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Magnesium's role in pediatric asthma
Pediatric Perspective
Michael Chesney, RN, CFRN, CCRN, FP-C, EMT-P I/C
Magnesium’s Role in Pediatric Asthma Asthma remains one of the most common diseases of childhood and accounts for 17% of pediatric visits to US emergency departments.1 Despite advancements in the understanding and treatment of pediatric asthma, mortality rates continue to rise and have more than doubled between 1980 and 1996, with the highest mortality rates occurring in adolescents.1 Limited access to care and delays in seeking medical attention are likely the most significant factors for this increase. This article provides a brief review of pediatric asthma and current treatment strategies, including the use of magnesium sulfate for the management of severe exacerbation. There is mounting evidence that intravenous magnesium sulfate can benefit both adults and children with severe asthma. Despite this evidence, the use of magnesium sulfate in both emergency departments and intensive care units remains inconsistent.
Review of Asthma Pathophysiology Asthma is a chronic inflammatory disorder of the airways and is characterized by bronchial hyperreactivity producing both bronchoconstriction and airway inflammation. These factors can lead to reversible airflow obstruction. An important distinction in clinical asthma management is that bronchoconstriction and airway inflammation are separate entities and treated separately. Another complication associated with asthma exacerbations is the overproduction of mucus that has a negative impact on airflow through the bronchioles and can lead to plugging of the airways. The exacerbation of asthma is usually precipitated by an offending stimulus such as an infection (commonly viral), environmental allergens, exercise, cold air, stress, or strong emotional responses.2 Airway obstruction from bronchospasm, airway inflammation, and mucus plugging leads to increased airway resistance and gas trapping. This in turn leads to a greater amount of work required to breathe during both inhalation and exhalation and is manifested by accessory muscle use. The airflow obstruction and increased work of breathing can be especially difficult for pediatric patients, given their relatively smaller airway diameters. Younger children will also have greater difficulty in maintaining the higher levels of exertion required to breathe because of their smaller glycogen reserves.
Physical Examination Coughing, wheezing, and dyspnea are the most common clinical signs of asthma. Other findings can include retractions, tachypnea, and a prolonged expiratory phase.2 Although wheezing is considered a hallmark of asthma, this sign may be 200
unreliable when assessing the degree of distress. Severe obstructions may have an absence of wheezing altogether. Physical signs that are useful in determining the degree of respiratory distress are respiratory rate, heart rate, use of accessory muscles, level of consciousness, and presence of cyanosis.2 Agitation and irritability may signal hypoxia. Lethargy, somnolence, and fatigue are seen with hypercarbia and may herald the beginning of respiratory failure (defined as a partial pressure of oxygen [PaO2] less than 50 mmHg and a partial pressure of carbon dioxide [PaCO2] greater than 50 mmHg). Bradypnea and bradycardia in the presence of a severe asthma attack may be ominous signs and should alert the clinician to possible impending cardiopulmonary arrest.2 Serial examinations are imperative in the pediatric patient to assess the response, if any, to treatment. Failure of patients in moderate to severe respiratory distress to respond to treatment describes status asthmaticus and is considered a medical emergency.
Management As in any transport, management begins with the evaluation and stabilization of the airway, breathing, and circulation (ABCs). Securing the airway with endotracheal intubation should be considered for any patient in severe distress, although intubation does nothing to alleviate the problem of small airway constriction. Providers must be alert to the possible complications of positive pressure ventilation (PPV) in the presence of severe bronchoconstriction. The most common complication is “breath stacking.” This occurs when patients are unable to fully expire before the beginning of the next inspiratory cycle. Clinically this results in hyperinflation, potential tension pneumothorax, and hypotension. Specific management goals for the treatment of severe asthma include the rapid reversal of airflow obstruction and the correction of hypoxemia or hypercapnia.3 Typically, most algorithms for improving oxygenation include the use of increasing positive end expiratory pressure (PEEP) levels when 100% forced inspiratory oxygen (FiO2) is no longer sufficient to maintain oxygenation. This intervention should be avoided given the physiology of the disease. During manual or mechanical ventilation the use of a lower respiratory rate with smaller tidal volumes and shorter inspiratory times coupled with longer expiratory times is often necessary.4 Mild hypoventilation (permissive hypercapnia) can reduce the risk of barotrauma and is typically well tolerated. Inhaled betaadrenergic agents such as albuterol and levalbuterol combined with anticholinergic agents such as ipratropium are the mainstay of acute asthma therapy and provide bronchodilatation Air Medical Journal 26:5
with minimal cardiac effects. Treatment of the airway inflammation component of asthma is accomplished through the early use of corticosteroids.
