Aminophylline at clinically relevant concentrations affects inward rectifier potassium current in a dual way.

Bronchodilator aminophylline may induce atrial or less often ventricular arrhythmias. The mechanism of this proarrhythmic side effect has not been fully explained. Modifications of inward rectifier potassium (Kir) currents including IK1 are known to play an important role in arrhythmogenesis; however, no data on the aminophylline effect on these currents have been published. Hence, we tested the effect of aminophylline (3-100 µM) on IK1 in enzymatically isolated rat ventricular myocytes using the whole-cell patch-clamp technique. A dual steady-state effect of aminophylline was observed; either inhibition or activation was apparent in individual cells during the application of aminophylline at a given concentration. The smaller the magnitude of the control IK1, the more likely the activation of the current by aminophylline and vice versa. The effect was reversible; the relative changes at -50 and -110 mV did not differ. Using IK1 channel population model, the dual effect was explained by the interaction of aminophylline with two different channel populations, the first one being inhibited and the second one being activated. Considering various fractions of these two channel populations in individual cells, varying effects observed in the measured cells could be simulated. We propose that the dual aminophylline effect may be related to the direct and indirect effect of the drug on various Kir2.x subunits forming the homo- and heterotetrameric IK1 channels in a single cell. The observed IK1 changes induced by clinically relevant concentrations of aminophylline might contribute to arrhythmogenesis related to the use of this bronchodilator in clinical medicine.

Use of ketamine in patients with refractory severe asthma exacerbations: systematic review of prospective studies.

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 ß-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.

Interventions for escalation of therapy for acute exacerbations of asthma in children: an overview of Cochrane Reviews.

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 beta2-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 beta2-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 beta2-agonists (low-certainty evidence); and (6) the addition of anticholinergic therapy to short-acting beta2-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 beta2-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.

Efficacy and safety of Linkus, Aminophylline diphenhydramine and acefyllin piperazine for the treatment of cough in children.

To evaluate the safety and efficacy of Linkus, Aminophylline with Diphenhydramine group and Acefyllin Piperazine with Diphenhydramine cough syrup on children having cough and sleep difficulty associated with cough. To determine the effects of Linkus polyherbal syrup (group A) and compared with other parallel allopathic groups (Group B and C) for cough on children and associated sleep quality and improvement. 360 children having cough inducted in 3 different groups randomly selected. Three parallel groups were the part of the study. The first study group was the herbal syrup Linkus, second group of children were taking a syrup of multinational pharmaceutical industry having Aminophylline plus Diphenhydramine however the third group received another famous brand having Acefyllin Piperazine with Diphenhydramine. Informed assent and informed consent have taken from the study subjects and their parents. Subjects with acute cough were included in the study however the subjects with chronic cough considered to be excluded. Every group of individual in the study was informed about the investigational drugs provided. Ethnic groups, frequency of cough and diseases illness (<0.05) were determine on every group on the investigational syrup. Cough impact on child and its sleep of three different syrups (every group) were assessed on day1 and day 14(p<0.001) via a likert scale. For the evaluation of pain assessment Wong baker face scale were used and level of significance in each group (p<0.001). Significant results were observed in the Linkus Group as compared to the other parallel groups including Aminophylline plus Diphenhydramine and Acefyllin Piperazine with Diphenhydramine on day 14 (p<0.001). Side effects on group B and group C (Aminophylline with Diphenhydramine and Acefyllin Piperazine with Diphenhydramine) were almost similar in number however Linkus syrup has minimum side effects on study duration. Polyherbal syrup Linkus shows better results in treatment of cough including side effects as compare to the other parallel groups B and C (Aminophylline with Diphenhydramine and Acefyllin Piperazine with Diphenhydramine). For nocturnal sleep Linkus providing better results in cough and associated problems. Pain were significantly reduce on day 14 with the herbal Linkus syrup group A (<0.001). Group B and C found less effective with more side effects as compared to Linkus syrup. Poly herbal Linkus syrup could substantially improve the clinical effect and relieves coughs and benefit lung functions and better sleep facilitation.

Arrhythmias in the paediatric intensive care unit: a prospective study of the rates and predictors of arrhythmias in children without underlying cardiac disease.

