In a severe asthma crisis all options are indicated or may be indicated before more aggressive options. In the case of a bad evolution with acidosis etc., the patient would be tributary to invasive medication.

A 55-year-old asthmatic patient comes to the ED with an exacerbation. One hour after administration of supplemental oxygen and two nebulizations of salbutamol the patient does not improve. On examination, he breathes at 42 rpm with supraclavicular pull v with scattered inspiratory and expiratory wheezing. Peak flow has decreased from 310 to 220 L/min. A blood gas drawn with 28% oxygen shows a p02 of 54 mmHg and a pC02 of 35 mm Hg. Which of the following do you think is LEAST indicated?

Administer 80 mg of methylprednisolone iv.

Nebulize ipratropium bromide together with salbutamol every 20 minutes.

Start noninvasive mechanical ventilation.

A randomized clinical trial of magnesium sulphate as a vehicle for nebulized salbutamol in the treatment of moderate to severe asthma attacks.

Although it is well known that intravenous administration of MgSO4 as an adjunct to conventional therapy is effective in treating asthma attacks, the effect of nebulized MgSO4 as a vehicle for salbutamol has been less evaluated. The aim of this study was to compare the effects of nebulized salbutamol administrated through either MgSO4 or isotonic saline solution on the 'peak expiratory flow rate' (PEFR), other respiratory and clinical parameters, and hospitalization rate of patients suffering from moderate to severe asthma attacks. Twenty-six patients with asthma attack were enrolled in the study in a randomized single blind fashion. After obtaining initial peak expiratory flow measurements (PEFR) and clinical evaluation, all patients received 1mg/kg corticosteroids and oxygen therapy and then either isotonic MgSO4 (2.5 ml, 6.3%)+salbutamol (2.5 ml) or saline (2.5 ml)+salbutamol (2.5 ml) through a jet nebulizer (group 1 (n=14) vs group 2 (n=12), respectively). The nebulizations were repeated every 20 min for the first hour and every hour for the rest of 4 h. The PEFR measurements and clinical assessment were performed after nebulization at 20th, 60th, 120th, 180th and 240th minutes. Patients were discharged when PEFR reached the target level of 70% of predicted. The baseline PEFRs and clinical parameters were similar between groups 1 and 2 (50.2+/-18.5 vs 44.1+/-13.9, respectively, p>0.05). The mean% increase in PEFR at different measurement levels was similar between the groups. When the treatment response was evaluated within the groups, group 2 showed statistically significant increase in PEFR (% of predicted) 1h earlier than group 1 (60th vs 120th minute, p=0.003 vs p=0.007). The mean duration of achieving target-PEFRs was 105.7+/-72.1 min for group 1 and 118.3+/-96.7 min for group 2 (p>0.05). This study suggested that the additional usage of MgSO4 to nebulized salbutamol has no beneficial effect on the treatment of asthma attacks.

Magnesium for acute exacerbation of chronic obstructive pulmonary disease: A systematic review of randomised trials.

The efficacy of magnesium sulphate in chronic obstructive pulmonary disease (COPD) was assessed by conducting a systematic review of published randomized clinical trials through extensive searches in MEDLINE and SCOPUS with no date limits, as well as manual review of journals. Outcome measures varied depending on route(s) of administration of magnesium sulphate and medications co-administered. Risk of bias was evaluated and quality of evidence was graded. Four (4) randomized trials were included. All trials had a moderate risk of bias and were of average methodological quality. Magnesium sulphate given intravenously did not seem to have an immediate bronchodilatory effect; however it appears to potentiate the bronchodilatory effect of inhaled beta-2 agonists. Increase in peak expiratory flow rate (PEFR) at 30 and 45 min was greater in those who received magnesium sulphate compared to placebo (P = 0.03), although the mean percentage change in PEFR was just 24%, without significant differences in dyspnoea scores, hospital admission rates, or emergency department readmission rates compared to placebo. Nebulized magnesium sulphate with salbutamol versus nebulized salbutamol with saline placebo showed no significant differences is forced expiratory volume in 1 s (FEV1) measured at 90 min after adjustment for baseline FEV1 (P = 0.34) or differences in the need for hospital admission. Combined inhalational and intravenous magnesium sulphate versus intravenous saline placebo and nebulized ipratropium bromide were comparable in terms of hospital admission, intubation and death, but the ipratropium bromide group showed better bronchodilator effect and improvement in arterial blood gas parameters. Overall, trial evidence for trial evidence for magnesium sulphate in acute exacerbation of COPD is poor, and further well-designed trials are needed.

Magnesium sulfate versus ipratropium bromide in chronic obstructive pulmonary disease exacerbation: a randomized trial.

Treatment with short-acting β2-agonists for exacerbations of chronic obstructive pulmonary disease (COPD) results in clinical improvement. It has not been established whether combining short-acting β2-agonists to other bronchodilators is more effective than β2-agonists alone. We conducted a study in patients presenting to the emergency department with exacerbation of COPD. They were randomized to receive nebulized ipratropium bromide (IB group; n = 62) or combined nebulized and intravenous bolus of magnesium sulfate (MgSO4 group; n = 62). All nebulized drugs were administered at 30-minute intervals for 2 hours. Primary outcome included hospital admission, endotracheal intubation, and hospital death rates. Secondary outcome measures were improvement in peak expiratory flow, dyspnea score, and arterial blood gas changes within the first 3 hours. There were no significant differences in primary outcome between MgSO4 and IB groups. Patients given IB average 32 L greater improvement in peak expiratory flow rate compared with magnesium sulfate (95% confidence interval, 19-43 L) at 180 minutes. Simultaneously, there was a significant reduction in PaCO2 compared with baseline values in IB group but not in MgSO4 group. There was a statistically nonsignificant trend toward a decrease in dyspnea score in both groups although adverse events were similar. Although the improvement in peak expiratory flow rate and arterial blood gas favored nebulized IB over magnesium sulfate, there was a nonsignificant difference between both drugs with regard to hospital admission, intubation, and hospital death rates in patients with COPD treated in the emergency department for acute exacerbation.

[Round Table: Severe asthma in pediatrics: treatment of acute crises].

