Use Of Methylxanthines Research Articles

Use of caffeine for managing apneia of premature

Apnea of prematurity is a common diagnosis in neonatal intensive care units, especially in preterm patients under 35 weeks or patients born with low birth weight (<1500g). From this perspective, the use of caffeine citrate has short and long-term benefits in this pathology, in addition to reducing the incidence of complications. Methodology: A narrative review of the literature was carried out using the PUBMED database, using the following keywords: “Apnea Prematurity”, “Caffeine” and “Treatment”, with a 6-year filter, analyzing 164 articles, of which only 34 were included and 130 were excluded. Results and Discussion: Apnea of prematurity is a common pathology in preterm and extremely preterm infants, with an incidence of 10% of newborns after 34 weeks and 20-85% of newborns born between 30-34 weeks. The pathophysiology of the disease is explained by the immaturity of the central nervous system in maintaining respiratory drive, in addition to impaired sensitivity in response to chemoreceptors and difficulty in maintaining REM sleep, in addition to the chronic losses inherent to chronic hypoxia. Methylxanthines, the active ingredient in caffeine, have the activation mechanism of inhibiting adenosine A1 and A2 receptors coupled to G protein. The recommended initial dose for therapy is 10 mg/kg for apnea of prematurity, but it must be monitored with concentrations serum levels of the drug to a safe therapeutic range, in addition to monitoring side effects in view of the patient's clinical impairment. The main signs of side effects from the use of caffeine are tachycardia, hyperglycemia, reduced growth rate, jaundice, irritability, agitation and convulsions. Conclusion: Apnea of prematurity is a very prevalent pathology in preterm newborns and its therapeutic possibility must be taken into account in view of its possible short and long-term complications, since the use of methylxanthines has different evidence of clinical improvement.

The use of near-infrared spectroscopy in the acute phase of hypoxic-ischemic encephalopathy in newborns

Detection of new markers of renal hypoperfusion in full-term infants during therapeutic cooling in moderate or severe hypoxic-ischemic encephalopathy to prevent the progression of acute kidney injury (AKI). Aim. To evaluate the significance of using continuous peripheral NIRS monitoring in full-term infants with hypoxic-ischemic encephalopathy for early detection of renal hypoperfusion against the background of prophylactic use of methylxanthines. Materials and methods. A prospective randomized controlled trial was conducted from 2019 to 2022 on the basis of the Neonatal Intensive Care Department of the Zaporizhzhia Regional Clinical Children’s Hospital. We included 50 full-term infants who underwent a program of total therapeutic hypothermia for moderate or severe hypoxic-ischemic encephalopathy. The infants were divided into 2 groups, each receiving methylxanthine to prevent the progression of AKI. Continuous NIRS monitoring of renal and brain tissues was performed throughout the cooling phase and until the end of the warming period. The relationship between NIRS and the development of AKI, which was determined according to the modified neonatal scale KDIGO (2012) by increasing serum creatinine and decreasing urine output during the first 5 days, was studied. Results. NIRS monitoring revealed that changes in cerebral CrSO2 were observed somewhat earlier than renal RrSO2, as the kidneys were less susceptible to autoregulation and perfusion changes than the brain. The level of CrSO2 was identical in 2 groups and did not change after the administration of caffeine citrate or theophylline. The average peripheral renal saturation rates were slightly higher than CrSO2 and tended to increase during the observation period due to the development of renal reperfusion after hypoxia. While the level of renal oxygen extraction decreased. The results obtained indicated that the warming period was characterized by normalization of perfusion, increase in regional renal saturation and decrease in renal oxygen excretion. In general, acute kidney injury in stage I developed in 4 (8.00 %) newborns, and stage II – in 1 (2.00 %), which was equivalent in both study groups (P = 0.8009; U = 299.00). Instead, the other children had stage 0 – 45 (90.00 %). None of the neonates had stage III according to KDIGO (2012) and required renal replacement therapy. Conclusions. The combined use of methylxanthines and the maintenance of optimal postnatal hemodynamics through NIRS diagnostics are vital for the prevention and treatment of acute kidney injury in neonates with moderate or severe hypoxic-ischemic encephalopathy.

Neonatal Acute Kidney Injury.

