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Objectives: Dexamethasone has become the standard of care for pediatric patients with status asthmaticus in the emergency department (ED) setting. Inpatient providers often must decide between continuing the second dose of dexamethasone or transitioning to prednisone. The effectiveness of receiving dexamethasone followed by prednisone (combination therapy) compared to only prednisone or dexamethasone remains unclear. This study compares patient characteristics and ED reutilization/hospital readmission outcomes of dexamethasone, prednisone, and combination therapy for inpatient asthma management., Methods: A retrospective study was conducted at our tertiary children's hospital of children aged 2 to 18 years hospitalized between March 2016 and December 2018 with a primary discharge diagnosis of asthma, reactive airway disease, or bronchospasm. The differences between steroid groups were compared using Fisher's exact or Chi-square tests for categorical variables, and a Kruskal-Wallis test for continuous variables. A multivariable logistic regression was performed to analyze ED reutilization and hospital readmission rates., Results: 1697 subjects met inclusion criteria. 115 (6.8%) patients received dexamethasone, 597 (35.2%) received prednisone, and 985 (58.0%) received combination therapy. Patients prescribed combination therapy had a lower exacerbation severity than patients prescribed prednisone, but higher severity than patients prescribed dexamethasone ( p  < .001, p  = .001, respectively). Dexamethasone and combination therapy were not associated with increased 30-day ED reutilization/hospital readmissions compared to prednisone ( p  > .05)., Conclusions: In our study, most patients hospitalized for status asthmaticus received combination therapy. Despite the differences in severity between steroid groups, outcomes of combination therapy and dexamethasone monotherapy, as measured by frequency of ED reutilizations/hospital readmissions, are comparable to prednisone monotherapy.

Background: To conduct a systematic review looking into the use of sevoflurane in the management of status asthmaticus (SA) in adults., Methods: We performed a systematic search on PubMed, EMBASE, and The Cochrane Library - CENTRAL through 23rd August 2023, restricting to studies reported in English. We included studies reporting use of sevoflurane in asthmatics beyond its use as an anaesthetic agent in surgeries i.e. in the emergency department (ED) and critical care setting, and focused on patient's clinical parameters, ventilation pressures and weaning of invasive ventilation., Results: A total of 13 publications fulfilled the inclusion criteria, comprising of 18 cases. All publications were of case reports/ series and conference abstracts, and no randomised trials were available. Most patients required intubation despite best medical management before sevoflurane administration, and high airway pressures and respiratory acidosis were apparent. There was significant heterogeneity regarding severity of asthma, treatment instituted, and the delivery, duration and concentration of sevoflurane administered. Many of the studies also did not quantify the changes in parameters pre- and post-sevoflurane. Sixteen patients experienced improvements in clinical status with sevoflurane administration-one required escalation to extracorporeal membrane oxygenation (ECMO), and another did not survive., Conclusion: The systematic review suggests sevoflurane can be a valuable treatment option in SA. As these cases are rare and heterogenous, further prospective case series are needed to support this., (© 2024. The Author(s).)

Background: In the state of Kentucky, many status asthmaticus (SA) patients require care in the Pediatric Intensive Care Unit (PICU) and a fraction of these patients may receive "rescue therapies" with inhaled volatile anesthetics (IVA) and/or Extracorporeal Membrane Oxygenation (ECMO). We present a series of such patients with the objective of comparing the clinical parameters of individual patients who received inhaled volatile anesthesia and subsequently the need for ECMO., Methods: Children between 2 and 18 years of age admitted to our PICU from January 2014 to July 2020 with SA were reviewed and categorized as 1) patients who received IVA alone, 2) patients who received IVA and then subsequently ECMO, and 3) patients on ECMO alone., Results: A total of 1772 children with SA episodes were identified with a mortality of 13 patients. Seven children with SA were identified who received either IVA, ECMO, or both. One patient received only IVA, 5 received both IVA and ECMO and one received only ECMO. All received standard asthma therapies of steroids, albuterol, magnesium sulphate, and aminophylline prior to escalation. Six out of seven refractory SA received IVA, and five (83%) of those were subsequently escalated to ECMO. There was an improvement in mean pH after cannulation compared to IVA. pCO 2 levels had no improvement after IVA administration but decreased by an average of 20 points after ECMO. Patients peak inspiratory pressures decreased within the 1st 24 h of ECMO cannulation from a mean of 30 to 18. There were no other complications related to ECMO placement., Conclusion: While we cannot decisively draw any conclusions from our study due to the small sample, it was noted that there was no clear advantage of using IVA prior to ECMO in our patients. Most patients who received IVA were escalated to ECMO indicating that early ECMO cannulation may be beneficial. Given the high cost and potential complications of both, there is a need for the development of well-defined guidelines for severe SA management in the PICU., (© The Author(s), published by EDP Sciences, 2024.)

The use of sedatives in Intensive Care Units (ICU) is essential for relieving anxiety and stress in mechanically ventilated patients, and it is related to clinical outcomes, duration of mechanical ventilation, and length of stay in the ICU. Inhaled sedatives offer benefits such as faster awakening and extubation, decreased total opioid and neuromuscular blocking agents (NMB) doses, as well as bronchodilator, anticonvulsant, and cardiopulmonary and neurological protective effects. Inhaled sedation is administered using a specific vaporizer. Isoflurane is the recommended agent due to its efficacy and safety profile. Inhaled sedation is recommended for moderate and deep sedation, prolonged sedation, difficult sedation, patients with acute respiratory distress syndrome (ARDS), status asthmaticus, and super-refractory status epilepticus. By offering these significant advantages, the use of inhaled sedatives allows for a personalized and controlled approach to optimize sedation in the ICU., (Copyright © 2024 Elsevier España, S.L.U. and SEMICYUC. All rights reserved.)

Introduction: Refractory status asthmaticus (RSA) is a severe, life-threatening form of asthma exacerbation that persists despite aggressive treatment with systemic corticosteroids, bronchodilators, and other supportive measures. Omalizumab, a monoclonal antibody that targets IgE, has been approved for treating severe allergic asthma and is effective in reducing the frequency of exacerbations and improving asthma control. Limited evidence exists regarding the use of Omalizumab in RSA, but some studies have suggested that it may have a role in its management., Case: A 39-year-old male with a decade-long history of asthma presented to the emergency department intubated and unresponsive to pharmacological therapy. The patient's IgE levels were elevated, and Omalizumab was administered after a comprehensive evaluation. The patient made a dramatic recovery and was successfully weaned off the ventilator within 24 h of receiving Omalizumab. He made an uneventful recovery and was discharged home on Omalizumab once every two weeks with regular follow-ups., Discussion and Conclusion: Per our literature search, only 3 cases have been reported where Omalizumab was administered to patients with RSA to wean them off ventilatory support successfully. This case study adds to the existing data on the potential benefits of Omalizumab in managing RSA. It suggests it may be a valuable treatment option for patients who do not respond to standard therapy. However, further research is needed to determine the efficacy and safety of Omalizumab in this population.

