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.

Aminophylline in combination with caffeine citrate in neurodevelopmental treatment and follow-up of high-risk preterm infants using GMs assessment.

To explore the application effect of aminophylline combined with caffeine citrate and GMs in the evaluation of neurodevelopmental treatment and follow-up in high-risk preterm infants. A retrospective analysis of 66 high-risk preterm infants admitted to Hengshui People's Hospital from January 2020 to June 2021 was conducted. The children who received only conventional treatment were set as the control group, while those who received aminophylline and caffeine citrate on the basis of conventional treatment were set as the experimental group, 33 cases each group; GMs were used to evaluate the neurodevelopmental function of the children, and the treatment effect was analyzed. The normal proportion of GMs assessment results in the twisting phase and restless movement phase of the experimental group was superior to the control group (P<0.05); The proportion of children with normal neurodevelopment in the experimental group was significantly higher than that in the control group (P<0.05). Aminophylline in combination with caffeine citrate can help promote the neurodevelopment of children and improve their physical health using GMs assessment in the treatment and follow-up of high-risk preterm infants.

The effect of preoperative aminophylline on the recovery profile after major pelvic-abdominal surgeries: a randomized controlled double-blinded study.

BACKGROUND: This study compared the effects of premedication with different doses of aminophylline on the recovery profile after general anaesthesia. METHODS: Forty-five patients scheduled for pelvic-abdominal surgeries were divided into 3 groups: Group C: the patients received 100 ml of IV normal saline, Group A1: the patients received 2 mg/kg IV aminophylline, and Group A2: the patients received 4 mg/kg IV aminophylline 30 min before induction of general anaesthesia. The following data were recorded: demographic data, ASA physical status, duration of anaesthesia and surgery, heart rate, mean arterial blood pressure, propofol dose, fentanyl dose, times to reach BIS (48 ± 2) after induction of anaesthesia and to reach a value of 80 after discontinuation of sevoflurane anaesthesia, time to recovery of consciousness and to tracheal extubation and to discharge from the post-anaesthesia care unit, and side effects of aminophylline. RESULTS: The time to reach a BIS of 48 ± 2 was significantly lower for the control group than group A2 (70.67 ± 22.50 and 106.67 ± 34.77 s for groups C and A2, respectively, p -value =0.01). The time to reach a BIS of 80 was significantly longer for the control group than group A1 andA2 (5.6 ± 1.40,3.5 ± 1.93and 2.53 ± 1.72 min for groups C,A1 and A2, respectively, p -value < 0.01). The time to ROC was significantly longer for the control group than groups A1 and A2 (8.93 ± 0.92, 5.6 ± 2.47 and 4.53 ± 3.33 min for groups C, A1 and A2, respectively; p -value < 0.01). The extubation time was significantly longer for the control group than groups A1 and A2 (12.4 ± 1.08, 7.87 ± 3.27 and 6.6 ± 2.47 min for groups C, A1 and A2, respectively; p -value < 0.01). CONCLUSION: Premedication with aminophylline enhanced the recovery profile after pelvic-abdominal surgeries under general anaesthesia without cardiovascular complications. CLINICAL TRIAL REGISTRATION: Name of the registry: Register@ClinicalTrials.gov Trial registration number: ClinicalTrials.gov Identifier: NCT04151381. Date of registration, November 5, 2019, 'Retrospectively registered'.

Análise Comparativa do Padrão de Fluxo de Artérias Coronárias das Hipertrofias Miocárdicas Secundárias e por Mutação Sarcomérica / Comparative Analysis of the Coronary Arteries Flow Pattern in Secondary Myocardial Hypertrophies and by Sarcomeric Mutation