Acute kidney injury (AKI) is a common occurrence in the neonatal intensive care unit (NICU). In recent years, our knowledge of the incidence and impact of neonatal AKI on outcomes has expanded exponentially. Neonatal AKI has been shown to be associated with adverse outcomes including increased length of mechanical ventilation, prolonged length of stay, and rise in mortality. There has also been increasing work suggesting that neonates with AKI are at higher risk of chronic kidney disease (CKD). In the past, AKI had been defined multiple ways. The utilization of the neonatal modified Kidney Disease: Improving Global Outcomes (KDIGO) criteria as the standard definition for neonatal AKI in research and clinical care has driven the advances in our understanding of neonatal AKI over the last 10 years. This definition has allowed researchers and clinicians to better understand the incidence, risk factors, and outcomes associated with neonatal AKI across populations through a multitude of single-center studies and the seminal, multicenter Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates (AWAKEN) study. As the impacts of neonatal AKI have become clear, a shift in efforts toward identifying those at highest risk, protocolizing AKI surveillance, improving prevention and diagnosis, and expanding kidney support therapy (KST) for neonates has occurred. These efforts also include improving risk stratification (identifying high risk populations, including those with nephrotoxic medication exposure) and diagnostics (novel biomarkers and diagnostic tools). Recent work has also shown that the targeted use of methylxanthines may prevent AKI in a variety of high-risk populations. One of the most exciting developments in neonatal AKI is the advancement in technology to provide KST to neonates with severe AKI. In this comprehensive review we will provide an overview of recent work and advances in the field of neonatal AKI. This will include a detailed review of (1) the definition of neonatal AKI, (2) the epidemiology, risk factors, and outcomes associated with neonatal AKI, (3) improvements in risk stratification and diagnostics, (4) mitigation and treatment, (5) advancements in the provision of KST to neonates, and (6) the incidence and risk of subsequent CKD.

Methylxanthines as Potential Inhibitor of SARS-CoV-2: an In Silico Approach.

The aim of the present study was to test the binding affinity of methylxanthines (caffeine/theine, methylxanthine, theobromine, theophylline and xanthine) to three potential target proteins namely Spike protein (6LZG), main protease (6LU7) and nucleocapsid protein N-terminal RNA binding domain (6M3M) of SARS-CoV-2. Proteins and ligand were generated using AutoDock 1.5.6 software. Binding affinity of methylxanthines with SARS-CoV-2 target proteins was determined using Autodock Vina. MD simulation of the best interacting complexes was performed using GROMACS 2018.3 (in duplicate) and Desmond program version 2.0 (academic version) (in triplicate) to study the stabile interaction of protein–ligand complexes. Among the selected methylxanthines, theophylline showed the best binding affinity with all the three targets of SARS-CoV-2 (6LZG − 5.7 kcal mol−1, 6LU7 − 6.5 kcal mol−1, 6M3M − 5.8 kcal mol−1). MD simulation results of 100 ns (in triplicate) showed that theophylline is stable in the binding pockets of all the selected SARS-CoV-2 proteins. Moreover, methylxanthines are safer and less toxic as shown by high LD50 value with Protox II software as compared to drug chloroquine. This research supports the use of methylxanthines as a SARS-CoV-2 inhibitor. It also lays the groundwork for future studies and could aid in the development of a treatment for SARS-CoV-2 and related viral infections.Graphical abstract Supplementary InformationThe online version contains supplementary material available at 10.1007/s40495-021-00276-3.

Explainable Machine Learning Model for Predicting First-Time Acute Exacerbation in Patients with Chronic Obstructive Pulmonary Disease.

