- Email: [email protected]
Bilevel Positive Airway Pressure ventilation efficiently improves respiratory distress in initial hours treating children with severe asthma exacerbation
+
MODEL
Journal of the Formosan Medical Association xxx (xxxx) xxx
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.jfma-online.com
Original Article
Bilevel Positive Airway Pressure ventilation efficiently improves respiratory distress in initial hours treating children with severe asthma exacerbation Chun-Min Kang a, En-Ting Wu a, Ching-Chia Wang a, Frank Lu a, Bor-Luen Chiang a,b, Ting-An Yen a,* a The Department of Pediatrics, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan b The Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
Received 8 August 2019; received in revised form 6 November 2019; accepted 13 November 2019
KEYWORDS Asthma; Non-invasive ventilation; Pediatric intensive care; Pediatric pulmonology; Pediatric immunology
Objective: Treatment of severe asthma exacerbation could be challenging, especially in the initial hours of acute attack when systemic corticosteroid is yet to take effect. In spite of using inhaled agents, the role of non-invasive ventilation (NIV), including Bilevel Positive Airway Pressure (BiPAP), had been addressed recently. Methods: We reviewed 5-year experience in our hospital for records of patients who were admitted to pediatric intensive care unit because of severe asthma attack. The included admission records from 2012 to 2017 were grouped according to BiPAP use (Yes/No). Clinical parameters (heart rate (HR), respiratory rate (RR), SpO2 and serum pCO2) at selected time intervals of treatment were collected for both groups and analyzed. Results: We included data of 46 admissions from 33 different patients (24 with BiPAP and 21 without BiPAP.) The BiPAP group had significantly higher initial RR as well as higher severity scores compared with the other group (p < 0.001). The RR improved significantly in the following time intervals in BiPAP group. There was no significant difference in HR between groups in any of the time intervals. The serum pCO2 levels decreased significantly after initiation of ventilation support in the BiPAP group, and SpO2 levels improved significantly for both groups. Conclusion: BiPAP seemed efficient in improving respiratory rate and oxygenation in our study. It does not seem to cause additional irritation regarding that HR was not increased in BiPAP
* Corresponding author. Department of Pediatrics, National Taiwan University Hospital, No. 8, Chung-Shan South Road, Taipei 100, Taiwan. E-mail address: [email protected] (T.-A. Yen). https://doi.org/10.1016/j.jfma.2019.11.013 0929-6646/Copyright ª 2019, Formosan Medical Association. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Please cite this article as: Kang C-M et al., Bilevel Positive Airway Pressure ventilation efficiently improves respiratory distress in initial hours treating children with severe asthma exacerbation, Journal of the Formosan Medical Association, https://doi.org/10.1016/ j.jfma.2019.11.013
+
MODEL
2
C.-M. Kang et al. group compared with non-BiPAP group. Overall, BiPAP ventilation is safe and efficient in treating children with severe asthma attack. Copyright ª 2019, Formosan Medical Association. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/bync-nd/4.0/).
Introduction Asthma is a chronic inflammatory condition of the airways that can result in episodic airflow obstruction, characterized by wheezing, prolonged coughing and chest tightness. The prevalence of childhood asthma has risen over the years, as well as severity and morbidity.1e3 In Taiwan, the prevalence of childhood asthma had increased from less than 5% in the 1980s to around 20% in the 2010s, and its impacts on personal quality of life and health policies and economics were addressed.4 In an acute asthma attack, the standard managements would include supplemental oxygen, inhaled bronchodilators and systemic corticosteroid. Consultation of pediatric intensive care unit (ICU) might be required in more severe cases. Status asthmaticus refers to an acute severe asthma exacerbation, in which bronchial obstruction gets severe, deteriorates, or stays the same, despite the institution of standard therapy.5 Children with status asthmaticus may need aggressive ventilation support and airway management, and admissions to a pediatric intensive care unit (ICU) are usually indicated. However, previous studies suggested that intubation and mechanical ventilation could be associated with significant adverse events in asthmatic patients, such as barotraumas, steroid/ neuromuscular blocking agent-associated myopathy, mucus plugging, and lung atelectasis.6 Non-invasive ventilation (NIV) has been proven beneficial for adult patients with chronic obstructive pulmonary disease (COPD) exacerbations.2,7 Bilevel Positive Airway Pressure (BiPAP), a form of NIV, being able to increase tidal volume, has the advantage of adding external positive endexpiratory pressure (PEEP) to offset the intrinsic PEEP that builds up during an asthmatic attack, thus further decreasing the work of the inspiratory muscles.2 In asthma, the evidence regarding the role of NIV is insufficient, whereas increasing studies have demonstrated the potential efficacy of NIV in treating patients with status asthmaticus. One prospective crossover study by Thill PJ et al.8 of early initiation of noninvasive positive pressure ventilation (NPPV) in children with lower airway obstruction showed significantly improved clinical scores, in terms of accessory muscle use, presence of wheezes and dyspnea respectively as well as total scores, after 2 h of NPPV support. A reversed trend was also found in the study compared with standard therapy after treatment crossover. Another randomized controlled trial by Yanez LJ et al. in children with acute respiratory failure also showed encouraging result,9 that installment of NIV improves hypoxemia and symptoms and signs of acute respiratory failure, in both infants and older children. Sangita Basnet, MD et al. conducted a prospective, pilot study in 2012, which
showed that early initiation of noninvasive positive pressure ventilation, along with short acting b-agonists and systemic steroids can be safe, well-tolerated, and effective in the management of children with status asthmaticus. However, the case number is limited.10 Despite the proven efficacy in those small-scaled studies, we still lack clinical evidence because of the paucity, the difficulty of a more strictly protocolled study design and the small cohort. Neither Global Initiative for Asthma (GINA) nor Cochrane Review placed NPPV in a concrete or strategic position in treatment of status asthmaticus.11,12 It is still regarded as an “experimental approach.” There was no available data in Taiwan to demonstrate the clinical effect using NPPV on childhood asthma. We therefore conducted a retrospective study of Taiwanese children who admitted to pediatric intensive care unit (PICU) under the diagnosis of severe asthma exacerbation or status asthmaticus, and were treated with or without BiPAP. The purpose of the study is to assess the treatment efficacy and tolerability of BiPAP usage in severe asthmatic children.