Fundamento: O fluxo coronariano com predomínio diastólico aumenta duas a cinco vezes na hiperemia, mediada por vasodilatação (reserva de fluxo coronariano), podendo, na hipertrofia, ocorrer isquemia relativa. Na hipertrofia secundária, o fluxo em repouso torna-se isquêmico pelo aumento da demanda. Na cardiomiopatia hipertrófica com fibrose perivascular, há funcionalização de vasos colaterais, para aumentar a irrigação dos segmentos hipertrofiados. Objetivo: Determinar o padrão do fluxo coronariano em pacientes com hipertrofia secundária e cardiomiopatia hipertrófica, avaliando a reserva de fluxo coronariano. Métodos: Avaliamos o fluxo coronariano em 34 pacientes com hipertrofia secundária, em 24 com cardiomiopatia hipertrófica e em 16 controles. A artéria descendente anterior foi detectada com Doppler transtorácico com calibração adequada do equipamento. Nos grupos controle e com hipertrofia secundária, foi calculada a reserva de fluxo coronariano com dipiridamol (0,84 mg/kg) endovenoso. O mesmo procedimento foi realizado em seis pacientes do grupo com cardiomiopatia hipertrófica, nos quais também foi avaliado o fluxo das colaterais da região hipertrófica. Os dados foram comparados por variância com significância de 5%. Resultados: Na hipertrofia secundária, houve aumento do índice de massa e, na cardiomiopatia hipertrófica, predominou o aumento da espessura relativa. A fração de ejeção e a disfunção diastólica foram maiores no grupo com cardiomiopatia hipertrófica. A reserva de fluxo coronariano foi menor no grupo com cardiomiopatia hipertrófica, sendo detectado, também, fluxo de colaterais com redução da reserva de fluxo coronariano. Conclusão: A análise da circulação coronariana com Doppler transtorácico é possível em indivíduos normais e hipertróficos. Pacientes com hipertrofia secundária e cardiomiopatia hipertrófica apresentam diminuição da reserva de fluxo coronariano, e aqueles com cardiomiopatia hipertrófica mostram fluxo de vasos colaterais dilatados observados na região hipertrófica, com diminuição da reserva de fluxo coronariano.(AU)

Background: Coronary flow with a diastolic predominance increases two to five times in hyperemia, mediated by vasodilation (coronary flow reserve, CFR) and, in hypertrophy, relative ischemia may occur. In secondary hypertrophy (LVH), the flow, normal at rest, becomes ischemic due to increased demand. In hypertrophic cardiomyopathy (HCM) with perivascular fibrosis, collateral vessels appear to increase the irrigation of hypertrophied segments. Objective: To determine the coronary flow pattern in patients with secondary hypertrophy and hypertrophic cardiomyopathy, evaluating the coronary flow reserve. Methods: Coronary flow was evaluated in 34 patients with secondary hypertrophy, 24 with hypertrophic cardiomyopathy and in 16 controls. The anterior descending artery was detected with transthoracic Doppler with adequate equipment calibration. In the hypertrophic cardiomyopathy group, the flow of collaterals from the hypertrophic region was evaluated. In the control and secondary hypertrophy groups and in six patients in the hypertrophic cardiomyopathy group, the intravenous dipyridamole (0.84 mg) coronary flow reserve was calculated. The data were compared by variance with a significance of 5%Results: In secondary hypertrophy there was an increase in mass index and blood pressure, and in hypertrophic cardiomyopathy an increase in relative thickness predominated. Ejection fraction and diastolic dysfunction were higher in the hypertrophic cardiomyopathy group. The coronary flow reserve was lower in the hypertrophic cardiomyopathy group, and flow of collaterals was also detected, with a reduction in the coronary flow reserve. Conclusion: the analysis of coronary circulation with transthoracic Doppler is possible in normal and hypertrophic individuals. Patients with secondary hypertrophy and hypertrophic cardiomyopathy have a decrease in the coronary flow reserve, and patients with hypertrophic cardiomyopathy show a hyper flow of dilated collateral vessels observed in the hypertrophic region, with a decrease in the coronary flow reserve.(AU)

Theophylline dosing and pharmacokinetics for renal protection in neonates with hypoxic-ischemic encephalopathy undergoing therapeutic hypothermia.

