Search

Background: Salbutamol-induced lactic acidosis is a rare presentation that could manifest in specific clinical context as acute asthmatic attack treatment. An increase of glycolysis pathway leading to pyruvate escalation is the mechanism of hyperlactatemia in β2-adrenergic agonist drug., Case Presentation: A 40-year-old man who had poor-controlled asthma, presented with progressive dyspnea with coryza symptom for 6 days. He was intubated and admitted into medical intensive care unit due to deteriorated respiratory symptom. Severe asthmatic attack was diagnosed and approximate 1.5 canisters of salbutamol inhaler was administrated within 24 h of admission. Initial severe acidosis consisted of acute respiratory acidosis from ventilation-perfusion mismatch and acute metabolic acidosis resulting from bronchospasm and hypoxia-related lactic acidosis, respectively. The lactate level was normalized in 6 h after hypoxemia and ventilation correction. Given the lactate level re-elevated into a peak of 4.6 mmol/L without signs of tissue hypoxia nor other possible etiologies, the salbutamol toxicity was suspected and the inhaler was discontinued that contributed to rapid lactate clearance. The patient was safely discharged on the 6th day of admission., Conclusion: The re-elevation of serum lactate in status asthmaticus patient who had been administrated with the vast amount of β2-adrenergic agonist should be considered for salbutamol-induced lactic acidosis and promptly discontinued especially when there were no common potentials.

Objectives : Continuous nebulized albuterol is frequently used to treat children with status asthmaticus in the pediatric intensive care unit (PICU) but can have cardiovascular side effects. Limited data exist comparing different dosages. The purpose of this study was to compare hemodynamic side effects of two continuous albuterol doses (10 vs. 25 mg/h). Our hypothesis was that lower dose albuterol would be associated with lower toxicity without increased need for adjunctive therapies. Methods : We conducted a retrospective cohort study of all children over 2 years old receiving continuous nebulized albuterol for status asthmaticus in our PICU from 2011 to 2013. Standard initial therapy was intravenous steroids and continuous nebulized albuterol. Patients receiving 10 mg/h albuterol were compared to those receiving 25 mg/h. Clinical outcomes, including the need for additional asthma therapies as well as hypotension requiring fluid resuscitation, were evaluated. Results : About 632 patients were studied (342 received 10 mg/h, 290 received 25 mg/h). Children in the lower-dose group received less fluid resuscitation without increased adjunctive therapies when adjusted for confounders. Those in the 25 mg/h group receiving 17% higher bolus volume. Those receiving lower-dose albuterol had shorter adjusted PICU and hospital lengths of stay. Conclusions : In our PICU cohort of children with status asthmaticus, use of 10 mg/h continuous albuterol was associated with lower fluid bolus resuscitation without more adjunctive therapies. These findings support the safety of lower doses in this population. Prospective studies evaluating the efficacy and toxicity of specific continuous albuterol dosages in critically ill children with status asthmaticus are warranted.

Background: Intravenous salbutamol is used to treat children with refractory status asthmaticus, however insufficient pharmacokinetic data are available to guide initial and subsequent dosing recommendations for its intravenous use. The pharmacologic activity of salbutamol resides predominantly in the (R)-enantiomer, with little or no activity and even concerns of adverse reactions attributed to the (S)-enantiomer., Objective: Our aim was to develop a population pharmacokinetic model to characterize the pharmacokinetic profile for intravenous salbutamol in children with status asthmaticus admitted to the pediatric intensive care unit (PICU), and to use this model to study the effect of different dosing schemes with and without a loading dose., Methods: From 19 children (median age 4.9 years [range 9 months-15.3 years], median weight 18 kg [range 7.8-70 kg]) treated with continuous intravenous salbutamol at the PICU, plasma samples for R- and S-salbutamol concentrations (111 samples), as well as asthma scores, were collected prospectively at the same time points. Possible adverse reactions and patients' clinical data (age, sex, weight, drug doses, liver and kidney function) were recorded. With these data, a population pharmacokinetic model was developed using NONMEM 7.2. After validation, the model was used for simulations to evaluate the effect of different dosing regimens with or without a loading dose., Results: A two-compartment model with separate clearance for R- and S-salbutamol (16.3 L/h and 8.8 L/h, respectively) best described the data. Weight was found to be a significant covariate for clearance and volume of distribution. No other covariates were identified. Simulations showed that a loading dose can result in higher R-salbutamol concentrations in the early phase after the start of infusion therapy, preventing accumulation of S-salbutamol., Conclusions: The pharmacokinetic model of intravenous R- and S-salbutamol described the data well and showed that a loading dose should be considered in children. This model can be used to evaluate the pharmacokinetic-pharmacodynamic relationship of intravenous salbutamol in children, and, as a next step, the effectiveness and tolerability of intravenous salbutamol in children with severe asthma.

Purpose: The results of a study to determine if rates of poor response differ in patients receiving continuous nebulized albuterol (CNA) therapy with or without the preservative benzalkonium chloride are presented., Methods: A retrospective analysis of the records of all patients who received CNA therapy at a large academic medical center from July 2015 to January 2016 was conducted. Data from patient evaluations performed before and after a change to benzalkonium chloride-containing albuterol were collected. The primary outcome was the rate of poor patient response, defined as a composite endpoint. Secondary outcomes included duration of therapy, dosing requirements, and duration of supplemental oxygen therapy., Results: There was no significant difference in rates of poor response between patients exposed ( n = 80) and patients not exposed ( n = 48) to benzalkonium chloride (16% and 17%, respectively; p = 0.95). The cohort not exposed to benzalkonium chloride had a median CNA duration of 7.0 hours, as compared with 10.5 hours for the cohort exposed to benzalkonium chloride, but this difference was not significant ( p = 0.19). There were no significant differences between the benzalkonium chloride-exposed and nonexposed cohorts in the maximum dosing requirement (12.6 mg/hr versus 12.8 mg/hr, p = 0.89) or median duration of supplemental oxygen use (27.5 hours versus 16.5 hours, p = 0.77)., Conclusion: A study of hospitalized patients receiving CNA detected no significant difference in the frequency of poor response to therapy between groups receiving benzalkonium chloride-free versus benzalkonium chloride-containing albuterol products., Competing Interests: DisclosuresThe authors have declared no potential conflicts of interest., (Copyright © 2018 by the American Society of Health-System Pharmacists, Inc. All rights reserved.)