Background: The study developed accurate explainable machine learning (ML) models for predicting first-time acute exacerbation of chronic obstructive pulmonary disease (COPD, AECOPD) at an individual level. Methods: We conducted a retrospective case–control study. A total of 606 patients with COPD were screened for eligibility using registry data from the COPD Pay-for-Performance Program (COPD P4P program) database at Changhua Christian Hospital between January 2017 and December 2019. Recursive feature elimination technology was used to select the optimal subset of features for predicting the occurrence of AECOPD. We developed four ML models to predict first-time AECOPD, and the highest-performing model was applied. Finally, an explainable approach based on ML and the SHapley Additive exPlanations (SHAP) and a local explanation method were used to evaluate the risk of AECOPD and to generate individual explanations of the model’s decisions. Results: The gradient boosting machine (GBM) and support vector machine (SVM) models exhibited superior discrimination ability (area under curve [AUC] = 0.833 [95% confidence interval (CI) 0.745–0.921] and AUC = 0.836 [95% CI 0.757–0.915], respectively). The decision curve analysis indicated that the GBM model exhibited a higher net benefit in distinguishing patients at high risk for AECOPD when the threshold probability was <0.55. The COPD Assessment Test (CAT) and the symptom of wheezing were the two most important features and exhibited the highest SHAP values, followed by monocyte count and white blood cell (WBC) count, coughing, red blood cell (RBC) count, breathing rate, oral long-acting bronchodilator use, chronic pulmonary disease (CPD), systolic blood pressure (SBP), and others. Higher CAT score; monocyte, WBC, and RBC counts; BMI; diastolic blood pressure (DBP); neutrophil-to-lymphocyte ratio; and eosinophil and lymphocyte counts were associated with AECOPD. The presence of symptoms (wheezing, dyspnea, coughing), chronic disease (CPD, congestive heart failure [CHF], sleep disorders, and pneumonia), and use of COPD medications (triple-therapy long-acting bronchodilators, short-acting bronchodilators, oral long-acting bronchodilators, and antibiotics) were also positively associated with AECOPD. A high breathing rate, heart rate, or systolic blood pressure and methylxanthine use were negatively correlated with AECOPD. Conclusions: The ML model was able to accurately assess the risk of AECOPD. The ML model combined with SHAP and the local explanation method were able to provide interpretable and visual explanations of individualized risk predictions, which may assist clinical physicians in understanding the effects of key features in the model and the model’s decision-making process.

Methylxanthine Treatment in Patients Hospitalized for Acute Exacerbation of Chronic Obstructive Pulmonary Disease in China: A Real-World Study Using Propensity Score Matching Analysis.

Background: Although medical guidelines discourage the use of methylxanthines in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD), they are still widely used in clinical practice. This study investigated the real-world use of methylxanthines in the management of AECOPD. Methods: Patient data from the Acute exacerbation of Chronic obstructive pulmonary disease Using REgistry data (ACURE, NCT02657525) study database were screened. Enrolled patients were divided into treatment and control groups. Propensity score (PS) matching and Cox regression analyses were used to minimize confounding factors and determine the association between methylxanthine treatment and the length of stay (LOS). Results: Among the 2088 eligible patients, 1,563 (74.9%) were in the methylxanthine treatment group. Patients treated with methylxanthines had more severe respiratory symptoms and worse lung function than those in the control group. Doxophylline was the most commonly used methylxanthine in both secondary and tertiary hospitals. After PS matching, 966 patients were equally divided into two groups. The LOS of patients in the two groups was similar [median: 8 days, interquartile range (IQR): 7–11 days, p = 0.730]. Patients in the treatment group (median: 8, IQR: 4–12) had a more significant decrease in the COPD Assessment Test score from admission to discharge than those in the control group (median: 6, IQR: 2–10, p < 0.001). Among all matched patients, the LOS was not significantly associated with methylxanthine treatment [adjusted hazard ratio (HR): 1.02, 95% confidence intervals (CIs): 0.89–1.16]. However, in the subgroup analysis, methylxanthines were significantly associated with a short LOS in patients with blood eosinophil count >4% (adjusted HR: 1.56, 95% CIs: 1.12–2.17). Conclusion: This study revealed that methylxanthines, especially doxophylline, are widely used in China. Methylxanthines were effective in improving symptoms in AECOPD patients. Higher blood eosinophil count may be associated with a better efficacy of methylxanthine treatment.

Caffeine for the Treatment of Central Apnea in Trisomy 18: A Case Study in the Novel Use of Methylxanthines in Palliative Transport.

Central apnea is a major cause of death in neonates with trisomy 18 (T18) and is likely due to immaturity of the respiratory drive, similar to the pathological mechanism in apnea of prematurity. Although caffeine has long been used for apnea of prematurity, its use has not yet been reported for infants with T18. Here we describe an infant with T18 receiving comfort-focused care and palliative transport home. Of utmost importance to her family was enabling the patient to spend time at home before her death. However, immediately before transport, she developed severe central apnea, raising concern that she may not survive the transfer. Caffeine was trialed in the hopes of reducing central apnea events. Its use was successful and facilitated safe transport, allowing the patient to uneventfully transition home, where she spent several meaningful weeks with her family before her death.

