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Biomedical subjects

H W Kelly

Publications and source records attributed to H W Kelly.

At least 37 records · Page 2Linked to original sources
PubMed1993

Safety of continuous nebulized albuterol for bronchospasm in infants and children.

OBJECTIVE: To determine the incidence of cardiotoxicity in infants and children who receive continuous nebulized albuterol (CNA) for bronchospasm. DESIGN: Prospective, case series. SETTING: A university pediatric intensive care and pediatric subacute units. PATIENTS: Nineteen infants and children who received CNA for at least 24 hours. INTERVENTIONS: None. MEASUREMENTS: Creatinine phosphokinase (CK) was measured at the time of admission and then at 12, 24, 48, and 72 hours while the patient received CNA. Isoenzyme CK-MB fractions were measured if CK concentration was > or = 250 IU/L. One electrocardiogram was obtained for each patient during CNA treatment. All patients had continuous cardiac monitoring during continuous nebulization therapy. MAIN RESULTS: Creatinine phosphokinase levels remained within normal limits for 16 patients during CNA treatment. Three patients had elevated CK and in two CK-MB fractions were elevated at one measurement. None of the electrocardiograms showed evidence of ischemia and no arrhythmias were noted during CNA therapy, even in the patients with elevated CK-MB fractions. CONCLUSIONS: Continuous albuterol therapy appears to be safe in our patient population as there was no significant evidence of cardiotoxicity. The significance of the transient elevation of CK-MB without other evidence of cardiotoxicity remains to be determined.

Acute Disease↗
PubMed1992

Issues and advances in the pharmacotherapy of asthma.

Evidence is accumulating that inflammation of the airways is directly responsible for the increased bronchial hyperresponsiveness (BHR) and lung function obstruction in asthma. Bronchoprovocation with non-specific, direct bronchoconstrictors (methacholine and/or histamine) can be used as an indirect measurement of inflammation. Thus bronchoprovocation is a useful method for evaluating the long-term benefits of various therapies in asthma. The focus of asthma therapy research is now on the development of anti-inflammatory agents. Inhaled corticosteroids are currently the most potent anti-inflammatory agents in the treatment of asthma and so are generally the most effective in reducing BHR with long-term use. Non-corticosteroid anti-inflammatory agents that are currently available are reviewed. Recent studies have suggested that regular use of inhaled bronchodilators may actually be detrimental in asthma. At this time the data is still inconclusive but certainly warrants the attention of practitioners and requires further research, particularly in relation to the long-acting beta 2-agonists, formoterol and salmeterol.

Adrenal Cortex Hormones↗
PubMed1992

Effect of the addition of ciprofloxacin on theophylline pharmacokinetics in subjects inhibited by cimetidine.

OBJECTIVE: Although the effect of individual enzyme inhibitors on hepatic microsomal enzyme activity has been studied extensively, little data exist on the effects of combinations of inhibiting agents. The purpose of this study was to investigate the effect of the addition of a second hepatic oxidative enzyme inhibitor on the inhibition of metabolism in subjects already maximally inhibited by cimetidine. Ciprofloxacin was used as the second inhibitor. DESIGN: In a randomized crossover sequence, subjects received theophylline 5 mg/kg on day 6 of therapy with cimetidine 2400 mg/d, ciprofloxacin 1 g/d, both drugs, or while drug-free. SETTING: National Institutes of Health-funded General Clinical Research Center. PARTICIPANTS: Eight normal volunteers (6 men, 2 women; mean age 25.2 y). OUTCOME MEASURES: Theophylline pharmacokinetic parameters after each treatment were determined by model independent pharmacokinetic analysis. Statistical analysis of the data for differences between treatments was assessed by ANOVA for repeated measures. RESEARCH: When administered alone, ciprofloxacin and cimetidine caused a significant increase in theophylline elimination half-life and a decrease in clearance. Theophylline elimination half-life was significantly longer during combined therapy compared with either drug alone. Theophylline clearance was lower during combined treatment, although this relationship did not reach statistical significance. CONCLUSIONS: The addition of a second enzyme inhibitor in subjects receiving maximally inhibiting doses of cimetidine can produce a further decrease in the hepatic metabolism of drugs that are metabolized by the cytochrome P-450 microsomal enzyme system. As cimetidine and ciprofloxacin are frequently used together for a variety of common clinical indications, clinicians should be aware of this drug interaction and should consider that a similar effect may occur when other enzyme inhibitors are used concomitantly.