OBJECTIVE: Arrhythmias are common in patients admitted to the paediatric intensive care unit. We sought to identify the rates of occurrence and types of arrhythmias, and determine whether an arrhythmia was associated with illness severity and paediatric intensive care unit length of stay. DESIGN: This is a prospective, observational study of all patients admitted to the paediatric intensive care unit at the Children's Hospital at Montefiore from March to June 2012. Patients with cardiac disease or admitted for the treatment of primary arrhythmias were excluded. Clinical and laboratory data were collected and telemetry was reviewed daily. Tachyarrhythmias were identified as supraventricular tachycardia, ventricular tachycardia, and arrhythmias causing haemodynamic compromise or for which an intervention was performed. RESULTS: A total of 278 patients met the inclusion criteria and were analysed. There were 97 incidences of arrhythmia in 53 patients (19%) and six tachyarrhythmias (2%). The most common types of arrhythmias were junctional rhythm (38%), premature atrial contractions (24%), and premature ventricular contractions (22%). Tachyarrhythmias included three supraventricular tachycardia (50%) and three ventricular tachycardia (50%). Of the six tachyarrhythmias, four were related to placement or migration of central venous lines and two occurred during aminophylline infusion. Patients with an arrhythmia had longer duration of mechanical ventilation and paediatric intensive care unit stay (p<0.001). In multivariate analysis, central venous lines (odds ratio 3.1; 95% confidence interval 1.3-7.2, p=0.009) and aminophylline use (odds ratio 5.1; 95% confidence interval 1.7-14.9, p=0.003) were independent predictors for arrhythmias. CONCLUSIONS: Arrhythmias were common in paediatric intensive care unit patients (19%), although tachyarrhythmias occurred rarely (2%). Central venous lines and use of aminophylline were identified as two clinical factors that may be associated with development of an arrhythmia.

Salbutamol or aminophylline for acute severe asthma: how to choose which one, when and why?

Acute, severe exacerbations of asthma present a challenge due to the significant morbidity associated with this presentation. For exacerbations that are refractory to initial treatments with inhaled and oral therapies, there is still doubt about which intravenous therapies are most likely to be helpful. ß-2 agonists and aminophylline have differing mechanisms of action that also affect their adverse effects profiles and these are considered. A review of the available randomised control trials suggests that a bolus of intravenous salbutamol may reduce symptoms and hasten recovery. Aminophylline infusions may improve lung function, and in some studies have been shown to improve symptoms, but the evidence is not clear cut. Decisions about which treatment to use should include risk management considerations such as ease of prescription, preparation and administration factors and availability of high-dependency beds.

Initial experience using aminophylline to improve renal dysfunction in the pediatric cardiovascular ICU.

OBJECTIVE: To determine if aminophylline administration is associated with improved creatinine clearance and greater urine output in children with acute kidney injury in the cardiovascular ICU. DESIGN: Single-center retrospective cohort study. SETTING: Pediatric cardiovascular ICU, university-affiliated children's hospital. PATIENTS: Children with congenital or acquired heart disease in the cardiovascular ICU who received aminophylline to treat oliguric acute kidney injury and fluid overload. INTERVENTIONS: Patients received aminophylline after consultation with a pediatric nephrologist. Data were collected retrospectively over 7 days to assess if aminophylline was associated with improvement in creatinine clearance, urine output, and fluid overload. MEASUREMENTS AND MAIN RESULTS: Thirty-one patients received 52 aminophylline courses. Over the 7-day study period, serum creatinine decreased from a mean of 1.13 ± 0.91 to 0.87 ± 0.83 mg/dL (-0.05 mg/dL/d, p < 0.001). A concomitant increase was seen in estimated glomerular filtration rate from a mean of 50.0 ± 30.0 to 70.6 ± 58.1 mL/min/1.73 m (+3.66 mL/min/1.73 m/d, p < 0.001). Average daily urine output increased by 0.22 mL/kg/hr (p < 0.001), and fluid overload decreased on average by 0.42% per day in the 7-day study period (p = 0.005). Although mean furosemide dose increased slightly (0.12 mg/kg/d, p = 0.01), hydrochlorothiazide dosing did not significantly change over the study period. There were no complications related to aminophylline administration. CONCLUSIONS: Our study suggests that aminophylline therapy may be associated with significantly improved renal excretory function and may augment urine output in children who experience oliguric acute kidney injury in the cardiovascular ICU. Additionally, we did not identify any aminophylline-related side effects in this high-risk cardiac population. Future prospective studies are necessary to confirm the safety profile and to ensure that the beneficial effects are independent of other clinical interventions.

[Comparison of caffeine citrate and aminophylline for treating primary apnea in premature infants].