Patients and methods Design and enrolment criteria The study is conducted retrospectively by collecting data from previous medical records. Patients were identified by searching database in National Taiwan University Hospital (NTUH) and National Taiwan University Children’s Hospital (NTUCH) using ICD codes for asthma (ICD9: 439.9; ICD10: J45.9). Pediatric patients (age 18 years old) who had had admission at PICU during the time period of January, 2012 to February 2017 with the diagnosis of asthma were enrolled. The medical record for the selected patients were reviewed. Those with other significant co-morbidities that would serve as main indication for ICU (in this study: status epilepticus, acute myocarditis, pulmonary hemorrhage, pneumonia caused by respiratory syncytial virus (RSV)) rather than asthma, or those with certain identified respiratory pathogens that may further contribute to respiratory distress were excluded. Patients with documented chronic illness that possibly add impact on cardiopulmonary reserves (cerebral palsy, complex congenital heart diseases, dilated cardiomyopathy (DCM), chronic lung disease, tracheoesophageal fistula) were also excluded from the study. For those with multiple admissions, each admission was regarded as an individual event. The enrolled data were divided into two groups regarding whether BiPAP was used
Please cite this article as: Kang C-M et al., Bilevel Positive Airway Pressure ventilation efficiently improves respiratory distress in initial hours treating children with severe asthma exacerbation, Journal of the Formosan Medical Association, https://doi.org/10.1016/ j.jfma.2019.11.013
+
MODEL
BiPAP in treating Asthmatic Children
3
Figure 1 Enrollment and Exclusion Criteria. a. CHD: congenital heart disease. b. Other comorbidities in the group included hypoxic ischemic encephalopathy with cerebral palsy, and tracheoesophageal fistula status post operation. c. DCM: dilated cardiomyopathy. d. RSV: respiratory syncytial virus.
or not during admission. For each admission record, the following characteristics were documented with the medical records: age at admission, body weight, clinical symptoms, heart rate (HR), respiratory rate (RR), oxygen demand, partial pressure of carbon dioxide in serum (pCO2), oxygen saturation (SpO2), laboratory data and images of chest x-ray. Pediatric Asthma Severity Score (PASS) for acute exacerbation and Pediatric Respiratory Assessment Measure (PRAM) were calculated based on the medical record at the time of initial approach to the patients.13e15 Several clinical parameters (HR, RR, SpO2) were also documented longitudinally at selected time intervals (before intervention, after intervention: 0e2 h, 2e4 h, 4e8 h, 10e14 h, 16e20 h and 24 h) of the treatment courses. Time zero was defined as the initiation of BiPAP ventilation for the BiPAP-using group or the initiation of any other method of oxygen supplementation (nasal cannula, simple oxygen mask, or non-rebreathing mask) at PICU for the non-BiPAP-using group. If multiple records were found at certain time interval, we use median value for statistical analysis.
Statistics analysis All data analysis was conducted by SPSS statistics (version 23.0) for Windows. Fisher’s exact test was used for comparison of categorical variables. Non-parametric ManneWhitney U test was used to compare the differences of continuous variables at each selected time point between 2 groups. Wilcoxon Signed-Rank test was used to analyze the pCO2 and SpO2 levels before and after the intervention. All tests were two-sided and p-value < 0.05 was deemed as statistically significant.
Disclosure of Interest and Ethical Standards The authors have no conflict of interest to report. All the data used in the study were obtained in accordance with the ethical standards of the responsible committee at National Taiwan University Hospital.
Results Patient grouping There were 801 admissions between January, 2012 and February 2017. Data of 59 PICU admissions were obtained and 12 of them were excluded for either existence of comorbidities of other major organs that lead to ICU admission or the presence of other definite diagnosis of airway disease other than asthma that could cause respiratory distress (eg. croup; bronchopulmonary dysplasia with RSV infection). Among the enrolled data, one of the admissions was excluded from the analysis of which the patient had already been intubated when transferred from another medical unit. A total of 46 admissions were included for data analysis: 25 with BiPAP and 21 without BiPAP, which were shown in Fig. 1.
Clinical characteristics There were no significant statistical differences between the two groups in terms of age and body weight. However, there was significant discrepancy in sex ratio between 2 groups. Both initial PASS and PRAM of the BiPAP group were significantly higher than the other group. The BiPAP group had a longer mean hospital stay and ICU stay compared to
Please cite this article as: Kang C-M et al., Bilevel Positive Airway Pressure ventilation efficiently improves respiratory distress in initial hours treating children with severe asthma exacerbation, Journal of the Formosan Medical Association, https://doi.org/10.1016/ j.jfma.2019.11.013
+
MODEL
4
C.-M. Kang et al. Table 1
Clinical characteristics of PICU patients with severe asthma attack.
Patient number (n) Female, n (%) Age (months) Body Weight (kg) PRAM at admission PASS at admission BiPAP (hours) ICU stay (days) Admission (days) % of systemic steroid, n (%) % of antibiotic use, n (%) % of magnesium use, n (%) % of aminophylline use, n (%) pCO2 (mmHg) SpO2 (%) Respiratory Rate (times/min) Heart Rate (bpm)
Total
BiPAP
Non-BiPAP
p-value
46 27 (58.7) 51.24 28.16 16.44 5.35 7.22 2.04 3.93 1.06 e 1.80 1.20 5.15 2.10 42 (91.30%) 42 (91.30%) 6 (13.04%) 2 (4.44%) 39.42 9.31 92.55 5.31 41.35 10.47 147.37 36.38
25 18 (72.0) 53.76 34.59 16.19 6.03 8.12 1.64 4.40 1.00 35 21 2.28 1.40 5.88 2.24 22 (88.0%) 23 (92.0%) 6 (24.0%) 2 (8.0%) 38.83 9.29 93.38 4.35 46.88 9.75 153.80 18.57
21 9 (42.9) 48.24 18.18 16.73 4.55 6.14 1.98 3.38 0.87 e 1.24 0.54 4.29 1.55 20 (95.23%) 19 (90.48%) 0 0 40.84 9.20 91.55 6.24 33.67 5.41 139.41 49.50
0.046* 0.493 0.729 <0.001*** 0.001** e 0.002** 0.007** 0.385 0.855 0.016* 0.185 0.437 0.414 <0.001*** 0.589
*: p value < 0.05. **: p value < 0.01. ***: p value < 0.001.
non-BiPAP group. Magnesium sulfate was administered in 6 cases in the BiPAP group as alternative rescue treatment, but none in the other group, the difference was statistically significant. On the other hand, the usage of systemic corticosteroids and antibiotics had no proportional difference. Two cases in the BiPAP group received intravenous aminophylline, which made no statistical significance, either. The mean duration of BiPAP use was 35 21 h.
difference in HR, SpO2, and pCO2 (Table 1). In the time series comparison, the BiPAP group had significantly higher RR at time 0 (before intervention) (46.88 9.75 times/min versus 33.67 5.41, p < 0.001), but there was no significant difference between groups in the following time intervals (Fig. 2). As for HR, no significant difference was noted in any of the time intervals (Fig. 3).
pCO2 and SpO2 levels Respiratory rates and heart rates For the clinical parameters, only the initial RR is significantly different between 2 groups; there were no
Figure 2 Respiratory rate (RR) trends in different hours of treatment. The respiratory rates between the two groups were significantly different before treatment, with BiPAP-using group having a higher mean RR. However, there was no statistically significant difference between groups in the following time intervals.
pCO2 level improved significantly after BiPAP being used. The post-BiPAP serum pCO2 levels were lower than preBiPAP (39.42 9.31 mmHg versus 33.65 4.46 mmHg.) The highest documented pre-treatment pCO2 level in all
Figure 3 Heart rate (HR) trends in different hours of treatment. Despite the different devices used for ventilation support, there was no significant difference between heart rates of the two groups in any of the selected time intervals.
