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PloS One 2022Methylxanthine, including caffeine citrate and aminophylline, is the most common pharmacologic treatment for apnea of prematurity. However, due to the lack of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Methylxanthine, including caffeine citrate and aminophylline, is the most common pharmacologic treatment for apnea of prematurity. However, due to the lack of high-quality evidence, there are no clear recommendations or guidelines on how to choose between caffeine and aminophylline.
OBJECTIVE
This meta-analysis aimed to assess the comparative efficacy and safety of caffeine and aminophylline for apnea of prematurity, and provide reliable evidence for clinical medication in the treatment for apnea of prematurity.
METHODS
PubMed, Scopus, Embase, EBSCO, Web of Science, and Cochrane databases were systematically searched from May 1975 to June 2022.
RESULTS
Ten studies including a total of 923 preterm infants were evaluated. Our results showed that there was no significant difference in the effective rate of 1-3days between caffeine and aminophylline (OR 1.05, 95%CI: 0.40-2.74, P = 0.914). However, for side effects such as tachycardia (OR 0.22, 95%CI: 0.13-0.37, P<0.001) and feeding intolerance (OR 0.40, 95%CI: 0.23-0.70, P = 0.001), the incidence rate was lower in the caffeine group compared with the aminophylline group. No significant difference was found in hyperglycemia (OR 0.45, 95%CI: 0.19-1.05, P = 0.064).
CONCLUSION
This meta-analysis reveals that caffeine citrate and aminophylline have similar therapeutic effectiveness on respiratory function, but caffeine has fewer side effects and should be considered first for treatment.
Topics: Aminophylline; Apnea; Caffeine; Citrates; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Infant, Premature; Infant, Premature, Diseases
PubMed: 36121807
DOI: 10.1371/journal.pone.0274882 -
Pain Management Dec 2023Although the pathogenesis of migraine is not fully understood, accumulating evidence indicates migraine may be driven by impaired brain energy metabolism in the context... (Review)
Review
Although the pathogenesis of migraine is not fully understood, accumulating evidence indicates migraine may be driven by impaired brain energy metabolism in the context of pathologically high levels of adenosine. Considerable evidence indicates that aminophylline, an adenosine receptor antagonist, can provide strong therapeutic relief in pain, particularly post-dural headache. Moreover, direct observations from a previously published observational case series have demonstrated a strong therapeutic impact of low-dose aminophylline in patients with severe, unremitting migraine attacks. Although higher doses of aminophylline are associated with an unfavourable adverse effect profile, low doses of aminophylline are associated with minimal adverse effects. Despite this promise, double-blinded randomized trials will be needed to determine the true therapeutic efficacy of low-dose aminophylline in migraine.
Topics: Humans; Aminophylline; Migraine Disorders; Pain
PubMed: 38059379
DOI: 10.2217/pmt-2023-0076 -
The Cochrane Database of Systematic... Aug 2020Asthma is an illness that commonly affects adults and children, and it serves as a common reason for children to attend emergency departments. An asthma exacerbation is...
BACKGROUND
Asthma is an illness that commonly affects adults and children, and it serves as a common reason for children to attend emergency departments. An asthma exacerbation is characterised by acute or subacute worsening of shortness of breath, cough, wheezing, and chest tightness and may be triggered by viral respiratory infection, poor compliance with usual medication, a change in the weather, or exposure to allergens or irritants. Most children with asthma have mild or moderate exacerbations and respond well to first-line therapy (inhaled short-acting beta-agonists and systemic corticosteroids). However, the best treatment for the small proportion of seriously ill children who do not respond to first-line therapy is not well understood. Currently, a large number of treatment options are available and there is wide variation in management.
OBJECTIVES
Main objective - To summarise Cochrane Reviews with or without meta-analyses of randomised controlled trials on the efficacy and safety of second-line treatment for children with acute exacerbations of asthma (i.e. after first-line treatments, titrated oxygen delivery, and administration of intermittent inhaled short-acting beta-agonists and oral corticosteroids have been tried and have failed) Secondary objectives - To identify gaps in the current evidence base that will inform recommendations for future research and subsequent Cochrane Reviews - To categorise information on reported outcome measures used in trials of escalation of treatment for acute exacerbations of asthma in children, and to make recommendations for development and reporting of standard outcomes in future trials and reviews - To identify relevant randomised controlled trials that have been published since the date of publication of each included review METHODS: We included Cochrane Reviews assessing interventions for children with acute exacerbations of asthma. We searched the Cochrane Database of Systematic Reviews. The search is current to 28 December 2019. We also identified trials that were potentially eligible for, but were not currently included in, published reviews. We assessed the quality of included reviews using the ROBIS criteria (tool used to assess risk of bias in systematic reviews). We presented an evidence synthesis of data from reviews alongside an evidence map of clinical trials. Primary outcomes were length of stay, hospital admission, intensive care unit admission, and adverse effects. We summarised all findings in the text and reported data for each outcome in 'Additional tables'.