Magnesium Sulfate Magnesium sulfate is a drug with a variety of uses. It is commonly used in the treatment of eclampsia and preterm labor, as well as cardiac arrhythmias such as Torsades de Pointes.2 The benefit of using magnesium sulfate in the setting of status asthmaticus is a result of the smooth muscle relaxant properties of this medication. Magnesium sulfate is a calcium antagonist and causes bronchial dilation by inhibiting calcium uptake in smooth muscle.4 Smooth muscle lines the bronchial airways and relaxation of these muscles during an asthma exacerbation may aid in alleviating bronchospasm. This action is clearly evident when treating preterm labor. The smooth muscle relaxation provided by magnesium sulfate aids in slowing uterine contractions in the cervix, a structure also composed of smooth muscle. Smooth muscle also lines arterial walls. This accounts for one of the potential side effects of magnesium sulfate administration, mild blood pressure depression. Other possible side effects at recommended dosing levels include flushing and burning at the intravenous (IV) infusion site. Another possible mechanism for magnesium sulfate’s benefits is an increase in the total magnesium level. Although not yet fully understood, increasing intracellular magnesium levels may be beneficial for those with status asthmaticus.5 In a random adult population, Britton et al6 demonstrated that an increased magnesium intake of 100 mg/day was independently associated with a 27.7 mL (95% confidence interval, 11.9-43.5 mL) higher forced expiratory volume (FEV), and a reduction in the relative odds of bronchial hyperreactivity by a ratio of 0.82 (confidence interval, 0.72-0.93).6 The higher levels of magnesium (believed to improve patient’s conditions) are not found in the serum but rather intracellularly. Intracellular levels of magnesium are much more difficult to measure and do not fully correlate with serum levels.6 Interestingly, the use of inhaled beta-adrenergics can precipitate renal magnesium loss, often leading to a magnesium deficiency.6
References 1. Bolte RG. Emergency department treatment of pediatric asthma. Clinical Pediatric Emergency Medicine 2004;5:256-269. 2. Darr C. Pediatric respiratory emergencies: lower airway obstructions. In: JA Marx, RS Hockberger, RM Walls. Rosen’s emergency medicine: concepts and clinical practice. 6th ed. St Louis: Mosby; 2006. 3. Expert Panel Report 2. Guidelines for the diagnosis and management of asthma. National Institutes of Health Publication 97-4051. Bethesda, MD: National Institutes of Health; 1997. 4. Chipps B, Murphy K. Assessment and treatment of acute asthma in children. J Pediatr 2005; 147:288-294. 5. Fiser R, Torres A, Butch A, Valentine JL. Ionized magnesium concentrations in critically ill children. Crit Care Med 1998;26:2048-2052. 6. Britton J, Pavord I, Richards K,Wisniewski A, Knox A, Lewis S, et al. Dietary magnesium, lung function, wheezing and airway hyperreactivity in a random adult population sample. Lancet 1994; 344:357-362.
Michael Chesney, RN, CFRN, CCRN, FP-C, EMT-P I/C, is a flight nurse for Survival Flight at the University of Michigan Medical Center in Ann Arbor, MI. He can be reached at [email protected]. 1067-991X/$30.00 Copyright 2007 Air Medical Journal Associates doi:10.1067/j.amj.2007.06.004
Dosing and Routes Loading doses range from 25 to 100 mg/kg, with a maximum of 2 g given by IV over 20 minutes.2 It can also be given intramuscularly or via nebulized inhalation; however, studies have shown the intravenous route to be most effective.4
Conclusion Although not currently recognized by the National Institutes of Health as an approved therapy in the treatment of asthma, multiple clinical trials are showing magnesium sulfate to be an effective adjunct used in conjunction with conventional therapy for the treatment of severe asthma.4 Because transport teams are often called to transport and manage these patients, magnesium sulfate’s low cost, minimal adverse effects, and availability make this medication an attractive option when confronted with a severe asthmatic unresponsive to conventional therapy. September-October 2007
201
Michael Chesney, RN, CFRN, CCRN, FP-C, EMT-P I/C
Magnesium’s Role in Pediatric Asthma Asthma remains one of the most common diseases of childhood and accounts for 17% of pediatric visits to US emergency departments.1 Despite advancements in the understanding and treatment of pediatric asthma, mortality rates continue to rise and have more than doubled between 1980 and 1996, with the highest mortality rates occurring in adolescents.1 Limited access to care and delays in seeking medical attention are likely the most significant factors for this increase. This article provides a brief review of pediatric asthma and current treatment strategies, including the use of magnesium sulfate for the management of severe exacerbation. There is mounting evidence that intravenous magnesium sulfate can benefit both adults and children with severe asthma. Despite this evidence, the use of magnesium sulfate in both emergency departments and intensive care units remains inconsistent.
