Intravenous Aminophylline Research Articles

USEFULNESS OF LONG TERM PEF MONIITORING IN ASTHMATIC CHILDREN

To investigate the relationship between exacerbation of asthma and PEF variability, 32 institutionally hospitalized asthmatic children were enrolled in the study. Methods: PEF variability, asthma attack score, medication score were evaluated every one week for four weeks before 40 episodes of acute exacerbation, being required frequent inhalations of β-agonist, intravenous aminophylline, and/or systemic steroid during long-term hospitalization. Those parameters during most stable period were also evaluated to compare with 2 weeks before acute exacerbation. Subjects were divided into unstable group and stable group with or without asthma attack during 1 week before episode of acute exacerbation respectively. Results: 1. Averaged % PEF decreased and daily variability of PEF increased significantly in 1st week than in 2nd-4th week before acute exacerbation. 2. Averaged % PEF decreased and daily variability of PEF increased significantly in 2 weeks before acute exacerbation than in most stable periods. 3. Averaged daily variability of PEF was proportional to asthma attack score during 1 week before acute exacerbation. 4. Although no significant changes in % PEF and daily variability for 4 weeks before acute exacerbation were observed in stable group, averaged % PEF decreased and daily variability of PEF increased significantly in 2 weeks before acute exacerbation than in stable periods. Conclusions: These results suggest that information obtained by long term PEF monitoring is useful for predicting asthma exacerbation, and that measuring PEF and its daily variability even in stable period are also important to know individual PEF change.

Aspects of Theophylline Clearance in Children

Michaelis-Menten pharmacokinetic parameters for theophylline were estimated in a three-month infant following an accidental overdose of intravenous aminophylline. Fitting of time-concentration data was performed using nonlinear regression with MKMODEL. A mixed order elimination model was superior to a first order model. Parameter estimates were standardized to a 70 kg human using an allometric power model. Parameter estimates (SE) were: maximum rate of metabolism (Vmax) 71 (42) mg.h-1, Michaelis-Menten constant (Km) 32.3 (33.5) mg.l-1, volume of distribution (Vd) 46.9 (2.6)l. This Michaelis-Menten constant is lower than that reported for adults and consequently non-linear elimination will occur at lower plasma concentrations in infants than in adults. Theophylline clearance has traditionally been reported as directly proportional to body weight. This per kilogram model gives an erroneous impression that clearance is greatest in early childhood and then decreases with age until adult rates are reached in late adolescence. Age-related clearance values reported in the literature were reviewed using an allometric 3/4 power model. This size model demonstrates that clearance increases in infancy and reaches adult rates in the first one to two years of life.

Aminophylline as an Adjunct to Standard Advanced Cardiac Life Support in Prolonged Cardiac Arrest

Study objective: We hypothesized that the addition of aminophylline to Advanced Cardiac Life Support (ACLS) interventions would improve the initial resuscitation success rate in an animal model of prolonged cardiac arrest. Methods: We used a double-blind, placebo-controlled, randomized-block design with a follow-up open-label uncontrolled phase. We studied 24 female domestic mixed-breed swine (body mass, 20 to 25 kg). After electrical induction of ventricular fibrillation, animals were subjected to 8 minutes of no-flow cardiac arrest followed by 1 minute of mechanical ventilation and closed-chest compressions. Nine minutes after arrest, equal numbers of swine received 6 mg/kg intravenous aminophylline (treatment group) and a saline solution placebo (control group), another minute of basic CPR, and standardized ACLS interventions beginning at 10 minutes. Initial resuscitation efforts were continued for at least 20 minutes. In all animals, if initial efforts failed, 6.0 mg/kg intravenous aminophylline, open label, and 10 minutes of additional resuscitation were administered. The primary outcome variables were return of spontaneous circulation (ROSC) and 1-hour survival. We compared groups with the two-tailed Fisher exact test. Results: ROSC occurred in 4 of 12 animals in the treatment group (33%) and 3 of 12 in the control group (25%) ( P=.50). Late administration of aminophylline did not result in ROSC in any animal. Survival to 1 hour was greater in the treatment group (4 of 12, 33%) than in the control group (1 of 12, 8%) ( P=.16). Conclusion: Addition of aminophylline to standard ACLS interventions did not increase the incidence of ROSC or the 1-hour survival rate in a swine model of prolonged cardiac arrest. [Burton JH, Mass M, Menegazzi JJ, Yealy DM: Aminophylline as an adjunct to standard Advanced Cardiac Life Support in prolonged cardiac arrest. Ann Emerg Med August 1997;30:154-158.]