Morbidity and mortality derived from asthma continue to be a main public health problem in many countries, in spite of the advances in the knowledge on the disease and its treatment. There are several risk factors for asthma attack which have to be considered in the management of patients in order to prevent exacerbations and mortality. Smooth bronchial muscle constriction and inflammation with oedema of the bronchial wall are the facts that cause airway flow and resistance disturbances, with hyperinflation, leading to a bigger respiratory work. On the other hand, the bronchial obstruction leads to a ventilation-perfusion disequilibrium and hypoxia. At the beginning of the process there is hypocarbia, but when the attack progresses muscle fatigue happens, and retention of CO2, being a sing of alarm (predictive of respiratory failure) a normal and rising PaCO2. The evaluation of an acute asthmatic patient should accomplish a clinical and objective assessment (peak flow rate and saturation of O2), in order to classify the crisis in: mild, moderate or severe. Managing acute asthmatic patient includes: oxygen, bronchodilator ss2 agonists at high and even continuous doses and systemic corticosteroids to prevent the progression and to control inflammation. These procedures should be promptly instituted. Although there is less evidence on their beneficial effects other measures as intravenous aminophylline, nebulized anticholynergics, magnesium sulphate and intravenous ss2 agonists may be used when the conventional therapy is not quickly successful and the patient is in a critical situation, at a real risk of respiratory failure, and in order to avoid mechanical ventilation. If this is finally instituted, controlled hypoventilation with permissive hypercarbia is now recommended, to avoid barotrauma, which used to be a frequent complication when more aggressive attitude was the rule. Interaction between paralytic agents and corticosteroids may produce a miopathy, so the recommendation now is to try not to use paralytic agents, even with profound sedation of needed. Sixty four patients were treated on 77 occasions in the Pediatric Intensive Care Unit of our hospital. They were 0,5 to 13,9 years old, being 50% less than 5 years old. It was the first attack in 9 (14%) patients. The standard management consisted of oxygen, frequently or continuously nebulized salbutamol and intravenous methylprednisolone (1 to 6 mg/kg/day). Furthermore nebulized ipratropium bromide was administered 58 times (75%), as well as intravenous aminophylline 69 (89%), intravenous salbutamol 23 (30%), magnesium sulphate 16 (21%) and ketamine 10 (13%). Antibiotics were given 22 times (29%). Two 15 month old infants received mechanical ventilation in three occasions, and relevant complications happened (pneumothorax and myopathy, and pneumomediastinum and bronchiolitis obliterans respectively). Fifty six patients have been followed for a period of 3 to 110 months (median 48 months), and 16 (29%) have needed high doses (equal to or move than 800 mcg of budesonide or equivalent). There are data on lung function in 36 of them, FEV1 is normal (> 85% of predicted, between 86 and 127) in 26 (78%) and < 85% (65 to 84%) of predicted in 8 (22%) FEV1 rises more than 15% (16 to 23%) in four patients after the inhalation of a ss2 agonist. Inhaled anesthetic agents and heliox have been used in some pediatric cases. After a severe asthma attack the strategy of management should be reviewed, as well as the possible risk factors.

[Effect of intravenous magnesium sulfate on chronic obstructive pulmonary disease exacerbations requiring hospitalization: a randomized placebo-controlled trial].

Magnesium sulfate has been shown to have a bronchodilating effect in asthma, but this effect has not been clearly established in the context of chronic obstructive pulmonary disease (COPD). For this reason we investigated the possible bronchodilating effect of magnesium sulfate in COPD exacerbations. We studied 24 patients with exacerbated COPD who required admission to our hospital's pneumology department. All patients underwent baseline spirometry and were subsequently randomized to groups in a double-blind crossover design. Patients received 1.5 g of magnesium sulfate or placebo in an intravenous solution for 20 minutes. Those who received magnesium sulfate the first day were given placebo the second day, and vice versa. Spirometry was performed 15, 30, and 45 minutes after administration of magnesium sulfate or placebo. Finally, 400 microg of salbutamol were administered using a spacer and a final spirometry was performed 15 minutes later. All patients also received treatment with corticosteroids, intravenous antibiotics, oxygen, and regularly-scheduled bronchodilator therapy (salbutamol and ipratropium bromide every 6 hours). When we compared absolute increase in milliliters and percentage increase in forced expiratory volume in 1 second (FEV1) obtained with magnesium sulfate application to the increases obtained with placebo after 15, 30, and 45 minutes, no significant differences were found. When we compared absolute and percentage increases in FEV1 after administering salbutamol, we found significantly greater increases after magnesium sulfate administration. The mean (SD) absolute increase in FEV1 was 0.18 [corrected] (0.42) L after magnesium sulfate administration and 0.081 [0.01] L after placebo (P=.004). The percentage increase in FEV1 was 17.11% (3.7%) after magnesium sulfate and 7.06% (1.8%) after placebo (P=.008). Intravenous administration of magnesium sulfate has no bronchodilating effect in patients with COPD exacerbations. It does, however, enhance the bronchodilating effect of inhaled ss2-agonists.

Randomized, double-blind, placebo-controlled trial of intravenous salbutamol and nebulized ipratropium bromide in early management of severe acute asthma in children presenting to an emergency department.

In acute severe asthma, treatment must be initiated early to reverse the pathophysiology that may render airways less responsive to bronchodilation. The addition of nebulized ipratropium bromide to initial emergency department therapy improves pulmonary function, but it is unclear whether this approach results in earlier hospital discharge. The early use of bolus intravenous salbutamol has also been shown to improve outcome, including earlier discharge. We therefore assessed the relative benefits of intravenous salbutamol and nebulized ipratropium bromide in the early management of acute severe asthma in children by a double-blind, randomized, controlled trial. This study was undertaken at a tertiary children's hospital, The Children's Hospital at Westmead, The Royal Alexandra Hospital for Children, Westmead, Sydney, Australia. Only children with severe acute asthma as determined by the National Asthma Campaign guidelines criteria and pulmonary index were included. All children received initial nebulized salbutamol therapy (2.5-5 mg salbutamol in 4 mL of normal saline depending on age) at initial emergency department presentation. If asthma remained severe 20 mins later, an intravenous cannula was inserted and intravenous methylprednisolone (1 mg/kg) was administered to all children receiving nebulized salbutamol every 20 mins. Children were then randomized to one of three groups: intravenous salbutamol (15 microg/kg as a single bolus over 10 mins), ipratropium bromide (250 microg), or intravenous salbutamol plus ipratropium bromide. All observers were blinded to treatment groups. Children were randomly assigned to receive a single-dose intravenous bolus of either saline or salbutamol and either nebulized saline or ipratropium bromide determined by a number generated randomly in the hospital pharmacy. The primary outcomes were recovery time and discharge time of each group. Respiratory and hemodynamic monitoring were continuous during the first 2 hrs of the study and then children were monitored clinically for 24 hrs. A total of 55 children with acute severe asthma were entered into the study over an 18-month period. The three groups were similar demographically, with a mean age of 5.9 yrs, and mean duration of attack of 19.6 hrs. No side effects or treatment intolerance were reported. Children in the groups that received intravenous salbutamol had a significant reduction in recovery time to achieving second hourly inhaled salbutamol (p =.008) compared with those administered inhaled bronchodilator alone. The addition of ipratropium bromide to intravenous salbutamol provided no significant further benefit in terms of nebulizer therapy (intravenous salbutamol compared with intravenous salbutamol plus ipratropium bromide). Children administered intravenous salbutamol ceased supplemental oxygen therapy earlier than those administered ipratropium alone at 12 hrs post-randomization (p =.0003). Children administered intravenous salbutamol could be discharged from the hospital 28 hrs earlier than those administered ipratropium bromide (p =.013). Children administered intravenous salbutamol for severe acute asthma showed a more rapid recovery time, which resulted in earlier discharge from the hospital than those administered inhaled ipratropium bromide. There was no additional benefit obtained by combining ipratropium bromide and intravenous salbutamol administration.

Continuous versus intermittent nebulization of salbutamol in acute severe asthma: a randomized, controlled trial.

This study was conducted to compare the clinical and spirometric effects of continuous and intermittent nebulization of salbutamol in acute severe asthma. Forty-two consecutive patients presenting to the emergency department for acute severe asthma (peak expiratory flow [PEF] mean+/-SD, 24%+/-12% predicted) were prospectively randomly assigned to receive 27.5 mg of salbutamol by either continuous or intermittent nebulization over a 6-hour period. The continuous nebulization group received 15 mg of salbutamol during the first hour and 12.5 mg over the next 5 hours. The intermittent nebulization group received 5 mg of salbutamol every 20 minutes during the first hour and 2.5 mg hourly over the next 5 hours. All participants received oxygen and intravenous hydrocortisone. Clinical and spirometric assessment was performed at baseline, 40 minutes, 60 minutes, and at 3 and 6 hours after the start of the nebulization. Secondary endpoints were the respective rates of hospitalization and treatment failure. A significant clinical and spirometric improvement was observed in both groups over baseline as soon as the 40th minute and was sustained thereafter (absolute PEF increase at the sixth hour 30%+/-18% and 32%+/-22% in the continuous and intermittent nebulization groups, respectively; P <.01 over baseline). PEF and the clinical score evolved similarly in both groups. There was no difference between the groups regarding the failure rate of the initial bronchodilator treatment to terminate the asthma attack (3 [14%] in the continuous nebulization group and 2 [9.5%] in the intermittent nebulization group, absolute difference 4.5% [95% confidence interval -14% to 23%]). Eight (38%) patients and 9 (43%) patients from the continuous and intermittent nebulization groups, respectively, required hospitalization according to predefined criteria (absolute difference 4.8% [95% confidence interval -24% to 34%]). We did not observe an appreciable difference between continuous and intermittent nebulization of salbutamol in acute severe asthma. The decision to use one of these nebulization methods should be based on logistical considerations.

