3383. Management of supraventricular tachyarrhythmias.
Supraventricular tachyarrhythmias are common and treatment is based on the frequency and hemodynamic severity caused by these arrhythmias. Empiric therapy with currently available medications often satisfactorily controls symptomatic arrhythmias. Nonpharmocologic therapy with permanent antitachycardia pacemakers, percutaneous catheter ablation or surgery can be effective for selected patients with medically refractory supraventricular tachyarrhythmias after thorough electrophysiologic evaluation. In selected patients with life-threatening supraventricular tachyarrhythmias due to the WPW syndrome, surgical ablation is the therapy of choice.
3386. Managing critically ill patients with esmolol. An ultra short-acting beta-adrenergic blocker.
Esmolol is a new intravenous beta-adrenergic blocker with an ultrashort (nine-minute) elimination half-life, which has been studied predominantly for control of supraventricular tachycardia and management of certain types of hypertension. Clinical studies indicate that the efficacy of esmolol is equivalent to that of propranolol and verapamil for control of supraventricular tachycardia and to sodium nitroferricyanide (sodium nitroprusside) for control of postoperative hypertension. Esmolol also has been shown to control heart rate and blood pressure during episodes of acute myocardial ischemia. Cardioselectivity is similar to that of metoprolol, and the ability to titrate the effect of esmolol may provide additional assurance that beta-adrenergic blockade will remain within the cardioselective range. The most commonly observed adverse effect seen in clinical trials was asymptomatic hypotension. Hypotension may be minimized by titrating to the minimum effective dose and is readily reversed within 10 to 30 minutes of discontinuing the infusion of esmolol. These unique features represent advantages of great potential merit in critical care medicine.
3389. Hyperbaric oxygen. A therapy in search of diseases.
The application of HBO to the therapy of various human diseases developed over a 300 year period. Like most of medicine, the basis of these applications was and continues to be pragmatic in nature, and involves uncritical and untested judgments. The possibility of risks has been understated and possible benefits have been overstated. Individual physicians offering HBO and organized groups, such as the Undersea Medical Society, advocating its use may well be highly motivated, well meaning, and sincerely convinced that HBO is an important therapeutic approach. It may be that, buried among the host of indications, will be some disorders for which HBO is uniquely and highly effective. If so, the present nonsystem for evaluating responses to HBO will require modification, so that these potentially valuable additions to therapeutics are not lost. Because of its almost global application to a wide variety of diseases, HBO therapy lends itself easily to medical adventurism (therapy in search of a disease) and economic exploitation. If there is some patient benefit to come from the experience of the last 300 years, changes in approach, initiated by baromedical devotees or by medicine generally, or resulting from pressures outside of medicine, will be required.
3392. Theophylline and mucociliary clearance.
Abnormal mucociliary transport is improvement by the action of theophylline, and this effect can be attributed to several mechanisms. The drug may directly and indirectly mediate the increase in the secretory output of bronchial glands, and this effect is enhanced by the vagal gastropulmonary reflex which is stimulated by the irritant action of theophylline on the stomach. Theophylline can increase the transepithelial secretion of fluid into the respiratory tract lumen by stimulating the chloride pump which is controlled by cyclic AMP. Ciliary motility is stimulated by theophylline; most of this effect is confined to the proximal part of the respiratory tree. However, much of the improvement in mucociliary clearance may be a consequence of the bronchodilation induced by theophylline, since the improved airway patency is generally a prerequisite for enhanced mucokinesis. Nevertheless, the multiple sites of action of theophylline in the respiratory tract suggests that this drug should be considered to be of significant value in any disorder characterized by mucostasis.
3393. The effects of theophylline on airway inflammation.
One of the important modes of action of theophylline in asthma and chronic obstructive airway disease may be the inhibition of airway inflammation. This hypothesis is based on in vitro and in vivo studies demonstrating that theophylline at therapeutic concentrations has an inhibitory activity on airway inflammation induced by allergic and nonallergic stimuli. Indirect evidence suggests that airway inflammation is an important determinant in the long-term outcome of chronic obstructive airway disease. The effect of theophylline on the long-term evolution of chronic obstructive lung disease remains to be proven.
3394. Effect of theophylline on diaphragmatic muscle function.
Recent investigations have shown that theophylline improves diaphragmatic contractility of the respiratory muscles in isolated muscle preparations in animals and in normal human subjects. It has also been demonstrated that theophylline can reverse diaphragmatic fatigue and prevent fatigue of the diaphragm when given prophylactically. These effects have also been demonstrated in patients with severe chronic obstructive pulmonary disease, all of whom retained CO2 (PaCO2 53 +/- 3 mm Hg) and had hypoxia (PaO2 57 +/- 8 mm Hg). Theophylline, which increases respiratory muscle strength and delays the onset of diaphragmatic fatigue therefore could be a very useful agent in the treatment of patients with chronic airway obstruction.
3395. Favorable cardiovascular effects of theophylline in COPD.
Theophylline has been utilized widely as a bronchodilator. However, recent studies have shown the potential for administering this drug to enhance cardiovascular performance in patients with chronic obstructive pulmonary disease (COPD). Administered to COPD patients orally as a sustained-action preparation or intravenously as aminophylline, theophylline enhances both right and left heart systolic pump function and lowers both pulmonary artery pressure and pulmonary vascular resistance. These favorable cardiovascular actions suggest an additional use for theophylline in COPD beyond its effects as a bronchodilator.
3396. The role of theophylline in the treatment of dyspnea in COPD.
Dyspnea is influenced by both physiologic and psychologic factors. Breathlessness is common in patients with chronic obstructive pulmonary disease (COPD) and often is the reason that the individual patient seeks medical attention. In order to evaluate the different clinical studies involving the use of theophylline in COPD patients, it is important to consider the three distinct approaches for measuring dyspnea--psychophysical testing, clinical methods, and ratings during exercise. Four randomized, double-blind, placebo-theophylline trials from one to four weeks in duration have evaluated the impact of theophylline on lung function and breathlessness. In these studies, the overall improvement in forced expiratory volume in one second was quite consistent for theophylline compared with placebo therapy. When appropriate clinical methods for measuring dyspnea were used, theophylline showed a positive reduction in breathlessness. These reports suggest that theophylline provides modest objective and subjective improvement in patients with symptomatic chronic air flow obstruction.
3400. Theophylline as a bronchodilator in COPD and its combination with inhaled beta-adrenergic drugs.
The bronchodilating action of theophylline in COPD has been examined, with emphasis on its combined use with inhaled beta 2 agonists. The suggestion is made that failure to recognize the nonlinearity of the dose-response curves for bronchodilators has resulted in underestimating their combined action. Recent studies suggest that systemic theophylline has somewhat different actions on the airways in COPD than inhaled beta agonists, and that more bronchodilation may be possible when the two are used together than large doses of either one. By analogy, with asthma the suggestion is also made that the addition of theophylline is also likely to provide a more constant bronchodilation, reducing peak-trough variations in flow. The most complete clinical comparison to date suggests that, in currently sanctioned doses, a regimen containing both theophylline and an inhaled beta 2 agonist provides significantly greater bronchodilation than either drug alone, with fewer patient withdrawals. Further carefully designed studies are needed to resolve this issue, and particularly, to identify those patients who will derive the greatest benefit from a combined regimen.
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