Effects of aminophylline therapy on urine output and kidney function in children with acute kidney injury.

BACKGROUND: Acute kidney injury (AKI) is a frequent complication of children admitted to the paediatric intensive care unit. One key management modality of AKI is the use of diuretics to reduce fluid overload. Aminophylline, a drug that is well known for its use in the treatment of bronchial asthma, is also purported to have diuretic effects on the kidneys. This retrospective cohort study assesses the effect of aminophylline in critically ill children with AKI. METHODS: A retrospective chart review of children admitted to the paediatric intensive care unit of the Red Cross War Memorial Children's Hospital (RCWMCH) with AKI who received aminophylline (from 2012 to June 2018) was carried out. Data captured and analyzed included demographics, underlying disease conditions, medications, urine output, fluid balance, and kidney function. RESULTS: Data from thirty-four children were analyzed. Urine output increased from a median of 0.4 mls/kg/hr [IQR: 0.1, 1.1] at six hours prior to aminophylline administration to 0.6 mls/kg/hr [IQR: 0.2, 1.9] at six hours and 1.6 mls/kg/hr [IQR:0.2, 4.2] at twenty-four hours post aminophylline therapy. The median urine output significantly varied across the age groups over the 24-h time period post-aminophylline, with the most response in the neonates. There was no significant change in serum creatinine levels six hours post-aminophylline administration [109(IQR: 77, 227)-125.5(IQR: 82, 200) micromole/l] P-value = 0.135. However, there were significant age-related changes in creatinine levels at six hours post-aminophylline therapy. CONCLUSIONS: Aminophylline increases urine output in critically ill children with AKI. A higher resolution version of the Graphical abstract is available as Supplementary information.

[Clinical effect of Shenfu injection combined with glucocorticoid on patients with acute left heart failure complicated with bronchospasm].

OBJECTIVE: To investigate the clinical effect of Shenfu injection combined with glucocorticoid in the treatment of acute left heart failure complicated with bronchospasm. METHODS: A prospective study was conducted.Ninety patients with acute left heart failure complicated with bronchospasm admitted to Huai'an Second People's Hospital from January 2021 to July 2022 were selected and divided into conventional treatment group, hormone therapy group and combined treatment group according to random number table method, with 30 cases in each group. All patients in the 3 groups received basic Western medicine treatment. On this basis, the conventional treatment group was given 0.25-0.50 g aminophylline injection plus 5% glucose injection or 0.9% sodium chloride injection (diabetes patients) 100 mL slow intravenous infusion, 1-2 times a day. In the hormone treatment group, 1 mg of budesonide suspension for inhalation was diluted to 2 mL by 0.9% sodium chloride injection, twice a day, and applied until 48 hours after the pulmonary wheezing disappeared. The combined treatment group was given glucocorticoid combined with Shenfu injection 80 mL plus 5% glucose injection or 0.9% sodium chloride injection (diabetes patients) 250 mL intravenously, once a day. All treated for 1 week. The general data, traditional Chinese medicine (TCM) syndrome score, TCM syndrone efficacy index, acute left heart failure efficacy, bronchospasm efficacy, systolic blood pressure (SBP), mean arterial pressure (MAP), serum N-terminal pro-brain natriuretic peptide (NT-proBNP) level and safety of the 3 groups were compared. The patients were followed up for 6 months, and the mortality and re-hospitalization rate of the 3 groups were recorded. RESULTS: Among the 90 patients, a total of 83 patients completed the study, excluding the cases dropped due to death and other reasons. There were 29 cases in the combined treatment group, 25 cases in the hormone therapy group and 29 cases in the conventional treatment group. There were no significant differences in age, gender, course of disease, and previous history (history of diabetes, history of hypertension, history of hyperlipidemia) among the 3 groups. Therefore, they were comparable. The difference of TCM syndrome score before and after treatment, TCM syndrome efficacy index of combined treatment group and hormone therapy group were higher than those of conventional treatment group [difference of TCM syndrome score: 15.14±5.74, 13.24±5.75 vs. 10.62±5.87, TCM syndrome efficacy index: (67.84±14.31)%, (59.94±14.26)% vs. (48.92±16.74)%, all P < 0.05], and the difference of TCM syndrome score and TCM syndrome efficacy index of combined treatment group were higher than those of hormone treatment group (both P < 0.05). The total effective rate of acute left heart failure and bronchospasm in the combined treatment group was significantly higher than that in the conventional treatment group (total effective rate of acute left heart failure: 96.55% vs. 75.86%, total effective rate of bronchospasm: 93.10% vs. 65.52%, both P < 0.05). The difference of serum NT-proBNP before and after treatment in combination therapy group and hormone therapy group was significantly higher than that in conventional treatment group (ng/L: 7 922.86±5 220.31, 7 314.92±4 450.28 vs. 4 644.79±3 388.23, all P < 0.05), and the difference of serum NT-proBNP before and after treatment in the combined treatment group was significantly higher than that in the hormone treatment group (P < 0.05). There were no significant differences in SBP difference, MAP difference, mortality and re-hospitalization rate among the 3 groups. No adverse reactions occurred in the 3 groups during treatment. CONCLUSIONS: Shenfu injection combined with glucocorticoid is effective in the treatment of patients with acute left heart failure complicated with bronchospasm. It is superior to glucocorticoid and aminophylline in relieving bronchospasm, reducing NT-proBNP level and improving total effective rate, and has good prognosis and safety.

