Abstract
Background:
Chronic obstructive pulmonary disease (COPD) is one of the most common chronic illnesses in humans. Among both oral and intravenous diuretics, nebulizing furosemide (Lasix) is the most commonly used agent. The purpose of this study was to ascertain the therapeutic effects of nebulizing furosemide compared with placebo in the treatment of COPD using a systematic review and meta-analysis of clinical trials.
Materials and Methods:
This review was performed based on the preferred reporting items for systematic reviews and meta-analyses (PRISMA) protocol. The databases of Web of Science, Google Scholar, PubMed, and Scopus were independently searched by two researchers using MeSH keywords. Studies published between 2002 and 2018 in different parts of the world were considered. The meta-analysis was performed through STATA 14 software and the heterogeneity was assessed using Q statistic or I2 index.
Results:
From 40 selected articles, 8 articles were finally included in the systematic review process. The analyses were performed considering two groups; nebulizing furosemide treatment (i.e. case) and placebo (i.e. control). Based on the forest plots, the average values of PaCO2 were 48.3 (39.04–57.56) and 46.56 (39.94–53.18) in the case and control groups, respectively. Also, the mean forced expiratory volume in the first second (FEV1) was 49 (31.32–66.67) and 46.87 (31.44–62.30) in the case and control groups, respectively. Meta-regression analysis showed that both heart and pulse rates in the nebulizing furosemide group decreased by increasing the year of study and sample size (P <0.001). The heterogeneity among the studies was found to be 72.2%, which is classified as severe heterogeneity.
Conclusion:
nebulizing furosemide can improve and normalize the vital signs and other respiratory variables in patients with COPD.
Keywords: Nebulizing Furosemide, COPD, Meta-Analysis, Clinical Trial
INTRODUCTION
Chronic obstructive pulmonary disease (COPD) is a chronic obstructive lung disease with failures in breathing or dyspnea, airflow limitation, shortness of breath, sputum cough, and physical activity-related breathlessness, which progressively exacerbate over time (1–2). This disease continues to be the leading cause of morbidity and mortality around the world with an enormous healthcare burden (3).
About 16 million Americans have been diagnosed with COPD, and the disease has been estimated as the sixth cause of death in the United States (4). In developing countries, such as Iran, the rate of mortality due to COPD has risen during the last 15 years (5).
The most common cause of COPD is smoking, but other factors, such as air pollution and hereditary factors may also contribute to this condition (5, 6). COPD is diagnosed based on the presentation of dyspnea in lung functional tests (2, 7). Collectively, for the diagnosis of COPD, a comprehensive clinical test, such as spirometry, chest radiography, complete blood count, and pulse oximetry are mandatory (8).
Patients with COPD have a broad range of respiratory symptoms and signs (8). However, the most common symptoms of COPD include sputum production, difficulty in breathing or breathlessness, and cough (7, 9). The management of COPD necessitates quitting smoking, pulmonary rehabilitation, using bronchodilators, maintenance of physical activity, administrating corticosteroids, long-term oxygen therapy, and finally lung transplantation in some patients (10–12). The non-drug and drug interventions showed the same impacts on improving the quality of life and alleviating the symptoms and outcomes of COPD (13).
Regarding drug therapy, except oxygen, no drug has been accompanied by the reduced risk of mortality in patients with COPD. Therefore, drugs are predominately prescribed for improving the quality of life, reducing the disease symptoms, and improving the functional capacity of the lung (14).
A wide range of drugs, such as inhaled short-acting beta-agonist (15), long-acting muscarinic antagonist, and long-acting beta-agonist (16, 17) are currently used for the treatment of COPD, which is associated with adverse effects (13).