Acute severe asthma describes serious asthmatic attacks, which remain a major treatment challenge and a significant source of morbidity in adults. It places the patient in danger of developing respiratory failure, a condition known as status asthmaticus. It is often fatal if not recognized and treated early. Many patients are at risk for numerous reasons; thus, the key issues are early detection, assessment and management. A multidisciplinary and collaborative approach is needed to effectively treat acute respiratory failure (ARF). Considerable research has investigated the range of opportunities available for treating asthma. Current treatment options include conventional agents, such as inhalational corticosteroids, â-agonists, leukotriene modulators, monoclonal antibodies, and oral corticosteroids (OCS). Nurses are in a perfect position to assess patients' risk of developing respiratory failure, monitor them, evaluate their care, and coordinate a multidisciplinary approach. In this review, we discuss acute asthma and the role of the nursing officer (NO) in the management of the illness. The review will also emphasize various current treatment approaches available for the NO that can effectively target and prevent respiratory failure. This review provides nurses and other healthcare workers with updated information on timely, effective and safe supportive management of patients with asthma.

Background: Severe, refractory asthma is a life-threatening emergency that may be treated with isoflurane and extracorporeal life support. The objective of this study was to describe the clinical response to isoflurane and outcomes after discharge of children who received isoflurane and/or extracorporeal life-support for near-fatal asthma., Methods: This was a retrospective descriptive study using electronic medical record data from two pediatric intensive care units within a single healthcare system in Atlanta, GA., Results: Forty-five children received isoflurane, and 14 children received extracorporeal life support, 9 without a trial of isoflurane. Hypercarbia and acidosis improved within four hours of starting isoflurane. Four children died during the index admission for asthma. Twenty-seven percent had a change in Functional Status Score of three or more points from baseline to PICU discharge. Patients had median percent predicted FEV1 and FEV1/FVC ratios pre- and post-bronchodilator values below normal pediatric values., Conclusion: Children who received isoflurane and/or ECLS had a high frequency of previous PICU admission and intubation. Improvement in ventilation and acidosis occurred within the first four hours of starting isoflurane. Children who required isoflurane or ECLS may develop long-lasting deficits in their functional status. Children with near-fatal asthma are a high-risk group and require improved follow-up in the year following PICU discharge.

Background: Severe asthma exacerbations in pediatric patients occur frequently and can require pediatric intensive care unit (PICU) admission., Objective: To determine if early administration of intravenous magnesium sulfate (IVMg) to pediatric patients experiencing severe asthma exacerbations, defined as a respiratory clinical score (RCS) of 9 to 12, resulted in fewer PICU admissions., Methods: Retrospective chart review of pediatric patients aged from 2 to 17 years presenting with a severe asthma exacerbation to a single tertiary care pediatric emergency department. Univariable and multivariable logistic regression analyses were used to determine if admission to the PICU was associated with early IVMg treatment, within 60 minutes of registration., Results: A total of 1911 patients were included in the study, of which 1541 received IVMg. The average time to IVMg was 79 minutes, with 35% of the patients receiving it within 60 minutes of arrival. Two hundred forty-eight (13%) were admitted to the PICU, 641 (34%) were admitted to the general inpatient floor, and 1022 (53%) were discharged home. Factors associated with increased odds ratio (OR) of PICU admission were: early IVMg (OR, 1.63; 95% CI: 1.16-2.28), arrival mode to the emergency department via ambulance (OR, 2.23; 95% CI: 1.45-3.43), history of PICU admission for asthma (OR, 1.73; 95% CI: 1.22-2.44), and diagnosis of status asthmaticus (OR, 8.88; 95% CI: 3.49-30.07). Calculated OR of PICU admission subcategorized by RCS for early IVMg patients, after controlling for PICU risk factors, are as follows: RCS 9 (reference), RCS 10 (OR, 2.52; 95% CI: 0.89-2.23), RCS 11 (OR, 2.19; 95% CI: 1.3-3.70), and RCS 12 (OR, 4.12; 95% CI: 2.13-7.95)., Conclusions: Early administration of IVMg to pediatric patients experiencing severe asthma exacerbations does not result in fewer PICU admissions., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Hospital admission trends of children with status asthmaticus diminished during the Coronavirus-19 (COVID-19) pandemic of 2020, possibly secondary to several factors such as school closures and use of face masks. What effect this had on antibiotic prescribing practices has yet to be described. The objective of our study was to evaluate the use of antibiotics in hospitalized children with a diagnosis of status asthmaticus before and during the COVID pandemic. Methods: A retrospective cross-sectional analysis was conducted using the TriNetX® cloud-based program with a national and institutional database. Each database was queried for all inpatient pediatric encounters from 3 to 18 years old, admitted with a diagnosis of status asthmaticus in the spring seasons of 2017-2019. Admission data and antibiotic usage were queried during the COVID-19 pandemic year of 2020 from both databases and compared amongst all study years. Results: In 2020, there was an overall decrease in the number of admissions as compared to the average number from 2017-2019, by 76.9% in the national database ( p <  0.05) and 91.2% in the institutional database. The rates of antibiotic prescriptions significantly dropped among the national database ( p  < 0.001, z  = 3.39) and remained non-significantly changed among the institutional database ( p  = 0.944 and z  = 0.073). Conclusions: Our study demonstrates that the COVID-19 pandemic year of 2020 coincided with a significant decrease in hospital admissions and antibiotic prescribing prevalence among children with status asthmaticus on a national level. Nonetheless, our reported trends in antibiotic prescribing are still grossly similar to that of pre-pandemic times and may demonstrate a continued need for antimicrobial stewardship.