Review of Asthma Pathophysiology Asthma is a chronic inflammatory disorder of the airways and is characterized by bronchial hyperreactivity producing both bronchoconstriction and airway inflammation. These factors can lead to reversible airflow obstruction. An important distinction in clinical asthma management is that bronchoconstriction and airway inflammation are separate entities and treated separately. Another complication associated with asthma exacerbations is the overproduction of mucus that has a negative impact on airflow through the bronchioles and can lead to plugging of the airways. The exacerbation of asthma is usually precipitated by an offending stimulus such as an infection (commonly viral), environmental allergens, exercise, cold air, stress, or strong emotional responses.2 Airway obstruction from bronchospasm, airway inflammation, and mucus plugging leads to increased airway resistance and gas trapping. This in turn leads to a greater amount of work required to breathe during both inhalation and exhalation and is manifested by accessory muscle use. The airflow obstruction and increased work of breathing can be especially difficult for pediatric patients, given their relatively smaller airway diameters. Younger children will also have greater difficulty in maintaining the higher levels of exertion required to breathe because of their smaller glycogen reserves.
Physical Examination Coughing, wheezing, and dyspnea are the most common clinical signs of asthma. Other findings can include retractions, tachypnea, and a prolonged expiratory phase.2 Although wheezing is considered a hallmark of asthma, this sign may be 200
unreliable when assessing the degree of distress. Severe obstructions may have an absence of wheezing altogether. Physical signs that are useful in determining the degree of respiratory distress are respiratory rate, heart rate, use of accessory muscles, level of consciousness, and presence of cyanosis.2 Agitation and irritability may signal hypoxia. Lethargy, somnolence, and fatigue are seen with hypercarbia and may herald the beginning of respiratory failure (defined as a partial pressure of oxygen [PaO2] less than 50 mmHg and a partial pressure of carbon dioxide [PaCO2] greater than 50 mmHg). Bradypnea and bradycardia in the presence of a severe asthma attack may be ominous signs and should alert the clinician to possible impending cardiopulmonary arrest.2 Serial examinations are imperative in the pediatric patient to assess the response, if any, to treatment. Failure of patients in moderate to severe respiratory distress to respond to treatment describes status asthmaticus and is considered a medical emergency.
Management As in any transport, management begins with the evaluation and stabilization of the airway, breathing, and circulation (ABCs). Securing the airway with endotracheal intubation should be considered for any patient in severe distress, although intubation does nothing to alleviate the problem of small airway constriction. Providers must be alert to the possible complications of positive pressure ventilation (PPV) in the presence of severe bronchoconstriction. The most common complication is “breath stacking.” This occurs when patients are unable to fully expire before the beginning of the next inspiratory cycle. Clinically this results in hyperinflation, potential tension pneumothorax, and hypotension. Specific management goals for the treatment of severe asthma include the rapid reversal of airflow obstruction and the correction of hypoxemia or hypercapnia.3 Typically, most algorithms for improving oxygenation include the use of increasing positive end expiratory pressure (PEEP) levels when 100% forced inspiratory oxygen (FiO2) is no longer sufficient to maintain oxygenation. This intervention should be avoided given the physiology of the disease. During manual or mechanical ventilation the use of a lower respiratory rate with smaller tidal volumes and shorter inspiratory times coupled with longer expiratory times is often necessary.4 Mild hypoventilation (permissive hypercapnia) can reduce the risk of barotrauma and is typically well tolerated. Inhaled betaadrenergic agents such as albuterol and levalbuterol combined with anticholinergic agents such as ipratropium are the mainstay of acute asthma therapy and provide bronchodilatation Air Medical Journal 26:5
with minimal cardiac effects. Treatment of the airway inflammation component of asthma is accomplished through the early use of corticosteroids.
