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Three Part Question

In [children with suspected asthma] does [oral salbutamol] compared to [inhaled salbutamol] provide [any advantages]?

Clinical Scenario

A one year old girl presents to the Emergency Department with acute wheeze and suspected asthma. Her GP had given her salbutamol syrup which did not appear to help. You use salbutamol via a spacer and want to know if oral bronchodilators are effective at relieving asthma symptoms.

Search Strategy

PubMed. Similar searches were conducted for: Embase, Google Scholar, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Australian New Zealand Clinical Trials Registry, and ClinicalTrials.gov
[oral OR liquid OR syrup OR elixir] AND [inhaled or aerosol] AND [salbutamol OR albuterol OR ventolin OR terbutaline OR bricanyl OR beta 2 agonist] AND asthma AND [child* OR pediatric OR paediatric] LiIMIT to Humans and Clinical Trial or Randomised Controlled Trial and All Child: 0-18 years

Search Outcome

14 papers were identified; six were relevant comparisons of oral and inhaled salbutamol use in the treatment of asthma in children less than 18 years of age.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Scalabrin DMF and Naspitz CK 1993 Brazil	21 asthmatic children (aged 7-14 years) treated for acute asthma with: oral salbutamol, open continuous nebulisation of salbutamol, or closed-port intermittent nebulisation of salbutamol.	RCT	Mean percent change in FEV1 from baseline values	Closed-port intermittent nebulisation of salbutamol caused a significantly greater increase in FEV1 compared with oral administration of salbutamol (P < 0.05)	Small study population.
			Mean duration of bronchodilator effect	Closed-port intermittent nebulisation resulted in a statistically longer duration of bronchodilation than oral salbutamol (P < 0.05)
			Time of peak bronchodilator effect (measured by percentage change in FEV1 from baseline)	60 minutes for nebulised salbutamol, and 120 minutes for oral salbutamol
Grimwood K et. al. 1981 New Zealand	17 asthmatic children (aged 4-12 years) treated with: nebulised salbutamol, salbutamol inhalational powder, or oral salbutamol (tablet)	RCT	Percentage improvement in PEFR	Nebulised salbutamol produced a greater percentage improvement in PEFR compared with oral salbutamol (P < 0.05)	Small study population. Salbutamol inhalational powder was delivered without spacers; this would have reduced the efficiency of administration and increased the swallowed fraction of inhaled doses.
Bartfield JM et. al. 1995 USA	34 patients with reactive airway disease (aged 4 months to 5 years) treated with oral (syrup) or aerosol salbutamol (with spacer/mask)	RCT	Hyperactivity	Reported for 5 of 11 patients treated with oral salbutamol, and for 1 of 13 patients treated with inhaled salbutamol (P = 0.06)	Small study population. Steroid use not controlled between treatment groups (4/11 patients treated with oral salbutamol were administered steroids; 0/13 patients treated with aerosol salbutamol received steroids, P < 0.01). Complete data was only available for 22 patients (telephone follow-up data was available for 2 patients, no follow-up data was available for 10 patients)
Berg IM et. al. 1982 Sweden	10 asthmatic children (aged 9-15 years) treated with oral salbutamol, aerosol salbutamol, a combination of oral and aerosol salbutamol, or placebo (oral and inhaled)	RCT	Changes in FEV1, FVC and VC	Comparable for inhaled and oral administration	Small study population. Spacers were not used, which would have decreased the efficiency of aerosolised administration and increased the swallowed fraction of inhaled doses.
Grimwood K et. al. 1983 New Zealand	18 children with severe asthma (aged 5-12 years). Patients were treated with inhaled salbutamol powder, oral salbutamol (tablet), or a combination of oral and inhaled salbutamol	RCT	Peak percentage improvement in PEFR	Reached 30 minutes after administration of inhaled salbutamol and 2 hours after administration of oral salbutamol	Small study population. Spacers were not used, which would have decreased the efficiency of inhaled administration and increased the fraction of inhalation powder swallowed.
			Tremor	Reported in one patient treated with oral salbutamol
			Hyperactivity and tachycardia	Reported in one patient treated with oral salbutamol
			Pulse rate	Significant increase observed in patient treated with oral salbutamol compared with those administered inhaled salbutamol (P < 0.01)
Francis PWJ et. al. 1980 Canada	16 asthmatic children (aged 7.5-16.9 years) subject to exercise tests. Patients were treated with: oral (tablet) salbutamol, aerosol salbutamol, or placebo (oral or inhaled)	RCT	Peak bronchodilator effect (measured by percent of predicted FEV1 value)	Observed after 40 minutes for inhaled salbutamol and after 120 minutes for oral salbutamol	Small study population. Study conducted in exercise-induced asthma (conclusions cannot inherently be applied to acute or chronic asthma).
			Tremor	Observed in 10/16 patients administered oral salbutamol, and in 2/9 patients administered salbutamol aerosol

Comment(s)

None of the found studies demonstrated benefit. We also searched for Terbutaline studies and none were found. One study was identified of oral and inhaled salbutamol use in the prevention of exercise-induced asthma in children. A review of the pharmacokinetics of salbutamol syrup suggests that oral administration is very unlikely to be effective. (1). 1. Boulton DW, Fawcett JP. Pharmacokinetics and pharmacodynamics of single oral doses of albuterol and its enantiomers in humans. Clin Pharmacol Ther. 1997 Aug.;62(2):138–144.

Clinical Bottom Line

Oral salbutamol is ineffective in the treatment of paediatric asthma and is associated with an increased incidence of adverse events compared with inhaled formulations. Paediatric masks and spacers can facilitate administration of inhaled salbutamol to all patients; therefore, there is no role for oral salbutamol. Oral salbutamol should be excluded from use in the treatment of childhood asthma.

References

1. Scalabrin DMF, Naspitz CK Efficacy and Side Effects of Salbutamol in Acute Asthma in Children: Comparison of Oral Route and Two Different Nebulizer Systems J Asthma 1993; 30(1): 51-59
2. Grimwood K, Johnson-Barrett JJ, Taylor B Salbutamol: tablets, inhalational powder, or nebuliser? Br Med J 1981; 282: 105-106
3. Bartfield JM, Boenau IB, Lozon J, Raccio-Robak N Comparison of metered dose inhaler and oral administration of albuterol in the outpatient treatment of infants and children Am J Emerg Med 1995; 13 (3): 375-377
4. Berg IM, Berg T, Ringqvist I Salbutamol in the treatment of asthmatic children Eur J Respir Dis 1982; 63(4): 305-309
5. Grimwood K, Fergusson DM, Dawson KP Combination of salbutamol inhalation powder and tablets in asthma Arch Dis Child 1983; 58: 283-285
6. Francis PWJ, Krastins IRB, Levison H Oral and Inhaled Salbutamol in the Prevention of Exercise-Induced Bronchospasm Pediatrics 1980; 66(1): 103-108