Doxapram for the prevention and treatment of apnea in preterm infants.

BACKGROUND: Apnea of prematurity is a common problem in preterm infants that may have significant consequences on their development. Methylxanthines (aminophylline, theophylline, and caffeine) are effective in the treatment of apnea of prematurity. Doxapram is used as a respiratory stimulant in cases refractory to the methylxanthine treatment. OBJECTIVES: To evaluate the benefits and harms of doxapram administration on the incidence of apnea and other short-term and longer-term clinical outcomes in preterm infants. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was March 2023. SELECTION CRITERIA: We included randomized controlled trials (RCTs) assessing the role of doxapram in prevention and treatment of apnea of prematurity and prevention of reintubation in preterm infants (less than 37 weeks' gestation). We included studies comparing doxapram with either placebo or methylxanthines as a control group, or when doxapram was used as an adjunct to methylxanthines and compared to methylxanthines alone as a control group. We included studies of doxapram at any dose and route. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were clinical apnea, need for positive pressure ventilation after initiation of treatment, failed apnea reduction after two to seven days, and failed extubation (defined as unable to wean from invasive intermittent positive pressure ventilation [IPPV] and extubate or reintubation for IPPV within one week). We used GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: We included eight RCTs enrolling 248 infants. Seven studies (214 participants) provided data for meta-analysis. Five studied doxapram for treatment of apnea in preterm infants. Three studied doxapram to prevent reintubation in preterm infants. None studied doxapram in preventing apnea in preterm infants. All studies administered doxapram intravenously as continuous infusions. Two studies used doxapram as an adjunct to aminophylline compared to aminophylline alone and one study as an adjunct to caffeine compared to caffeine alone. When used to treat apnea, compared to no treatment, doxapram may result in a slight reduction in failed apnea reduction (risk ratio [RR] 0.45, 95% confidence interval [CI] 0.20 to 1.05; 1 study, 21 participants; low-certainty evidence). The evidence is very uncertain about the effect of doxapram on need for positive pressure ventilation after initiation of treatment (RR 0.31, 95% CI 0.01 to 6.74; 1 study, 21 participants; very low-certainty evidence). Doxapram may result in little to no difference in side effects causing cessation of therapy (0 events in both groups; risk difference [RD] 0.00, 95% CI -0.17 to 0.17; 1 study, 21 participants; low-certainty evidence). Compared to alternative treatment, the evidence is very uncertain about the effect of doxapram on failed apnea reduction (RR 1.35, 95% CI 0.53 to 3.45; 4 studies, 84 participants; very low-certainty evidence). The evidence is very uncertain about the effect of doxapram on need for positive pressure ventilation after initiation of treatment (RR 2.40, 95% CI 0.11 to 51.32; 2 studies, 37 participants; very-low certainty evidence; note 1 study recorded 0 events in both groups. Thus, the RR and CIs were calculated from 1 study rather than 2). Doxapram may result in little to no difference in side effects causing cessation of therapy (0 events in all groups; RD 0.00, 95% CI -0.15 to 0.15; 37 participants; 2 studies; low-certainty evidence). As adjunct therapy to methylxanthine, the evidence is very uncertain about the effect of doxapram on failed apnea reduction after two to seven days (RR 0.08, 95% CI 0.01 to 1.17; 1 study, 10 participants; very low-certainty evidence). No studies reported on clinical apnea, chronic lung disease at 36 weeks' postmenstrual age (PMA), death at any time during initial hospitalization, long-term neurodevelopmental outcomes in the three comparisons, and need for positive pressure ventilation and side effects when used as adjunct therapy to methylxanthine. In studies to prevent reintubation, when compared to alternative treatment, the evidence is very uncertain about the effect of doxapram on failed extubation (RR 0.43, 95% CI 0.10 to 1.83; 1 study, 25 participants; very low-certainty evidence). As adjunct therapy to methylxanthine, doxapram may result in a slight reduction in 'clinical apnea' after initiation of treatment (RR 0.36, 95% CI 0.13 to 0.98; 1 study, 56 participants; low-certainty evidence). Doxapram may result in little to no difference in failed extubation (RR 0.92, 95% CI 0.52 to 1.62; 1 study, 56 participants; low-certainty evidence). The evidence is very uncertain about the effect of doxapram on side effects causing cessation of therapy (RR 6.42, 95% CI 0.80 to 51.26; 2 studies, 85 participants; very low-certainty evidence). No studies reported need for positive pressure ventilation, chronic lung disease at 36 weeks' PMA, long-term neurodevelopmental outcomes in the three comparisons; failed extubation when compared to no treatment; and clinical apnea, death at any time during initial hospitalization, and side effects when compared to no treatment or alternative treatment. We identified two ongoing studies, one conducted in Germany and one in multiple centers in the Netherlands and Belgium. AUTHORS' CONCLUSIONS: In treating apnea of prematurity, doxapram may slightly reduce failure in apnea reduction when compared to no treatment and there may be little to no difference in side effects against both no treatment and alternative treatment. The evidence is very uncertain about the need for positive pressure ventilation when compared to no treatment or alternative treatment and about failed apnea reduction when used as alternative or adjunct therapy to methylxanthine. For use to prevent reintubation, doxapram may reduce apnea episodes when administered in adjunct to methylxanthine, but with little to no difference in failed extubation. The evidence is very uncertain about doxapram's effect on death when used as adjunct therapy to methylxanthine and about failed extubation when used as alternative or adjunct therapy to methylxanthine. There is a knowledge gap about the use of doxapram as a therapy to prevent apnea. More studies are needed to clarify the role of doxapram in the treatment of apnea of prematurity, addressing concerns about long-term outcomes. The ongoing studies may provide useful data.

