Administration Of Aminophylline Research Articles

Evaluation of the effect of aminophylline on inflammatory parameters in COVID-19 patients with acute respiratory distress syndrome

Background: In Acute respiratory distress syndrome (ARDS), invasion and activation of pro- and anti-inflammatory mediators and cytokines result in oxidative damage to the lung tissue. Aminophylline is a combination of theophylline and ethyl diamine, has anti-inflammatory, bronchodilator, ROS inhibitor effects, and stimulates surfactant release. Mortality of ARDS in COVID-19 patients is high; aminophylline is expected to reduce the incidence of mortality. Information regarding the use of aminophylline in COVID-19 patients with ARDS is still limited. Objective: To evaluate the efficacy of aminophylline in inflammatory parameters in COVID-19 patients with ARDS. Methods: It was a retrospective cohort observational study at the Universitas Airlangga Hospital. Samples were hospitalised COVID-19 patients with ARDS who received a loading dose of 240-480 mg and a maintenance dose of 720-960 mg aminophylline. The primary outcomes were improved C-reactive protein (CRP), IL-6, lymphocytes, neutrophils, and Neutrophil-lymphocyte ratio (NLR), which were measured before and after administration of aminophylline with a duration of therapy of 1-5 days. Result: A total of 50 patients with ARDS were enrolled in the study. Lymphocyte and CRP decreased (p = 0.002; p = 0.128). IL-6, neutrophil, and NLR increased (p = 0.255; p = 0.064; p = 0.005). Conclusion: It can be concluded that the administration of aminophylline has not improved inflammatory parameters.

Aminophylline Improves Ventilator-Induced Diaphragmatic Dysfunction by Targeting IGF-1-FOXO1-MURF1 Pathway.

The usage of life-saving mechanical ventilation (MV) could cause ventilator-induced diaphragmatic dysfunction (VIDD), increasing both mortality and morbidity. Aminophylline (AP) has the potential to enhance the contractility of animal skeletal muscle fibers and improve the activity of human respiratory muscles, and the insulin-like growth factor-1 (IGF-1)- forkhead box protein O1 (FOXO1)-muscle RING finger-1 (MURF1) pathway plays a crucial role in skeletal muscle dysfunction. This study aimed to investigate the impact of AP on VIDD and to elucidate the role of the IGF-1-FOXO1-MURF1 pathway as an underlying mechanism. Rat models of VIDD were established through MV treatment. IGF-1 lentiviral (LV) interference (LV-IGF-1-shRNA; controlled by lentiviral negative control LV-NC) was employed to inhibit IGF-1 expression and thereby block the IGF-1-FOXO1-MURF1 pathway. Protein and mRNA levels of IGF-1, FOXO1, and MURF1 were assessed using western blot and real-time reverse transcriptase-polymerase chain reaction (RT-qPCR), respectively. Diaphragm contractility and morphometry were examined through measurement of compound muscle action potentials (CMAPs) and hematoxylin and eosin (H&E) staining. Oxidative stress was evaluated by levels of hydrogen peroxide (H2O2), superoxide dismutase (SOD), antioxidant glutathione (GSH), and carbonylated protein. Mitochondrial stability was assessed by measuring the mitochondrial membrane potential (MMP), and mitochondrial fission and mitophagy were examined through protein levels of dynamin-related protein 1 (DRP1), mitofusin 2 protein (MFN2), phosphatase and tensin homolog (PTEN)-induced kinase 1 (PINK1), and Parkin (western blot). Apoptosis was evaluated using the terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate (UTP) nick-end labeling (TUNEL) assay and levels of Bax, B-cell lymphoma 2 (BCL-2), and Caspase-3. Levels of Atrogin-1, neuronally expressed developmentally downregulated 4 (NEDD4), and muscle ubiquitin ligase of SCF complex in atrophy-1 (MUSA1) mRNA, as well as ubiquitinated protein, were utilized to determine protein degradation. Furthermore, the SUnSET (surface sensing of translation) method was employed to determine rates of protein synthesis. MV treatment upregulated IGF-1 while downregulated FOXO1 and MURF1 (p < 0.05). AP administration reversed IGF-1, FOXO1 and MURF1 (p < 0.05), which was suppressed again by IGF-1 inhibition (p < 0.05), demonstrating the blockage of the IGF-1-FOXO1-MURF1 pathway. MV treatment caused decreased CMAP and cross-sectional areas of diaphragm muscle fibers, and increased time course of CMAP (p < 0.05). Additionally, oxidative stress, cell apoptosis, and protein degradation were increased and mitochondrial stability was decreased by MV treatment (p < 0.05). Conversely, AP administration reversed all these changes induced by MV, but this reversal was disrupted by the blockage of the IGF-1-FOXO1-MURF1 pathway. In this study, MV treatment induced symptoms of VIDD in rats, which were all effectively reversed by AP regulating the IGF-1-FOXO1-MURF1 pathway, demonstrating the potential of AP in ameliorating VIDD.