MAIN RESULTS
We identified 17 potentially eligible Cochrane Reviews but extracted data from, and rated the quality of, 13 reviews that reported results for children alone. We excluded four reviews as one did not include any randomised controlled trials (RCTs), one did not provide subgroup data for children, and the last two had been updated and replaced by subsequent reviews. The 13 reviews included 67 trials; the number of trials in each review ranged from a single trial up to 27 trials. The vast majority of comparisons included between one and three trials, involving fewer than 100 participants. The total number of participants included in reviews ranged from 40 to 2630. All studies included children; 16 (24%) included children younger than two years of age. Most of the reviews reported search dates older than four years. We have summarised the published evidence as outlined in Cochrane Reviews. Key findings, in terms of our primary outcomes, are that (1) intravenous magnesium sulfate was the only intervention shown to reduce hospital length of stay (high-certainty evidence); (2) no evidence suggested that any intervention reduced the risk of intensive care admission (low- to very low-certainty evidence); (3) the risk of hospital admission was reduced by the addition of inhaled anticholinergic agents to inhaled beta-agonists (moderate-certainty evidence), the use of intravenous magnesium sulfate (high-certainty evidence), and the use of inhaled heliox (low-certainty evidence); (4) the addition of inhaled magnesium sulfate to usual bronchodilator therapy appears to reduce serious adverse events during hospital admission (moderate-certainty evidence); (5) aminophylline increased vomiting compared to placebo (moderate-certainty evidence) and increased nausea and nausea/vomiting compared to intravenous beta-agonists (low-certainty evidence); and (6) the addition of anticholinergic therapy to short-acting beta-agonists appeared to reduce the risk of nausea (high-certainty evidence) and tremor (moderate-certainty evidence) but not vomiting (low-certainty evidence). We considered 4 of the 13 reviews to be at high risk of bias based on the ROBIS framework. In all cases, this was due to concerns regarding identification and selection of studies. The certainty of evidence varied widely (by review and also by outcome) and ranged from very low to high.
AUTHORS' CONCLUSIONS
This overview provides the most up-to-date evidence on interventions for escalation of therapy for acute exacerbations of asthma in children from Cochrane Reviews of randomised controlled trials. A vast majority of comparisons involved between one and three trials and fewer than 100 participants, making it difficult to assess the balance between benefits and potential harms. Due to the lack of comparative studies between various treatment options, we are unable to make firm practice recommendations. Intravenous magnesium sulfate appears to reduce both hospital length of stay and the risk of hospital admission. Hospital admission is also reduced with the addition of inhaled anticholinergic agents to inhaled beta-agonists. However, further research is required to determine which patients are most likely to benefit from these therapies. Due to the relatively rare incidence of acute severe paediatric asthma, multi-centre research will be required to generate high-quality evidence. A number of existing Cochrane Reviews should be updated, and we recommend that a new review be conducted on the use of high-flow nasal oxygen therapy. Important priorities include development of an internationally agreed core outcome set for future trials in acute severe asthma exacerbations and determination of clinically important differences in these outcomes, which can then inform adequately powered future trials.
Topics: Acute Disease; Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Aminophylline; Anti-Asthmatic Agents; Anti-Bacterial Agents; Asthma; Bias; Bronchodilator Agents; Child; Child, Preschool; Cholinergic Antagonists; Disease Progression; Helium; Humans; Infant; Length of Stay; Leukotriene Antagonists; Magnesium Sulfate; Nausea; Oxygen; Positive-Pressure Respiration; Randomized Controlled Trials as Topic; Systematic Reviews as Topic; Vomiting; Work of Breathing
PubMed: 32767571
DOI: 10.1002/14651858.CD012977.pub2 -
Journal of Cystic Fibrosis : Official... May 2022Two CFTR-dependent β-adrenergic sweat rate tests applying intradermal drug injections were reported to better define diagnosis and efficacy of CFTR-directed therapies....