Caffeine versus other methylxanthines for the prevention and treatment of apnea in preterm infants.

BACKGROUND: Methylxanthines, including caffeine, theophylline, and aminophylline, work as stimulants of the respiratory drive, and decrease apnea of prematurity, a developmental disorder common in preterm infants. In particular, caffeine has been reported to improve important clinical outcomes, including bronchopulmonary dysplasia (BPD) and neurodevelopmental disability. However, there is uncertainty regarding the efficacy of caffeine compared to other methylxanthines. OBJECTIVES: To assess the effects of caffeine compared to aminophylline or theophylline in preterm infants at risk of apnea, with apnea, or in the peri-extubation phase. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, Epistemonikos, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), and clinicaltrials.gov in February 2023. We also checked the reference lists of relevant articles to identify additional studies. SELECTION CRITERIA: Studies: randomized controlled trials (RCTs) and quasi-RCTs Participants: infants born before 34 weeks of gestation for prevention and extubation trials, and infants born before 37 weeks of gestation for treatment trials Intervention and comparison: caffeine versus theophylline or caffeine versus aminophylline. We included all doses and duration of treatment. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We evaluated treatment effects using a fixed-effect model with risk ratio (RR), risk difference (RD), and 95% confidence intervals (CI) for categorical data, and mean, standard deviation, and mean difference for continuous data. We used the GRADE approach to evaluate the certainty of evidence. MAIN RESULTS: We included 22 trials enrolling 1776 preterm infants. The indication for treatment was prevention of apnea in three studies, treatment of apnea in 13 studies, and extubation management in three studies. In three studies, there were multiple indications for treatment, and in one study, the indication for treatment was unclear. In 19 included studies, the infants had a mean gestational age between 28 and 32 weeks and a mean birth weight between 1000 g and 1500 g. One study's participants had a mean gestational age of more than 32 weeks, and two studies had participants with a mean birth weight of 1500 g or more. Caffeine administrated for any indication may result in little to no difference in all-cause mortality prior to hospital discharge compared to other methylxanthines (RR 1.12, 95% CI 0.68 to 1.84; RD 0.02, 95% CI -0.05 to 0.08; 2 studies, 396 infants; low-certainty evidence). Only one study enrolling 79 infants reported components of the outcome moderate to severe neurodevelopmental disability at 18 to 26 months. The evidence is very uncertain about the effect of caffeine on cognitive developmental delay compared to other methylxanthines (RR 0.17, 95% CI 0.02 to 1.37; RD -0.12, 95% CI -0.24 to 0.01; 1 study, 79 infants; very low-certainty evidence). The evidence is very uncertain about the effect of caffeine on language developmental delay compared to other methylxanthines (RR 0.76, 95% CI 0.37 to 1.58; RD -0.07, 95% CI -0.27 to 0.12; 1 study, 79 infants; very low-certainty evidence). The evidence is very uncertain about the effect of caffeine on motor developmental delay compared to other methylxanthines (RR 0.50, 95% CI 0.13 to 1.96; RD -0.07, 95% CI -0.21 to 0.07; 1 study, 79 infants; very low-certainty evidence). The evidence is very uncertain about the effect of caffeine on visual and hearing impairment compared to other methylxanthines. At 24 months of age, visual impairment was seen in 8 out of 11 infants and 10 out of 11 infants in the caffeine and other methylxanthines groups, respectively. Hearing impairment was seen in 2 out of 5 infants and 1 out of 1 infant in the caffeine and other methylxanthines groups, respectively. No studies reported the outcomes cerebral palsy, gross motor disability, and mental development. Compared to other methylxanthines, caffeine may result in little to no difference in BPD/chronic lung disease, defined as 28 days of oxygen exposure at 36 weeks' postmenstrual age (RR 1.40, 95% CI 0.92 to 2.11; RD 0.04, 95% CI -0.01 to 0.09; 3 studies, 481 infants; low-certainty evidence). The evidence is very uncertain about the effect of caffeine on side effects (tachycardia, agitation, or feed intolerance) leading to a reduction in dose or withholding of methylxanthines compared to other methylxanthines (RR 0.17, 95% CI 0.02 to 1.32; RD -0.29, 95% CI -0.57 to -0.02; 1 study, 30 infants; very low-certainty evidence). Caffeine may result in little to no difference in duration of hospital stay compared to other methylxanthines (median (interquartile range): caffeine 43 days (27.5 to 61.5); other methylxanthines 39 days (28 to 55)). No studies reported the outcome seizures. AUTHORS' CONCLUSIONS: Although caffeine has been shown to improve important clinical outcomes, in the few studies that compared caffeine to other methylxanthines, there might be little to no difference in mortality, bronchopulmonary dysplasia, and duration of hospital stay. The evidence is very uncertain about the effect of caffeine compared to other methylxanthines on long-term development and side effects. Although caffeine or other methylxanthines are widely used in preterm infants, there is little direct evidence to support the choice of which methylxanthine to use. More research is needed, especially on extremely preterm infants born before 28 weeks of gestation. Data from four ongoing studies might provide more evidence on the effects of caffeine or other methylxanthines.