Nebulized magnesium sulphate versus nebulized salbutamol in acute bronchial asthma: a clinical trial.

Intravenous magnesium sulphate (MgSO4) has successfully been used in the treatment of acute asthma. The present study investigated the efficacy of nebulized MgSO4 as a bronchodilator in acute asthma as compared to nebulized salbutamol. This was a randomized, double-blind, controlled clinical trial. Asthmatics aged 12-60 yrs in acute exacerbation, with a peak expiratory flow (PEF) <300 L x min(-1), not having taken bronchodilators and not requiring assisted ventilation were included. Patients were randomized to receive treatment with serial nebulizations of either 3 mL (3.2% solution, 95 mg) MgSO4 solution or 3 mL (2.5 mg) salbutamol solution. All patients were also given 100 mg hydrocortisone i.v., and were monitored continuously for 2 h after which they were given supplemental treatment (if and when needed) and either discharged or admitted. Fischl index, PEF improvements (in % predicted) and admission rates were the outcome variables. Thirty-three patients were studied. Fischl score improvement was comparable and significant in both groups (4.31 to 0.43 in the MgSO4 group and 4.29 to 0.76 in the salbutamol group). The increase in PEF was statistically significant and comparable in both groups (by 35% pred in the MgSO4 and by 42% pred in the salbutamol group). Two patients warranted admission in the salbutamol group and one in the MgSO4 group. Nebulized MgSO4 had a significant bronchodilatory effect in acute asthma. This effect was not significantly different from that of nebulized salbutamol.

Bronchodilators in patients with chronic obstructive pulmonary disease on mechanical ventilation. Utilization of metered-dose inhalers.

Bronchodilators are used widely in the acute exacerbations of chronic obstructive pulmonary disease (COPD), although their effectiveness is not clearly established. We used three bronchodilators in 20 patients with COPD who were being mechanically ventilated. Two of the bronchodilators, ipratropium bromide and salbutamol, were administered from metered-dose inhalers (MDI) through an adapter to the endotracheal tube, and the third, aminophylline, was administered in the form of intravenous infusion. Before administering each drug, peak airway pressure, end-inspiratory pressure, resistive pressure, and auto positive end-expiratory pressure (auto-PEEP) were measured, and inspiratory resistance (Rins) and compliance were calculated. Heart rate (HR) and blood pressure were also recorded, and arterial pH and blood gas determinations were made. These measurements were repeated 60 min after the administration of aminophylline, 15 and 60 min after administering salbutamol, and 30 and 60 min after administering ipratropium bromide. With these three drugs, airway pressures were reduced, as well as auto-PEEP and Rins, with respect to basal values (p less than 0.05). The changes in compliance were only significant with salbutamol (p less than 0.05). HR was only significantly modified with aminophylline (p less than 0.05). No blood gas change was observed with any of the three drugs. It can be concluded that: (1) the three drugs used in this study were equally effective in producing significant bronchodilation in patients on mechanical ventilation for severe acute exacerbation of COPD; (2) the administration of bronchodilators by MDI in intubated patients through a special adapter was as effective as the intravenous administration of aminophylline.

[Efficacy of early administration of nebulized ipratropium bromide in children with asthmatic crisis].

To determine the efficacy of adding ipratropium bromide to nebulized salbutamol in the treatment of children with moderate-to-severe acute asthma attacks. A total of 102 patients aged between 5 months and 16 years were included in a double-blind randomized trial. All patients were given nebulized salbutamol (0.2 mg/kg) and oral steroids (1 mg/kg). Patients in group A received two doses of nebulized ipratropium bromide (250 mg per dose) and patients in group B were given placebo. Oxygen saturation (SaO2) and a clinical score (heart rate, respiratory rate, dyspnea, retraction of the intercostal spaces, and wheezing) rated from 0 to 5 were measured before treatment and at 120 min. Patients in both groups showed similar SaO2 values and clinical scores at baseline (group A, 93.05% and 4.45; group B, 92.78% and 4.43) and at 120 min (group A, 94.33% and 2.45; group B, 94.03% and 2.74), but the percentage of patients admitted to the hospital was higher in group B than in group A (53% vs 35%, p = 0.07). In the subset of patients with the most severe attacks (baseline score 5), the clinical score after treatment and the percentage of admissions were significantly higher in group B (n = 22) than in group A (n = 23) (3.32 vs 2.69 and 73% vs 39%, p < 0.05). Coadministration of ipratropium bromide and repeat doses of nebulized salbutamol produced a small beneficial clinical effect compared with administration of nebulized salbutamol alone. This beneficial effect was related to a decrease in the hospitalization rate, particularly in patients with severe asthma attacks.

Salbutamol and ipratropium by inhaler is superior to nebulizer in children with severe acute asthma exacerbation: Randomized clinical trial.

In moderate-severe asthma exacerbation, salbutamol by inhaler (MDI) is superior to salbutamol delivered by nebulizer (NEB); however, to our knowledge, no studies in children with exclusively severe exacerbations were performed. To compare the efficacy of salbutamol and ipratropium bromide by MDI versus by NEB in severe asthma exacerbations. We performed a clinical trial enrolling 103 children (2-14 years of age) with severe asthma exacerbations (defined by the Pulmonary Score ≥ 7) seen at the emergency room in Asuncion, Paraguay. One group received salbutamol and ipratropium (two puff every 10 min for 2 h and then every 30 min for 2 h more) by MDI with a valved-holding chamber and mask along with oxygen by a cannula separately (MDI-SIB); and the other received nebulization with oxygen (NEB-SIB) of salbutamol and ipratropium (1 every 20 min for 2 h and then every 30 min for 2 h more). Primary outcome was the rate of hospitalization (Pulmonary Score ≥ 7) after 4 h and secondary outcome was oxygen saturation. Fifty two children received MDI-SIB and 51 NEB-SIB. After the 4th hour, children on MDI-SIB had significantly (P = 0.003) lower rate of hospital admission than on NEB-SIB (5.8% vs 27.5%, RR: 0.21 [0.06-0.69], respectively). Similarly, a significant improved clinical score after 60 min and increase in oxygen saturation after 90 min of treatment was observed in MDI-SIB versus NEB-SIB group (4.46 ± 0.7 vs 5.76 ± 0.65, P < 0.00001; and 90.5 ± 1.7 vs 88.43 1 ± 1, P < 0.00001, respectively). Even in severe asthma exacerbations administration of salbutamol and ipratropium by MDI with valved-holding chamber and mask along with oxygen by a cannula separately was more effective than by a nebulizer.