Aim: Magnesium is an adjunctive therapy used in patients with status asthmaticus who do not respond to conventional therapy. The optimal time from initiation of therapy, to determination of response and administration of magnesium has not yet been resolved. Our objective was to determine if magnesium administered in the non-intensive care setting can decrease duration of continuous albuterol and hospital length of stay., Methods: We performed a retrospective cohort analysis of children ages 2-18 years admitted to the pediatric unit on continuous albuterol between January 2014 and December 2015 in a tertiary care children's hospital. Cohorts were matched on respiratory assessment score (RAS) obtained at a similar duration of albuterol therapy and evaluated for the total duration of continuous albuterol, length of stay (LOS), and adverse events., Results: Thirty-three patients who received magnesium were matched to 33 patients with the same RAS at a similar duration of continuous albuterol therapy who did not receive magnesium. Those who received magnesium had longer duration on continuous albuterol (34 vs 18 h; P = 0.001; 95% confidence interval [CI] 4-20; effect size 0.41) and longer LOS (72 vs 49 h; P = 0.037; 95% confidence interval [CI] 1-33; effect size 0.26) than those who did not receive magnesium., Conclusion: Children requiring continuous albuterol for status asthmaticus can be administered magnesium sulfate outside the PICU with a low incidence of adverse events; however, among a RAS matched cohort, those who received magnesium did not experience shorter time on continuous albuterol, or hospital length of stay., (© 2018 Wiley Periodicals, Inc.)

Objectives: Evaluate the effects of an asthma de-escalation clinical pathway on selected outcomes for patients admitted to a PICU with status asthmaticus., Design: Time series quality improvement trial., Setting: PICU in a tertiary care children's hospital., Patients: Children age 2-18 years old with a known diagnosis of asthma presenting with status asthmaticus., Intervention: One-hundred five admissions to a PICU for status asthmaticus were treated according to a new de-escalation pathway between August 15, 2015, and August 30, 2016. This group was compared with a prepathway group of 141., Measurements and Main Results: Primary outcome was variability in PICU length of stay. Secondary outcomes were median PICU length of stay, median hospital length of stay, and median duration a patient received continuous nebulized albuterol. The effectiveness of the intervention was tracked using control charts. The postpathway group demonstrated decreased variability of PICU length of stay and time receiving continuous albuterol. Statistically significant decreases were seen in median PICU length of stay (16 vs 13 hr; p = 0.0009), median duration a child spent receiving continuous nebulized albuterol (10.8 vs 7.3 hr; p = 0.0008), and median hospital length of stay (37 vs 31 hr; p = 0.02). Total number of asthma assessments completed by respiratory therapists increased from 741 to 1,087., Conclusions: Implementation of a PICU asthma de-escalation pathway demonstrated statistical decrease in the reported measures for children with status asthmaticus. Although the clinical significance of these changes may be debatable, the results demonstrate that efforts to standardize asthma care in the PICU setting is an area in need of further study.

Background: The ideal dosing of albuterol via metered-dose inhalers for acute childhood asthma is not well established. We hypothesized that greater doses of albuterol would result in less time in the hospital and lower admission rates., Methods: This was a randomized controlled double-blind multicenter study, conducted in emergency rooms (ER). We included patients with 2-17 years old with moderate to severe acute asthma (Pediatric Respiratory Assessment Measure, PRAM, score ≥5). Dosages administered during the first hour included: 6 (up to 25 kg) or 12 puffs (>25 kg) in the control group and 9 (up to 15 kg), 12 (>15-20 kg), 15 (>20-25 kg), or 18 puffs (>25 kg) in the study group. Several efficacy (changes in PRAM score, pulse oximetry, and FEV 1 , length of stay, and admission rates) and safety (albuterol plasma levels, heart rate, serum potassium, glucose and bicarbonate levels, EKG, and tremor rates) outcome measures were assessed., Results: We included 119 patients with similar baseline conditions, and no significant differences were observed between groups in the length of stay (P = 0.48) or admission rate (P = 0.55). No significant differences were observed in FEV 1 , PRAM score, and pulse oximetry changes after 1 hr and at discharge or admission. No significant differences were observed in safety outcomes between groups., Conclusions: Higher albuterol dosage regimens did not result in lower admission rate or shorter length of stay in the ER, but showed similar safety profile for children with moderate to severe acute asthma. Pediatr Pulmonol. 2016;51:1122-1130. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Objective: To compare the efficacy of nebulised salbutamol alone and in combination with ipratropium bromide in acute severe asthma in children., Methods: The randomised controlled trial was conducted at the National Institute of Child Health, Karachi, from October 2012 to March 2013, and comprised patients with acute severe asthma who were randomised into two equal groups. Group A patients received 3 doses of nebulised salbutamol alone (0.03 ml/kg/dose) at 15-minute intervals and Group B received 3 similar doses of salbutamol along with ipratropium (250 ug/dose). Acute severe asthma was categorised as serve exacerbation (clinical score >10) and moderate (5-10 score) based on Bentur Modification. Efficacy was measured after 5minutes of the last dose by change in severity score from severe exacerbation (baseline) to low score. SPSS 10 was used for statistical analysis., Results: There were two groups of 100(50%) patients each. The mean age in Group A was 9.1±3 years and 9.3±2.8 years in Group B. Male-Female ratio in Group A was 1.5:1 and in Group B it was 1.2:1. In Group B, 93(93%) children showed improvement in clinical score (<10 score) while it was 84(84%) in Group A. There was better response in clinical score in Group A than Group B, but it was not significant (p>0.05)., Conclusions: The combination of nebulised salbutamol along with ipratropium bromide in the treatment of acute asthma exacerbation was not superior to salbutamol alone.