Allergic Reaction to Aminophylline in a Case of Lower Respiratory Tract Infection with Measles: A Rare Case Report

Measles is an acute respiratory infectious disease caused by the measles virus. It leads to respiratory involvement with manifestations such as pneumonia, laryngobronchitis, pneumonitis, etc. It can also cause secondary bacterial and fungal infections. Aminophylline is a methylxanthine bronchodilator composed of theophylline and ethylenediamine. Airway blockage is reversed by bronchial smooth muscle relaxation, increased myosin light chain kinase activity, and decreased intracellular calcium concentration. It relaxes the smooth muscle of the bronchial airways and pulmonary blood vessels, reducing airway responsiveness to histamine, methacholine, adenosine, and allergens. Allergic skin reactions secondary to aminophylline administration have been rarely seen. Aminophylline can be given orally as well as intravenously. A seven-month-old male infant presented with a lower respiratory tract infection and a maculopapular rash involving the face and trunk. A history of contact with measles was present. Intravenous aminophylline was administered for persistent wheezing. The infant developed a generalised erythematous papular rash with a more widespread distribution than before within one hour of administration. The child was treated with antihistamines for the same. After a detailed physical examination, looking at the pattern of the rash and excluding other causes like environmental factors and drug history, the diagnosis of an allergic reaction to aminophylline was made. Early identification of allergic reactions is paramount, as prompt cessation of the offending agent and initiation of appropriate medical interventions can significantly mitigate the severity of the reaction and prevent potential life-threatening complications.

Effects of administration of local aminophylline on patients undergoing ureteroscopic lithotripsy.

The presence of ureteral stones can cause pain, infections of urinary tract and hydronephrosis, resulting in the loss of renal function. For two decades, Ureteroscopy and laser stone fragmentation (URSL) attained a big rise and is the first line management for large ureteric stones and renal stones up to 2 cm. The present study was conducted to assess the success rate of ureteroscopic lithotripsy in treatment of ureteric calculus after local administration of aminophylline. 100 patients having ureteric calculi <20 mm in size, aged 20-60 years were included in the study and randomly divided into Group A (n = 50) with administration of local aminophylline and Group B (n = 50) with administration of saline infusion. Ureteroscopy was performed after 5 min of administration of the solution. URSL was done using pneumatic lithoclast and/or laser. Various parameters like duration of procedure, ease of ureteral access, requirement of DJ Stent and need of further operative interventions were compared between case and control groups. The data was collected and then subjected to statistical analysis using IBM SPSS 20.0 version at significance level of p < 0.05. The mean age of study subjects having ureteral stones was found to be between 31 and 40 years of age with males being more affected. We observed less mean duration of surgery, higher success rate, easy ureteral access (p-value < 0.05) with aminophylline use than control group. The need of ureteral stent and Auxiliary procedures was significantly higher in the control than in the case group (38%). The use of aminophylline has been found to be highly useful and effective in reducing the need of stents and secondary surgery, decreased pain, and increased success rate. Thus, the use of aminophylline is recommended during URSL procedure for the successful management of ureteral calculi.