Please cite this article as: Kang C-M et al., Bilevel Positive Airway Pressure ventilation efficiently improves respiratory distress in initial hours treating children with severe asthma exacerbation, Journal of the Formosan Medical Association, https://doi.org/10.1016/ j.jfma.2019.11.013
+
MODEL
BiPAP in treating Asthmatic Children
5
Figure 4 SpO2 and serum pCO2 levels comparison before and after treatment. (A) BiPAP usage significantly improves oxygenation in PICU patients with severe asthma, p < 0.001%. (before: round symbols; after: triangle symbols). (B) SpO2 also improved significantly in non-BiPAP group, p < 0.001. (before: round symbols; after: triangle symbols). (C) The serum pCO2 levels were reduced significantly with BiPAP usage, p Z 0.0126. The pCO2 levels before treatment had no difference statistically between two groups. (BiPAP group: before: round symbols; after: square symbols) (Non-BiPAP group: triangle symbols). *: p value < 0.05. **: p value < 0.01. ***: p value < 0.001.
patients was 56.6 mmHg. Six of the 25 patients (24%) in the BiPAP group had a pCO2 level > 45 mmHg before intervention, and all of them had pCO2 levels < 45 mmHg after 1e3 h of BiPAP used (Fig. 4C). In contrast, 7 of the 21 patients (33.33%) in the non-BiPAP-using group had a pCO2 higher than 45 mmHg before intervention, with the highest pCO2 level being 57.1 mmHg. Most of the patients in the non-BiPAP-using group had only one blood gas test and was not available for pre- and post-treatment comparison. We compared the SpO2 level before treatment and three hours after treatment. For both groups, the SpO2 level was better after treatment, and the improvement was statistically significant (p-value: < 0.001 for BiPAP group and 0.001 for non-BiPAP group.) (Fig. 4A & B).
Discussion Severe acute asthma exacerbation may lead to CO2 retention and respiratory failure and could be life threatening. Relievers such as b2 agonists and systemic steroid are effective in most cases, but additional treatment choices should be considered in more severe situation.5 NPPV could be of choice in order to improve ventilation and prevent further CO2 retention or respiratory failure.1,10,12,16 In our study, we compared the clinical courses of patients using BiPAP/not using BiPAP for treatment of acute asthma attack in PICU. The only significant difference between two groups is the initial RR, a factor which is also suggested to be associated with NIV requirement in a multivariant logistic regression analysis of an ICU cohort study by Al-Eyadhy A. A, et al.5 Over time, all patients showed improvements in RR and HR. There was no marked increase in HR in the BiPAP-using group, implying that using BiPAP would not cause extra agitation and uncooperativeness in pediatric patients. The findings are similar to a previous
prospective study on adult, which has also been found with more significant decrease in RR in those using BiPAP and similar decrease pattern of HR between groups.2 From our study, BiPAP use is effective in improving SpO2 and preventing further CO2 retention. It may help to reduce the potential risk of endotracheal intubation in children with severe asthma attack. We chose to compare the serum PCO2 levels before intervention and 1e3 h after initiation of ventilation support. The time interval may most possibly eliminate the confounding effect of systemic corticosteroid. The pCO2 levels after BiPAP support were significantly lower than that before intervention. The mean initial pCO2 level of the BiPAP-using group was lower than that of the non-BiPAP-using group (38.83 9.29 versus 40.84 9.20) though statistically insignificant, and so was the percentage patient having pCO2 level > 45 mmHg, a value that indicates respiratory failure suggested by 2018 Global Initiatives of Asthma. This finding suggests that the decision to use BiPAP did not solely rely on the value of pCO2, it was a comprehensive evaluation both from clinical presentation (whether there are respiratory distress symptoms) and other objective information. Of note, the mean initial serum pCO2 level of all PICU patients is 39.78 mmHg, quite lower than the mean pCO2 in other studies on PICU asthmatic patients.2 This may imply a patient being in the status of respiratory compensation, resulting in increased respiratory rate and relatively low pCO2 concentration. It could also mean a rather low threshold of admitting asthmatic patients to PICU, which is possibly a consequence of the high accessibility to medical service in Taiwan, that asthmatic patients usually get early management at Emergency Units before CO2 starts to retain. Endotracheal intubation is usually undesirable in asthma management, since it is associated with longer ICU stay and higher rate of morbidity, such as pneumonia or
Please cite this article as: Kang C-M et al., Bilevel Positive Airway Pressure ventilation efficiently improves respiratory distress in initial hours treating children with severe asthma exacerbation, Journal of the Formosan Medical Association, https://doi.org/10.1016/ j.jfma.2019.11.013
+
MODEL
6 pneumothorax, and should be reserved unless other noninvasive methods fail to resolve respiratory distress.17,18 Among all cases in our study, only one patient was intubated because of unresolved CO2 retention under O2 mask and BiPAP, in one of her multiple PICU admissions for asthma exacerbation. Statistical analysis of risk factors leading to intubation was not available for solitary case, but this patient did have identifiable risk factors that had been proven to be associated with recurrent and more severe asthma attack, including poor adhesion to controllers and increased exposure to secondhand and thirdhand smoke.19e22 Fortunately, the patient does not seem to have significant sequelae of intubation and was able to recover and be discharged. Of note, a majority of the patients enrolled had history of readmission for asthma attack, and six of them had readmissions at PICU. All of PICU readmissions were female patients, causing and overwhelming gender disproportion in our study, while sex is not an identified risk factor for more severe attack.23e25 Magnesium sulfate was administered in 6 (24%) of the cases in BiPAP group as rescue treatment, resulting in statistical difference between groups. Patients in BiPAP group had more severe respiratory difficulties compared to non-BIPAP group and therefore would more likely to have recue therapy. Of note, all patients received MgSO4 “after” the initiation of BiPAP due to clinical condition. In our analysis of the BiPAP group with exclusion of cases who used MgSO4 (See Supplementary data for analysis excluding cases with magnesium usage), statistical trends and significances were similar to that of original data, suggesting that in our study, MgSO4 might not have strong confounding effect in improving symptoms during initial hours of treatment. There was no mortality in studied cases. Our study is by far the first study to evaluate the effect of BiPAP on treating Asian pediatric patients with severe asthma in a real clinical setting. Given that there is neither large-scale study to validate the effect of BiPAP-using on asthma treatment nor standardized protocol to be suggested in current guidelines, the clinical experiences may help us establish a strategy of NPPV utilization. There are several limitations for our study. Firstly, it is done mainly by retrospective chart review, and the vital sign data could not be as exactly recorded at certain time interval as we expected in a real clinical setting, especially during the patient’s stay at ER. Thus some of the patients had no data at certain time intervals. Secondly, arterial line is not routinely established in our patient group, for difficulties in keeping the lines when the patients were not under sedation. Therefore, we could not get serial blood sampling for every patient and was not able to address the before- and after-blood gas change in non-BiPAP-using group. Thirdly, we calculated asthma severity score with individual bias, and indication for ICU and choice of ventilation support are mainly based on the patient’s clinical presentation and the opinions of primary care givers. The fact that the decision for each patient is made by clinician’s experience hence adds heterogeneity to our patient group, which was reflected in the variability in our statistical result. Last, as mentioned earlier, patients in the BiPAP group had more severe respiratory condition, therefore had increased use of MgSO4 compared to non-BIPAP group. However, due to the nature of this retrospective study, the confounding
C.-M. Kang et al. effect by MgSO4 might modify the result of BiPAP, which was also one of our limitations. In conclusion, we found that there was a significant improvement of respiratory rate in patients after BiPAP support. BiPAP is also well-tolerated compared with other means of non-invasive ventilation or oxygen support (nebulizer, mask). The improving trends also reflected in RR, HR and CO2 similarly in both groups. Taken together, BiPAP ventilation is safe and efficient for relief of respiratory symptoms in children with severe asthma attack.
