Predicting the need for hospitalization in children with acute asthma

In an attempt to identify factors which influence the decision of physicians to admit patients with acute asthma to the hospital, we studied prospectively 200 children (age 5.6 +/- 3.1 years, mean +/- SD) presenting to our emergency room with acute asthma. The children were assessed on arrival, and on disposition from the Emergency Room by one of the investigators. After obtaining historic data, a clinical score was assigned, and oxygen saturation and pulmonary function were measured. Of the 134 (67 percent) children who were discharged home from the Emergency Room, five returned within seven days and one was subsequently admitted. The clinical score on disposition was the sole variable found to best predict the decision for hospitalization (sensitivity 73 percent, specificity 95 percent). Of the variables obtained at presentation, the resulting decision tree found the clinical score to predict the decision for hospitalization (sensitivity 79 percent, specificity 75 percent). When the individual components of the clinical score were analyzed, the degree of dyspnea, as assessed by the investigator, was chosen as the rule to predict the hospitalization decision (sensitivity 88 percent, specificity 71 percent). We conclude that the decision with respect to the need for hospitalization in acute childhood asthma, is in practice based mainly on careful clinical evaluation. Pulmonary function and SaO2 measurements, although helpful adjuncts in the assessment of acute asthma, do not appear to contribute to the identification of patients who need hospital admission.     

Blood gas analysis and chest x-ray findings in infants and preschool children with acute airway obstruction

BACKGROUND: The importance of SaO2 in the assessment of respiratory distress in bronchial asthma has been reported. OBJECTIVES: To evaluate the correlation between blood gas analysis and chest X-ray lung opacities in young children presenting with acute respiratory symptoms. METHODS: Eighty patients (43 males and 37 females aged 0.5-24 months; mean+/-SD 9.1+/-7.2 months), either with acute wheezing respiratory symptoms and/or with crackles were enrolled in our study. In all children, blood gas analysis and chest X-rays were performed within 12 h following admission to the emergency department. RESULTS: In 55 children (68.75%) chest X-rays demonstrated lung opacities. Subjects with normal X-rays had paO2 and SaO2 higher than subjects with lung opacities (p<0.0001 and p=0.0001, respectively). Children with lung opacities almost always presented paO2<80 mm Hg. Sensitivity and specificity for the presence of lung opacities of paO2<80 mm Hg were 81 and 90%, respectively, while sensitivity and specificity of SaO2<95% were 92 and 40%, respectively. paO2<80 mm Hg in association with SaO2<95% had a positive predictive value for the diagnosis of pneumonia of 90.9%. CONCLUSIONS: Our study suggests that blood gas analysis, particularly paO2, may help in predicting the presence of lung opacities in patients aged less than 2 years. However, chest X-rays may still be needed to define the actual extension of opacities as well as the possible concomitant presence of complications.     

Use of pulse oximetry in the hospital management of acute asthma in childhood

Oxyhemoglobin saturation values were recorded before and 10 minutes after 5 mg of nebulized salbutamol in 75 children (age, 1.5–14.6 years) admitted to hospital with acute asthma. Other assessments included heart rate, respiratory rate, peak expiratory flow rate, pulsus paradoxus, and an asthma severity score. All assessments were performed by the same observer (GC) and subsequent hospital care was transferred to the on-call pediatricians, who were not told the initial saturation values. Six children required intravenous therapy after hospital admission when their symptoms were not improved after nebulized salbutamol. Cutoff points for each continuous variable were selected so that they identified at least 5 of these 6 children (i.e., with a sensitivity of at least 83 percent). The resulting specificities and positive predictive values were calculated for each variable before and after nebulized therapy. A postnebulizer saturation of less than 91 % had a sensitivity of 100% [95% confidence interval (CI), (54–1001 with a specificity of 98%] (95% CI, 92–100) and a positive predictive value of 86%. This was the best predictor of the need for intravenous (IV) therapy. Correlation coefficients were calculated for the 75 admissions and 2 others who required immediate IV treatment to determine how closely saturation values were related to the other recorded clinical variables. Saturation values were significantly, though weakly, correlated with asthma severity scores and prenebulizer heart rate, but they were not associated with any of the other variables. These results highlight the difficulties encountered when assessing acute asthma in a hospital population with a large number of preschool children. Saturation measurements are easy to obtain in all age groups and help identify those children who require intensive therapy and close supervision after hospital admission. © 1993 Wiley-Liss, Inc.     