Objectives: Concerns have been raised regarding cardiac side effects of continuous high-dose albuterol nebulization in status asthmaticus management. Our study goal was to determine prevalence and potential risk factors for hypotension development during continuous albuterol administration in pediatric patients., Methods: A retrospective cohort study was conducted at Children's Memorial Hermann Hospital from 1 January 2011 to 31 August 2012. A total of 152 patients admitted to pediatric intensive or intermediate care units who received continuous albuterol nebulization for management of status asthmaticus were analyzed., Results: Diastolic hypotension, defined as a value < 50 mmHg or <5th percentile of normal for age, developed in 90% of patients and a positive correlation with increasing doses of albuterol was demonstrated. The overall median time to onset of hypotension was 4 h (interquartile range (IQR): 2-6.5) and was significantly lower among patients admitted to the intensive care unit rather than intermediate care (p = 0.005). The odds of hypotension were 82% lower among patients who received fluid boluses prior to continuous albuterol nebulization. None of the potential risk factors demonstrated statistical significance., Conclusions: Diastolic hypotension is a common occurrence among patients who receive continuous albuterol nebulization for status asthmaticus. Total albuterol dose appeared to be directly related to risk of developing diastolic hypotension. Administration of supplemental fluid boluses before continuous nebulized albuterol appeared to provide a significant protective effect. The clinical impact and the significance of diastolic hypotension and the importance of prophylactic administration of intravenous fluid boluses in patients experiencing status asthmaticus are yet to be determined.

Objectives: Continuous albuterol nebulization is generally administered at 2.5-20 mg/hr at most centers. We examined the effect of high-dose (75 or 150 mg/hr) albuterol on clinical variables in children with status asthmaticus., Design: Retrospective analysis of inpatient medical records and prospectively collected computerized PICU respiratory therapy database., Setting: Twenty-five-bed multidisciplinary PICU in a tertiary care children's hospital., Patients: Children admitted to the PICU between January 2006 and December 2007 with status asthmaticus receiving high-dose continuous albuterol nebulization. (Those with cerebral palsy, cardiac pathology, and ventilator dependence were excluded.), Interventions: : Chart review for PICU length of stay, albuterol dose, duration of nebulization, occurrence of chest pain, vomiting, tremors, hypokalemia (serum potassium < 3.0 mEq/L), and cardiac arrhythmia. Maximal heart rate, lowest diastolic blood pressure, and mean arterial pressure were compared to the variables at initiation of therapy and at hospital discharge., Measurements and Main Results: Forty-two patients (22 boys and 20 girls) received high-dose continuous albuterol nebulization. Twenty-three received 75 mg/hr and 19 received 150 mg/hr (3.7 mg/kg/hr [interquartile range, 2.4-5.8 mg/kg/hr]) for a duration of 22.3 hours (interquartile range, 6.6-31.7 hr). Heart rate increased and diastolic blood pressure and mean arterial pressure were significantly lower during nebulization compared to initiation of therapy or at hospital discharge (p < 0.05). No patient required fluid resuscitation or inotropic support, and one had self-limited premature ventricular contractions. Hypokalemia occurred in five of 33 patients who had serum electrolytes measured but did not require supplementation. One patient required endotracheal intubation after initiation of nebulization, and seven patients (16.7%) received noninvasive ventilation. PICU length of stay was 2.3 ± 1.7 days; there were no deaths., Conclusions: High-dose continuous albuterol nebulization is associated with a low rate of subsequent mechanical ventilation and fairly short PICU length of stay without significant toxicity. Prospective studies comparing conventional and high-dose albuterol nebulization are needed to determine the optimum dose providing maximum efficacy with the least adverse effects.

Objective: To describe the design features, utilization, and outcomes of a protocol treating children with status asthmaticus with continuous albuterol in the inpatient setting., Methods: We performed a retrospective cohort analysis of children ages 2 to 18 treated in the non-intensive care, inpatient setting on a standardized treatment protocol for status asthmaticus from July 2011 to June 2013. We assessed characteristics associated with continuous albuterol therapy and, for those treated, duration of therapy and the proportion who clinically deteriorated (ICU transfer or progression to enhanced respiratory support) or who were identified as having hypokalemia or an arrhythmia. Using multivariable logistic regression, we determined which factors were associated with clinical deterioration or prolonged (>24 hours) continuous albuterol., Results: Of 3003 children meeting study criteria, 1298 (43%) received continuous albuterol. Older age, black race, lower initial oxygen saturation, and higher initial age-standardized heart rate and respiratory rate were associated with initiation of continuous albuterol therapy (P < .001 for all). Median duration of therapy was 14.4 hours (interquartile range, 7.7, 24.6); 340 children (26%) experienced prolonged therapy. Seventy children (5%) experienced clinical deterioration, and 33 children (3%) had identified hypokalemia or arrhythmia. Comorbid pneumonia and emergency department administration of intravenous magnesium or subcutaneous terbutaline were associated with prolonged therapy and clinical deterioration., Conclusions: With appropriate support structures and care processes, continuous albuterol can be delivered effectively in the non-ICU, inpatient setting with low rates of adverse outcomes. Certain initial clinical characteristics may help identify patients needing more intensive therapy., (Copyright © 2014 by the American Academy of Pediatrics.)

