Page 681 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

500 PART 4: Pulmonary Disorders

no difference in clinical outcomes between low-dose corticosteroids vehicle for nebulized albuterol in a randomized, double-blind fashion.
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(≤80 mg/d methylprednisolone or ≤400 mg/d hydrocortisone) and At 20 minutes, patients treated with MgSO and albuterol had a greater
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higher doses in the initial management of hospitalized asthmatics. PEFR compared to the saline-albuterol group (134 ± 70 L/min vs 86 ±
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Haskell and colleagues demonstrated that 125 mg IV methylpredniso- 64 L/min). Hughes and colleagues published similar data. To the con-
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lone every 6 hours resulted in faster improvement compared to 40 mg trary, Aggarwal and colleagues reported no therapeutic benefit to adding
every 6 hours, but there was no difference in peak improvement. Both MgSO to albuterol nebulization in their randomized trial of acute severe
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doses were superior to 15 mg every 6 hours in terms of rate and abso- asthmatics. One systematic review has reported inhaled magnesium
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lute response. Emerman and Cydulka compared 500 mg and 100 mg of improves lung function in patients with severe attacks, whereas a more
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methylprednisolone and found no benefit to the higher dose. 120 recent systematic review states the data are insufficient to draw strong
The Expert Panel from the National Institutes of Health (NIH) rec- conclusions. A recent Cochrane review also concluded that inhaled
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ommends 40 to 80 mg/d of prednisone or methylprednisolone in one MgSO added little to treatment with inhaled β-agonists, did not reduce
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or two divided doses for all patients with moderate to severe exacerba- hospital admissions, but might have an effect on improving pulmonary
tions until PEFR reaches 70% predicted or personal best. Prednisone function in patients with an FEV less than 50% of predicted. 140
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is tapered at variable rates depending on a number of factors, including
PEFR, the duration of high-dose therapy required to treat the acute Leukotriene Modifiers: Preliminary data demonstrating benefit to a
exacerbation, and whether oral steroids had been used for maintenance leukotriene receptor antagonist came from a double-blind, randomized
therapy. Automatic tapering schedules are not recommended because trial of two doses (20 and 160 mg) of zafirlukast orally versus placebo
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patients may taper prematurely. in 641 asthmatics after 30 minutes of standard treatment. Zafirlukast
Although data demonstrate efficacy of ICSs in the treatment of acute 160 mg decreased admission rates, relapses, and treatment failures.
asthma, there is no established role for their use in most patients. 62,122 In another double-blind, placebo-controlled study of 20 patients not
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However, ICSs play a pivotal role in achieving outpatient asthma con- receiving systemic steroids in an ED, oral montelukast 10 mg resulted
trol and are generally underused for this purpose. Patients discharged in a trend toward a shorter duration of stay and higher peak flows,
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from the ED or hospital after an asthma attack should be considered and fewer patients requiring aminophylline or steroids. In the most
for an ICS-based treatment program, combined with optimal education compelling trial to date, Camargo and colleagues randomized 201
regarding ICS use. acute asthmatics to standard therapy plus montelukast 7 or 14 mg IV or
placebo. Montelukast improved FEV over the first 20 minutes (14.8%
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Aminophylline: There is no benefit to adding aminophylline to inhaled vs 3.6% with placebo). Benefits were seen within 10 minutes and lasted
β-agonists in the initial treatment of acute asthma. In a meta-analysis for 2 hours; both treatment doses were equivalent. Montelukast also
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by Parameswaran and colleagues there was a trend toward higher PEFR tended to result in less β-agonist use and fewer treatment failures. More
at 12 and 24 hours, but at the cost of arrhythmias and vomiting. recently Ramsay and colleagues reported the results of their random-
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Others have reported a delayed benefit. Nonbronchodilating proper- ized, placebo controlled trial of oral montelukast in 87 patients admitted
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ties of aminophylline may be useful in refractory cases; indeed anti- with acute asthma with a mean PEFR of approximately 48% of predicted
inflammatory effects and enhanced diaphragm function may explain at baseline. Montelukast improved PEFR compared to placebo the