[Randomized clinical trial of intravenous magnesium sulfate versus salbutamol in early management of severe acute asthma in children]

OBJECTIVE: To study the efficacy of intravenous magnesium sulfate and intravenous salbutamol in the treatment of severe asthma in children. METHODS: Randomized, double-blind, placebo-controlled clinical trial, including children above 2 years of age with severe acute asthma admitted to the observation ward of the Pediatric Intensive Care Unit of Hospital São Lucas. All patients received conventional treatment (oxygen, corticoids, beta-adrenergics) on admission, and later received one of the following solutions: a) IVMg (50 mg/kg); b) intravenous salbutamol (1 micro g/kg); c) saline solution. Clinical assessments, electrolyte concentration, and arterial blood gas analyses were recorded before intravenous infusion and one hour after that. RESULTS: Fifty patients participated in this study (of whom 53% were females, mean age = 4.5 years). There were no significant differences among the three groups. The group that received IVMg presented lower blood pressure during administration, which reached normal levels one hour afterwards, along with an increase in serum magnesium (P<0,001) and serum pH, and reduction of PaCO(2). The group that received intravenous salbutamol had lower respiratory rate (P=0.05) and higher blood pressure (P=0.01), and one hour after administration, these patients showed decreased respiratory rate (P=0.02); lower levels of serum potassium (P=0.009); higher pH, and reduced PaCO(2). This group required fewer nebulizations (P=0.009), fewer nebulizations per day (P<0.001) and less oxygen therapy than the IVMg and placebo groups. Acidosis was more persistent (P<0.01) in the placebo group. No difference as to the length of hospital stay was observed in any of the three groups. Artificial ventilation was necessary in 10% of the patients. CONCLUSIONS: The early intravenous administration of magnesium sulfate, especially salbutamol, achieved a rapid clinical response with excellent prognosis and no significant side effects.

[Effects of ipratropium bromide (IPB) and its combination with salbutamol sulfate (SAS) in acute asthmatic attack].

34 patients with acute asthmatic attack were studied in double-blind, randomized and crossover manner. Each of them was treated with following two protocols during two sequential days: 0.5 mg of ipratropium bromide (IPB), followed by 5 mg of salbutamol sulfate (SAS) 75 minutes later; or 5 mg of SAS, followed by another dose 35 minutes late. The drugs were delivered via a jet nebulizer. The effects and side-effects of the treatment were evaluated immediately before the first inhalation and at peak of bronchodilatation (60-75 minutes after IPB or 20-35 minutes after SAS). Compared with inhaled SAS, IPB produced considerable improvement in central airway parameters such as forced expiratory volume in one second (FEV1) peak expiratory flow (PEF) and respiratory resistance (Rrs) (P greater than 0.05), but less improvement in peripheral airway parameters such as forced vital capacity (FVC) and maximal mid-expiratory flow (MMEF) (P less than 0.01). The sequential inhaled SAS after IPB improved all five parameters (P less than 0.01), but the repeated dose of SAS increased only MMEF (P less than 0.01). Compared with double-dose SAS, the sequential treatment with IPB and SAS 1 ed to considerable improvement in FVC and MMEF (P greater than 0.05), but greater improvement in FEV1, PEF and Rrs (P less than 0.01). Heart (rate and tremor scores after two doses of SAS increased significantly (P less than 0.01). It is concluded that IPB alone is less effective than beta-adrenoceptor agonist, but its combination with SAS would be an effective and safe treatment in acute asthmatic attack.

Inhaled budesonide in acute asthma.

To evaluate the efficacy of aerosolized budesonide therapy (with metered dose inhaler and spacer) early in the emergency room treatment of acute moderate exacerbations of bronchial asthma in children. Randomized, double-blind, placebo-controlled trial. Paediatric Emergency Service of an urban teaching hospital and a tertiary case referral centre. Sixty children between 3 and 12 years of age with an acute moderate exacerbation of asthma. All patients received humidified oxygen (5-8 L/min by Venturi(R) mask; Hudson Respiratory Care, Temecula, CA, USA), nebulized salbutamol (0.15 mg/kg in 3 mL saline) and were randomized to receive either budesonide (400 microg) or placebo inhalation (MDI and spacer) at half hourly intervals for three doses. If there was an inadequate response or no response to treatment at the end of 2 h, oxygen and salbutamol therapy were continued and the patient was given one of dose intravenous hydrocortisone and was started on an aminophylline infusion. If there was no response at the end of a further 4 h, the patient was hospitalized. INITIAL EVALUATION AND MONITORING: Colour, respiratory rate (RR), heart rate, accessory muscle usage, chest retraction, wheeze, oxygen saturation (by pulse oximetery) and peak expiratory flow rate (PEFR) was recorded at admission and thereafter at hourly intervals for 3 h or until till the child recovered. The need for oxygen therapy after 2 h and need for hospitalization were recorded. Both groups showed a significant improvement in respiratory status at the end of 2 h. However, children in the intervention group showed greater improvements in RR and PEFR (P < 0. 05) and respiratory distress score (P < 0.1). A significantly lower proportion of the intervention group patients required oxygen therapy for more than 2 h (23% vs 50%; P < 0.05) and aminophylline infusion and systemic corticosteroid therapy (7% vs 27%; P < 0.05). None of the children in the budesonide group, in contrast to 23% of those in the placebo group, required hospitalization (P < 0.05). The length of hospital stay (i.e. time taken to recover from acute asthma) was significantly shorter in the intervention group (3.2 +/- 2.5 h) than in the placebo group (7.8 +/- 11.3 h; P < 0.01). Aerosolized budesonide therapy (with MDI and spacer) together with nebulized salbutamol early in the emergency room treatment of acute moderate exacerbations of asthma helped in early recovery and decreased the need for hospitalization. It may be worthwhile calculating this regimen for home-based early treatment of acute exacerbations.

[The efficacy of nebulized budesonide in acute moderate to severe exacerbations of asthma in children].

To evaluate the effect of nebulized budesonide (BUD) in acute moderate to severe exacerbations of asthma in children. Forty children, 5 to 15 years of age, with acute moderate to severe attacks of asthma, were randomized into BUD group and control group, receiving nebulized 0.5% salbutamol (150 µg/kg) + 0.025% ipratropium bromide (1 ml) + 0.05% budesonide (2 ml) or nebulized 0.5% salbutamol (150 µg/kg) + 0.025% ipratropium bromide (1 ml) + saline (2 ml) at half-hourly intervals for 3 doses respectively. Lung function, respiratory rate (RR), heart rate(HR), oxygen saturation (SaO2) and clinical score (CS) were monitored. The baseline characteristics of the 2 groups were similar. After 3 doses of nebulization, CS, RR, SaO2, FEV(1) and FEV(1)% were significantly improved in both groups (P < 0.05). The CS in BUD group was significantly lower than that in control group at the end of 2 h after the third dose of nebulization 0 (0) vs 0 (1), Z = 2.522, P = 0.012. There were no significant differences in RR, HR and SaO2 between 2 groups (P > 0.05). The improvement of FEV(1)% in the first hour and the second hour after 3 doses of nebulization was 8.0 (6.8)% and 5.5 (6.5)% in BUD group, and 6.0 (8.5)% and 1.0 (6.5)% in control group, the improvement in BUD group being significantly greater than that in control group (Z = 2.270 and 2.686, P = 0.023 and 0.007 respectively). The improvement of FEV(1) in the second hour after 3 doses of nebulization was significantly greater in BUD group than in control group 0.07 (0.12) L vs 0.01 (0.10) L, Z = 2.455, P = 0.014. The full recovery rate in BUD group at the end of 2 h after completion of nebulization was significantly higher than that in control group (17/20, 85.0% vs 9/18, 50.0%, χ(2) = 5.371, P = 0.024). The proportion of patients who needed to use oral corticosteroids was significantly lower in BUD group than in control group (3/20, 15.0% vs 8/18, 44.4%, χ(2) = 3.993, P = 0.046). The hospitalization rate was 5% (1/20) in BUD group, and 17% (3/18) in control group, but the difference was not statistically significant (P > 0.05). Nebulized BUD in high dose and at short intervals combined with rapid-acting bronchodilators has an additional bronchodilator response, associated with more rapid and better improvement in clinical symptoms and lung function, indicating that it is preferred in the early management of acute moderate to severe exacerbation of asthma in children.

