Intravenous beta agonist in severe acute asthma.

STUDY OBJECTIVE--To determine whether salbutamol is more effective in treating severe asthma when given intravenously or by inhalation. DESIGN--Randomised trial of short term response to intravenous versus nebulised salbutamol in acute severe asthma. SETTING--District general hospital (secondary care centre). PARTICIPANTS--76 patients aged 16-70 admitted to hospital with acute severe asthma (peak expiratory flow rate less than 50% of predicted) during study period. Five withdrawn because of adverse effects of treatment or non-response. Of remaining 71, 34 allocated to nebuliser group and 37 to intravenous treatment group. Patients with history of cardiovascular disease or recent corticosteroid or intravenous bronchodilator treatment excluded. Admission characteristics similar in the two groups. INTERVENTIONS--All patients given 5 mg nebulised salbutamol on admission before randomisation plus 200 mg hydrocortisone bolus intravenously and 35% inspired oxygen throughout. Nebuliser group received two more 5 mg doses of nebuliser salbutamol at 30 minutes and 2 hours; intravenous group received 4 hours'' continuous salbutamol infusion (12 micrograms/min) starting at 30 minutes plus supplementary intravenous potassium chloride. No other bronchodilators used. ENDPOINT--Change in peak expiratory flow rate over 4 hours. MEASUREMENTS and MAIN RESULTS--Peak expiratory flow rate improved more in intravenous group (25.2%) than in nebuliser group (14.3%) (p less than 0.01, 95% confidence interval 2.4 to 19.1%). Tachycardia caused two withdrawals from intravenous group; non-response caused three withdrawals from nebuliser group. CONCLUSIONS--Intravenous salbutamol is more effective than nebulised salbutamol in acute severe asthma but may have unacceptable cardiovascular effects.     

Comparison of salbutamol given intravenously and by intermittent positive-pressure breathing in life-threatening asthma.

A double-blind crossover trial was carried out during 22 episodes of life-threatening asthma in 19 patients to compare salbutamol given as a 500 microgram intravenous injection and as a 0 . 5% solution administered by intermittent positive-pressure breathing (IPPB) for three minutes. Relief of pulsus paradoxus was significantly better after IPPB than the intravenous treatment. Both treatments significantly improved the peak expiratory flow rate. Salbutamol given intravenously produced a mean increase in heart rate of over 20 beats/min five minutes after treatment compared with the relief of tachycardia that occurred after administration by IPPB. Four patients had noticeable cardiovascular side effects after salbutamol given intravenously, but no such effects were noticed after administration by IPPB. Two patients withdrawn shortly after entry into the trial because of a worsening clinical condition had received intravenous salbutamol. It is concluded that salbutamol given by IPPB is better than that given by slow intravenous injection in severe acute asthma.     

Effect of intravenous infusion of salbutamol on ventilatory response to carbon dioxide and hypoxia and on heart rate and plasma potassium in normal men.

Intravenous infusion of salbutamol 10 mug/min in seven healthy subjects significantly increased their ventilatory responses to inhaled CO2 in both hypoxia and hyperoxia. These changes in chemical control of breathing are unlikely to be significant when the drug is used in severe asthma but may benefit patients with acute exacerbations of chronic ventilatory failure. The infusion also increased heart rate, which was most pronounced when hypoxia was combined with hypercapnia. The infusion produced an average fall in plasma potassium from 3-99 to 3-10 mmol/l, which was associated with an increase in plasma glucose and serum insulin, suggesting that this arose from a shift of potassium from the extracellular to the intracellular space. Routine monitoring of plasma potassium and the electrocardiogram is indicated when an intravenous salbutamol infusion is used to treat severe asthma as the drug may predispose to cardiac dysrhythmias.     

Salbutamol: tablets,inhalational powder,or nebuliser?