BACKGROUND: Theophylline, a non-selective adenosine receptor antagonist, improves renal perfusion in the setting of hypoxia-ischemia and may offer therapeutic benefit in neonates with hypoxic-ischemic encephalopathy (HIE) undergoing hypothermia. We evaluated the pharmacokinetics and dose-exposure relationships of theophylline in this population to guide dosing strategies. METHODS: A population pharmacokinetic analysis was performed in 22 neonates with HIE undergoing hypothermia who were part of a prospective study or retrospective chart review. Aminophylline (intravenous salt form of theophylline) was given per institutional standard of care for low urine output and/or rising serum creatinine (5 mg/kg intravenous (i.v.) load then 1.8 mg/kg i.v. q6h). The ability of different dosing regimens to achieve target concentrations (4-10 mg/L) associated with clinical response was examined. RESULTS: Birth weight was a significant predictor of theophylline clearance and volume of distribution (p < 0.05). The median half-life was 39.5 h (range 27.2-50.4). An aminophylline loading dose of 7 mg/kg followed by 1.6 mg/kg q12h was predicted to achieve target concentrations in 84% of simulated neonates. CONCLUSIONS: In neonates with HIE undergoing hypothermia, theophylline clearance was low with a 50% longer half-life compared to full-term normothermic neonates without HIE. Dosing strategies need to consider the unique pharmacokinetic needs of this population. IMPACT: Theophylline is a potential renal-protective therapy in neonates with HIE undergoing therapeutic hypothermia; however, the pharmacokinetics and dose needs in this population are not known. Theophylline clearance was low in neonates with HIE undergoing therapeutic hypothermia with a 50% longer half-life compared to full-term normothermic neonates without HIE. As theophylline is advanced in clinical development, dosing strategies will need to consider the unique pharmacokinetic needs of neonates with HIE undergoing therapeutic hypothermia.

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.

Peri-transplant aminophylline in pediatric kidney transplant recipients of donation after brain death: a double-blinded placebo-controlled randomized clinical trial.

BACKGROUND: During kidney transplantation, the transplanted kidney undergoes ischemia reperfusion injury, with adenosine being a major mediator. This study aimed to assess whether aminophylline, an adenosine receptor antagonist, improves early graft function and reduces incidence of delayed graft function (DGF) and slow graft function (SGF). METHODS: Single center, double-blinded, placebo-controlled randomized clinical trial. Pediatric patients admitted for renal transplantation from donation after brain death donors were randomized into a treatment arm receiving aminophylline and a placebo arm receiving normal saline infusions. Primary outcome was estimated glomerular filtration rate (eGFR) at 5 days post-transplant. Secondary outcomes were rates of DGF/SGF and urinary neutrophil gelatinase-associated lipocalin (NGAL) levels. RESULTS: Twenty-three patients were randomized to aminophylline and 27 to placebo. There was no difference in day 5 eGFR, rate of DGF/SGF, or urine NGAL/Creatinine level between aminophylline vs. placebo arm (eGFR 67.39 ± 38.9 ml/min/1.73m2 vs. 80.48 ± 52.1 ml/min/1.73m2p = 0.32; DGF/SGF 5/23 (21.7%) vs. 3/27 (11.1%) p = 0.31; urine NGAL/creatinine 300.5 ng/mg IQR 105.5-1464.5 ng/mg vs. 425.4 ng/mg IQR 140.3-1126.2 ng/mg, p = 0.95; respectively). At 12 months, there was 100% patient survival and 98% graft survival. eGFR at 12 months was similar between the two arms. CONCLUSIONS: There was no benefit in peri-transplant aminophylline administration. Our results are limited by small sample size, since sample calculations were based on primary outcome of day 5 eGFR and low rate of DGF/SGF, which may have precluded us from demonstrating efficacy. Further clinical studies are necessary to determine any benefit of aminophylline in kidney transplant recipients, particularly from high-risk donors.