Management of acute childhood asthma: a prospective multicentre study.

Children with acute asthma account for a significant proportion of paediatric hospital admissions, and clear guidelines exist for their care. The aim of this study was to determine their management in the UK. Over 1 year (February 1995 to January 1996), children aged 1-14 yrs admitted with acute asthma were studied in both teaching and district general hospitals. An admission pro forma was used to collect data prospectively, with a computer-based information management system for the input of admissions in each centre. Ten centres collected data prospectively, with 1,578 admissions involving 1,352 children (median age 3.6 yrs). Sixty two per cent of children were <5 yrs of age. Sixty three per cent of admissions had initial arterial oxygen saturation (Sa,O2) recorded, and, in those older than 5 yrs, 36% had their initial peak expiratory flow rate recorded. Systemic steroids were given to 78%. An initial Sa,O2 of <92% was associated with a longer stay in hospital, and also with intravenous treatment. Preventative treatment increased from 42% on admission to 53% on discharge. The rates of documented education were low. This is the largest UK study following publication of national guidelines and shows that there is still room for improvement in the management of children admitted with acute asthma.     

Severe Exacerbations in Children with Mild Asthma: Characterizing a Pediatric Phenotype

Background: NHLBI guidelines classify asthma in children as intermittent, mild persistent, moderate persistent, and severe persistent asthma based on baseline symptoms and pulmonary function. However, this may not capture the spectrum of asthma in children, since even mild baseline disease can have significant effects on quality of life. Our objective was to describe a population of children with mild asthma admitted to the ICU with severe exacerbations. Methods: We examined data from all children with asthma who were admitted to the ICU with an acute exacerbation between April 1997, and December 2006. Children were defined as having mild asthma if their disease was classified as intermittent or mild persistent according to NHLBI criteria. Results: Of the 298 children admitted to the ICU with asthma, 164 (55%) were classified as having mild baseline asthma. Compared with children with more severe baseline asthma, mild asthmatic children were younger and less likely to have been previously admitted to the hospital for asthma. Other demographics, including admission severity of illness, gender, and prevalence of overweight, were similar in the two groups. There were no differences between the groups in ICU length of stay, hospital length of stay or types of therapies received. Thirteen children with mild asthma were intubated, although less frequently than those with more severe disease. Conclusions: Children with mild asthma have severe exacerbations. This suggests that chronic asthma severity does not necessarily predict asthma phenotypes during acute exacerbations.     

Risks for developing critical illness with GI hemorrhage

STUDY OBJECTIVES: To define risk factors, identifiable on initial presentation, that predict subsequent physiologic derangements that are consistent with critical illness in patients presenting to hospital with GI hemorrhage (GIH). DESIGN: Observational, cohort study. SETTING: Fourteen-bed medical ICU in a 300-bed community teaching hospital. PATIENTS: One hundred ninety-three patients were studied during 199 separate hospital admissions for GIH. METHODS AMD MEASUREMENTS: Demographic and physiologic variables were extracted from the medical records of patients admitted with GIH. Comprehensive data, from after 2 h in the emergency department to the time of discharge or death, were used to determine whether patients met established ICU admission criteria. Physiologic and demographic data from the initial 2-h period were then compared for patients who subsequently met and for those who did not meet ICU admission criteria. Independent predictors of meeting ICU admission criteria were identified using multiple logistic regression analyses. Sensitivity and specificity associated with the combined use of these predictors were assessed. RESULTS: Thirty-four patients satisfied ICU admission criteria after the initial 2-h period in the emergency department. Sixty-five patients, including 29 of 34 patients who met ICU admission criteria, were actually admitted to the ICU. Among those who never fulfilled ICU admission criteria, the duration of hospital stay was longer for those admitted to the ICU than for those not admitted to ICU (6.6 +/- 0.6 days vs 5.2 +/- 0.3 days; p = 0.04). The admission prothrombin time (international normalized ratio > 1.2), hypotension (systolic BP < 90 mm Hg), acute neurologic changes, and initial APACHE (acute physiology and chronic health evaluation) II score ( > or =15) were the best independent predictors for meeting the defined criteria for admission to ICU. The presence of one or more of these in the first 2 h of presentation was associated with a sensitivity of 88% and specificity of 74% for predicting subsequent critical instability. The area under the receiver operator characteristic curve for use of these four variables was 86% for predicting whether patients met ICU admission criteria. CONCLUSIONS: Many patients with GIH were admitted to the ICU who never met local criteria for admission, and these patients experienced a significantly longer length of hospital stay than other, similarly ill patients. Coagulopathy, hypotension, neurologic dysfunction, and a higher (> or = 15) APACHE II score in the first 2 h of hospitalization were the best independent predictors of the subsequent development of critical illness.     