A study was carried out to ascertain the most effective method of giving salbutamol. Seventeen children with severe asthma received active salbutamol (4 mg via a nebuliser, 400 micrograms as an inhalational powder, or a 4 mg tablet) together with complementary placebos on a double-blind, triple-dummy randomly allocated basis. The bronchodilatation effect was assessed by measuring the peak expiratory flow rate. The bronchodilatation effect was greatest when patients received nebulised salbutamol (p less than 0.05) but lasted longest when they received the tablet (p less than 0.0001); the onset of the effect was rapid with all forms of administration. These results indicate that nebulised salbutamol gives the best relief in severe asthma; in less severe cases, however, a regimen combining the inhalational powder and tablets is sufficient and more convenient.     

Serevent nationwide surveillance study: comparison of salmeterol with salbutamol in asthmatic patients who require regular bronchodilator treatment.

OBJECTIVE--To compare safety of salmeterol and salbutamol in treating asthma. DESIGN--Double blind, randomised clinical trial in parallel groups over 16 weeks. SETTING--General practices throughout the United Kingdom. SUBJECTS--25,180 patients with asthma considered to require regular treatment with bronchodilators who were recruited by their general practitioner (n = 3516). INTERVENTIONS--Salmeterol (Serevent) (50 micrograms twice daily) or salbutamol (200 micrograms four times a day) randomised in the ratio of two patients taking salmeterol to one taking salbutamol. All other drugs including prophylaxis against asthma were continued throughout the study. MAIN OUTCOME MEASURES--All serious events and reasons for withdrawals (medical and non-medical) whether or not they were considered to be related to the drugs. RESULTS--Fewer medical withdrawals due to asthma occurred in patients taking salmeterol than in those taking salbutamol (2.91% v 3.79%; chi 2 = 13.6, p = 0.0002). Mortality and admissions to hospital were as expected. There was a small but non-significant excess mortality in the group taking salmeterol and a significant excess of asthma events including deaths in patients with severe asthma on entry. Use of more than two canisters of bronchodilator a month was particularly associated with the occurrence of an adverse asthma event. CONCLUSIONS--Treatment over 16 weeks with either salmeterol or salbutamol was not associated with an incidence of deaths related to asthma in excess of that predicted. Overall control of asthma was better in patients allocated to salmeterol. Serious adverse events occurred in patients most at risk on entry and were probably due to the disease rather than treatment.     

Montelukast in asthma treatment in Croatia

The aim of this study was to determine the efficacy and safety of montelukast added to previous medication in the treatment of a mild and moderate asthma. Data were obtained via questionnaires given to the physicians and given further to their patients. Patients were divided in two groups, first followed 4 weeks (612 patients) and second followed 8 weeks (91 patients). We found out that there was a significant improvement in FEV1 (forced expiratory volume in first second) and general condition of patients and decreased number of salbutamol inhalations after using montelukast. In the second group of patients we find out the same significant improvement in FEV1, general condition and decrease in salbutamol inhalations after 4 weeks of using montelukast and further improvement after the next month of therapy. We conclude that montelukast is an efficient drug with little side effects and with a good compliance. Montelukast managed to achieve a good asthma control; therefore it has a significant place in asthma therapy.     

Comparison of aerosol ipratropium bromide and salbutamol in chronic bronchitis and asthma.

The effects of inhaling 200 mu g of salbutamol were compared with those of inhaling 40 mu g of ipratropium bromide singly and in combination with salbutamol in eight patients with bronchitis and eight asthmatic patients in a double-blind controlled trial. Changes in airways resistance were assessed by measuring the forced expiratory volume in 1 second and specific airways conductance. Both drugs were significantly better in relieving airways obstruction than placebo. Salbutamol was significantly more effective than ipratropium bromide in patients with asthma, but in the patients with bronchitis there was no significant difference between salbutamol and ipratropium bromide. The combination of the two drugs produced a slightly greater and longer response than either drug alone but this was not significant.     

Metabolic effects of salbutamol: comparison of aerosol and intravenous administration.

