Why is levosalbutamol (albuterol) preferred over salbutamol (albuterol) in patients with status asthmaticus?

Levosalbutamol vs Salbutamol in Status Asthmaticus

Levosalbutamol is NOT actually preferred over salbutamol in status asthmaticus according to major asthma guidelines—both are acceptable short-acting beta-2 agonists (SABAs), with levosalbutamol administered at half the milligram dose of salbutamol to provide comparable efficacy and safety. 1

Guideline Recommendations

The National Asthma Education and Prevention Program (NAEPP) Expert Panel Report 3 explicitly states that both albuterol (salbutamol) and levalbuterol (levosalbutamol) are acceptable SABAs for acute asthma exacerbations, including status asthmaticus 1. The guidelines note that:

• Levosalbutamol administered in half the milligram dose of albuterol provides comparable efficacy and safety 1
• For status asthmaticus in adults: levosalbutamol 1.25-2.5 mg every 20 minutes for 3 doses equals salbutamol 2.5-5 mg every 20 minutes for 3 doses 1
• For children: levosalbutamol 0.075 mg/kg (minimum 1.25 mg) equals salbutamol 0.15 mg/kg (minimum 2.5 mg) 1

Neither drug is listed as "preferred" over the other—they are presented as equivalent therapeutic options 1.

The Theoretical Rationale (Not Supported by Clinical Evidence)

The theoretical argument for levosalbutamol stems from the pharmacology of racemic salbutamol:

• Salbutamol is a 50:50 racemic mixture of (R)-salbutamol and (S)-salbutamol 2, 3, 4
• Only the (R)-enantiomer (levosalbutamol) provides bronchodilation 2, 3, 4, 5
• The (S)-enantiomer has been shown in vitro and animal studies to potentially cause bronchospasm, pro-inflammatory effects, and increased airway hyperreactivity 3, 4, 5
• (S)-salbutamol is metabolized 12 times slower than (R)-salbutamol, leading to higher plasma concentrations of the (S)-enantiomer over time 3

Clinical Reality: No Consistent Superiority

Despite strong experimental evidence suggesting (S)-salbutamol may be harmful, well-designed clinical studies in patients with asthma have failed to find evidence of significant toxicity or consistent clinical superiority of levosalbutamol over racemic salbutamol 3, 4.

Research Evidence Shows Equivalence:

• A 2007 randomized, double-blind crossover study found that 100 mcg levosalbutamol via MDI produced similar bronchodilator response as 200 mcg salbutamol over 6 hours, with equivalent time to onset, maximum response, and duration 2
• A 2023 pediatric study did show levosalbutamol superiority in some parameters (respiratory rate, heart rate, SpO₂, PEFR, asthma score), but this represents a single study and is not reflected in major guideline recommendations 6
• Expert reviews conclude that "despite strong experimental evidence, (R)-salbutamol has not shown consistent superiority over (S)- or racemic salbutamol in human asthma or COPD" 4

Important Clinical Caveats

Levosalbutamol has NOT been evaluated by continuous nebulization, which is a critical limitation since continuous nebulization is often used in severe status asthmaticus 1. This means:

• For continuous nebulization protocols (0.5 mg/kg/hour in children or 10-15 mg/hour in adults), only standard salbutamol has guideline support 1
• Levosalbutamol may be used for intermittent dosing every 20 minutes initially, then every 1-4 hours 1

Practical Algorithm for Status Asthmaticus

Use either salbutamol OR levosalbutamol based on availability and cost, as they are clinically equivalent:

1. Initial treatment (first hour):

   • Salbutamol 2.5-5 mg nebulized every 20 minutes × 3 doses, OR
   • Levosalbutamol 1.25-2.5 mg nebulized every 20 minutes × 3 doses 1

2. If requiring continuous nebulization:

   • Use salbutamol 10-15 mg/hour (levosalbutamol not studied for this) 1

3. Add ipratropium bromide 0.5 mg to the first 3 doses for severe exacerbations 1

4. Monitor for tachycardia: Some evidence suggests racemic salbutamol causes more tachycardia than levosalbutamol 6, though this is not emphasized in major guidelines

The choice between these agents should be driven by institutional availability and cost rather than perceived clinical superiority, as major asthma guidelines do not preferentially recommend one over the other for status asthmaticus 1.