Comparison of salbutamol and ipratropium bromide versus salbutamol alone in the treatment of acute severe asthma.

The use of nebulized Ipratropium bromide, quaternary anticholinergic bronchodilators in combination with beta-agonist for the treatment of acute asthma in adults is controversial. In a view of different recommendation the present study is undertaken in Bangladeshi patients. Combination of inhaled Ipratropium bromide and Salbutamol provides greater bronchodilatation than mono therapy with Salbutamol alone in acute severe asthma. Patients of severe asthma (PEFR <50% of predicted) were enrolled into control group (Salbutamol only) and case (Salbutamol + Ipratropium bromide) group. After measurement of peak expiratory flow, patient received 3 doses of 2.5 mg Salbutamol (n=40) only or 3 doses of both 2.5mg Salbutamol and 500mcg Ipratropium bromide at an interval of 20 minutes (n=40) through a jet nebulizer. Peak flow was reassessed 30 & 60 minutes after treatment. Peak flow at baseline was similar in two groups. Then at 30 minutes after nebulization, the mean±SD percentage increase in peak flow was greater in combination group (60.01±35.01%) than Salbutamol group (44.47±25.03%) with difference of 16% (p=0.025). At 60 minutes the percentage increase in peak flow was about 32% greater in combination group than Salbutamol group (94.44±33.70% vs. 62.57±29.26%, p=0.000) and combination group reached percentage predicted peak flow more than 60% while Sabutamol group did not. Ipratropium Bromide and Salbutamol nebulized combinedly have better bronchodilating effect than Salbultamol alone in acute severe asthma.

Acute asthma and the life threatening episode.

To present a clinical approach to the management of acute asthma and the life threatening episode of asthma. A review of published peer-review articles and studies reported from 1966 to 1999 and identified through a MEDLINE search on the management of acute asthma, status asthmaticus and acute fulminant asthma. Asthma is a disease caused by a chronic desquamative eosinophilic bronchitis with airway hyper-responsiveness to specific and non-specific stimuli. It is characterised clinically by episodic airflow obstruction. A life threatening episode indicates the presence of one of the three clinical types; acute severe asthma (an acute episode of bronchospasm where the FEV(1) is 30% or less than the predicted value), status asthmaticus (where the episode becomes resistant to beta-adrenergic agonists and corticosteroids), or acute fulminant asthma (where the onset is rapid and severe and the patient is obtunded). Management of acute severe asthma includes oxygen, continuous nebulised salbutamol (until an adequate clinical response occurs) and intravenous hydrocortisone (200 mg/70 kg i.v. followed by 50 mg/70 kg hourly or 200 mg 4-hourly). The patient's speech, conscious state, pulse and respiratory rate, peak expiratory flow rate, oximetry and blood gases should be monitored, and if there is no improvement or the patient deteriorates, admission to an intensive care unit is required. Additional therapy includes intravenous aminophylline (2mg/kg, followed by 4 mg/kg over 30 minutes), nebulised ipratropium (500 microg 6-hourly), high dose inhaled corticosteroids, intravenous magnesium sulphate (5-10 mmol as a bolus with 40 mmol over 1-2 hours), and even inhaled helium oxygen mixtures. With further deterioration or for the management of acute fulminant asthma, intravenous adrenaline (20-200microg bolus followed by an infusion of 1-10 microg/min) is often used. Endotracheal intubation, with mechanical ventilation (using low tidal volumes and low respiratory rates) ketamine anaesthesia (1-2 mg/kg followed by 50 microg/kg/min), inhaled anaesthetic agents (e.g. diethyl ether) and even extracoporeal life support (using extracorporeal membrane oxygenation) may be required. Inhaled salbutamol and intravenous corticosteroids are initially administered to manage the episode of acute severe asthma. Management of acute fulminant asthma or status asthmaticus requires admission to the intensive care unit and may require anaesthetic agents and complex life support techniques.

The efficacy of nebulized magnesium sulfate alone and in combination with salbutamol in acute asthma.

Evaluation of the efficacy of nebulized magnesium sulfate (MgSO4) alone and in combination with salbutamol in acute asthma. A double-blind randomized controlled study was conducted in Chest and Emergency Departments. Thirty patients of acute attack of bronchial asthma were randomized into three groups: MgSO4 nebulization (group A), salbutamol nebulization (group B), and their combination (group C). All patients were monitored before and after nebulization (each 20 minutes) for peak expiratory flow rate (PEFR), respiratory rate (RR), heart rate (HR), blood pressure, pulsus paradoxus, oxygen saturation, clinical examination, and Fischl index. A highly significant improvement in PEFR, PEFR percentage, and Fischl index and significant decrease in RR and HR was observed in all groups. A similar improvement in PEFR was observed in group A and group B (P=0.389). The difference in peak expiratory flow (PEF) improvement was insignificant between group B and group C (P=0.101), while there was a significant difference between group A and group C (P=0.014) in favor of group C. Nebulized MgSO4 alone or combined with salbutamol has a clinically significant bronchodilator effect in acute asthma and leads to clinical improvement, increase in PEFR, reduction in HR, and reduction in RR. The response to nebulized MgSO4 alone (PEFR improvement 54±35.6 L/min, P=0.001) is comparable (P=0.389) to that of nebulized salbutamol (PEFR improvement 67.0±41.9 L/min, P=0.001) and is significantly less than (P=0.014) that of nebulized combination (PEFR improvement 92.0±26.9 L/min, P=0.000).

Heliox improves pulsus paradoxus and peak expiratory flow in nonintubated patients with severe asthma.

Heliox is a blend of helium and oxygen with a gas density less than that of air that decreases airway resistance (Raw) in patients ventilated for status asthmaticus. We tested whether breathing an 80:20 mixture of helium:oxygen would reduce pulsus paradoxus (PP) and increase peak expiratory flow (PEF) in patients presenting to the emergency room with an exacerbation of asthma. After receiving 30 min of beta-agonist aerosols and intravenously administered methylprednisolone, 27 patients whose PP remained greater than 15 mm Hg and whose PEF remained less than 250 L/min consented to breathe heliox or room air for 15 min. PP decreased and PEF increased with time in control patients, indicating a time-related effect of routine bronchodilator therapy (p < 0.05). PP decreased in 15 of 16 patients during heliox, and the change with heliox was significantly greater than that during air breathing (p < 0.01). PEF measured with a Wright's peak flow meter calibrated for heliox increased in all patients breathing heliox. Again, the increase in PEF during heliox breathing was significantly greater than the corresponding change in control patients breathing air (p < 0.001). To the extent that PP reflects the inspiratory fall in pleural pressure, this reduction in PP indicates a substantial reduction in inspiratory Raw when the less dense gas is inspired through narrowed bronchi having turbulent flow regimes. The 35% increase in PEF while breathing heliox signals a similar reduction in expiratory Raw, which might diminish the hyperinflation often observed during an exacerbation of asthma.(ABSTRACT TRUNCATED AT 250 WORDS)

A controlled trial of nebulized salbutamol and adrenaline in acute severe asthma.