OBJECTIVES
Two CFTR-dependent β-adrenergic sweat rate tests applying intradermal drug injections were reported to better define diagnosis and efficacy of CFTR-directed therapies. The aim of this work was to develop and test a needle-free image-based test and to provide an accurate analysis of the responses.
METHODS
The modified method was conducted by applying two successive iontophoresis sessions using the Macroduct device. Efficiency of drug delivery was tested by evaporimetry. Cholinergically stimulated sweating was evoked by pilocarpine iontophoresis. β-adrenergically stimulated sweating was obtained by iontophoresis of isoproterenol and aminophylline in the presence of atropine and ascorbic acid. A nonlinear mixed-effects (NLME) approach was applied to model volumes of sweat and subject-specific effects displaying inter- and intra-subject variability.
RESULTS
Iontophoresis provided successful transdermal delivery of all drugs, including almost neutral isoproterenol and aminophylline. Pilocarpine was used at a concentration ∼130-times lower than that used in the classical Gibson and Cooke sweat test. Addition of ascorbic acid lowered the pH of the solution, made it stable, prevented isoproterenol degradation and promoted drug iontophoresis. Maximal secretory capacity and kinetic rate of β-adrenergic responses were blunted in CF. A cutoff of 5.2 minutes for ET50, the time to reach the half maximal secretion, discriminated CF from controls with a 100% sensitivity and specificity. Heterozygous showed an apparently reduced kinetic rate and a preserved secretory capacity.
CONCLUSION
We tested a safe, well-tolerated needle-free image-based sweat test potentially applicable in children. Modelling responses by NLME allowed evaluating metrics of CFTR-dependent effects reflecting secretory capacity and kinetic rate.
Topics: Adrenergic Agents; Aminophylline; Ascorbic Acid; Child; Chlorides; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Humans; Iontophoresis; Isoproterenol; Pilocarpine; Sweat
PubMed: 34489187
DOI: 10.1016/j.jcf.2021.08.012 -
European Journal of Clinical... Oct 2022Asthma is a heterogeneous disease with a wide range of symptoms. Severe asthma exacerbations (SAEs) are characterized by worsening symptoms and bronchospasm requiring... (Review)
Review
PURPOSE
Asthma is a heterogeneous disease with a wide range of symptoms. Severe asthma exacerbations (SAEs) are characterized by worsening symptoms and bronchospasm requiring emergency department visits. In addition to conventional strategies for SAEs (inhaled β-agonists, anticholinergics, and systemic corticosteroids), another pharmacological option is represented by ketamine. We performed a systematic review to explore the role of ketamine in refractory SAEs.
METHODS
We performed a systematic search on PubMed and EMBASE up to August 12th, 2021. We selected prospective studies only, and outcomes of interest were oxygenation/respiratory parameters, clinical status, need for invasive ventilation and effects on weaning.
RESULTS
We included a total of seven studies, five being randomized controlled trials (RCTs, population range 44-92 patients). The two small prospective studies (n = 10 and n = 11) did not have a control group. Four studies focused on adults, and three enrolled a pediatric population. We found a large heterogeneity regarding sample size, age and gender distribution, inclusion criteria (different severity scores, if any) and ketamine dosing (bolus and/or continuous infusion). Of the five RCTs, three compared ketamine to placebo, while one used fentanyl and the other aminophylline. The outcomes evaluated by the included studies were highly variable. Despite paucity of data and large heterogeneity, an overview of the included studies suggests absence of clear benefit produced by ketamine in patients with refractory SAE, and some signals towards side effects.
CONCLUSION
Our systematic review does not support the use of ketamine in refractory SAE. A limited number of prospective studies with large heterogeneity was found. Well-designed multicenter RCTs are desirable.