The risk of development of acute kidney injury in full-term infants with administration of methylxanthines

Exploring new possibilities for the use of methylxanthines to prevent the development of acute kidney injury (AKI) in full-term infants with perinatal asphyxia. Aim: to evaluate the efficacy and safety of methylxanthines in full-term infants for the prevention and conservative treatment of acute kidney injury. Materials and methods. To test the effectiveness of the proposed method of AKI treatment, 38 infants were chosen and divided into 2 groups by random selection. Nursing and intensive care were according to current legislation (Order of the Ministry of Health of Ukraine No. 225 of March 28, 2014). The main group (n = 20) received therapy with caffeine citrate, the comparison group (n = 18) – theophylline. Both of these drugs were used to prevent the development of acute kidney injury – stage II and III according to KDIGO. Results. A significant difference in serum creatinine was found in the main group - the level of serum creatinine was higher than in the comparison group, but did not exceed the physiological norm. GFR on the 3rd day of life was higher with administration of theophylline, but in the group of caffeine did not exceed the reference values of the norm. No differences between urea levels and diuresis rates were found in the groups. The initial results indicate the lack of statistical significance when using various drugs of the methylxanthine group, namely theophylline and caffeine citrate. This is explained by the fact that in the main group 65.00 % (n = 13) of patients had AKI stage 0 according to KDIGO, and 35.00 % (n = 7) had stage I. In the comparison group, 55.56 % (n = 10) and 44.44 % (n = 8), respectively. Stages II and III in both groups of the study did not develop, the obtained data are equivalent – U = 163,00; P = 0,6296. However, the use of caffeine citrate may become a priority due to a better safety profile compared to theophylline. Caffeine is less likely to cause adverse effects in the form of non-pathological bile vomiting and has significantly lower relative risk of non-pathological bile vomiting in infants (RR 0.26 (95 % CI 0.10; 0.66)). Conclusions. Conservative methylxanthine therapy in full-term infants with perinatal asphyxia prevents the development of stages II and III of AKI according to KDIGO. However, it is necessary to continue the collection of material to increase the statistical significance, as well as to study the early and long-term consequences of this therapy.

Influence of selected storage temperatures on wood properties and its biological resistance after the use of methylxanthines

Methylxanthine’s fungicidal properties were investigated, with attention to the temperature of treatment. Caffeine and theophylline treatments of beech and spruce woods were applied for three months in the temperature range of -20 to 40 °C, simulating potential weather conditions in the European region and temperatures specific for various wood applications (cellars, wine cellars, room indoor temperatures, interior trusses). Effects of the selected temperatures were considered without the influence of the other possible factors, which have been considered in previous studies (e.g. effects of temperature in combination with other factors such as UV radiation, humidity, and chemical or biological degradation). Then, the specimens were exposed to a mix of molds and fungi for three months under controlled laboratory conditions in order to analyze a possible subsequent biological attack. The results did not show any effect of temperature of the methylxanthine treatment within the studied range on the organismal activity. Caffeine exhibited a better protective potential than theophylline and was more effective for spruce than for beech. The results indicated the suitability of caffeine for protection of spruce and spruce-based materials in interior applications at a stable temperature without significant effects of UV and humidity.

Methylxanthine use for acute asthma in the emergency department in Japan: a multicenter observational study.

