Efficacy and safety of intravenous theophylline administration for treatment of mild acute exacerbation of bronchial asthma

OBJECTIVE: The present study was designed to evaluate the efficacy and safety of intravenously administered theophylline (IAT) for the treatment of an acute exacerbation of bronchial asthma. The theophylline was solubilized and not combined with ethylenediamine. METHODOLOGY: The subjects were 22 asthmatic patients with mild acute exacerbation of bronchial asthma. All patients had been taking oral sustained-release theophylline and their serum concentrations of theophylline were measured. The 16 patients whose serum theophylline concentrations were <13 microg/mL were randomly selected and treated with IAT (200 mg theophylline in 200 mL saline) for 2 h. Six patients were randomly selected as controls and received 200 mL of saline. Pulmonary function and asthma severity (Borg scale) before and after treatment were measured. RESULTS: After IAT, both PEF (before IAT, 313+/-79 L/min; after IAT, 335+/-107; P<0.05) and FEV(1) (before IAT, 1.66+/-0.47 L; after IAT, 1.83+/-0.44; P<0.05) increased significantly. Furthermore, their severity of asthma as assessed by the Borg scale (before IAT, 2.5+/-1.2; after IAT, 1.3+/-1.0; P<0.05) improved significantly. In contrast, neither FEV(1), PEF, severity of asthma or Borg scale changed significantly in the group who only received saline. None of the patients treated in this study had any adverse effects. CONCLUSION: These results suggest that IAT is useful for patients with mild acute exacerbation of bronchial asthma and is safe if serum theophylline concentrations are measured.     

Comparison of the oral and intravenous routes for treating asthma with methylprednisolone and theophylline

To compare intravenous and orally administered corticosteroids and theophylline in treating acute episodes of airways obstruction, patients with recent worsening of obstructive symptoms were randomly divided into two groups. Group A received methylprednisolone, 80 mg/24 h, and aminophylline by continuous infusion. Group B received a comparable dose of a sustained-release theophylline and methylprednisolone, 80 mg in two equally divided doses, by mouth. Assessment of response was based on daily spirometric tests and evaluation of dyspnea and wheezing. Arterial blood gas and serum theophylline levels were also measured. The groups were comparable with respect to age, sex distribution, smoking history, and spirometric evidence of obstruction. Initial spirometric test results showed moderate obstruction, equal in the two groups. Obstruction improved markedly by both spirometric and clinical criteria in the four-day study period. The improvement in FEV1 and dyspnea index was slightly greater for group B, but the differences were not significant. We conclude that oral administration of steroids and theophylline is as effective as intravenous use in treating hospitalized patients with moderate exacerbations of airways obstruction.     

Comparison of inhaled corticosteroid combined with theophylline and double-dose inhaled corticosteroid in moderate to severe asthma

OBJECTIVE: Recent studies have found that theophylline exerts anti-inflammatory and immunomodulatory effects. This study was performed to compare the efficacy of inhaled corticosteroids (ICS) combined with slow-release theophylline (SRT) with that of double-dose ICS in asthma control, anti-inflammatory activity and safety. METHODOLOGY: In a randomized, open, parallel, control trial, 41 patients with asthma were randomly treated with either beclomethasone dipropionate 500 microg b.i.d. (BDP group) or a combination of BDP 250 microg b.i.d and SRT 0.2 g b.i.d. (SRT/BDP group) for 6 weeks. At the start and at the end of treatment, lung function testing and sputum induction were performed, and plasma cortisol levels were measured. Sputum was analyzed for cell differential counts and the interleukin (IL)-5 level. Patients kept a record of peak expiratory flow (PEF), symptom score, and beta2-agonist use. RESULTS: Significant increases in the morning and the evening PEF and FEV1 were observed (P < 0.05), together with an obvious reduction in symptom score and beta2-agonist use (P < 0.01). Significant decreases in the percentage eosinophils and IL-5 level in induced sputum also occurred (P < 0.05). However, there was no difference between the two groups for all these parameters. There was no significant change in the plasma cortisol level for either group. CONCLUSIONS: Both ICS combined with SRT and double-dose ICS had the same effect on asthma control, improving symptoms and ameliorating lung function. Both therapies had similar anti-airway inflammatory effects and therapeutic safety. Combining SRT with ICS may allow a reduction in ICS dose when treating asthma.     