Adult↗
PubMed1992

Beta-adrenergic agonists for acute, severe asthma.

OBJECTIVE: To critically review the use of beta-adrenergic agonists in acute, severe asthma with particular focus on aerosol administration. DATA SOURCES: English language articles published since 1971 on the use of beta-agonists for acute asthma. Studies were identified from bibliographies of book chapters, review articles, and other research articles. STUDY SELECTION: All studies (21 total) comparing systemic with inhaled beta-agonists were reviewed, regardless of their design or outcome. Selected studies highlighting specific aspects of beta-agonist use in acute asthma such as beta-agonists versus other bronchodilators, aerosol delivery, and intravenous beta-agonists were also reviewed. DATA EXTRACTION: Performed subjectively by the authors with specific aspects of quality discussed within the body of the article. DATA SYNTHESIS: The beta-agonists provide superior bronchodilation in acute severe asthma compared with either the methylxanthines and/or anticholinergics. The majority of studies found aerosolized beta-agonists to be either as effective as or more effective than parenteral beta-agonists and to produce fewer adverse cardiovascular effects. Studies showing preference for parenteral therapy have either been of poor design or used low doses of an aerosolized beta-agonist. Based on studies of aerosol delivery, there is no advantage of jet nebulization over metered-dose inhalers; however, other aspects, including ease of administration, favor nebulization as the delivery method of choice. The articles recommending intravenous beta-agonists consist of a series of uncontrolled cases. CONCLUSIONS: Aerosolized selective beta 2-agonists are the bronchodilator treatments of choice for acute, severe asthma. Attention to the details of dosing and delivery are required for optimal results. The final dose and dosing interval are determined by the patient's response. Intravenous beta-agonists are hazardous and cannot be recommended.

Administration, Inhalation↗
PubMed1991

Delivery of aerosolized medication to intubated babies.

We studied the delivery of aerosolized cromolyn sodium to intubated babies, and evaluated the effect of changes in delivery techniques. In addition, we compared these results with an in vitro model of aerosol delivery. Cromolyn sodium was used as a marker because once the drug is absorbed, it is excreted unchanged, approximately 50% in urine and 50% in bile. We demonstrated that, in vitro, a conventional, jet-type nebulizer aerosolized 20.5% of a test dose of cromolyn, and only 5.5% of the dose was recovered after passage through 60 cm of ventilator tubing and an endotracheal tube adapter. This increased to 44.5% nebulized and 19% recovered when the volume nebulized was increased from 2 mL to 5 mL. A submicronic nebulizer aerosolized 40% and delivered 33.5% of the test dose. A 20 mg dose of nebulized cromolyn sodium was used as a test dose in infants, after which urine was collected for 4 hours. Forty-three urine samples were collected, after the delivery of cromolyn test doses, from nine babies (16-128 days old) intubated for bronchopulmonary dysplasia. Both the jet and submicronic nebulizers were tested in two positions: 1) in place of the ventilator humidifier, and 2) at the endotracheal tube adapter. There were no statistically significant differences in cromolyn delivery for any system configuration. In all situations, means of less than 0.1% of the test dose were recovered in the urine. We estimated that in all cases, less than 1% of the test dose (approximately 50-100 micrograms of cromolyn) had been deposited in the lung. These results show that although the submicronic nebulizer aerosolized cromolyn more efficiently, no additional cromolyn could be detected in infants. We speculate that a significant portion of the smaller particles are exhaled.

Administration, Inhalation↗
PubMed1991

Corticosteroids for acute, severe asthma.