AimMethylxanthines are no longer recommended for emergency department (ED) patients with acute asthma according to international guidelines. We aimed to describe the current methylxanthine use for acute asthma and to determine factors related to its use in the ED.MethodsWe undertook a multicenter retrospective study in 23 EDs across Japan. From each participating hospital, we randomly identified 60 ED patients aged 18–54 years with acute asthma from 2009 through 2011. We examined the associations of ED and patient characteristics with methylxanthine use by constructing a multivariable logistic regression model adjusting for a predefined set of ED‐ and patient‐level factors.ResultsAmong 1,380 patients, methylxanthines were used for 79 patients (5.7%, 95% confidence interval [CI], 4.6–7.0%). The proportion of methylxanthine treatment varied substantially among EDs, ranging from 0% to 26.1%. In the multivariable analysis, the number of annual ED patients with acute asthma (odds ratio [OR] per 100 increase in annual asthma patients, 0.12; 95% CI, 0.04–0.34; P < 0.001) and having a protocol for asthma treatment (OR 2.91; 95% CI, 1.06–8.00; P = 0.04) at the ED level, and systemic corticosteroid use (OR 6.39; 95% CI, 3.34–12.22; P < 0.001) at the patient level were associated with likelihood of methylxanthine use.ConclusionsIn this multicenter study, approximately 6% of ED patients with acute asthma were treated with methylxanthines, with a wide variation across EDs. The number of annual ED patients with acute asthma was significantly associated with a lower likelihood of methylxanthine use, whereas having an ED asthma treatment protocol and systemic corticosteroid use in the ED were associated with a higher likelihood of methylxanthine treatment.

Predictors of Nebulized Arformoterol Treatment: A Retrospective Analysis of Medicare Beneficiaries with Chronic Obstructive Pulmonary Disease*

This study examined sociodemographic and clinical characteristics, treatment patterns, and health resource utilization among Medicare beneficiaries with chronic obstructive pulmonary disease (COPD) to identify predictors of nebulized arformoterol treatment. Using Medicare administrative data from 2010 to 2014, beneficiaries with ≥2 COPD outpatient visits ≥30 d apart or ≥1 COPD-related hospitalization(s) (ICD-9-CM 491.xx, 492.xx, and 496) were identified. Inclusion criteria required ≥1 COPD medication claim(s) and continuous enrollment in Parts A, B, and D. Four cohorts were identified: (a) 11,887 arformoterol users, (b) a subsample of arformoterol users (n = 1,778) who were hospitalized and discharged 30 d before initiating arformoterol, (c) 450,178 controls who had not received arformoterol, and (d) a subsample of controls (n = 21,910) who had hospitalizations. Logistic regression analysis was used to evaluate predictors of arformoterol treatment. The majority of beneficiaries were older than 70 years of age, female, Caucasian, and 47% were dual-eligible. The strongest predictors of arformoterol treatment were oxygen therapy, systemic corticosteroid or methylxanthine use, an exacerbation, a COPD-related hospitalization, and receiving care from a pulmonologist (all p < .001). Dual-eligibility, being a racial/ethnic minority, and having severe psychiatric comorbidity or immunodeficiency lowered the odds of receiving nebulized arformoterol (all p < .001). Among beneficiaries with recent hospitalizations, exacerbations and COPD-related admissions increased the odds of receiving arformoterol (p < .001). Nebulized arformoterol treatment was more likely to be initiated in sicker patients with COPD. Ensuring access to nebulized maintenance therapy is important and particularly warranted for COPD populations with greater medical needs.

Health benefits of methylxanthines in neurodegenerative diseases.

Methylxanthines (MTXs) are consumed by almost everybody in almost every area of the world. Caffeine, theophylline and theobromine are the most well-known members of this family of compounds; they are present, inter alia, in coffee, tea, cacao, yerba mate and cola drinks. MTXs are readily absorbed in the gastrointestinal tract and are able to penetrate into the central nervous system, where they exert significant psychostimulant actions, which are more evident in acute intake. Coffee has been paradigmatic, as its use was forbidden in many diseases, however, this negative view has radically changed; evidence shows that MTXs display health benefits in diseases involving cell death in the nervous system. This paper reviews data that appraise the preventive and even therapeutic potential of MTXs in a variety of neurodegenerative diseases. Future perspectives include the use of MTXs to advance the understanding the pathophysiology of, inter alia, Alzheimer's disease (AD) and Parkinson's disease (PD), and the use of the methylxanthine chemical moiety as a basis for the development of new and more efficacious drugs.

