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Is IV aminophylline better than IV salbutamol in the treatment of moderate to severe asthma

Three Part Question

In [patients with moderate to severe asthma resistant to inhaled beta-2-agonists] does [IV aminophylline or IV salbutamol] result in [quicker relief with less side effects]?

Clinical Scenario

A 20-year-old male is brought to the Emergency Department in acute respiratory distress with asthma. He has a history of poor compliance with unstable asthma and several hospital admissions in the past. His old notes are available and you notice whenever IV treatment has been commenced he has been given aminophylline. You feel that the best drug is a beta-2 agonist and that if it is not getting to the receptors via the airways then IV is the next best route. There is some dismay among the nursing staff when you formulate an IV regime. They say they have never given it before. You wonder whether your approach is evidence-based.

Search Strategy

Medline 1966-10/03 using the OVID interface.
[(exp albuterol/ OR AND] AND [exp asthma/ OR exp bronchial spasm/ OR exp bronchoconstriction/ OR] AND [exp aminophylline/ OR OR exp theophylline/ OR] LIMIT to human AND English.

Search Outcome

Altogether 71 papers found of which 62 were considered irrelevant or of insufficient quality for inclusion. The remaining 9 papers are shown in the table.

Relevant Paper(s)

Author, date and country Patient group Study type (level of evidence) Outcomes Key results Study Weaknesses
Beswick K et al,
20 patients in GP setting with acute bronchospasmSingle blinded randomised trial of IV slabutamol or aminophyllineVital signsSameSmall non-ED study (majority treated at home)
PEFR FEV1 FVCDifference favouring salbutamol at 10 and 20 mins but not significant
Side effectsSignificantly worse profile for aminophylline
Williams SJ et al,
20 acute asthmatics with peak flow < 25% predicted, PaO2 < 68mmHgDBRCT One hour infusion of either 500gm aminophylline or 500mcgm salbutamolPeak flowIncreased but not significant for salbutamolSmall numbers
PulseMore tachycardia (significant) with salbutamol
BPFall in diastole
Side effectsLess tremor, nausea, no difference in plasma [K+]
Tribe AE et al,
23 acute asthma patientsDBRCT of IV aminophylline vs salbutamolSpirometryNon-significant benefit and peak effect of aminophyllineSub-optimal dose of salbutamol Variable pre-trial treatment
ABGQuicker improvement in oxygen tension with salbutamol
Femi-Pearse D et al,
50 patients with peak flow < 165l/minSingle and double blinded trials of salbutamol and aminophylline5 minutely pulse and peak flow measuresSignificant benefit in peak flow at 5 mins(p<0.005) and 20 mins (p<0.05) for single blinded trial only for salbutamol. No difference in pulse rateSmall trial Low dose of salbutamol
Johnson AJ et al,
39 of 62 acute asthmatics unresponsive to initial IV 10 min aminophylline infusion and nebulised salbutamolSingle blinded RCT Either 1mg/min aminophylline or 10mcgm/min salbutamolPeak expiratory flowNon-significant benefit of aminophyllineAll received IV aminophylline initially No initial bolus of salbutamol Variable used of nebulised salbutamol acutely Not blinded to physicians Variable background preventive treatment
FEV1Non-significant benefit of salbutamol
FVCNon-significant benefit of aminophylline
Arterial gasesNo difference
Pulse & BPSignificant tachycardia in salbutamol group
Evans WV et al,
21 acute asthma patientsSingle blinded RCT comparing aminophylline, salbutamol or combined IVSpirometryNon-significantly quicker time to improvement with aminophylline and combined infusionSmall numbers Variable baseline severity Sub-therapeutic salbutamol dosing
Sahay JN et al,
20 adults with FEV1<70% predictedDouble Blinded RCT crossover of aminophylline, turbutaline and salbutamolSpirometryAll produced significant improvement, salbutamol significantly better than aminophylline to 30 mins post dose then no difference with better peak effect.Small group, not acutely unwell
Vital signs and side effectsSalbutamol significantly more tachycardia and palpitations which return to no difference at 90 mins
Sharma TN et al,
30 known asthmatics with acute bronchospasmRCT of aminophylline, salbutamol or turbutalineSpirometrySalbutamol significantly better FEV1Blinding not clear Salbutamol 250mcgm given as 1 min. bolus
Side effectsSignificantly more palpitations with salbutamol
Grief J et al,
21 patients (mean age 38 years) with acute on chronic asthmaSingle Blinded crossover 20 min infusion of salbutamol or aminophylline% increase in peak flowSalbutamol shows significant benefit to 30 mins (p<0.01) and 45 mins (p<0.05) post infusionSmall study Not fully blinded
Pulse rateTachcardia with salbutamol
BPNo difference
Plasma [K+]Average drop of 0.6 mmol/l
TremorMore in salbutamol group


Multiple small trials of reasonable quality show IV salbutamol to be as good if not better at reversing obstructive airflow in asthmatics. Those studies which were equivocal used drug regimes that could be considered sub-therapeutic or confounded. Side effects, although present appear to be well tolerated. Recent or high-powered trials comparing the two drugs do not exist.

Clinical Bottom Line

IV salbutamol should be considered a first line agent in the acute management of severe asthma in adults.


  1. Beswick K, Davies J, Davey AJ. A comparison of intravenous aminophylline and salbutamol in the treatment of severe bronchospasm. Practitioner 1975;214:561-66.
  2. Williams SJ, Parrish RW, Seaton A. Comparison of intravenous aminophylline and salbutamol in severe asthma. BMJ 1975;4(5998):685.
  3. Tribe AE, Wong RM, Robinson JS. A controlled trial of intravenous salbutamol and aminophylline in acute asthma. Med J Australia 1976;2:749-52.
  4. Femi-Pearse D, George WO, Ilechukwu ST et al. Comparison of intravenous aminophylline and salbutamol in severe asthma. BMJ 1977;1(6059):491.
  5. Johnson AJ, Spiro SG, Pidgeon J et al. Intravenous infusion of salbutamol in severe acute asthma. BMJ 1978;1(6119):1013-5.
  6. Evans WV, Monie RD, Crimmins J et al. Aminophylline, salbutamol and combined intravenous infusions in acute severe asthma. Br J Dis Chest 1980;74(4):385-9.
  7. Sahay JN, Bell R, Chatterjee SS et al. Comparative study of effects of intravenous administration of aminophylline, salbutamol and terbutaline in patients suffering from reversible airways obstruction. Curr Med Res Opin 1984;9(1):1-6.
  8. Sharma TN, Gupta RB, Gupta PR et al. Comparison of intravenous aminophylline, salbutamol and terbtaline in acute asthma. Indian J Chest Dis & All Sci 1984;26(3):155-58.
  9. Grief J, Markovitz L, Topilsky M et al. Comparison of intravenous salbutamol (albuterol) and aminophylline in the treatment of acute asthmatic attacks. Ann Allergy 1985;55(3):504-6.