Topics: Adrenal Cortex Hormones; Adult; Aminophylline; Anti-Asthmatic Agents; Asthma; Child; Cholinergic Antagonists; Fentanyl; Humans; Ketamine; Multicenter Studies as Topic; Prospective Studies
PubMed: 36008492
DOI: 10.1007/s00228-022-03374-3 -
Clinical Pharmacology and Therapeutics May 2018We hypothesized that concomitant pharmacological inhibition of the endothelin and adenosine pathway is safe and improves exercise performance in hypoxic humans, via a... (Randomized Controlled Trial)
Randomized Controlled Trial
We hypothesized that concomitant pharmacological inhibition of the endothelin and adenosine pathway is safe and improves exercise performance in hypoxic humans, via a mechanism that does not involve augmentation of blood oxygenation. To test this hypothesis, we established safety and drug interactions for aminophylline (500 mg) plus ambrisentan (5 mg) in normoxic volunteers. Subsequently, a placebo-controlled study was employed to test the combination in healthy resting and exercising volunteers at simulated altitude (4,267 m). No serious adverse events occurred. Drug interaction was minimal or absent. Aminophylline alleviated hypoxia-induced headaches. Aminophylline, ambrisentan, and their combination all significantly (P < 0.05 vs. placebo) improved submaximal hypoxic exercise performance (19.5, 20.6, and 19.1% >placebo). Single-dose ambrisentan increased blood oxygenation in resting, hypoxic subjects. We conclude that combined aminophylline and ambrisentan offer promise to safely increase exercise capacity in hypoxemic humans without relying on increasing blood oxygen availability.
Topics: Adenosine; Adolescent; Adult; Altitude; Aminophylline; Double-Blind Method; Drug Therapy, Combination; Endothelins; Exercise; Female; Humans; Hypoxia; Male; Middle Aged; Phenylpropionates; Pyridazines; Signal Transduction; Young Adult
PubMed: 28857147
DOI: 10.1002/cpt.860 -
The Cochrane Database of Systematic... 2001Bronchiectasis is characterised by chronic sputum production,bronchial wall dilation,recurrent infection and airflow limitation. Methylxanthines are used in the... (Review)
Review
BACKGROUND
Bronchiectasis is characterised by chronic sputum production,bronchial wall dilation,recurrent infection and airflow limitation. Methylxanthines are used in the management of airflow limitation associated with asthma and COPD, where they are also purported to have anti-inflammatory properties. In theory they may be of use in bronchiectasis.
OBJECTIVES
To determine the efficacy of methylxanthines in the treatment of bronchiectasis.
SEARCH STRATEGY
The Cochrane Airways Group clinical trials register derived from MEDLINE,EMBASE and hand searches using the terms bronchiectasis, aminophylline, theophylline and methyl- xanthine
SELECTION CRITERIA
Only randomised controlled trials were to be considered.
DATA COLLECTION AND ANALYSIS
The results of the searches were reviewed by two authors. Searches yielded seven trials none of which met the inclusion criteria.
MAIN RESULTS
No randomised controlled trials were identified.
REVIEWER'S CONCLUSIONS
Further research is required to establish if the methylxanthines have a role in the treatment of bronchiectasis.
Topics: Administration, Oral; Aminophylline; Bronchiectasis; Bronchodilator Agents; Humans; Randomized Controlled Trials as Topic; Theophylline
PubMed: 11279764
DOI: 10.1002/14651858.CD002734 -
Pediatrics and Neonatology Feb 2016
Topics: Aminophylline; Humans; Infant, Premature; Infant, Premature, Diseases
PubMed: 26806848
DOI: 10.1016/j.pedneo.2015.12.002 -
The Cochrane Database of Systematic... Dec 2012Asthma is a chronic condition in which sufferers may have occasional or frequent exacerbations resulting in visits to the emergency department (ED). Aminophylline has... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Asthma is a chronic condition in which sufferers may have occasional or frequent exacerbations resulting in visits to the emergency department (ED). Aminophylline has been used extensively to treat exacerbations in acute asthma settings; however, it's role is unclear especially with respect to any additional benefit when added to inhaled beta(2)-agonists.
OBJECTIVES
To determine the magnitude of effect of the addition of intravenous aminophylline to inhaled beta(2)-agonists in adult patients with acute asthma treated in the ED setting.
SEARCH METHODS
We identified trials from the Cochrane Airways Group register (derived from MEDLINE, EMBASE, CINAHL standardised searches) and handsearched respiratory journals and meeting abstracts. Two independent review authors screened and obtained potentially relevant articles and handsearched their bibliographic lists for additional articles. In the original version of this review published in 2000 we included searches of the database up to 1999. The 2012 review was updated with a revised search from inception to September 2012.
SELECTION CRITERIA
Randomised controlled trials comparing intravenous aminophylline versus placebo in adults with acute asthma and treated with inhaled beta(2)-agonists. We included patients who were treated with or without corticosteroids or other bronchodilators provided this was not part of the randomised treatment.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and one review author entered data into RevMan, which was checked by a second review author. Results are reported as mean differences (MD) or odds ratios (OR) with 95% confidential intervals (CI).