Among short-acting beta-agonists, nebulizing furosemide is the most common agent used for the treatment of COPD (18). Furosemide is also useful in the treatment of left ventricular dysfunction reducing central blood and capillary hydrostatic pressures (19). It has been shown that the inhalation of furosemide in patients with stable COPD could relieve the dyspnea symptom and significantly improve bronchodilator during constant-load activities (20). Furthermore, in another study, it has been exhibited that the prescription of nebulized furosemide (40 mg) for COPD patients hampered COPD exacerbation (20). Despite the mentioned data, a more recent study by Waskiw-Ford et al. has questioned the effect of nebulized furosemide on exertional breathlessness in healthy men (21). In this study, the inhalation of furosemide at the doses of 40 and 120 mg did not relieve the breathlessness caused by endurance exercise test in normal men. Furthermore, optimal and controlled administration of nebulized furosemide did not create greater easement of breathlessness compared with placebo (aerosol saline) in healthy subjects (21, 22). The reason for these inconstancies has not been strictly addressed; therefore, further investigations are needed.
The mechanism, by which inhaled furosemide relives exertional dyspnea in COPD patients is multifactorial, but modulating the activity of pulmonary stretch receptors (23), which in turn alters pulmonary vagal afferent and improves airway function and dynamic ventilator (24) is also a contributory factor. Increasing the activity of the pulmonary vagal afferent by inhaled furosemide provokes larger tidal volume, leading to alleviating the sensation of breathlessness (25). It seems that the benefits of furosemide in dyspnea for COPD may outweigh its adverse effects, but further studies are required (4).
Drug delivery by nebulizers is a method for administering non-inhalable medications (26). Regarding furosemide, although intravenous delivery has been able to reduce breathing discomfort, nebulizers are more effective (22). Nebulizer application depends on features, such as particle size, shape, and density, surface tension, and the anatomy of the respiratory system (21). The main advantage of nebulizers is obviating the need for drugs to be digested and pass into the blood circulation; therefore, they are rapidly absorbed through the respiratory system (27).
The aim of meta-analysis studies is to provide a comprehensive and integrated approach regarding a specific subject (28, 29). No meta-analyses have yet been done on the clinical trials assessing the therapeutic effects of furosemide in patients with COPD. Additionally, knowledge obtained from the aforementioned studies cannot provide a definite result for COPD in a clinical setting. Considering numerous studies in this field, and in order to validate the results of these studies, we compared the therapeutic effects of furosemide and placebo in patients with COPD through a systematic review and meta-analysis on clinical trials.
MATERIALS AND METHODS
This systematic review was performed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The five steps followed in this study included the initial design, literature search, collection and evaluation of articles, qualification of articles, and finally data analysis. In order to prevent publication bias, the search was independently conducted by two researchers, and the results of the studies were combined by a third scholar.
Search strategy
A comprehensive search was independently performed by two researchers using the national and international scientific resources (Magiran, Iran Medex, PubMed, Cochrane, Web of Science, and Scopus), as well as the Google scholar search engine to obtain the literature related to the research question. Accordingly, nebulizing furosemide, placebo, and COPD keywords were first used individually, and then in combination, to perform a comprehensive search. In the end, all references of the articles were also searched to find relevant articles. To select relevant articles and exclude duplicated ones, the full texts of the articles were provided to the researchers.
Inclusion criteria
The clinical trials comparing the therapeutic effects of nebulizing furosemide and placebo in patients with COPD were included.
Exclusion criteria
Low-quality studies, irrelevant articles, studies with inadequate data, reviews, case reports, letters to editors, qualitative studies, and abstracts of congress papers that contained incomplete information were excluded.
Screening and qualifying the studies
The STROBE checklist was used to evaluate the quality of the articles (21, 27). Two authors individually scored each part of the checklist between 0 and 2. Based on the scores obtained from the checklist, the quality of the articles was divided into three groups as weak, moderate, and good with scores of 1–15, 16–30, and 31–44, respectively. Articles that obtained a good score of at least 16 entered into the meta-analysis process.
Measurement tools used in the articles
Studies that compared the therapeutic effects of nebulizing furosemide versus placebo in patients with COPD were systematically reviewed and included in the meta-analysis process.