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

BackgroundAcute 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.MethodsA 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.ResultsData 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.ConclusionsAminophylline increases urine output in critically ill children with AKI.Graphical abstractA higher resolution version of the Graphical abstract is available as Supplementary information

The effect of aminophylline on the recovery profile after hysterectomy: A randomized controlled double-blinded study.

In anesthesia practice, aminophylline is clinically used to treat bronchospasm. However, due to its antagonistic effect on adenosine, studies have recently focused on the drug's ability to enhance the recovery profile. The aim of this study was to investigate the hypothesis that the administration of aminophylline leads to better recovery after general anesthesia in hysterectomy. This randomized controlled double-blinded study, was conducted at Alzahra academic hospital in Guilan, Iran. During December 2022 to March 2023, 70 eligible women scheduled for elective abdominal hysterectomy were divided into two groups. Group A: received 3 mg/kg IV aminophylline diluted in 100 mL of normal saline and Group C: received 100 mL IV normal saline. The time to recovery of consciousness, tracheal extubation and discharge from post anesthesia care unit were recorded. In addition, heart rate, and mean arterial blood pressure were measured at 10 point times including; baseline (T0), immediately before the administration of aminophylline (T1), every 5 min until the end of the surgery(T2,T3,T4,T5,T6), and every 15 min in PACU(T7,T8,T9). There was no significant difference in terms of demographic data between the study groups. Comparing the two groups, the time of ROC was shorter in Group A than group C; 5.95 ± 1.12 and 8.5 ± 1.77 for Groups A and C, respectively (p < 0.001). The extubation time was shorter in Group A than group C; 7.79 ± 1.48 and 10.55 ± 3.02, for Groups A and C, respectively (p < 0.001). In addition, the discharge time was also shorter in group A than Group C; 30.17 ± 5.24 and 37.57 ± 4.41 for Groups A and C, respectively (p < 0.001). Not serious side effects were reported among 71.4% of cases in Group A and 51.4% in Group C (p = 0.086). Administration of aminophylline at a dose of 3 mg/kg IV improves the recovery profile after abdominal hysterectomy without serious adverse effects.

Post-dural puncture headache prevention and treatment with aminophylline or theophylline: a systematic review and meta-analysis.

Post-dural puncture headache (PDPH) is one of the most common complications in patients undergoing spinal anesthesia. The present systematic review and meta-analysis aimed to assess the therapeutic and prophylactic effects of aminophylline and theophylline on PDPH. Relevant studies were identified by searching the following electronic databases, without language restriction, until June 2020: Scopus, EMBASE, MEDLINE, Google Scholar, Web of Science, Cochrane Library-CENTRAL, and CINAHL Complete. Random effects models were used to calculate the standardized mean difference (SMD) and risk ratios (RRs) with 95% confidence intervals (95% CI) to assess the therapeutic and prophylactic effects of aminophylline and theophylline on PDPH, respectively. The Cochrane tool was used for the quality assessment of the included studies. The certainty of the evidence was rated using the Grading of Recommendations Assessment, Development, and Evaluation method. Of the 1,349 initial records, 15 met our eligibility criteria (6 studies on therapeutic and 9 on prophylactic effects). A significant reduction in the pain score was observed following aminophylline/theophylline treatment (SMD = -1.67; 95% CI, -2.28 to -1.05; P < 0.001, I2 = 84.7%; P < 0.001). Subgroup analysis revealed that the therapeutic effect was significantly higher when these agents were compared to placebo than when conventional therapies were used. The risk of PDPH after aminophylline administration was not significantly reduced (RR = 0.74; 95% CI, 0.42 to 1.31; P = 0.290). Theophylline and aminophylline have therapeutic, but not prophylactic, effects on PDPH.

Use of Aminophylline to Reverse Acute Kidney Injury in Pediatric Critical Care Patients.

