Severe equine asthma, also known as heaves or recurrent airway obstruction, is a chronic respiratory disease affecting approximately 15% of adult horses in the Northern Hemisphere.1 Exacerbations of asthma are induced by airborne antigens mostly present in hay and are characterized by episodes of airway inflammation and obstruction. The clinical signs are primarily attributed to bronchoconstriction, mucus accumulation, and airway remodeling. Bronchoconstriction is thought to account for 60% to 70% of acute airway obstruction during clinical exacerbation of asthma.2 Interventions are directed at controlling antigen exposure, decreasing inflammation, and counteracting bronchoconstriction. Corticosteroid administration and antigen avoidance result in improved lung function, but only after days and weeks of intervention, respectively.3,4 Intravenously administered bronchodilators, such as atropine or N-butylscopolammonium bromide,5 can rapidly induce bronchodilatation, but adverse effects (ie, colic or tachycardia) limit their administration to horses undergoing severe exacerbation. Inhalation of bronchodilators is associated with fewer adverse effects, but devices used to administer the medications are not always available to practitioners. Also, some horses cannot tolerate this form of drug administration; therefore, the clinical response to inhaled bronchodilators varies.6
As a consequence, it is of interest to investigate treatment alternatives that could be used as a rescue medication during severe asthma exacerbations in horses. Magnesium sulfate solution has bronchodilator effects and is used as a second-line treatment in combination with corticosteroids and bronchodilators to treat humans hospitalized because of acute asthma attacks.7 Administration of MgSO4 solution has been shown to decrease the number of hospitalizations and need for assisted ventilation in adults and children with asthma.7,8 In 1987, Okayama et al9 determined that MgSO4 infusion administered alone had bronchodilator effects in humans with asthma and improved their lung function in a manner comparable to that achieved by treatment with albuterol (salbutamol). However, results of other studies10,11 indicated that MgSO4 infusion had a lesser effect than other bronchodilators. A possible potentiation effect of MgSO4 and inhaled bronchodilators on smooth muscle relaxation has been described,12 but it is not clear whether true potentiation was observed or if an additive effect was more likely.13 Reported adverse effects of MgSO4 infusion in humans are usually minor and transient and include hypotension, nausea, vomiting, flushing, headaches, and a burning sensation at the catheter site.7
Magnesium sulfate solution is readily available to equine practitioners, relatively easy to administer, and inexpensive, and it can be given to horses orally as a laxative or IV as an anti-arrhythmic agent with few adverse effects. Only 1 recent reporta has described some bronchodilator effects of MgSO4 infusion in horses, to our knowledge. The purpose of the study reported here was to evaluate whether MgSO4 solution administered IV would improve the clinical signs and lung function of horses with severe asthma and potentiate the effects of inhaled salbutamol in those horses. We hypothesized that treatment with MgSO4 solution would have bronchodilator effects and potentiate the effects of inhaled salbutamol in severely asthmatic horses.
Supported by the Fonds en santé équine de l'Université de Montréal, Zoetis, and the Fonds du Centenaire. Funding sources did not have any involvement in the study design, data analysis and interpretation, or writing and publication of the manuscript. The authors declare that there were no conflicts of interest.
Presented as a poster at the 35th Annual American College of Veterinary Internal Medicine Forum, National Harbor, Md, June 2017.
The authors thank Guy Beauchamp for assistance with statistical analysis.
Impulse oscillometry system
Resistance at 1 Hz
Resistance at 5 Hz to resistance at 10 Hz
Reactance at 1 Hz
Bowser J, Wenzel C, Wills R, et al. Intravenous magnesium sulfate as a rescue therapeutic for bronchoconstriction in horses (abstr), in Proceedings. 34th Annu Am Coll Vet Intern Med Forum 2016;703.
Ventolin HFA, GlaxoSmithKline Inc, Mississauga, ON, Canada.
AeroHippus Equine Aerosol Chamber, Trudel Medical International, London, ON, Canada.
Gentes and Bolduc Pharmacy, St-Hyacinthe, QC, Canada.
Equine MasterScreen IOS system, LabManager version 4.53, Jaeger, Würzburg, Germany.
FAMOS, imc Meßsysteme, Berlin, Germany.
SAS, version 9.1, SAS Institute Inc, Cary, NC.
1. Hotchkiss JW, Reid SW, Christley RM. A survey of horse owners in Great Britain regarding horses in their care. Part 2: risk factors for recurrent airway obstruction. Equine Vet J 2007;39:301–308.
3. Leclere M, Lavoie-Lamoureux A, Joubert P, et al. Corticosteroids and antigen avoidance decrease airway smooth muscle mass in an equine asthma model. Am J Respir Cell Mol Biol 2012;47:589–596.
4. Couëtil LL, Chilcoat CD, DeNicola DB, et al. Randomized, controlled study of inhaled fluticasone propionate, oral administration of prednisone, and environmental management of horses with recurrent airway obstruction. Am J Vet Res 2005;66:1665–1674.
5. de Lagarde M, Rodrigues N, Chevigny M, et al. N-butylscopolammonium bromide causes fewer side effects than atropine when assessing bronchoconstriction reversibility in horses with heaves. Equine Vet J 2014;46:474–478.
6. Bertin FR, Ivester KM, Couetil LL. Comparative efficacy of inhaled albuterol between two hand-held delivery devices in horses with recurrent airway obstruction. Equine Vet J 2011;43:393–398.
7. Kew KM, Kirtchuk L, Michell CI. Intravenous magnesium sulfate for treating adults with acute asthma in the emergency department. Cochrane Database Syst Rev 2014;(5):CD010909.