Objectives: Tachycardia and diastolic hypotension have been associated with β-2 agonist use. In the setting of β-agonist-induced chronotropy and inotropy, diastolic hypotension may limit myocardial blood flow. We hypothesized that diastolic hypotension is associated with β-agonist use and that diastolic hypotension and tachycardia are associated with biochemical evidence of myocardial injury in children with asthma., Design: Two patient cohorts were collected. The first, consisting of patients transported for respiratory distress having received at least 10 mg of albuterol, was studied for development of tachycardia and hypotension. The second, consisting of patients who had troponin measured during treatment for status asthmaticus with continuous albuterol, was studied for factors associated with elevated troponin. Exclusion criteria for both cohorts included age younger than 2 years old, sepsis, pneumothorax, cardiac disease, and antihypertensive use. Albuterol dose, other medications, and vital signs were collected. Diastolic and systolic hypotension were defined as an average value below the fifth percentile for age and tachycardia as average heart rate above the 98th percentile for age., Patients: Ninety of 1,390 children transported for respiratory distress and 64 of 767 children with status asthmaticus met inclusion criteria., Measurements and Main Results: Diastolic hypotension occurred in 56% and 98% of the first and second cohorts, respectively; tachycardia occurred in 94% and 95% of the first and second cohorts, respectively. Diastolic hypotension and tachycardia had a weak linear correlation with albuterol dose (p = 0.02 and p = 0.005, respectively). Thirty-six percent had troponin > 0.1 ng/mL (range, 0-12.6). In multivariate analysis, interaction between diastolic hypotension and tachycardia alone was associated with elevated troponin (p = 0.02)., Conclusions: Diastolic hypotension and tachycardia are dose-dependent side effects of high-dose albuterol. In high-risk patients with status asthmaticus treated with albuterol, diastolic hypotension and tachycardia are associated with biochemical evidence of myocardial injury. Diastolic hypotension, especially combined with tachycardia, could be a reversible risk factor for myocardial injury related to β-agonist use.

A 7-year-old known asthmatic presented with an acute severe asthma attack to the Accident and Emergency department. Following a poor response to salbutamol and ipratropium nebulisers, he was given intravenous salbutamol and aminophylline. Over the course of the following 3 h, there was improvement in his bronchospasm with decreasing oxygen requirement, however, his respiratory rate showed an upward trend. Serial blood gas estimations showed a worsening metabolic acidosis unresponsive to two fluid boluses of 20 ml/kg of normal saline. Lactate levels were subsequently measured and found to be high, accounting for the metabolic acidosis. High lactate levels were attributed to intravenous salbutamol. His blood gases and lactate level returned to normal within 3 h after stopping intravenous salbutamol. He was recommended on salbutamol nebulisers while still continuing on intravenous aminophylline. He continued to improve and was discharged home after 4 days.

Objectives: We investigated the effect of heliox-powered albuterol therapy on hospital length of stay and clinical status in children with moderate to severe status asthmaticus., Design: Prospective, randomized, placebo-controlled trial., Setting: Twenty-five-bed pediatric intensive care unit at an academic children's medical center., Patients: Forty-two children (2-21 yrs of age) with moderate to severe status asthmaticus., Interventions: Patients were randomized to receive either heliox-powered nebulized albuterol or air/oxygen-powered nebulized albuterol (placebo) until they were transitioned to albuterol delivered by a metered dose inhaler., Measurements and Main Results: Clinical asthma scores were recorded on enrollment and every 4 hrs thereafter. Patients in the heliox group (n = 22) and the control group (n = 20) had similar ages (mean +/- sem: 88 +/- 9.9 vs. 98 +/- 11.1 months, respectively; p = .51), time to study enrollment (618 +/- 70.4 vs. 597 +/- 84.1 mins, respectively; p = .72), and clinical asthma scores at study entry (5.9 +/- 0.2 vs. 5.7 +/- 0.3, respectively; p = .72). There were no significant differences between groups in time to eligibility to hospital discharge (66.2 +/- 8.7 vs. 63.4 +/- 8.6 hrs, respectively; p = .61), time to clinical asthma score <3 (22 +/- 2.8 vs. 21.2 +/- 5.3 hrs, respectively; p = .27), or time to eligibility for intensive care unit discharge (34.4 +/- 6.8 vs. 33.3 +/- 8.2 hrs, respectively; p = .64). There were no significant differences in adverse events between groups., Conclusions: Despite the previously demonstrated effects of heliox on improved aerosol particle delivery into the distal airways, heliox-powered nebulized albuterol therapy for children admitted to the hospital with moderate to severe status asthmaticus does not shorten hospital length of stay or hasten rates of clinical improvement when compared with air/oxygen-powered nebulized albuterol.

Background: Due to changing evidence on efficacy of MDI+spacer as compared to nebuliser, two types of managements were going on in our Day unit, depending on the presence of different medical professionals. We wanted to find out the evidence of the best practice from within our unit, and then to formulate guidelines based on it for the management of paediatric acute asthma., Methods: We isolated 54 cases of children suffering from acute asthma attack from admissions during Oct 2004-March 2005 within the age range of 3-14 yrs. We categorised them into four classes of mild, moderate, severe and life threatening acute attack depending on its severity and then separated them in two groups. Group I received salbutamol Via MDI+spacer and Group II received salbutamol via nebuliser. Our outcome measure was time to clinical improvement and duration of hospital stay., Results: We didn't find any major difference between the two groups, moreover MDI+spacer was better than nebuliser for the treatment of severe acute asthma attack in children., Conclusion: Our study supported and confirmed the evidence that MDI+spacer is least as effective as nebuliser in the management of acute asthma in children.

