Is IV aminophylline better than IV salbutamol in the treatment of moderate to severe asthma
Date First Published:
October 27, 2000
Last Updated:
January 21, 2004
Report by:
Andrew Munro, Emergency Medicine Registrar (Christchurch Hospital, NZ)
Search checked by:
Michelle Jacobs, Christchurch Hospital, NZ
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.
Search Details:
[(exp albuterol/ OR salbutamol.mp) AND intravenous.mp] AND [exp asthma/ OR exp bronchial spasm/ OR exp bronchoconstriction/ OR bronchoconstriction.mp] AND [exp aminophylline/ OR aminophylline.mp OR exp theophylline/ OR theophylline.mp] LIMIT to human AND English.
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):
| Study Title | Patient Group | Study type (level of evidence) | Outcomes | Key results | Study Weaknesses |
|---|---|---|---|---|---|
| A comparison of intravenous aminophylline and salbutamol in the treatment of severe bronchospasm. Beswick K, Davies J, Davey AJ. 1975, UK | 20 patients in GP setting with acute bronchospasm | Single blinded randomised trial of IV slabutamol or aminophylline | Vital signs | Same | Small non-ED study (majority treated at home) |
| PEFR FEV1 FVC | Difference favouring salbutamol at 10 and 20 mins but not significant | ||||
| Side effects | Significantly worse profile for aminophylline | ||||
| Comparison of intravenous aminophylline and salbutamol in severe asthma. Williams SJ, Parrish RW, Seaton A. 1975, Wales | 20 acute asthmatics with peak flow < 25% predicted, PaO2 < 68mmHg | DBRCT One hour infusion of either 500gm aminophylline or 500mcgm salbutamol | Peak flow | Increased but not significant for salbutamol | Small numbers |
| Pulse | More tachycardia (significant) with salbutamol | ||||
| BP | Fall in diastole | ||||
| Side effects | Less tremor, nausea, no difference in plasma [K+] | ||||
| A controlled trial of intravenous salbutamol and aminophylline in acute asthma. Tribe AE, Wong RM, Robinson JS. 1976, Australia | 23 acute asthma patients | DBRCT of IV aminophylline vs salbutamol | Spirometry | Non-significant benefit and peak effect of aminophylline | Sub-optimal dose of salbutamol Variable pre-trial treatment |
| ABG | Quicker improvement in oxygen tension with salbutamol | ||||
| Comparison of intravenous aminophylline and salbutamol in severe asthma. Femi-Pearse D, George WO, Ilechukwu ST et al. 1977, Nigeria | 50 patients with peak flow < 165l/min | Single and double blinded trials of salbutamol and aminophylline | 5 minutely pulse and peak flow measures | Significant 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 rate | Small trial Low dose of salbutamol |
| Intravenous infusion of salbutamol in severe acute asthma. Johnson AJ, Spiro SG, Pidgeon J et al. 1978, UK | 39 of 62 acute asthmatics unresponsive to initial IV 10 min aminophylline infusion and nebulised salbutamol | Single blinded RCT Either 1mg/min aminophylline or 10mcgm/min salbutamol | Peak expiratory flow | Non-significant benefit of aminophylline | All received IV aminophylline initially No initial bolus of salbutamol Variable used of nebulised salbutamol acutely Not blinded to physicians Variable background preventive treatment |
| FEV1 | Non-significant benefit of salbutamol | ||||
| FVC | Non-significant benefit of aminophylline | ||||
| Arterial gases | No difference | ||||
| Pulse & BP | Significant tachycardia in salbutamol group | ||||
| Aminophylline, salbutamol and combined intravenous infusions in acute severe asthma. Evans WV, Monie RD, Crimmins J et al. 1980, UK | 21 acute asthma patients | Single blinded RCT comparing aminophylline, salbutamol or combined IV | Spirometry | Non-significantly quicker time to improvement with aminophylline and combined infusion | Small numbers Variable baseline severity Sub-therapeutic salbutamol dosing |
| Comparative study of effects of intravenous administration of aminophylline, salbutamol and terbutaline in patients suffering from reversible airways obstruction. Sahay JN, Bell R, Chatterjee SS et al. 1984, UK | 20 adults with FEV1<70% predicted | Double Blinded RCT crossover of aminophylline, turbutaline and salbutamol | Spirometry | All 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 effects | Salbutamol significantly more tachycardia and palpitations which return to no difference at 90 mins | ||||
| Comparison of intravenous aminophylline, salbutamol and terbtaline in acute asthma. Sharma TN, Gupta RB, Gupta PR et al. 1984, India | 30 known asthmatics with acute bronchospasm | RCT of aminophylline, salbutamol or turbutaline | Spirometry | Salbutamol significantly better FEV1 | Blinding not clear Salbutamol 250mcgm given as 1 min. bolus |
| Side effects | Significantly more palpitations with salbutamol | ||||
| Comparison of intravenous salbutamol (albuterol) and aminophylline in the treatment of acute asthmatic attacks. Grief J, Markovitz L, Topilsky M et al. 1985, Israel | 21 patients (mean age 38 years) with acute on chronic asthma | Single Blinded crossover 20 min infusion of salbutamol or aminophylline | % increase in peak flow | Salbutamol shows significant benefit to 30 mins (p<0.01) and 45 mins (p<0.05) post infusion | Small study Not fully blinded |
| Pulse rate | Tachcardia with salbutamol | ||||
| BP | No difference | ||||
| Plasma [K+] | Average drop of 0.6 mmol/l | ||||
| Tremor | More in salbutamol group |
Author Commentary:
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.
Bottom Line:
IV salbutamol should be considered a first line agent in the acute management of severe asthma in adults.
References:
- Beswick K, Davies J, Davey AJ.. A comparison of intravenous aminophylline and salbutamol in the treatment of severe bronchospasm.
- Williams SJ, Parrish RW, Seaton A.. Comparison of intravenous aminophylline and salbutamol in severe asthma.
- Tribe AE, Wong RM, Robinson JS.. A controlled trial of intravenous salbutamol and aminophylline in acute asthma.
- Femi-Pearse D, George WO, Ilechukwu ST et al.. Comparison of intravenous aminophylline and salbutamol in severe asthma.
- Johnson AJ, Spiro SG, Pidgeon J et al.. Intravenous infusion of salbutamol in severe acute asthma.
- Evans WV, Monie RD, Crimmins J et al.. Aminophylline, salbutamol and combined intravenous infusions in acute severe asthma.
- 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.
- Sharma TN, Gupta RB, Gupta PR et al.. Comparison of intravenous aminophylline, salbutamol and terbtaline in acute asthma.
- Grief J, Markovitz L, Topilsky M et al.. Comparison of intravenous salbutamol (albuterol) and aminophylline in the treatment of acute asthmatic attacks.