To compare efficacy and safety of nebulisation of adrenaline (2 mg over 10 min) and salbutamol (5 mg over 10 min) in acute severe asthma. Prospective randomized and double blind study. Intensive care unit of a University teaching hospital. 22 asthmatic patients presenting to the emergency room with acute severe asthma. Patients were randomly assigned to receive either adrenaline (n = 11) or salbutamol (n = 11) via a nebulizer. Additional treatment comprised hydrocortisone hemisuccinate (100 mg) and supplemental oxygen (71/min). The efficacy and safety of both drugs were evaluated at 20 and 40 min. A statistically significant increase in the Peak Expiratory Flow (PEF) was achieved at the 20th min in both groups (from 85 +/- 38 l/min to 120 +/- 45 l/min; p < 0.001; and from 107 +/- 28 l/min to 145 +/- 19 l/min; p < 0.001; in adrenaline group and salbutamol group respectively). With both drugs, PEF further increased at 40 min to a level that was statistically significant when compared to the 20 min evaluation. The magnitude of the absolute variation in PEF was similar with both drugs. Both drugs induced a significant decrease in heart rate, respiratory frequency and PaCO2 while the increase of PaO2/FIO2 ratio was not significant. The decrease of respiratory frequency at 40 min was more important with salbutamol (p = 0.03). No side effects were recorded in both groups. After a single dose, nebulized adrenaline (2 mg) proved as effective and safe as salbutamol (5 mg) in acute severe asthma.

Heliox for treatment of exacerbations of chronic obstructive pulmonary disease.

Due to its low density properties, helium-oxygen mixtures have the potential to decrease the work of breathing and possibly avoid the need for intubation and mechanical ventilation in patients with respiratory failure. To determine the effect of the addition of helium/oxygen mixtures (heliox) to standard medical care during ventilated and nonventilated acute exacerbations of COPD. Randomized controlled trials were identified from the Cochrane Airways Review Group asthma Register. Primary authors and experts were contacted. References from included and excluded studies, known reviews and texts were also searched. Studies were selected for inclusion if they compared treatment with heliox to placebo (oxygen or air) in randomized controlled trials in adults with an exacerbation of COPD. Data from all trials were combined using the Review Manager (version 4.1). We planned to perform: 1) random effects weighted mean difference (WMD), with 95% confidence intervals (95% CI), 2) Homogeneity of effect sizes with the Dersimonian and Laird method with p<0.1 as the cut point for significance, and 3) sensitivity analysis on different helium-oxygen mixtures (80/20 vs 70/30), and 4) methodological quality (Jadad score >2 vs. <3). Four studies, all published between 1997 and 2000 met the inclusion criteria. Two studies compared heliox-oxygen vs. air-oxygen in decompensated COPD patients who were not ventilated. One study was performed in mechanical ventilated patients and one in patients undergoing noninvasive pressure support (NIPSV) ventilated patients. Data could be obtained for only two of the studies. One was a randomized crossover study of 70:30 helium-oxygen vs air-oxygen that involved nineteen patients with acute severe COPD, hospitalized in an intensive care unit for NIPSV. In the patients receiving heliox, arterial PCO2 fell more; WMD 0.8 kPa (95% CI 0.26, -1.34). The second was a randomized trial involved 47 patients with acute COPD, who presented to an Emergency Department randomized to receive updraft nebulization of albuterol and ipratropium bromide using 80% helium and 20% oxygen or compressed air as the driving gas. Treatments were administered at 0, 20, 40, and 120 minutes after randomization. There were no significant differences in the change of FEV1 and FVC between the two groups by either the 1 or 2 hours point. although a small improvement in FEF 25-75 was significantly greater in the heliox group than in the air group. There is currently insufficient evidence to support the use of helium-oxygen mixtures to treat acute exacerbations of COPD in either ventilated or nonventilated patients. Suitably designed randomised controlled trials with the endpoint being the avoidance of mechanical ventilation may be justified.

Salbutamol Nebulization During Noninvasive Ventilation in Exacerbated Chronic Obstructive Pulmonary Disease Patients: A Randomized Controlled Trial.

<b<iBackground:</i</b Although nebulizing beta 2-agonists during noninvasive ventilation (NIV) could prove helpful, this administration route has to date never been studied in unstable chronic obstructive pulmonary disease (COPD) patients. We sought to demonstrate that salbutamol could be nebulized through an NIV circuit in COPD exacerbation and improve forced expiratory volume in 1 second (FEV1) as compared with placebo. <b<iPatient and Methods:</i</b This is a bench study to determine the optimal pattern of nebulization followed by a randomized double-blind parallel-group trial comparing salbutamol and placebo aerosols delivered during NIV to 43 intensive care unit patients. Aerosols were generated by a vibrating mesh nebulizer positioned just after the Y-piece. Spirometry was performed immediately before and at several predetermined time points after nebulization. Clinical and biological safety parameters were recorded. <b<iResults:</i</b We failed to demonstrate a difference between salbutamol and placebo when changes in FEV1 were assessed immediately after nebulization (-20 vs. -35 mL, <ip</i = 0.66). However, FEV1 increased significantly from baseline to 40 minutes after the end of salbutamol nebulization, as compared with placebo (+30 vs. -50 mL, <ip</i = 0.04). Nebulization was well tolerated. <b<iConclusion:</i</b When assessing FEV1 changes 40 minutes after the end of 5 mg salbutamol nebulization in patients undergoing NIV, we observed a slight improvement that was statistically significant compared with the changes observed with an equivalent saline volume.

Nebulized Salbutamol with or without Magnesium Sulphate in the Management of Acute Asthma in Children in India: A Randomized Controlled Trial.

There is inconclusive evidence on the role of nebulized magnesium sulphate (MgSO4) in the management of acute asthma in paediatric population. Whether the use of nebulized salbutamol with or without MgSO4 in the management of acute asthma results in clinically significant improvement in lung function in Indian children? The primary outcome measure was to assess improvements in peak expiratory flow rate (PEFR), heart rate, respiratory rate and SpO2. This was a single centre; prospective double-blind randomized control trial conducted in paediatric intensive care unit of a tertiary care centre. Ninety children of 6-14 years with acute exacerbations of bronchial asthma were enrolled to receive either inhaled magnesium sulphate (95 mg) with salbutamol (5 mg) or inhaled salbutamol (5 mg) alone. All patients got three nebulizations done during the first hour at 20 min intervals, two nebulizations during the second hour at 30 min intervals, hourly for the next 2 h and then at 24 and 48 h. Eighty-five patients were finally analysed as per protocol analysis. The trial showed that PEFR increased gradually in both groups over the study duration, but it was statistically not significant. Heart rate decreased significantly in both groups over the study duration. Respiratory rate decreased significantly between the groups at 24 and 48 h only. SpO2 improved too in both groups but was not significant statistically. The addition of nebulized MgSO4 to salbutamol does not seem to result in improvement in lung function in the management of acute asthma in Indian children.

Intravenous aminophylline confers no benefit in acute asthma treated with intravenous steroids and inhaled bronchodilators.