Declaration of Competing Interest The authors have no conflicts of interest relevant to this article.
Acknowledgments This work was supported by Ministry of Science and Technology of Taiwan (MOST 107-2314-B-002-252 -) and National Taiwan University Hospital (NTUH107-S3878).
Appendix A. Supplementary data Supplementary data to this article can be found online at https://doi.org/10.1016/j.jfma.2019.11.013.
References 1. Ferna ´ndez MM, Villagra ´ A, Blanch L, Ferna ´ndez R. Non-invasive mechanical ventilation in status asthmaticus. Intensive Care Med 2014;27(3):486e92. 2. Soroksky A, Stav D, Shpirer I. A pilot prospective, randomized, placebo-controlled trial of bilevel positive airway pressure in acute asthmatic attack. Chest 2003;123(4):1018e25. 3. Alangari AA. Corticosteroids in the treatment of acute asthma. Ann Thorac Med 2014;9(4):187e92. 4. Ma YC, Lin CC, Li CI, Chiang JH, Li TC, Lin JG. Time-trend analysis of prevalence, incidence and traditional Chinese medicine use among children with asthma: a population-based study. J Public Health (Oxford) 2016;38(3):e263e71. 5. Al-Eyadhy AA, Temsah MH, Alhaboob AA, Aldubayan AK, Almousa NA, Alsharidah AM, et al. Asthma changes at a pediatric intensive care unit after 10 years: observational study. Ann Thorac Med 2015;10(4):243e8. 6. Zimmerman JL, Dellinger RP, Shah AN, Taylor RW. Endotracheal intubation and mechanical ventilation in severe asthma. Crit Care Med 1993;21(11):1727e30. 7. Murase K, Tomii K, Chin K, Tsuboi T, Sakurai A, Tachikawa R, et al. The use of non-invasive ventilation for life-threatening asthma attacks: changes in the need for intubation. Respirology 2010;15(4):714e20. 8. Thill PJ, McGuire JK, Baden HP, Green TP, Checchia PA. Noninvasive positive-pressure ventilation in children with lower airway obstruction. Pediatr Crit Care Med 2004;5(4): 337e42. 9. Yanez LJ, Yunge M, Emilfork M, Lapadula M, Alcantara A, Fernandez C, et al. A prospective, randomized, controlled trial of noninvasive ventilation in pediatric acute respiratory failure. Pediatr Crit Care Med 2008;9(5):484e9. 10. Basnet S, Mander G, Andoh J, Klaska H, Verhulst S, Koirala J. Safety, efficacy, and tolerability of early initiation of noninvasive positive pressure ventilation in pediatric patients
Please cite this article as: Kang C-M et al., Bilevel Positive Airway Pressure ventilation efficiently improves respiratory distress in initial hours treating children with severe asthma exacerbation, Journal of the Formosan Medical Association, https://doi.org/10.1016/ j.jfma.2019.11.013
+
MODEL
BiPAP in treating Asthmatic Children
11. 12.
13.
14.
15.
16.
17.
18.
admitted with status asthmaticus: a pilot study. Pediatr Crit Care Med 2012;13(4):393e8. Global Initiative for Asthma. Global strategy for the diagnosis and prevention. Global Initiative for Asthma; 2019. Lim WJ, Mohammed Akram R, Carson KV, Mysore S, Labiszewski NA, Wedzicha JA, et al. Non-invasive positive pressure ventilation for treatment of respiratory failure due to severe acute exacerbations of asthma. Cochrane Database Syst Rev 2012;12:CD004360. Gorelick MH, Stevens MW, Schultz TR, Scribano PV. Performance of a novel clinical score, the pediatric asthma severity score (pass), in the evaluation of acute asthma. Acad Emerg Med 2004;11(1):10e8. Alnaji F, Zemek R, Barrowman N, Plint A. Pram score as predictor of pediatric asthma hospitalization. Acad Emerg Med 2014;21(8):872e8. Ducharme FM, Chalut D, Plotnick L, Savdie C, Kudirka D, Zhang X, et al. The pediatric respiratory assessment measure: a valid clinical score for assessing acute asthma severity from toddlers to teenagers. J Pediatr 2008;152(4):476e80. 480 e471. Korang SK, Feinberg J, Wetterslev J, Jakobsen JC. Non-invasive positive pressure ventilation for acute asthma in children. Cochrane Database Syst Rev 2016;9:CD012067. Roberts JS, Bratton SL, Brogan TV. Acute severe asthma: differences in therapies and outcomes among pediatric intensive care units. Crit Care Med 2002;30(3):581e5. Rampa S, Allareddy V, Asad R, Nalliah RP, Allareddy V, Rotta AT. Outcomes of invasive mechanical ventilation in
7
19.
20.
21.
22.
23.
24.
25.
children and adolescents hospitalized due to status asthmaticus in United States: a population based study. J Asthma 2015; 52(4):423e30. Ciaccio CE, DiDonna A, Kennedy K, Barnes CS, Portnoy JM, Rosenwasser LJ. Secondhand tobacco smoke exposure in lowincome children and its association with asthma. Allergy Asthma Proc 2014;35(6):462e6. Farber HJ, Knowles SB, Brown NL, Caine L, Luna V, Qian Y, et al. Secondhand tobacco smoke in children with asthma: sources of and parental perceptions about exposure in children and parental readiness to change. Chest 2008;133(6):1367e74. Ferrante G, Simoni M, Cibella F, Ferrara F, Liotta G, Malizia V, et al. Third-hand smoke exposure and health hazards in children. Monaldi Arch Chest Dis 2013;79(1):38e43. Hang B, Sarker AH, Havel C, Saha S, Hazra TK, Schick S, et al. Thirdhand smoke causes DNA damage in human cells. Mutagenesis 2013;28(4):381e91. Buyantseva LV, Brooks J, Rossi M, Lehman E, Craig TJ. Risk factors associated with 30-day asthma readmissions. J Asthma 2016;53(7):684e90. Chung HS, Hathaway DK, Lew DB. Risk factors associated with hospital readmission in pediatric asthma. J Pediatr Nurs 2015; 30(2):364e84. Visitsunthorn N, Lilitwat W, Jirapongsananuruk O, Vichyanond P. Factors affecting readmission for acute asthmatic attacks in children. Asian Pac J Allergy Immunol 2013; 31(2):138e41.