Objective: The β2-agonists such as salbutamol are the mainstay of asthma management. Pharmacokinetic-pharmacodynamic (PKPD) models to guide paediatric dosing are lacking. We explored the relationship between salbutamol dose, serum concentration, effectiveness and adverse effects in children by developing a PKPD model., Design: A prospective cohort study of children admitted to hospital with acute asthma, who received intravenous salbutamol., Setting: Children were recruited in two cohorts: the emergency departments of two London hospitals or those retrieved by the Children's Acute Transport Service to three London paediatric intensive care units., Patients: Patients were eligible if aged 1-15 years, admitted for acute asthma and about to receive or receiving intravenous salbutamol., Interventions: Treatment was according to local policy. Serial salbutamol plasma levels were taken. Effectiveness measurements were recorded using the Paediatric Asthma Severity Score (PASS). Toxicity measurements included lactate, pH, glucose, heart rate, blood pressure and arrhythmias. PKPD modelling was performed with non-linear mixed-effect models., Main Outcomes: Fifty-eight children were recruited with 221 salbutamol concentration measurements from 54 children. Median (range) age was 2.9 (1.1-15.2) years, and weight was 13.6 (8-57.3) kg. Ninety-five PASS measurements and 2078 toxicity measurements were obtained., Results: A two-compartment PK model adequately described the time course of salbutamol-plasma concentrations. An E MAX (maximum drug effect) concentration-effect relationship described PASS and toxicity measures. PKPD simulations showed an infusion of 0.5 µg/kg/min (maximum 20 µg/min) for 4 hours after bolus achieves >90% maximal bronchodilation for 12 hours., Conclusions: A paediatric PKPD model for salbutamol is described. An infusion of 0.5 µg/kg/min after bolus achieves effective bronchodilation. Higher rates are associated with greater tachycardia and hyperglycaemia., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Short-acting bronchodilators for asthma and chronic obstructive pulmonary disease (COPD) exacerbations are commonly delivered by nebulizers although administration using metered dose inhaler with space chamber (MDI spacer) has been shown to be equally efficacious. There are few studies examining patients' and healthcare providers' attitudes on the two administration methods in adults. This study explores patients' and healthcare providers' attitudes on the use of nebulizer versus MDI spacer for acute asthma and COPD exacerbations in adults., Methods: Patients admitted for asthma or COPD exacerbations, doctors, and nurses in a university-affiliated hospital were surveyed from 1 April 2021 to 30 September 2021 regarding their views on the effectiveness, ease of use, preparation and administration, side effects, and infection risk of the two administration methods., Results: Ninety-nine patients, 103 doctors, and 650 nurses completed the survey. 60.6% of patients perceived nebulizer to be more effective. Patients who found nebulizer more comfortable were more likely to prefer nebulizer (OR 43.97, p  = 0.01), while those who associated it with a greater infection risk were less likely to prefer nebulizer (OR 0.15, p  = 0.03). 49.5% of doctors and 49.1% of nurses perceived nebulizer to be more effective, compared to 10.7% and 34.5%, respectively, for MDI spacer. Effectiveness and patient comfort influenced doctors' and nurses' preference for nebulizer while ease of preparation and administration influenced nurses' preference only., Conclusions: Patients and healthcare providers perceived nebulizer to be more effective. Factors unique to each group influenced their preference for nebulizer.

Objective: To characterize adolescents' practical knowledge of asthma self-management and experiences during acute asthma episodes, and compare practical knowledge between minority and non-minority groups., Methods: We conducted a secondary analysis using a qualitative descriptive design of textual data collected from 126 adolescents that participated in a randomized controlled trial of an asthma self-management program. Directed content analysis was conducted using four constructs of asthma self-management including symptom prevention, symptom monitoring, acute symptom management, and symptom communication., Results: Most of the adolescents knew how to prevent exercised-induced bronchoconstriction, but had limited understanding about how to assess and monitor the severity of acute symptoms, appropriately use bronchodilators, seek timely medical help, and communicate acute symptoms to caregivers or healthcare providers during a slow-onset and rapid-onset asthma attack. More minority participants monitored asthma using peak expiratory flow than non-minority participants, who often relied on symptom-based monitoring. Minority adolescents more frequently mentioned bronchodilator use to manage asthma attacks, while non-minority adolescents often reported use of complementary and alternative approaches. Minority youth mentioned accessing healthcare services for acute episodes more often than their non-minority counterparts. Minority participants mentioned communicating acute symptoms to their providers, or family members less frequently than non-minority youth., Conclusions: Adolescents have insufficient practical knowledge about ways to prevent and manage acute asthma. Periodic assessment of learning needs related to asthma attacks should be considered a routine part of clinical visits for adolescents to provide targeted information support to address their identified needs.

Background: Standardized acute asthma management with score-based, respiratory therapist (RT)-driven pathways and protocols improves outcomes including decreased length of stay (LOS) and time on continuous albuterol therapy. Limited data are available for the safety of continuous albuterol used outside of pediatric ICU (PICU). We use a modified pediatric asthma score (PAS) for the asthma pathway at our institution. The safety and effectiveness of using PAS to initiate/stop continuous albuterol as part of a score-based, RT-driven asthma pathway were evaluated., Methods: A retrospective review of children ≥ 2 y admitted for asthma exacerbation to the PICU and step-down unit who received continuous albuterol as part of the asthma pathway during 2017-2019 was completed. Demographic and clinical data were extracted including PAS, dose and duration of continuous albuterol, LOS, and complications. Outcomes of subjects admitted to the PICU and step-down unit were compared., Results: Results are expressed as median (interquartile range). The study included 412 children (61% male, 59.9% Black, 92.7% non-Hispanic, 44.9% moderate persistent asthma) with age and weight of 6.4 (4.0-10.0) y and 24.8 (17.3-39.5) kg, respectively. Most children were admitted to step-down unit (71.1%). Initial albuterol dose, duration, and LOS were 15 (10-20) mg/h, 9.1 (5.7-16.0) h, and 1.4 (0.9-2.3) d, respectively. Respiratory support was required by 29% of subjects. Need to restart therapy (2.9%), transfer to PICU (1.7%), and intubation (0.5%) were infrequent. No pneumothoraces or deaths were reported. Emergency department visits (3.9%) or readmissions (0.7%) within 30 d of discharge were low. Subjects admitted to the PICU were sicker and required more therapies and respiratory support than those admitted to the step-down unit., Conclusions: Use of an RT-driven, score-based pathway for initiation and discontinuation of continuous albuterol for treatment of pediatric asthma exacerbation was safe and effective in the PICU and step-down unit., Competing Interests: Dr Berlinski discloses relationships with Cystic Fibrosis Foundation, Mylan, National Institutes of Health, Therapeutic Development Network, Trudell Medical International, Vertex, and the International Pharmaceutical Aerosol Consortium on Regulation and Science. Ms Willis is a section editor for Respiratory Care. The remaining authors have disclosed no conflicts of interest., (Copyright © 2022 by Daedalus Enterprises.)

Objective: Various intravenous (IV) corticosteroids are available for acute severe asthma (ASA) treatment. The choice of IV corticosteroids varies broadly and depends on institution, country, or physician preferences. In this study, we compared the efficacy of IV methylprednisolone, hydrocortisone and dexamethasone in ASA treatment during pediatric intensive care unit (PICU) admission., Methods: The study was a prospective randomized clinical trial. We enrolled patients of 1-21 years after they were admitted to the PICU requiring continuous beta-2 agonist treatment. Patients were randomized into three groups: Group A: IV Methylprednisolone, Group B: IV Hydrocortisone and Group C: IV Dexamethasone. The primary outcomes measured were durations of beta-2 agonist continuous nebulization treatment. Secondary outcomes, included PICU and hospital length of stay (LOS), pediatric asthma severity score (PASS), need for mechanical ventilation and maximum dose of beta-2 agonist treatment., Results: 61 patients were included in the analysis. 22 patients recruited in Group A, 20 in group B and 19 group C. Median durations of beta-2-agonist treatment were 23 h (QR 16-38) for methylprednisolone, 27 h (QR 16-40) for hydrocortisone, and 32 h (QR 16-48) for dexamethasone ( p  = 0.90). There was no difference in PICU LOS, hospital LOS, PASS score, B2 agonist maximum dose, or need for ventilation support., Conclusions: The use of IV methylprednisolone, hydrocortisone, and dexamethasone have equivalent efficacy when used at the appropriate doses. Studies with larger cohorts are needed to compare the effectiveness of IV corticosteroids in the management of ASA in the PICU setting.

