What is racemic epinephrine?

Racemic Epinephrine: Clinical Applications and Administration

Racemic epinephrine is a nebulized medication containing a 1:1 mixture of D-epinephrine and L-epinephrine isomers, primarily used for treating acute airway edema in conditions like croup, available as a 2.25% inhalation solution. 1

Composition and Formulation

• Racemic epinephrine inhalation solution contains 11.25 mg of racepinephrine USP (as 13.5 mg of racepinephrine HCl) in each 0.5 ml vial 1
• Available as a 2.25% solution for nebulization 2
• Should be stored between 2°C and 25°C (36°F and 77°F), protected from light, excessive heat, and freezing 1

Primary Clinical Applications

Croup (Laryngotracheobronchitis)

• Standard dosing: 0.05 mL/kg of 2.25% solution (maximum: 0.5 mL) in 2 mL of normal saline administered by nebulizer 2
• Many institutions use a standardized 0.5 mL dose for all patients regardless of weight 2
• If racemic epinephrine is unavailable, L-epinephrine (1:1000) can be substituted at a dose of 0.5 mL/kg up to 5 mL 2
• Clinical studies have shown significant improvement in croup symptoms at 10 and 30 minutes after administration, though effects typically diminish by 120 minutes 3

Acute Airway Edema

• Same dosing as for croup: 0.05 mL/kg of 2.25% solution (maximum: 0.5 mL) in 2 mL of normal saline administered by nebulizer 2
• Provides temporary relief of airway edema through vasoconstriction and decreased mucosal edema 2

Efficacy and Evidence

• Randomized controlled trials have demonstrated that nebulized racemic epinephrine is effective for treating acute signs of croup with significant improvement in clinical scores at 10 and 30 minutes post-treatment 3
• L-epinephrine has been shown to be at least as effective as racemic epinephrine in treating laryngotracheitis without additional adverse effects 4
• The clinical effect is typically temporary (1-2 hours), requiring observation for symptom recurrence 3

Clinical Management Considerations

Observation After Administration

• Patients who receive racemic epinephrine for croup in the emergency department should be observed for 2-3 hours after administration to monitor for symptom rebound 2
• Evidence suggests that patients who remain stable 3-4 hours after racemic epinephrine administration can be safely discharged home, which is more cost-effective than automatic admission 5

Multiple Doses and Admission Criteria

• Traditionally, patients requiring 2 or more doses of racemic epinephrine in the ED were admitted for observation 2
• Recent evidence suggests that up to 3 doses may be appropriate before admission, with most patients who will need additional doses requiring them within 8-12 hours of presentation 6
• Quality improvement initiatives have shown that changing admission criteria from 2 to 3 doses of racemic epinephrine can reduce hospital admissions by 37-57% without increasing adverse outcomes 2

Risk Factors for Treatment Failure

• Recent use of steroids within 1 day prior to presentation is associated with greater need for >2 doses of racemic epinephrine during hospitalization 6
• Variation in racemic epinephrine use across emergency departments ranges from 14% to 48% of croup visits, suggesting inconsistent practice patterns 7

Administration in Other Conditions

Bronchiolitis

• While sometimes used, evidence does not support routine use of racemic epinephrine for bronchiolitis among inpatients 2
• Some evidence suggests epinephrine may be favorable to albuterol and placebo in outpatient settings for bronchiolitis 2
• If used in bronchiolitis, clinical response should be objectively documented to justify continued use 2

Asthma

• Epinephrine can be used in acute severe asthma, though selective β2-agonists are generally preferred 2
• Subcutaneous epinephrine (1:1000) can be given at 0.01 mg/kg in 3 doses of approximately 0.3 mg at 20-minute intervals 2
• Low-quality evidence suggests that epinephrine and selective β2-agonists have similar efficacy in acute asthma 2

Safety Considerations

• Racemic epinephrine should not be used in the home setting due to its short duration of action and potential adverse effects 2
• Adverse effects include increased heart rate, myocardial irritability, and increased oxygen demand 2
• When used appropriately in the clinical setting, it is generally well-tolerated even in patients >35 years of age 2

Clinical Decision Algorithm for Croup Management

1. Assess severity of croup symptoms
2. For moderate to severe croup with stridor at rest:
   • Administer dexamethasone
   • Consider racemic epinephrine 0.5 mL of 2.25% solution nebulized 2
3. Observe for 2-3 hours after racemic epinephrine administration
4. If symptoms improve and remain stable:
   • Consider discharge with follow-up 5
5. If symptoms recur or worsen:
   • Administer additional dose(s) of racemic epinephrine
   • Consider admission if requiring >3 doses 2