OBJECTIVE: To investigate the clinical efficacy and safety of caffeine citrate and aminophylline in the treatment of primary apnea in premature infants. METHODS: The clinical data of 125 premature infants with primary apnea from March 2013 to March 2014 were retrospectively analyzed. According to the therapeutic strategy, the patients were divided into caffeine citrate group (n=65) and aminophylline group (n=60). The overall response rates and adverse reaction rates in the two groups were compared. RESULTS: The overall response rate in the caffeine citrate group was 86% (56 cases), which was significantly higher than that in the aminophylline group (72%, 43 cases) (P<0.05). The adverse reactions in the caffeine citrate group included tachycardia (1 case), restlessness (5 cases), feeding intolerance (7 cases), electrolyte disturbance (2 cases), and high blood glucose (5 cases), the incidence of which was significantly lower than that in the aminophylline group (P<0.05). CONCLUSIONS: Caffeine citrate is more effective and causes fewer adverse reactions than aminophylline in the treatment of primary apnea in premature infants.

ß1-Adrenoceptor blocker aggravated ventricular arrhythmia.

OBJECTIVES: To assess the impact of ß1 -adrenoceptor blockers (ß1 -blocker) and isoprenaline on the incidence of idiopathic repetitive ventricular arrhythmia that apparently decreases with preprocedural anxiety. METHODS: From January 2010 to July 2012, six patients were identified who had idiopathic ventricular arrhythmias that apparently decreased (by greater than 90%) with preprocedural anxiety. The number of ectopic ventricular beats per hour (VPH) was calculated from Holter or telemetry monitoring to assess the ectopic burden. The mean VPH of 24 hours from Holter before admission (VPH-m) was used as baseline (100%) for normalization. ß1 -Blockers, isoprenaline, and/or aminophylline were administrated successively on the ward and catheter lab to evaluate their effects on the ventricular arrhythmias. RESULTS: Among 97 consecutive patients with idiopathic ventricular arrhythmias, six had reduction in normalized VPHs in the hour before the scheduled procedure time from (104.6 ± 4.6%) to (2.8 ± 1.6%) possibly due to preprocedural anxiety (P < 0.05), then increased to (97.9 ± 9.7%) during ß1 -blocker administration (P < 0.05), then quickly reduced to (1.6 ± 1.0%) during subsequent isoprenaline infusion. Repeated ß1 -blocker quickly counteracted the inhibitory effect of isoprenaline, and VPHs increased to (120.9 ± 2.4%) from (1.6 ± 1.0%; P < 0.05). Isoprenaline and ß1 -blocker showed similar effects on the arrhythmias in catheter lab. CONCLUSIONS: In some patients with structurally normal heart and ventricular arrhythmias there is a marked reduction of arrhythmias associated with preprocedural anxiety. These patients exhibit a reproducible sequence of ß1 -blocker aggravation and catecholamine inhibition of ventricular arrhythmias, including both repetitive ventricular premature beats and monomorphic ventricular tachycardia.

Aminophylline in pain and migraine.

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.

Addition of intravenous aminophylline to inhaled beta(2)-agonists in adults with acute asthma.

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.

Intravenous beta(2)-agonists versus intravenous aminophylline for acute asthma.