Please cite this article as: Kang C-M et al., Bilevel Positive Airway Pressure ventilation efficiently improves respiratory distress in initial hours treating children with severe asthma exacerbation, Journal of the Formosan Medical Association, https://doi.org/10.1016/ j.jfma.2019.11.013
MODEL
Journal of the Formosan Medical Association xxx (xxxx) xxx
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.jfma-online.com
Original Article
Bilevel Positive Airway Pressure ventilation efficiently improves respiratory distress in initial hours treating children with severe asthma exacerbation Chun-Min Kang a, En-Ting Wu a, Ching-Chia Wang a, Frank Lu a, Bor-Luen Chiang a,b, Ting-An Yen a,* a The Department of Pediatrics, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan b The Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
Received 8 August 2019; received in revised form 6 November 2019; accepted 13 November 2019
KEYWORDS Asthma; Non-invasive ventilation; Pediatric intensive care; Pediatric pulmonology; Pediatric immunology
Objective: Treatment of severe asthma exacerbation could be challenging, especially in the initial hours of acute attack when systemic corticosteroid is yet to take effect. In spite of using inhaled agents, the role of non-invasive ventilation (NIV), including Bilevel Positive Airway Pressure (BiPAP), had been addressed recently. Methods: We reviewed 5-year experience in our hospital for records of patients who were admitted to pediatric intensive care unit because of severe asthma attack. The included admission records from 2012 to 2017 were grouped according to BiPAP use (Yes/No). Clinical parameters (heart rate (HR), respiratory rate (RR), SpO2 and serum pCO2) at selected time intervals of treatment were collected for both groups and analyzed. Results: We included data of 46 admissions from 33 different patients (24 with BiPAP and 21 without BiPAP.) The BiPAP group had significantly higher initial RR as well as higher severity scores compared with the other group (p < 0.001). The RR improved significantly in the following time intervals in BiPAP group. There was no significant difference in HR between groups in any of the time intervals. The serum pCO2 levels decreased significantly after initiation of ventilation support in the BiPAP group, and SpO2 levels improved significantly for both groups. Conclusion: BiPAP seemed efficient in improving respiratory rate and oxygenation in our study. It does not seem to cause additional irritation regarding that HR was not increased in BiPAP
* Corresponding author. Department of Pediatrics, National Taiwan University Hospital, No. 8, Chung-Shan South Road, Taipei 100, Taiwan. E-mail address: [email protected] (T.-A. Yen). https://doi.org/10.1016/j.jfma.2019.11.013 0929-6646/Copyright ª 2019, Formosan Medical Association. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Please cite this article as: Kang C-M et al., Bilevel Positive Airway Pressure ventilation efficiently improves respiratory distress in initial hours treating children with severe asthma exacerbation, Journal of the Formosan Medical Association, https://doi.org/10.1016/ j.jfma.2019.11.013
+
MODEL
2
C.-M. Kang et al. group compared with non-BiPAP group. Overall, BiPAP ventilation is safe and efficient in treating children with severe asthma attack. Copyright ª 2019, Formosan Medical Association. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/bync-nd/4.0/).
Introduction Asthma is a chronic inflammatory condition of the airways that can result in episodic airflow obstruction, characterized by wheezing, prolonged coughing and chest tightness. The prevalence of childhood asthma has risen over the years, as well as severity and morbidity.1e3 In Taiwan, the prevalence of childhood asthma had increased from less than 5% in the 1980s to around 20% in the 2010s, and its impacts on personal quality of life and health policies and economics were addressed.4 In an acute asthma attack, the standard managements would include supplemental oxygen, inhaled bronchodilators and systemic corticosteroid. Consultation of pediatric intensive care unit (ICU) might be required in more severe cases. Status asthmaticus refers to an acute severe asthma exacerbation, in which bronchial obstruction gets severe, deteriorates, or stays the same, despite the institution of standard therapy.5 Children with status asthmaticus may need aggressive ventilation support and airway management, and admissions to a pediatric intensive care unit (ICU) are usually indicated. However, previous studies suggested that intubation and mechanical ventilation could be associated with significant adverse events in asthmatic patients, such as barotraumas, steroid/ neuromuscular blocking agent-associated myopathy, mucus plugging, and lung atelectasis.6 Non-invasive ventilation (NIV) has been proven beneficial for adult patients with chronic obstructive pulmonary disease (COPD) exacerbations.2,7 Bilevel Positive Airway Pressure (BiPAP), a form of NIV, being able to increase tidal volume, has the advantage of adding external positive endexpiratory pressure (PEEP) to offset the intrinsic PEEP that builds up during an asthmatic attack, thus further decreasing the work of the inspiratory muscles.2 In asthma, the evidence regarding the role of NIV is insufficient, whereas increasing studies have demonstrated the potential efficacy of NIV in treating patients with status asthmaticus. One prospective crossover study by Thill PJ et al.8 of early initiation of noninvasive positive pressure ventilation (NPPV) in children with lower airway obstruction showed significantly improved clinical scores, in terms of accessory muscle use, presence of wheezes and dyspnea respectively as well as total scores, after 2 h of NPPV support. A reversed trend was also found in the study compared with standard therapy after treatment crossover. Another randomized controlled trial by Yanez LJ et al. in children with acute respiratory failure also showed encouraging result,9 that installment of NIV improves hypoxemia and symptoms and signs of acute respiratory failure, in both infants and older children. Sangita Basnet, MD et al. conducted a prospective, pilot study in 2012, which
showed that early initiation of noninvasive positive pressure ventilation, along with short acting b-agonists and systemic steroids can be safe, well-tolerated, and effective in the management of children with status asthmaticus. However, the case number is limited.10 Despite the proven efficacy in those small-scaled studies, we still lack clinical evidence because of the paucity, the difficulty of a more strictly protocolled study design and the small cohort. Neither Global Initiative for Asthma (GINA) nor Cochrane Review placed NPPV in a concrete or strategic position in treatment of status asthmaticus.11,12 It is still regarded as an “experimental approach.” There was no available data in Taiwan to demonstrate the clinical effect using NPPV on childhood asthma. We therefore conducted a retrospective study of Taiwanese children who admitted to pediatric intensive care unit (PICU) under the diagnosis of severe asthma exacerbation or status asthmaticus, and were treated with or without BiPAP. The purpose of the study is to assess the treatment efficacy and tolerability of BiPAP usage in severe asthmatic children.