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 aminophylline on the pharmacokinetics of amikacin in Sprague-Dawley rats.

INTRODUCTION: In most resource-poor settings, amikacin is normally co-administered with aminophylline among preterm newborns with infection and apnea of prematurity. There is the likelihood of an interaction between concurrently administered amikacin that is excreted almost solely via kidneys, and aminophylline, which is known to increase filtration fraction. The aim of this study was to evaluate the effect of aminophylline on the pharmacokinetics of amikacin using an animal model. METHODOLOGY: Twelve male Sprague-Dawley rats (7 - 8 weeks old) were put into 2 equal groups. The test group received amikacin (10 mg/kg/day) with aminophylline (5 mg/kg/day) via the intraperitoneal route, and the control group received only amikacin (10 mg/kg/day) via the same route. On Day 4, after daily administration of drugs, tail vein blood samples were collected at different time points. Serum samples at each time point for each group were pooled and analyzed by fluorescence polarization immunoassay. Non-compartment pharmacokinetic analysis was used to estimate pharmacokinetic parameters. Area under the concentration-time curves (AUCs) were extrapolated from time 0 to infinity (AUC0→∞). Elimination rate constant (Ke) and elimination half-life (t1/2e) were also estimated. RESULTS: Pharmacokinetic parameters of the control group (amikacin only) vis-a-vis the test group were as follows: Cmax; 42.4 µmol/L vs 19.0 µmol/L, AUC0→∞; 84.9 µmol/L/h vs 41.4 µmol/L/h, Ke; 0.12 hours-1 vs 0.24 hours-1, and t1/2; 5.87 hours vs 2.88 hours, respectively. CONCLUSION: This study suggests possible interaction between aminophylline and amikacin. However, further studies need to be conducted in humans to ascertain this finding.

Effects of a topical lotion containing aminophylline, caffeine, yohimbe, l-carnitine, and gotu kola on thigh circumference, skinfold thickness, and fat mass in sedentary females.

BACKGROUND AND OBJECTIVE: Topical aminophylline, caffeine, yohimbe, l-carnitine, and gotu kola (Centella asiatica) may aid in reducing body fat. Lipoxyderm™ contains these ingredients and was used to test if fat loss of the thigh, in conjunction with a low intensity exercise program and restricted calorie intake, was enhanced via the topical application of this lotion. METHODS: This was a double-blind, placebo-controlled, within-group study that investigated the effects of Lipoxyderm™ on thigh fat mass, circumference, and skinfold thickness. Seven participants underwent pre/post-exercise testing for weight, bilateral thigh circumference/skinfold thickness, and body composition/thigh fat mass assessment via dual-energy X-ray absorptiometry. Participants followed a hypocaloric diet, walked 150 minutes/wk, and were randomly assigned to apply a placebo to one leg and Lipoxyderm™ to their other leg for 28 days. Separate two-way mixed factorial repeated measures ANOVAs were used to compare the effects of Lipoxyderm™ to the placebo on thigh circumference, skinfold thickness, and fat mass. RESULTS: A significant time x group interaction was found for thigh circumference (F1,6  = 18.2, P = 0.005), skinfold thickness (F1,6  = 14.6, P = 0.009), and fat mass (F1,6  = 37.1, P = 0.001). CONCLUSIONS: A twice-daily topical application of Lipoxyderm™ for 28 days compared to a placebo combined with a walking program and a restricted caloric intake is more effective at reducing thigh circumference (1.2 vs 0.8 cm), thigh skinfold thickness (3.7 vs 2.0 mm), and thigh fat mass (100.0 g vs 57.3 g).

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.

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.

Aminophylline shortage and current recommendations for reversal of vasodilator stress: an ASNC information statement endorsed by SCMR.