A mix of aminophylline and heparin plus nitroglycerin can reduce bradycardia during rotational atherectomy on the right coronary artery and dominant circumflex artery.

BACKGROUND: Rotational atherectomy (RA) may cause bradyarrhythmias and transitory atrioventricular block when performed in the right coronary artery (RCA) or a dominant circumflex (CX) coronary artery. However, there are no studies of a solution that can prevent coronary flow deterioration and bradycardia complications that may occur during RA. We aimed to create an alternative rota-flush solution to minimize the risk of bradycardia and complete atrioventricular block (AVB) that can occur during RA. MATERIALS AND METHODS: The study comprised 60 patients who were randomly divided into two groups: 30 received rotaphylline (= 240 mg aminophylline, 10,000 U unfractionated heparin, and 2000 mcg nitroglycerin to 1000 mL saline), and 30 received the traditional rota-flush (= 10,000 U unfractionated heparin, 2000 mcg nitroglycerin, and 1000 mL saline). The incidence of bradycardia or high-grade AVB (HAVB) during RA, coronary slow-flow phenomenon or no-reflow phenomenon, and coronary spasm were the primary endpoints of the study. Procedure success and RA-related procedural complications were secondary endpoints. RESULTS: The use of rotaphylline was an independent predictor of bradycardia and HAVB after accounting for all other factors (OR: 0.47, 95% CI: 0.24-0.79, p < 0.001). Lesion length (OR: 2.17, 95% CI: 1.24-3.04, p < 0.001), burr-to-artery ratio (OR: 0.59, 95% CI: 0.39-1.68, p < 0.001), and total run duration (OR: 0.79, 95% CI: 0.35-1.43, p < 0.001) were additional independent predictors. CONCLUSION: Bradycardia and the development of HAVB may be avoided by rotaphylline intracoronary infusion during RA applied to the RCA and dominant CX lesions. Multicenter studies including sizable patient populations should be conducted to validate the present findings.

Safety and efficacy of IV theophylline for regadenoson-associated side effect reversal.

BACKGROUND: Aminophylline injection has been on an intermittent nation-wide shortage due to manufacturing delays leaving a need for an alternative reversal agent for regadenoson-associated side effects. Intravenous theophylline should be a logical acceptable pharmacological alternative; however, data regarding its safety and efficacy as a reversal agent are lacking. METHODS: Utilizing electronic medical records at the University of Colorado hospital, we identified patients ≥ 18 years of age who had a pharmacologic stress test using regadenoson during periods of aminophylline shortage (3/1/2013 to 5/31/2013 and 4/1/2018 to 8/30/2018) in which theophylline was used as an alternative antidote for side effect reversal. Intravenous theophylline was prepared by the inpatient pharmacy to a concentration of 0.8 mg/mL in a total volume of 100 mL D5W. Specific side effects and side effect resolution were evaluated. RESULTS: Of the 122 patients evaluated, theophylline was administered in doses ranging from 40 to 75 mg with the majority receiving 40 mg. Complete resolution of regadenoson side effects occurred in 98 patients with 12 experiencing partial resolution and 1 without resolution. No adverse effects or events were reported. CONCLUSION: Due to limited availability of aminophylline, theophylline may be a safe and effective alternative to reverse regadenoson-associated side effects.