The role of intravenous aminophylline in acute asthma is unclear despite meta-analysis of many studies comparing aminophylline with other bronchodilator therapies. The aim of this study is to determine whether continuous aminophylline infusion confers any benefit in acute severe asthmatics treated with intravenous steroids and inhaled bronchodilators. The study was randomised, double-blind and placebo-controlled. All patients received nebulised salbutamol (1 mL of 0.5%) and ipratropium bromide (1 mL of 0.025%) with glycol diluent (1 mL) at 0, two, four, six, eight and 12 hours, and six-hourly thereafter. In addition all patients were given intravenous hydrocortisone 250 mg six-hourly and oxygen to maintain normoxia. Aminophylline infusions were adjusted to maintain therapeutic levels. Peak expiratory flow rate (PEFR) was measured before and after nebulised bronchodilator on a two-hourly basis in the Emergency Department (ED) and six-hourly on the inpatient wards. Thirty-one patients were clinically sufficiently improved within 12 hours to be discharged home from the ED. The remaining 28 patients were admitted to the inpatient ward for a total trial duration of 48 hours. No significant difference was found between the placebo and treatment groups for measurements of PEFR, or for the duration of stay of the patients in hospital. The power of the study was 80% for a 25% to 33% difference at a 5% level of significance. Presentation values of PEFR and arterial blood gases did not predict which patients would require inpatient admission and which could be safely discharged home from the ED.

Bronchospasm

Additionally, the pediatric population is more susceptible to disease and complications from bronchospasm due to their airway diameter being smaller; applying Poiseuille's Law to the airways it is clear that airflow resistance through a tube is inversely related to the radius of the tube to the fourth power, therefore, decreases in airway results in significant flow impediments. Diagnosis Signs and symptoms: Wheezing Diminished breath sounds Prolonged expiration Increase airway pressures (in ventilated patients) Treatment Beta 2 agonists Beta2-adrenergic agonists are recommended for bronchospasm. Short acting (SABA) Terbutaline Salbutamol Levosalbutamol Long acting (LABA) Formoterol Salmeterol Others Dopamine Norepinephrine Epinephrine - titrate to effect (e.g. 10-50 mcg IV), especially in setting of hemodynamic compromise increasing anesthetic depth IV magnesium Increase FiO2 to 100% and consider manual ventilation Muscarinic Acetylcholine receptor antagonist

The efficacy of nebulized furosemide and salbutamol compared with salbutamol alone in reactive airway disease: a double blind randomized, clinical trial.

We undertook this randomized clinical trial to investigate whether adding furosemide to salbutamol could improve the peak expiratory flow rate (PEFR) and clinical signs of reactive airway disease (RAD) patients. Eligible 18- to 55-year-old patients were randomly divided into intervention and control groups. Patients received 5 mg of nebulized salbutamol and 40 mg of nebulized furosemide in the intervention group and 5 mg of nebulized salbutamol alone in the control group. Patients in both groups received 100 mg of methylprednisolone intravenously stat. Severity of the RAD was estimated before and 45 minutes after treatment in both groups. PEFR was estimated before treatment and at 15, 30, and 45 minutes later. Ninety patients were enrolled, 45 in each group. There were no significant differences between two groups regarding gender, mean age, and normalized PEFR. The baseline mean PEFR was not significantly different between groups (P = 0.58). A repeated measure analysis of variance revealed that the differences between the two treatments was significant (P = 0.0001) and the behavior of two treatments was not similar across the time (P = 0.001). Comparison of clinical severity of acute RAD revealed no significant differences between groups at the end of the trial (0.06). This study showed that adding nebulized furosemide to salbutamol in RAD patients improved PEFR.

[Management of severe acute asthma in adults].

Any life-threatening episode of asthma requires early pre-hospital specialized medical management by emergency medical crews. Gravity depends on both clinical criteria and a peak expiratory flow rate (PEFR) more than 30% below either the level predicted by the reference graph or the patient's reference value. Initial treatment combines continuous nebulizations containing a beta2-agonist and ipratropium bromide, with oxygen administration and intravenous corticosteroid bolus. Recommended as second-line treatment in the absence of adequate response are: intravenous magnesium sulphate and continuous-perfusion beta2-agonists (electric syringe), or, in the case of shock, epinephrine. If mechanical ventilation is required, its settings should aim for low tidal volumes, low frequency, and increased expiratory time.

Acute severe asthma: new approaches to assessment and treatment.

The precise definition of a severe asthmatic exacerbation is an issue that presents difficulties. The term 'status asthmaticus' relates severity to outcome and has been used to define a severe asthmatic exacerbation that does not respond to and/or perilously delays the repetitive or continuous administration of short-acting inhaled beta(2)-adrenergic receptor agonists (SABA) in the emergency setting. However, a number of limitations exist concerning the quantification of unresponsiveness. Therefore, the term 'acute severe asthma' is widely used, relating severity mostly to a combination of the presenting signs and symptoms and the severity of the cardiorespiratory abnormalities observed, although it is well known that presentation does not foretell outcome. In an acute severe asthma episode, close observation plus aggressive administration of bronchodilators (SABAs plus ipratropium bromide via a nebulizer driven by oxygen) and oral or intravenous corticosteroids are necessary to arrest the progression to severe hypercapnic respiratory failure leading to a decrease in consciousness that requires intensive care unit (ICU) admission and, eventually, ventilatory support. Adjunctive therapies (intravenous magnesium sulfate and/or others) should be considered in order to avoid intubation. Management after admission to the hospital ward because of an incomplete response is similar. The decision to intubate is essentially based on clinical judgement. Although cardiac or respiratory arrest represents an absolute indication for intubation, the usual picture is that of a conscious patient struggling to breathe. Factors associated with the increased likelihood of intubation include exhaustion and fatigue despite maximal therapy, deteriorating mental status, refractory hypoxaemia, increasing hypercapnia, haemodynamic instability and impending coma or apnoea. To intubate, sedation is indicated in order to improve comfort, safety and patient-ventilator synchrony, while at the same time decrease oxygen consumption and carbon dioxide production. Benzodiazepines can be safely used for sedation of the asthmatic patient, but time to awakening after discontinuation is prolonged and difficult to predict. The most common alternative is propofol, which is attractive in patients with sudden-onset (near-fatal) asthma who may be eligible for extubation within a few hours, because it can be titrated rapidly to a deep sedation level and has rapid reversal after discontinuation; in addition, it possesses bronchodilatory properties. The addition of an opioid (fentanyl or remifentanil) administered by continuous infusion to benzodiazepines or propofol is often desirable in order to provide amnesia, sedation, analgesia and respiratory drive suppression. Acute severe asthma is characterized by severe pulmonary hyperinflation due to marked limitation of the expiratory flow. Therefore, the main objective of the initial ventilator management is 2-fold: to ensure adequate gas exchange and to prevent further hyperinflation and ventilator-associated lung injury. This may require hypoventilation of the patient and higher arterial carbon dioxide (PaCO(2)) levels and a more acidic pH. This does not apply to asthmatic patients intubated for cardiac or respiratory arrest. In this setting the post-anoxic brain oedema might demand more careful management of PaCO(2) levels to prevent further elevation of intracranial pressure and subsequent complications. Monitoring lung mechanics is of paramount importance for the safe ventilation of patients with status asthmaticus. The first line of specific pharmacological therapy in ventilated asthmatic patients remains bronchodilation with a SABA, typically salbutamol (albuterol). Administration techniques include nebulizers or metered-dose inhalers with spacers. Systemic corticosteroids are critical components of therapy and should be administered to all ventilated patients, although the dose of systemic corticosteroids in mechanically ventilated asthmatic patients remains controversial. Anticholinergics, inhaled corticosteroids, leukotriene receptor antagonists and methylxanthines offer little benefit, and clinical data favouring their use are lacking. In conclusion, expertise, perseverance, judicious decisions and practice of evidence-based medicine are of paramount importance for successful outcomes for patients with acute severe asthma.

[Efficiency of nebulised magnesium sulphate in infective exacerbations of chronic obstructive pulmonary disease].