Objective: To determine if the addition of intravenous terbutaline provides any clinical benefit to children with acute severe asthma already on continuous high-dose nebulized albuterol., Methods: We conducted a prospective, randomized, double blind, placebo-controlled trial on pediatric patients with acute severe asthma presenting to a large inner city tertiary children's emergency department. Consecutive patients between 2 and 17 years of age who failed acute asthma management and needed intensive care unit admission underwent informed consent and were enrolled into the study. Patients not requiring intubation were randomized to receive either intravenous terbutaline or intravenous normal saline while on continuous high-dose nebulized albuterol, ipratropium bromide, and systemic corticosteroids. Outcome measures included a clinical asthma severity score, hours on continuous nebulized albuterol, and duration of stay in the pediatric intensive care unit. In addition, electrocardiograms, electrolytes, lactic acid, and troponin I levels were obtained at routine intervals during the first 24 hours after admission. Patients who significantly worsened while enrolled in the study received intravenous aminophylline according to protocol., Results: Forty-nine patients were enrolled in the study. Patients on terbutaline had a mean improvement in the clinical asthma severity score over the first 24 hours of 6.5 points compared with 4.8 points in the placebo group (P = 0.073). Patients on terbutaline spent 38.19 hours on continuous nebulized albuterol compared with their placebo counterparts who spent 51.93 hours (P = 0.25). The length of stay in the PICU was on average 12.95 hours longer for those patients in the placebo group as compared with the terbutaline group (P = 0.345). One patient was removed from the study for a significant cardiac dysrhythmia. This patient was in the terbutaline group and recovered without complications. Troponin I values at 12 hours and 24 hours were elevated in 3 patients each, all within the terbutaline group., Conclusions: No outcome measures demonstrated statistical significance. Outcome measures revealed a trend toward improvement in the terbutaline group. Before recommending routine use of intravenous terbutaline for acute severe asthma, further study to determine safety and efficacy is necessary.

Emergency medical services (EMS) is an important part of the continuum of asthma management. The magnitude of the EMS responsibility is very large, with millions of patients with asthma treated each year by EMS personnel. In response to inconsistencies between the 1997 National Asthma Education and Prevention Program asthma guidelines and a variety of existing EMS protocols on the management of asthma exacerbations, the Centers for Disease Control and Prevention convened a workgroup in 2004 to discuss the various opportunities and challenges ahead. At the meeting, and over the ensuing year, the workgroup created a model protocol that was derived from the National Asthma Education and Prevention Program guidelines. The model protocol is available in both text and algorithm format and offers guidance for EMS systems to develop and implement treatment protocols in their local areas. The workgroup recommendations emphasize flexibility, simplicity, and low-risk practices. By integrating these recommendations into existing protocols, we believe that EMS systems could improve prehospital care for patients with asthma. Demonstration projects are needed to carefully examine the implementation process and the actual impact of the model protocol on various outcomes. The workgroup also encourages more research on EMS management of asthma exacerbations. In the meantime, improved collaboration between EMS and national asthma organizations is an immediate priority and will continue to advance future discussions on how to improve asthma management in the prehospital setting. The workgroup hopes that state and local EMS systems will see the value of the model protocol and encourage its use.

Objective: To compare the effectiveness of salbutamol administration by metered-dose inhaler with a home-made spacer versus jet nebulizer in children with moderate wheezing attacks., Material and Methods: A randomized, single-blinded trial was performed with a convenience sample of children presenting wheezing. The children were enrolled in an emergency room and randomly assigned to one of two treatment groups: home-made spacer group or nebulizer group. Clinical scores and oxygen saturation were recorded at baseline and 15 minutes after salbutamol administration. Treatment with salbutamol (100 microg/3 kg in the spacer group, and 250 microg/3 kg in the nebulizer group) was repeated at 20-minute intervals, until the child was considered to have improved significantly, with no need of any further dose, or until three doses were delivered. Treatment cost, time spent to prepare and deliver the drug, and level of parental satisfaction with the treatment were recorded., Results: Fifty-four children with age between 22 days and 11.7 years were enrolled--27 in each group. Baseline and demographic characteristics were similar for both groups. The spacer was as effective as the nebulizer in terms of clinical score and oxygen saturation. The different doses (100 microg/3 kg with the spacer, and 250 microg/3 kg with the nebulizer) were shown to be clinically equivalent. Treatment cost was significantly lower in the spacer group, as was the time to prepare and deliver the drug. Parental satisfaction was similar for both inhaler devices., Conclusion: The home-made spacer with a metered-dose inhaler is a cost-effective alternative to a jet nebulizer in the delivery of salbutamol to children with moderate wheezing attacks.

Asthma is a common chronic disorder, with a prevalence of 8 to 10 percent in the U.S. population. From 5 to 10 percent of patients have severe disease that does not respond to typical therapeutic interventions. To prevent life-threatening sequelae, it is important to identify patients with severe asthma who will require aggressive management of exacerbations. Objective monitoring of pulmonary status using a peak flow meter is essential in patients with persistent asthma. Patients who have a history of fragmented health care, intubation, or hospitalization for asthma and those with mental illness or psychosocial stressors are at increased risk for severe asthma. Oxygen, beta2 agonists, and systemic corticosteroids are the mainstays of acute asthma therapy. Inhaled anticholinergic medications provide additional bronchodilation. In patients who deteriorate despite usual therapeutic efforts, evidence supports individualized use of parenteral beta2 agonists, magnesium sulfate, aminophylline, leukotriene inhibitors, or positive pressure mask ventilation before intubation.

Objective: To compare the efficacy of a commercial spacer device versus an improvised spacer device in delivering aerosolized beta-2 agonist through metered dose inhaler in an acute exacerbation of bronchial asthma., Design: Randomized controlled trial., Setting: Urban tertiary care teaching hospital., Methods: 60 children between 1 to 12 years of age with acute asthma were prospectively enrolled and randomized into two groups. Detailed history, clinical evaluation and appropriate laboratory investigations were recorded on a pretested proforma. One group received inhaled salbutamol using metered dose inhaler via commercial spacer device (Group 1), while the other received it via improvised spacer device (Group II). The response was sequentially assessed after 20, 40 and 60 minutes of institution of therapy., Results: The two groups were comparable with respect to various parameters at presentation (p > 0.05). All the outcome parameters showed a significant improvement with time in both groups (p < 0.05). There was no statistical difference between the response in the two groups (p< 0.05)., Conclusion: Metered dose inhaler with improvised spacer device is equivalent in efficacy and a more cost effective alternative to metered dose inhaler with commercial spacer for administration of beta-2 agonist in acute asthma.