缓释茶碱对哮喘患者PEF值改善效果的探讨

目的探讨缓释茶碱在支气管哮喘(哮喘)患者临床治疗中的地位。方法哮喘治疗选择晨起最大呼气量(PEF)不满80%最佳值的哮喘患者26例,其中20例予每日定时两次分别口服缓释茶碱(葆乐辉)200 mg两周,另6例除缓释茶碱外,其余治疗治疗方案与使用组完全相同,两组均在治疗观察全期间分别统计观察患者的PEF值以及患者夜醒次数、自觉症状、一秒钟用力呼气容积(FEV1)和一秒钟用力呼气容积比例(FEV1%)变化。结果晨起及夜间PEF值明显改善(均P<0.05),24 h内PEF变化率由平均23.4±11.7%显著减少为16.5±7.1%(P<0.01),夜醒次数(4.1±2.5减少为1.3±2.1,P<0.01),但日间PEF值及患者的自觉症状、FEV1和FEV1%在用药组与非用药组之间未见明显差异。结论缓释茶碱对不同病期以及不同严重度的哮喘均有效,但其用药效果与用药时机有一定的关系。     

The effects of esmolol on the hemodynamics of acute theophylline toxicity

The effects of esmolol, a beta 1-selective adrenergic receptor antagonist with a short duration of action, were studied in a canine model of the hemodynamics of theophylline toxicity. Animals were anesthetized, then given 50 mg/kg aminophylline IV over 20 minutes followed by a continuous infusion of 1.75 mg/kg/hr. Hemodynamic parameters, including heart rate, cardiac output, systemic blood pressure, pulmonary arterial pressure, and pulmonary artery wedge pressure, were measured every 30 minutes along with plasma catecholamines and theophylline levels. Marked tachycardia was seen in the intoxicated state, with heart rate rising from a baseline of 128.0 +/- 8.3 beats per minute (BPM) to 179.0 +/- 7.4 BPM (P = .012). This was associated with increases in catecholamines (baseline norepinephrine .04 +/- .04 ng/mL plasma rose to .42 +/- .21 ng/mL plasma after intoxication, P = .048). The average serum theophylline level during the experiment was 44.0 +/- 1.1 micrograms/mL serum. Esmolol then was given by IV infusion in these animals in doses of 25, 50, and 100 micrograms/kg/min. It returned the heart rate to the preintoxication baseline in a dose-related manner. Esmolol did not decrease cardiac output or lower blood pressure.     

Comparison of intraosseous, central, and peripheral routes of sodium bicarbonate administration during CPR in pigs

Obtaining venous access continues to be one of the most difficult problems faced by a physician caring for the pediatric patient in cardiac arrest. Our study examined the use of the intraosseous route (through the bone) to obtain venous access for sodium bicarbonate administration in a cardiac arrest model. Ventricular fibrillation was induced in 23 domestic swine. Cardiopulmonary resuscitation was performed for five minutes and sodium bicarbonate (1 mEq/kg) was administered through a peripheral IV line (n = 6), a central IV line (n = 5), or intraosseously (n = 6). Controls (n = 6) did not receive bicarbonate. Blood pH was sampled every two minutes for 30 minutes from the right ventricle, left ventricle, and femoral artery. An analysis of variance revealed that the central and intraosseous routes were significantly different (P less than .05) from the peripheral group, and that all three groups were significantly different (P less than .05) from the control. Pathology studies revealed only minor damage to bone when sodium bicarbonate was administered intraosseously. These data demonstrate that the intraosseous route is a rapid and effective alternative for venous access in a cardiac arrest model.     