Plasma elevations of histamine and a prostaglandin metabolite in acute asthma

Recent studies of laboratory-provoked asthma have suggested that asthma is an inflammatory disease of lower airways. The purpose of this study was to measure the systemic elaboration of 2 bronchoconstrictive inflammatory mediators during naturally acquired acute asthma utilizing a prospective, serial-sampling protocol. Plasma levels of 13,14-dihydro-15-keto-PGF2 alpha and histamine were measured by radioimmunoassay and radioenzymatic assay, respectively, in 23 children with acute asthma. Mean PG metabolite and histamine values (pg/ml) before (167 +/- 72, 1,029 +/- 378) and 10 to 90 min after (377 +/- 145, 1,000 +/- 489) initial therapy were significantly higher than those of the same children after resolution of asthma (2.9 +/- 0.2, 260 +/- 42) and those of normal children (4.3 +/- 0.9, 240 +/- 14). Peak PG metabolite levels were significantly higher in children who presented with PEFR values (% predicted) less than 40% (1,234 +/- 432) compared with those who presented with greater than 40% (404 +/- 296), and in children with post-therapy improvement in PEFR of less than 20% (1,281 +/- 470) compared with those with greater than 20% (365 +/- 226). Histamine levels were significantly higher in children with post-therapy improvement in PEFR of less than 20% (2,560 +/- 1,600) compared with those with greater than 20% (475 +/- 100), and in hospitalized (3,915 +/- 1,910) compared with nonhospitalized (408 +/- 130) children. Significant differences were not observed on the basis of corticosteroid dependence, allergic disposition, or type of initial therapy. These data suggest a role for histamine and PGF2 alpha in the pathogenesis of airway inflammation in acute asthma.     

The availability and use of oxygen saturation monitoring in primary care in order to assess asthma severity.

INTRODUCTION: The BTS/SIGN guideline recommends oxygen saturation (SaO2) monitoring as an objective measure of acute asthma severity, particularly in children, in both primary and secondary care. We assessed the availability and use of SaO2 monitoring for acute asthma assessment in primary care. METHODS: Fax and telephone questionnaire of Primary Care services in the Edinburgh region to assess use of SaO2 monitoring in the past 24 months, in association with a 24-month retrospective assessment of A&E attendances with acute wheeze. Children over 12 months of age registered with eligible general practices attending A&E with wheeze and/or asthma were included. RESULTS: There were replies from 103 general practices (100%) and eight Out-of-hours cooperatives (100%). Oxygen saturation monitoring was available in four general practices (3.9%) and three Out-of-hours cooperatives (37.5%). 1408 children attended A&E with wheeze/asthma, 721 referred by primary care. Oxygen saturation monitoring was available to 7.9% of A&E attendees from primary care, but documented in only 1.8% of primary care referrals. CONCLUSIONS: SaO2 monitoring is not widely available in primary care and is infrequently used for the assessment of acute asthma. SaO2 measurement as an adjunct to clinical assessment of asthma in primary care needs encouragement.     