The diuretic effect of adding aminophylline or theophylline to furosemide in pediatric populations: a systematic review.

The diuretic effect of the combined furosemide and aminophylline/theophylline among pediatric patients remains unclear. The primary aim of this systematic review was to examine the clinical diuretic effects (urine output and fluid balance) of co-administration of furosemide and aminophylline/theophylline as compared to furosemide alone in pediatric population. Ovid MEDLINE, CENTRAL, and EMBASE were searched from its inception until March 2022 for observational studies and randomized controlled trials (RCTs) comparing the administration of furosemide versus furosemide and aminophylline/theophylline in pediatric population. Case reports, case series, commentaries, letters to editors, systematic reviews, and meta-analyses were excluded. Five articles with a total sample population of 187 patients were included in this systematic review. As compared to the furosemide alone, our pooled data demonstrated that co-administration of furosemide and aminophylline/theophylline was associated with higher urine output (mean difference: 2.91 [90% CI 1.54 to 4.27], p < 0.0001, I2 = 90%) and a more negative fluid balance (mean difference - 28.27 [95% CI: - 46.21 to - 10.33], p = 0.002, I2 = 56%) than those who received furosemide alone. CONCLUSION: This is the first paper summarizing the evidence of combined use of furosemide with aminophylline/theophylline in pediatric population. Our systematic review demonstrated that the co-administration of furosemide and aminophylline/theophylline could potentially yield better diuretic effects of urine output and negative fluid balance than furosemide alone in pediatric patients with fluid overload. Given the substantial degree of heterogeneity and low level of evidence, future adequately powered trials are warranted to provide evidence regarding the combined use of aminophylline/theophylline and furosemide as diuretic in the pediatric population. WHAT IS KNOWN: • Fluid overload is associated with poor prognosis for children in the intensive care unit. • The ineffective result of furosemide alone, even at high dose, as diuretic agent for children with diuretic resistant fluid overload in the intensive care unit. WHAT IS NEW: • This is the first systematic review that compares furosemide alone and co-administration of furosemide and aminophylline/theophylline. • This paper showed potential benefit of co-administration of furosemide and aminophylline/theophylline promoting urine output and negative fluid balance compared to furosemide alone.

Effects of early aminophylline therapy on clinical outcomes in premature infants.

BACKGROUND: Aminophylline use and the association between clinical outcomes and therapy timing have been less investigated. The objective of this study was to determine the efficacy of early aminophylline use (within the first two days of life) in premature infants. METHOD: A retrospective observational cohort of infants weighing <1500 g and <30 weeks of gestational age at Kaohsiung Veterans General Hospital received aminophylline either within the first two days of life (EA, early aminophylline group), after the third day of life (LA, late aminophylline group), or without aminophylline during the first month of life (WA, without aminophylline group). Demographic data and neonatal clinical outcomes were compared among the three groups. RESULTS: This study included 89 preterm infants (EA = 33, LA = 38, WA = 18). The EA group had a lower incidence of bronchopulmonary dysplasia (BPD) than the WA group (adjusted odds ratio [aOR] = 8.86(1.56-59.32); P = 0.024). Although there was no significant difference in BPD incidence between the EA and LA groups (aOR = 2.66(0.51-13.81), P = 0.244), a trend remained. Birth body weight less than 1000 g was also a significant risk factor for BPD (aOR = 8.86(1.32-47.41), P = 0.014). The duration of mechanical ventilation was shorter in the infants in the EA group compared to the WA group (estimated beta = -11.344(-19.57-3.12); P = 0.008). CONCLUSION: Early aminophylline administration may be associated with a decreased incidence of BPD in preterm infants. However, the clinical benefits of aminophylline treatment require further investigation. In addition, a birth body weight of less than 1000 g was a crucial risk factor for BPD.

Plasma Concentration Detection of Aminophylline with Multi-Walled Carbon Nanotube-Modified Electrodes in the Treatment of Ticagrelor-Related Dyspnea.