Patients and methods Design and enrolment criteria The study is conducted retrospectively by collecting data from previous medical records. Patients were identified by searching database in National Taiwan University Hospital (NTUH) and National Taiwan University Children’s Hospital (NTUCH) using ICD codes for asthma (ICD9: 439.9; ICD10: J45.9). Pediatric patients (age 18 years old) who had had admission at PICU during the time period of January, 2012 to February 2017 with the diagnosis of asthma were enrolled. The medical record for the selected patients were reviewed. Those with other significant co-morbidities that would serve as main indication for ICU (in this study: status epilepticus, acute myocarditis, pulmonary hemorrhage, pneumonia caused by respiratory syncytial virus (RSV)) rather than asthma, or those with certain identified respiratory pathogens that may further contribute to respiratory distress were excluded. Patients with documented chronic illness that possibly add impact on cardiopulmonary reserves (cerebral palsy, complex congenital heart diseases, dilated cardiomyopathy (DCM), chronic lung disease, tracheoesophageal fistula) were also excluded from the study. For those with multiple admissions, each admission was regarded as an individual event. The enrolled data were divided into two groups regarding whether BiPAP was used
Please cite this article as: Kang C-M et al., Bilevel Positive Airway Pressure ventilation efficiently improves respiratory distress in initial hours treating children with severe asthma exacerbation, Journal of the Formosan Medical Association, https://doi.org/10.1016/ j.jfma.2019.11.013
+
MODEL
BiPAP in treating Asthmatic Children
3
Figure 1 Enrollment and Exclusion Criteria. a. CHD: congenital heart disease. b. Other comorbidities in the group included hypoxic ischemic encephalopathy with cerebral palsy, and tracheoesophageal fistula status post operation. c. DCM: dilated cardiomyopathy. d. RSV: respiratory syncytial virus.
or not during admission. For each admission record, the following characteristics were documented with the medical records: age at admission, body weight, clinical symptoms, heart rate (HR), respiratory rate (RR), oxygen demand, partial pressure of carbon dioxide in serum (pCO2), oxygen saturation (SpO2), laboratory data and images of chest x-ray. Pediatric Asthma Severity Score (PASS) for acute exacerbation and Pediatric Respiratory Assessment Measure (PRAM) were calculated based on the medical record at the time of initial approach to the patients.13e15 Several clinical parameters (HR, RR, SpO2) were also documented longitudinally at selected time intervals (before intervention, after intervention: 0e2 h, 2e4 h, 4e8 h, 10e14 h, 16e20 h and 24 h) of the treatment courses. Time zero was defined as the initiation of BiPAP ventilation for the BiPAP-using group or the initiation of any other method of oxygen supplementation (nasal cannula, simple oxygen mask, or non-rebreathing mask) at PICU for the non-BiPAP-using group. If multiple records were found at certain time interval, we use median value for statistical analysis.
Statistics analysis All data analysis was conducted by SPSS statistics (version 23.0) for Windows. Fisher’s exact test was used for comparison of categorical variables. Non-parametric ManneWhitney U test was used to compare the differences of continuous variables at each selected time point between 2 groups. Wilcoxon Signed-Rank test was used to analyze the pCO2 and SpO2 levels before and after the intervention. All tests were two-sided and p-value < 0.05 was deemed as statistically significant.
Disclosure of Interest and Ethical Standards The authors have no conflict of interest to report. All the data used in the study were obtained in accordance with the ethical standards of the responsible committee at National Taiwan University Hospital.
Results Patient grouping There were 801 admissions between January, 2012 and February 2017. Data of 59 PICU admissions were obtained and 12 of them were excluded for either existence of comorbidities of other major organs that lead to ICU admission or the presence of other definite diagnosis of airway disease other than asthma that could cause respiratory distress (eg. croup; bronchopulmonary dysplasia with RSV infection). Among the enrolled data, one of the admissions was excluded from the analysis of which the patient had already been intubated when transferred from another medical unit. A total of 46 admissions were included for data analysis: 25 with BiPAP and 21 without BiPAP, which were shown in Fig. 1.
Clinical characteristics There were no significant statistical differences between the two groups in terms of age and body weight. However, there was significant discrepancy in sex ratio between 2 groups. Both initial PASS and PRAM of the BiPAP group were significantly higher than the other group. The BiPAP group had a longer mean hospital stay and ICU stay compared to
Please cite this article as: Kang C-M et al., Bilevel Positive Airway Pressure ventilation efficiently improves respiratory distress in initial hours treating children with severe asthma exacerbation, Journal of the Formosan Medical Association, https://doi.org/10.1016/ j.jfma.2019.11.013
+
MODEL
4
C.-M. Kang et al. Table 1
Clinical characteristics of PICU patients with severe asthma attack.
Patient number (n) Female, n (%) Age (months) Body Weight (kg) PRAM at admission PASS at admission BiPAP (hours) ICU stay (days) Admission (days) % of systemic steroid, n (%) % of antibiotic use, n (%) % of magnesium use, n (%) % of aminophylline use, n (%) pCO2 (mmHg) SpO2 (%) Respiratory Rate (times/min) Heart Rate (bpm)
Total
BiPAP
Non-BiPAP
p-value
46 27 (58.7) 51.24 28.16 16.44 5.35 7.22 2.04 3.93 1.06 e 1.80 1.20 5.15 2.10 42 (91.30%) 42 (91.30%) 6 (13.04%) 2 (4.44%) 39.42 9.31 92.55 5.31 41.35 10.47 147.37 36.38
25 18 (72.0) 53.76 34.59 16.19 6.03 8.12 1.64 4.40 1.00 35 21 2.28 1.40 5.88 2.24 22 (88.0%) 23 (92.0%) 6 (24.0%) 2 (8.0%) 38.83 9.29 93.38 4.35 46.88 9.75 153.80 18.57
21 9 (42.9) 48.24 18.18 16.73 4.55 6.14 1.98 3.38 0.87 e 1.24 0.54 4.29 1.55 20 (95.23%) 19 (90.48%) 0 0 40.84 9.20 91.55 6.24 33.67 5.41 139.41 49.50
0.046* 0.493 0.729 <0.001*** 0.001** e 0.002** 0.007** 0.385 0.855 0.016* 0.185 0.437 0.414 <0.001*** 0.589
*: p value < 0.05. **: p value < 0.01. ***: p value < 0.001.
non-BiPAP group. Magnesium sulfate was administered in 6 cases in the BiPAP group as alternative rescue treatment, but none in the other group, the difference was statistically significant. On the other hand, the usage of systemic corticosteroids and antibiotics had no proportional difference. Two cases in the BiPAP group received intravenous aminophylline, which made no statistical significance, either. The mean duration of BiPAP use was 35 21 h.
difference in HR, SpO2, and pCO2 (Table 1). In the time series comparison, the BiPAP group had significantly higher RR at time 0 (before intervention) (46.88 9.75 times/min versus 33.67 5.41, p < 0.001), but there was no significant difference between groups in the following time intervals (Fig. 2). As for HR, no significant difference was noted in any of the time intervals (Fig. 3).
pCO2 and SpO2 levels Respiratory rates and heart rates For the clinical parameters, only the initial RR is significantly different between 2 groups; there were no
Figure 2 Respiratory rate (RR) trends in different hours of treatment. The respiratory rates between the two groups were significantly different before treatment, with BiPAP-using group having a higher mean RR. However, there was no statistically significant difference between groups in the following time intervals.
pCO2 level improved significantly after BiPAP being used. The post-BiPAP serum pCO2 levels were lower than preBiPAP (39.42 9.31 mmHg versus 33.65 4.46 mmHg.) The highest documented pre-treatment pCO2 level in all
Figure 3 Heart rate (HR) trends in different hours of treatment. Despite the different devices used for ventilation support, there was no significant difference between heart rates of the two groups in any of the selected time intervals.