Objective: To determine whether the addition of repeated doses of nebulized ipratropium bromide (IB) to a standardized inpatient asthma care algorithm (ACA) for children with status asthmaticus improves clinical outcome., Study Design: Children with acute asthma (N = 210) age 1 to 18 years admitted to the ACA were assigned to the intervention or placebo group in randomized double-blind fashion. Both groups received nebulized albuterol, systemic corticosteroids, and oxygen according to the ACA. The intervention group received 250 microg IB combined with 2.5 mg albuterol by jet nebulization in a dosing schedule determined by the ACA phase. The placebo group received isotonic saline solution substituted for IB. Progression through each ACA phase occurred based on assessments of oxygenation, air exchange, wheezing, accessory muscle use, and respiratory rate performed at prescribed intervals., Results: No significant differences were observed between treatment groups in hospital length of stay (P =.46), asthma carepath progression (P =.37), requirement for additional therapy, or adverse effects. Children >6 years (N = 70) treated with IB had shorter mean hospital length of stay (P =.03) and more rapid mean asthma carepath progression (P =.02) than children in the placebo group. However, after adjustment was done for baseline group differences, the observed benefit of IB therapy in older children no longer reached statistical significance., Conclusion: The routine addition of repeated doses of nebulized IB to a standardized regimen of systemic corticosteroids and frequently administered beta-2 agonists confers no significant enhancement of clinical outcome for the treatment of hospitalized children with status asthmaticus.

Aim: To determine the efficacy of adding ipratropium bromide to nebulized salbutamol in the treatment of children with moderate-to-severe acute asthma attacks., Methods: 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., Results: 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)., Conclusions: 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.

This review assesses the evidence regarding the use of long-acting beta(2)-agonists in the management of pediatric asthma. Thirty double-blind, randomized, controlled trials on the effects of formoterol and salmeterol on lung function in asthmatic children were identified. Single doses of inhaled salmeterol or formoterol cause prolonged bronchodilatation (>12 h) and extended bronchoprotection against exercise-induced bronchoconstriction in children, some children achieving full protection for more than 12 h. Heterogeneity in bronchoprotection has been observed, and individual dose-titration may be attempted. The onset of action of formoterol is comparable to salbutamol, while salmeterol has a slower onset of action. Partial tolerance develops when long-acting beta(2)-agonists are used as regular treatment, including cross-tolerance to short-acting beta(2)-agonists. Regular treatment with salmeterol in children with or without corticosteroids provides statistically significant bronchodilatation, but the degree of improvement in lung function or bronchoprotection against exercise and nonspecific irritants is small with regular use. There is no evidence of anti-inflammatory effects from inhaled long-acting beta(2)-agonists, which is reflected by unchanged or increased bronchial hyperreactivity and no reduction of exacerbation rates. The evidence does not support a recommendation for long-acting beta(2)-agonists as monotherapy, nor does it support their general use as regular add-on therapy. In conclusion, long-acting beta(2)-agonists provide effective bronchodilatation and bronchoprotection when used as intermittent, single-dose treatment of asthma in children, but not when used as regular treatment. Future studies should examine the positioning of long-acting beta(2)-agonists as an "as needed" rescue medication instead of short-acting beta(2)-agonists for pediatric asthma management., (Copyright 2000 Wiley-Liss, Inc.)

beta 2 agonists are first election drugs for the treatment of asthma exacerbations. However, rates of complications derived from this asthma therapy like cardiovascular effects have addressed question marks on a possible paradoxical condition, leading to an increased mortality rate. The study was open label, non controlled and aimed to assess the effect of albuterol nebulizations on serum potassium levels, arterial oxygen saturation and electrocardiographic changes in asthma exacerbation in pediatric patients. Albuterol was administered at a dose of 150 mcg/kg/course for 10 minutes in two occasions. Thirty children with mild to moderate asthmatic exacerbation, admitted to emergency room, were included in the study. Bronchodilators administration in the previous 24 hours and history of cardiac or metabolic disease were considered exclusion criteria. Drugs affecting serum potassium were not allowed. Severity of exacerbation was rated by the Wood-Downes criteria. Average sample age was 7.4 +/- 1 years, heart rate increased from 111 +/- 23.23 to 130.0 +/- 22.14 beats/minute, with no clinical significance; serum potassium levels decreased from 4.47 +/- 0.52 to 3.73 +/- 0.49 mEq/L between baseline and final visits, respectively; QTc interval was significantly enlarged from 0.397 to 0.418 milliseconds between initial and final records (p < 0.001), but had no clinical meaning. No arrhythmias were recorded. Pulse oxymetry did not show significant changes (90.6 +/- 3.0% and 92.1 +/- 3.2 at baseline and final visits). The most common reported adverse event was distal tremor, which was present in 80% of the cases. Neither serum potassium decrement nor prolonged QTc after albuterol had clinical significance. Albuterol is a safe drug for the treatment of mild to moderate asthma exacerbations in pediatric patients.

Acute myopathy occurred in a 49-year-old woman hospitalized in the intensive care unit for status asthmaticus. She was given high-dose intravenous steroid therapy and intubated. Pancuronium bromide was used for prolonged curarization. Flaccid quadriplegia developed with preservation of the deep tendon reflexes. Muscle biopsy showed a myogenic process with disorganized myofibrils and selective loss of thick myosin filaments. This mainly myogenic process would result from the toxic effect of corticosteroids favored by prolonged curarization although the effect of other factors still remains unknown.

We prospectively examined the efficacy and safety of continuous albuterol nebulization (CAN) therapy for children diagnosed with impending respiratory failure and status asthmaticus. Serum creatine phosphokinase (CPK) levels were measured, and other factors associated with cardiotoxicity were monitored. Seventeen patients (20 months to 17 years old) were enrolled in the study. No chest pain, arrhythmias, or signs of clinical deterioration occurred in any patient receiving CAN. No study subject required therapy with isoproterenol or mechanical ventilation. An elevation of total serum CPK was found in three patients; however, only one of these patients had an elevated (positive) CPK-MB isoenzyme fraction. We feel that CAN is safe for use in children diagnosed with status asthmaticus. Monitoring of serum CPK enzymes during CAN therapy is warranted until further studies have determined the significance of elevated CPK-MB isoenzymes in otherwise asymptomatic children treated for severe status asthmaticus.