Acute kidney injury (AKI) is a complication encountered in 18% to 51% of pediatric critical care patients admitted for treatment of other primary diagnoses and is an independent risk factor for increased morbidity and mortality. Aminophylline has shown promise as a medication to treat AKI, but published studies have shown conflicting results. Our study seeks to assess the reversal of AKI following the administration of aminophylline in critically ill pediatric patients. We performed a single-institution retrospective chart review of pediatric inpatients who were diagnosed with AKI and subsequently treated with non-continuous dose aminophylline between January 2016 and December 2018. Data were collected beginning 2 days prior to the initial dose of aminophylline through completion of the 5-day aminophylline course. Nineteen therapies among 17 patients were included in analysis. Twelve of the therapies resulted in resolution of AKI during the study period. We observed urine output increase of 19% (p = 0.0063) on the day following initiation of aminophylline therapy in the subset of patients whose AKI resolved. Trends toward decreased serum creatinine and lower inotropic support were also noted. Based on these findings, aminophylline could be considered a potentially effective medication for use as rescue therapy in critically ill children with AKI. Limitations include small study population and retrospective nature. Further research in this area with a larger study population and a randomized control trial would allow for better characterization of the efficacy of aminophylline in reversal of AKI.

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

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. A retrospective observational cohort of infants weighing <1500g 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. 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 1000g 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). 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 1000g was a crucial risk factor for BPD.

The Effect of Aminophylline on Urine Output and Fluid Balance after a Single Dose in Children Admitted to the Pediatric Cardiac Intensive Care Unit

AbstractThe purpose of this retrospective study was to investigate the effects of a single dose of aminophylline on urine output and fluid balance in children admitted to the cardiac intensive care unit. A retrospective study was performed to compare variables of interest before and 24 hours after aminophylline administration in children under the age of 18 years who were admitted to the cardiac intensive care unit at our institution from January 2011 onwards. Variables of interest included age, weight, aminophylline dose, concurrently administered diuretics, specific hemodynamic parameters, and blood urea nitrogen and creatinine levels. Variables such as urine output and fluid balance were measured through a binary endpoint. Data were compared in a paired fashion and continuous variables were compared through paired t-tests. Analyses were conducted using SPSS Version 23.0. A total of 14 patients were included in the study. There was no significant change in hemodynamic parameters or creatinine levels before and after intravenous aminophylline administration of 5 mg/kg. There was a significant difference in urine output, fluid balance, and blood urea nitrogen levels from the baseline value. Concurrent usage of diuretics did not show significant association with a difference in urine output or fluid balance from baseline. No significant adverse reactions were noted 24 hours after administration of aminophylline. Use of aminophylline dosed at 5 mg/kg is safe and leads to improvement in urine output and fluid balance without negatively impacting systemic oxygen delivery or renal filtration function.

Prophylactic Administration of Aminophylline to Prevent Renal Dysfunction in Asphyxiated Neonates

Prophylactic Administration of Aminophylline to Prevent Renal Dysfunction in Asphyxiated Neonates

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.

The potential effect of topical aminophylline on acute glaucoma model

Objectives: to study the oculo- hypotensive effect of non-selective phosphodiestrase inhibitor aminophylline. Methods: The study was conducted on fifteen albino rabbits (2.5–2.8 Kg) and model of acute ocular hypertension was obtained by 5% glucose water administration at 15ml/kg through the marginal vein of the rabbit’s ear. Aminophylline was dissolved in vehicle of phosphate buffer saline and diluted to desired concentration as 0.5%. Phosphate buffer saline solution also served as control. The left eye of rabbit was received one drop of aminophylline (0.5%) on the other hand the right eye treated by the vehicle and considered as control parameter. The pressure measurement was recorded at 15, 30, 45, 60, 90, 120, 135, 150 and 165 min after drug instillation. Results: After 30 minutes of topical 0.5% aminophylline administration the normal tension of the eye remain unchanged. However topical 0.5% aminophylline eye drop significantly (p &lt; 0.05) successes in the decrease of the acute elevation of ocular pressure due to 5% glucose infusion. Moreover, in this study aminophylline pretreatment has the ability to facilitating the returns of the IOP to normal levels Conclusions: Topical administration of aminophylline (0.5%) significantly prevent acute rise in the ocular pressure induced by 5% glucose administration. The IOP lowering effect of aminophylline can be considered as potential antiglaucoma drug.