Corticosteroids have been used in the therapy of acute, severe asthma since the early 1950s. Numerous randomized, double-blind, placebo-controlled trials in adults and children have proven corticosteroids to be efficacious. Only the results from less rigorously designed trials have failed to show a beneficial effect. The onset of response, dose, and mode of administration have been relatively well defined; however, other aspects (i.e., duration of therapy, need to taper the dose, and risks of multiple short bursts) require further study. Early institution of corticosteroids in well-defined patient populations will decrease the need for hospitalizations. However, administration of corticosteroids to every patient presenting to the clinician's office or emergency room prior to aggressive bronchodilator therapy is unwarranted. All patients demonstrating an incomplete response or the inability to maintain a complete response following one to two hours of aggressive bronchodilator therapy should receive a course of corticosteroids. Courses as short as three to five days have proven efficacy in outpatients, whereas hospitalized patients usually are treated for seven to ten days. The duration of therapy depends on the individual rate of response.

Acute Disease↗
PubMed1991

Management of acute asthma.

The principal goal of treatment of the acute exacerbation of asthma is the rapid reversal of the airway obstruction which is best accomplished by the frequent administration of inhaled beta 2-agonists. In addition, the early addition of systemic corticosteroids improves the response in patients who incompletely respond to beta 2-agonists. If present, hypoxemia should be corrected with administration of supplemental oxygen. Close monitoring of the patient's response to treatment is essential and if the patient is over 4 years of age and can cooperate, this should include peak expiratory flow rate (PEFR) measurement.

Acute Disease↗
PubMed1990

Should anticholinergics be used in acute severe asthma?

Anticholinergic drugs have been used in Western medicine for the treatment of asthma since the early 19th century. Studies evaluating drug efficacy in acute severe asthma over the last decade have renewed interest in the optimal use of anticholinergics in this condition. Unlike other bronchodilators (i.e., beta 2-agonists and methylxanthines), the anticholinergics produce bronchodilation only by inhibiting cholinergic-mediated bronchospasm. Therefore, anticholinergic drugs are more dependent on the mechanism of bronchospasm than other bronchodilators. The 18 clinical trials of anticholinergics in acute severe asthma are critically reviewed for design and endpoint measurements. Anticholinergics alone produce a modest bronchodilation in acute severe asthma but are not as consistently effective as beta 2-agonists. Anticholinergics consistently produce an added bronchodilation to aerosolized beta 2-agonists in single- and multiple-dose studies. This bronchodilation appears to be greater in the more severely obstructed patients. This bronchodilation is generally modest (10-20 percent), has not yet been shown to produce greater overall outcome, and has not been evaluated against high-dose frequent administration of aerosolized beta 2-agonists. Currently, only the quaternary amine derivatives are recommended for use in acute asthma. These agents should be reserved as second-line agents for acute severe asthma except possibly for those patients presenting with more severe obstruction (peak expiratory flow rate less than 35 percent of predicted).

Acute Disease↗
PubMed1990

Sympathomimetics for acute severe asthma: should only beta 2-selective agonists be used?

Sympathomimetics have become a mainstay of the treatment of acute asthma. Aerosolization of sympathomimetics provides as great or greater bronchodilation in acute severe asthma with fewer systemic effects than parenteral therapy. Despite the broncho-selectivity achieved with this route of administration, cardiostimulation remains the major, dose-limiting factor in the safe use of sustained, high-dose therapy with these agents. This article reviews the pharmacology, adverse effects, and toxicities of selected beta agonists, as well as clinical studies relevant to the question posed in the title. Although the ideal study to answer this question has not yet been performed, the authors feel that available evidence supports the preferential use of selective beta 2 agonists in patients with acute, severe asthma who will require high doses of beta agonists.

Acute Disease↗
PubMed1990

Safety of frequent high dose nebulized terbutaline in children with acute severe asthma.