Five percent of children in the United States have asthma. Status asthmaticus is one of the most common conditions for which children seek care in a pediatric emergency department. beta 2-Agonists such as albuterol are the mainstay of emergency therapy for such children. We present a case of a 4-year-old boy who experienced supraventricular tachycardia (SVT) following albuterol therapy. This is believed to be the first report of adenosine being successfully used to treat a child with albuterol-induced SVT. We also briefly review the recognition and management of SVT in children and the pharmacokinetics of and indications for adenosine.

The role of continuous nebulization therapy (CNT) with low-dose beta (beta) agonist was retrospectively reviewed in 7 children admitted to a pediatric intensive care unit for treatment of acute severe asthma. Clinical asthma score (CAS), alveolar-arterial oxygen difference (A-aDO2), PaCO2, heart rate, and respiratory rate were recorded at 0, 12, and 24 hr of CNT. All patients had a decrease in CAS at 12 hr (p < 0.008) and decreased A-aDO2, PaCO2, respiratory rate, and heart rate at 24 hr (p < 0.008). No patient required escalation of dosage or additional intervention such as intravenous beta-agonist therapy or mechanical ventilation. No patient experienced significant cardiovascular toxicity or hypokalemia. We conclude that CNT with low-dose beta agonists should be considered in the initial approach to therapy in children with acute severe asthma.

Objectives: a) to determine if continuous nebulization of albuterol is more effective than intermittent nebulization in the treatment of children with status asthmaticus and impending respiratory failure; b) to determine the effect of continuous nebulization and intermittent nebulization on duration of hospital stay and bedside respiratory therapy care., Design: Prospective, randomized study., Setting: A pediatric intensive care unit (ICU) in a university children's hospital., Patients: Seventeen pediatric asthmatic patients with severe status asthmaticus, with impending respiratory failure (Woods asthma score > or = 5), and without evidence of cardiac or other preexisting lung disease were admitted to the pediatric ICU. The patients were randomized to receive continuous nebulization (n = 9) or intermittent nebulization (n = 8) of albuterol., Interventions: The asthmatic patients were randomized into two groups. The continuous group received 0.3 mg/kg/hr of albuterol by continuous nebulization; the intermittent group received 0.3 mg/kg of albuterol over 20 mins every hour. All patients received aerosol therapy through the same delivery system., Measurements: Responses to therapy were evaluated by following asthma score, arterial blood gas values, hemodynamics, FIO2, and arterial oxygen saturation initially and at 30 mins, 1 hr, 2 hrs, 4 hrs, then every 4 hrs for a 24-hr time period. Patients were determined to no longer be in impending respiratory failure when their asthma score was < 5 for four consecutive hours. Electrocardiograms, serum electrolyte values, and creatine phosphokinase total and MB fraction values were obtained before and after treatment. Hospital stay and respiratory therapy time, in relative value units (one relative value unit = 10 mins) were analyzed from data collected from therapist bedside flow sheets., Results: The patient characteristics (demographics, hemodynamics, arterial blood gas values, asthma severity, corticosteroid use, theophylline, and beta 2-adrenergic receptor agonist administration) before entry into the study did not differ between groups. Patients in the continuous group improved more rapidly and were out of impending respiratory failure sooner than patients in the intermittent group (continuous group = 12 (median) hrs (range 4 to 24) vs. intermittent group = 18 (median) hrs (range 12 to 24; p = .03). Bedside respiratory therapy time evaluated by relative value units was less for patients who received continuous nebulization of albuterol (continuous group = 14 (median) relative value units (range 6 to 26) vs. intermittent group = 33 (median) relative value units (range 25 to 49; p = .001). Hospital stay was shorter for patients who received continuous nebulization of albuterol (continuous group = 80 [median] hrs [range 51 to 173] vs. intermittent group = 147 [median] hrs [range 95 to 256]; p = .043). Hemodynamics, serum potassium, and creatine phosphokinase concentrations did not differ before and after the study in either group., Conclusions: In children with impending respiratory failure due to status asthmaticus, continuous nebulization of albuterol is safe and results in more rapid clinical improvement than intermittent nebulization. Respiratory therapy required at the bedside and duration of hospital stay were substantially less for patients receiving continuous nebulization of albuterol, which suggests that continuous nebulization of albuterol is more cost effective than intermittent nebulization.

A trial was conducted of continuous nebulised salbutamol and oral once a day prednisolone in a group of 11 children with status asthmaticus (group A) and compared with a conventional protocol comprising aminophylline infusion and intravenous hydrocortisone every six hours in a matched control group (group B). Monitoring by a clinical asthma score, pulse oximetry (oxygen saturation, SaO2), and peak expiratory flow rate (PEFR) revealed earlier improvement in these parameters in group A. Significant differences in mean SaO2 values appeared after 12 and 18 hours respectively. Mean PEFR percentage values were higher in group A compared with group B. A larger number (9/11) of patients could be discharged from hospital within 24 hours in group A compared with group B where only 3/11 could be discharged. All patients recovered without any side effects. It is concluded that continuous nebulised salbutamol and oral once a day prednisolone is safe and effective in treatment of children with status asthmaticus.

In a double blind study, 20 patients who presented with acute episodes of asthma were randomized to treatment with nebulized salbutamol (5 mg) of subcutaneous salbutamol (0.5 mg). The clinical conditions were not significantly different before or after treatment in both groups. Significant bronchial dilation was obtained to a similar level in both groups. The heart rate increased significantly in the group treated by subcutaneous injection. Other side effects were minor and similar in both groups. Thus nebulized salbutamol may be used to treat acute asthma in selected patients.