The effects of intravenous salbutamol (4 mug/kg) were compared with those of aerosol salbutamol (200 mug) in 10 asthmatic patients in a double-blind placebo-controlled study. Both methods of administration produced equal bronchodilatation. Intravenous salbutamol caused significant increases in plasma insulin and glucose levels and a fall in serum potassium concentration in addition to tachycardia and tremor, whereas aerosol salbutamol produced only a small transient increase in the plasma glucose level. The initially raised non-esterified fatty acid levels decreased significantly after aerosol and placebo but not after intravenous salbutamol.     

普米克都保联合沙丁胺醇对咳嗽变异性哮喘患儿的疗效分析

目的:探讨普米克都保联合沙丁胺醇对咳嗽变异性哮喘(CVA)患儿的疗效分析。方法:选取100例CVA患者,沙丁胺醇组(48例)给予沙丁胺醇联合用药组(52例)给予沙丁胺醇和普米克都保,观察并记录两组患者治疗后的疗效,咳嗽缓解及消失时间,治疗前后的用力肺活量(FVC),第1秒用力呼气容积(FEV1)、呼气峰流速(PEF)及最大呼气中段流速(MMEF)等肺功能指标及随访1个月期间的不良反应,评价普米克都保联合沙丁胺醇对咳嗽变异性哮喘的疗效。结果:治疗后联合用药组有效率明显高于沙丁胺醇组(P0.05),联合用药组中有92.3%患者,沙丁胺醇组有72.9%患者咳嗽症状在2周内消失,治疗后联合用药组咳嗽缓解时间和消失时间明显短于沙丁胺醇组(P0.05)。治疗前后,两组在FVC,FEVl,PEF上相比,差异没有统计学意义(P0.05),治疗前,两组MMEF水平均明显低于体检健康者(P0.05),其他肺功能指标与体检健康者相比,无统计学差异(P0.05)。治疗后联合用药组MMEF明显高于治疗前,且高于沙丁胺醇组(P0.05)。沙丁胺醇组治疗前后MMEF未出现明显变化(P0.05)。随访1个月期间,两组不良反应率相比,差异没有统计学意义(P0.05)。结论:普米克都保联合沙丁胺醇能对CVA具有较好的治疗作用,能缩短咳嗽症状消失时间,改善患儿肺功能,值得临床推广使用。     

Effect on beta adrenergic receptors of tachyphylaxis on the sensitivity of smooth muscle in the bronchi to beta adrenergic receptor agonists in bronchial asthma

The study involved 30 subjects: 15 healthy individuals and 15 patients with atopic bronchial asthma of the moderate degree. Salbutamol was administered to asthmatic patients in the intravenous infusion for 7 days. beta-adrenergic receptor density in the lymphocytes and FEV1 were evaluated before and after therapy. Moreover, isoprenaline test was carried out to evaluate the sensitivity of the bronchial smooth muscle to beta-agonist. The test was performed prior to and after salbutamol therapy. It was found that beta-receptor agonist statistically significantly decreases beta-adrenergic receptor density. Equivalently, bronchial smooth muscle is less sensitive to beta-agonist in the same degree as a decrease in beta-adrenergic receptor density in the peripheral blood lymphocytes.     

Use of Benzoctamine as Sedative in Patients with Respiratory Failure

Benzoctamine (Tacitin) was given by mouth as night sedation to patients admitted to hospital with respiratory failure. Fourteen patients had chronic obstructive bronchitis and six had acute severe asthma. One patient with asthma needed intravenous sedation with benzoctamine. No adverse effects were observed, and there was no significant change of forced expiratory volume in one second (FEV₁), forced vital capacity (FVC), or Pco₂ in any patient after benzoctamine. Nevertheless, further clinical experience of the drug is required before its use can be safely recommended in respiratory failure.     