Please cite this article as: Kang C-M et al., Bilevel Positive Airway Pressure ventilation efficiently improves respiratory distress in initial hours treating children with severe asthma exacerbation, Journal of the Formosan Medical Association, https://doi.org/10.1016/ j.jfma.2019.11.013
+
MODEL
BiPAP in treating Asthmatic Children
5
Figure 4 SpO2 and serum pCO2 levels comparison before and after treatment. (A) BiPAP usage significantly improves oxygenation in PICU patients with severe asthma, p < 0.001%. (before: round symbols; after: triangle symbols). (B) SpO2 also improved significantly in non-BiPAP group, p < 0.001. (before: round symbols; after: triangle symbols). (C) The serum pCO2 levels were reduced significantly with BiPAP usage, p Z 0.0126. The pCO2 levels before treatment had no difference statistically between two groups. (BiPAP group: before: round symbols; after: square symbols) (Non-BiPAP group: triangle symbols). *: p value < 0.05. **: p value < 0.01. ***: p value < 0.001.
patients was 56.6 mmHg. Six of the 25 patients (24%) in the BiPAP group had a pCO2 level > 45 mmHg before intervention, and all of them had pCO2 levels < 45 mmHg after 1e3 h of BiPAP used (Fig. 4C). In contrast, 7 of the 21 patients (33.33%) in the non-BiPAP-using group had a pCO2 higher than 45 mmHg before intervention, with the highest pCO2 level being 57.1 mmHg. Most of the patients in the non-BiPAP-using group had only one blood gas test and was not available for pre- and post-treatment comparison. We compared the SpO2 level before treatment and three hours after treatment. For both groups, the SpO2 level was better after treatment, and the improvement was statistically significant (p-value: < 0.001 for BiPAP group and 0.001 for non-BiPAP group.) (Fig. 4A & B).
Discussion Severe acute asthma exacerbation may lead to CO2 retention and respiratory failure and could be life threatening. Relievers such as b2 agonists and systemic steroid are effective in most cases, but additional treatment choices should be considered in more severe situation.5 NPPV could be of choice in order to improve ventilation and prevent further CO2 retention or respiratory failure.1,10,12,16 In our study, we compared the clinical courses of patients using BiPAP/not using BiPAP for treatment of acute asthma attack in PICU. The only significant difference between two groups is the initial RR, a factor which is also suggested to be associated with NIV requirement in a multivariant logistic regression analysis of an ICU cohort study by Al-Eyadhy A. A, et al.5 Over time, all patients showed improvements in RR and HR. There was no marked increase in HR in the BiPAP-using group, implying that using BiPAP would not cause extra agitation and uncooperativeness in pediatric patients. The findings are similar to a previous
prospective study on adult, which has also been found with more significant decrease in RR in those using BiPAP and similar decrease pattern of HR between groups.2 From our study, BiPAP use is effective in improving SpO2 and preventing further CO2 retention. It may help to reduce the potential risk of endotracheal intubation in children with severe asthma attack. We chose to compare the serum PCO2 levels before intervention and 1e3 h after initiation of ventilation support. The time interval may most possibly eliminate the confounding effect of systemic corticosteroid. The pCO2 levels after BiPAP support were significantly lower than that before intervention. The mean initial pCO2 level of the BiPAP-using group was lower than that of the non-BiPAP-using group (38.83 9.29 versus 40.84 9.20) though statistically insignificant, and so was the percentage patient having pCO2 level > 45 mmHg, a value that indicates respiratory failure suggested by 2018 Global Initiatives of Asthma. This finding suggests that the decision to use BiPAP did not solely rely on the value of pCO2, it was a comprehensive evaluation both from clinical presentation (whether there are respiratory distress symptoms) and other objective information. Of note, the mean initial serum pCO2 level of all PICU patients is 39.78 mmHg, quite lower than the mean pCO2 in other studies on PICU asthmatic patients.2 This may imply a patient being in the status of respiratory compensation, resulting in increased respiratory rate and relatively low pCO2 concentration. It could also mean a rather low threshold of admitting asthmatic patients to PICU, which is possibly a consequence of the high accessibility to medical service in Taiwan, that asthmatic patients usually get early management at Emergency Units before CO2 starts to retain. Endotracheal intubation is usually undesirable in asthma management, since it is associated with longer ICU stay and higher rate of morbidity, such as pneumonia or
Please cite this article as: Kang C-M et al., Bilevel Positive Airway Pressure ventilation efficiently improves respiratory distress in initial hours treating children with severe asthma exacerbation, Journal of the Formosan Medical Association, https://doi.org/10.1016/ j.jfma.2019.11.013
+
MODEL
6 pneumothorax, and should be reserved unless other noninvasive methods fail to resolve respiratory distress.17,18 Among all cases in our study, only one patient was intubated because of unresolved CO2 retention under O2 mask and BiPAP, in one of her multiple PICU admissions for asthma exacerbation. Statistical analysis of risk factors leading to intubation was not available for solitary case, but this patient did have identifiable risk factors that had been proven to be associated with recurrent and more severe asthma attack, including poor adhesion to controllers and increased exposure to secondhand and thirdhand smoke.19e22 Fortunately, the patient does not seem to have significant sequelae of intubation and was able to recover and be discharged. Of note, a majority of the patients enrolled had history of readmission for asthma attack, and six of them had readmissions at PICU. All of PICU readmissions were female patients, causing and overwhelming gender disproportion in our study, while sex is not an identified risk factor for more severe attack.23e25 Magnesium sulfate was administered in 6 (24%) of the cases in BiPAP group as rescue treatment, resulting in statistical difference between groups. Patients in BiPAP group had more severe respiratory difficulties compared to non-BIPAP group and therefore would more likely to have recue therapy. Of note, all patients received MgSO4 “after” the initiation of BiPAP due to clinical condition. In our analysis of the BiPAP group with exclusion of cases who used MgSO4 (See Supplementary data for analysis excluding cases with magnesium usage), statistical trends and significances were similar to that of original data, suggesting that in our study, MgSO4 might not have strong confounding effect in improving symptoms during initial hours of treatment. There was no mortality in studied cases. Our study is by far the first study to evaluate the effect of BiPAP on treating Asian pediatric patients with severe asthma in a real clinical setting. Given that there is neither large-scale study to validate the effect of BiPAP-using on asthma treatment nor standardized protocol to be suggested in current guidelines, the clinical experiences may help us establish a strategy of NPPV utilization. There are several limitations for our study. Firstly, it is done mainly by retrospective chart review, and the vital sign data could not be as exactly recorded at certain time interval as we expected in a real clinical setting, especially during the patient’s stay at ER. Thus some of the patients had no data at certain time intervals. Secondly, arterial line is not routinely established in our patient group, for difficulties in keeping the lines when the patients were not under sedation. Therefore, we could not get serial blood sampling for every patient and was not able to address the before- and after-blood gas change in non-BiPAP-using group. Thirdly, we calculated asthma severity score with individual bias, and indication for ICU and choice of ventilation support are mainly based on the patient’s clinical presentation and the opinions of primary care givers. The fact that the decision for each patient is made by clinician’s experience hence adds heterogeneity to our patient group, which was reflected in the variability in our statistical result. Last, as mentioned earlier, patients in the BiPAP group had more severe respiratory condition, therefore had increased use of MgSO4 compared to non-BIPAP group. However, due to the nature of this retrospective study, the confounding
C.-M. Kang et al. effect by MgSO4 might modify the result of BiPAP, which was also one of our limitations. In conclusion, we found that there was a significant improvement of respiratory rate in patients after BiPAP support. BiPAP is also well-tolerated compared with other means of non-invasive ventilation or oxygen support (nebulizer, mask). The improving trends also reflected in RR, HR and CO2 similarly in both groups. Taken together, BiPAP ventilation is safe and efficient for relief of respiratory symptoms in children with severe asthma attack.