The use of continuously nebulized beta agonists may be considered in the treatment of status asthmaticus, particularly when conventional therapy is failing. Methods of administration of continuously nebulized beta agonists may be cumbersome. We describe a delivery method which allowed simplification of this process, yielded accurate delivery of a specified dose of albuterol, and was beneficial in a reported case of status asthmaticus.

The present study was undertaken to determine if beta-agonists delivered by nebulizer provide better clinical responses than MDI therapy in status asthmaticus. We divided 28 hospitalized asthmatic patients into three groups. Group 1 received albuterol by MDI with InspirEase. Group 2 received nebulized albuterol. Group 3 received nebulized metaproterenol. Both nebulizer regimens resulted in significant improvements in both FVC and FEV1 by 30 min after initial hospital beta-agonist treatment. No significant improvement was noted in initial spirometry in the MDI with InspirEase group. In spite of the superiority of nebulizer therapy in the initial phase of hospitalization, the daily rates of spirometric improvement and duration of hospitalization were not significantly different among the three groups. Our results indicate that nebulizer therapy provides superior spirometric improvement in the initial phase of status asthmaticus. However, both MDI and nebulizer regimens provided similar rates of spirometric improvement and duration of hospitalization.

The management of status asthmaticus using a continuous iv infusion of salbutamol was studied in 14 children with a total of 16 episodes of respiratory failure, unresponsive to conventional bronchodilator therapy. The mean PaCO2 at the start of the infusion was 60 +/- 6 torr. A loading dose of 1 microgram/kg X min body weight was given over 10 min, followed by an infusion of 0.2 microgram/kg X min which was increased in 0.1-microgram/kg steps according to response. The maximum dose was 4 microgram/kg X min. On 11 (69%) occasions a sustained reduction in PaCO2 was achieved within 4 h of starting the infusion. In 5 (11%) instances no reduction in PaCO2 was seen and mechanical ventilation was instituted because of increasing respiratory distress and CO2 retention. Mean heart rate during the infusion increased from 161 to 183 beat/min. Comparison with previous data from 30 pediatric patients (40 infusions) receiving iv isoproterenol showed less effect on heart rate and a more sustained fall in PaCO2 without the recurrence of bronchospasm. We found salbutamol to be a safe and effective bronchodilator capable of reversing severe bronchospasm in most children who would otherwise require mechanical ventilation. Its greater specificity for beta 2-receptors may make it preferable to isoproterenol.

A prospective study has been made in order to asses the efficacy of subcutaneous salbutamol as acute treatment for asthmatic crisis, comparing the results with those of adrenaline. The series consisted of 30 cases, divided into two groups according to the administered treatment, with ages ranging between 5 to 18 years. Once the clinical examination and spirometric measurements were made the first group was treated with subcutaneous adrenaline 0.1 cc/kg (max.; 0.5 cc), while the second was treated with subcutaneous salbutamol 20 micrograms/kg (max.: 500 micrograms). A clinical and spirometric examination was performed at 15, 30, 60 and 90 minutes. A similar increase in FEV1 was observed in the two groups at 15 minutes, maintaining this increase for 90 minutes in the group treated with salbutamol and decreasing in the group treated with adrenaline, being the difference statistically significant (p less than 0.001). In view of this results it seems advisable to administer subcutaneous salbutamol as urgent treatment for an acute asthmatic crisis.

As a bronchodilator, inhaled salbutamol has been shown to be as pharmacologically effective as epinephrine. However the use of the pressurised aerosol is difficult for pediatric patients (mainly under the age of six). The use of spacers (inhalation chambers) could solve this problem. This study was undertaken to compare the clinical effectiveness and toxicity of these two drugs and to try to establish dosage schedules of inhaled salbutamol with spacer in the treatment of acute asthma. The study population consisted of 100 children who were admitted to the emergency room at our hospital with acute asthma. One group receives 0.01 mg/kg of epinephrine (A) (maximum 0.3 mg), the other two groups received inhaled salbutamol (S-1 = 4 puffs and S-2 = 7 puffs) in a period of 20 minutes. Clinical effectiveness was measured by the score of Wood-Downes at 0, 30 and 60 minutes; and no statistical differences were observed between the three groups. The clinical effectiveness was similar in the three groups and the side effects (especially the increase of heart rate) was higher in epinephrine group. Inhaled salbutamol is as effective as subcutaneous epinephrine in management of children in acute bronchoconstricting episodes with less side effects.

Thirty-two children were treated with nebulized salbutamol for acute asthma. Seventy-five per cent of the treatments were efficient, either after a first nebulization at 0.15 mg/kg (47% = group I), or after a second nebulization 45 min later, at 0.05 mg/kg (27% = group II). Twenty-five per cent of the treatments (group III) were inefficient or only partly efficient. The clinical tolerance was good except in two children. Group I and II presented differences only for the auscultation score. Children from group I and II were older and had less severe asthma than those from group III. On the basis of this study, nebulized salbutamol appears to be an affective and safe treatment for acute asthma. The repeated administration of low doses, shortly after the first nebulization increases the quality of the response.

A case is reported of a 56 year old woman admitted for status asthmaticus. She had no known history of cardiovascular disease. During the infusion of salbutamol, there appeared signs of myocardial infarction on the ECG trace. The patient did not complain of any symptoms suggestive of myocardial infarction. Closer cardiac examination and ultrasound revealed features of hypertrophic cardiomyopathy. The first ECG carried out on admission was in fact in favour of this diagnosis. The pathogenesis of this myocardial infarction is discussed: the long lasting hypoxaemia and the tachycardia induced by the salbutamol simulated hard exercise, poorly tolerated by patients suffering from hypertrophic cardiomyopathy. Also, this type of cardiomyopathy is known to be associated with impaired myocardial vasodilator reserve and small vessel coronary artery disease.