The effectiveness of inhaled corticosteroids in the emergency department treatment of acute asthma: a meta-analysis

STUDY OBJECTIVE: Inhaled corticosteroids (ICSs) are of proven benefit in the treatment of chronic asthma; however, their role in the management of acute asthma is unclear. METHODS: We performed a systematic review of randomized controlled trials involving children or adults treated in the emergency department for acute asthma with or without the addition of ICSs. Outcome measures included hospital admission, pulmonary function tests, and side effects. RESULTS: Seven trials were selected for inclusion in the primary analyses. ICSs versus placebo were compared; data were not available on 1 of these trials. In the remaining 6 trials, a total of 352 patients were studied (179 ICS-treated and 173 non-ICS-treated patients). Two trials compared ICSs plus systemic corticosteroids versus placebo plus systemic corticosteroids; 4 trials compared ICSs versus placebo. Patients treated with ICSs were less likely to be admitted to the hospital (odds ratio 0.30; 95% confidence interval [CI] 0.16 to 0.57) and showed small improvements in peak expiratory flows (weighted mean difference 8%; 95% CI 3% to 13%) Overall, the treatment was well tolerated, with few reports of adverse side effects. A secondary analysis compared ICSs alone versus systemic corticosteroids alone; in the 4 included trials, significant heterogeneity between the study results for admission rates precluded meaningful pooling of admission data. CONCLUSION: There is evidence of decreased admission rates for patients with acute asthma treated with ICSs. However, there is insufficient evidence that ICS therapy results in clinically important changes in pulmonary function when used in acute asthma, and there is insufficient evidence that ICSs alone are as effective as systemic corticosteroids.     

Sex differences among adults presenting to the emergency department with acute asthma. Multicenter Asthma Research Collaboration Investigators.

BACKGROUND: Asthma is an increasing problem worldwide, particularly among women. Sex differences in acute asthma presentation, management, or outcome would have important medical and economic implications. OBJECTIVE: To compare emergency department (ED) visits for acute asthma among women vs men. METHODS: We performed a prospective cohort study as part of the Multicenter Asthma Research Collaboration. Patients in the ED, aged 18 to 54 years, who presented with acute asthma underwent a structured interview in the ED and another by telephone 2 weeks later. The study was performed at 36 EDs in 18 states. Pregnant women with asthma were excluded (n=53). RESULTS: Of 1228 patients, 64.3% were women. Women did not differ significantly from men by age or education level, but women were more likely to be insured, have a primary care provider, and use inhaled corticosteroids. Women had a higher mean+/-SD peak expiratory flow rate than men, both early (expressed as percent predicted) (53%+/-21% vs 41%+/-18%; P<.001) and late (77%+/-24% vs 65%+/-21%; P<.001) in the ED stay. Despite this, women were more likely to be admitted to a hospital (multivariate odds ratio, 2.2; 95% confidence interval; 1.3-4.0) than men. At 2-week follow-up, women had not experienced more relapse events (odds ratio, 1.1) but were 1.5 times more likely to report an ongoing exacerbation (95% confidence interval; 1.0-2.4). CONCLUSIONS: Of adults who presented to the ED with acute asthma, women were almost twice as common as men. Although men received less outpatient care and had worse pulmonary function, women were more likely to be admitted to the hospital and to report an ongoing exacerbation at follow-up. Further studies are needed to better understand the complex relationship between sex and acute asthma.     

Socio-economic disadvantage, quality of medical care and admission for acute severe asthma

Background: In asthma, socio-economic and health care factors may operate by a number of mechanisms to influence asthma morbidity and mortality.
Aim: To determine the quality of medical care including the patient perception of the doctor-patient relationship, and the level of socio-economic disadvantage in patients admitted to hospital with acute severe asthma.
Methods: One hundred and thirty-eight patients (15–50 years) admitted to hospital (general ward or intensive care unit) with acute asthma were prospectively assessed using a number of previously validated instruments.
Results: The initial subjects had severe asthma on admission (pH=7.3±0.2, PaCO2=7.1 ±5.0 kPa, n =90) but short hospital stay (3.7±2.6 days). Although having high morbidity (40% had hospital admission in the last year and 60% had moderate/severe interference with sleep and/or ability to exercise), they had indicators of good ongoing medical care (96% had a regular GP, 80% were prescribed inhaled steroids, 84% had a peak flow meter, GP measured peak flow routinely in 80%, 52% had a written crisis plan and 44% had a supply of steroids at home). However, they were severely economically disadvantaged (53% had experienced financial difficulties in the last year, and for 35% of households the only income was a social security benefit). In the last year 39% had delayed or put off GP visit because of cost. Management of the index attack was compromised by concern about medical costs in 16% and time off work in 20%.
Conclusion: Patients admitted to hospital with acute asthma have evidence of good quality on-going medical care, but are economically disadvantaged. If issues such as financial barriers to health care are not acknowledged and addressed, the health care services for asthmatics will not be effectively utilised and the current reductions in morbidity and mortality may not be maintained.     