one report that ED administration of aminophylline decreased hospi- morning after admission (81.4% vs 69.8% of predicted). 144
talizations, even when airflow rates were no different than placebo. 126
Aminophylline should be used sparingly in refractory patients; Heliox: Heliox is a mixture of 20% oxygen and 80% helium (30% : 70%
however, it is reasonable to continue its use in the rare patient taking and 40% : 60% mixtures are also available). As the percentage of helium
theophylline as an outpatient after confirming a nontoxic serum con- decreases, so does the benefit of breathing this gas blend. Concentrations
centration. This approach is safe if attention is paid to serum drug of helium less than 60% are ineffective, precluding its use in significant
levels and to factors that increase levels, such as congestive heart failure, hypoxemia. Heliox is slightly more viscous than air, but significantly less
ciprofloxacin, macrolide antibiotics, and cimetidine, and if the drug is dense, resulting in a more than threefold increase in kinematic viscosity
discontinued for signs and symptoms of toxicity. (the ratio of gas viscosity to gas density) compared to air. Theoretically,
this property decreases the driving pressure required for gas flow by two
Magnesium Sulfate: Three early prospective trials failed to confirm a mechanisms. First, for any level of turbulent flow, breathing low-density gas
benefit to administering magnesium sulfate (MgSO ) to asthmatics in decreases the pressure gradient required for flow. Second, heliox decreases
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the ED. 127-129 In 135 asthmatics randomized to 2 g MgSO IV or placebo the Reynolds number, favoring conversion of turbulent flow to laminar
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after 30 minutes and followed for 4 hours, admission rates and FEV flow. Heliox does not treat bronchospasm or airway wall inflammation.
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were no different between magnesium-treated patients and controls. Heliox promptly improves dyspnea, work of breathing, and arterial
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However, subgroup analysis revealed MgSO decreased admission blood gases in upper airway obstruction. Benefits have also been
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rates and improved FEV in subjects with FEV <25% of predicted. reported in acute asthma. In adults treated in an ED, an 80 : 20 mix
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Subsequently, a placebo-controlled, double-blind, randomized trial in delivered by tight-fitting face mask increased PEFR and decreased
248 patients with FEV ≤30% showed a small but statistically signifi- PP, suggesting improved airway resistance and work of breathing.
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cant increase in FEV after 240 minutes in the magnesium group, but Similar results have been published in children. Other studies have
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no difference in hospitalization rates. Subsequent meta-analysis of failed to demonstrate benefit. 149-151 In a meta-analysis by Rodrigo and
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7 trials (5 adult, 2 pediatric) and 665 patients did not support the rou- colleagues the authors commented on the heterogeneity among studies
tine use of IV magnesium in all ED patients, but did demonstrate that and concluded that the evidence does not support the use of heliox in
magnesium was safe and beneficial in patients with severe attacks. all nonintubated asthmatics in the ED. However, they did conclude
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A similar conclusion was reached by the authors of a systematic review in a cautionary manner that the evidence suggests a beneficial effect in
that included 10 randomized trials. Additional evidence supporting the subgroup of patients with severe exacerbations.
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benefit in severe disease comes from an uncontrolled study of five intu- If heliox is effective, it may give time for concurrent therapies to work,
bated asthmatics given magnesium. In this study, there was a fall in and thereby avert the need for intubation in some cases. Of theoretical
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peak airway pressure (43-32 cm H O) after high doses of MgSO (10-20 g) concern is the potential for heliox to mask worsening airflow obstruc-
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were administered over 1 hour. Other investigators have suggested that tion, so there is less time (and no margin for error) to control the airway
gender may play a role in magnesium responsiveness, since estrogen when intubation is required.
augments the bronchodilator effect of magnesium. 134,135 Whether heliox augments the bronchodilator effect of inhaled
Magnesium sulfate can also be administered by inhalation. Nannini β-agonists compared to delivery in air (presumably due to low-density
and colleagues studied the effects of MgSO (225 mg) versus saline as the gas facilitating albuterol deposition) is unclear. Data are available
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