Effect of oral aminophylline in patients with angina and normal coronary arteriograms (cardiac syndrome X).

BACKGROUND: Patients with syndrome X (exertional angina, positive exercise test, normal coronary arteriogram) have an altered perception of cardiac pain. This symptom may arise from increased sensitivity to adenosine. Previous...

Effects of dihydropyridines on the components of the ethanol withdrawal syndrome: possible evidence for involvement of potassium, as well as calcium?

Comparison was made of the ability of two dihydropyridine calcium channel antagonists, nitrendipine and felodipine, to prevent a range of signs of ethanol withdrawal. The increases in handling-induced behavior seen in mice during withdrawal from chronic ethanol treatment were prevented by administration of nitrendipine, 50 mg/kg, but not by, felodipine, 10 mg/kg, a dose that caused a similar displacement of dihydropyridine binding in central nervous system tissue, in vivo and in vitro. A higher dose of felodipine, 20 mg/kg, also had no effects. Nitrendipine, but not felodipine, prevented audiogenic seizures during the withdrawal phase. Similarly, nitrendipine prevented both the decrease in thresholds for N-methyl-DL-aspartate seizures and the increase in thresholds for convulsions due to 4-aminopyridine, which were seen during the withdrawal period, while felodipine did not alter either of these changes. Withdrawal from the ethanol chronic treatment increased the thresholds to seizures produced by intravenous aminophylline; this change was also prevented by nitrendipine. The significance of this increase in thresholds was lost after felodipine administration. In naive mice (not treated with ethanol) the doses of nitrendipine and felodipine used in the withdrawal studies were tested against the effects of convulsant drugs. Both dihydropyridines increased, to similar extents, the thresholds for seizures produced by bicuculline, pentylenetetrazol, and by N-methyl-DL-aspartate. The thresholds for aminophylline were unaltered by either dihydropyridine. In contrast, the thresholds for seizures due to 4-aminopyridine in the naive animals were not changed by felodipine, but were increased by nitrendipine. The results suggest that changes in potassium, as well as calcium, may possibly be involved in some of the stages of the ethanol withdrawal syndrome.

Asthma treatment during pregnancy. What can be safely taken?

'Safe' pharmacological therapy for gestational asthma is defined as therapy during which the apparent risks of the drug appear to be lower than the maternal and potential fetal risks of uncontrolled asthma that could result if the drug were not used. Major malformations occur in 2 to 4% of all newborns, 1% of which can be attributed to medication in general. Information regarding the effects of drugs administered during pregnancy may come from animal studies, human case reports, and prospective cohort studies. Based on a review of the available information, it is recommended that mild asthma during pregnancy be managed with inhaled beta 2-agonists, as required; step therapy for moderate asthma would include inhaled sodium cromoglycate (cromolyn sodium), inhaled beclomethasone dipropionate and oral theophylline. Severe gestational asthma should be treated with oral corticosteroids at the lowest effective dosage. The pharmacological management of acute asthma during pregnancy should include nebulised beta 2-agonists and ipratropium bromide, and intravenous methylprednisolone. Intravenous aminophylline would not generally be recommended, unless the patient requires hospitalisation. Optimal medical practice medico-legal considerations demand that the patient's informed consent be obtained for that recommended gestational management programme.

Intravenous aminophylline increases the degree of saturation of urine with calcium phosphate and struvite.

This study was designed to assess the effect of i.v. treatment with aminophylline (AMPH) on the risk of calcium phosphate and struvite stone formation. We administered AMPH in doses of 4 mg/kg body weight in 15-min i.v. infusions to 60 infants with clinical symptoms of obstructive bronchitis with dyspnoea. During 3 hours after infusion we observed a significant increase in urine saturation with brushite, octocalcium phosphate and struvite. This rise in urine saturation may increase the risk of kidney stone formation.