A synthetic VIP peptide analogue inhibits neutrophil recruitment in rat airways in vivo

Currently, there is no effective pharmacotherapy against exaggerated mobilisation of neutrophils in human airway diseases such as chronic obstructive pulmonary disease and asthma. We evaluated the effect of two synthetic vasoactive intestinal peptide (VIP)-like analogues on cytokine-induced neutrophil recruitment in airways in vivo. Recombinant interleukin (IL)-1 beta was administered intratracheally (i.t.) to intubated, spontaneously breathing Sprague-Dawley rats. The rats were pretreated either with a VIP synthetic peptide analogue, a pituitary adenylate cyclase-activating peptide (PACAP)-1-27 synthetic analogue, the beta(2)-adrenoceptor agonist salbutamol or vehicle, systemically or locally. Differential cell counts were performed on bronchoalveolar lavage fluid (BALf) cytospins. Effects on mean arterial blood pressure (MAP) were monitored in separate experiments. Systemic administration of the VIP analogue, the PACAP analogue and salbutamol attenuated the cytokine-induced increase in BALf neutrophil number. Local administration of the VIP analogue and salbutamol, but not the PACAP analogue, also decreased the neutrophil number in BALf. Local administration of the VIP analogue and salbutamol caused a transient decrease in MAP. Systemic or local administration of a synthetic VIP peptide analogue inhibits cytokine-induced neutrophil recruitment in airways in vivo. This action is exerted without severe, sustained cardiovascular side effects, and deserves to be further evaluated in obstructive pulmonary diseases in human.     

Evaluation of peak flow and symptoms only self management plans for control of asthma in general practice.

OBJECTIVE--To compare a peak flow self management plan for asthma with a symptoms only plan. DESIGN--Randomisation to one of the self management plans and follow up for a year. SETTING--Four partner, rural training practice in Norfolk. SUBJECTS--115 Patients (46 children and 69 adults) with asthma who were having prophylactic treatment for asthma and attending a nurse run asthma clinic. MAIN OUTCOME MEASURES--The number of doctor consultations, courses of oral steroids, and short term nebulised salbutamol treatments and the number of patients who required doctor consultations, courses of oral steroids, and short term nebulised salbutamol. RESULTS--Both self management plans produced significant reductions in the outcome measures but there were no significant differences in the degree of improvement between the groups. The results were similar for children and adults. The proportions of patients requiring a doctor consultation fell from 98% (50/51) to 66% (34/51) in the peak flow group and from 97% (62/64) to 53% (34/64) in the symptoms only group and the proportions requiring oral steroids from 73% (34/46) to 47% (21/46) and 52% (31/60) to 12% (7/60). The median number of doctor consultations was reduced from 8.0 to 2.0 in the peak flow group and from 4.5 to 1.0 in the symptoms only group. CONCLUSIONS--The peak flow meter was not the crucial ingredient in the improved illness of the two groups. Teaching patients the importance of their symptoms and the appropriate action to take when their asthma deteriorates is the key to effective management of asthma. Simply prescribing peak flow meters without a system of self management and regular review will be unlikely to improve patient care.     

Domiciliary nebulisers in asthma: a district survey.

Fifty three patients who were found to be using a home nebuliser for asthma completed a questionnaire. The results showed some confusion about the criteria for recommending whether a patient should buy a nebuliser and for its correct use. Twelve patients had not received any instruction on the use of their nebuliser, and only 11 of those old enough used a peak flow meter in conjunction with it. Eight patients aged 7-15 were using inhaled sympathomimetic aerosols only at the time of buying a nebuliser as compared with most of the older patients, who were using regular oral steroids. Forty nine patients assessed their asthma as moderate to severe, but eight of these were not attending a hospital clinic. Several patients were using 20 mg salbutamol or more every day, and on occasion doses of up to 50 mg a day were reported. It is recommended that patients should be assessed before they buy a nebuliser and advice given on correct use by a district nebuliser service, organised either by respiratory function technicians or in physiotherapy departments for adults together with a paediatric health visitor for children.     

Interaction and dose equivalence of salbutamol and salmeterol in patients with asthma.