Conflicting results has been achieved in a small number of clinical studies evaluating the efficiency of magnesium sulphate (MS) in COPD exacerbations. We aimed to investigate the efficiency of nebulised MS in COPD exacerbations. Twenty patients who met the study criteria were randomized into two groups. All patients were treated with O2, antibiotics and oral corticosteroids. Additionally one group received ipratropium bromide (IB) 500 µg together with MS 151 mg/dose, while the other group received IB together with placebo. The patients were followed-up with forced expiratory volume in 1 second (FEV1) and visual analogue scale dyspnea scores for 48 hours. Peak expiratory flow rates (PEFRs) were measured before and 10, 30, 60 and 120 minutes after each nebule treatment. The baseline characteristics of the patients in both groups were similar. The FEV1 values measured at 24 and 48 hours did not show significant changes compared to baseline in both groups. Dyspnea scores in both groups decreased significantly in the first day, and in only MS group in the second day. The % change in the dyspnea score at the end of first day was significantly more in the MS group [-23.8% (13.6)] compared with the placebo group [-9.4% (12.9)] (p= 0.002). The % changes in PEFRs at 10 minutes [4.7 (7.5) and -3.5 (6.0), p= 0.005] and 30 minutes [8.2 (6.7) and 1.3 (5.5), p= 0.03] were significantly greater in the MS group compared with the placebo group on the first day. No side effects developed due to MS. Nebulised MS is a cheap, feasible and safe drug that can be added to the standart bronchodilator treatment since it provides additional relief of dyspnea in patients with COPD exacerbations. This needs to be evaluated in future clinical studies including greater number of patients.

Usefulness of inhaled magnesium sulfate in the coadjuvant management of severe asthma crisis in an emergency department.

Treatment of severe asthma may be difficult despite the use of several medications including parenteral corticosteroids. Intravenous magnesium sulfate (MgSO(4)) is one ancillary drug for severe crisis; its inhaled use is controversial. To evaluate the usefulness of inhaled MgSO(4) compared to placebo in improving lung function, oxygen saturation, and reducing hospital admission as an adjunct to standard treatment in severe asthma crisis. We conducted a placebo-controlled, double-blind clinical trial with asthmatic patients >18 years of age with asthmatic crisis and FEV(1)<60% of predicted (%p). All subjects received 125 mg of IV methylprednisolone followed by nebulization with the combination of albuterol (7.5mg) and ipratropium bromide (1.5mg) diluted in 3 ml of isotonic saline solution (as placebo) or 3 ml (333 mg) of MgSO(4). After 90 min, subjects with FEV(1)<60%p or SpO(2)<88% or persistent symptoms were admitted to the emergency department (ED). We included 30 patients per group who were similar at baseline. The MgSO(4) group showed higher post-bronchodilator (post-BD) FEV(1)%p (69+/-13 vs. 61+/-12, p<0.014) and SpO(2) (92+/-4 vs. 88+/-5%, p<0.006) than the placebo group. Fewer treated patients were admitted to the ED (5 vs. 13) (p<0.047), with relative risk (RR) of 0.26 (95% CI 0.079-0.870). Adding inhaled MgSO(4) treatment to standard therapy in severe asthma crisis improves FEV(1)%p and SpO(2) post-BD and reduces the rate of ED admissions.

Management of phosgene-induced acute lung injury.

Phosgene is a substance of immense importance in the chemical industry. Because of its widespread industrial use, there is potential for small-scale exposures within the workplace, large-scale accidental release, or even deliberate release into a built-up area. This review aims to examine all published studies concerning potential treatments for phosgene-induced acute lung injury and incorporate them into up-to-date clinical guidance. In addition, it aims to contrast the approaches when dealing with small numbers of patients known to be exposed (possibly with dose information) with the presentation of a large and heterogeneous population of casualties following a significant industrial accident or deliberate release; no published guidelines have specifically addressed this second problem. PubMed and Embase were searched for all available years till April 2010 and 584 papers were identified and considered. Because of the nature of the injury, there have been no human trials of patients exposed to phosgene. Multiple small and large animal studies have been performed to examine potential treatments of phosgene-induced acute lung injury, but many of these used isolated organ models, pretreatment regimens, or clinically improbable doses. Recent studies in large animals using both realistic time frames and dosing regimens have improved our knowledge, but clinical guidance remains based on incomplete data. Management of a small-scale, confirmed exposure. In the circumstance of a small-scale, confirmed industrial release where a few individuals are exposed and present rapidly, an intravenous bolus of high-dose corticosteroid (e.g., methylprednisolone 1 g) should be considered, although there are no experimental data to support this recommendation. The evidence is that there is no benefit from nebulized steroid even when administered 1 h after exposure, or methylprednisolone if administered intravenously ≥6 h after exposure. Consideration should also be given to administration of nebulized acetylcysteine 1-2 g, though there is no substantive evidence of benefit outside a small animal, isolated lung model and there is a possibility of adverse effects. If the oxygen saturation falls below 94%, patients should receive the lowest concentration of supplemental oxygen to maintain their SaO(2) in the normal range. Once patients require oxygen, nebulized β-agonists [e.g., salbutamol (albuterol) 5 mg by nebulizer every 4 h] may reduce lung inflammation if administered within 1 h of exposure. Elective intubation should be considered early using an ARDSnet protective ventilation strategy. Management of a large-scale, non-confirmed exposure. In the circumstances of a large-scale industrial or urban release, not all patients presenting will have been exposed and health services are likely to be highly stretched. In this situation, patients should not be treated immediately as there is no evidence that delaying therapy causes harm, rather they should be rested and observed with regular physical examination and measurement of peripheral oxygen saturations. Once a patient's oxygen saturation falls below 94%, treatment with the lowest concentration of oxygen required to maintain their oxygen saturations in the normal range should be started. Once oxygen has been started, nebulized β-agonists [e.g., salbutamol (albuterol) 5 mg by nebulizer every 4 h] may reduce lung inflammation if administered within 1 h of exposure, though delayed administration which is likely following a large-scale release has not been tested formally. There is no benefit from nebulized steroid even when administered 1 h after exposure, or high-dose corticosteroid if administered intravenously ≥6 h after exposure. Although there are no experimental data to support this recommendation, an intravenous bolus of high-dose corticosteroid (e.g., methylprednisolone 1 g) may be considered if presentation is <6 h and resources allow. Depending on the numbers of casualties presenting, invasive ventilation should be initiated either electively once symptoms present (especially where there is a short latent period, indicating likelihood of more significant injury), or delayed until required. Ventilation should be with high positive end expiratory pressure, ARDSnet recommended ventilation. The mechanisms underlying the phosgene-induced acute lung injury are not well understood. Future experimental work should ensure that potential treatments are tested in a large animal model using realistic dosing regimens and clinically relevant timings, such as those that might be found in a mass casualty situation.

Intravenous or inhaled salbutamol in severe acute asthma?

Ten patients with life-threatening attacks of asthma (status asthmatiucus') were treated with salbutamol inhaled by intermittent positive pressure breathing, and their response in terms of rise in peak flow rate was measured. They were then given intravenous salbutamol and any further increment in peak flow was measured. Hydrocortisone treatment was started simultaneously and the responses to salbutamol were re-measured on each of the next three days. Only two patients initially responded to the aerosol, whereas all save one responded to the intravenous drug. The two who responded initially to the aerosol were the two who were able to produce sputum at the time of admission. All patients subsequently responded to the aerosol, and the onset of this response correlated closely with the beginning of sputum production. Sympathominetics should be given parenterally to patients in severe asthma if the response to inhaled drug is reduced or absent.