Role of Aminophylline Intravesical Instillation on Enhancing Ureteral Dilatation prior to Ureteroscopy

Abstract Background Semi-rigid uretroscopy (URS) is a common intervention approach for lower ureteric stones. Ureteral dilatation is frequently needed before URS to enable ureter accessing. Aminophylline is known by its muscle relaxant effect and has been suggested to be effective in ureteral dilation. Objectives To evaluate the effect of intravesical administration of aminophylline on ureteroscopy and to measure intraureteral pressure Methods This prospective randomized controlled study included 50 before and after aminophylline injection. patients with lower ureteral calculi. In group A, the ureter was dilated by intravesical aminophylline whereas in group B balloon dilator was used. Intraureteral pressure was measured using pressure transducer connected to invasive pressure monitor. Results No statistically significant difference was noticed between both groups in operative time, intra operative complication, need for ureteral stenting or stone free rate. However, post-operative pain and haematuria were statistically significantly higher among balloon group compared to aminophylline group. In group A, there was statistically significant decrease in intraureteral pressure after injection of aminophylline (7.80 ± 1.71) compared to before injection (12.2 ± 1.85) with p-value &amp;lt; 0.001. Conclusion Aminophylline is effective in ureteral dilatation when intravesically injected with less frequent post-operative pain and hematuria.

Aminophylline modulates the permeability of endothelial cells via the Slit2-Robo4 pathway in lipopolysaccharide-induced inflammation.

Sepsis and septic shock are the main cause of mortality in intensive care units. The prevention and treatment of sepsis remains a significant challenge worldwide. The endothelial cell barrier plays a critical role in the development of sepsis. Aminophylline, a non-selective phosphodiesterase inhibitor, has been demonstrated to reduce endothelial cell permeability. However, little is known regarding the role of aminophylline in regulating vascular permeability during sepsis, as well as the potential underlying mechanisms. In the present study, the Slit2/Robo4 signaling pathway, the downstream protein, vascular endothelial (VE)-cadherin and endothelial cell permeability were investigated in a lipopolysaccharide (LPS)-induced inflammation model. It was indicated that, in human umbilical vein endothelial cells (HUVECs), LPS downregulated Slit2, Robo4 and VE-cadherin protein expression levels and, as expected, increased endothelial cell permeability in vitro during inflammation. After administration of aminophylline, the protein expression levels of Slit2, Robo4 and VE-cadherin were upregulated and endothelial cell permeability was significantly improved. These results suggested that the permeability of endothelial cells could be mediated by VE-cadherin via the Slit2/Robo4 signaling pathway. Aminophylline reduced endothelial permeability in a LPS-induced inflammation model. Therefore, aminophylline may represent a promising candidate for modulating vascular permeability induced by inflammation or sepsis.

A single dose of aminophylline administration during therapeutic hypothermia; does it make a difference in glomerular filtration rate?