Methods used to decrease lithium absorption or enhance elimination.

To review current methods, well documented and investigational, being used to decrease lithium absorption or enhance lithium elimination. The basic science and clinical literature on lithium were reviewed by a comprehensive Medline search from 1984 to 1996. Additional references were identified by reviewing the reference citations from the results of the Medline search. Prevention of Absorption: Whole bowel irrigation has been demonstrated to be an effective means of enhancing lithium removal from the gastrointestinal tract. Sodium polystyrene sulfonate resin administration has been shown to be effective in binding lithium elimination in animal and human models. However, the lower limits of effective sodium polystyrene sulfonate dosing and the extent of potassium lowering in humans are questions that need to be answered before sodium polystyrene sulfonate resin can be recommended for routine, use. Enhancement of Elimination: Saline or forced diuresis is not effective in enhancing lithium elimination unless the patient is volume or sodium depleted. The use of continuous arteriovenous hemodiafiltration or low dose dopamine to enhance lithium elimination has only been documented in case reports. Intravenous aminophylline (theophylline) is not consistently effective and its risks outweigh possible benefits. The literature supports hemodialysis as a well documented and effective means of enhancing lithium elimination. Controversy exists over the appropriate indications for its initiation. Given the wide interpatient variability in lithium pharmacokinetics, single case reports do not provide sufficient evidence of the effectiveness of a given method to enhance

The effect of intravenous aminophylline on essential tremor

Aims The effects of intravenous aminophylline (375 mg) or placebo (saline) were studied in 10 patients with benign essential tremor. Methods This was a single‐blind crossover study. Patients received aminophylline by i.v. infusion over 15 min or sahne at least 1 week apart. Tremor was measured by a peizoresistive accelerometer at 15 min intervals predose and up to 2 h. Plasma theophylline concentrations were measured by h.p.1.c. Results Tremor power was significantly greater following aminophylline (5.67–6.2 Hz) than placebo (5.6–5.9 Hz). Conclusions We conclude that intravenous aminophylline potentiates benign essential tremor when given acutely by the intravenous route in the doses required to achieve therapeutic benefits in asthma.

Furosemide Given by Inhalation Ameliorates Acute Exacerbation of Asthma

Previous studies have suggested that inhaled furosemide may have a protective effect against a wide variety of bronchoconstrictor agents, but a therapeutic effect has not been established in acute exacerbation of asthma. The purpose of this study was to investigate whether inhaled furosemide would exhibit any therapeutic benefit in acute asthma. We conducted a double-blind, placebo-controlled, randomized study in 40 patients with acute mild or moderate exacerbation of asthma. All patients received intravenous (IV) aminophylline 250 mg for 90 min and IV hydrocortisone 100 mg at entry. After randomization, 3 patients were excluded from the final analysis. At 30 min after starting IV aminophylline, 20 patients were given inhaled furosemide 20 mg and 17 patients received normal saline as placebo-control. Both inhalations were given by a jet nebulizer. The baseline forced expiratory volume at 1 sec (FEV1), peak expiratory flow rate (PEFR), and serum concentration of theophylline did not differ between the two groups. An increase in FEV1 in the furosemide group by 28.2 ± 5.9% (mean ± SE) was noted at 60 min, and this was significantly higher than in the control group. PEFR at 60 min was also significantly higher in the furosemide group than in control group. We conclude that inhaled furosemide has a bronchodilator effect on mild to moderate exacerbation of asthma when it is used with IV theophylline. Inhaled furosemide may benefit certain acute asthma patients, especially those suffering complications from the adverse effects of β2-agonists.