Data extraction
The collected data from each article included the first author’s name, the year and location of the study, sample size, and the therapeutic effects of nebulizing furosemide and placebo. The outcomes included changes in the vital signs (i.e. respiratory rate, blood pressure, and heart rate) and respiratory parameters (i.e. PaCo2, Pao2, Hco3, pH, forced expiratory volume in the first second (FEV1), peak expiratory flow rate (PEFR), and SaO2). The obtained data were recorded in a checklist designed by the researcher.
Statistical analysis
Given the type of the data extracted and the number of final included studies (i.e. less than 10), the publication bias was not assessed, and a funnel plot was not drawn. The I-squared (I2) index was used to calculate the heterogeneity among the studies for each variable, including the vital signs (i.e. respiratory rate, blood pressure, and heart rate) and respiratory parameters (i.e. PaCo2, PaO2, HCo3, pH, FEV1, PEFR, and SaO2). Considering the significant heterogeneity among the studies (P <0.001), a meta-analysis was conducted using a random-effects model to combine the results of different studies. The data were analyzed using STATA software version 14.
RESULTS
At first, a list of all the titles and abstracts of the selected articles was prepared. After hiding the specifications of the articles, including the names of the journals and authors, the full texts of the articles were provided to the researchers. In the initial search, 40 articles related to the subject were obtained, of which 20 articles were omitted due to the lack of proper communication and inadequate results. Finally, by reviewing the full texts of the articles, 12 additional studies were omitted due to not fulfilling the inclusion criteria. At last, eight articles were evaluated and entered into the meta-analysis phase. The steps of the study selection are shown in Figure 1.
Figure 1.
Flowchart of the present systematic review and meta-analysis
Totally, 465 patients with COPD had been analyzed with a mean sample size of 58 patients in each study. The characteristics of the articles and their findings on the therapeutic effects of nebulizing furosemide in the treatment of COPD are provided in Table 1. Comparison of the vital signs between the two study groups showed that patients treated with nebulizing furosemide had values closer to normal (Table 2). The respiratory parameters in the two study groups are provided in Table 3. The results showed that patients who had received nebulizing furosemide had respiratory values closer to the normal levels indicating good therapeutic efficacy for this agent.
Table 1.
The specifications of the studies comparing the therapeutic effects of nebulizing furosemide and placebo in patients with COPD
| References | Author | Year | Place | N Total |
|---|---|---|---|---|
| 30 | Vahedi, et al. | 2013 | Iran | 100 |
| 31 | Brijker, et al. | 2002 | Netherlands | 20 |
| 32 | van de Ven, et al. | 2002 | Netherlands | 70 |
| 21 | Waskiw-Ford, et al. | 2018 | Canada | 24 |
| 33 | Zhang, et al. | 2012 | China | 60 |
| 34 | Alshehri, et al. | 2005 | Saudi Arabia | 60 |
| 35 | Masoumi, et al. | 2014 | Iran | 90 |
| 36 | Panahi, et al. | 2008 | Iran | 41 |
Table 2.
Comparison of vital signs between the two studied groups
| Group | Vital signs | Articles(N) | Mean | CI/95 | I2 | P Value |
|---|---|---|---|---|---|---|
| Case group | Respiratory Rate | 3 | 17.82 | 13.44. –22.20 | 78.2 | 0.000 |
| Control group | Respiratory Rate | 3 | 19.98 | 14.13–25.84 | 57.2 | 0.121 |
| Case group | Blood Pressure | 2 | 10.23 | 8.68–11.78 | 0 | 0.647 |
| Control group | Blood Pressure | 2 | 10.51 | 9.29. –11.73 | 0 | 0.932 |
| Case group | Heart Rate | 4 | 77.5 | 72.18–82.82 | 0 | 0.710 |
| Control group | Heart Rate | 4 | 83.78 | 69.11–98.44 | 81.2 | 0.001 |
Table 3.