MAIN RESULTS
Fifteen studies were included in the previous version of the review, and we included two new studies in this update, although we were unable to pool new data. Overall, the quality of the studies was moderate; concealment of allocation was assessed as clearly adequate in only seven (45%) of the trials. There was significant clinical heterogeneity between studies as the doses of aminophylline and other medications and the severity of the acute asthma varied between studies.There was no statistically significant advantage when adding intravenous aminophylline with respect to hospital admissions (OR 0.58; 95% CI 0.30 to 1.12; 6 studies; n = 315). In 2000 it was found that there was no statistically significant effect of aminophylline on airflow outcomes at any time period; the addition of two trials in 2012 has not challenged this conclusion. People treated with aminophylline and beta(2)-agonists had similar peak expiratory flow (PEF) values compared to those treated with beta(2)-agonists alone at 12 h (MD 8.30 L/min; 95% CI -20.69 to 37.29 L/min) or (MD -1.21% predicted; 95% CI -14.21% to 11.78% predicted) and 24 h (MD 22.20 L/min; 95% CI -56.65 to 101.05 L/min). Two subgroup analyses were performed by grouping studies according to mean baseline airflow limitation (11 studies) and the use of any corticosteroids (nine studies). There was no relationship between baseline airflow limitation or the use of corticosteroids on the effect of aminophylline. Aminophylline-treated patients reported more palpitations/arrhythmias (OR 3.02; 95% CI 1.15 to 7.90; 6 studies; n = 249) and vomiting (OR 4.21; 95% CI 2.20 to 8.07; 7 studies; n = 321); however, no significant difference was found in tremor (OR 2.60; 95% CI 0.62 to 11.02; 5 studies; n = 249).
AUTHORS' CONCLUSIONS
The use of intravenous aminophylline did not result in significant additional bronchodilation compared to standard care with inhaled beta(2)-agonists in patients experiencing an asthma exacerbation in the ED setting, or in a significant reduction in the risk of hospital admission. For every 100 people treated with aminophylline an additional 20 people had vomiting and 15 people arrhythmias or palpitations. No subgroups in which aminophylline might be more effective were identified. Our update in 2012 is consistent with the original conclusions that the risk-benefit balance of intravenous aminophylline is unfavourable.
Topics: Acute Disease; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Adult; Aminophylline; Asthma; Bronchodilator Agents; Drug Therapy, Combination; Emergency Service, Hospital; Hospitalization; Humans; Injections, Intravenous; Randomized Controlled Trials as Topic
PubMed: 23235591
DOI: 10.1002/14651858.CD002742.pub2 -
Chinese Medical Journal Dec 2022Sepsis is a serious disease caused by infection. Aminophylline has anti-asthma and anti-inflammatory effects. We aimed to explore the safety and effect of aminophylline... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Sepsis is a serious disease caused by infection. Aminophylline has anti-asthma and anti-inflammatory effects. We aimed to explore the safety and effect of aminophylline in sepsis.
METHODS
We conducted a clinical randomized controlled trial involving 100 patients diagnosed with sepsis within 48 h after intensive care unit (ICU) admission in two sites. All patients were randomized in a 1:1 ratio to receive standard therapy with or without aminophylline. The primary clinical outcome was all-cause mortality at 28 days.
RESULTS
From September 27, 2018 to February 12, 2020, we screened 277 septic patients and eventually enrolled 100 patients, with 50 assigned to the aminophylline group and 50 to the usual-care group. At 28 days, 7 of 50 patients (14.0%) in the aminophylline group had died, compared with 16 of 50 (32.0%) in the usual-care group ( P = 0.032). Cox regression showed that the aminophylline group had a lower hazard of death (hazard ratio = 0.312, 95% confidence interval: 0.129-0.753). Compared with the usual-care group, patients in the aminophylline group had a longer survival time ( P = 0.039 by the log-rank test). The effects of aminophylline on vasopressor dose, oxygenation index, and sequential organ failure assessment score were time-dependent with treatment. There were no significant differences in total hospitalization days, ICU hospitalization days, and rates of serious adverse events (all P > 0.05). No adverse events were observed in the trial.
CONCLUSIONS
Aminophylline as an adjunct therapy could significantly reduce the risk of death and prolong the survival time of patients with sepsis.
TRIAL REGISTRATION
ChiCTR.org.cn, ChiCTR1800019173.
Topics: Humans; Aminophylline; Sepsis; Intensive Care Units; Hospitalization; Proportional Hazards Models
PubMed: 36728571
DOI: 10.1097/CM9.0000000000002282