Asthma treatment in pregnancy: A randomized controlled study

OBJECTIVE: Our purpose was to study the effect of inhaled corticosteroids on asthma exacerbations in pregnancy. STUDY DESIGN: We prospectively studied 84 pregnant women with 105 asthma exacerbations. Women were hospitalized if the forced expiratory volume in 1 second was <70% after sequential bronchodilator therapy. They were randomly assigned to receive either intravenous aminophylline and inhaled β 2-adrenergic receptor agonist or intravenous methylprednisolone and a β 2-adrenergic receptor agonist. At discharge women were randomly assigned to receive either inhaled beclomethasone, β 2-adrenergic receptor agonist, and an oral corticosteroid taper or a β 2-adrenergic receptor agonist and a corticosteroid taper. RESULTS: Sixty-five (62%) of 105 women with exacerbation required hospitalization. Aminophylline did not shorten response time or decrease hospital stay. Readmission rate was decreased by 55% in women given inhaled beclomethasone (33% vs 12%, p < 0.05, odds ratio 3.63, 95% confidence interval 1.01 to 13.08). Pregnancy-induced hypertension and cesarean delivery were increased over those of the general population. CONCLUSIONS: Intravenous aminophylline offers no therapeutic advantages. Continuous inhaled corticosteroids reduced the need for subsequent admissions. (Am J Obstet Gynecol 1996;175:150-4.)

Prediction of in‐hospital cardiac events using dipyridamole‐thallium scintigraphy performed very early after acute myocardial infarction

Ischemic complications occur frequently during hospitalization after acute myocardial infarction. Dipyridamole-thallium scintigraphy performed early after admission can detect residual ischemia, may have additional prognostic value and be useful in the management of these patients. Dipyridamole infusion and 201thallium imaging were performed on the third day of infarction in 114 consecutive patients. Coronary angiography was performed before hospital discharge in 90% of patients and exercise testing was performed at the time of discharge in patients without contraindications. Side effects occurred in 28 patients, but they were mild and transient or rapidly reversed with intravenous aminophylline. During hospitalization, three patients died and four had a nonfatal reinfarction. Patients with these major cardiac events had previously shown a higher prevalence of reversible perfusion defects during testing (71 vs. 31%, p < 0.05). In addition, 19 patients had early recurrent ischemia requiring early in-hospital revascularization. Overall, cardiac events defined as death, reinfarction, or early myocardial revascularization occurred in 22 patients. Of the patients with these events, 68% had thallium redistribution on initial myocardial scanning compared with 25% of patients without events (p = 0.0001). Patients with cardiac events also showed a higher number of myocardial segments with reversible perfusion defects (1.8 +/- 2.2 vs. 0.6 +/- 1.3, p = 0.001). Logistic regression analysis revealed that among all the other clinical, scintigraphic, and angiographic variables, the presence of thallium redistribution on the dipyridamole-thallium scan was the only independent predictor of cardiac events, increasing the risk by sixfold. Furthermore, during a 1-year follow-up, 14 other patients had ischemic events. Of these, 64% had previously shown thallium redistribution during early dipyridamole testing compared with 19% of patients without cardiac events (p < 0.001). Intravenous dipyridamole-thallium-scintigraphy performed very early after myocardial infarction is safe and useful to predict in-hospital ischemic events.

Significance of the Therapeutic Range of Serum Theophylline Concentration in the Treatment of an Attack of Bronchial Asthma.

The purpose of this study was to evaluate the accuracy of the recommended theophylline therapeutic range in the treatment of acute airway obstruction. Twenty seven patients (20 to 64 years) with acute asthma attack were given aminophylline intravenously to obtain a theophylline concentration between 10 and 20 micrograms/ml. Peak expiratory flow rates (PEFR) and serum theophylline concentrations were measured before and after aminophylline injection. When a marked improvement was not seen after aminophylline injection, the treatment was followed by inhalation of a beta-agonist and intravenously administered hydrocortisone. In order to clarify the relationship between theophylline efficacy at a therapeutic level and PEFR, as measured before aminophylline administration, the patients were classified into four groups. Group A (n = 7): asthma attack persisted regardless of treatment with aminophylline, beta-agonist and hydrocortisone, group B (n = 7): asthma attack improved by aminophylline, beta-agonist and hydrocortisone, group C (n = 6): asthma attack improved by both aminophylline and beta-agonist, group D (n = 7): asthma attack improved by intravenous aminophylline alone. The means (+/- S.E.) PEFR before aminophylline administration were 94.3 +/- 11.31/min in group A, 114.3 +/- 10.01/min in group B, 196.7 +/- 22.21/min in group C, and 220.0 +/- 12.51/min in group D, respectively. There were significant differences in PEFR between the A and C, A and D, B and C, and B and D groups. These findings suggest that theophylline efficacy is not expected in patients with low PEFR (less than 2001/min) at the time of treatment of an attack, even if a therapeutic theophylline concentration was obtained.