Objective: Status asthmaticus is commonly treated in pediatric patients by using continuous albuterol, which can cause hypokalemia. The primary aim of this study was to determine if serial potassium monitoring is necessary by examining treatment frequency of hypokalemia., Methods: This retrospective analysis was performed in 185 pediatric patients admitted with status asthmaticus requiring continuous albuterol between 2017 and 2019. All patients were placed on intravenous fluids containing potassium. The primary outcome measure was the treatment of hypokalemia in relation to the number of laboratory draws for potassium levels. The secondary outcome measure was hypokalemia frequency and relation to the duration and initial dose of continuous albuterol., Results: Included were 156 patients with 420 laboratory draws (average, 2.7 per patient) for potassium levels. The median lowest potassium level was 3.40 mmol/L (interquartile range, 3.2-3.7). No correlation was found between initial albuterol dose and lowest potassium level (P = .52). Patients with hypokalemia had a mean albuterol time of 12.32 (SD, 15.76) hours, whereas patients without hypokalemia had a mean albuterol time of 11.50 (SD, 12.53) hours (P = .29). Potassium levels were treated 13 separate times., Conclusions: The number of laboratory draws for potassium levels was high in our cohort, with few patients receiving treatment for hypokalemia beyond the potassium routinely added to maintenance fluids. Length of time on albuterol and dose of albuterol were not shown to increase the risk of hypokalemia. Serial laboratory measurements may be decreased to potentially reduce health care costs, pain, and anxiety surrounding needlesticks., Competing Interests: CONFLICTS OF INTEREST DISCLOSURES: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2022 by the American Academy of Pediatrics.)

Introduction: Corticosteroids are important part of acute severe asthma (ASA) management in pediatric intensive care units. Few studies look at the efficacy of inhaled corticosteroids (ICS) in critical care settings. We aimed to investigate the potential beneficial effects of ICS when added to intravenous corticosteroids in pediatric patients with ASA admitted to the pediatric intensive care unit (PICU)., Methods: This was a randomized controlled trial involving pediatric patients aged 1-21 years admitted to PICU with ASA. Patients were randomized into 2 groups using block randomization. Patients in Group A received intravenous methylprednisolone (2 mg/kg/day) alone and patients in Group B received intravenous methylprednisolone (2 mg/kg/day) plus budesonide nebulization (0.5 mg every 12 h). Main outcomes were duration of continuous albuterol treatment, PICU and hospital length of stay (LOS), and need and duration of respiratory support. Kruskal-Wallis and Chi-square tests were used for statistical analysis, in which a p-value < 0.05 was considered statistically significant., Results: Duration of continuous albuterol treatment was not different between the 2 groups median/(QR), 30/(18-51) vs. 25/(14-49). ( p  = 0.38) PICU and hospital LOS between the 2 groups was similar, median/(QR), 44/(30-64) vs. 46/(30-62), ( p  = 0.75) and 78/(65-95) vs.72/(58-92), ( p  = 0.19). Number of patients requiring respiratory support was 22(58%) in Group A and 25(64%) in Group B ( p  = 0.19)., Conclusions: In critically ill children with ASA, intravenous methylprednisolone combined with inhaled budesonide did not shorten the duration of continuous albuterol inhalation treatment, the PICU and hospital LOS, and the need for respiratory support.

Background: Protocol-driven therapy has been successful in managing patients with asthma on pediatric wards, but there is wide variability in ICU-level management that is often provider-dependent. This study aimed to determine if a standardized protocol for critical asthma treatment could improve clinical outcomes., Methods: A pre-intervention cohort consisting of subjects age 2-18 y, excluding patients with airway obstruction that was not felt to be due to asthma, who were admitted to the ICU for critical asthma. Demographics and data along with medication administration information were gathered using the hospital electronic medical record. A post-intervention cohort was obtained over 13 months in an identical manner. The primary end point was time on continuous albuterol. Subjects adhering to the protocol were examined as a subset., Results: 71 post-intervention subjects were compared with a historical cohort of 52 pre-intervention subjects over a similar time frame. There were no significant differences in demographic characteristics. Median time on continuous albuterol (14.4 h vs 8.1 h, P = .14) and secondary end points of median ICU length of stay (LOS), hospital LOS, and time from discontinuing continuous albuterol to transfer out of ICU were not significantly reduced in the post-intervention cohort. Overall adherence to the clinical protocol through completion was 42%. When comparing the pre-intervention cohort with the protocol-adherent subjects, significant reductions were seen in time on continuous albuterol (14.4 h vs 3.0 h, P < .001), ICU LOS (38.7 h vs 21.0 h, P < .001), and hospital LOS (2.8 d vs 1.7 d, P = .005)., Conclusions: Implementation of an asthma protocol in the pediatric ICU did not result in significant improvements in time on continuous albuterol or hospital and pediatric ICU LOS, likely due to low adherence to the protocol. However, in subjects who did adhere to the protocol there were significant reductions in the outcome measures., Competing Interests: The authors have disclosed no conflicts of interest. This work was supported by National Institutes of Health’s National Center for Advancing Translational Sciences Grant UL1TR002494. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health’s National Center for Advancing Translational Sciences., (Copyright © 2021 by Daedalus Enterprises.)

Competing Interests: Competing interests: ML reports personal fees from Clement Clarke International, personal fees from Teva, personal fees from Astra Zeneca, non-financial support and other from Global Initiative on Asthma (GINA), USA, personal fees from Chiesi, grants from Consorcio Ricerca in Futura, personal fees from Soar Beyond, personal fees from Orion Pharmaceuticals, other from Napp Pharmaceuticals, personal fees from National Services for Health Improvement, a company providing services for practices (Nurse asthma Reviews), personal fees from Novartis Pharmaceuticals, personal fees from GLaxo Smith Klein, non-financial support from Asthma and COPD (Joint) Lead for Whole Systems Integrated Care (WSIC) NorthWest London, personal fees from Trudel Pharmaceuticals, personal fees from AstraZeneca, outside the submitted work.