Rhinovirus is associated with severe asthma exacerbations and raised nasal interleukin-12

BACKGROUND: Rhinovirus (RV) is associated with asthma exacerbations in longitudinal studies, but the role in patients with acute severe asthma who require admission to a hospital emergency room remains to be fully defined. The cytokines interleukin-10 (IL-10) and IL-12 may be elevated or suppressed by viral infections and contribute to a worsening of airway inflammation in asthmatics. OBJECTIVES: We assessed the association of RV with acute severe asthma and nasal IL-10 and IL-12. METHODS: Patients admitted to a hospital emergency asthma service had nasal aspirates (NAs) taken and peak expiratory flow (PEF) measured on admission and again 7, 28 and 56 days after admission. RV was sought in all NAs using a validated polymerase chain reaction assay and IL-10 and IL-12 were measured on admission and after 56 days in a subgroup of 22 asthmatics and 6 normal controls. RESULTS: Thirty-seven asthmatics with a reduced PEF (% predicted) of 50.4 +/- 2.5% (mean +/- SEM) on admission were studied. RV was detected in NAs of 13 patients (35%) on admission, in 6 of the 13 patients after 7 days (16%), in 1 patient after 28 and 56 days and was absent in controls. IL-10 was not increased on admission or after 56 days. Measurements of IL-12 were raised on admission compared to 56 days later in asthmatics with RV detectable (p = 0.04). In asthmatics without RV, nasal IL-12 levels were correlated with PEF measurements over this period (r = 0.5, p < 0.05). CONCLUSIONS: A temporal relationship between the presence of nasal RV and emergency room admission for acute severe asthma was found in one third of patients. Low levels of IL-10 during RV infections could contribute to unopposed synthesis of pro-inflammatory cytokines whilst increases in IL-12 may amplify nasal and endobronchial inflammation.     

Sex differences in the presentation and course of asthma hospitalizations

OBJECTIVE: To distinguish between differences in prevalence, asthma severity, and treatment to explain sex-related differences in hospitalized asthma patients. DESIGN: Medical record review. SETTING: Thirty US hospitals as part of the University HealthSystem Consortium Asthma Clinical Benchmarking Project. PATIENTS: A random sample of patients aged 2 to 54 years and admitted to the hospital for acute asthma from 1999 to 2000. MEASUREMENTS: Demographics, medical history, initial oxygen saturation, initial peak expiratory flow (adults), initial pulmonary index (children), emergency department course, length of hospital stay, and discharge plans. RESULTS: The cohort included 606 pediatric (aged 2 to 17 years) and 680 adult (aged 18 to 54 years) inpatients. The sex ratio varied significantly by age: 40% were girls 2 to 17 years of age, and 68% were women 18 to 54 years of age p < 0.001). Among children, girls did not differ from boys according to asthma history, pulmonary index scores, or hospital length of stay. Among adults, women were more likely to have a primary care provider (90% vs 73%, p < 0.001) but did not differ according to asthma history or recent medication use. Women had a higher mean initial PEF compared to men (43% of predicted vs 36% of predicted, p < 0.001) and higher median initial oxygen saturation (95% vs 93%, p = 0.002) but did not differ by hospital length of stay. No sex differences in discharge regimens were identified in children or adults. CONCLUSIONS: Among US inpatients with acute asthma, male children are more common than female children, while women are more common in adults. The results in children are probably explained by prevalence differences, since no sex differences were seen in markers of asthma severity or treatment. In adults, increased symptoms in response to a given level of airway obstruction in women may contribute to the female predominance in asthma hospitalizations.     