It was aimed at the plasma concentration detection of aminophylline under multi-walled carbon nanotube (MWNT) modified electrodes and the curative effect of aminophylline for ticagrelor-related dyspnea (TRD). 120 patients with TRD and coronary atherosclerotic heart disease (CAHD) in Wuhan Sixth Hospital Hospital were randomly divided into an intervention group and a control group, with 60 cases in each. The novel chitosan/gold nanoparticles-MWNTs (CTS/Au NPs-MWNTs) composite was prepared for studying the electrochemical behaviors of aminophylline on the electrodes. The clinical curative effect of aminophylline, as well as the levels of peripheral blood T lymphocyte subsets and inflammatory cytokines, was observed in the treatment of TRD. The actual plasma molar concentration of aminophylline was 23.6-47.8 µmol/L. After treatment, the total effective rate in the intervention group was higher than that in the control group significantly (95% VS 65%) (P<0.05). The forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) of the intervention group were better than those of the control group remarkably (P<0.05). The intervention group showed lower levels of tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 as well as the higher IL-10 significantly in serum compared with the control group (P<0.05). After follow-up, there was no cardiovascular death in either group. The CTS/Au NPs-MWNTs could be used for detecting the plasma concentration of aminophylline in blood samples. Aminophylline could notably relieve the clinical symptoms, reduce the inflammatory response, and regulate the immunity of patients with good safety.

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.

Alterations in the gut microbiome and metabolome profiles of septic rats treated with aminophylline.

The treatment of sepsis remains a major challenge worldwide. Aminophylline has been shown to have anti-inflammatory effects; however, the role of aminophylline in sepsis, a disease characterized by immune dysregulation, is unknown. In this study, we combined microbiome sequencing and metabolomic assays to investigate the effect of aminophylline administration on the intestinal flora and metabolites in septic rats. Sixty SD rats were randomly divided into three groups: a sham-operated (SC) group, a sepsis model (CLP) group and a CLP + aminophylline treatment (Amino) group. The intestinal flora and metabolic profile of rats in the CLP group were significantly different than those of the SC group, while aminophylline administration resulted in a return to a state similar to healthy rats. Differential abundance analysis showed that aminophylline significantly back-regulated the abundance of Firmicutes, unidentified_Bacteria, Proteobacteria, Lactobacillus, Escherichia-Shigella and other dominant bacteria (P < 0.05) and altered chenodeoxycholic acid, isolithocholic acid and a total of 26 metabolites (variable importance in the projection (VIP) > 1, P < 0.05). In addition, we found that there were significant correlations between differential metabolites and bacterial genera of the Amino and CLP groups. For example, Escherichia-Shigella was associated with 12 metabolites, and Lactobacillus was associated with two metabolites (P < 0.05), suggesting that differences in the metabolic profiles caused by aminophylline were partly dependent on its influence on the gutmicrobiome. In conclusion, this study identified a novel protective mechanism whereby aminophylline could regulate disordered intestinal flora and metabolites in septic rats.

Adjunctive sepsis therapy with aminophylline (STAP): a randomized controlled trial.

BACKGROUND: Sepsis is a serious disease caused by infection. Aminophylline has anti-asthma and anti-inflammatory effects. We aimed to explore the safety and effect of aminophylline in sepsis. METHODS: We conducted a clinical randomized controlled trial involving 100 patients diagnosed with sepsis within 48 h after intensive care unit (ICU) admission in two sites. All patients were randomized in a 1:1 ratio to receive standard therapy with or without aminophylline. The primary clinical outcome was all-cause mortality at 28 days. RESULTS: From September 27, 2018 to February 12, 2020, we screened 277 septic patients and eventually enrolled 100 patients, with 50 assigned to the aminophylline group and 50 to the usual-care group. At 28 days, 7 of 50 patients (14.0%) in the aminophylline group had died, compared with 16 of 50 (32.0%) in the usual-care group ( P  = 0.032). Cox regression showed that the aminophylline group had a lower hazard of death (hazard ratio = 0.312, 95% confidence interval: 0.129-0.753). Compared with the usual-care group, patients in the aminophylline group had a longer survival time ( P  = 0.039 by the log-rank test). The effects of aminophylline on vasopressor dose, oxygenation index, and sequential organ failure assessment score were time-dependent with treatment. There were no significant differences in total hospitalization days, ICU hospitalization days, and rates of serious adverse events (all P > 0.05). No adverse events were observed in the trial. CONCLUSIONS: Aminophylline as an adjunct therapy could significantly reduce the risk of death and prolong the survival time of patients with sepsis. TRIAL REGISTRATION: ChiCTR.org.cn, ChiCTR1800019173.

Effects of aminophylline on the levels of neutrophil gelatinase-associated lipocalin (NGAL) in asphyxiated term neonates.

