the need for ICU admission in patients with acute exacerbation of COPD.
PubMed: 37417087
DOI: 10.4103/lungindia.lungindia_473_22 -
Frontiers in Pharmacology 2023Opioid-induced hyperalgesia (OIH) is an adverse event of prolonged opioid use that increases pain intensity. The optimal drug to prevent these adverse effects is still...
Opioid-induced hyperalgesia (OIH) is an adverse event of prolonged opioid use that increases pain intensity. The optimal drug to prevent these adverse effects is still unknown. We aimed to conduct a network meta-analysis to compare different pharmacological interventions for preventing the increase in postoperative pain intensity caused by OIH. Several databases were searched independently for randomized controlled trials (RCTs) comparing various pharmacological interventions to prevent OIH. The primary outcomes were postoperative pain intensity at rest after 24 h and the incidence of postoperative nausea and vomiting (PONV). Secondary outcomes included pain threshold at 24 h after surgery, total morphine consumption over 24 h, time to first postoperative analgesic requirement, and shivering incidence. In total, 33 RCTs with 1711 patients were identified. In terms of postoperative pain intensity, amantadine, magnesium sulphate, pregabalin, dexmedetomidine, ibuprofen, flurbiprofen plus dexmedetomidine, parecoxib, parecoxib plus dexmedetomidine, and S (+)-ketamine plus methadone were all associated with milder pain intensity than placebo, with amantadine being the most effective (SUCRA values = 96.2). Regarding PONV incidence, intervention with dexmedetomidine or flurbiprofen plus dexmedetomidine resulted in a lower incidence than placebo, with dexmedetomidine showing the best result (SUCRA values = 90.3). Amantadine was identified as the best in controlling postoperative pain intensity and non-inferior to placebo in the incidence of PONV. Dexmedetomidine was the only intervention that outperformed placebo in all indicators. https://www.crd.york.ac. uk/prospero/display_record.php?, CRD42021225361.
PubMed: 37426819
DOI: 10.3389/fphar.2023.1199794