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Three Part Question

In [an adult with asthma] is [nebulised beta agonist with nebulised furosemide better than nebulised beta agonist alone] at [improving airflow and reducing morbidity]?

Clinical Scenario

A known asthmatic adult patient is brought into the emergency department with signs consistent with acute asthma. Little improvement is noted with nebulised beta agonist therapy. You wonder if adjunctive nebulised furosemide would provide any benefit.

Search Strategy

Medline 1966-12/04 and Embase: Drugs & Pharmacology 1980-1/03 using the OVID interface, The Cochrane Library, Issue 2, 2005.
Medline: {(exp furosemide OR furosemide$.mp OR lasix$.mp) AND (nebuli$.mp OR vapori$.mp OR inhal$.mp OR aerosoli$.mp) AND (exp asthma OR exp asthma, exercise-induced OR asthma$.mp OR exp bronchial spasm OR bronchial spasm$.mp OR bronchospasm$.mp)} LIMIT to human AND English.
Embase: {(exp furosemide OR furosemide$.mp OR lasix$.mp) AND (nebuli$.mp OR vapori$.mp OR inhal$.mp OR aerosoli$.mp) AND (exp asthma OR exp exercised induced asthma OR exp allergic asthma OR exp occupational asthma OR exp bronchospasm OR bronchial spasm$.mp OR bronchospasm$.mp)} LIMIT to human AND English.
Cochrane Library: 'furosemide'.

Search Outcome

Altogether 87 papers from Medline and 156 from Embase were found of which two were considered to be original research of high quality (randomised controlled trials) and relevant to the topic of interest. A further reference was found after scanning of paper references. These three papers are summarised in the table. Thirty-four papers were found in the Cochrane Library and none of which were relevant to the three part question.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Pendino JC et al. 1998 Canada	42 patients (age 18-45) with acute asthma randomised to nebulised salbutamol/furosemide or salbutamol/normal saline	PRCT	PEFR (percentage increase) in all patients	No significant difference in PEFR between both groups at 15min and 30min.	Small sample Unclear randomisation and blinding procedure Post-hoc analysis of patients with short duration of exacerbations
			PEFR (percentage increase) in patients with short duration of exacerbations (<8hr)	Salbutamol/furosemide 82(SD 48)% and 113(SD 49)% versus salbutamol/normal saline 35(SD 40)% and 61(SD 35)%, at 15min (p=0.03) and 30min (p=0.014) respectively
Karpel JP et al. 1994 USA	24 patients (age 18-45) with acute asthma randomised to nebulised furosemide or nebulised metaproterenol or nebulised metaproterenol/furosemide	PRCT	FEV1	No statistical difference between the metaproterenol group and the metaproterenol/furosemide group	Small sample
Nannini LJ et al 1992 Canada	20 patients with acute asthma randomised to inhaled salbutamol/furosemide (age 31 (SD 11)) or inhaled salbutamol/normal saline (age 41 (SD12))	PRCT	PEFR (percentage increase)	Salbutamol/furosemide 83(SD 61)% versus salbutamol/normal saline 35(SD 24)% at 30min, p<0.05	Small sample Unclear randomisation and blinding procedure Unknown exclusion and inclusion criteria Poor comparability of baseline data between two groups

Comment(s)

A number of mechanisms have been postulated to explain the bronchodilating effect of nebulised furosemide, including: (1) induction of relaxant prostaglandins; (2) blockade of mediator production from inflammatory cells; (3) regulation of ion exchange in the airway epithelium. Of the few randomised controlled studies that relate to the efficacy of nebulised furosemide in the treatment of acute adult asthma, samples remain small and conflicting results persist. More large-scale studies are needed to determine whether nebulised furosemide has any therapeutic benefit in acute adult asthma.

Clinical Bottom Line

There is currently insufficient evidence to support the routine addition of nebulised furosemide to standard beta agonist therapy in acute asthma in adults.

References

1. Pendino JC, Nannini LJ, Chapman KR, Slutsky A, Molfino NA. Effect of inhaled furosemide in acute asthma. J Asthma 1998;35:89-93.
2. Karpel JP, Dworkin F, Hager D, Feliciano S, Shapiro D, Posner L, Luks D. Inhaled furosemide is not effective in acute asthma. Chest 1994;106:1396-400.
3. Nannini LJ, Pendino JC, Molfino NA, Slutsky AS. Inhaled furosemide and salbutamol in acute asthma. Am Rev Respir Dis 1992;145:A422.