Comparing a High-Dose Dipyridamole SPECT Imaging Protocol with Dobutamine and Exercise Stress Testing Protocols

To determine the safety, sensitivity, specificity, and accuracy of high-dose dipyridamole compared with treadmill and dobutamine stress imaging protocols. Nuclear imaging studies using standard dose dipyridamole provide similar results to those obtained when treadmill stress is used. Recently dobutamine tomography and planar imaging with high-dose dipyridamole have been shown no improve nuclear imaging results. One hundred fifty-nine patients were imaged with thallium, teboroxime, or sestamibi per standard single photon emission computed tomography (SPECT) protocols. Pharmacologic stress was performed in 85 people with the remainder undergoing exercise testing by Bruce protocol. In this study, 0.852 mg dipyridamole was used per kilogram body weight and was infused over a four-minute period. Results from nuclear imaging were compared with those from coronary arteriograms. The sensitivity and specificity of high-dose dipyridamole was 100% and 88.9%, respectively, which is statistically greater (P < 0.005) than that achieved when patients were stressed by treadmill. Side effects with the higher dose of dipyridamole were easily reversed with aminophylline. The sensitivity and specificity of intravenous dobutamine was 100%, but it was used in a limited number of subjects. When patients were stressed by Bruce protocol the sensitivity was 92.5% and specificity was 42.8%. The differences were not attributable to inadequate exercise duration. High-dose dipyridamole is safe and easily reversed with intravenous aminophylline. The sensitivity and specificity of dipyridamole and dobutamine stress testing were statistically more accurate than results obtained with treadmill protocols when SPECT is used to image the heart. High-dose dipyridamole resulted in greater changes in heart rate and blood pressure response than seen with standard-dose dipyridamole. Associated side effects can be easily reversed with the administration of intravenous aminophylline without significant complications. The sensitivity, specificity, and accuracy of single photon emission computed tomography using high-dose dipyridamole are 100%, 88.9%, and 97.9%, respectively, for the overall presence or absence of disease when compared with coronary arteriography. This is significantly (P < 0.005) greater than that obtained by treadmill nuclear imaging protocols, independent imaging agent.

Myocardial Infarction and Dynamic Left Ventricular Outflow Obstruction Induced by Bronchodilator Therapy

Objective: To report a case of myocardial infarction with patent coronary arteries and left ventricular outflow obstruction induced by a combination of aminophylline and beta2-agonists treatment. Case Summary: A 61-year-old woman, without risk factors for coronary artery disease, was admitted with an exacerbation of bronchial asthma. She received intravenous aminophylline and aerosolized beta2-agonists. She developed hemodynamic and echocardiographic features of obstructive hypertrophic cardiomyopathy and had a myocardial infarction. Her serum theophylline concentration was normal. At cardiac catheterization the coronary arteries were patent and the obstructive features disappeared when the asthma drug treatment was discontinued. Discussion: This case describes the occurrence of a very unusual combination of cardiovascular adverse effects induced by drugs widely used for treatment of bronchial asthma. Aminophylline and beta2-agonists can cause myocardial ischemia by inducing tachycardia, hypercontractility, and coronary artery spasm. Conclusions: Aminophylline and beta2-agonists can induce severe and life-threatening myocardial ischemia, even when used at therapeutic drug concentrations.