Objective: To determine if the Pediatric Asthma Severity Score (PASS) can distinguish "late-rescues" (transfer to the pediatric intensive care unit [PICU] within 24-hours of general pediatric floor admission), "PICU readmissions" (readmission within 24-h after transfer to a lower inpatient level of care), and unplanned 30-day hospital readmission in children admitted with status asthmaticus. Methods: We performed a single center, retrospective cohort study in 328 children admitted for asthma exacerbation aged 5-18 years from May 2015 to October 2017. We sought to determine if PASS values preceding admission from the emergency department or transfer to the general pediatric unit will be greater in children with late rescues and PICU readmissions and if a cutoff PASS values exist to discriminate these events prior to intrafacility transfer. Results : Nine (5%) late-rescues and 5 (3%) PICU readmissions accounted for 14/328 (4%) composite outcomes. PASS values were greater in children with these events (8 [IQR:5-8] vs. 5 [IQR:3-6], p  < .01). Logistic regression of PASS on composite outcome yielded an odds ratio of 1.4 (1.1-1.8, p  < .01) and ROC curve of PASS on a composite outcome yielded an AUC of 0.74 (0.61-0.87) with a threshold of ≥ 9. Nine (3%) children experienced unplanned 30-day hospital readmissions but PASS preceding hospital discharge was neither discriminative nor associated with hospital readmission. Conclusions: PASS values ≥ 9 identify children at increased risk for late-rescue and PICU readmission. Applied with traditionally criteria for selection of inpatient level of care, PASS may assist providers in reducing acute inpatient disposition errors.

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.

Objective: To determine the frequency of clinically important bleeding (CIB) among children hospitalized for status asthmaticus with and without exposure to stress ulcer prophylaxis (SUP). Methods: We performed a single-center, retrospective cohort in 217 children admitted for asthma exacerbation aged 5-18 years from May 2015 to May 2017. We assessed cohorts with and without exposure to SUP to determine if differences in frequency of CIB exist. Study outcomes included frequency of CIB, gastrointestinal complications (occult bleeding, macroscopic bleeding, gastric perforation, and acquired gastritis), and SUP-related adverse events (ventilator associated pneumonia, C. difficile colitis, necrotizing enterocolitis, and acute thrombocytopenia). Results: Ninety-two (42%) children received SUP of which 82 were admitted to the pediatric intensive care unit (PICU). There were no differences in asthma severity or known risk factors for CIB in children with and without SUP in the PICU subcohort. We observed no CIB or SUP-related adverse events. Two subjects acquired gastritis in the no-SUP cohort and one additional subject experienced occult gastrointestinal bleeding with spontaneous symptom resolution. Conclusion : Children admitted for status asthmaticus with and without SUP had no observed incidence of CIB. In this specific population, we propose a prerequisite assessment for the presence of known stress ulcer related gastrointestinal bleeding risk factors prior to the blanket administration of SUP.

Objective: Asthma is the most common chronic disease of childhood. Although asthma admissions to the pediatric intensive care unit (PICU) are increasing, there are no evidence-based guidelines on preferred escalation of therapies for patients with status asthmaticus who fail to respond to inhaled bronchodilators and systemic corticosteroids. The purpose of this study was to assess outcomes of PICU patients receiving aminophylline versus terbutaline as second-tier therapies for status asthmaticus., Design: Retrospective cohort study using Pediatric Health Information System from 2016-2019., Setting: Fifty-three tertiary children's hospitals., Subjects: Children aged 2 to 18 years admitted to the PICU in children's hospitals contributing data to the Pediatric Health Information System with a primary diagnosis of status asthmaticus., Interventions: None., Measurements and Main Results: Of 11 133 pediatric patients treated for status asthmaticus in the PICU during the study period, 1144 received either terbutaline or aminophylline. There was no difference in intubation and mechanical ventilation between patients who received aminophylline and those who received terbutaline. However, in African American patients, those who received terbutaline had a significantly higher odds of intubation and mechanical ventilation compared to those who received aminophylline (OR, 12.41; 95%CI, 1.61,95)., Conclusions: The use of aminophylline is associated with lower odds of intubation and mechanical ventilation in African American patients with status asthmaticus as compared to terbutaline., (© 2020 Wiley Periodicals LLC.)

Intravenous (IV) magnesium is used as an adjunct therapy in management of status asthmaticus with a goal of reducing intubation rate. A recent review suggests that IV magnesium use in status asthmaticus reduces admission rates. This is contrary to the observation of practicing emergency room physicians. The goal of this study was to assess trends in IV magnesium use for status asthmaticus in US children's hospitals over 8 years through a retrospective analysis of children younger than 18 years using the Pediatric Health Information System database. Outcomes were IV magnesium use, inpatient and intensive care unit admission rate, geometric mean length of stay, and 7-day all-cause readmission rate. IV magnesium use for asthma hospitalization more than doubled over 8 years (17% vs. 36%; P < .001). Yearly trends were not significantly associated with hospital or intensive care unit admission rate or 7-day all-cause readmissions, although length of stay was reduced (P < .001).

Objectives: The primary aim of this study was to reduce duration of continuous albuterol and hospital length of stay in critically ill children with severe status asthmaticus., Design: Observational prospective study from September 2012 to May 2016., Setting: Medicine ICU and intermediate care unit., Patients: Children greater than 2 years old with admission diagnosis of status asthmaticus admitted on continuous albuterol and managed via a standardized protocol., Interventions: The protocol was an iterative algorithm for escalation and weaning of therapy. The algorithm underwent three revisions. Iteration 1 concentrated on reducing duration on continuous albuterol; iteration 2 concentrated on reducing hospital length of stay; and iteration 3 concentrated on reducing helium-oxygen delivered continuous albuterol. Balancing measures included adverse events and readmissions., Measurements and Results: Three-hundred eighty-five patients were treated as follows: 123, 138, and 124 in iterations 1, 2, and 3, respectively. Baseline data was gathered from an additional 150 patients prior to protocol implementation. There was no difference in median age (6 vs 8 vs 7 vs 7 yr; p = 0.130), asthma severity score (9 vs 9 vs 9 vs 9; p = 0.073), or female gender (42% vs 41% vs 43% vs 48%; p = 0.757). Using statistical process control charts, the mean duration on continuous albuterol decreased from 24.9 to 17.5 hours and the mean hospital length of stay decreased from 76 to 49 hours. There was no difference in adverse events (0% vs 1% vs 4% vs 0%; p = 0.054) nor in readmissions (0% vs 0% vs 1% vs 2%; p = 0.254)., Conclusions: Implementation of a quality improvement protocol in critically ill patients with status asthmaticus was associated with a decrease in continuous albuterol duration and hospital length of stay.

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.