OBJECTIVE: Our study evaluates the effects of aminophylline in the reduction of NGAL levels in perinatal asphyxia. METHODS: Term neonates with hypoxic ischaemic encephalopathy who were divided into two groups, the treatment and placebo. Urine NGAL levels were measured on day one and four of the treatment using BIOPORTO kits in both the groups. RESULTS: Day 1 NGAL levels were not statistically different in either group irrespective of the age, gender and the mode of delivery. on 4th day, NGAL in treatment group significantly decreased as compared to day 1 levels and placebo day-4 levels. significant differences were seen between first and fourth day NGAL levels among children with normal and caesarean birth and among female and male neonates. CONCLUSIONS: Following the treatment with aminophylline, NGAL levels in asphyxiated neonates are likely to reduce. Further studies based on other kidney dysfunction parameters can lead to the better and accurate conclusions.

Magnesium sulfate vs aminophylline as a second line of treatment in children with severe acute asthma. Randomized clinical trial. / Sulfato de magnesio vs aminofilina como segunda línea de manejo en niños con asma aguda severa. Ensayo clínico aleatorizado.

INTRODUCTION: Second-line drugs for acute asthma, such as salbutamol, magnesium sulfate, and aminophylline, are generally intravenously administered. OBJECTIVE: To compare the efficacy and safety of using mag nesium sulfate or aminophylline in children who did not respond to initial treatment. PATIENTS AND METHOD: Randomized clinical trial. Children who did not improve the Modified Pulmonary Index Score (mPSI) receive at random magnesium sulfate (50 mg/kg/single dose) or aminophylline (5 mg/ kg/dose followed by continuous infusion at 1 mg/kg/hour for 3 hours). Primary endpoints were changes in mPSI and oxygen saturation; secondary endpoints: hospitalization rate, need for transfer to the intensive care unit, use of a third intervention, and adverse effects. RESULTS: 131 patients were studied (66 patients in the aminophylline group and 65 MgSO4). The mean age was 5 ± 2.3 years, the demographic and clinical parameters did not differ between the groups. In the group that received magnesium sulfate, the mPSI and oxygen saturation changed significantly in favor from 13.1 ± 1.3 to 4.9 ± 2.5 (p < 0.001) and from 3.3 ± 2.5; (p 0.021), respectively, and their risk of hospital admission (RR 0.68 95% CI [0.56, 0.82]) and of secondary failure (0.16 95% CI 95% [0 , 07; 0.38]) decreased. Only one adverse event (tachycardia) was recorded. CONCLUSION: The administration of a single dose of magnesium sulfate proved to be more effective and safe than the use of aminophylline as a second- line drug.

The impact of aminophylline on incidence and severity of post-dural puncture headache: A meta-analysis of randomised controlled trials.

BACKGROUND: This meta-analysis aimed at addressing the impact of aminophylline use on risk and severity of post-dural puncture headache (PDPH). METHODS: Electronic databases (i.e., Medline, Embase, and the Cochrane controlled trials register) were searched from inception to the 12th of January 2021 for randomised controlled trials (RCTs) that assessed the efficacy of aminophylline for treatment (i.e., primary outcome) or prophylaxis (i.e., secondary outcome) against PDPH in various clinical settings. The study is registered with PROSPERO (CRD42020207713). RESULTS: A total of ten RCTs (n = 976) were included for analysis. Five studies (n = 270) revealed a lower pain score in patients with PDPH receiving aminophylline than that in the placebo group (standardised mean differences = -1.34, 95% confidence interval (CI): -1.76 to -0.91). In contrast, five trials (four on Caesarean sections and one on lower extremity surgeries, n = 706) demonstrated no prophylactic effect of aminophylline against PDPH at 24 [risk ratio (RR) = 0.70, 95% CI: 0.30-1.63, n = 637], 48 (RR = 0.48, 95% CI: 0.22-1.05, n = 506), and 72 (RR = 0.89, 95% CI: 0.54-1.48, n = 317) hours. Nevertheless, sensitivity analysis demonstrated significant prophylactic efficacy after removal of one study adopting a relatively low dose of aminophylline (RR = 0.36, 95% CI: 0.19-0.67). Most studies reported no increase in the incidence of adverse events associated with aminophylline use compared with that in the control group. CONCLUSION: Our results indicated that aminophylline might be a reasonable alternative for treating PDPH. However, its use for prevention was not established in this meta-analysis and further large-scale studies are warranted to support this option.

Variability in care for children with severe acute asthma in Latin America.