Knowledge of asthma and its management in newly qualified doctors in Accra, Ghana

This study assessed first-year doctors' (House Officers) knowledge of asthma at the Korle-Bu Teaching Hospital. Seventy-two out of 80 doctors answered 32 questions on various aspects of asthma. Many of these doctors managed between one to three asthmatics per week. Few, however, did so by acceptable standards. In assessing the severity of asthma, 88% looked for cyanosis, 69% looked for pulsus paradoxicus and 63% looked for a fast pulse rate. Only 63% considered the measurement of peak expiratory flow useful. Ninety-four per cent used intravenous aminophylline, 82% intravenous hydrocortisone and 74% oxygen as the drug of choice for acute severe asthma. In moderate forms of acute asthma, 54% used salbutamol inhaler or intravenous aminophylline, 28% oxygen, 15% steroid inhaler and 14% oral prednisolone. Nebulized bronchodilators are not well known for use in either severe or moderate asthma and only 19–21% of doctors had prescribed their use. In chronic asthma, 55–65% of respondents prescribed bronchodilators compared to 19–35% who gave anti-inflammatory drugs. These results reveal insufficient knowledge of the pathophysiology of asthma, the use of standard drugs in asthma therapy and international guidelines for the management of asthma. The results also show that the pragmatic constraints which exist in developing countries preclude the adoption of international guidelines without local modification.

Protective effects of inhaled aminophylline on methacholine-induced airway responses in greyhound dogs

Aminopylline can be delivered as a heated aerosol via an air-powered small-volume nebulizer. We tested the hypothesis that inhaled aminophylline could attenuate the effects of inhaled methacholine on the airways. Five greyhound dogs were anesthetized, intubated, and ventilated. An esophageal balloon and flow transducer were placed in the ventilator circuit and connected to a BICORE CP-100 respiratory monitor. We measured mean lung resistance, lung dynamic compliance, and work of breathing. Each dog was pretreated for 30 minutes with three different formulations given randomly on separate days: aerosolized saline and intravenous saline, aerosolized aminophylline and intravenous saline, and aerosolized saline and intravenous aminophylline. The dogs were then exposed to a series of five inhalations of methacholine of increasing concentrations given at 15-minute intervals. The results demonstrated a significant reduction in the work of breathing and lung resistance and significantly increased compliance after treatment with aerosolized aminophylline but not with intravenous aminophylline. These findings support our hypothesis that aerosolized aminophylline has a protective effect against methacholine-induced bronchospasm. The results further suggest the possible use of aerosolized aminophylline for the treatment of obstructive lung disease.

EVALUATION OF FACTORS TO INFLUENCE TEOHPYLLINE CLEARANCE IN YOUNG CHILDREN WITH ACUTE ASTHMA

We evaluated the factors which influenced theophylline clearance during continuous intravenous aminophylline infusion in young athmatic children less than 2 years of age. We examined the relationship between the theophylline clearance and various factors sach as age, sex, body weight, fever, diarrhea and vomiting, in each of four deviled age groups.We analyzed these relationship using multi variant analysiswith the rate of discrimination of 84%.Low age (especialy under 6 months old), fever and diarrhea decreased theophylline clearance, but sex, body weight and vomiting were not related to theophylline clearance.These resalts suggest that the be age, diarrhea and fever should be considered when we start the continuous intravenous aminophylline infusion.

Effect of Single Dose Fluoxetine on Theophylline Serum Concentrations.

Fluoxetine has been previously reported to elevate plasma concentrations of several hepatically metabolized medications. Eight healthy male volunteers received intravenous aminophylline (approximately 6 mg kg(minus sign1)) on two occasions separated by 2 weeks. A 40-mg dose of oral fluoxetine was administered 8 h prior to the second administration of fluoxetine. Blood samples were collected and assayed for theophylline. Fluoxetine administration was not associated with any significant differences with respect to peak theophylline serum concentration, total body clearance, or half-life. Possible explanations include the fact that only a single dose of fluoxetine was administered and low fluoxetine serum concentrations were present at the time of aminophylline administration. The most likely explanation, however, is the fact that fluoxetine inhibits cytochrome P450 2D6 activity, whereas theophylline is predominately metabolized by cytochrome P450 1A2. In summary, a single 40-mg dose of fluoxetine failed to alter the plasma concentrations of theophylline when administered intravenously as aminophylline.

High-grade atrioventricular block during dipyridamole stress testing

Dipyridamole stress testing may be used in the diagnosis of coronary artery disease and risk assessment of patients who are unable to exercise. Although dipyridamole perfusion imaging has a good safety record, serious side-effects may rarely occur. We present a case in which dipyridamole induced high-grade atrioventricular (AV) block that responded promptly to intravenous aminophylline but not to atropine.