Pharmacologic reversal of serious or intolerable side effects (SISE) from vasodilator stress is an important safety and comfort measure for patients experiencing such effects. While typically performed using intravenous aminophylline, recurrent shortages of this agent have led to a greater need to limit its use and consider alternative agents. This information statement provides background and recommendations addressing indications for vasodilator reversal, timing of a reversal agent, incidence of observed SISE with vasodilator stress, clinical and logistical considerations for aminophylline-based reversal, and alternative non-aminophylline based reversal protocols.

Intravenous regadenoson with aminophylline reversal is safe and equivalent to intravenous adenosine infusion for fractional flow reserve measurements.

BACKGROUND: Small studies have shown that adenosine is equivalent to regadenoson when obtaining coronary fractional flow reserve (FFR) measurements. A study that also evaluates time and safety of aminophylline reversal of regadenoson effects has not been presented. HYPOTHESIS: Reversal of regadenoson with aminophylline is safe and equivalent to adenosine for FFR measurements. METHODS: Forty-six consecutive patients who underwent clinically indicated FFRs at the time of coronary angiography were enrolled between 4/2012 and 5/2014. Each patient had FFR measured using adenosine 140 mcg/kg/min IV, and following return to baseline, FFR was measured using regadenoson 400 mcg IV, which then was reversed with aminophylline 150 mg IV. Time to baseline hemodynamics was measured. Agreement between the two assessments was compared using linear regression. RESULTS: FFR results were similar with both agents (R2 = 0.935, P < 0.0001). Also, using the 0.80 cutoff for significantly depressed FFR, there was no divergence regarding studies' significance. After aminophylline reversal of regadenoson, hemodynamics returned to baseline in 111 ± 71 seconds. There were no unexpected side effects or complications. CONCLUSIONS: For FFR measurement, regadenoson and adenosine are equivalent hyperemic agents. Regadenoson with aminophylline reversal may be considered as an alternative to adenosine for FFR measurements.

No Requirement for Targeted Theophylline Levels for Diuretic Effect of Aminophylline in Critically Ill Children.

OBJECTIVES: To determine the relationship between theophylline trough levels and urine output in critically ill children administered aminophylline as adjunctive diuretic therapy. DESIGN: Retrospective cohort study. SETTING: The PICU of a tertiary care children's hospital. PATIENTS: A mixed population of medical/surgical including postoperative cardiothoracic surgery patients less than 18 years old. INTERVENTIONS: Electronic medical records of all PICU patients admitted from July 2010 to June 2015 were reviewed, and patients who received aminophylline as diuretic therapy were identified. MEASUREMENTS AND MAIN RESULTS: Patient cohort data including demographics, daily aminophylline, furosemide and chlorothiazide dosing, theophylline trough levels, fluid intake, urine output and total fluid balance, blood urea nitrogen, and creatinine levels were abstracted. Multivariate analysis based on a generalized estimating equations approach demonstrated that aminophylline administration, when analyzed as a categorical variable, was associated with an increase in urine output and decreased fluid balance. However, aminophylline dosing, when analyzed as a continuous variable, was associated with neither an increase in urine output nor decreased fluid balance. Theophylline trough levels were not correlated with urine output at 24 hours (p = 0.78) and were negatively correlated with urine output at 48 hours (r = 0.078; p < 0.005). CONCLUSIONS: Aminophylline administration provided a measure of increased diuresis, regardless of dosage, and theophylline trough levels. Therefore, achieving a prescribed therapeutic trough level may not be necessary for full diuretic effect. Because, as opposed to the diuretic effect, the side effect profile of aminophylline is dose-dependent, low maintenance dosing may optimize the balance between providing adjunctive diuretic effect while minimizing the risk of toxicity.

Aminophylline for Preventing Bradyarrhythmias During Orbital or Rotational Atherectomy of the Right Coronary Artery.