Forty-four Pediatric Intensive Care Unit (PICU) admissions for acute severe asthma in 27 children between 8/80 and 10/86 were reviewed to determine the safety of prolonged administration of frequently nebulized terbutaline. The mean dose of nebulized terbutaline was 0.2 mg/kg/dose (range = 0.1 to 0.4 mg/kg/dose) given at a mean frequency of 2.4 +/- 1.2 hours. Seven patients received continuous nebulization at a dose of 0.4 +/- 0.2 mg/kg/h. All patients were placed on continuous cardiorespiratory monitoring. Emergency room therapy was determined by the primary emergency room physicians. Upon admission to the PICU, the mean +/- SD heart rate was 150 +/- 21 bpm and the respiratory rate was 44 +/- 16 bpm. After institution of therapy, these parameters decreased to a similar degree in parallel. The maximum decrease after 36 hours was 28% and 37% for heart rate and respiratory rate, respectively. No cardiac arrhythmias were noted. The initial PaCO2 upon admission to the PICU was 32 mm Hg (range = 24 to 44 mm Hg), the maximum decrease in PaCO2 generally occurred during the 6-hour to 12-hour time interval following admission. We conclude that frequent administration of high doses of nebulized terbutaline is safe in the management of acute severe childhood asthma even in the setting of prolonged administration to the hospitalized child.

Acute Disease↗
PubMed1990

Repeated oral administration of activated charcoal for treating aspirin overdose in young children.

The data from our two patients indicates that gastrointestinal dialysis with repeated oral doses of activated charcoal may significantly enhance the elimination of overdoses of salicylate in young children. Limited experience precludes precise recommendations, but current evidence suggests that gastrointestinal dialysis should be evaluated further for treating pediatric salicylate intoxication.

Administration, Oral↗
PubMed1989

The need for a loading dose of gentamicin in neonates.

We studied pharmacokinetic variables in 100 neonates to evaluate the need for a loading dose of gentamicin. The mean volume of distribution for gentamicin in this population was .542 +/- .205 L/kg. Forty-five percent of these patients would not achieve peak serum concentrations of greater than or equal to 5 micrograms/ml after one dose of 2.5 mg/kg. A loading dose of 4 mg/kg would result in a level of greater than or equal to 5 micrograms/ml in 92% of the patients. After this study, a 4 mg/kg loading dose was initiated at our institution. Peak and trough concentrations at steady state were compared in 50 patients receiving a loading dose and 40 patients who had not received a loading dose. No significant differences were found in peak or trough concentrations after three or more doses, verifying that a loading dose does not affect steady-state concentrations. Because gentamicin toxicities are related to accumulation over time, whereas therapeutic efficacy may be related to early attainment of therapeutic peak serum concentrations, we recommend a loading dose of 4 mg/kg in all neonates beginning gentamicin therapy.

Gentamicins↗
PubMed1989

Effect of norfloxacin on theophylline metabolism.

The purpose of this study was to investigate the effect of norfloxacin on theophylline elimination. Ten normal volunteers were studied. In a randomized crossover sequence, each subject received 6 mg of aminophylline per kg of body weight by a 30-min intravenous infusion on day 4 of taking norfloxacin (400 mg every 12 h) or while drug free. Mean theophylline clearance decreased and mean elimination half-life increased after norfloxacin administration (from 0.036 +/- 0.006 to 0.033 +/- 0.004 liter/h per kg and from 8.7 +/- 1.2 to 9.5 +/- 1.5 h, respectively; P less than 0.05, Wilcoxon signed-ranks test). We conclude that norfloxacin taken in recommended doses for 3 days has a small inhibitory effect on theophylline metabolism that would probably not cause clinically important elevations in theophylline concentrations in most patients.

Adult↗
PubMed1989

Should we stop using theophylline for the treatment of the hospitalized patient with status asthmaticus?

Recent reviews and editorials have indicated that theophylline may not be effective for the therapy of acute severe asthma. This judgment is primarily based on data comparing the efficacy of theophylline to inhaled beta 2-agonists in the emergency room treatment of asthma. The authors believe that it is inappropriate to extrapolate data from short-term studies in the emergency room setting to the hospitalized patients with status asthmaticus. Studies of hospitalized patients in which the patients were monitored for at least 24 hours all demonstrate a positive therapeutic effect for theophylline. The possible reasons for the discrepancies between hospitalized patients and emergency room patients are discussed. Theophylline is still recommended for the management of the hospitalized patient with status asthmaticus.

Asthma↗