Comparison of respiratory parameters between the two studied groups
| Group | Parameters | Articles(N) | Mean | CI/95 | I2 | P Value |
|---|---|---|---|---|---|---|
| Case group | PH | 3 | 7.41 | 7.35. –7.47 | 59.4 | 0.085 |
| Control group | PH | 3 | 7.38 | 7.38–7.45 | 64.6 | 0.059 |
| Case group | Pa CO2 | 4 | 48.3 | 39.04–57.56 | 77.7 | 0.004 |
| Control group | Pa CO2 | 4 | 46.56 | 39.94. –53.18 | 52.8 | 0.096 |
| Case group | H3CO3 | 3 | 28.52 | 25.3–31.74 | 16.4 | 0.302 |
| Case group | H3CO3 | 3 | 25.68 | 23.83–27.53 | 0 | 0.808 |
| Control group | FEV1* | 6 | 49 | 31.32–66.67 | 73.7 | 0.002 |
| Case group | FEV1 | 6 | 46.87 | 31.44–62.30 | 71.8 | 0.002 |
| Control group | FVEF/FEV | 3 | 72.27 | 52.42–92.13 | 98.4 | 0.000 |
| Case group | FVEF/FEV | 3 | 64.06 | 28.15–99.98 | 99.6 | 0.000 |
| Case group | PEFR** | 4 | 52.22 | 45.57–62.87 | 0 | 0.697 |
| Control group | PEFR | 4 | 46.63 | 34.07–59.2 | 0 | 0.892 |
| Case group | Pa O2 | 4 | 81.37 | 70.2–92.54 | 73.7 | 0.010 |
| Control group | Pa O2 | 4 | 81.07 | 67.75–94.39 | 81.1 | 0.001 |
| Case group | SA O2 | 4 | 92.55 | 87.75–97.36 | 45.6 | 0.138 |
| Case group | SA O2 | 4 | 91.1 | 86.15–96.04 | 71.2 | 0.015 |
FEV= Forced expiratory volume
PEFR=Peak expiratory flow
Figure 2 shows the forest plot of PaCo2 in the case (Figure 2a) and control (Figure 2b) groups with the mean values of 48.3 (39.04–57.56) and 46.56 (39.94–53.18), respectively. Figure 3 displays the forest plot of FEV1 in the case (Figure 3a) and control (Figure 3b) groups with the mean values of 49 (31.32–66.67) and 46.87(31.44–62.30), respectively. The meta-regression analysis based on the year of study showed that the heart rate decreased with an increase in the year of study (P <0.001) while it increased in studies with larger sample sizes (P <0.001, Figure 3). Also, pulse rate significantly decreased by increasing in the study year and sample size (P <0.001, Figure 4). The heterogeneity among the studies was 72.2%, which is considered as a high heterogeneity (28, 29).
Figure 2(a).
Shows the forest plot of PaCo2 in the case group with the mean level of48.33 (39.04–57.56).
The midpoint in each line represents the mean value in each study. The diamond shape indicates the confidence interval of the overall mean for all the studies.
Figure 2b).
Demonstrates the forest plot of PaCo2 in the control group with the mean value of 46.56 (39.94. –53.18).
The midpoint in each line represents the mean value in each study. The diamond shape indicates the confidence interval of the overall mean for all the studies.
Figure 3a).
The forest plot of FEV1 has been shown in the case group with the mean value as 49 (31.32–66.67).
FEV= Forced expiratory volume
The midpoint in each line represents the mean value in each study. The diamond shape indicates the confidence interval of the overall mean for all the studies.
Figure 3b).
Shows the forest plot of FEV1in the control group with the mean level of 46.87 (31.44–62.30)
The midpoint son each line is an estimate of the mean value in each study. The diamond shape indicates the confidence interval of the overall mean for all the studies.
FEV= Forced expiratory volume
Figure 4a).
Meta-regression of heart rate based on the year of study
Figure 4b).
Meta-regression of heart rate based on the sample sizes
Figure 4c).