BACKGROUND: Coronary atherectomy, orbital or rotational, is frequently used for plaque modification in patients with heavily calcified lesions. Atherectomy can be associated with clinically significant bradyarrhythmias or transient atrioventricular block requiring temporary pacemaker insertion, mainly in lesions involving the right coronary artery or a dominant left circumflex artery. Bradyarrhythmias may be mediated by endogenous release of adenosine from red blood cell breakdown. Aminophylline, an adenosine antagonist, can prevent adenosine-mediated bradyarrhythmias. METHODS: This retrospective analysis examined 7 patients in whom aminophylline (250-300 mg intravenously over 10 min) was administered before coronary atherectomy. The study endpoint was the occurrence of any bradyarrhythmia. RESULTS: Orbital atherectomy was used in 3 cases, rotational atherectomy was used in 3 cases, and both systems were used in 1 case. Technical success was 100% and all patients had Thrombolysis in Myocardial Infarction 3 flow at the end of the procedure. Preprocedural aminophylline administration successfully prevented bradyarrhythmias or atrioventricular block in all cases. CONCLUSIONS: Intravenous aminophylline represents a simple, safe, widely available, and low-cost intervention for preventing bradyarrhythmias during atherectomy of the right coronary artery or a dominant circumflex artery.

[Comparative Study of the Efficacy and Safety of Caffeine and Aminophylline for the Treatment of Apnea in Preterm Infants].

　Methylxanthine is widely administered for the treatment of apnea of prematurity in many countries, and previous reports have clearly established that caffeine is effective for the treatment of apnea of prematurity. In Japan, caffeine has been available since December 2014. Thus, we compared the efficacy and safety of caffeine with that of aminophylline in our hospital. There was no significant difference between the caffeine group and aminophylline group regarding the characteristics of the study patients. The mean efficacy rate from day 1 to day 10 was 89.5% in the caffeine group, and 81.9% in the aminophylline group, although the rate of improvement in apnea episodes each day from day 1 to day 10 was not significantly different between the two groups. On the other hand, the adverse event rates in the caffeine group and the aminophylline group were 70.6% and 75.0%, respectively. No significant difference was observed in the adverse event rates between the two groups. Moreover, suspected abdominal distension due to the drug administration was more frequently observed with the aminophylline group. Our findings indicate that caffeine is as effective as aminophylline, while it is superior to aminophylline regarding its overall safety.

Reversal of Ticagrelor-Induced Arrhythmias and Cheyne-Stokes Respiration With Aminophylline Infusion.

Dyspnea and bradyarrhythmias are frequent adverse effects (AEs) of ticagrelor. AEs commonly occur within the first week of therapy, are dose related and usually mild, but sometimes they may cause drug discontinuation. Currently, the exact mechanisms of ticagrelor-related AEs have not been definitively explained. In addition to the prevalent theory of adenosine overload, other reasonable mechanism like a direct central stimulation hypothesis was suggested. We present a case of incessant Cheyne-Stokes respiration associated with heart rate instability in patient with congestive heart failure and non-ST-segment elevation myocardial infarction, supporting the use of aminophylline as a potential reversal agent of ticagrelor-related AEs.

An interquartile relationship between polyherbal extract based lozenges linkus a phase IV comparative randomised control trial.

The aim of the study is to determine the efficacy of polyherbal linkus with the other pharmaceutical marketed syrup having Acefyllin Piperazine, Diphenhydramine group and Aminophylline Diphenhydramine group on the basis of interquartile ranges on children. It was open label multi centric randomize control trial. The study was conducted on different private schools of East and West Malir, Karachi Pakistan with the special approval from the school's honors .informed consent and assents were taking before the enrollment of the study subjects .The study enrolled participants were 147 who evaluate on cough. Participants were divided into 3 interventional group according to the treatment regimen .One group of participant received Linkus Syrup however the 2nd group received Acefyllin Piperazine and 3rd group received Aminophylline Diphenhydramine group. The frequency of the cough on linkus syrup was considered to be achieved on the basis of interquartile relationship and impact has been observed on child and parent sleep and found significant (p <0.01).Poly herbal Linkus Syrup has the significant impact on cough frequency and associated problem on children and parent's sleep with minimum side effects (p<0.01) however the pharmacological treatments are considered to be more unwanted effects on human subjects.