OBJECTIVE--To examine the pharmacological interaction of salmeterol and salbutamol and to derive an estimate of dose equivalence of salmeterol for airway and systemic effects in patients with asthma. DESIGN--Randomised double blind crossover study. SUBJECTS--12 patients with mild asthma. INTERVENTION--Placebo or salmeterol 50, 100, 200 micrograms given on separate days followed two hours later by inhaled salbutamol in cumulative doses up to 3600 micrograms. MAIN OUTCOME MEASURES--Change in forced expiratory volume in one second (FEV1), heart rate, plasma potassium concentration, QTc interval, tremor amplitude, and creatine kinase myocardial isoenzyme concentration. RESULTS--Compared with placebo, the mean (95% confidence interval) changes in FEV1 and heart rate after salmeterol 200 micrograms were 0.61 (0.32 to 0.90) l and 7.0 (3.8 to 10.2) beats/min. Adding salbutamol caused a large increase in FEV1 after placebo (0.69 l) with progressively smaller changes after increasing doses of salmeterol (0.19 l after salmeterol 200 micrograms). Heart rate and QTc interval increased and plasma potassium concentration decreased roughly in parallel on the four study days with a suggestion of convergence at higher doses of salbutamol. Geometric mean dose equivalences for salmeterol 50 micrograms and 100 micrograms compared with salbutamol were 4.9 and 7.8 (mean 6.4) for FEV1 and ranged from 7.1 (2.9 to 17.0) to 12.6 (4.4 to 36.4) for heart rate, plasma potassium, and tremor (mean 9.5). CONCLUSIONS--The effect of adding salbutamol to salmeterol is largely additive. Weight for weight salmeterol may be up to 10 times more potent than salbutamol. Considering its longer duration of action salmeterol 50 micrograms twice daily could be equivalent to salbutamol in doses up to 500 micrograms four to six hourly.     

Children with asthma: will nebulised salbutamol reduce hospital admissions?

To find out how many children with acute asthma responded to one or two doses of nebulised salbutamol and whether this response could be predicted 100 children were studied prospectively from two district hospitals. Twenty three children needed only one nebulised dose and 19 responded to two. Significant factors differentiating these responders from the remainder were age (24 (63%) of those aged 6 or more responded compared with only six (19%) of those aged 3 or less); regular treatment with a beta 2 sympathomimetic; and use of a rotahaler or aerosol. Those requiring more intensive treatment had faster pulse and respiratory rates on admission and one hour after the first nebulised dose. Another useful clinical sign was persistent supraclavicular indraw. Pulsus paradoxus and peak expiratory flow rate were of limited value in the younger children who had worse asthma. Of 29 children receiving intravenous treatment, 18 (62%) were aged 3 or less, whereas only two (7%) were aged 6 or over. The older children who responded initially to nebulised salbutamol could have been safely reassessed at home, which would have considerably reduced hospital admissions.     

Controlled Comparison of the Bronchodilator Effects of Three β-Adrenergic Stimulant Drugs Administered by Inhalation to Patients with Asthma

In a double-blind trial of the effect of inhaling three different β-adrenergic stimulants (isoprenaline sulphate 1,000 μg., orciprenaline sulphate 1,500 μg., and salbutamol 200 μg.) and a placebo on ventilatory function in 24 patients with chronic asthma salbutamol was found to have a much longer action than isoprenaline, and it produced a slightly more intense and prolonged effect than orciprenaline. In a double-blind subjective assessment 13 of the 24 patients selected salbutamol as the most effective preparation, while only five preferred isoprenaline and three orciprenaline. Hence salbutamol, given by inhalation, may prove to be the most effective drug at present available for the short-term relief of asthmatic symptoms.     

Salbutamol: comparison of bronchodilating effect of inhaled powder and aerosol in asthmatic subjects.

In the treatment of asthma salbutamol can be administered as an aerosol with a metered-dose inhaler or as a powder with a breath-actuated device (Rotahaler). The two forms of the drug were compared in a double-blind placebo-controlled study involving 10 asthmatic adults who were known to respond to salbutamol. The bronchodilating effect of the aerosol and the powder at doses of 200 micrograms and of the powder at doses of 200 and 400 micrograms was compared, bronchodilation being measured in terms of forced expiratory volume and vital capacity. The response was far greater to salbutamol than to placebo, but there was no significant difference between the two forms of the drug or between the lower and higher doses of powder. No side effects were observed.