Abstract
BACKGROUND—Beta-2 adrenoceptor agonists have been associated with sudden death in asthma patients but the cause and underlying mechanism are unclear. Animal experiments indicate that the combination of hypoxia and β2 agonists may result in detrimental cardiovascular effects. A study was undertaken to investigate the effect of hypoxia on the systemic vascular effects of salbutamol in patients with asthma who are hypoxic by assessing forearm blood flow (FBF) as a measure of peripheral vasodilatation. METHODS—Eight men with mild asthma underwent the following treatments: normoxia + placebo (NP), normoxia + salbutamol (NS), hypoxia+ placebo (HP), and hypoxia + salbutamol (HS). The period of mask breathing started at t=0 minutes, lasted for 60 minutes, and at 30 minutes 800 µg salbutamol was inhaled. The experiment was completed 30 minutes after the inhalation (t=60 minutes). For the hypoxia treatment the SpO2 level was 82%. Differences between treatments were sought using factorial ANOVA on percentage change from the pretreatment value. RESULTS—There were no significant differences in blood pressure and potassium levels between the treatments. After 60 minutes the increase in FBF was 13% (95% CI -12 to 39) more for HP treatment than for NP, 21% (95% CI -5 to 46) more for NS than for NP, and 32% (95% CI 7 to 58) more for HS than for HP (p=0.016). The inhalation of salbutamol during hypoxia resulted in a significant increase in FBF of 45% (95% CI 20 to 71) compared with NP (p=0.001). CONCLUSION—Patients with asthma who are hypoxic and inhale β2 agonists have serious systemic vascular side effects which may be an additional explanation for the association between asthma treatment and sudden death.
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Selected References
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- Arrighi H. M. US asthma mortality: 1941 to 1989. Ann Allergy Asthma Immunol. 1995 Apr;74(4):321–326. [PubMed] [Google Scholar]
- Barriot P., Riou B. Prevention of fatal asthma. Chest. 1987 Sep;92(3):460–466. doi: 10.1378/chest.92.3.460. [DOI] [PubMed] [Google Scholar]
- Beasley R., Burgess C., Pearce N., Woodman K., Crane J. Confounding by severity does not explain the association between fenoterol and asthma death. Clin Exp Allergy. 1994 Jul;24(7):660–668. doi: 10.1111/j.1365-2222.1994.tb00970.x. [DOI] [PubMed] [Google Scholar]
- Bengtsson-Hasselgren B., Rönn O., Blychert L. O., Edgar B., Raner S. Acute effects of felodipine and nifedipine on hepatic and forearm blood flow in healthy men. Eur J Clin Pharmacol. 1990;38(6):529–533. doi: 10.1007/BF00278576. [DOI] [PubMed] [Google Scholar]
- Blauw G. J., Westendorp R. G. Asthma deaths in New Zealand: whodunnit? Lancet. 1995 Jan 7;345(8941):2–3. doi: 10.1016/s0140-6736(95)91143-x. [DOI] [PubMed] [Google Scholar]
- Blauw G. J., Westendorp R. G., Simons M., Chang P. C., Frölich M., Meinders A. E. beta-Adrenergic receptors contribute to hypoxaemia induced vasodilation in man. Br J Clin Pharmacol. 1995 Nov;40(5):453–458. [PMC free article] [PubMed] [Google Scholar]
- Collins J. M., McDevitt D. G., Shanks R. G., Swanton J. G. The cardio-toxicity of isoprenaline during hypoxia. Br J Pharmacol. 1969 May;36(1):35–45. doi: 10.1111/j.1476-5381.1969.tb08301.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Corn B., Hamrung G., Ellis A., Kalb T., Sperber K. Patterns of asthma death and near-death in an inner-city tertiary care teaching hospital. J Asthma. 1995;32(6):405–412. doi: 10.3109/02770909409077751. [DOI] [PubMed] [Google Scholar]
- Crane J., Burgess C., Beasley R. Cardiovascular and hypokalaemic effects of inhaled salbutamol, fenoterol, and isoprenaline. Thorax. 1989 Feb;44(2):136–140. doi: 10.1136/thx.44.2.136. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fuller R. W. The asthma death problem revisited. Br J Clin Pharmacol. 1996 Jul;42(1):11–14. doi: 10.1046/j.1365-2125.1996.03663.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Garrett J. E., Lanes S. F., Kolbe J., Rea H. H. Risk of severe life threatening asthma and beta agonist type: an example of confounding by severity. Thorax. 1996 Nov;51(11):1093–1099. doi: 10.1136/thx.51.11.1093. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gross N. J., Bankwala Z. Effects of an anticholinergic bronchodilator on arterial blood gases of hypoxemic patients with chronic obstructive pulmonary disease. Comparison with a beta-adrenergic agent. Am Rev Respir Dis. 1987 Nov;136(5):1091–1094. doi: 10.1164/ajrccm/136.5.1091. [DOI] [PubMed] [Google Scholar]
- Hindi-Alexander M. C., Middleton E., Jr Asthma deaths: are they preventable? N Engl Reg Allergy Proc. 1986 Sep-Oct;7(5):462–466. doi: 10.2500/108854186778984745. [DOI] [PubMed] [Google Scholar]
- Jalaludin B. B., Smith M. A., Chey T., Orr N. J., Smith W. T., Leeder S. R. Risk factors for asthma deaths: a population-based, case-control study. Aust N Z J Public Health. 1999 Dec;23(6):595–600. doi: 10.1111/j.1467-842x.1999.tb01543.x. [DOI] [PubMed] [Google Scholar]
- Mason D. T., Braunwald E. The effects of nitroglycerin and amyl nitrite on arteriolar and venous tone in the human forearm. Circulation. 1965 Nov;32(5):755–766. doi: 10.1161/01.cir.32.5.755. [DOI] [PubMed] [Google Scholar]
- McFadden E. R., Jr The beta 2-agonist controversy revisited. Ann Allergy Asthma Immunol. 1995 Aug;75(2):173–176. [PubMed] [Google Scholar]
- Pearce N., Grainger J., Atkinson M., Crane J., Burgess C., Culling C., Windom H., Beasley R. Case-control study of prescribed fenoterol and death from asthma in New Zealand, 1977-81. Thorax. 1990 Mar;45(3):170–175. doi: 10.1136/thx.45.3.170. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Somerville M., Williams E. M., Pearson M. G. Asthma deaths in Mersey region 1989-1990. J Public Health Med. 1995 Dec;17(4):397–403. [PubMed] [Google Scholar]
- Suissa S., Ernst P., Boivin J. F., Horwitz R. I., Habbick B., Cockroft D., Blais L., McNutt M., Buist A. S., Spitzer W. O. A cohort analysis of excess mortality in asthma and the use of inhaled beta-agonists. Am J Respir Crit Care Med. 1994 Mar;149(3 Pt 1):604–610. doi: 10.1164/ajrccm.149.3.8118625. [DOI] [PubMed] [Google Scholar]
- Westendorp R. G., Blauw G. J., Frölich M., Simons R. Hypoxic syncope. Aviat Space Environ Med. 1997 May;68(5):410–414. [PubMed] [Google Scholar]