Pentoxifylline and its active metabolite lisofylline attenuate transforming growth factor β1-induced asthmatic bronchial fibroblast-to-myofibroblast transition

Bronchial asthma is characterized by persistent airway inflammation and airway wall remodeling. Among many different cells and growth factors triggering changes in bronchi structure, transforming growth factor β1-induced fibroblast to myofibroblast transition is believed to be very important. The aim of this study was to evaluate whether theophylline (used in asthma therapy) and two other methylxanthines (pentoxifylline and its active metabolite lisofylline), may affect transforming growth factor β1-induced fibroblast to myofibroblast transition in bronchial fibroblasts derived from asthmatic patients. We show here for the first time that selected methylxanthines effectively reduce transforming growth factor β1-induced myofibroblast formation in asthmatic bronchial fibroblast populations. PTX was found to be the most effective methylxanthine. The number of differentiated myofibroblasts after PTX, LSF and THEO administration was reduced at least twofold. Studies on the use of methylxanthines opens a new perspective in the development of novel strategies in asthma therapy through their two-pronged, anti-inflammatory and anti-fibrotic action. In the future they can be considered as promising anti-fibrotic drugs.

Serious complications associated with regadenoson administration for myocardial perfusion imaging

To the Editor, The Editorial by Hage and Iskandrian1 regarding “Serious complications associated with regadenoson administration for myocardial perfusion imaging: A commentary” (September/October 2014 issue) includes a table as a guide for serious complications associated with regadenoson administration. In the table, the authors reported whether or not each listed event occurs with exercise and/or adenosine and that seizures have not been reported with adenosine. Astellas has received spontaneous post-marketing reports of seizures in patients administered adenosine, and the package insert for Adenoscan® was updated in 2005 to reflect these reports. The current package insert includes “seizure” in the Warnings section.2 In addition, there is one published case report of bradyasystole and seizures associated with the use of adenosine to terminate supraventricular tachycardia.3 Astellas would like to clarify that seizures can occur following the administration of adenosine, and prescribers should be aware of this risk and prepared to treat if necessary.2 The use of methylxanthines (e.g., caffeine, aminophylline, and theophylline) is not recommended in patients who experience seizures in association with adenosine and regadenoson.2

The Effect of Acebrophylline vs Sustained Release Theophylline in Patients of COPD- A Comparative Study.

Over the past several decades, the use of drug therapy in COPD has expanded, and provides an optimistic picture. Methyixanthines are used freely in COPD. Of them, Theophylline is an age old bronchodilator and anti-inflammatory agent while Acebrophylline is a newer one. Both are used as add on therapy in management of stable COPD patients on LAMA (long acting muscarinic antagonists like Tiotropium) in present day respiratory practice. This study was designed to compare the efficacy as well as tolerability/side-effects of these two drugs at recommended doses. An open randomized comparative longitudinal study was conducted on 40 moderate degree COPD patients over a period of one year. The patients were randomized into Group-1:receiving Acebrophylline 100mg twice daily and Group-2: receiving sustained release (SR) Theophylline 300mg once daily orally, in addition to 18μgm Tiotropium inhalation per day through metered dose inhaler. Spirometric variables, symptomatic benefit and adverse effects were recorded on three visits (day '0', '21' and '42'). All the data were analyzed by SPSS version 17. A comparable clinical improvement of symptoms score and spirometric parameters with both the drugs has been observed (p-value>0.05). Amount of sputum, frequency of use of reliever medication and dyspnoea showed improvement with both the drugs but cardiovascular side effects are less with Acebrophylline. This study reaffirms the rationale of use of Methylxanthines as add on therapy with LAMA in COPD management and cardiac safety level with Acebrophylline was considerable.

Methylxanthines inhibit late‐onset circulatory collapse in preterm infants

Several drugs, when used chronically in very preterm infants, are considered to be associated with the development of late-onset circulatory collapse (LCC), which can lead to neurodevelopmental impairment. Despite its clinical importance, conclusive risk factors for LCC have yet to be identified. The aim of the present study was to investigate the relationship between LCC and diuretics, methylxanthines, levothyroxine, and sodium chloride. Infants born at <28 weeks gestational age were enrolled and divided into two groups: the LCC group and the non-LCC group. Use of diuretics, methylxanthines, or levothyroxine, and the sodium intake in each infant were recorded. We then determined if these represented primary risk factors associated with the development of LCC, using multivariate analysis to exclude confounding factors. Thirty-seven preterm infants were eligible for this study. LCC developed in 10 infants; 27 infants did not develop the disease. Only methylxanthine was significantly associated with a decrease in the incidence of LCC (odds ratio, 0.04; P < 0.05). We also observed a significant positive correlation between sodium intake and the period from diuretic treatment to LCC onset. Methylxanthine use was significantly associated with LCC onset. Diuretics may have the ability to provoke LCC through sodium wasting, resulting in a negative balance of the electrolyte. The incidence of LCC could be lowered by paying particular attention to infants' sodium balance, and by aggressive methylxanthine treatment.