Declaration of Competing Interest The authors have no conflicts of interest relevant to this article.
Acknowledgments This work was supported by Ministry of Science and Technology of Taiwan (MOST 107-2314-B-002-252 -) and National Taiwan University Hospital (NTUH107-S3878).
Appendix A. Supplementary data Supplementary data to this article can be found online at https://doi.org/10.1016/j.jfma.2019.11.013.
References 1. Ferna ´ndez MM, Villagra ´ A, Blanch L, Ferna ´ndez R. Non-invasive mechanical ventilation in status asthmaticus. Intensive Care Med 2014;27(3):486e92. 2. Soroksky A, Stav D, Shpirer I. A pilot prospective, randomized, placebo-controlled trial of bilevel positive airway pressure in acute asthmatic attack. Chest 2003;123(4):1018e25. 3. Alangari AA. Corticosteroids in the treatment of acute asthma. Ann Thorac Med 2014;9(4):187e92. 4. Ma YC, Lin CC, Li CI, Chiang JH, Li TC, Lin JG. Time-trend analysis of prevalence, incidence and traditional Chinese medicine use among children with asthma: a population-based study. J Public Health (Oxford) 2016;38(3):e263e71. 5. Al-Eyadhy AA, Temsah MH, Alhaboob AA, Aldubayan AK, Almousa NA, Alsharidah AM, et al. Asthma changes at a pediatric intensive care unit after 10 years: observational study. Ann Thorac Med 2015;10(4):243e8. 6. Zimmerman JL, Dellinger RP, Shah AN, Taylor RW. Endotracheal intubation and mechanical ventilation in severe asthma. Crit Care Med 1993;21(11):1727e30. 7. Murase K, Tomii K, Chin K, Tsuboi T, Sakurai A, Tachikawa R, et al. The use of non-invasive ventilation for life-threatening asthma attacks: changes in the need for intubation. Respirology 2010;15(4):714e20. 8. Thill PJ, McGuire JK, Baden HP, Green TP, Checchia PA. Noninvasive positive-pressure ventilation in children with lower airway obstruction. Pediatr Crit Care Med 2004;5(4): 337e42. 9. Yanez LJ, Yunge M, Emilfork M, Lapadula M, Alcantara A, Fernandez C, et al. A prospective, randomized, controlled trial of noninvasive ventilation in pediatric acute respiratory failure. Pediatr Crit Care Med 2008;9(5):484e9. 10. Basnet S, Mander G, Andoh J, Klaska H, Verhulst S, Koirala J. Safety, efficacy, and tolerability of early initiation of noninvasive positive pressure ventilation in pediatric patients
Please cite this article as: Kang C-M et al., Bilevel Positive Airway Pressure ventilation efficiently improves respiratory distress in initial hours treating children with severe asthma exacerbation, Journal of the Formosan Medical Association, https://doi.org/10.1016/ j.jfma.2019.11.013
+
MODEL
BiPAP in treating Asthmatic Children
11. 12.
13.
14.
15.
16.
17.
18.
admitted with status asthmaticus: a pilot study. Pediatr Crit Care Med 2012;13(4):393e8. Global Initiative for Asthma. Global strategy for the diagnosis and prevention. Global Initiative for Asthma; 2019. Lim WJ, Mohammed Akram R, Carson KV, Mysore S, Labiszewski NA, Wedzicha JA, et al. Non-invasive positive pressure ventilation for treatment of respiratory failure due to severe acute exacerbations of asthma. Cochrane Database Syst Rev 2012;12:CD004360. Gorelick MH, Stevens MW, Schultz TR, Scribano PV. Performance of a novel clinical score, the pediatric asthma severity score (pass), in the evaluation of acute asthma. Acad Emerg Med 2004;11(1):10e8. Alnaji F, Zemek R, Barrowman N, Plint A. Pram score as predictor of pediatric asthma hospitalization. Acad Emerg Med 2014;21(8):872e8. Ducharme FM, Chalut D, Plotnick L, Savdie C, Kudirka D, Zhang X, et al. The pediatric respiratory assessment measure: a valid clinical score for assessing acute asthma severity from toddlers to teenagers. J Pediatr 2008;152(4):476e80. 480 e471. Korang SK, Feinberg J, Wetterslev J, Jakobsen JC. Non-invasive positive pressure ventilation for acute asthma in children. Cochrane Database Syst Rev 2016;9:CD012067. Roberts JS, Bratton SL, Brogan TV. Acute severe asthma: differences in therapies and outcomes among pediatric intensive care units. Crit Care Med 2002;30(3):581e5. Rampa S, Allareddy V, Asad R, Nalliah RP, Allareddy V, Rotta AT. Outcomes of invasive mechanical ventilation in
7
19.
20.
21.
22.
23.
24.
25.
children and adolescents hospitalized due to status asthmaticus in United States: a population based study. J Asthma 2015; 52(4):423e30. Ciaccio CE, DiDonna A, Kennedy K, Barnes CS, Portnoy JM, Rosenwasser LJ. Secondhand tobacco smoke exposure in lowincome children and its association with asthma. Allergy Asthma Proc 2014;35(6):462e6. Farber HJ, Knowles SB, Brown NL, Caine L, Luna V, Qian Y, et al. Secondhand tobacco smoke in children with asthma: sources of and parental perceptions about exposure in children and parental readiness to change. Chest 2008;133(6):1367e74. Ferrante G, Simoni M, Cibella F, Ferrara F, Liotta G, Malizia V, et al. Third-hand smoke exposure and health hazards in children. Monaldi Arch Chest Dis 2013;79(1):38e43. Hang B, Sarker AH, Havel C, Saha S, Hazra TK, Schick S, et al. Thirdhand smoke causes DNA damage in human cells. Mutagenesis 2013;28(4):381e91. Buyantseva LV, Brooks J, Rossi M, Lehman E, Craig TJ. Risk factors associated with 30-day asthma readmissions. J Asthma 2016;53(7):684e90. Chung HS, Hathaway DK, Lew DB. Risk factors associated with hospital readmission in pediatric asthma. J Pediatr Nurs 2015; 30(2):364e84. Visitsunthorn N, Lilitwat W, Jirapongsananuruk O, Vichyanond P. Factors affecting readmission for acute asthmatic attacks in children. Asian Pac J Allergy Immunol 2013; 31(2):138e41.
Please cite this article as: Kang C-M et al., Bilevel Positive Airway Pressure ventilation efficiently improves respiratory distress in initial hours treating children with severe asthma exacerbation, Journal of the Formosan Medical Association, https://doi.org/10.1016/ j.jfma.2019.11.013