Aminophylline has been demonstrated to be effective in improving renal functions of the infants suffering from acute kidney injury (AKI) due to perinatal asphyxia. We aimed to evaluate the effect of a single-dose aminophylline on estimated glomerular filtration rate (eGFR), urine output (UO), and incidence and severity of AKI according to the pediatric-modified RIFLE and neonatal RIFLE criteria in newborns with perinatal asphyxia under therapeutic hypothermia. This was a single-center, retrospective cohort study including newborns (gestational age ≥36 weeks) who underwent therapeutic hypothermia due to hypoxic ischemic encephalopathy between 2016 and 2019. Demographic and clinical data were obtained from electronic medical records and patient files. Two patient groups were established: aminophylline group and control group which were only under therapeutic hypothermia. Twenty-one newborns were in the aminophylline group and 13 newborns were in the control group. Our study revealed that on the third day of life (DOL), eGFR was significantly higher in the control group (p=0.025), but UO was significantly higher in the aminophylline group (p=0.021). In the aminophylline group, eGFR on the first DOL was higher than the value on the second DOL (p=0.017) while UO was higher on the second and third DOL compared to the first DOL (1-2 DOL p=0.006, and 1-3 DOL p=0.004). However, in the control group, there was no statistically significant difference in UO over the four DOL. Both groups were similar in the presence, severity, and outcome of AKI.Conclusion: This study demonstrated that aminophylline increases UO even in the infants under therapeutic hypothermia. However, the eGFR did not significantly increase in the aminophylline group. Understanding how therapeutic hypothermia affects pharmacokinetics may help us improve our results in future studies. What is known: • Therapeutic hypothermia (TH) reduces the incidence of acute kidney injury in asphyxiated newborns. • Aminophylline is effective in improving renal functions in asphyxiated newborns. What is new: • This is the first study evaluating the effect of a single dose of aminophylline on renal functions in newborns under TH. • A single dose of aminophylline administration in newborns under TH was associated with increased urine output especially on the third day of life. However, no significant increase was detected in glomerular filtration rate associated with aminophylline administration.

COMPARISON OF LOCAL ADMINISTRATION OF AMINOPHYLLINE VERSUS NORMAL SALINE ON TRANSURETERAL LITHOTRIPSY IN PATIENTS PRESENTING WITH ACUTE RENAL COLIC

ABSTRACT&#x0D; BACKGROUND &amp; OBJECTIVE: Acute renal colic is most common disease presented with agonizing pain worldwide. Our study aims to compare outcomes (mean operative time and frequency of complete stone removal) between local administrations of aminophylline versus saline on Transureteral lithotripsy (TUL) in patients presented with acute renal colic.&#x0D; METHODOLOGY: Our study design was randomized clinical trial, conducted at department of Urology &amp; Kidney in Pakistan Institute of Medical Sciences, Islamabad. Study duration was 6 months (February 2017-July 2017). Ethical approval and consent forms were taken in our study. A sample size of 90 cases was calculated (1:1 randomization that is 45 patients in each group) using WHO calculator. Acute renal colic patients were selected through consecutive (non-probability) sampling. A random division of patients is done in two groups; Group-A underwent local administration of aminophylline and group-B patients were given placebo. SPSS version 24 was used for analysis purpose. Post stratification chi-square and t-test was utilized in analysis for comparisons. In our study, p-value≤0.05 was found significant.&#x0D; RESULTS: Total 90 cases were included in study. Mean age of patients was 47.56±18.1SD.Mean operative time was found to be significantly lower in Group-A (aminophylline group) as compared to group-B (placebo group) p=0.000. Group-A patients showed significantly high stone removal frequency as compared to group-B (44.4% vs 35.6%, p=0.03).&#x0D; CONCLUSION: Aminophylline is an effective and safe drug in terms of lower operative time and complete stone removal among acute renal colic patients undergoing transureteral lithotripsy.

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

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). 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 5days post-transplant. Secondary outcomes were rates of DGF/SGF and urinary neutrophil gelatinase-associated lipocalin (NGAL) levels. 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 ± 38.9ml/min/1.73m2 vs. 80.48 ± 52.1ml/min/1.73m2p = 0.32; DGF/SGF 5/23 (21.7%) vs. 3/27 (11.1%) p = 0.31; urine NGAL/creatinine 300.5ng/mg IQR 105.5-1464.5ng/mg vs. 425.4ng/mg IQR 140.3-1126.2ng/mg, p = 0.95; respectively). At 12months, there was 100% patient survival and 98% graft survival. eGFR at 12months was similar between the two arms. 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.

Daily Caffeine Consumption Is Associated with Decreased Incidence of Symptoms and Hemodynamic Changes During Pharmacologic Stress with Regadenoson.