Magnesium Sulfate Magnesium sulfate is a drug with a variety of uses. It is commonly used in the treatment of eclampsia and preterm labor, as well as cardiac arrhythmias such as Torsades de Pointes.2 The benefit of using magnesium sulfate in the setting of status asthmaticus is a result of the smooth muscle relaxant properties of this medication. Magnesium sulfate is a calcium antagonist and causes bronchial dilation by inhibiting calcium uptake in smooth muscle.4 Smooth muscle lines the bronchial airways and relaxation of these muscles during an asthma exacerbation may aid in alleviating bronchospasm. This action is clearly evident when treating preterm labor. The smooth muscle relaxation provided by magnesium sulfate aids in slowing uterine contractions in the cervix, a structure also composed of smooth muscle. Smooth muscle also lines arterial walls. This accounts for one of the potential side effects of magnesium sulfate administration, mild blood pressure depression. Other possible side effects at recommended dosing levels include flushing and burning at the intravenous (IV) infusion site. Another possible mechanism for magnesium sulfate’s benefits is an increase in the total magnesium level. Although not yet fully understood, increasing intracellular magnesium levels may be beneficial for those with status asthmaticus.5 In a random adult population, Britton et al6 demonstrated that an increased magnesium intake of 100 mg/day was independently associated with a 27.7 mL (95% confidence interval, 11.9-43.5 mL) higher forced expiratory volume (FEV), and a reduction in the relative odds of bronchial hyperreactivity by a ratio of 0.82 (confidence interval, 0.72-0.93).6 The higher levels of magnesium (believed to improve patient’s conditions) are not found in the serum but rather intracellularly. Intracellular levels of magnesium are much more difficult to measure and do not fully correlate with serum levels.6 Interestingly, the use of inhaled beta-adrenergics can precipitate renal magnesium loss, often leading to a magnesium deficiency.6
References 1. Bolte RG. Emergency department treatment of pediatric asthma. Clinical Pediatric Emergency Medicine 2004;5:256-269. 2. Darr C. Pediatric respiratory emergencies: lower airway obstructions. In: JA Marx, RS Hockberger, RM Walls. Rosen’s emergency medicine: concepts and clinical practice. 6th ed. St Louis: Mosby; 2006. 3. Expert Panel Report 2. Guidelines for the diagnosis and management of asthma. National Institutes of Health Publication 97-4051. Bethesda, MD: National Institutes of Health; 1997. 4. Chipps B, Murphy K. Assessment and treatment of acute asthma in children. J Pediatr 2005; 147:288-294. 5. Fiser R, Torres A, Butch A, Valentine JL. Ionized magnesium concentrations in critically ill children. Crit Care Med 1998;26:2048-2052. 6. Britton J, Pavord I, Richards K,Wisniewski A, Knox A, Lewis S, et al. Dietary magnesium, lung function, wheezing and airway hyperreactivity in a random adult population sample. Lancet 1994; 344:357-362.
Michael Chesney, RN, CFRN, CCRN, FP-C, EMT-P I/C, is a flight nurse for Survival Flight at the University of Michigan Medical Center in Ann Arbor, MI. He can be reached at [email protected]. 1067-991X/$30.00 Copyright 2007 Air Medical Journal Associates doi:10.1067/j.amj.2007.06.004
Dosing and Routes Loading doses range from 25 to 100 mg/kg, with a maximum of 2 g given by IV over 20 minutes.2 It can also be given intramuscularly or via nebulized inhalation; however, studies have shown the intravenous route to be most effective.4
Conclusion Although not currently recognized by the National Institutes of Health as an approved therapy in the treatment of asthma, multiple clinical trials are showing magnesium sulfate to be an effective adjunct used in conjunction with conventional therapy for the treatment of severe asthma.4 Because transport teams are often called to transport and manage these patients, magnesium sulfate’s low cost, minimal adverse effects, and availability make this medication an attractive option when confronted with a severe asthmatic unresponsive to conventional therapy. September-October 2007
201