8. Torres S, Sticco N, Boscha JJ, et al. Effectiveness of magnesium sulfate as initial treatment of acute severe asthma in children, conducted in a tertiary-level university hospital. A randomized, controlled trial. Arch Argent Pediatr 2012;110:291–296.
9. Okayama H, Aikawa T, Okayama M, et al. Bronchodilating effect of intravenous magnesium sulfate in bronchial asthma. JAMA 1987;257:1076–1078.
10. Noppen M, Vanmaele L, Impens N, et al. Bronchodilating effect of intravenous magnesium sulfate in acute severe bronchial asthma. Chest 1990;97:373–376.
11. Sharma SK, Bhargava A, Pande JN. Effect of parenteral magnesium sulfate on pulmonary functions in bronchial asthma. J Asthma 1994;31:109–115.
12. Shivanthan MC, Rajapakse S. Magnesium for acute exacerbation of chronic obstructive pulmonary disease: a systematic review of randomised trials. Ann Thorac Med 2014;9:77–80.
13. Kose M, Ozturk MA, Poyrazolu H, et al. The efficacy of nebulized salbutamol, magnesium sulfate, and salbutamol/magnesium sulfate combination in moderate bronchiolitis. Eur J Pediatr 2014;173:1157–1160.
14. Marr CM, Reimer JM. The cardiovascular system. In: Higgins AJ, Wright IM, eds. The equine manual. Philadelphia: WB Saunders Co, 1995;381–408.
15. van Erck E, Votion DM, Kirschvink N, et al. Use of the impulse oscillometry system for testing pulmonary function during methacholine bronchoprovocation in horses. Am J Vet Res 2003;64:1414–1420.
16. Vogel J, Smidt U. Impulse oscillometry: analysis of lung mechanics in general practice and the clinic, epidemiology and experimental research. Frankfurt, Germany: Pmi-Verlagsgruppe, 1994.
18. Young SS, Tesarowski D, Viel L. Frequency dependence of forced oscillatory respiratory mechanics in horses with heaves. J Appl Physiol 1997;82:983–987.
19. Bullone M, Chevigny M, Allano M, et al. Technical and physiological determinants of airway smooth muscle mass in endobronchial biopsy samples of asthmatic horses. J Appl Physiol 2014;117:806–815.
20. Robinson NE, Olszewski MA, Boehler D, et al. Relationship between clinical signs and lung function in horses with recurrent airway obstruction (heaves) during a bronchodilator trial. Equine Vet J 2000;32:393–400.
21. Nadler JL, Goodson S, Rude RK. Evidence that prostacyclin mediates the vascular action of magnesium in humans. Hypertension 1987;9:379–383.
22. Kemp PA, Gardiner SM, March JE, et al. Effects of NG-nitro-L-arginine methyl ester on regional haemodynamic responses to MgSO4 in conscious rats. Br J Pharmacol 1994;111:325–331.
23. Ceneviva GD, Thomas NJ, Kees-Folts D. Magnesium sulfate for control of muscle rigidity and spasms and avoidance of mechanical ventilation in pediatric tetanus. Pediatr Crit Care Med 2003;4:480–484.
24. Kim YH, Lee PB, Oh TK. Is magnesium sulfate effective for pain in chronic postherpetic neuralgia patients comparing with ketamine infusion therapy? J Clin Anesth 2015;27:296–300.
25. Demiroglu M, Ün C, Ornek DH, et al. The effect of systemic and regional use of magnesium sulfate on postoperative tramadol consumption in lumbar disc surgery. BioMed Res Int 2016;2016;3216246.
26. Dodd JA, Doran G, Harris P, et al. Magnesium aspartate supplementation and reaction speed response in horses. J Equine Vet Sci 2015;35:401–402.
27. Bloch H, Silverman R, Mancherje N, et al. Intravenous magnesium sulfate as an adjunct in the treatment of acute asthma. Chest 1995;107:1576–1581.
28. Porter RS, Nester BA, Braitman LE, et al. Intravenous magnesium is ineffective in adult asthma, a randomized trial. Eur J Emerg Med 2001;8:9–15.
29. Silverman RA, Osborn H, Runge J, et al. IV magnesium sulfate in the treatment of acute severe asthma: a multicenter randomized controlled trial. Chest 2002;122:489–497.
30. Van Erck E, Votion DM, Art T, et al. Qualitative and quantitative evaluation of equine respiratory mechanics by impulse oscillometry. Equine Vet J 2006;38:52–58.
31. Richard EA, Fortier GD, Denoix JM, et al. Influence of subclinical inflammatory airway disease on equine respiratory function evaluated by impulse oscillometry. Equine Vet J 2009;41:384–389.
32. Takeda T, Oga T, Niimi A, et al. Relationship between small airway function and health status, dyspnea and disease control in asthma. Respiration 2010;80:120–126.
33. Olaguíbel JM, Alvarez-Puebla MJ, Anda M, et al. Comparative analysis of the bronchodilator response measured by impulse oscillometry (IOS), spirometry and body plethysmography in asthmatic children. J Investig Allergol Clin Immunol 2004;15:102–106.
34. Thomson JR, McPherson EA. Effects of environmental control on pulmonary function of horses affected with chronic obstructive pulmonary disease. Equine Vet J 1984;16:35–38.
35. Van Erck E, Votion DM, Kirschvink N, et al. Influence of breathing pattern and lung inflation on impulse oscillometry measurements in horses. Vet J 2004;168:259–269.
36. Cheuk DK, Chau TC, Lee SL. A meta-analysis on intravenous magnesium sulphate for treating acute asthma. Arch Dis Child 2005;90:74–77.
37. Bullone M, Murcia RY, Lavoie JP. Environmental heat and airborne pollen concentration are associated with increased asthma severity in horses. Equine Vet J 2016;48:479–484.