Meta-regression of pulse rate based on the year of study
Figure 4d).
Meta-regression of pulse rates based on the sample size
DISCUSSION
This systematic review and meta-analysis of clinical trials compared the effects of nebulizing furosemide and placebo on cardiovascular and respiratory parameters in patients with COPD. Based on the results of the clinical trials investigated in the present review, nebulizing furosemide showed significant regulatory effects on respiratory rate, heart rate, blood pressure, FEV1, and PEFR; however, no significant impacts had been noticed on pH, PaCo2 SaO2, H3CO3, and PaO2.
The results of this study showed that respiratory and heart rates were closer to the normal range in patients treated with nebulizing furosemide than those who had received a placebo indicating the efficiency of this agent on these parameters. In a clinical trial conducted by Ong et al. in 2004, it was found that the inhalation of nebulizing furosemide significantly increased bronchodilator compared with the placebo in patients with stable COPD performing exercise (20).
The results of this study showed that treatment with nebulizing furosemide improved pulse rate and blood pressure in comparison with the control group suggesting that nebulizing furosemide can be helpful in regulating cardiac and vascular functions in patients with COPD. A study by Brijker et al. revealed that discontinuation of furosemide in patients with COPD reduced PaCo2; nonetheless, no noticeable effect was described on the oxygenation level (31).
There were no significant differences in the levels of PaCo2, SaO2, HCO3, and PaO2 comparing furosemide and placebo groups with almost the same levels in both groups. The results of this study showed that FEV1 and PEFR were closer to the reference range in COPD patients receiving furosemide than those treated with placebo. This finding suggests that furosemide can improve FEV1 and PEFR in these patients. In a clinical trial study by Sheikh Motahar Vahedi et al. on100 patients with COPD, the administration of 40 mg furosemide significantly improved FEV1, dyspnea, pH, mean blood pressure, and heart rate (30). Likewise, a double-blind randomized clinical trial has recently shown that furosemide inhalation at the doses of 40 and 120 mg along with physical activity had no effects on respiratory parameters in healthy men (21).
Limitations
The variables evaluated in the studies were limited. In some studies, different therapeutic duration and courses, as well as different furosemide doses had not been applied. In some studies, no comparisons had been conducted between males and females or among different age groups with merely mentioning overall alternations.
CONCLUSION
According to our results, nebulizing furosemide can improve and normalize the vital signs and other respiratory variables in patients with COPD. Also, the nebulizing furosemide has few complications and can be used according to the patient’s clinical condition.
Acknowledgement
This research was approved by Ilam University of Medical Sciences. We thank the Deputy of Research and Technology of the University for financial support (IR.MEDILAM.REC.1398.174).
REFERENCES
- 1.Mohammadi F, Jowkar Z, Reza Khankeh H, Fallah Tafti S. Effect of home-based nursing pulmonary rehabilitation on patients with chronic obstructive pulmonary disease: a randomised clinical trial. Br J Community Nurs 2013;18(8):398, 400–3. [DOI] [PubMed] [Google Scholar]
- 2.Putcha N, Drummond MB, Wise RA, Hansel NN. Comorbidities and Chronic Obstructive Pulmonary Disease: Prevalence, Influence on Outcomes, and Management. Semin Respir Crit Care Med 2015;36(4):575–91. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Mannino DM, Buist AS. Global burden of COPD: risk factors, prevalence, and future trends. Lancet 2007;370(9589):765–73. [DOI] [PubMed] [Google Scholar]