BACKGROUND: Inhaled beta(2)-agonist therapy is central to the management of acute asthma. For rapid bronchodilation in severe cases, penetration of inhaled drug to the affected small conducting airway may be impeded, and the intravenous (IV) rather than inhaled administration of bronchodilators may provide an earlier response. IV beta(2)-agonist agents and IV aminophylline may also be considered as additional interventions in this setting and this review compares IV beta-agonist agents and IV aminophylline in the treatment of people with acute asthma. OBJECTIVES: To compare the benefit of IV beta(2)-agonists versus IV aminophylline for acute asthma treated in the emergency department and in patients admitted to hospital with acute severe asthma. SEARCH METHODS: Randomised controlled trials (RCTs) were identified using the Cochrane Airways Group Register, which is compiled from systematic searches of bibliographic databases as well as handsearching of respiratory journals and conference abstracts. The latest search was run in September 2012. We searched bibliographies from included studies and known reviews were also searched. Primary authors and content experts were contacted to identify eligible studies. SELECTION CRITERIA: We included RCTs of patients who presented to the emergency department with acute asthma, and patients admitted to hospital with acute severe asthma, and were treated with IV beta(2)-agonists versus IV aminophylline. Two review authors independently selected potentially relevant articles and selected articles for inclusion. Methodological quality was independently assessed using two scoring systems and two review authors. DATA COLLECTION AND ANALYSIS: Data were extracted independently by two review authors. Missing data were obtained from authors or calculated from data present in the papers. Trials were combined using a random-effects model for odds ratios (OR) or mean differences (MD) and reported with 95% confidence intervals (95% CI). MAIN RESULTS: Eleven studies met our inclusion criteria and in total they included 350 patients. However, opportunities to combine these studies in meta-analyses were limited by the variations in the range of outcomes reported in the trials.Length of stayTwo studies reported length of stay. They were both paediatric trials (with one in paediatric intensive care unit), and there was no significant difference between the two groups (MD 23.19 hours; 95% CI -2.40 to 48.77 hours; 2 studies; N = 73). Individual separate MD analyses for the two studies also indicated no significant difference between the aminophylline and beta(2)-agonist on this outcome. However, this finding should be interpreted with caution owing to the small number of trials and participants the analysis.Pulmonary functionThere were no significant differences in the sequential or summative pulmonary function demonstrated across the studies.Heart rateData for serial heart rates were reported in three studies at various points from 15 to 60 minutes and in each case there were no significant differences between people in the IV aminophylline or beta(2)-agonist groups. The difference between the two groups with respect to final heart rate was statistically significant (MD 10.00; 95% CI 0.99 to 19.01), although these data are from a single, small study and should be interpreted with caution.Adverse effectsThe analyses for giddiness (OR 59.22; 95% CI 2.80 to 1253.05; 1 study; N = 30), nausea/vomiting (where reported as a combined outcome) (OR 14.18; 95% CI 1.62 to 124.52; 2 studies; N = 96) and nausea (OR 6.53; 95% CI 1.60 to 26.72; 2 studies; N = 49) all significantly favoured beta(2)-agonists. In view of the very small number of studies and number of patients contributing to these analyses these results should be interpreted with caution. A closely related review considering the possible benefits of adding IV aminophylline to beta-agonists in adults with acute asthma also indicates a higher incidence of adverse effects associated with IV aminophylline. AUTHORS' CONCLUSIONS: In the included RCTs there was no consistent evidence favouring either IV beta(2)-agonists or IV aminophylline for patients with acute asthma. The opportunity to draw clear conclusions is limited by the heterogeneity of outcomes evaluated and the small sample sizes in the included studies. It is recommended that these data should be viewed carefully alongside the conclusions from separate Cochrane reviews comparing IV beta(2)-agonists plus inhaled beta(2)-agonists versus inhaled beta(2)-agonists alone and IV aminophylline plus inhaled beta(2)-agonists versus inhaled beta(2)-agonists alone.

Comparative efficacy and safety of caffeine citrate and aminophylline in treating apnea of prematurity: A systematic review and 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.

Efficacy and safety of modified sequential three-step empirical therapy for chronic cough.

BACKGROUND AND OBJECTIVE: Sequential three-step empirical therapy is useful for the management of chronic cough. The purpose of this study was to evaluate the efficacy and safety of modified sequential three-step empirical therapy. METHODS: Consecutive patients (n = 240) with chronic cough were recruited and randomly assigned to receive modified (modified group) or primary (primary group) sequential three-step empirical therapy. The primary end-point was the overall rate of control of chronic cough. Secondary end-points were the rate of control of chronic cough at each step of therapy, the duration of treatment required, changes in cough symptom score, health-related quality of life and possible adverse effects. RESULTS: The study was completed by 106 patients in the modified group and 108 patients in the primary group. The overall rate of control of chronic cough was 88.7% in the modified group and 91.7% in the primary group (chi(2) = 0.54, P > 0.05). There were no obvious differences in the rate of control of cough at each step of therapy, the duration of treatment required, patterns of cough symptom scores or improvements in the health-related quality of life between the modified and primary groups. However, the incidence of drowsiness was significantly lower in the modified group than in the primary group (11.7% vs 21.7%, chi(2) = 4.32, P = 0.04). CONCLUSIONS: Modified three-step empirical therapy was as efficacious as primary three-step therapy for chronic cough, but was preferable because it had fewer side-effects.

Effect of Brewer's yeast-induced pyrexia on aminophylline-elicited convulsions in mice.