Objective: Magnesium sulfate (Mg) is one of several "second-tier" therapies for treating severe status asthmaticus. Pediatric reports primarily describe bolus use with limited data regarding prolonged infusions. We sought to describe the safety of prolonged Mg infusions during therapy of status asthmaticus in critically ill children., Design: Single center, retrospective study., Setting: Thirty-four-bed tertiary level medical/surgical/cardiac surgical pediatric intensive care unit., Patients: Pediatric patients 2 to 18 years of age admitted with status asthmaticus receiving Mg infusion for more than 24 hours., Interventions: None., Measurements and Main Findings: A total of 154 children received Mg infusions for a median of 53.4 hours (interquartile range = 36.6-74.8). The most common adverse event (AE) was hypotension (48.1%), almost exclusively diastolic (94%), and was mostly limited to 1 blood pressure measurement (78%). 2.9% of events required intervention (fluids, decrease Mg infusion). Other AEs included nausea/emesis (22.7%), transient weakness (14.9%), and flushing (6.5%). Five patients experienced serious AEs including hypotonia (n = 1), escalation to continuous or bilevel positive airway pressure (n = 3), and sedation (n = 1), all attributed to progression of underlying medical disease. No patient required endotracheal intubation. Supratherapeutic levels (>6 mg/dL) were uncommon (2%) and were not more likely to be associated with AEs. Most (81%) patients were therapeutic by the 2nd Mg level check., Conclusion: Prolonged Mg infusions were well tolerated in pediatric status asthmaticus patients. While diastolic hypotension was not uncommon, rarely were interventions deemed necessary. No serious AEs were attributed to Mg. Toxicity was uncommon suggesting that Mg levels could potentially be checked less frequently than historically reported., (© 2019 Wiley Periodicals, Inc.)

Background: Asthma is a common cause of pediatric hospitalization. Nonadherence to asthma medications is associated with worse outcomes; however, there is a paucity of data regarding posthospitalization prescription filling and hospital reuse. Our objective was to identify patients at risk for hospital reuse after being hospitalized for asthma., Methods: This is a retrospective study of patients with asthma who were discharged from a children's hospital in which we use Medicaid claims data to evaluate prescription fills within 30 days and 12 months. Chart reviews were used for demographics, chronic asthma severity, admission severity, and hospital reuse. t and χ 2 tests were performed for continuous and categorical variables. A generalized linear mixed model was fitted to predict the odds of hospital reuse, which was defined as requiring an emergency department visit or rehospitalization. Survival analysis using log-rank testing was used for modeling the time to hospital reuse., Results: Fifty-four percent of patients discharged with asthma had hospital reuse within 1 year of discharge. There was no association between hospital reuse and prescription filling for systemic steroids (odds ratio [OR] 1.30; confidence interval [CI]: 0.85-2.00; P = .21) or controller medications (OR 1.5; CI: 0.92-2.52; P = .10). There was a higher number of controller and systemic steroid prescription fills over 12 months for patients with hospital reuse. The factors associated with greater odds of hospital reuse were severity of chronic asthma diagnosis ( P = .03) as well as African American race (OR 1.92; CI: 1.17-3.13; P = .01)., Conclusions: For Medicaid-insured patients discharged with asthma, worse chronic asthma severity and African American race were associated with greater odds of hospital reuse. Decreased prescription filling was not associated with greater odds of hospital reuse., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2019 by the American Academy of Pediatrics.)

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.

Introduction: The present study describes our experience with the high-flow humidified nasal cannula (HFNC) versus non-invasive ventilation (NIV) in children with severe acute asthma exacerbation (SA)., Methods: An observational study of a retrospective cohort of 42 children with SA admitted to a Pediatric Intensive Care Unit (PICU) for non-invasive respiratory support was made. The primary outcome measure was failure of initial respiratory support (need to escalate from HFNC to NIV or from NIV to invasive ventilation). Secondary outcome measures were the duration of respiratory support and PICU length of stay (LOS)., Results: Forty-two children met the inclusion criteria. Twenty (47.6%) received HFNC and 22 (52.3%) NIV as initial respiratory support. There were no treatment failures in the NIV group. However, 8 children (40%) in the HFNC group required escalation to NIV. The PICU LOS was similar in both the NIV and HFNC groups. However, on considering the HFNC failure subgroup, the median length of respiratory support was 3-fold longer (63h) and the PICU LOS was also longer compared with the rest of subjects exhibiting treatment success., Conclusions: Despite its obvious limitations, this observational study could suggest that HFNC in some subjects with SA may delay NIV support and potentially cause longer respiratory support, and longer PICU LOS., (Copyright © 2017 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.)