BACKGROUND: Care variability for children with severe acute asthma has been well documented in high-income countries, yet data from low- and middle-income regions are lacking. We sought to characterize the magnitude of practice variability in the care of Latin American children to identify opportunities for standardization of care. METHODS: A cross-sectional study performed through a retrospective analysis of contemporaneously collected data of children with severe acute asthma admitted to a center contributing to the LARed Network registry between May 2017 and May 2019. Centers were grouped by geographic location: Atlantic (AT), South Pacific (SP), and North Central (NC). RESULTS: Among 434 children, most received care in hospitals in the AT group (54% [235/434]), followed by the NC (23% [101/434]) and SP (23% [98/434]) groups. The majority of children in the AT (92% [215/235]) and SP (91% [89/98]) groups received nebulized salbutamol/albuterol, while metered-dose inhalers were preferred in the NC group (72% [73/101]). There was a wide variation in the use of antibiotics: AT (57% [135/235]), SP (48% [47/98]), and NC (14% [14/101]). The same was true for ipratropium bromide: AT (67% [157/235]), SP (90% [88/98]), and NC (17% [17/101]), and aminophylline: AT (57% [135/235]), NC (5% [5/101]), and SP (0% [0/98]). High-flow nasal cannula was the preferred respiratory support modality in the AT (60% [141/235]) and NC (40% [40/101]) groups, while bilevel positive airway pressure (BiPAP) use was more common in the SP group (80% [78/98]). CONCLUSION: We identified significant variability in care for severe acute asthma. Our findings will help to inform the design of future studies, quality improvement initiatives, and development of practice guidelines within Latin America.

Terbutaline and aminophylline as second-line therapies for status asthmaticus in the pediatric intensive care unit.

OBJECTIVE: Asthma is the most common chronic disease of childhood. Although asthma admissions to the pediatric intensive care unit (PICU) are increasing, there are no evidence-based guidelines on preferred escalation of therapies for patients with status asthmaticus who fail to respond to inhaled bronchodilators and systemic corticosteroids. The purpose of this study was to assess outcomes of PICU patients receiving aminophylline versus terbutaline as second-tier therapies for status asthmaticus. DESIGN: Retrospective cohort study using Pediatric Health Information System from 2016-2019. SETTING: Fifty-three tertiary children's hospitals. SUBJECTS: Children aged 2 to 18 years admitted to the PICU in children's hospitals contributing data to the Pediatric Health Information System with a primary diagnosis of status asthmaticus. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 11 133 pediatric patients treated for status asthmaticus in the PICU during the study period, 1144 received either terbutaline or aminophylline. There was no difference in intubation and mechanical ventilation between patients who received aminophylline and those who received terbutaline. However, in African American patients, those who received terbutaline had a significantly higher odds of intubation and mechanical ventilation compared to those who received aminophylline (OR, 12.41; 95%CI, 1.61,95). CONCLUSIONS: The use of aminophylline is associated with lower odds of intubation and mechanical ventilation in African American patients with status asthmaticus as compared to terbutaline.

Effect of Aminophylline in Preventing Renal Dysfunction among Neonates with Prenatal Asphyxia: A Clinical Trial.

BACKGROUND: As there are different views on the effects of aminophylline on neonatal renal function, we intended to observe the effects of aminophylline on renal dysfunction in neonates with prenatal asphyxia. METHODS: This randomized trial was conducted in the Obstetrics and Gynecology Hospital, Tehran, Iran, from June 2016 to May 2017, in neonates with moderate to severe asphyxia during birth. Fifty-six neonates were divided randomly into two groups. The intervention group received one dose of 5mg/kg slow intravenous aminophylline injection and the placebo group received 2 mL/kg of intravenous 10% solution of dextrose saline during the first hour of life. They were monitored and compared for renal functional indices, electrolytes, and complications of asphyxia during the three days of life. RESULTS: The mean of Cr (37.9 ± 8.8 vs 38.5 ± 9.4 and 20.8 ± 4.8 vs 30.1 ± 5.2 µmol/L), GFR (21.55 ± 4.7 vs 20.25 ± 4.4 and 30.8 ± 7.1 vs 20.1 ± 6.5 mL/minute/1.73 m2), Na (135.1 ± 12.4 vs134.5 ± 11.2 and 128.9 ± 11.5 vs 134.2 ± 10.9 mEq/L), and urine output (98.2 ± 25 vs 96.8 ± 23 and 148.7 ± 35 vs 108.8 ± 20 cc) were in the aminophylline treated and placebo group on the 1st and 3rd days, respectively. The mean difference of Cr (-9.3 (-8.9; -9.7) µmol/L); (P = 0.02), GFR (10.7 (10.1; 11.3) mL/minute/1.73 m2) (P = 0.009), Na (-5.3 (-5.9; -4.7) mEq/L) (P = 0.002), and urine volume (39.9 (24.9; 54.9) cc) (P = 0.001) presented statistically significant differences on the third day between the intervention and placebo group. CONCLUSION: Aminophylline was effective in preventing renal dysfunction in neonates with asphyxia. Neonates who received aminophylline indicated a significant improvement in GFR and urine output on the first day of life.