Theophylline-associated convulsions have been observed most frequently in children with fever, but the mechanism is not fully understood. In this study, we investigated the basic mechanism of aminophylline [theophylline-2-ethylenediamine]-induced convulsions and the effects of Brewer's yeast-induced pyrexia in mice. Diazepam (5-10mg/kg, i.p.), a benzodiazepine receptor agonist, significantly prolonged the onset and significantly decreased the incidence of convulsions induced by aminophylline (350 mg/kg, i.p.). However, the gamma aminobutyric acid (GABA)A receptor agonist muscimol (1-4 mg/kg, i.p.), the GABAB receptor agonist baclofen (2-4 mg/kg, i.p.) and the N-methyl-D-aspartic acid receptor antagonist dizocilpine (0.1-0.3 mg/kg, i.p.) failed to protect against the convulsions. 20% Brewer's yeast (0.02 ml/g, s.c.) increased body temperature by 1.03, and also significantly shortened the onset and significantly increased the incidence of convulsions induced by aminophylline. The anticonvulsant action of diazepam (2.5-10mg/kg, i.p.) on the convulsions induced by aminophylline was reduced by Brewer's yeast-induced pyrexia. The proconvulsant actions of the GABAA receptor antagonists picrotoxin (3-4 mg/kg, i.p.) and pentylenetetrazol (40-60 mg/kg, i.p.) were enhanced by Brewer's yeast. These results suggest that the anticonvulsant action of diazepam against aminophylline is reduced by Brewer's yeast-induced pyrexia, and that GABAA receptors are involved in the aggravation of the convulsions by Brewer's yeast in mice.

Risk factors for necrotizing enterocolitis in very preterm infants: a case-control study in southwest China.

OBJECTIVE: The objective of this study is to investigate perinatal risk factors for necrotizing enterocolitis (NEC) in very preterm infants. METHODS: This retrospective study included all preterm infants with a gestational age <32 weeks attending our institution from 2013 to 2016. The NEC group comprised patients with NEC enrolled according to the inclusion criteria. Controls were selected from the database and were matched for gender, gestational age, and birth weight. Enumeration data are expressed as percentages (%) and were compared using the χ2 test. Quantitative data are expressed as the mean (standard deviation) and were compared using Student's t-test. Conditional logistic regression analyses were performed to identify the factors significantly associated with NEC. RESULTS: During the study period, 945 very preterm infants were admitted to the neonatal intensive care unit, of whom 46 (4.87%) acquired NEC. A total of 33 cases were enrolled in the NEC group, and 33 controls were selected from the database. Univariate analyses revealed significant differences between groups in the incidence of maternal placenta previa, neonatal infection symptoms, septicemia, and intravenous aminophylline administration (p < .05). Conditional logistic regression analysis demonstrated statistically significant associations of neonatal septicemia (odds ratio [OR] = 4.000, p = .043) and intravenous aminophylline (OR = 4.922, p = .035) with NEC. CONCLUSION: Neonatal septicemia and intravenous aminophylline use are risk factors associated with NEC development in very preterm infants.

Caffeine not associated with irritable behaviour in very low-birth-weight infants.

This paper is an examination of irritable behaviour in very low-birth-weight infants in relation to caffeine or aminophylline. We assessed tremulous movement (a sub-score of General Movements Optimality Score) in 18 caffeine-treated subjects and 18 aminophylline-treated subjects. Caffeine, unlike aminophylline, was not associated with irritable behaviour at standard dose.

Effect of pre-administration with aminophylline on the occurrence of post-dural puncture headache in women undergoing caesarean section by combined spinal-epidural anaesthesia.

OBJECTIVE: To investigate the effect of the pre-administration with aminophylline on the occurrence of post-dural puncture headache (PDPH) in women undergoing caesarean section by combined spinal-epidural anaesthesia (CSEA). METHODS: The study enrolled women undergoing elective caesarean sections with CSEA and randomly allocated them into two groups; for 30 min immediately after the infant was delivered, group A received 250 mg aminophylline intravenously and group B received an equal volume of normal saline. Demographic data, operation time, intraoperative blood loss, intraoperative transfusion volume and the occurrence of PDPH during the first 7 days after the operation were recorded. Side-effects such as hypersensitivity, convulsion and arrhythmia were also recorded in the patients and infants in group A within 24 h after aminophylline administration. RESULTS: A total of 120 patients aged 24-38 years (pregnancy range, 38-42 weeks) were randomly allocated into two groups ( n = 60). The incidence of PDPH in group A was significantly lower than group C (two of 59 [3.4%] versus 10 of 58 [17.2%], respectively). There were no related side-effects within 24 h after aminophylline administration in group A. CONCLUSIONS: Intraoperative intravenous infusion of 250 mg aminophylline reduced the incidence of PDPH after caesarean section under CSEA with no side-effects.