Regadenoson is an adenosine A2A receptor agonist widely used as a pharmacologic stress agent for myocardial perfusion imaging. Approximately 3.4 million regadenoson pharmacologic stress tests were performed annually as of 2011. Caffeine is a competitive antagonist of all adenosine receptor subtypes; thus, caffeine is typically withheld 12-24 h before stress with regadenoson. However, the effects of daily caffeine intake on regadenoson stress are unknown. This study assessed the effects of daily caffeine intake on symptoms and hemodynamic changes during stress testing with regadenoson. Methods: Patients presenting for regadenoson stress myocardial perfusion imaging were asked their amounts of daily caffeine intake. Chart review was used to collect data on demographics, comorbidities, and use of β-blockers. Data collected from the regadenoson stress test included symptoms, administration of aminophylline, heart rate, blood pressure, and arrhythmias. χ2 testing and ANOVA were used to analyze data divided into 3 categories of caffeine intake (<200, 200-400, and >400 mg daily). χ2 testing was used for nominal data, and unpaired t testing was used for continuous data. Results: In total, 101 patients were enrolled: 53% men and 47% women. Of the 101 patients, 89% reported caffeine intake, with 13% reporting heavy caffeine intake (>400 mg daily). The last intake of caffeine was at least 12 h before the test. During the test, 63% of patients reported symptoms, but the test was completed successfully in all patients. Compared with those who do not use caffeine, intake for caffeine users was associated with less chest pain (P = 0.0013), less aminophylline administration (P = 0.0371), lower resting and peak heart rate (P = 0.0497 and 0.0314, respectively), and lower diastolic blood pressure response (P = 0.0468). No associations were found between caffeine intake and arrhythmia or systolic blood pressure response. Conclusion: The use of regadenoson stress for myocardial perfusion imaging in caffeine consumers is very common, safe, and associated with a lower incidence of certain symptoms than in non-caffeine consumers. Specifically, caffeine intake was associated with less aminophylline use and chest pain.

Protective effects of Gαq‐RGS2 signalling inhibitor in aminophylline induced cardiac arrhythmia

An over activation of GPCR mediated Gαq dependent signalling pathway is widely associated with the development of cardiovascular abnormalities. The objective of study was to evaluate the effects of (1-(5-chloro-2-hydroxyphenyl)-3-(4-(trifluoromethyl)phenyl)-1H-1,2,4-triazol-5(4H)-one) Gαq-RGS2 signalling inhibitor on aminophylline induced cardiac arrhythmia in rats. Rats were divided into four groups; normal rats, disease control (DC, aminophylline treated 100mg/kg/d, i.p., 7days), Gαq-RGS2 signalling inhibitor (1 and 10mg/kg/d, p.o., 7days) treated arrhythmic rats. Gαq-RGS2 signalling inhibitor was administered 1hour prior to the administration of aminophylline from 1st day. At the end of study, heart rate (HR), QRS complex, QT and RR interval were measured by electrocardiogram (ECG) of anesthetized rats. Systolic and diastolic blood pressure (SBP, DBP) by invasive method, cardiac damage markers (CK-MB, LDH) in the serum, antioxidant enzymes (SOD, catalase, glutathione) and cAMP level were measured. The treatment of Gαq-RGS2 signalling inhibitor (10mg/kg) significantly abolished the aminophylline induced increase of heart rate, prolongation of RR and QT interval as compared to DC rats. Gαq-RGS2 signalling inhibitor (1 and 10mg/kg) significantly attenuated the prolongation in QRS complex, increase of SBP, DBP and cardiac damage markers as compared to DC. Gαq-RGS2 signalling inhibitor treatment (10mg/kg) significantly reduced the cAMP level and increased the antioxidant enzyme level as compared to DC. Gαq-RGS2 signalling inhibitor (10mg/kg) showed the protective effect against the aminophylline induced cardiac arrhythmia and it might be due to improvement in cAMP level and antioxidant enzymes.