Early replacement of intravenous aminophylline administration with oral theophylline in treating acute exacerbation of asthma]

Intravenous (i.v.) administration of aminophylline has been used to relieve acute exacerbation of bronchial asthma for almost a century. Despite confidence in its effectiveness, controversy has arisen about its efficacy. We currently use aminophylline in the routine treatment of asthma since the drug is essentially useful. Continuous aminophylline infusion tends to be used rather haphazardly in hospital wards, and the criteria for termination of an infusion have not been clarified. We therefore attempted to determine: 1) whether continuous aminophylline infusion is actually beneficial, 2) whether the TDM (treatment drug monitoring) system can be used to establish a protocol for prescribed dosing after an early switch from i.v. to oral administration, and 3) whether adherence to the protocol would contribute to decreases in the duration of hospitalization and in medical expenses. Seventeen patients with acutely exacerbated asthma were enrolled in this study. Nine patients were prescribed oral theophylline on the second hospital day (p.o. group), while eight received continuous i.v. aminophylline (i.v. group). The serum theophylline concentrations were maintained in the therapeutic range in both groups. Peak flow, symptom scores, and QOL scores showed significant improvements in the p.o. group on the third hospital day. It might therefore be possible, by using the TDM system, to set the dosage of theophylline so that hospitalization is shortened.     

Cardiovascular effects of toxic concentrations of theophylline in the dog

A canine model of theophylline toxicity was used to study the cardiovascular effects seen in severe theophylline poisoning. Eight mongrel dogs were divided equally into two groups. The dogs were anesthetized with pentobarbital and paralyzed with pancuronium bromide. They were ventilated with 100% oxygen and underwent the placement of pulmonary arterial, central venous, femoral arterial, and peripheral venous lines. Group 1 animals received 5.6 mL/kg D5W intravenously (IV) over 20 minutes. Group 2 animals received 140 mg/kg (5.6 mL/kg) of aminophylline IV over the same period. Peak theophylline levels in Group 2 animals averaged 208.9 micrograms/mL. Group 2 animals suffered a marked fall in mean arterial pressure (MAP) and an increase in heart rate. In spite of the fall in MAP (P less than .01), cardiac index actually was increased almost two-fold over Group 1 animals, due mainly to a fall in systemic vascular resistance index (P less than .01). There were no physiologically significant differences in ventricular filling pressures or stroke index between the two groups.     

ICS联合茶碱对哮喘患者呼吸功能及血浆H_2S、血清IL-35的影响

目的研究探讨ICS联合茶碱对哮喘患者呼吸功能及血浆H2S、血清IL-35的影响。方法随机选取2012年5月至2014年12月在我院就诊的哮喘患者120例,随机分成研究组(62例)和对照组(58例),研究组使用ICS联合茶碱治疗,对照组使用ICS联合LABA进行治疗,比较两组患者呼吸功能和血浆H2S、血清IL-35等指标。结果两组患者治疗后FEV1、PEER、ACT评分等指标评分相比治疗前均有明显改善,研究组FEV1、PEER、ACT评分等指标均要明显高于对照组,血浆H2S浓度和血清IL-35浓度均明显高于对照组,差异有统计学意义(P0.05),且经Pearson相关分析,血浆H2S浓度和血清IL-35浓度呈正相关(r=0.422,P=0.001)。治疗后研究组的总有效率(93.55%)明显高于对照组(81.03%),差异具有统计学意义(P0.05)。结论 ICS联合茶碱治疗哮喘患者的疗效明显优于ICS联合LABA,且血浆H2S、血清IL-35水平可以作为哮喘控制水平的评价指标,具有重要的临床应用价值。     

Comparison between theophylline and an adenosine non-blocking xanthine in acute asthma

Enprofylline, a drug without adenosine antagonism and theophylline, a potent adenosine antagonist, were compared, double-blind, randomized, in acute asthma (n = 33). The drugs were given intravenously as loading over 10 min followed by maintenance infusion for 24 h. Mean final plasma levels were very high with enprofylline (14 mg.l), and larger than calculated with theophylline (16 mg.l). Seven patients had maximum levels of enprofylline ranging between 16 and 42 mg.l. Extreme plasma levels of enprofylline were not associated with any theophylline-like central nervous system excitatory effects related to seizure-inducing ability. Some irregularities in the heart rhythm did not raise clinical problems and no significant difference between enprofylline and theophylline was recorded. At 1 h patients on enprofylline (mean plasma level: 5.7 mg.l) and theophylline (12.2 mg.l) had improved their peak expiratory flow rates by 31% and 15% (p less than 0.05), respectively. The improvement in lung function after 24 hours did not differ between treatments suggesting that the high levels of enprofylline were supramaximal for its anti-asthma effects in this situation. In conclusion, with enprofylline it is demonstrated that an adenosine non-blocking xanthine derivative may lack CNS-excitatory effects, but be more potent than theophylline in the treatment of acute asthma.     