Methylxanthine use for apnea of prematurity among an international cohort of neonatologists

A recent multinational clinical trial in preterm infants has demonstrated pulmonary and neurodevelopmental benefits from caffeine therapy. Indications for caffeine use in that study were predominantly for treatment of apnea and facilitation of extubation rather than prophylaxis. There are no recent studies that describe current practice of neonatologists and regional differences in regards to indications for starting, monitoring and discontinuing methylxanthine therapy in premature infants. To characterize the spectrum of current practice and demonstrate the extent to which methylxanthine therapy varies by location. A cross-sectional survey of all neonatologists in Thailand, Lebanon, Australia, and a representative sample in the USA regarding management of apnea of prematurity. The response rate was 50% (342/681). The methylxanthine of choice varied greatly across study locations. Prophylactic methylxanthine use is common (62%) among neonatologists in all four study locations. Significant variation exists in almost all aspects of apnea pharmacotherapy practice among neonatologists in different international locations. Prophylactic use of methylxanthine therapy for apnea of prematurity is widespread. We speculate that this expanded use is possibly attributed to the beneficial effects of caffeine therapy in the Caffeine for Apnea of Prematurity (CAP) Trial.

Caffeine therapy for apnoea of prematurity in very low-birthweight infants

Caffeine and other methylxanthines have been used to treat apnoea of prematurity for over 30 years. However, until recently, experimental evidence of the potential harm and lack of rigorous evaluation of this drug therapy in controlled clinical trials resulted in substantial uncertainty about the safety of the routine use of methylxanthines in preterm infants. The international Caffeine for Apnoea of Prematurity (CAP) trial group was formed in 1998. This collaborative research team enrolled over 2000 very low-birthweight infants in North America, Australia and Europe, and followed the children to the end of their second year of life. The CAP trial investigators showed for the first time that neonatal caffeine therapy reduces the rates of important short- and long-term morbidities such as bronchopulmonary dysplasia, severe retinopathy of prematurity, cerebral palsy and cognitive delay. Of all the neonatal treatments that have been subjected to economic evaluations, caffeine therapy is the most certain to be both cost saving and beneficial. It is therefore imperative that responsible drug manufacturers make safe and affordable formulations of caffeine available worldwide.

Effects of prenatal exposure to cigarette smoke on use of xanthine and pneumogram evaluation at discharge in premature infants

Objective: Prenatal exposure to cigarette smoke is associated with an increased risk of sudden infant death syndrome and possible rate increase of obstructive apnea in full-term infants but unknown in premature infants. Therefore, the objective was to study the effect of prenatal exposure to cigarette smoke on the use of methylxanthines and discharge pneumograms in premature infants. Methods: Preterm infants [gestational age (GA) ≤34 weeks] born between January 1997 and September 2007 were studied. A four-channel pneumogram was performed at discharge. Relevant clinical data were collected from the infant’s records. Infants with prenatal exposure to cigarette smoke were compared with infants not exposed (controls). Results: A total of 1656 infants were studied: 263 infants {birth weight (BW) (mean ± SD) 1682 ± 566 g, GA 31.0 ± 2.8 weeks} exposed to prenatal cigarette smoke and 1393 infants (BW 1638 ± 575 g, GA 31.1 ± 2.7 weeks) not exposed. Baseline patient characteristics were similar between the two groups. When comparing the smoking versus control groups, there was no significant difference in the infants for the following: xanthine therapy and abnormal pneumograms; presence of central, obstructed or mixed apnea and home discharge on monitors, oxygen and xanthines. Conclusions: Prenatal exposure to cigarette smoke was not associated with increased use of xanthines or abnormal pneumogram in premature infants.

Losing sleep over the caffeination of prematurity

Losing sleep over the caffeination of prematurity