Background: Status asthmaticus is an acute exacerbation of asthma that is persistent and intractable and remains unresponsive to initial treatment with bronchodilators and systemic corticosteroids and that the condition can result in hypoxemia, hypercarbia, and secondary respiratory failure., Objective: To review treatment and recent patents on management of status asthmaticus., Method: A PubMed search was completed in Clinical Queries using the key term "status asthmaticus". The search included meta-analyses, randomized controlled trials, clinical trials, reviews and pertinent references. Patents were searched using the key term status "asthmaticus" from www.google.com/patents, www.uspto.gov, and www.freepatentsonline.com., Results: Supplemental oxygen should be given to maintain an oxygen saturation of ≥ 92% in room air. Mainstay of pharmacologic treatment of status asthmaticus includes short-acting, β2 agonists such as salbutamol (albuterol) administered by metered-dose inhaler with spacer or, preferably, by nebulizer and oral corticosteroids. There is no advantage to intravenous corticosteroids unless the child cannot tolerate oral corticosteroids (e.g., protracted vomiting), or unable to take oral corticosteroid (e.g., intubated or unconscious). Inhaled ipratropium bromide and intravenous magnesium sulfate should be considered in children with severe asthma exacerbations not responsive to conventional therapy. Subcutaneous and intramuscular β2 agonists such as terbutaline and epinephrine may be considered for children with severe asthma exacerbation who have poor air entry, are uncooperative with nebulized therapy, or have poor response to nebulized therapy. Monoclonal anti-IgE antibody (omalizumab) and humanized monoclonal antibodies targeting interleukin pathway have shown great promise in severe refractory eosinophilic asthma. Failing therapeutic interventions necessitate non-invasive or invasive ventilation support. Severe exhaustion, deteriorating consciousness, poor air entry, worsening hypoxemia, hypercapnia, and cardiopulmonary arrest are indications for mechanical ventilation and intubation. For chronic treatment of asthma, inhaled corticosteroids, bronchodilator, and oral montelukasts are the mainstay. Some formulations of herbal medicine are efficacious but evidence of other modalities of complementary and alternative medicine are generally lacking. This review also discusses recent patents related to the management of asthma. These recent patents describe a few immunomodulating medications useful for the treatment of chronic severe asthma. There have been no recent patents for the management of status asthmaticus., Conclusion: Inhaled bronchodilators and systematic corticosteroids are the mainstay of therapy in the management of severe and status asthmaticus., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Objective: To update the 2002 version of "Clinical practice guidelines for sustained neuromuscular blockade in the adult critically ill patient.", Design: A Task Force comprising 17 members of the Society of Critical Medicine with particular expertise in the use of neuromuscular-blocking agents; a Grading of Recommendations Assessment, Development, and Evaluation expert; and a medical writer met via teleconference and three face-to-face meetings and communicated via e-mail to examine the evidence and develop these practice guidelines. Annually, all members completed conflict of interest statements; no conflicts were identified. This activity was funded by the Society for Critical Care Medicine, and no industry support was provided., Methods: Using the Grading of Recommendations Assessment, Development, and Evaluation system, the Grading of Recommendations Assessment, Development, and Evaluation expert on the Task Force created profiles for the evidence related to six of the 21 questions and assigned quality-of-evidence scores to these and the additional 15 questions for which insufficient evidence was available to create a profile. Task Force members reviewed this material and all available evidence and provided recommendations, suggestions, or good practice statements for these 21 questions., Results: The Task Force developed a single strong recommendation: we recommend scheduled eye care that includes lubricating drops or gel and eyelid closure for patients receiving continuous infusions of neuromuscular-blocking agents. The Task Force developed 10 weak recommendations. 1) We suggest that a neuromuscular-blocking agent be administered by continuous intravenous infusion early in the course of acute respiratory distress syndrome for patients with a PaO2/FIO2 less than 150. 2) We suggest against the routine administration of an neuromuscular-blocking agents to mechanically ventilated patients with status asthmaticus. 3) We suggest a trial of a neuromuscular-blocking agents in life-threatening situations associated with profound hypoxemia, respiratory acidosis, or hemodynamic compromise. 4) We suggest that neuromuscular-blocking agents may be used to manage overt shivering in therapeutic hypothermia. 5) We suggest that peripheral nerve stimulation with train-of-four monitoring may be a useful tool for monitoring the depth of neuromuscular blockade but only if it is incorporated into a more inclusive assessment of the patient that includes clinical assessment. 6) We suggest against the use of peripheral nerve stimulation with train of four alone for monitoring the depth of neuromuscular blockade in patients receiving continuous infusion of neuromuscular-blocking agents. 7) We suggest that patients receiving a continuous infusion of neuromuscular-blocking agent receive a structured physiotherapy regimen. 8) We suggest that clinicians target a blood glucose level of less than 180 mg/dL in patients receiving neuromuscular-blocking agents. 9) We suggest that clinicians not use actual body weight and instead use a consistent weight (ideal body weight or adjusted body weight) when calculating neuromuscular-blocking agents doses for obese patients. 10) We suggest that neuromuscular-blocking agents be discontinued at the end of life or when life support is withdrawn. In situations in which evidence was lacking or insufficient and the study results were equivocal or optimal clinical practice varies, the Task Force made no recommendations for nine of the topics. 1) We make no recommendation as to whether neuromuscular blockade is beneficial or harmful when used in patients with acute brain injury and raised intracranial pressure. 2) We make no recommendation on the routine use of neuromuscular-blocking agents for patients undergoing therapeutic hypothermia following cardiac arrest. 3) We make no recommendation on the use of peripheral nerve stimulation to monitor degree of block in patients undergoing therapeutic hypothermia. 4) We make no recommendation on the use of neuromuscular blockade to improve the accuracy of intravascular-volume assessment in mechanically ventilated patients. 5) We make no recommendation concerning the use of electroencephalogram-derived parameters as a measure of sedation during continuous administration of neuromuscular-blocking agents. 6) We make no recommendation regarding nutritional requirements specific to patients receiving infusions of neuromuscular-blocking agents. 7) We make no recommendation concerning the use of one measure of consistent weight over another when calculating neuromuscular-blocking agent doses in obese patients. 8) We make no recommendation on the use of neuromuscular-blocking agents in pregnant patients. 9) We make no recommendation on which muscle group should be monitored in patients with myasthenia gravis receiving neuromuscular-blocking agents. Finally, in situations in which evidence was lacking or insufficient but expert consensus was unanimous, the Task Force developed six good practice statements. 1) If peripheral nerve stimulation is used, optimal clinical practice suggests that it should be done in conjunction with assessment of other clinical findings (e.g., triggering of the ventilator and degree of shivering) to assess the degree of neuromuscular blockade in patients undergoing therapeutic hypothermia. 2) Optimal clinical practice suggests that a protocol should include guidance on neuromuscular-blocking agent administration in patients undergoing therapeutic hypothermia. 3) Optimal clinical practice suggests that analgesic and sedative drugs should be used prior to and during neuromuscular blockade, with the goal of achieving deep sedation. 4) Optimal clinical practice suggests that clinicians at the bedside implement measure to attenuate the risk of unintended extubation in patients receiving neuromuscular-blocking agents. 5) Optimal clinical practice suggests that a reduced dose of an neuromuscular-blocking agent be used for patients with myasthenia gravis and that the dose should be based on peripheral nerve stimulation with train-of-four monitoring. 6) Optimal clinical practice suggests that neuromuscular-blocking agents be discontinued prior to the clinical determination of brain death.

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.)

A 31-year-old female asthmatic patient received an infusion of metamizole and tramadol for chronic pain at a GP surgery. After a few minutes, the patient developed breaing difficulties and died in spite of resuscitation measures. The general practitioner was suspected of medical malpractice. Medico-legal investigations confirmed the assumption that death was caused by anaphylacitic shock. In spite of temporary intubation into the oesophagus no evidence of medical malpractice was found, however.

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.

Background: In our institution's pediatric emergency department, adherence to evidence-based asthma guidelines was noted to be suboptimal for patients with asthma exacerbations. We hypothesized that an evidence-based asthma protocol would improve time to treatment and adherence to National Institutes of Health guidelines for patients presenting to the emergency department with status asthmaticus., Methods: Subjects at our institution were retrospectively identified through an electronic medical record search following institutional review board approval. The asthma protocol was initiated in February 2012. All pediatric subjects who received continuous albuterol in the emergency department before (February 26, 2009, to February 22, 2012, n = 193) and after (February 23, 2012, to December 31, 2012, n = 68) protocol initiation were analyzed. The post-protocol data were collected as part of routine quality assurance monitoring with a target of 60 post-protocol subjects. Subjects were identified at the end of each month, which resulted in a total of 68 subjects being included. Primary outcomes measured included time to initial treatment with inhaled bronchodilator therapy, time to treatment with systemic corticosteroids, and total number of ipratropium bromide treatments delivered., Results: Two-hundred sixty-one subjects (7.1 ± 4.6 y of age, 66% male) were included. Demographics were similar in the pre- and post-protocol groups. Compared with the pre-protocol group, more subjects in the post-protocol group received bronchodilators within 30 min (60% vs 77%, P = .02), at least one dose of ipratropium bromide (55% vs 87%, P < .001), 3 doses of ipratropium bromide (14% vs 54%, P < .001), and corticosteroids within 60 min (62% vs 77%, P = .04). There were no statistically significant differences between the pre- and post-protocol cohorts in the mean time to first bronchodilator treatment (32 ± 41 vs 26 ± 52 min, P = .34), mean time to corticosteroid administration (74 ± 68 vs 54 ± 63 min, P = .06), or mean emergency department length of stay (342 ± 143 vs 364 ± 183 min, P = .31)., Conclusions: An asthma protocol resulted in improved adherence to National Institutes of Health guidelines in children with status asthmaticus and improved efficiency in the administration of rescue bronchodilator and systemic corticosteroid therapy., (Copyright © 2015 by Daedalus Enterprises.)