Treatment and evaluation of patients with acute exacerbation of asthma before and during a visit to the ER in Denmark

Background: Acute exacerbation of asthma may be life‐threatening and quite often results in a visit to the emergency room (ER) or admission to a hospital. The aim was to evaluate the treatment and the quality of clinical management of asthma exacerbations, and finally, to identify the factors leading to admission. Material and methods: In a retrospective design, we audited the hospital records of all patients aged 18–40 years admitted to five Danish university hospitals with an acute exacerbation of asthma in 2004. Results: We found records covering 323 asthmatic patients (186 women). Before admission, the mean (standard deviation) duration of the exacerbation was 5.2 (7.5) days. Of those admitted, 14% did not use any medication, 39% used inhaled corticosteroids (ICS) either with a β₂‐agonist or alone, systemic steroids, and 34% used a β₂‐agonist alone. Lung function (peak flow or forced expiratory volume in first second) was measured in 60% on admission, in 58% on discharge and in 47% on both occasions (P < 0.01). Temperature, heart rate and oxygen saturation were measured in 231 of the patients (72%), but the respiratory frequency rate was measured in only 16% of the patients, with some differences between the five hospitals. On discharge, 50% were treated with systemic steroids, and a further 20% had ICS prescribed (P < 0.01, admission vs discharge). In 21% of the cases, inadequate treatment was identified as the most likely reason for their ER visit/admission to a hospital. Conclusions: The assessment and treatment of patients admitted with acute asthma exacerbation was often suboptimal. Under‐treatment with the anti‐asthmatic medication was the main reason for admission. Please cite this paper as: Backer V, Harving H, Søes‐Petersen U, Ulrik CS, Plaschke P and Lange P. Treatment and evaluation of patients with acute exacerbation of asthma before and during a visit to the ER in Denmark. The Clinical Respiratory Journal 2008; 2: 54–59.     

Identifying An At-Risk Population of Children With Recurrent Near-Fatal Asthma Exacerbations

Background. Children are frequently admitted to hospitals for treatment of severe asthma exacerbations. Anecdotally, a cohort of these children are thought to have multiple readmissions to the intensive care unit (ICU), yet this group of children has not been characterized. The purpose of this study was to examine the factors related to recurrent ICU admissions in children with asthma. Methods. The authors conducted a retrospective study of all children admitted to the pediatric ICU for asthma between April 1997 and December 2007. Children with more than one ICU admission were defined as having recurrent near-fatal asthma exacerbations. Results. During this period, 306 children with asthma were admitted to the ICU on 350 occasions; 269 children had only one ICU admission and 33 children (11%) had two or more ICU admissions. To predict who might require readmission, the authors compared the first hospitalization of all children. When compared with children admitted to the ICU only once, children admitted to the ICU more than once were more likely to be overweight (odds ratio [OR] 2.3; 95% confidence interval [CI] 1.1, 4.9), to have public insurance (OR 3.6; 95% CI 1.5, 8.5), and less likely to be Caucasian (OR 0.34; 95% CI 0.14, 0.86). There was no difference in Nation Heart, Lung and Blood Institute (NHLBI) asthma classification, admission illness severity, durations of therapy, or length of stay (LOS) that might identify those who would require readmission. To determine the effect of readmission analysis on subsequent hospitalization, the authors used multiple logistic regression to identify factors associated with increased LOS in all hospitalizations of the subset of children with recurrent near-fatal asthma exacerbations. In this analysis, LOS was most closely associated with admission severity of illness (p = .002), but not with number of hospitalizations. Conclusions. In this single hospital cohort, there were identifiable factors in children admitted to the ICU that are associated with an increased risk of developing recurrent near-fatal asthma exacerbations. Specifically, overweight children with public insurance were more likely and Caucasian children less likely to be readmitted to the ICU for asthma. These children may represent a group to which specific interventions should be targeted prospectively to prevent readmission.     