A meta-analysis on the efficacy of oral theophylline in patients with stable COPD

Background

Theophylline is a nonspecific inhibitor of phosphodiesterases that, despite exerting bronchodilator and anti-inflammatory effects, is a third-line therapy rarely used to treat chronic airflow limitation. We wished to evaluate the efficacy of oral theophylline as measured by improvements in trough (pre-dose) or peak (post-dose) FEV₁ and FVC in patients with clinically stable COPD.

Design

Meta-analysis of randomized, placebo-controlled trials reported as of June 2005 in which theophylline was orally administered to stable COPD patients and the functional evaluations included pre- and post-theophylline values for FEV₁ and FVC.

Results

A total of 18 trials were included in the meta-analysis. The weighted mean differences (WMD) with 95% confidence intervals (95% CI) for improvement over placebo in trough FEV₁ and FVC were 0.108L (0.053–0.163) and 0.186L (0.036–0.336), respectively, while peak FEV₁ and FVC improved by 0.096L (0.044–0.147) and 0.242L (0.11–0.374), respectively.

Conclusions

Treatment with oral theophylline improves both trough and peak FEV₁ and FVC in clinically stable COPD patients. These results support previously reported benefits of theophylline in COPD.     

Comparison of antiarrhythmic effects of oral prajmalium bitartrate and intravenous lidocaine in acute myocardial infarction

In 35 patients with acute myocardial infarction premature ventricular complexes were quantified from stored continuous electrocardiographic tape recordings using a semiautomated arrhythmia detection system. Seventeen patients, separated at random, received no antiarrhythmic drug and formed the control group. In nine patients prajmalium bitartrate was given orally at a dose of 60 mg. (20 mg. every 4 hours). Nine patients had permanent infusions of 2.1 mg./minute lidocaine (corresponding to a daily dose of 3 g.). In both treated groups premature ventricular complexes decreased significantly as compared to the spontaneous frequency in the control group. Six hours after the onset of therapy premature ventricular complexes were reduced to 37% of the initial value in the prajmalium bitartrate group and to 51% in the lidocaine group, whereas in the control group frequency increased (169%). The peak effect was reached after ten hours when premature ventricular complexes were reduced to 5% under prajmalium bitartrate and to 20% under lidocaine administration.Runs of premature ventricular complexes were nearly completely suppressed after administration of prajmalium bitartrate. Under lidocaine administration runs were moderately and not significantly reduced. Eight hours after the onset of therapy, runs were reduced to 8% of the initial value under prajmalium bitartrate and to only 79% under lidocaine. The effect of prajmalium bitartrate on runs of premature ventricular complexes was significantly more pronounced than the effect of lidocaine.The present study documents that orally administered prajmalium bitartrate is an alternative to intravenous administration of lidocaine in the treatment of ventricular arrhythmias after acute myocardial infarction.     

小剂量皮质类固醇吸入合并小剂量茶碱口服对支气管哮喘 …

目的 研究小剂量茶碱合并小剂量皮质类固醇对哮喘患者的疗产及对下丘脑－垂体－肾上腺轴的影响。方法 ４３例以轻、中度的哮喘患者随机分成两组。茶碱激素组（Ａ）组２１例：给予无水缓释放茶口服,每晚２００ｍｇ,加二丙酸倍氯米松（ＢＤＰ）每天３００μｇ吸入;单纯激素组（Ｂ）组２２例：仅给予ＢＤＰ每天６００μｇ吸入及每晚口服安慰剂,疗程１３周。结果 治疗前、后的症状计分、呼气峰流速值（ＰＥＦ）及其变异率（ＰＥＦ