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.

Status asthmaticus is both a common and dangerous cause of acute dyspnea in the emergency department (ED) setting. Although most cases respond favorably to standard treatment, there are rare cases in which therapy beyond traditional treatment is needed. One of these treatment modalities includes inhalational anesthesia. We present a case in which inhaled sevoflurane was initiated out of the ED for a life-threatening asthma exacerbation refractory to conventional treatment. To our knowledge, this is only the second case to report the use of inhaled anesthetics initiated out of the ED for status asthmaticus and is the first report of its kind to thoroughly detail the respiratory response noted while inhalation anesthesia was being implemented. A brief review of other case reports involving the use of sevoflurane for asthma is included. This case, as well as the others reviewed, illustrates the significant beneficial effect inhaled anesthetics can have on asthma, making this a treatment modality that must be recognized and appreciated by all emergency medicine providers.

Status asthmaticus is an acute, intractable asthma attack refractory to standard interventions that can lead to progressive respiratory failure. Successful management requires a fundamental understanding of the disease process, its clinical presentation, and proper evaluation. Treatment must be instituted early and is aimed at reversing the airway inflammation, bronchoconstriction, and hyper-reactivity that often lead to lower airway obstruction, impaired ventilation, and oxygenation. Most patients are effectively treated with standard therapy including beta2-adrenergic agonists and corticosteroids. Others necessitate adjunctive therapies and escalation to noninvasive ventilation or intubation. We will review the pathophysiology, evaluation, and treatment options for pediatric patients presenting with status asthmaticus with a particular focus on refractory status asthmaticus treated with volatile anesthetics. In addition, we include a proven approach to the management of these patients in the critical care setting, which requires close coordination between critical care and anesthesia providers. We present a case series of three patients, two of which have the longest reported cases of continuous isoflurane use in status asthmaticus. This series was obtained from a retrospective chart review and highlights the efficacy of the volatile anesthetic, isoflurane, in three pediatric patients with refractory life-threatening status asthmaticus., (© 2015 John Wiley & Sons Ltd.)

Objective: To compare the efficacy of nebulised budesonide with that of oral prednisone in the treatment of acute severe asthma in children., Methods: Children aged 5-12 y with acute exacerbation of bronchial asthma were included. The study (budesonide) group received budesonide respirator solution (800 μg) at intervals of 20 min and a single dose of placebo tablets. The control (prednisolone) group received placebo solution at intervals of 20 min and a single dose of oral prednisolone (2 mg/kg). Both groups received three doses of nebulised salbutamol (0.15 mg/kg). Heart rate, respiratory rate, oxygen saturation, PEFR (Peak Expiratory Flow Rate) and fitness for discharge were assessed., Results: Both groups showed a progressive decrease in tachycardia with treatment, but it was significantly greater in study group (p = 0.0002). There was significant decrease in tachypnea and improvement in oxygen saturation in both groups, but the difference between the groups (p = 0.334 and p = 0.814 respectively) was not significant. There was significant improvement in PEFR values in budesonide group (p = 0.024). Both groups showed significant improvement in clinical severity scores at the end of 2 h (p < 0.0001). Budesonide group had significantly higher proportion of patients fit for discharge at 2 h (based on clinical severity scores) (p = 0.0278)., Conclusions: Nebulised budesonide significantly improves PEFR levels and fitness for discharge at 2 h when compared to oral prednisolone in children between 5 and 12 y with acute severe asthma.

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.)

This report describes the treatment of eight patients with status asthmaticus, six of whom were already maximally treated. They were consequently treated with enoximone, a selective phosphodiesterase III inhibitor, in their refractory phase. Bronchodilatation in these patients was immediate. No side-effects were observed. Enoximone appears to be a valuable addition to the treatment of status asthmaticus. I.V. administration bypasses inhalation incapability in severe asthma. It is likely to reduce or altogether prevent the need for resorting to secondary or tertiary high-tech therapy such as mechanical ventilation or anaesthetics, thus avoiding complications, as well as for transfers to specialized intensive care units. Not only do these aspects enable substantial cost savings, but they also may spare the patient a lot of anguish and a prolonged recovery., (© The Author [2014]. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Intrapulmonary arteriovenous anastomoses (IPAVs) are large-diameter pathways that directly connect the arterial and venous networks, bypassing the pulmonary capillaries. Ubiquitously present in healthy humans, these pathways are recruited in experimental conditions by exercise, hypoxia, and catecholamines and have been previously shown to be closed by hyperoxia. Whether they play a role in pulmonary pathophysiology is unknown. Here, we describe IPAV recruitment associated with hypoxemia and right-to-left shunt in a patient with status asthmaticus, treated with agonists of the B2-adrenergic pathway. Our observation of IPAVs in a pediatric patient, mechanically ventilated with 100% O₂, suggests that these pathways are recruited in clinically important circumstances and challenges the notion that IPAVs are always closed by alveolar hyperoxia.

Introduction: The role of aminophylline in the treatment of severe acute asthma in the pediatric critical care unit (PCCU) is not clear. We sought to examine the association of aminophylline treatment with PCCU length of stay and time to symptom improvement., Material and Methods: Patients with severe acute asthma who were admitted to our PCCU and received aminophylline infusion were retrospectively compared with similar patients who did not receive aminophylline. The primary outcome measure was functional length of stay (i.e. time to which patients could be transferred to a general pediatric ward bed). A secondary outcome was time to symptom improvement., Results: Adjusted functional length of stay was longer for subjects who received aminophylline (n = 49) than for the patients who did not (n = 47) (hazard ratio 0.396, p < 0.001), as well as the time for symptom improvement (hazard ratio 0.359, p < 0.001). In the group of subjects receiving aminophylline, those with a serum theophylline level ≥ 10 mcg/ml (therapeutic) (n = 31) had longer functional length of stay (hazard ratio 0.457, p = 0.0225) and time to symptom improvement (hazard ratio 0.403, p = 0.0085) than those with levels < 10 mcg/ml (sub-therapeutic) (n = 18)., Conclusions: The addition of aminophylline to therapy with corticosteroids and inhaled β-agonists was associated with statistically and clinically significant increases in functional length of stay and time to symptom improvement in the PCCU. This potential morbidity supports the National Asthma Education and Prevention Program guideline proscribing aminophylline use in acute asthma., (Copyright © 2013 Elsevier Ltd. All rights reserved.)