- 4.Jokar Z, Mohammadi F, Khankeh HR, Tafti SF. Effect of Home-based Pulmonary Rehabilitation on Fatigue in Patients with COPD. Hayat 2012;18(5):64–72. [Google Scholar]
- 5.Varmaghani M, Kebriaeezadeh A, Sharifi F, Sheidaei A, Rashidian A, Moradi-Lakeh M, et al. Death-specific rate due to asthma and chronic obstructive pulmonary disease in Iran. Clin Respir J 2018;12(6):2075–2083. [DOI] [PubMed] [Google Scholar]
- 6.Pleasants RA, Heidari K, Wheaton AG, Ohar JA, Strange C, Croft JB, et al. Targeting Persons With or At High Risk for Chronic Obstructive Pulmonary Disease by State-based Surveillance. COPD 2015;12(6):680–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Gupta D, Agarwal R, Aggarwal AN, Maturu VN, Dhooria S, Prasad KT, et al. Jindal for the COPD Guidelines Working Group. Guidelines for diagnosis and management of chronic obstructive pulmonary disease: Joint ICS/NCCP (I) recommendations. Lung India 2013;30(3):228–67. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Stephens MB, Yew KS. Diagnosis of chronic obstructive pulmonary disease. Am Fam Physician 2008;78(1):87–92. [PubMed] [Google Scholar]
- 9.Gea J, Pascual S, Casadevall C, Orozco-Levi M, Barreiro E. Muscle dysfunction in chronic obstructive pulmonary disease: update on causes and biological findings. J Thorac Dis 2015;7(10):E418–38. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Hillas G, Perlikos F, Tsiligianni I, Tzanakis N. Managing comorbidities in COPD. Int J Chron Obstruct Pulmon Dis 2015;10:95–109. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Yoon HK, Park YB, Rhee CK, Lee JH, Oh YM, Committee of the Korean COPD Guideline 2014 . Summary of the Chronic Obstructive Pulmonary Disease Clinical Practice Guideline Revised in 2014 by the Korean Academy of Tuberculosis and Respiratory Disease. Tuberc Respir Dis (Seoul) 2017;80(3):230–240. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Pleasants RA, Riley IL, Mannino DM. Defining and targeting health disparities in chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis 2016;11:2475–2496. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Clini EM, Ambrosino N. Nonpharmacological treatment and relief of symptoms in COPD. Eur Respir J 2008;32(1):218–28. [DOI] [PubMed] [Google Scholar]
- 14.Jenkins C. Drugs for chronic obstructive pulmonary disease. Aust Prescr 2017;40(1):15–19. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Global Initiative for Chronic Obstructive Lung Disease . Global strategy for the diagnosis, management and prevention of COPD. http://goldcopd.org [cited 2017 Jan 9]
- 16.Karner C, Cates CJ. Long-acting beta(2)-agonist in addition to tiotropium versus either tiotropium or long-acting beta(2)-agonist alone for chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2012;4(4):CD008989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Bateman ED, Ferguson GT, Barnes N, Gallagher N, Green Y, Henley M, et al. Dual bronchodilation with QVA149 versus single bronchodilator therapy: the SHINE study. Eur Respir J 2013;42(6):1484–94. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Schivo M, Albertson TE, Haczku A, Kenyon NJ, Zeki AA, Kuhn BT, et al. Paradigms in chronic obstructive pulmonary disease: phenotypes, immunobiology, and therapy with a focus on vascular disease. J Investig Med 2017;65(6):953–963. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Banzett RB, Schwartzstein RM, Lansing RW, O’Donnell CR. Aerosol furosemide for dyspnea: High-dose controlled delivery does not improve effectiveness. Respir Physiol Neurobiol 2018;247:24–30. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Ong KC, Kor AC, Chong WF, Earnest A, Wang YT. Effects of inhaled furosemide on exertional dyspnea in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2004;169(9):1028–33. [DOI] [PubMed] [Google Scholar]