Early administration of two intravenous bolus of aminophylline added to the standard treatment of children with acute asthma

OBJECTIVES: Evaluate the efficacy of adding two intravenous bolus of aminophylline to the standard treatment of acute asthma episode in children admitted to the pediatric emergency room (PER). METHODS: Between March 2001 and February 2002, 60 children (2-5 years old), admitted to the PER at Hospital de Clínicas de Porto Alegre (Brazil), due to an episode of acute asthma, refractory to conventional therapy (an oral dose of steroids and at least three doses of inhaled albuterol, associated or not with oxygen) were enrolled in a randomized, double blind, placebo controlled clinical trial. The randomization was performed in blocks of 10 patients, who received a "bronchodilator solution" (either saline or aminophylline), in two doses: on arrival at the PER and again 6h later. The intervention group received aminophylline 5mg/kg/dose diluted in normal saline (NS) solution up to a 20 mL volume, while the placebo group received plain NS, both in an infusion rate of 1 cc/min. The main outcomes were total length of hospital stay, length of supplemental oxygen use, number of bronchodilator nebulizations and/or aerosol inhalations performed and patient destination. The groups were compared using the Students t-test, Mann-Whitney test and Chi-Square test, accepting p<0.05 as significant. RESULTS: Comparing the main outcomes, we did not find differences between the placebo and aminophylline groups: 29.0+/-14.7 versus 26.2+/-13.4 beta-agonist nebulizations per patient (p=0.46); 2.4+/-10.6 versus 5.6+/-14.2 aerosol inhalations per patient (p=0.32); 24.7+/-30.0 versus 26.0+/-25.2h for oxygen supplement (p=0.86); 43.2+/-30.0 versus 43.6+/-23.7h for length of hospital stay (p=0.95). We also did not find differences between the two groups related to the blood pressure, heart rate, respiratory rate and oxygen saturation. CONCLUSION: In children aged 2-5 years admitted to a PER with asthma, two intravenous doses of 5mg/kg of aminophylline given 6h apart did not change the length of stay in hospital, the number of nebulizations given or the duration of oxygen therapy required. We are unable to tell whether there would be benefit with higher doses of aminophylline designed to give levels in the usual therapeutic range.     

First-line therapy for adult patients with acute asthma receiving a multiple-dose protocol of ipratropium bromide plus albuterol in the emergency department

We designed a larger, double-blind, randomized, prospective trial to test our hypothesis that patients with acute asthma given combination high dose therapy with ipratropium bromide (IB) and beta(2)-agonists will have greater improvement in pulmonary function and fewer hospital admissions than those given beta(2)-agonists alone. One hundred eighty patients (mean age +/- SD, 34.3 +/- 10.5 yr) who presented to an emergency department (ED) for treatment of an exacerbation of asthma (baseline FEV(1) < 50% of predicted) were assigned in a randomized, double-blind fashion to receive albuterol and placebo (n = 92) or albuterol and IB (n = 88). Both drugs were administered through a metered-dose inhaler and spacer at 10-min intervals for 3 h (24 puffs or 2,880 microg of albuterol and 504 microg of IB each hour). Primary outcome measures were improvement in pulmonary function (FEV(1) or peak expiratory flow [PEF]), and hospital admission rates. In both groups, pulmonary function improved significantly over baseline values (p < 0.01). Subjects who received IB had an overall 20.5% (95% CI: 2.6 to 38.4%) (p = 0.02) greater improvement in PEF and a 48.1% (95% CI: 19.8 to 76.4%) (p = 0.001) greater improvement in FEV(1) from the control group. At the end of protocol (3 h), 39% (n = 36) of patients in the control group and 20% (n = 18) in the IB group were admitted (p = 0.01). The use of high doses of IB reduced the risk of hospital admission 49% (relative risk = 0.51, 95% CI: 0.31 to 0.83). Five (95% CI: 3 to 17) patients would need to be treated with high doses of IB to prevent a single admission. Kaplan-Meier-estimated curves of the proportion of patients who reached the discharge threshold during the 3 h of treatment, showed a significant difference in favor of the IB group (log-rank test = 0.005). A subgroup analysis showed that patients most likely to benefit from the addition of high doses of IB were those with more severe obstruction (FEV(1) /= 24 h). On the contrary, previous use of inhaled beta(2)-agonists did not modify the admission rate and the pulmonary function response to IB. In conclusion, our data support a substantial therapeutic benefit from the addition of IB to albuterol administered in high doses through MDI plus spacer, particularly in patients with FEV(1) less than 30%, and with long duration of symptoms before the ED presentation (>/= 24 h).