- 21.Waskiw-Ford M, Wu A, Mainra A, Marchand N, Alhuzaim A, Bourbeau J, et al. Effect of Inhaled Nebulized Furosemide (40 and 120 mg) on Breathlessness during Exercise in the Presence of External Thoracic Restriction in Healthy Men. Front Physiol 2018;9:86. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Morélot-Panzini C, O’Donnell CR, Lansing RW, Schwartzstein RM, Banzett RB. Aerosol furosemide for dyspnea: Controlled delivery does not improve effectiveness. Respir Physiol Neurobiol 2018;247:146–155. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Nishino T. Dyspnoea: underlying mechanisms and treatment. Br J Anaesth 2011;106(4):463–74. [DOI] [PubMed] [Google Scholar]
- 24.Jensen D, Amjadi K, Harris-McAllister V, Webb KA, O’Donnell DE. Mechanisms of dyspnoea relief and improved exercise endurance after furosemide inhalation in COPD. Thorax 2008;63(7):606–13. [DOI] [PubMed] [Google Scholar]
- 25.Moosavi SH, Binks AP, Lansing RW, Topulos GP, Banzett RB, Schwartzstein RM. Effect of inhaled furosemide on air hunger induced in healthy humans. Respir Physiol Neurobiol 2007;156(1):1–8. [DOI] [PubMed] [Google Scholar]
- 26.Pacifici GM. Clinical pharmacology of furosemide in neonates: a review. Pharmaceuticals (Basel) 2013;6(9):1094–129. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Yen ZS, Chen SC. Best evidence topic report. Nebulised furosemide in acute adult asthma. Emerg Med J 2005;22(9): 654–5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Badfar G, Shohani M, Nasirkandy MP, Mansouri A, Abangah G, Rahmati S, et al. Epidemiology of hepatitis B in pregnant Iranian women: a systematic review and meta-analysis. Arch Virol 2018;163(2):319–330. [DOI] [PubMed] [Google Scholar]
- 29.Badfar G, Shohani M, Mansouri A, Soleymani A, Azami M. Vitamin D status in Iranian pregnant women and newborns: a systematic review and meta-analysis study. Expert Rev Endocrinol Metab 2017;12(5):379–389. [DOI] [PubMed] [Google Scholar]
- 30.Sheikh Motahar Vahedi H, Mahshidfar B, Rabiee H, Saadat S, Shokoohi H, Chardoli M, et al. The adjunctive effect of nebulized furosemide in COPD exacerbation: a randomized controlled clinical trial. Respir Care 2013;58(11):1873–7. [DOI] [PubMed] [Google Scholar]
- 31.Brijker F, Heijdra YF, van den Elshout FJ, Folgering HT. Discontinuation of furosemide decreases PaCO(2) in patients with COPD. Chest 2002;121(2):377–82. [DOI] [PubMed] [Google Scholar]
- 32.van de Ven MJ, Colier WN, van der Sluijs MC, Oeseburg B, Vis P, Folgering H. Effects of acetazolamide and furosemide on ventilation and cerebral blood volume in normocapnic and hypercapnic patients with COPD. Chest 2002;121(2):383–92. [DOI] [PubMed] [Google Scholar]
- 33.Zhang J, Zhao G, Yu X, Pan X. Intravenous diuretic and vasodilator therapy reduce plasma brain natriuretic peptide levels in acute exacerbation of chronic obstructive pulmonary disease. Respirology 2012;17(4):715–20. [DOI] [PubMed] [Google Scholar]
- 34.Alshehri M, Almegamesi T, Alfrayh A. Efficacy of nebulized furosemide in children with moderate attack of asthma. West Afr J Med 2005;24(3):246–51. [DOI] [PubMed] [Google Scholar]
- 35.Masoumi K, Forouzan A, Haddadzadeh Shoushtari M, Porozan S, Feli M, Fallah Bagher Sheidaee M, et al. The efficacy of nebulized furosemide and salbutamol compared with salbutamol alone in reactive airway disease: a double blind randomized, clinical trial. Emerg Med Int 2014;2014:638102. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 36.Panahi Y, Motiei-Langroudi R, Alaeddini F, Naghizadeh MM, Aslani J, Ghanei M. Furosemide inhalation in dyspnea of mustard gas-exposed patients: a triple-blind randomized study. Inhal Toxicol 2008;20(9):873–7. [DOI] [PubMed] [Google Scholar]